Miracle-dz/UniFAR-FTUs huggingface dataset:
Lopinavir/Ritonavir plus Lamivudine and Abacavir or Zidovudine dose Ratios for Paediatric Fixed-Dose Combinations

Background Lopinavir/ritonavir (LPV/r) is available in a liquid formulation that is far from ideal for treatment of children in resource-poor settings. Flexible, low-cost, solid, oral fixed-dose combinations (FDC) of LPV/r with nucleoside reverse transcriptase inhibitors (LPV/r/abacavir [ABC]/lamivudine [3TC] and LPV/r/zidovudine [ZDV]/3TC) are needed to improve both management and adherence of children. This work aimed to develop appropriate drug ratios and dosing for each FDC. Methods Data from 25 combined datasets included therapeutic drug monitoring and clinical studies from IMPAACT and PENTA. Population pharmacokinetic analyses were performed using Monolix. Monte-Carlo simulations of WHO and FDA dosing recommendations were performed to assess their ability to provide optimal exposure in children weighing 4 to 25 kg based on consensus plasma targets. The LPV/r:3TC:ZDV(ABC) dose ratios were 2.67:1:2(2), respectively. Results Using WHO dosage, LPV efficacy target was reached in all weight bands. Given the recommended drug ratios, the dosage for the 4–5.9 kg weight band (LPV/ZDV: 120/90 mg twice daily [bid]) showed more than 20% of subjects had ZDV levels at high risk of neutropenia. Reducing the LPV/ZDV dose to 80/60 mg bid decreased frequency of high ZDV concentrations but retained the LPV efficacy criteria. Conclusions This defined a flexible and simple FDC containing 40 mg LPV, 10 mg ritonavir, 15 mg 3TC and 30 mg ABC or ZDV. According to the weight bands defined by WHO, 4–5.9 kg, 6–9.9 kg, 10–13.9 kg, 14–19.9 kg, 20–24.9 kg, therapeutic doses would be 2, 3, 4, 5 or 6 individual units administered by oral route bid.
A Growing Consensus for Change in Interpretation of Clinical Research Evidence.

CONTEXT The paradigm of evidence-based practice (EBP) is well established among the health care professions, but perspectives on the best methods for acquiring, analyzing, appraising, and using research evidence are evolving. BACKGROUND The EBP paradigm has shifted away from a hierarchy of research-evidence quality to recognize that multiple research methods can yield evidence to guide clinicians and patients through a decision-making process. Whereas the "frequentist" approach to data interpretation through hypothesis testing has been the dominant analytical method used by and taught to athletic training students and scholars, this approach is not optimal for integrating evidence into routine clinical practice. Moreover, the dichotomy of rejecting, or failing to reject, a null hypothesis is inconsistent with the Bayesian-like clinical decision-making process that skilled health care providers intuitively use. We propose that data derived from multiple research methods can be best interpreted by reporting a credible lower limit that represents the smallest treatment effect at a specified level of certainty, which should be judged in relation to the smallest effect considered to be clinically meaningful. Such an approach can provide a quantifiable estimate of certainty that an individual patient needs follow-up attention to prevent an adverse outcome or that a meaningful level of therapeutic benefit will be derived from a given intervention. CONCLUSIONS The practice of athletic training will be influenced by the evolution of the EBP paradigm. Contemporary practice will require clinicians to expand their critical-appraisal skills to effectively integrate the results derived from clinical research into the care of individual patients. Proper interpretation of a credible lower limit value for a magnitude ratio has the potential to increase the likelihood of favorable patient outcomes, thereby advancing the practice of evidence-based athletic training.
The Effect on Knowledge and Attitude of an Interprofessional Education Curriculum for Optometry and Physician Assistant Students

| 1 Abstract The World Health Organization defines interprofessional education (IPE) as occurring when students from two or more disciplines learn with, from and about each other in order to prepare them for interprofessional collaborative practice (IPC). Due to the heterogeneous delivery of IPE, no consensus has been reached on the optimal number of course hours or instructional activities. As a result, there is limited data validating learning outcomes related to changes in knowledge, attitude and behavior. During the 2014-2015 academic year, students in the physician assistant and optometry programs at Marshall B. Ketchum University underwent an IPE curriculum. Survey comparison of pre-instruction and post-instruction showed no marked change in student readiness for IPC; however, the students’ knowledge of the roles of their counterparts increased. The lessons learned have helped further development of the IPE curriculum at Marshall B. Ketchum University.
Glaucoma detection using texture features extraction

