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Hypothesis testing is a valuable method used to investigate ideas and test predictions arising from theories based on available data. In the context of critical system architecture, there is a need to effectively utilize hypothesis testing to identify faulty paths and improve system safety. This research aims to propose guidelines and best practices for presenting hypothesis testing in critical system architecture. The problem addressed in this study is the underutilization of hypothesis testing in life-critical system methods, resulting in a lack of identification of faulty paths. To address this challenge, we propose an enhanced pathway analysis technique that integrates error-derived information from a system's architectural description, thereby augmenting traditional hypothesis testing methods. By investigating various paths, we aim to identify false positive and false negative errors in life-critical system architecture. Furthermore, the proposed method is validated based on specific validation criteria for each step such as system boundary, assumption, content/architecture, and traceability validations. Also, the method is evaluated based on our claims. The results of our research highlight the significance of tracing errors in early system knowledge. By leveraging the augmented hypothesis testing method, we are able to identify hazards, safety constraints, and specific causes of unsafe actions more effectively. The findings emphasize the importance of integrating early design knowledge into hypothesis testing for enhanced hazard identification and improved system safety. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a major public health problem in Afghanistan, but experience in implementing effective strategies to prevent and control TB in urban areas and conflict zones is limited. This study shares programmatic experience in implementing DOTS in the large city of Kabul. We analyzed data from the 2009-2015 reports of the National TB Program (NTP) for Kabul City and calculated treatment outcomes and progress in case notification using rates, ratios, and confidence interval. Urban DOTS was implemented by the NTP in partnership with United States Agency for International Development (USAID)-funded TB projects, the World Health Organization (WHO), and the private sector. Between 2009 and 2015, the number of DOTS-providing centers in Kabul increased from 22 to 85. In total, 24,619 TB patients were enrolled in TB treatment during this period. The case notification rate for all forms of TB increased from 59 per 100,000 population to 125 per 100,000. The case notification rate per 100,000 population for sputum-smear-positive TB increased from 25 to 33. The treatment success rate for all forms of TB increased from 31% to 67% and from 47% to 77% for sputum-smear-positive TB cases. The treatment success rate for private health facilities increased from 52% in 2010 to 80% in 2015. In 2013, contact screening was introduced, and the TB yield was 723 per 100,000-more than two times higher than the estimated national prevalence of 340 per 100,000. Contact screening contributed to identifying 2,509 child contacts of people with TB, and 76% of those children received isoniazid preventive therapy. The comprehensive urban DOTS program significantly improved service accessibility, TB case finding, and treatment outcomes in Kabul. Public- and private-sector involvement also improved treatment outcomes; however, the treatment success rate remains higher in private health facilities. While the treatment success rate increased significantly, it remains lower than the national average, and more efforts are needed to improve treatment outcomes in Kabul. We recommend that the urban DOTS approach be replicated in other countries and cities in Afghanistan with settings similar to Kabul.

Hypothesis testing is a valuable method used to investigate ideas and test predictions arising from theories based on available data. In the context of critical system architecture, there is a need to effectively utilize hypothesis testing to identify faulty paths and improve system safety. This research aims to propose guidelines and best practices for presenting hypothesis testing in critical system architecture. The problem addressed in this study is the underutilization of hypothesis testing in life-critical system methods, resulting in a lack of identification of faulty paths. To address this challenge, we propose an enhanced pathway analysis technique that integrates error-derived information from a system's architectural description, thereby augmenting traditional hypothesis testing methods. By investigating various paths, we aim to identify false positive and false negative errors in life-critical system architecture. Furthermore, the proposed method is validated based on specific validation criteria for each step such as system boundary, assumption, content/architecture, and traceability validations. Also, the method is evaluated based on our claims. The results of our research highlight the significance of tracing errors in early system knowledge. By leveraging the augmented hypothesis testing method, we are able to identify hazards, safety constraints, and specific causes of unsafe actions more effectively. The findings emphasize the importance of integrating early design knowledge into hypothesis testing for enhanced hazard identification and improved system safety.

The oxytocin (Oxt) and vasopressin (Avp) magnocellular neurons (MCNs) in the hypothalamus are the only neuronal phenotypes that are present in the supraoptic nucleus (SON), and are characterized by their robust and selective expression of either the Oxt or Avp genes. In this paper, we take advantage of the differential expression of these neuropeptide genes to identify and isolate these two individual phenotypes from the rat SON by laser capture microdissection (LCM), and to analyze the differential expression of several of their transcription factor mRNAs by qRT-PCR. We identify these neuronal phenotypes by stereotaxically injecting recombinant Adeno-Associated Viral (rAAV) vectors which contain cell-type specific Oxt or Avp promoters that drive expression of EGFP selectively in either the Oxt or Avp MCNs into the SON. The fluorescent MCNs are then dissected by LCM using a novel Cap Road Map protocol described in this paper, and the purified MCNs are extracted for their RNAs. qRT-PCR of these RNAs show that some transcription factors (RORA and c-jun) are differentially expressed in the Oxt and Avp MCNs.

