Search results for: drug target

Authors: Asma Rashid, Shazia Iram, Iftikhar Ahmad

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Mango sudden death is an emerging problem in Pakistan. As its prevalence is observed in almost all mango growing areas and severity varied from 2-5% in Punjab and 5-10% in Sindh. Symptoms on affected trees include bark splitting, discoloration of the vascular tissue, wilting, gummosis and at the end rapid death. Total of n= 45 isolates were isolated from different mango growing areas of Punjab and Sindh. Pathogenicity of these fungal isolates was tested through artificial inoculation method on different hosts (potato tubers, detached mango leaves, detached mango twigs and mango plants) under controlled conditions and all were proved pathogenic with varying degree of aggressiveness in reference to control. The findings of the present study proved that out of these four methods, potato tubers inoculation method was the most ideal as this fix the inoculums on the target site. Increased fungal growth and spore numbers may be due to soft tissues of potato tubers from which Ceratocystis isolates can easily pass. Lesion area on potato tubers was in the range of 7.09-0.14 cm2 followed by detached mango twigs which were ranged from 0.48-0.09 cm2). All pathological results were proved highly significant at P<0.05 through ANOVA but isolate to isolate showed non-significant behaviour but they have the positive effect on lesion area. Re-isolation of respective fungi was achieved with 100 percent success which results in the verification of Koch’s postulates. DNA of fungal pathogens was successfully extracted through phenol chloroform method. Amplification was done through ITS, b-tubulin gene, and Transcription Elongation Factor (EF1-a) gene primers and the amplified amplicons were sequenced and compared from NCBI which showed 99-100 % similarity with Ceratocystis manginecans. Fungus Ceratocystis manginecans formed one of strongly supported sub-clades through phylogenetic tree. Results obtained through this work would be supportive in establishment of relation of isolates with their region and will give information about pathogenicity level of isolates that would be useful to develop the management policies to reduce the afflictions in orchards caused by mango sudden death.

Keywords: artificial inoculation, mango, Ceratocystis manginecans, phylogenetic, screening

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Authors: Nan Hu, Chao Wang, Xi Li, Xuehai Zhou

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The field-programmable gate array (FPGA) has been widely adopted in the high-performance computing domain. In recent years, the embedded system-on-a-chip (SoC) contains coarse granularity multi-core CPU (central processing unit) and mobile GPU (graphics processing unit) that can be used as general-purpose accelerators. The motivation is that algorithms of various parallel characteristics can be efficiently mapped to the heterogeneous architecture coupled with these three processors. The CPU and GPU offload partial computationally intensive tasks from the FPGA to reduce the resource consumption and lower the overall cost of the system. However, in present common scenarios, the applications always utilize only one type of accelerator because the development approach supporting the collaboration of the heterogeneous processors faces challenges. Therefore, a systematic approach takes advantage of write-once-run-anywhere portability, high execution performance of the modules mapped to various architectures and facilitates the exploration of design space. In this paper, A servant-execution-flow model is proposed for the abstraction of the cooperation of the heterogeneous processors, which supports task partition, communication and synchronization. At its first run, the intermediate language represented by the data flow diagram can generate the executable code of the target processor or can be converted into high-level programming languages. The instantiation parameters efficiently control the relationship between the modules and computational units, including two hierarchical processing units mapping and adjustment of data-level parallelism. An embedded system of a three-dimensional waveform oscilloscope is selected as a case study. The performance of algorithms such as contrast stretching, etc., are analyzed with implementations on various combinations of these processors. The experimental results show that the heterogeneous computing system with less than 35% resources achieves similar performance to the pure FPGA and approximate energy efficiency.

Keywords: FPGA-CPU-GPU collaboration, design space exploration, heterogeneous computing, intermediate language, parameterized instantiation

Procedia PDF Downloads 118

Authors: Ábrám Zoltán

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Introduction: Climate change is now a major health risk, and its environmental and health effects have become frequently discussed topics. The consequences of climate change are clearly visible in natural disasters and excess deaths caused by extreme weather conditions. Global warming and the increasingly frequent extreme weather events have direct, immediate effects or long-term, indirect effects on health. For this reason, it is a need to teach the health effects of climate change in medical schools. Material and methods: We looked for various surveys, studies, and reports on the main pathways through which global warming affects health. Medical schools face the challenge of teaching the health implications of climate change and integrating knowledge about the health effects of climate change into medical training. For this purpose, there were organised World Café workshops for three target groups: medical students, academic staff, and practising medical doctors. Results: Among the goals of the research is the development of a detailed curriculum for medical students, which serves to expand their knowledge in basic education. At the same time, the project promotes the increase of teacher motivation and the development of methodological guidelines for university teachers; it also provides further training for practicing doctors. The planned teaching materials will be developed in a format suitable for traditional face-to-face teaching, as well as e-learning teaching materials. CLIMATEMED is a project based on the cooperation of six universities and institutions from four countries, the aim of which is to improve the curriculum and expand knowledge about the health effects of climate change at medical universities. Conclusions: In order to assess the needs, summarize the proposals, to develop the necessary strategy, World Café type, one-and-a-half to two-hour round table discussions will take place separately for medical students, academic staff, and practicing doctors. The CLIMATEMED project can facilitate the integration of knowledge about the health effects of climate change into curricula and can promote practical use. The avoidance of the unwanted effects of global warming and climate change is not only a public matter, but it is also a challenge to change our own lifestyle. It is the responsibility of all of us to protect the Earth's ecosystem and the physical and mental health of ourselves and future generations.

Keywords: climate change, health effects, medical schools, World Café, medical students

Procedia PDF Downloads 83

Authors: Ergin Toros, Manar Aslan

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This study was planned as a descriptive study in order to learn the opinions of the students who are studying in nursing undergraduate program about their theoretical/practical lessons and departments. The education in the undergraduate nursing programs has great importance because it contains the knowledge and skills to prepare student nurses to the clinic in the future. In order to provide quality-nursing services in the future, the quality of nursing education should be measured, and opinions of student nurses about education should be taken. The research population was composed of students educated in a university with 1-4 years of theoretical and clinical education (N=550), and the sample was composed of 460 students that accepted to take part in the study. It was reached to 83.6% of target population. Data collected through a survey developed by the researchers. Survey consists of 48 questions about sociodemographic characteristics (9 questions), theoretical courses (9 questions), laboratory applications (7 questions), clinical education (14 questions) and services provided by the faculty (9 questions). It was determined that 83.3% of the nursing students found the nursing profession to be suitable for them, 53% of them selected nursing because of easy job opportunity, and 48.9% of them stayed in state dormitory. Regarding the theoretical courses, 84.6% of the students were determined to agree that the question ‘Course schedule is prepared before the course and published on the university web page.’ 28.7% of them were determined to do not agree that the question ‘Feedback is given to students about the assignments they prepare.’. It has been determined that 41,5% of the students agreed that ‘The time allocated to laboratory applications is sufficient.’ Students said that physical conditions in laboratory (41,5%), and the materials used are insufficient (44.6%), and ‘The number of students in the group is not appropriate for laboratory applications.’ (45.2%). 71.3% of the students think that the nurses view in the clinics the students as a tool to remove the workload, 40.7% of them reported that nurses in the clinic area did not help through the purposes of the course, 39.6% of them said that nurses' communication with students is not good. 37.8% of students stated that nurses did not provide orientation to students, 37.2% of them think that nurses are not role models for students. 53.7% of the students stated that the incentive and support for the student exchange program were insufficient., %48 of the students think that career planning services, %47.2 security services,%45.4 the advisor spent time with students are not enough. It has been determined that nursing students are most disturbed by the approach of the nurses in the clinical area within the undergraduate education program. The clinical area education which is considered as an integral part of nursing education is important and affect to student satisfaction.