Glaucoma is a second leading cause of the disease in the world. The World Health Organization has estimated that by 2020, about 80 million people would suffer from glaucoma. As the disease progresses, it leads to structural changes in the Optic Nerve Head (ONH). Optic Nerve Head is the region which consists of Optic Cup and Optic Disc. The region of interest is extracted from the fundus image by using Hough Transformation. It is an automated way of segmentation used to obtain the accurate results and it replaces the manual segmentation. The k-mean clustering also used for segmentation which is another approach. From the segmented ONH, the different features like Gray Level Cooccurrence Matrix (GLCM) and Markov Random Field (MRF) are extracted. As the structural changes taken place in ONH, the texture and the intensity values also changes. The features are used to classify the images as normal and glaucoma. The algorithm speed increases by applying the technique on region of interest instead of using complete image directly. Hence the algorithm results about 94% of accuracy in segmentation using Hough Transform, 84% for segmentation using k-means clustering and about 86% for classification using support vector machine.
Effects of a Home‐Based Telephone‐Supported Physical Activity Program for Older Adult Veterans With Chronic Low Back Pain

Background. Chronic low back pain (CLBP) is highly prevalent in older adults, leading to functional decline. Objective. The objective of this study was to evaluate physical activity (PA) only and PA plus cognitive‐behavioral therapy for pain (CBT‐P) among older adult veterans with CLBP. Design. This study was a pilot randomized trial comparing a 12‐week telephone‐supported PA‐only intervention group (PA group) or PA plus CBT‐P intervention group (PA + CBT‐P group) and a wait‐list control group (WL group). Setting. The study setting was the Durham Veterans Affairs Health Care System. Participants. The study participants were 60 older adults with CLBP. Interventions. The PA intervention included stretching, strengthening, and aerobic activities; CBT‐P covered activity pacing, relaxation techniques, and cognitive restructuring. Measurements. Feasibility measures included enrollment and completion metrics; acceptability was measured by completed phone calls. Primary outcomes included the Timed “Up & Go” Test and the PROMIS Health Assessment Questionnaire. Generalized linear mixed models were used to estimate changes within and between groups. Effect sizes were calculated with the Cohen d. Adverse effects were measured by self‐report. Results. The mean participant age was 70.3 years; 53% were not white, and 93% were men. Eighty‐three percent of participants completed the study, and the mean number of completed phone calls was 10 (of 13). Compared with the results for the WL group, small to medium treatment effects were found for the intervention groups in the Timed “Up & Go” Test (PA group: −2.94 [95% CI = −6.24 to 0.35], effect size = −0.28; PA + CBT‐P group: ‐3.26 [95% CI = −6.69 to 0.18], effect size = −0.31) and the PROMIS Health Assessment Questionnaire (PA group: −6.11 [95% CI = −12.85 to 0.64], effect size = −0.64; PA + CBT‐P group: ‐4.10 [95% CI = ‐11.69 to 3.48], effect size = −0.43). Small treatment effects favored PA over PA + CBT‐P. No adverse effects were noted. Limitations. This was a pilot study, and a larger study is needed to verify the results. Conclusions. This pilot trial demonstrated that home‐based telephone‐supported PA interventions were feasible, acceptable, and safe for older adult veterans. The results provide support for a larger trial investigating these interventions.
How to use prior knowledge and still give new data a chance?