Conventional banks are 'indirectly' allowed to take more risk under the shadow of sovereign guarantees. Banks commit moral hazards as any major banking crisis will be 'cushioned' by deposit insurance and bailed out using the taxpayer's money. This study offers an alternative explanation for the determinants of banks' credit risk, particularly those from the Islamic regions. Although conventional banks and Islamic banks may share state and social cushioning systems, Islamic banks are strictly prohibited by moral and religious principles from gambling with depositors' funds, even if there is a cushion available to bail them out. However, banks belonging to collective societies, such as those in the MENA area, may be inclined to take more risks due to the perception of having a larger safety net to protect them in the event of failure. We analyse these theoretical intersections by utilising a dataset consisting of 320 banks from 20 countries, covering the time span from 2006 to 2021. Our analysis employs a combination of Ordinary Least Squares (OLS), Fixed Effects (FE), and 2-step System-GMM methodologies. Our analysis reveals that Islamic banks are less exposed to credit risk compared to conventional banks. We contend that the stricter ethical and moral ground and multi-layer monitoring system amid protracted geopolitical and post-pandemic crises impacting Islamic countries contribute to the lower credit risk. We examine the consequences for credit and liquidity management in Islamic banks and the risk management strategies employed by Islamic banks, which can serve as a valuable reference for other banks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abdeljawad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Community-based health interventions often demonstrate efficacy in clinical trial settings but fail to be implemented in the real-world. We sought to identify the key operational and contextual elements of the Los Angeles Barbershop Blood Pressure Study (LABBPS), an objectively successful community-based health intervention primed for real-world implementation. LABBPS was a cluster randomized control trial that paired the barbers of Black-owned barbershops with clinical pharmacists to manage uncontrolled hypertension in Black male patrons, demonstrating a substantial 21.6 mmHg reduction in systolic blood pressure. Despite this success, the LABBPS intervention has not expanded beyond the original clinical trial setting. The aim of this study was to determine the facilitating and limiting factors to expansion of the LABBPS intervention., Methods: We undertook a qualitative assessment of semi-structured interviews with study participants performed after trial completion. Interviews included a total of 31 participants including 20 (6%) of the 319 LABBPS program participants ("patrons"), 10 (19%) barbers, and one (50%) clinical pharmacist. The semi-structured interviews were focused on perceptions of the medical system, study intervention, and influence of social factors on health., Results: Several common themes emerged from thematic analysis of interview responses including: importance of care provided in a convenient and safe environment, individual responsibility for health and health-related behaviors, and engagement of trusted community members. In particular, patrons reported that receiving the intervention from their barber in a familiar environment positively influenced the formation of relationships with clinical pharmacists around shared efforts to improve medication adherence and healthy habits. All interviewee groups identified the trust diad, comprising the familiar environment and respected community member, as instrumental in increasing health-related behaviors to a degree not usually achieved by traditional healthcare providers., Discussion: In conclusion, participants of an objectively successful community-based intervention trial consistently identified key features that could facilitate wider implementation and efficacy: social trust relationships, soliciting insights of trust bearers, and consistent engagement in a familiar community setting. These findings can help to inform the design and operations of future community-based studies and programs aiming to achieve a broad and sustainable impact., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kohrman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Brown spot caused by Bipolaris oryzae is a major damaging fungal disease of rice which can decrease the yield and value of produce due to grain discoloration. The objectives of the current study were to investigate and understand the biochemical indices of brown spot disease resistance in rice. A total of 108 genotypes (mutant and hybrid) along with Super Basmati and parent RICF-160 were evaluated against brown spot disease. The genotypes exhibiting resistant and susceptible responses to brown spot disease according to the IRRI standard disease rating scale were screened and selected. To study the biochemical response mechanism, forty five selected genotypes along with Super Basmati and RICF-160 were analyzed using the biochemical markers. The physiological and biochemical analysis provided valuable insights and confirmed the resistance of rice hybrids and mutants against brown spot disease. Positive correlations were observed among stress bio-markers and disease response. Rice genotypes i.e. Mu-AS-8, Mu-AS-19, Mu-AS-20 and Mu-AS-35 exhibited moderate resistant response while Hy-AS-92, Hy-AS-98, Hy-AS-99, Hy-AS-101, Hy-AS-102 and Hy-AS-107 showed resistant response to brown spot disease. Brown spot resistant rice genotypes had lesser values of malondialdehyde and total oxidant status and higher antioxidant activities i.e. superoxide dismutase, peroxidase, total phenolic content and lycopene. The selected resistant rice genotypes had resistance capacity against Bipolaris oryzae stress. In conclusion, identified resistant mutants i.e. Mu-AS-8, Mu-AS-19, Mu-AS-20 and Mu-AS-35 and hybrids i.e. Hy-AS-92, Hy-AS-98, Hy-AS-99, Hy-AS-101, Hy-AS-102 and Hy-AS-107 could be used in rice breeding program to achieve sustainable rice production by coping the emerging challenge of brown spot disease under variable climate conditions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shamshad et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The prevalence of multimorbidity in patients with acute myocardial infarction (AMI) is increasing. It is unclear whether comorbidities cluster into distinct phenogroups and whether are associated with clinical trajectories., Methods: Survey-weighted analysis of the United States Nationwide Inpatient Sample (NIS) for patients admitted with a primary diagnosis of AMI in 2018. In-hospital outcomes included mortality, stroke, bleeding, and coronary revascularisation. Latent class analysis of 21 chronic conditions was used to identify comorbidity classes. Multivariable logistic and linear regressions were fitted for associations between comorbidity classes and outcomes., Results: Among 416,655 AMI admissions included in the analysis, mean (±SD) age was 67 (±13) years, 38% were females, and 76% White ethnicity. Overall, hypertension, coronary heart disease (CHD), dyslipidaemia, and diabetes were common comorbidities, but each of the identified five classes (C) included ≥1 predominant comorbidities defining distinct phenogroups: cancer/coagulopathy/liver disease class (C1); least burdened (C2); CHD/dyslipidaemia (largest/referent group, (C3)); pulmonary/valvular/peripheral vascular disease (C4); diabetes/kidney disease/heart failure class (C5). Odds ratio (95% confidence interval [CI]) for mortality ranged between 2.11 (1.89-2.37) in C2 to 5.57 (4.99-6.21) in C1. For major bleeding, OR for C1 was 4.48 (3.78; 5.31); for acute stroke, ORs ranged between 0.75 (0.60; 0.94) in C2 to 2.76 (2.27; 3.35) in C1; for coronary revascularization, ORs ranged between 0.34 (0.32; 0.36) in C1 to 1.41 (1.30; 1.53) in C4., Conclusions: We identified distinct comorbidity phenogroups that predicted in-hospital outcomes in patients admitted with AMI. Some conditions overlapped across classes, driven by the high comorbidity burden. Our findings demonstrate the predictive value and potential clinical utility of identifying patients with AMI with specific comorbidity clustering., Competing Interests: SSZ, LYS, EK, MKR, DS, DMA MAM, MR declare no competing interests. SW is a currently an employee of GSK. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Zghebi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: We have had 3 coronavirus-related pandemics in the last two decades. Each has brought significant toll and with each case there was no cure. Even as vaccines have been developed for the current strain of the virus thereby increasing the prospects of bringing transmissions in communities to a minimum, lessons from this pandemic should be explored in preparation for future pandemics. Other studies have looked at differences in characteristics of patients and mortality rates between the first two waves. In our study we not only identify the differences in outcomes but also explore differences in hospital specific interventions that were implemented at Jersey City Medical Center, NJ, a community-based hospital., Aim: The aim of this study is to assess the differences between the first two waves of the COVID -19 pandemic in terms of management and outcomes to help identify any key lessons in the handling of future pandemics. We compared the population demographics, interventions and outcomes used during the first two waves of COVID-19 in a community-based hospital., Methods: This is a retrospective single-center cross-sectional study including Laboratory confirmed COVID-19 patients requiring oxygen supplementation admitted at Jersey City Medical Center during the first wave (April 1 to June 30, 2020) and the second wave between (October 1, 2020, and January 1, 2021). The Chi-squared test was used to assess the relationship between categorical variables and the T- test for continuous variables. A Logistic regression model was built comparing the second to the first wave while accounting for important covariates., Results: There was a combined total of 473 patients from both waves. Patients in the first wave were older (66.17 years vs 60.38 years, p <0.01), had more comorbidities (2.75 vs 2.29, p 0.003), had more severe disease (50% vs 38.78% p of 0.002), had a longer length of stay (14.18 days vs 8.77 days, p <0.001) and were more likely to be intubated (32.49% vs 21.9 4%, p 0.01). In the univariate model, the odds of mortality in the second wave compared to the first wave was 0.63 (CI, 0.41-0.96) and 1.73 (CI, 0.65-4.66) in the fully adjusted model., Conclusion: Overall, there was no statistically significant difference in mortality between the two waves. Interventions that were noted to be significantly different between the two waves were, increased likelihood of mechanical intubation in the first wave and increased use of steroids in the second wave compared to the first., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Alebna et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Smoking is one of the leading causes of premature deaths worldwide. The cigarette is the commonest form of tobacco smoking. This study investigated the factors associated with cigarette smoking among men in five South Asian countries. We analyzed nationally representative cross-sectional study (Demographic and Health Survey) data conducted in Afghanistan, India, Maldives, Nepal, and Pakistan from 2015-2018. Our study population was men aged between 15 and 49 years. The outcome variable was the prevalence of cigarette smoking. We performed both pooled and country-specific analyses using multivariable logistic regression. The prevalence of cigarette smoking among men is the highest (41.2%) in the Maldives and the lowest (20.1%) in Pakistan. Our pooled analysis found that higher age, lower education, lower wealth status, and involvement in any occupations were strongly associated with cigarette smoking (p-value &lt;0.001). However, we did not find a significant association between age and wealth status in Afghanistan, occupations in Nepal and Pakistan, and education in Pakistan with cigarette smoking when country-specific analyses were performed. In this study, socioeconomic position, age, and urban area are strongly associated with cigarette smoking in South Asian countries. The country-specific circumstances should be considered in planning and designing national smoking control strategies and interventions. However, improving access to smoking cessation services could be an effective intervention for all studied countries, Afghanistan, India, Maldives, Nepal, and Pakistan., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Shariful Islam et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The success of any randomized clinical trial relies on the willingness of people to be recruited in the trial. However, 90% of all clinical trials worldwide have been reported to have failed to recruit the required number of trial participants within the scheduled time. This study aimed to qualitatively explore the motivations and barriers for healthy participants to participate in herbal remedy clinical trials in Tanzania., Materials and Methods: This study used a qualitative descriptive research design based on the theory of planned behaviour. A total of five Focus Group Discussions (FGD) were conducted at Bagamoyo Clinical Trial Facility from 29 to 30 May 2021. Each group consisted of 5 to 10 participants. The participants of the study were 30 healthy males aged 18 to 45 male who participated in the clinical trial that evaluated the safety, tolerability, and efficacy of Maytenus Senegalensis. The focus group discussions were recorded audio-recorded. Verbatim transcription and thematic analysis were performed on the data., Results: The prominent motivations mentioned were the opportunity for self-development, altruism, flexible study visit schedule, and financial compensation. Furthermore, the Participants' mothers and friends were reported as those most likely to approve of participation in an herbal remedy. The most mentioned barriers were inconvenience related to time commitment requirements, possible side effects, inflexible study visit schedule, and having other commitments. Moreover, the participants' father was reported to be more likely to disapprove of participation in a clinical trial of herbal remedy clinical trial., Conclusions: The results of this study showed that the motivations and barriers of healthy participants to participate in clinical trials of herbal remedies are varied and that participants are motivated by more than financial gains. The identified motivations and barriers can be used as a guideline to improve the design of recruitment and retention strategies for herbal remedy clinical trials., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Saroglitazar is a newer antidiabetic agent approved to manage dyslipidemia. The objective is tevaluate the efficacy and safety profiles of saroglitazar in patients with dyslipidemia., Methods: A systematic search was conducted using PubMed, Cochrane Library, Scopus, and Google Scholar from the inception until January 2022. Interventional studies comparing the anti-hyperlipidaemic effect and safety of saroglitazar with or without a control group(s) were included. The efficacy of saroglitazar was assessed concerning its effect on total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL)-cholesterol, triglycerides, fasting plasma glucose, and non-HDL cholesterol. The effects on serum creatinine levels, bodyweight reduction, alanine aminotransferase and aspartate aminotransferase were considered to be safety endpoint.The Cochrane risk of bias assessment tool was used to assess the methodological quality of the included studies., Results: A total of six studies with 581 adults with a mean age ranging from 40.2 to 62.6 years were included in this study. A significant decrease in low-density lipoprotein cholesterol was observed with saroglitazar 4 mg therapy compared to saroglitazar 2 mg [standardized mean difference (SMD): -0.23 mg/dL, 95% CI: -0.47 to 0.00; p  =  0.05; 2 studies], and control [SMD: -0.36 mg/dL, 95% CI -0.59 to -0.12; p  =  0.0026; 3 studies]. Also, a significant decrease in the total cholesterol was observed with saroglitazar 4 mg therapy compared to saroglitazar 2 mg [SMD - 0.28 mg/dL, 95% CI: - 0.52 to -0.04; p < 0.01; 2 studies], and control [SMD - 0.49 mg/dL, 95% CI: - 0.72 to -0.26; p < 0.0001; 3 studies]. Saroglitazar was not associated with adverse effects such as increase in serum creatinine levels, alanine aminotransferase and aspartate aminotransferase and bodyweight reduction., Conclusion: Saroglitazar appeared to be an effective and safer therapeutic option for improving dyslipidemia in patients. However, comparative studies of saroglitazar with the other pharmacological agents are warranted., Competing Interests: The authors have declared that no competing interests exist.