Keywords: nursing education, student, clinical area, opinion

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Authors: Nilanthi Ratnayake, Wen-Ling Liu

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Prior research indicates an increasing gap between the skills and capabilities of graduates in the contemporary workplace across the globe. The challenge of addressing this issue primarily lies on the hands of higher education institutes/universities. In particular, surveys of UK employers and retailers found that soft skills including communication, numeracy, teamwork, confidence, analytical ability, digital/IT skills, business sense, language, and social skills are highly valued by graduate employers, and in achieving this, there are various assessed and non-assessed learning exercises have already been embedded into the university curriculum. To this end, this research study aims to explore the reflections of postgraduate student participation in a live commercial project (i.e. designing an advertising campaign for open days, summer school etc.) implemented with the intention of offering a transformative experience by deploying this project. Qualitative research methodology has been followed in this study, collecting data from three types of target audiences; students, academics and employers via a series of personal interviews and focus group discussions. Recorded data were transcribed, entered into NVIVO, and analysed using meaning condensation and content analysis. Students reported that they had a very positive impact towards improving self-efficacy, especially in relation to soft skills and confidence in seeking employment opportunities. In addition, this project has reduced cultural barriers for international students in general communications. Academic staff and potential employers who attended on the presentation day expressed their gratitude for offering a lifelong experience for students, and indeed believed that these type of projects contribute significantly to enhance skills and capabilities of students to cater the demands of employers. In essence, key findings demonstrate that an integration of knowledge-based skills into a live commercial project facilitate individuals to make the transition from education to employment in terms of skills, abilities and work behaviours more effectively in comparison to some other activities/assuagements that are currently in place in higher education institutions/universities.

Keywords: soft skills, commercially live project, higher education, student participation

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Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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Authors: Samar Mousa, Ryan Kerstein, Mohanad Adam

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Regional anaesthesia has been associated with favourable outcomes in patients undergoing a wide range of surgeries. Beneficial effects have been demonstrated in terms of postoperative respiratory and cardiovascular endpoints, 7-day survival, time to ambulation and hospital discharge, and postoperative analgesia. Our project aimed at assessing the regional anaesthesia practice in the plastic surgery department of Buckinghamshire trust and finding out ways to improve the service in collaboration with the anaesthesia team. It is a retrospective study associated with a questionnaire filled out by plastic surgeons and anaesthetists to get the full picture behind the numbers. The study period was between 1/3/2022 and 23/5/2022 (12 weeks). The operative notes of all patients who had an operation under plastic surgery, whether emergency or elective, were reviewed. The criteria of suitable candidates for the regional block were put by the consultant anaesthetists as follows: age above 16, single surgical site (arm, forearm, leg, foot), no drug allergy, no pre-existing neuropathy, no bleeding disorders, not on ant-coagulation, no infection to the site of the block. For 12 weeks, 1061 operations were performed by plastic surgeons. Local cases were excluded leaving 319 cases. Of the 319, 102 patients were suitable candidates for regional block after applying the previously mentioned criteria. However, only seven patients had their operations under the regional block, and the rest had general anaesthesia that could have been easily avoided. An online questionnaire was filled out by both plastic surgeons and anaesthetists of different training levels to find out the reasons behind the obvious preference for general over regional anaesthesia, even if this was against the patients’ interest. The questionnaire included the following points: training level, time taken to give GA or RA, factors that influence the decision, percentage of RA candidates that had GA, reasons behind this percentage, recommendations. Forty-four clinicians filled out the questionnaire, among which were 23 plastic surgeons and 21 anaesthetists. As regards the training level, there were 21 consultants, 4 associate specialists, 9 registrars, and 10 senior house officers. The actual percentage of patients who were good candidates for RA but had GA instead is 93%. The replies estimated this percentage as between 10-30%. 29% of the respondents thought that this percentage is because of surgeons’ preference to have GA rather than RA for their operations without medical support for the decision. 37% of the replies thought that anaesthetists prefer giving GA even if the patient is a suitable candidate for RA. 22.6% of the replies thought that patients refused to have RA, and 11.3% had other causes. The recommendations were in 5 main accesses, which are protocols and pathways for regional blocks, more training opportunities for anaesthetists on regional blocks, providing a separate block room in the hospital, better communication between surgeons and anaesthetists, patient education about the benefits of regional blocks.

Keywords: regional anaesthesia, regional block, plastic surgery, general anaesthesia

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Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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Authors: Sinethemba Yakobi, Lindiwe Zuma, Ofentse Pooe

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Gonococcal infections present a notable public health issue, and the major approach for treatment involves using β-lactam antibiotics that specifically target penicillin-binding protein 2 (PBP2) in Neisseria gonorrhoeae. This study examines the influence of flavonoids, namely rutin, on the structural changes of PBP2 in both penicillin-resistant (FA6140) and penicillin-susceptible (FA19) strains. The research clarifies the structural effects of particular mutations, such as inserting an aspartate residue at position 345 (Asp-345a) in the PBP2 protein. The strain FA6140, which is resistant to penicillin, shows specific changes that lead to a decrease in penicillin binding. These mutations, namely P551S and F504L, significantly impact the pace at which acylation occurs and the stability of the strain under high temperatures. Molecular docking analyses investigate the antibacterial activities of rutin and other phytocompounds, emphasizing its exceptional binding affinity and potential as an inhibitor of PBP2. Quercetin and protocatechuic acid have encouraging antibacterial effectiveness, with quercetin displaying characteristics similar to those of drugs. Molecular dynamics simulations offer a detailed comprehension of the interactions between flavonoids and PBP2, highlighting rutin's exceptional antioxidant effects and strong affinity for the substrate binding site. The study's wider ramifications pertain to the pressing requirement for antiviral treatments in the context of the ongoing COVID-19 epidemic. Flavonoids have a strong affinity for binding to PBP2, indicating their potential as inhibitors to impair cell wall formation in N. gonorrhoeae. Ultimately, this study provides extensive knowledge on the interactions between proteins and ligands, the dynamics of the structure, and the ability of flavonoids to combat penicillin-resistant N. gonorrhoeae bacteria. The verified simulation outcomes establish a basis for creating potent inhibitors and medicinal therapies to combat infectious illnesses.