A common challenge for the development of drugs in rare diseases and special populations, eg, paediatrics, is the small numbers of patients that can be recruited into clinical trials. Extrapolation can be used to support development and licensing in paediatrics through the structured integration of available data in adults and prospectively generated data in paediatrics to derive conclusions that support licensing decisions in the target paediatric population. In this context, Bayesian analyses have been proposed to obtain formal proof of efficacy of a new drug or therapeutic principle by using additional information (data, opinion, or expectation), expressed through a prior distribution. However, little is said about the impact of the prior assumptions on the evaluation of outcome and prespecified strategies for decision‐making as required in the regulatory context.
Metamorphs: Bistable Planar Structures

Extreme deformation can drastically morph a structure from one structural form into another. Programming such deformation properties into the structure is often challenging and in many cases an impossible task. The morphed forms do not hold and usually relapse to the original form, where the structure is in its lowest energy state. For example, a stick, when bent, resists its bent form and tends to go back to its initial straight form, where it holds the least amount of potential energy. In this project, we present a computational design method which can create fabricable planar structure that can morph into two different bistable forms. Once the user provides the initial desired forms, the method automatically creates support structures (internal springs), such that, the structure can not only morph, but also hold the respective forms under external force application. We achieve this through an iterative nonlinear optimization strategy for shaping the potential energy of the structure in the two forms simultaneously. Our approach guarantees first and second-order stability with respect to the potential energy of the bistable structure.
Instructional methods in computing education judged by computer science teachers and educational experts

Abstract Answers to the questions of which instructional methods are suitable for school, what instructional methods should be applied in teaching individual subjects and how instructional methods support the act of learning represent challenges to general education and education in individual subjects. This article focuses on empirical examinations of instructional methods for computer science education supporting knowledge processes in the act of learning and their integration into the context of significant learning theories. The results of this article show that certain instructional methods are especially predestined for computer science education. They can also be attributed to behavioristic, cognitivist and constructivist learning theories; they are thereby localized and can profit from the empirical findings of the learning theories, especially in practical use on teaching computer science.
Magnetic Extraction of Microplastics from Environmental Samples

Separating microplastics (MPs) from environmental samples is challenging, but necessary to determine their environmental prevalence. Current methods are not standardized across environmental sample type, and it is unclear how well they recover smaller sized MPs. In response, we developed a method that extracts plastics magnetically, taking advantage of their hydrophobic surface to magnetize the plastics. We created hydrophobic Fe nanoparticles that bind to plastic, allowing magnetic recovery. With this principle applied to a simple method, we recovered 92% of 10–20 μm polyethylene and polystyrene beads and 93% of >1 mm MPs (polyethylene, polyethylene terephthalate, polystyrene, polyurethane, polyvinyl chloride, and polypropylene) from seawater. We also recovered 84% and 78% of MPs (polyethylene, polystyrene, polyurethane, polyvinyl chloride, and polypropylene) ranging from 200 μm to 1 mm from freshwater and sediments, respectively. Overall, the procedure is efficient for various sizes, polymer types, and .
Psychosocial Factors That Have an Influence on the Effects of Obesity Improvement Programs

Objective: The objective of the present study was to clarify the relationship between factors having an influence on obesity improvement programs and psychosocial factors from a more comprehensive point of view. Methods: We studied a total of 43 subjects with a body mass index (BMI) of 25 kg/m2 or higher who wished to take part in an obesity improvement program and agreed to participate in the study. We conducted an obesity improvement program based on behavior change theories for three months and evaluated physical composition, mental health, social support, stress-coping and the like before intervention and immediately after completion of the program. Results: The average weight showed a significant decrease from 69.0 ± 8.8 kg to 65.7 ± 8.7 kg before and after intervention (p<0.001), respectively. It was also shown that the presence or absence of chronic diseases, social support from a spouse and the decrease of avoidance stress coping were related to weight loss. Conclusion: The findings suggest that it will be further necessary to continue working on the need to enhance awareness about stress with a view to preventing occurrence of rebound after the end of weight loss programs and acquisition coping techniques, apart from the cooperation of attending doctors, strengthening of social support from family and friends and managing stress for the duration of the program.
Multitask Quantile Regression Under the Transnormal Model