Objective: This review evaluates the effectiveness of smartphone applications in improving academic performance and clinical practice among healthcare professionals and students., Methods: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were retrieved from PubMed, Scopus, and Cochrane library through a comprehensive search strategy. Studies that included medical, dental, nursing, allied healthcare professional, undergraduates, postgraduates, and interns from the same disciplines who used mobile applications for their academic learning and/or daily clinical practice were considered., Results: 52 studies with a total of 4057 learner participants were included in this review. 33 studies (15 RCTs, 1 cluster RCT, 7 quasi-experimental studies, 9 interventional cohort studies and 1 cross-sectional study) reported that mobile applications were an effective tool that contributed to a significant improvement in the knowledge level of the participants. The pooled effect of 15 studies with 962 participants showed that the knowledge score improved significantly in the group using mobile applications when compared to the group who did not use mobile applications (SMD = 0.94, 95% CI = 0.57 to1.31, P<0.00001). 19 studies (11 RCTs, 3 quasi-experimental studies and 5 interventional cohort studies) reported that mobile applications were effective in significantly improving skills among the participants., Conclusion: Mobile applications are effective tools in enhancing knowledge and skills. They can be considered as effective adjunct tools in medical education by considering their low expense, high versatility, reduced dependency on regional or site boundaries, online and offline, simulation, and flexible learning features of mobile apps., Competing Interests: The authors have declared that no competing interests exist.