Keywords: phytochemicals, penicillin-binding protein 2, gonococcal infection, ligand-protein interaction, binding energy, neisseria gonorrhoeae FA19, neisseria gonorrhoeae FA6140, flavonoids

Procedia PDF Downloads 69

Authors: Umer Malik, David Armstrong, Mark Ashworth, Alex Dregan, Veline L'Esperance, Lucy McDonnell, Mariam Molokhia, Patrick White

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Introduction: The microbiota lining epithelial surfaces is thought to play an important role in many human physiological functions including defense against pathogens and modulation of immune response. The microbiota is susceptible to disruption from external influences such as exposure to antibiotic medication. It is thought that antibiotic-induced disruption of the microbiota could predispose to pathogen overgrowth and invasion. We hypothesized that antibiotic use would be associated with increased risk of future infections. We carried out a systematic review of evidence of associations between antibiotic use and subsequent risk of community-acquired infections. Methods: We conducted a review of the literature for observational studies assessing the association between antibiotic use and subsequent community-acquired infection. Eligible studies were published before April 29th, 2016. We searched MEDLINE, EMBASE, and Web of Science and screened titles and abstracts using a predefined search strategy. Infections caused by Clostridium difficile, drug-resistant organisms and fungal organisms were excluded as their association with prior antibiotic use has been examined in previous systematic reviews. Results: Eighteen out of 21,518 retrieved studies met the inclusion criteria. The association between past antibiotic exposure and subsequent increased risk of infection was reported in 16 studies, including one study on Campylobacter jejuni infection (Odds Ratio [OR] 3.3), two on typhoid fever (ORs 5.7 and 12.2), one on Staphylococcus aureus skin infection (OR 2.9), one on invasive pneumococcal disease (OR 1.57), one on recurrent furunculosis (OR 16.6), one on recurrent boils and abscesses (Risk ratio 1.4), one on upper respiratory tract infection (OR 2.3) and urinary tract infection (OR 1.1), one on invasive Haemophilus influenzae type b (Hib) infection (OR 1.51), one on infectious mastitis (OR 5.38), one on meningitis (OR 2.04) and five on Salmonella enteric infection (ORs 1.4, 1.59, 1.9, 2.3 and 3.8). The effect size in three studies on Salmonella enteric infection was of marginal statistical significance. A further two studies on Salmonella infection did not demonstrate a statistically significant association between prior antibiotic exposure and subsequent infection. Conclusion: We have found an association between past antibiotic exposure and subsequent risk of a diverse range of infections in the community setting. Our findings provide evidence to support the hypothesis that prior antibiotic usage may predispose to future infection risk, possibly through antibiotic-induced alteration of the microbiota. The findings add further weight to calls to minimize inappropriate antibiotic prescriptions.

Keywords: antibiotic, infection, risk factor, side effect

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Authors: Sami W. Tabsh

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The strength of reinforced concrete depends on the member dimensions and material properties. The properties of concrete and steel materials are not constant but random variables. The variability of concrete strength is due to batching errors, variations in mixing, cement quality uncertainties, differences in the degree of compaction and disparity in curing. Similarly, the variability of steel strength is attributed to the manufacturing process, rolling conditions, characteristics of base material, uncertainties in chemical composition, and the microstructure-property relationships. To account for such uncertainties, codes of practice for reinforced concrete design impose resistance factors to ensure structural reliability over the useful life of the structure. In this investigation, the effects of reductions in concrete and reinforcing steel strengths from the nominal values, beyond those accounted for in the structural design codes, on the structural reliability are assessed. The considered limit states are flexure, shear and axial compression based on the ACI 318-11 structural concrete building code. Structural safety is measured in terms of a reliability index. Probabilistic resistance and load models are compiled from the available literature. The study showed that there is a wide variation in the reliability index for reinforced concrete members designed for flexure, shear or axial compression, especially when the live-to-dead load ratio is low. Furthermore, variations in concrete strength have minor effect on the reliability of beams in flexure, moderate effect on the reliability of beams in shear, and sever effect on the reliability of columns in axial compression. On the other hand, changes in steel yield strength have great effect on the reliability of beams in flexure, moderate effect on the reliability of beams in shear, and mild effect on the reliability of columns in axial compression. Based on the outcome, it can be concluded that the reliability of beams is sensitive to changes in the yield strength of the steel reinforcement, whereas the reliability of columns is sensitive to variations in the concrete strength. Since the embedded target reliability in structural design codes results in lower structural safety in beams than in columns, large reductions in material strengths compromise the structural safety of beams much more than they affect columns.

Keywords: code, flexure, limit states, random variables, reinforced concrete, reliability, reliability index, shear, structural safety

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Authors: Ginpreet Kaur, Mohammad Yasir Usmani, Mohammed Kamil Khan

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Diabetes mellitus is a disease with a high global burden and results in significant morbidity and mortality. In India, the number of people suffering with diabetes is expected to rise from 19 to 57 million in 2025. At present, interest in herbal remedies is growing to reduce the side effects associated with conventional dosage form like oral hypoglycemic agents and insulin for the treatment of diabetes mellitus. Our aim was to investigate the antidiabetic activities of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats. Thus, the present study was undertaken to screen postprandial glucose excursion potential through α- glucosidase inhibitory activity (In Vitro) and effect of combinatorial extract of N. sativa & C. cassia in Streptozotocin induced type-I Diabetic Rats (In Vivo). In addition changes in body weight, plasma glucose, lipid profile and kidney profile were also determined. The IC50 values for both extract and Acarbose was calculated by extrapolation method. Combinatorial extract of N. sativa & C. cassia at different dosages (100 and 200 mg/kg orally) and Metformin (50 mg/kg orally) as the standard drug was administered for 28 days and then biochemical estimation, body weights and OGTT (Oral glucose tolerance test) were determined. Histopathological studies were also performed on kidney and pancreatic tissue. In In-Vitro the combinatorial extract shows much more inhibiting effect than the individual extracts. The results reveals that combinatorial extract of N. sativa & C. cassia has shown significant decrease in plasma glucose (p<0.0001), total cholesterol and LDL levels when compared with the STZ group The decreasing level of BUN and creatinine revealed the protection of N. sativa & C. cassia extracts against nephropathy associated with diabetes. Combination of N. sativa & C. cassia significantly improved glucose tolerance to exogenously administered glucose (2 g/kg) after 60, 90 and 120 min interval on OGTT in high dose streptozotocin induced diabetic rats compared with the untreated control group. Histopathological studies shown that treatment with N. sativa & C. cassia extract alone and in combination restored pancreatic tissue integrity and was able to regenerate the STZ damaged pancreatic β cells. Thus, the present study reveals that combination of N. sativa & C. cassia extract has significant α- glucosidase inhibitory activity and thus has great potential as a new source for diabetes treatment.