Orthopedic disorders are common among horses, often leading to euthanasia, which often could have been avoided with earlier detection. These conditions often create varying degrees of subtle long-term pain. It is challenging to train a visual pain recognition method with video data depicting such pain, since the resulting pain behavior also is subtle, sparsely appearing, and varying, making it challenging for even an expert human labeller to provide accurate ground-truth for the data. We show that a model trained solely on a dataset of horses with acute experimental pain (where labeling is less ambiguous) can aid recognition of the more subtle displays of orthopedic pain. Moreover, we present a human expert baseline for the problem, as well as an extensive empirical study of various domain transfer methods and of what is detected by the pain recognition method trained on clean experimental pain in the orthopedic dataset. Finally, this is accompanied with a discussion around the challenges posed by real-world animal behavior datasets and how best practices can be established for similar fine-grained action recognition tasks. Our code is available at https://github.com/sofiabroome/painface-recognition., Competing Interests: The authors have declared that no competing interests exist.

Background: Sick leave due to musculoskeletal pain, particularly in the neck/shoulders and back, is one of the major public health problems in Western countries such as Sweden. The aim of this study was to identify predictors of return to work (RTW) among women on sick leave due to long-term neck/shoulder and/or back pain., Methods: This was a prospective cohort study with a 1-year follow-up. The study participants were recruited from a local Swedish Social Insurance Agency register and had all been on sick leave for ≥ 1 month due to long-term (≥ 3 months) neck/shoulder and/or back pain. Data on predictors and outcome were collected using a self-administered questionnaire. A total of 208 women aged 23-64 years were included at baseline, and 141 responded at the 1-year follow-up. Cluster analyses were performed to identify one predictor from each cluster for use in the regression model., Results: At the 1-year follow-up, 94 of the 141 women had RTW and 47 had not. Women who engaged in more coping through increasing behavioral activities (OR: 1.14, 95% CI: 1.03-1.25) and those who more strongly believed they would return to the same work within 6 months (OR: 1.22, 95% CI: 1.10-1.37) had an increased probability of RTW. Receiving more social support outside work (OR: 0.50, 95% CI: 0.28-0.92) decreased the odds of RTW at the 1-year follow-up., Conclusions: Behavioral activities, beliefs about returning to the same work, and social support outside work were predictors of RTW at the 1-year follow-up. Healthcare professionals should consider these predictors in their efforts to prevent prolonged sick leave and to promote RTW in this population., Competing Interests: The authors have declared that no competing interests exist.

Background &objectives: Though there are studies to evaluate the effectiveness of blended learning in pharmacy education, most of them originate from USA and have used previous year students' scores as control. Also there is less research in comparing use of self -regulated learning strategies between blended and other learning strategies. Primary aim was to evaluate the effectiveness of blended learning on knowledge score using clinical research modules. Secondary objective was designed to compare the use of self-regulated learning strategies between blended learning, web-based e-learning and didactic teaching., Materials and Methods: A prospective cluster randomized trial was conducted with didactic teaching as control and web-based e-learning and blended learning as interventions. The target population was final year Pharm D students. Outcome was assessed using a validated knowledge questionnaire, a motivated strategies for learning questionnaire and a feedback form. All statistical analyses were carried out using Statistical Package for Social Science (SPSS) Version 20., Results: A total of 241 students from 12 colleges completed the study. Mean knowledge score of students in blended learning group was higher than those in the didactic teaching and web- based e- learning program (64.26±18.19 Vs 56.65±8.73 Vs 52.11±22.06,p<0.001).Frequency of use of learning strategies namely rehearsal, elaboration, organization and critical thinking was statistically significantly higher in the blended learning group compared to those of didactic and web-based e-learning group (p<0.05) But there were no statistically significant difference of motivational orientations between didactic and blended learning group except strategies of extrinsic goal orientation and self-efficacy. Students preferred blended learning (86.5%) over didactic and web-based e-learning., Conclusion: Blended learning approach is an effective way to teach clinical research module. Students of blended learning group employed all motivational and learning strategies more often than students of the didactic and web- based e-learning groups except strategies of intrinsic goal orientation, task value, control of learning belief and help seeking., Competing Interests: The authors have declared that no competing interests exist.

Background & Objective: Though blended learning (BL), is widely adopted in higher education, evaluating effectiveness of BL is difficult because the components of BL can be extremely heterogeneous. Purpose of this study was to evaluate the effectiveness of BL in improving knowledge and skill in pharmacy education., Methods: PubMed/MEDLINE, Scopus and the Cochrane Library were searched to identify published literature. The retrieved studies from databases were screened for its title and abstracts followed by the full-text in accordance with the pre-defined inclusion and exclusion criteria. Methodological quality was appraised by modified Ottawa scale. Random effect model used for statistical modelling., Key Findings: A total of 26 studies were included for systematic review. Out of which 20 studies with 4525 participants for meta-analysis which employed traditional teaching in control group. Results showed a statistically significant positive effect size on knowledge (standardized mean difference [SMD]: 1.35, 95% confidence interval [CI]: 0.91 to 1.78, p<0.00001) and skill (SMD: 0.68; 95% CI: 0.19 to 1.16; p = 0.006) using a random effect model. Subgroup analysis of cohort studies showed, studies from developed countries had a larger effect size (SMD: 1.54, 95% CI: 1.01 to 2.06), than studies from developing countries(SMD: 0.44, 95% CI: 0.23 to 0.65, studies with MCQ pattern as outcome assessment had larger effect size (SMD: 2.81, 95% CI: 1.76 to 3.85) than non-MCQs (SMD 0.53, 95% CI 0.33 to 0.74), and BL with case studies (SMD 2.72, 95% CI 1.86-3.59) showed better effect size than non-case-based studies (SMD: 0.22, CI: 0.02 to 0.41)., Conclusion: BL is associated with better academic performance and achievement than didactic teaching in pharmacy education., Competing Interests: The authors have declared that no competing interests exist.

Horses have the ability to generate a remarkable repertoire of facial expressions, some of which have been linked to the affective component of pain. This study describes the facial expressions in healthy horses free of pain before and during transportation and social isolation, which are putatively stressful but ordinary management procedures. Transportation was performed in 28 horses by subjecting them to short-term road transport in a horse trailer. A subgroup (n = 10) of these horses was also subjected to short-term social isolation. During all procedures, a body-mounted, remote-controlled heart rate monitor provided continuous heart rate measurements. The horses' heads were video-recorded during the interventions. An exhaustive dataset was generated from the selected video clips of all possible facial action units and action descriptors, time of emergency, duration, and frequency according to the Equine Facial Action Coding System (EquiFACS). Heart rate increased during both interventions (p<0.01), confirming that they caused disruption in sympato-vagal balance. Using the current method for ascribing certain action units (AUs) to specific emotional states in humans and a novel data-driven co-occurrence method, the following facial traits were observed during both interventions: eye white increase (p<0.001), nostril dilator (p<0.001), upper eyelid raiser (p<0.001), inner brow raiser (p = 0.042), tongue show (p<0.001). Increases in 'ear flicker' (p<0.001) and blink frequency (p<0.001) were also seen. These facial actions were used to train a machine-learning classifier to discriminate between the high-arousal interventions and calm horses, which achieved at most 79% accuracy. Most facial features identified correspond well with previous findings on behaviors of stressed horses, for example flared nostrils, repetitive mouth behaviors, increased eye white, tongue show, and ear movements. Several features identified in this study of pain-free horses, such as dilated nostrils, eye white increase, and inner brow raiser, are used as indicators of pain in some face-based pain assessment tools. In order to increase performance parameters in pain assessment tools, the relations between facial expressions of stress and pain should be studied further., Competing Interests: The authors have declared that no competing interests exist.

During the last decade, a number of pain assessment tools based on facial expressions have been developed for horses. While all tools focus on moveable facial muscles related to the ears, eyes, nostrils, lips, and chin, results are difficult to compare due to differences in the research conditions, descriptions and methodologies. We used a Facial Action Coding System (FACS) modified for horses (EquiFACS) to code and analyse video recordings of acute short-term experimental pain (n = 6) and clinical cases expected to be in pain or without pain (n = 21). Statistical methods for analyses were a frequency based method adapted from human FACS approaches, and a novel method based on co-occurrence of facial actions in time slots of varying lengths. We describe for the first time changes in facial expressions using EquiFACS in video of horses with pain. The ear rotator (EAD104), nostril dilation (AD38) and lower face behaviours, particularly chin raiser (AU17), were found to be important pain indicators. The inner brow raiser (AU101) and eye white increase (AD1) had less consistent results across experimental and clinical data. Frequency statistics identified AUs, EADs and ADs that corresponded well to anatomical regions and facial expressions identified by previous horse pain research. The co-occurrence based method additionally identified lower face behaviors that were pain specific, but not frequent, and showed better generalization between experimental and clinical data. In particular, chewing (AD81) was found to be indicative of pain. Lastly, we identified increased frequency of half blink (AU47) as a new indicator of pain in the horses of this study., Competing Interests: No competing interests.

Significant number out of 2.2 billion vision impairments in the world can be attributed to genetics. The current study is aimed to decipher the genetic basis of Leber congenital Amaurosis (LCA), Anterior Segment dysgenesis (ASD), and Retinitis Pigmentosa (RP), segregating in four large consanguineous Pakistani families. The exome sequencing followed by segregation analysis via Sanger sequencing revealed the LCA phenotypes segregating in families GCUF01 and GCUF04 can be attributed to c.465G>T (p.(Gln155His)) missense and novel c.139&#95;140delinsA p.(Pro47Trhfster38) frameshift variant of AIPL1 and GUCY2D, respectively. The c.1843A>T (p.(Lys615*) truncating allele of MERTK is homozygous in all the affected individuals, presumably suffering with RP, of the GCUF02 family. Meanwhile, co-segregation of the ASD phenotype and the c.289A>G (p.(Ile97Val)) variant of FOXE3 was found in the GCUF06 family. All the identified variants were either absent or present in very low frequencies in the control databases. Our in-silico analyses and 3D molecular modeling support the deleterious impact of these variants on the encoded proteins. Variants identified in MERTK, GUCY2D, and FOXE3 were categorized as "pathogenic" or "likely pathogenic", while the missense variant found in AIPL1 was deemed to have "uncertain significance" based upon the variant pathogenicity guidelines from the American College of Medical Genetics and Genomics (ACMG). This paper highlights the genetic diversity of vision disorders in the Pakistani population and reports the identification of four novel mutations in families who segregate clinically heterogeneous eye diseases. Our results give insight into the genotype-phenotype correlations of AIPL1, FOXE3, MERTK, and GUCY2D variants., Competing Interests: No authors have competing interests.

In a serverless cloud computing environment, the cloud provider dynamically manages the allocation of resources whereas the developers purely focus on their applications. The data-driven applications in serverless cloud computing mainly address the web as well as other distributed scenarios, and therefore, it is essential to offer a consistent user experience across different connection types. In order to address the issues of data-driven application in a real-time distributed environment, the use of GraphQL (Graph Query Language) is getting more and more popularity in state-of-the-art cloud computing approaches. However, the existing solutions target the low level implementation of GraphQL, for the development of a complex data-driven application, which may lead to several errors and involve a significant amount of development efforts due to various users' requirements in real-time. Therefore, it is critical to simplify the development process of data-driven applications in a serverless cloud computing environment. Consequently, this research introduces UMLPDA (Unified Modeling Language Profile for Data-driven Applications), which adopts the concepts of UML-based Model-driven Architectures to model the frontend as well as the backend requirements for data-driven applications developed at a higher abstraction level. Particularly, a modeling approach is proposed to resolve the development complexities such as data communication and synchronization. Subsequently, a complete open source transformation engine is developed using a Model-to-Text approach to automatically generate the frontend as well as backend low level implementations of Angular2 and GraphQL respectively. The validation of proposed work is performed with three different case studies, deployed on Amazon Web Services platform. The results show that the proposed framework enables to develop the data-driven applications with simplicity., Competing Interests: The authors have declared that no competing interests exist.