Keywords: lipid levels, OGTT, diabetes, herbs, glucosidase

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Authors: Badriah Alayidi, Emad Alyahya

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Background: Most people with Multiple Sclerosis (MS) report worsening balance as the condition progresses. Poor balance control is also well known to be a significant risk factor for both falling and fear of falling. The increased risk of falls with disease progression thus makes balance control an essential target of gait rehabilitation amongst people with MS. Intervention programs have developed various methods to improve balance control, and accumulating evidence suggests that exercise programs may help people with MS improve their balance. Among these methods, virtual reality (VR) is growing in popularity as a balance-training technique owing to its potential benefits, including better compliance and greater user happiness. However, it is not clear if a VR environment will induce different balance control mechanisms in MS as compared to healthy individuals or traditional environments. Therefore, this study aims to examine how individuals with MS control their balance in a VR setting. Methodology: The proposed study takes an empirical approach to estimate and determine the role of balance response in persons with MS using a VR environment. It will use primary data collected through patient observations, physiological and biomechanical evaluation of balance, and data analysis. Results: The preliminary systematic review and meta-analysis indicated that there was variability in terms of the outcome assessing balance response in people with MS. The preliminary results of these assessments have the potential to provide essential indicators of the progression of MS and contribute to the individualization of treatment and evaluation of the interventions’ effectiveness. The literature describes patients who have had the opportunity to experiment in VR settings and then used what they have learned in the real world, suggesting that this VR setting could be more appealing than conditional settings. The findings of the proposed study will be beneficial in estimating and determining the effect of VR on balance control in persons with MS. In previous studies, VR was shown to be an interesting approach to neurological rehabilitation, but more data are needed to support this approach in MS. Conclusions: The proposed study enables an assessment of balance and evaluations of a variety of physiological implications related to neural activity as well as biomechanical implications related to movement analysis.

Keywords: multiple sclerosis, virtual reality, postural control, balance

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Authors: Asinguza P. Allan

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The Advocacy for Better Health aims to equip citizens with enabling environment and systems to effectively advocate for strong action plans to improve health services. This is because the 2020 Government target for Uganda to transform into a middle income country will be achieved if investment is made in keeping the population healthy and productive. Citizen participation as an important foundation for change has been emphasized to gather data through participatory rural appraisal and inform evidence-based advocacy for recruitment and motivation of human resources. Citizens conduct problem ranking during advocacy forums on staffing levels and health worker absenteeism. Citizens prioritised inadequate number of midwives and absenteeism. On triangulation, health worker to population ratio in Uganda remains at 0.25/1,000 which is far below the World Health Organization (WHO) threshold of 2.3/1,000. Working with IntraHealth, the project advocated for recruitment of critical skilled staff (doctors and midwives) and scale up health workers motivation strategy to reduce Uganda’s Neonatal Mortality Rate of 22/1,000 and Maternal Mortality Ratio of 320/100,000. Government has committed to increase staffing to 80% by 2018 (10 districts have passed ordinances and revived use of duty rosters to address health worker absenteeism. On the other hand, the better health advocacy debate has been elevated with need to increase health sector budget allocations from 8% to 10%. The project has learnt that building a body of evidence from citizens enhances the advocacy agenda. Communities will further monitor government commitments to reduce Neonatal Mortality Rate and Maternal Mortality Ratio. The project has learnt that interface meeting between duty bearers and the community allows for immediate feedback and the process is a strong instrument for empowerment. It facilitates monitoring and performance evaluation of services, projects and government administrative units (like district assemblies) by the community members themselves. This, in turn, makes the human resources in health to be accountable, transparent and responsive to communities where they work. This, in turn, promotes human resource performance.

Keywords: advocacy, empowerment, evidence, human resources

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Authors: Atoui Oussama, Maazoun Azer, Belkassem Bachir, Pyl Lincy, Lecompte David

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For many decades, researchers have been focused on understanding the dynamic behavior of different structures and materials subjected to fragment impact or blast loads separately. The explosion mechanics, as well as the impact physics studies dealing with the numerical modeling of the response of protective structures under the synergistic effect of a blast wave and the impact of fragments, are quite limited in the literature. This article numerically evaluates the nonlinear dynamic behavior and damage mechanisms of Aluminum plates EN AW-1050A- H24 under different combined loading scenarios varied by the sequence of the applied loads using the commercial software LS-DYNA. For one hand, with respect to the terminal ballistic field investigations, a Lagrangian (LAG) formulation is used to evaluate the different failure modes of the target material in case of a fragment impact. On the other hand, with respect to the blast field analysis, an Arbitrary Lagrangian-Eulerian (ALE) formulation is considered to study the fluid-structure interaction (FSI) of the shock wave and the plate in case of a blast loading. Four different loading scenarios are considered: (1) only blast loading, (2) only fragment impact, (3) blast loading followed by a fragment impact and (4) a fragment impact followed by blast loading. From the numerical results, it was observed that when the impact load is applied to the plate prior to the blast load, it suffers more severe damage due to the hole enlargement phenomenon and the effects of crack propagation on the circumference of the damaged zone. Moreover, it was found that the hole from the fragment impact loading was enlarged to about three times in diameter as compared to the diameter of the projectile. The validation of the proposed computational model is based in part on previous experimental data obtained by the authors and in the other part on experimental data obtained from the literature. A good correspondence between the numerical and experimental results is found.

Keywords: computational analysis, combined loading, explosion mechanics, hole enlargement phenomenon, impact physics, synergistic effect, terminal ballistic

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Authors: Avyarthana Dey, Naren P. Rao, Arpitha Jacob, Chaitra V. Hiremath, Shivarama Varambally, Ganesan Venkatasubramanian, Rose Dawn Bharath, Bangalore N. Gangadhar

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Objective: Impaired facial emotion recognition is widely reported in schizophrenia. Neuropeptide oxytocin is known to modulate brain regions involved in facial emotion recognition, namely amygdala, in healthy volunteers. However, its effect on facial emotion recognition deficits seen in schizophrenia is not well explored. In this study, we examined the effect of intranasal OXT on processing facial emotions and its neural correlates in patients with schizophrenia. Method: 12 male patients (age= 31.08±7.61 years, education= 14.50±2.20 years) participated in this single-blind, counterbalanced functional magnetic resonance imaging (fMRI) study. All participants underwent three fMRI scans; one at baseline, one each after single dose 24IU intranasal OXT and intranasal placebo. The order of administration of OXT and placebo were counterbalanced and subject was blind to the drug administered. Participants performed a facial emotion recognition task presented in a block design with six alternating blocks of faces and shapes. The faces depicted happy, angry or fearful emotions. The images were preprocessed and analyzed using SPM 12. First level contrasts comparing recognition of emotions and shapes were modelled at individual subject level. A group level analysis was performed using the contrasts generated at the first level to compare the effects of intranasal OXT and placebo. The results were thresholded at uncorrected p < 0.001 with a cluster size of 6 voxels. Neuropeptide oxytocin is known to modulate brain regions involved in facial emotion recognition, namely amygdala, in healthy volunteers. Results: Compared to placebo, intranasal OXT attenuated activity in inferior temporal, fusiform and parahippocampal gyri (BA 20), premotor cortex (BA 6), middle frontal gyrus (BA 10) and anterior cingulate gyrus (BA 24) and enhanced activity in the middle occipital gyrus (BA 18), inferior occipital gyrus (BA 19), and superior temporal gyrus (BA 22). There were no significant differences between the conditions on the accuracy scores of emotion recognition between baseline (77.3±18.38), oxytocin (82.63 ± 10.92) or Placebo (76.62 ± 22.67). Conclusion: Our results provide further evidence to the modulatory effect of oxytocin in patients with schizophrenia. Single dose oxytocin resulted in significant changes in activity of brain regions involved in emotion processing. Future studies need to examine the effectiveness of long-term treatment with OXT for emotion recognition deficits in patients with schizophrenia.