Background: Rotator cuff tendon repair in humans is a commonly performed procedure aimed at restoring the tendon-bone interface. Despite significant innovation of surgical techniques and suture anchor implants, only 60% of repairs heal successfully. One strategy to enhance repair is the use of bioactive sutures that provide the native tendon with biophysical cues for healing. We investigated the tissue response to a multifilament electrospun polydioxanone (PDO) suture in a sheep tendon injury model characterised by a natural history of failure of healing., Methodology and Results: Eight skeletally mature English Mule sheep underwent repair with electrospun sutures. Monofilament sutures were used as a control. Three months after surgery, all tendon repairs healed, without systemic features of inflammation, signs of tumour or infection at necropsy. A mild local inflammatory reaction was seen. On histology the electrospun sutures were densely infiltrated with predominantly tendon fibroblast-like cells. In comparison, no cellular infiltration was observed in the control suture. Neovascularisation was observed within the electrospun suture, whilst none was seen in the control. Foreign body giant cells were rarely seen with either sutures., Conclusion: This study demonstrates that a tissue response can be induced in tendon with a multifilament electrospun suture with no safety concerns., Competing Interests: I declare that I am the inventor on a patent application related to the technology underlying the manufacturing of the ES suture (WO2015040399, Electrospun filaments, filed in September 2013). This does not alter our adherence to PLOS ONE policies on sharing data and materials. I also confirm on behalf of all authors that there is no other competing interests.

Background: Prior studies have reported inconsistencies in the baseline risk profile, comorbidity burden and their association with clinical outcomes in women compared to men. More importantly, there is limited data around the sex differences and how these have changed over time in contemporary percutaneous coronary intervention (PCI) practice., Methods and Results: We used the Nationwide Inpatient Sample to identify all PCI procedures based on ICD-9 procedure codes in the United States between 2004-2014 in adult patients. Descriptive statistics were used to describe sex-based differences in baseline characteristics and comorbidity burden of patients. Multivariable logistic regressions were used to investigate the association between these differences and in-hospital mortality, complications, length of stay and total hospital charges. Among 6,601,526 patients, 66% were men and 33% were women. Women were more likely to be admitted with diagnosis of NSTEMI (non-ST elevation acute myocardial infarction), were on average 5 years older (median age 68 compared to 63) and had higher burden of comorbidity defined by Charlson score ≥3. Women also had higher in-hospital crude mortality (2.0% vs 1.4%) and any complications compared to men (11.1% vs 7.0%). These trends persisted in our adjusted analyses where women had a significant increase in the odds of in-hospital mortality men (OR 1.20 (95% CI 1.16,1.23) and major bleeding (OR 1.81 (95% CI 1.77,1.86)., Conclusion: In this national unselected contemporary PCI cohort, there are significant sex-based differences in presentation, baseline characteristics and comorbidity burden. These differences do not fully account for the higher in-hospital mortality and procedural complications observed in women., Competing Interests: The authors have declared that no competing interests exist.

Recent research on speech segregation and music fingerprinting has led to improvements in speech segregation and music identification algorithms. Speech and music segregation generally involves the identification of music followed by speech segregation. However, music segregation becomes a challenging task in the presence of noise. This paper proposes a novel method of speech segregation for unlabelled stationary noisy audio signals using the deep belief network (DBN) model. The proposed method successfully segregates a music signal from noisy audio streams. A recurrent neural network (RNN)-based hidden layer segregation model is applied to remove stationary noise. Dictionary-based fisher algorithms are employed for speech classification. The proposed method is tested on three datasets (TIMIT, MIR-1K, and MusicBrainz), and the results indicate the robustness of proposed method for speech segregation. The qualitative and quantitative analysis carried out on three datasets demonstrate the efficiency of the proposed method compared to the state-of-the-art speech segregation and classification-based methods.

Birth weight, length and circumferences of the head, chest and arm are key measures of newborn size and health in developing countries. We assessed maternal socio-demographic factors associated with multiple measures of newborn size in a large rural population in Bangladesh using partial least squares (PLS) regression method. PLS regression, combining features from principal component analysis and multiple linear regression, is a multivariate technique with an ability to handle multicollinearity while simultaneously handling multiple dependent variables. We analyzed maternal and infant data from singletons (n = 14,506) born during a double-masked, cluster-randomized, placebo-controlled maternal vitamin A or β-carotene supplementation trial in rural northwest Bangladesh. PLS regression results identified numerous maternal factors (parity, age, early pregnancy MUAC, living standard index, years of education, number of antenatal care visits, preterm delivery and infant sex) significantly (p<0.001) associated with newborn size. Among them, preterm delivery had the largest negative influence on newborn size (Standardized β = -0.29 - -0.19; p<0.001). Scatter plots of the scores of first two PLS components also revealed an interaction between newborn sex and preterm delivery on birth size. PLS regression was found to be more parsimonious than both ordinary least squares regression and principal component regression. It also provided more stable estimates than the ordinary least squares regression and provided the effect measure of the covariates with greater accuracy as it accounts for the correlation among the covariates and outcomes. Therefore, PLS regression is recommended when either there are multiple outcome measurements in the same study, or the covariates are correlated, or both situations exist in a dataset.

In this study, the antioxidative fraction of white mulberry (Morus alba) was found to have an apotogenic effect on Ehrlich's ascites carcinoma cell-induced mice (EAC mice) that correlate with upregulated p53 and downregulated NFκB signaling. The antioxidant activities and polyphenolic contents of various mulberry fractions were evaluated by spectrophotometry and the ethyl acetate fraction (EAF) was selected for further analysis. Strikingly, the EAF caused 70.20% tumor growth inhibition with S-phase cell cycle arrest, normalized blood parameters including red/white blood cell counts and suppressed the tumor weight of EAC mice compared with untreated controls. Fluorescence microscopy analysis of EAF-treated EAC cells revealed DNA fragmentation, cell shrinkage, and plasma membrane blebbing. These characteristic morphological features of apoptosis influenced us to further investigate pro- and anti-apoptotic signals in EAF-treated EAC mice. Interestingly, apoptosis correlated with the upregulation of p53 and its target genes PARP-1 and Bax, and also with the down-regulation of NFκB and its target genes Bcl-2 and Bcl-xL. Our results suggest that the tumor- suppressive effect of the antioxidative fraction of white mulberry is likely due to apoptosis mediated by p53 and NFκB signaling., Competing Interests: The authors have declared that no competing interests exist.

With the recent evolution of technology, the number of image archives has increased exponentially. In Content-Based Image Retrieval (CBIR), high-level visual information is represented in the form of low-level features. The semantic gap between the low-level features and the high-level image concepts is an open research problem. In this paper, we present a novel visual words integration of Scale Invariant Feature Transform (SIFT) and Speeded-Up Robust Features (SURF). The two local features representations are selected for image retrieval because SIFT is more robust to the change in scale and rotation, while SURF is robust to changes in illumination. The visual words integration of SIFT and SURF adds the robustness of both features to image retrieval. The qualitative and quantitative comparisons conducted on Corel-1000, Corel-1500, Corel-2000, Oliva and Torralba and Ground Truth image benchmarks demonstrate the effectiveness of the proposed visual words integration.

Background: Poverty and blindness are believed to be intimately linked, but empirical data supporting this purported relationship are sparse. The objective of this study is to assess whether there is a reduction in poverty after cataract surgery among visually impaired cases., Methodology/principal Findings: A multi-centre intervention study was conducted in three countries (Kenya, Philippines, Bangladesh). Poverty data (household per capita expenditure--PCE, asset ownership and self-rated wealth) were collected from cases aged ≥50 years who were visually impaired due to cataract (visual acuity<6/24 in the better eye) and age-sex matched controls with normal vision. Cases were offered free/subsidised cataract surgery. Approximately one year later participants were re-interviewed about poverty. 466 cases and 436 controls were examined at both baseline and follow-up (Follow up rate: 78% for cases, 81% for controls), of which 263 cases had undergone cataract surgery ("operated cases"). At baseline, operated cases were poorer compared to controls in terms of PCE (Kenya: $22 versus £35 p = 0.02, Bangladesh: $16 vs $24 p = 0.004, Philippines: $24 vs 32 p = 0.0007), assets and self-rated wealth. By follow-up PCE had increased significantly among operated cases in each of the three settings to the level of controls (Kenya: $30 versus £36 p = 0.49, Bangladesh: $23 vs $23 p = 0.20, Philippines: $45 vs $36 p = 0.68). There were smaller increases in self-rated wealth and no changes in assets. Changes in PCE were apparent in different socio-demographic and ocular groups. The largest PCE increases were apparent among the cases that were poorest at baseline., Conclusions/significance: This study showed that cataract surgery can contribute to poverty alleviation, particularly among the most vulnerable members of society. This study highlights the need for increased provision of cataract surgery to poor people and shows that a focus on blindness may help to alleviate poverty and achieve the Millennium Development Goals.

Background: Cataract is the leading cause of blindness in the world, and blindness from cataract is particularly common in low-income countries. The aim of this study is to explore the impact of cataract surgery on daily activities and time-use in Kenya, Bangladesh and the Philippines., Methods/principal Findings: A multi-centre intervention study was conducted in three countries. Time-use data were collected through interview from cases aged >or=50 years with visually impairing cataract (VA <6/24) and age- and gender-matched controls with normal vision (VA>or=6/18). Cases were offered free/subsidized cataract surgery. Approximately one year later participants were re-interviewed about time-use. At baseline across the three countries there were 651 cases and 571 controls. Fifty-five percent of cases accepted surgery. Response rate at follow up was 84% (303 out of 361) for operated cases, and 80% (459 out of 571) for controls. At baseline, cases were less likely to carry out and spent less time on productive activities (paid and non-paid work) and spent more time in "inactivity" compared to controls. Approximately one year after cataract surgery, operated cases were more likely to undertake productive activities compared to baseline (Kenya from 55% to 88%; Bangladesh 60% to 95% and Philippines 81% to 94%, p<0.001) and mean time spent on productive activities increased by one-two hours in each setting (p<0.001). Time spent in "inactivity" in Kenya and Bangladesh decreased by approximately two hours (p<0.001). Frequency of reported assistance with activities was more than halved in each setting (p<0.001)., Conclusions/significance: The empirical evidence provided by this study of increased time spent on productive activities, reduced time in inactivity and reduced assistance following cataract surgery among older adults in low-income settings has positive implications for well-being and inclusion, and supports arguments of economic benefit at the household level from cataract surgery.