Keywords: recognition, functional connectivity, oxytocin, schizophrenia, social cognition

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Authors: Samuel O. Alamu, Seong W. Lee, Blaise Kalmia, Marc J. Louise Caballes, Xuejun Qian

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The application of combustion technologies for thermal conversion of biomass and solid wastes to energy has been a major solution to the effective handling of wastes over a long period of time. Lab-scale biomass combustion systems have been observed to be economically viable and socially acceptable, but major concerns are the environmental impacts of the process and deviation of temperature distribution within the combustion chamber. Both high and low combustion chamber temperature may affect the overall combustion efficiency and gaseous emissions. Therefore, there is an urgent need to develop a control system which measures the deviations of chamber temperature from set target values, sends these deviations (which generates disturbances in the system) in the form of feedback signal (as input), and control operating conditions for correcting the errors. In this research study, major components of the feedback control system were determined, assembled, and tested. In addition, control algorithms were developed to actuate operating conditions (e.g., air velocity, fuel feeding rate) using ladder logic functions embedded in the Programmable Logic Controller (PLC). The developed control algorithm having chamber temperature as a feedback signal is integrated into the lab-scale swirling fluidized bed combustor (SFBC) to investigate the temperature distribution at different heights of the combustion chamber based on various operating conditions. The air blower rates and the fuel feeding rates obtained from automatic control operations were correlated with manual inputs. There was no observable difference in the correlated results, thus indicating that the written PLC program functions were adequate in designing the experimental study of the lab-scale SFBC. The experimental results were analyzed to study the effect of air velocity operating at 222-273 ft/min and fuel feeding rate of 60-90 rpm on the chamber temperature. The developed temperature-based feedback control system was shown to be adequate in controlling the airflow and the fuel feeding rate for the overall biomass combustion process as it helps to minimize the steady-state error.

Keywords: air flow, biomass combustion, feedback control signal, fuel feeding, ladder logic, programmable logic controller, temperature

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Authors: Amirul Adlan, Robert A McCulloch, Neil Jenkins, MIchael Parry, Jonathan Stevenson, Lee Jeys

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Background and Objectives: The current antibiotic prophylaxis for oncological patients is based upon evidence from primary arthroplasty despite significant differences in both patient group and procedure. The aim of this study was to compare the microbiology organisms responsible for PJI in patients who underwent two-stage revision for infected primary knee replacement with those of infected oncological endoprostheses of the lower limb in a single institution. This will subsequently guide decision making regarding antibiotic prophylaxis at primary implantation for oncological procedures and empirical antibiotics for infected revision procedures (where the infecting organism(s) are unknown). Patient and Methods: 118 patients were treated with two-stage revision surgery for infected knee arthroplasty and lower limb endoprostheses between 1999 and 2019. 74 patients had two-stage revision for PJI of knee arthroplasty, and 44 had two-stage revision of lower limb endoprostheses. There were 68 males and 50 females. The mean age for the knee arthroplasty cohort and lower limb endoprostheses cohort were 70.2 years (50-89) and 36.1 years (12-78), respectively (p<0.01). Patient host and extremity criteria were categorised according to the MSIS Host and Extremity Staging System. Patient microbiological culture, the incidence of polymicrobial infection and multi-drug resistance (MDR) were analysed and recorded. Results: Polymicrobial infection was reported in 16% (12 patients) from knee arthroplasty PJI and 14.5% (8 patients) in endoprostheses PJI (p=0.783). There was a significantly higher incidence of MDR in endoprostheses PJI, isolated in 36.4% of cultures, compared to knee arthroplasty PJI (17.2%) (p=0.01). Gram-positive organisms were isolated in more than 80% of cultures from both cohorts. Coagulase-negative Staphylococcus (CoNS) was the commonest gram-positive organism, and Escherichia coli was the commonest Gram-negative organism in both groups. According to the MSIS staging system, the host and extremity grade of knee arthroplasty PJI cohort were significantly better than endoprostheses PJI(p<0.05). Conclusion: Empirical antibiotic management of PJI in orthopaedic oncology is based upon PJI in arthroplasty despite differences in both host and microbiology. Our results show a significant increase in MDR pathogens within the oncological group despite CoNS being the most common infective organism in both groups. Endoprosthetic patients presented with poorer host and extremity criteria. These factors should be considered when managing this complex patient group, emphasising the importance of broad-spectrum antibiotic prophylaxis and preoperative sampling to ensure appropriate perioperative antibiotic cover.

Keywords: microbiology, periprosthetic Joint infection, knee arthroplasty, endoprostheses

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Authors: Nazish Badar

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In early 2009, Pandemic type A (H1N1) Influenza virus emerged globally. Since then, it has continued circulation causing considerable morbidity and mortality. The purpose of this study was to evaluate the evolutionary changes in Influenza A (H1N1) pdm09 viruses from 2009-15 and their relevance with the current vaccine viruses. Methods: Respiratory specimens were collected with influenza-like illness and Severe Acute Respiratory Illness. Samples were processed according to CDC protocol. Sequencing and phylogenetic analysis of Haemagglutinin (HA) and neuraminidase (NA) genes was carried out comparing representative isolates from Pakistan viruses. Results: Between Jan2009 - Feb 2016, 1870 (13.2%) samples were positive for influenza A out of 14086. During the pandemic period (2009–10), Influenza A/ H1N1pdm 09 was the dominant strain with 366 (45%) of total influenza positives. In the post-pandemic period (2011–2016), a total of 1066 (59.6%) cases were positive Influenza A/ H1N1pdm 09 with co-circulation of different Influenza A subtypes. Overall, the Pakistan A(H1N1) pdm09 viruses grouped in two genetic clades. Influenza A(H1N1)pdm09 viruses only ascribed to Clade 7 during the pandemic period whereas viruses belong to clade 7 (2011) and clade 6B (2015) during the post-pandemic years. Amino acid analysis of the HA gene revealed mutations at positions S220T, I338V and P100S specially associated with outbreaks in all the analyzed strains. Sequence analyses of post-pandemic A(H1N1)pdm09 viruses showed additional substitutions at antigenic sites; S179N,K180Q (SA), D185N, D239G (CA), S202A (SB) and at receptor binding sites; A13T, S200P when compared with pandemic period. Substitution at Genetic markers; A273T (69%), S200P/T (15%) and D239G (7.6%) associated with severity and E391K (69%) associated with virulence was identified in viruses isolated during 2015. Analysis of NA gene revealed outbreak markers; V106I (23%) among pandemic and N248D (100%) during post-pandemic Pakistan viruses. Additional N-Glycosylation site; HA S179N (23%), NA I23T(7.6%) and N44S (77%) in place of N386K(77%) were only found in post-pandemic viruses. All isolates showed histidine (H) at position 275 in NA indicating sensitivity to neuraminidase inhibitors. Conclusion: This study shows that the Influenza A(H1N1)pdm09 viruses from Pakistan clustered into two genetic clades, with co-circulation of some variants. Certain key substitutions in the receptor binding site and few changes indicative of virulence were also detected in post-pandemic strains. Therefore, it is imperative to continue monitoring of the viruses for early identification of potential variants of high virulence or emergence of drug-resistant variants.

Keywords: Influenza A (H1N1) pdm09, evolutionary analysis, post pandemic period, Pakistan

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Authors: Hind Alshoubaki

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The world is now confronting a widespread urban phenomenon: refugee camps, which have mostly been established in ‘rushing mode,’ pointing toward affording temporary settlements for refugees that provide them with minimum levels of safety, security and protection from harsh weather conditions within a very short time period. In fact, those emergency settlements are transforming into permanent ones since time is a decisive factor in terms of construction and camps’ age. These play an essential role in transforming their temporary character into a permanent one that generates deep modifications to the city’s territorial structure, shaping a new identity and creating a contentious change in the city’s form and history. To achieve a better understanding for the transformation of refugee camps, this study is based on a mixed-methods approach: the qualitative approach explores different refugee camps and analyzes their transformation process in terms of population density and the changes to the city’s territorial structure and urban features. The quantitative approach employs a statistical regression analysis as a reliable prediction of refugees’ satisfaction within the Zaatari camp in order to predict its future transformation. Obviously, refugees’ perceptions of their current conditions will affect their satisfaction, which plays an essential role in transforming emergency settlements into permanent cities over time. The test basically discusses five main themes: the access and readiness of schools, the dispersion of clinics and shopping centers; the camp infrastructure, the construction materials, and the street networks. The statistical analysis showed that Syrian refugees were not satisfied with their current conditions inside the Zaatari refugee camp and that they had started implementing changes according to their needs, desires, and aspirations because they are conscious about the fact of their prolonged stay in this settlement. Also, the case study analyses showed that neglecting the fact that construction takes time leads settlements being created with below-minimum standards that are deteriorating and creating ‘slums,’ which lead to increased crime rates, suicide, drug use and diseases and deeply affect cities’ urban tissues. For this reason, recognizing the ‘temporary-eternal’ character of those settlements is the fundamental concept to consider refugee camps from the beginning as definite permanent cities. This is the key factor to minimize the trauma of displacement on both refugees and the hosting countries. Since providing emergency settlements within a short time period does not mean using temporary materials, having a provisional character or creating ‘makeshift cities.’

Keywords: refugee, refugee camp, temporary, Zaatari

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Authors: Fatimah AlSaiari

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In recent years, newspapers in the United Kingdom have been no longer just a means of sharing news about what happens in the world; they are also used to influence target readers by having them become more up-to-date, well-informed, entertained, exasperated, delighted, and infuriated. To achieve these objectives and maintain influence on public opinion, journalists use a particular language in which they can convey emotions and opinions, organize their discourse, and establish solidarity with their audience. This type of language has been widely analyzed under different labels, such as evaluation, appraisal, and stance. There is a considerable amount of linguistic and non-linguistic research devoted to analyzing this type of interpersonal language in journalistic discourse, and most of these studies were carried out to challenge the traditional assumptions of the objectivity and impartiality of news reporting. However, very little research has been undertaken on evaluative language in newspaper institutional editorials, and there is hardly any systematic or exhaustive analysis of this type of language in British tabloid and broadsheet newspapers. This study will attempt to provide new insights into the nature of authorial and non-authorial evaluation in leading articles in popular and quality British newspapers, along with their targets, sources, and discourse functions. The study will also attempt to develop a framework of evaluation that can be applied to evaluative lexical items in newspaper opinion texts. The framework is both theory-driven (i.e., it builds on and modifies previous frameworks of evaluation such as appraisal theory and parameter-based approach) and data-driven (i.e., it elicits the evaluative categories from the analysis of the corpus, which helps in the development of the current framework). To achieve this aim, a corpus of 140 leading articles were selected. The findings revealed that the tabloids tended to express their stance through explicitness, dramatization, frequent reference to social actors’ emotions and beliefs, and exaggeration in negativity, while the broadsheets preferred to express their stance through mitigation ambiguity and implicitness. conceptual themes and propositions were more preferable targets for expressing stance in the broadsheets while human behavior and characters were preferable targets for the tabloids.

Keywords: appraisal theory, evaluative language, British newspapers, broadsheets & tabloids, evaluative adjectives

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Authors: Nihal Kartaltepe Behram, Göksel Ataman, Dila Okçu

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With the development of foreign direct investments, the social, cultural, political and economic interactions between countries and institutions have become visible and they have become determining factors for the strategic structuring and market goals. In this context the purpose of this study is to investigate the effects of cultural distance and institutions on foreign direct investment choices in terms of location and investment model. For international establishments, the concept of culture, as well as the concept of cultural distance, is taken specifically into consideration, especially in the selection of methods for entering the market. In the researches and empirical studies conducted, a direct relationship between cultural distance and foreign direct investments is set and institutions and effective variable factors are examined at the level of defining the investment types. When the detailed calculation strategies and empirical researches and studies are taken into consideration, the most common methods for determining the direct investment model, considering the cultural distances, are full-ownership enterprises and joint ventures. Also, when all of the factors affecting the investments are taken into consideration, it was seen that the effect of institutions such as Government Intervention, Intellectual Property Rights, Corruption and Contract Enforcements is very important. Furthermore agglomeration is more intense and effective on the investment, compared to other factors. China has been selected as the target country, due to its effectiveness in world economy and its contributions to developing countries, which has commercial relationships with. Qualitative research methods are used for this study conducted, to measure the effects of determinative variable factors in the hypotheses of study, on the direct foreign investors and to evaluate the findings. In this study in-depth interview is used as a data collection method and the data analysis is made through descriptive analysis. Foreign Direct Investments are so reactive to institutions and cultural distance is identified by all interviews and analysis. On the other hand, agglomeration is the most strong determiner factor on foreign direct investors in Chinese Market. The reason of this factors, which comprise the sectorial aggregate, are not the strongest factors as agglomeration that the most important finding. We expect that this study became a beneficial guideline for developed and developing countries and local and national institutions’ strategic plans.

Keywords: China, cultural distance, Foreign Direct Investments, institutions

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Authors: Gaurav Vaidya, N. R. Mandal

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UN Summit, 2000 had resolved to provide access to sanitation to whole humanity as part of ‘Millennium Development Goals -2015’. However, more than one third of world’s population still did not have the access to basic sanitation facilities by 2015. Therefore, it will be a gigantic challenge to achieve goal-6 of ‘UN Sustainable Development Goal’ to ensure availability and sustainable management of sanitation for all by the year 2030. Countries attempt to find out own ways of meeting this challenge of providing access to safe sanitation and as part of monitoring the actions have prepared varied types of ‘performance assessment frameworks (PAF)’. India introduced Service Level Benchmarking (SLB) in 2010 to set targets and achieve the goals of NUSP. Further, a method of reviewing performance was introduced as ‘Swachh Sarvekshan’ (Cleanliness Surveys) in 2016 and in 2017 guidelines for the same was revised. This study, as a first step, reviews the documents in use in India with a conclusion that the frameworks adopted are based on target setting, financial allocation and performance in achieving the targets set. However, it does not focus upon sanitation needs holistically i.e., areas and aspects not targeted through projects are not covered in the performance assessment. In this context, as a second step, this study reviews literature available on performance assessment frameworks for urban sanitation in selected other countries and compares the same with that in India. The outcome of the comparative review resulted in identification of unaddressed aspects as well as inadequacy of parameters in Indian context. Thirdly, in an attempt to restructure the performance assessment process and develop an index in urban sanitation, researches done in other urban services such as health and education were studied focusing on methods of measuring under-performance. As a fourth step, a tentative modified framework is suggested with the help of understanding drawn from above for urban sanitation using stages of Urban Sanitation Service Chain Management (SSCM) and modified set of parameters drawn from the literature review in the first and second steps. This paper reviews existing literature on SSCM procedures, Performance Index in sanitation and other urban services and identifies a tentative list of parameters and a framework for measuring under-performance in sanitation services. This may aid in preparation of a Service Delivery Under-performance Index (SDUI) in future.

Keywords: assessment, performance, sanitation, services

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Authors: Radwa Mabrook

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Virtual Reality (VR) content creation is a complex and an expensive process, which requires multi-disciplinary teams of content creators. Grant schemes from technology companies help media organisations to explore the VR potential in journalism and factual storytelling. Media organisations try to do as much as they can in-house, but they may outsource due to time constraints and skill availability. Journalists, game developers, sound designers and creative artists work together and bring in new cultures of work. This study explores the collaborative experimental nature of VR content creation, through tracing every actor involved in the process and examining their perceptions of the VR work. The study builds on Actor Network Theory (ANT), which decomposes phenomena into their basic elements and traces the interrelations among them. Therefore, the researcher conducted 22 semi-structured interviews with VR content creators between November 2017 and April 2018. Purposive and snowball sampling techniques allowed the researcher to recruit fact-based VR content creators from production studios and media organisations, as well as freelancers. Interviews lasted up to three hours, and they were a mix of Skype calls and in-person interviews. Participants consented for their interviews to be recorded, and for their names to be revealed in the study. The researcher coded interviews’ transcripts in Nvivo software, looking for key themes that correspond with the research questions. The study revealed that VR content creators must be adaptive to change, open to learn and comfortable with mistakes. The VR content creation process is very iterative because VR has no established work flow or visual grammar. Multi-disciplinary VR team members often speak different languages making it hard to communicate. However, adaptive content creators perceive VR work as a fun experience and an opportunity to learn. The traditional sense of competition and the strive for information exclusivity are now replaced by a strong drive for knowledge sharing. VR content creators are open to share their methods of work and their experiences. They target to build a collaborative network that aims to harness VR technology for journalism and factual storytelling. Indeed, VR is instilling collaborative and experimental cultures in journalism.

Keywords: collaborative culture, content creation, experimental culture, virtual reality

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Authors: Shaimaa Eltanani, Thangal Yumnamcha, Ahmed S. Ibrahim

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Purpose: Mitochondria dysfunction is central to breaking the barrier integrity of retinal endothelial cells (RECs) in various blinding eye diseases such as diabetic retinopathy and retinopathy of prematurity. Therefore, we aimed to dissect the role of different mitochondrial components, specifically, those of oxidative phosphorylation (OxPhos), in maintaining the barrier function of RECs. Methods: Electric cell-substrate impedance sensing (ECIS) technology was used to assess in real-time the role of different mitochondrial components in the total impedance (Z) of human RECs (HRECs) and its components; the capacitance (C) and the total resistance (R). HRECs were treated with specific mitochondrial inhibitors that target different steps in OxPhos: Rotenone for complex I; Oligomycin for ATP synthase; and FCCP for uncoupling OxPhos. Furthermore, data were modeled to investigate the effects of these inhibitors on the three parameters that govern the total resistance of cells: cell-cell interactions (Rb), cell-matrix interactions (α), and cell membrane permeability (Cm). Results: Rotenone (1 µM) produced the greatest reduction in the Z, followed by FCCP (1 µM), whereas no reduction in the Z was observed after the treatment with Oligomycin (1 µM). Following this further, we deconvoluted the effect of these inhibitors on Rb, α, and Cm. Firstly, rotenone (1 µM) completely abolished the resistance contribution of Rb, as the Rb became zero immediately after the treatment. Secondly, FCCP (1 µM) eliminated the resistance contribution of Rb only after 2.5 hours and increased Cm without considerable effect on α. Lastly, Oligomycin had the lowest impact among these inhibitors on Rb, which became similar to the control group at the end of the experiment without noticeable effects on Cm or α. Conclusion: These results demonstrate differential roles for complex I, complex V, and coupling of OxPhos in maintaining the barrier functionality of HRECs, in which complex I being the most important component in regulating the barrier functionality and the spreading behavior of HRECs. Such differences can be used in investigating gene expression as well as for screening selective agents that improve the functionality of complex I to be used in the therapeutic approach for treating REC-related retinal diseases.

Keywords: human retinal endothelial cells (hrecs), rotenone, oligomycin, fccp, oxidative phosphorylation, oxphos, capacitance, impedance, ecis modeling, rb resistance, α resistance, and barrier integrity

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Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: Wan-Ting Liao, Angela K. Tzeng

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Empathy has been an important issue in psychology, education, as well as cognitive neuroscience. Empathy has two major components: cognitive and emotional. Cognitive component refers to the ability to understand others’ perspectives, thoughts, and actions, whereas emotional component refers to understand how others feel. Empathy can be induced, attitude can then be changed, and with enough attitude change, helping behavior can occur. This finding leads us to two questions: is attitude change really necessary for prosocial behavior? And, what roles cognitive and affective empathy play? For the second question, participants with different psychopathic personality (PP) traits are critical because high PP people were found to suffer only affective empathy deficit. Their cognitive empathy shows no significant difference from the control group. 132 college students voluntarily participated in the current three-stage study. Stage 1 was to collect basic information including Interpersonal Reactivity Index (IRI), Psychopathic Personality Inventory-Revised (PPI-R), Attitude Scale, Visual Analogue Scale (VAS), and demographic data. Stage two was for empathy induction with three controversial scenarios, namely domestic violence, depression with a suicide attempt, and an ex-offender. Participants read all three stories and then rewrite the stories by one of two perspectives (empathetic vs. objective). They would then complete the VAS and Attitude Scale one more time for their post-attitude and emotional status. Three IVs were introduced for data analysis: PP (High vs. Low), Responsibility (whether or not the character is responsible for what happened), and Perspective-taking (Empathic vs. Objective). Stage 3 was for the action. Participants were instructed to freely use the 17 tokens they received as donations. They were debriefed and interviewed at the end of the experiment. The major findings were people with higher empathy tend to take more action in helping. Attitude change is not necessary for prosocial behavior. The controversy of the scenarios and how familiar participants are towards target groups play very important roles. Finally, people with high PP tend to show more public prosocial behavior due to their affective empathy deficit. Pre-existing value and belief as well as recent dramatic social events seem to have a big impact and possibly reduce the effect of the independent variables (IV) in our paradigm.

Keywords: empathy, cognitive, emotional, psychopathy

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Authors: Devyani Shete, Sudeep Rai

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Background: The COVID-19 pandemic has caused one of the highest disruptions to the NHS (National Health Service), especially to the fundamental cervical cancer screening service. To prioritize screening response effectively, it is vital to understand the underlying disease risks amongst groups of women who are less likely to resume their screening/follow up at General Practices. The current government target is to have>=80% of women have an adequate test within the previous 3.5 years (ages 25-49) or 5.5 years (ages 50-64). Aims/Objectives: To increase the number of eligible people aged 25-49 attending cervical screening by 5% at Lakeside Healthcare (a General Practice in Corby). Methods: An online survey was posted on the Lakeside Healthcare website to find out what the barriers towards cervical screening were. It was apparent that patients needed more information catered to their responses. 6 informational videos and a “Cervical Screening Guide” were created for Lakeside patients about cervical screening, which were posted on the Healthcare website. Lakeside also started sending reminder texts to those eligible, with a link to a booking form. Results: On 18th January 2022, 69.7% of patients aged 25-49 years (7207) had an adequate cervical screening test in the last 3.5 years. There were 80 total responders to the online survey. In response to “which of the following are reasons why you have not attended screening”, 30% ticked “I kept putting it off/did not get around to it,” and 13% ticked “I was worried it would be painful or daunting.” In response to “which of the following would make you more likely to book an appointment”, 23% ticked “More detailed explanations of what the risks are if I don’t have screening,” and 20% ticked “I would like more information about the test and what the smear entails.” 10% of responders had previous trauma, whilst 28% of responders said the pandemic had impacted them getting a smear. Survey results were used to carry out interventions to increase smear uptake. On 23rdMarch 2022 (after a 2-month period), 75%of patients aged 25-49 (7119) attended the screening, which was a 5.3% increase from January. Discussion/Conclusion: The survey was vital in carrying out the exact interventions that were required for patients to increase screening uptake, as it is important to know what the populations’ needs are in order to create personalized invitations. This helps to optimise response during a pandemic. A HPV self-sample kit at home could be a popular method of dealing with further outbreaks.

Keywords: gynaecology, cervical screening, public health, COVID-19

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Authors: Daphne Sobolev, Niklas Voege

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During the last three decades, consumer ethics perceptions have attracted the attention of a large number of researchers. Nevertheless, little is known about the effect of the cognitive and situational contexts of the decision on ethics judgments. In this paper, the interrelationship between consumers’ ethics perceptions, legality evaluations and mind-sets are explored. Legality evaluations represent the cognitive context of the ethical judgments, whereas mind-sets represent their situational context. Drawing on moral development theories and priming theories, it is hypothesized that both factors are significantly related to consumer ethics perceptions. To test this hypothesis, 289 participants were allocated to three mind-set experimental conditions and a control group. Participants in the mind-set conditions were primed for aggressiveness, politeness or awareness to the negative legal consequences of breaking the law. Mind-sets were induced using a sentence-unscrambling task, in which target words were included. Ethics and legality judgments were assessed using consumer ethics and internet ethics questionnaires. All participants were asked to rate the ethicality and legality of consumer actions described in the questionnaires. The results showed that consumer ethics and legality perceptions were significantly correlated. Moreover, including legality evaluations as a variable in ethics judgment models increased the predictive power of the models. In addition, inducing aggressiveness in participants reduced their sensitivity to ethical issues; priming awareness to negative legal consequences increased their sensitivity to ethics when uncertainty about the legality of the judged scenario was high. Furthermore, the correlation between ethics and legality judgments was significant overall mind-set conditions. However, the results revealed conflicts between ethics and legality perceptions: consumers considered 10%-14% of the presented behaviors unethical and legal, or ethical and illegal. In 10-23% of the questions, participants indicated that they did not know whether the described action was legal or not. In addition, an asymmetry between the effects of aggressiveness and politeness priming was found. The results show that the legality judgments and mind-sets interact with consumer ethics perceptions. Thus, they portray consumer ethical judgments as dynamical processes which are inseparable from other cognitive processes and situational variables. They highlight that legal and ethical education, as well as adequate situational cues at the service place, could have a positive effect on consumer ethics perceptions. Theoretical contribution is discussed.

Keywords: consumer ethics, legality judgments, mind-set, priming, aggressiveness

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Authors: Einat E. Peles, Shaul Schreiber, Miriam Adelson

Abstract:

Background: Since established more than 50 years ago, methadone maintenance treatment (MMT) is the most effective treatment for opioid addiction, a chronic relapsing brain disorder that became an epidemic in western societies. Treatment includes daily individual optimal medication methadone dose (a long acting mu opioid receptor full agonist), accompanied with psychosocial therapy. It is well established that the longer retention in treatment the better outcome and survival occur. It reduces the likelihood to infectious diseases and overdose death that associated with drug injecting, enhanced social rehabilitation and eliminate criminal activity, and lead to healthy productive life. Aim: To evaluate predictors for long term retention in treatment we analyzed our prospective follow up of a major MMT clinic affiliated to a big tertiary medical center. Population Methods: Between June 25, 1993, and June 24, 2016, all 889 patients ( ≥ 18y) who ever admitted to the clinic were prospectively followed-up until May 2017. Duration in treatment from the first admission until the patient quit treatment or until the end of follow-up (24 years) was taken for calculating cumulative retention in treatment using survival analyses (Kaplan Meier) with log-rank and Cox regression for multivariate analyses. Results: Of the 889 patients, 25.2% were females who admitted to treatment at younger age (35.0 ± 7.9 vs. 40.6 ± 9.8, p < .0005), but started opioid usage at same age (22.3 ± 6.9). In addition to opioid use, on admission to MMT 58.5% had positive urine for benzodiazepines, 25% to cocaine, 12.4% to cannabis and 6.9% to amphetamines. Hepatitis C antibody tested positive in 55%, and HIV in 7.8% of the patients and 40%. Of all patients, 75.7% stayed at least one year in treatment, and of them, 67.7% stopped opioid usage (based on urine tests), and a net reduction observed in all other substance abuse (proportion of those who stopped minus proportion of those who have started). Long term retention up to 24 years was 8.0 years (95% Confidence Interval (CI) 7.4-8.6). Predictors for longer retention in treatment (Cox regression) were being older on admission ( ≥ 30y) Odds Ratio (OR) =1.4 (CI 1.1-1.8), not abusing opioids after one year OR=1.8 (CI 1.5-2.1), not abusing benzodiazepine after one year OR=1.7 (CI 1.4-2.1) and treating with methadone dose ≥ 100mg/day OR =1.8 (CI 1.5-2.3). Conclusions: Treating and following patients over 24 years indicate success of two main outcomes, high rate of retention after one year (75.7%) and high proportion of opiate abuse cessation (67.7%). As expected, longer cumulative retention was associated with patients treated with high adequate methadone dose that successfully result in opioid cessation. Based on these findings, in order to reduce morbidity and mortality, we find the establishment of more MMT clinics within a general hospital, a most urgent necessity.

Keywords: methadone maintenance treatment, epidemic, opioids, retention

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