ABSTRACT We consider estimating multitask quantile regression under the transnormal model, with focus on high-dimensional setting. We derive a surprisingly simple closed-form solution through rank-based covariance regularization. In particular, we propose the rank-based ℓ1 penalization with positive-definite constraints for estimating sparse covariance matrices, and the rank-based banded Cholesky decomposition regularization for estimating banded precision matrices. By taking advantage of the alternating direction method of multipliers, nearest correlation matrix projection is introduced that inherits sampling properties of the unprojected one. Our work combines strengths of quantile regression and rank-based covariance regularization to simultaneously deal with nonlinearity and nonnormality for high-dimensional regression. Furthermore, the proposed method strikes a good balance between robustness and efficiency, achieves the “oracle”-like convergence rate, and provides the provable prediction interval under the high-dimensional setting. The finite-sample performance of the proposed method is also examined. The performance of our proposed rank-based method is demonstrated in a real application to analyze the protein mass spectroscopy data. Supplementary materials for this article are available online.
Granule-stored MUC5B mucins are packed by the non-covalent formation of N-terminal head-to-head tetramers

Most MUC5B mucin polymers in the upper airways of humans and pigs are produced by submucosal glands. MUC5B forms N-terminal covalent dimers that are further packed into larger assemblies because of low pH and high Ca2+ in the secretory granule of the mucin-producing cell. We purified the recombinant MUC5B N-terminal covalent dimer and used single-particle electron microscopy to study its structure under intracellular conditions. We found that, at intragranular pH, the dimeric MUC5B organized into head-to-head noncovalent tetramers where the von Willebrand D1–D2 domains hooked into each other. These N-terminal tetramers further formed long linear complexes from which, we suggest, the mucin domains and their C termini project radially outwards. Using conventional and video microscopy, we observed that, upon secretion into the submucosal gland ducts, a flow of bicarbonate-rich fluid passes the mucin-secreting cells. We suggest that this unfolds and pulls out the MUC5B assemblies into long linear threads. These further assemble into thicker mucin bundles in the glandular ducts before emerging at the gland duct opening. We conclude that the combination of intracellular packing of the MUC5B mucin and the submucosal gland morphology creates an efficient machine for producing linear mucin bundles.
Smartphone Use and Multitasking Behaviour in a Teacher Education Program (TEP)

This paper reports on a small scale investigation into preservice teachers’ multitasking behaviours during a course in a teacher education program (TED). Specifically, it addresses three research questions, 1) how frequent do preservice teachers do multitasks with smartphone, 2) what are the types of preservice teachers’ multitasking behaviour, and 3) to what extent does multitasking behaviour affect preservice teachers’ learning. To this end, we did a classroom observation where smartphone was used to facilitate learning. During the observation, we wrote notes concerning preservice teachers’ multitasking behaviour with their smartphone. In addition, a total of 35 preservice teachers was surveyed. Findings of this study show that 97.14% of preservice teachers do multitasking in class; although the frequency and types of multitasking with smartphone vary. The findings also highlight fifteen types of multitasking behaviour with two most common activities: texting and searching. The analysis of preservice teachers’ responses on the survey as well as the observation data suggest that multitasking behaviour contributes both positively and negatively to preservice teachers’ learning. In reference to the findings, implications of the study to TEP are offered.
ATP-sensitive potassium channels in the sinoatrial node contribute to heart rate control and adaptation to hypoxia

ATP-sensitive potassium channels (KATP) contribute to membrane currents in many tissues, are responsive to intracellular metabolism, and open as ATP falls and ADP rises. KATP channels are widely distributed in tissues and are prominently expressed in the heart. They have generally been observed in ventricular tissue, but they are also expressed in the atria and conduction tissues. In this study, we focused on the contribution and role of the inwardly rectifying KATP channel subunit, Kir6.1, in the sinoatrial node (SAN). To develop a murine, conduction-specific Kir6.1 KO model, we selectively deleted Kir6.1 in the conduction system in adult mice (cKO). Electrophysiological data in single SAN cells indicated that Kir6.1 underlies a KATP current in a significant proportion of cells and influences early repolarization during pacemaking, resulting in prolonged cycle length. Implanted telemetry probes to measure heart rate and electrocardiographic characteristics revealed that the cKO mice have a slow heart rate, with episodes of sinus arrest in some mice. The PR interval (time between the onset of the P wave to the beginning of QRS complex) was increased, suggesting effects on the atrioventricular node. Ex vivo studies of whole heart or dissected heart regions disclosed impaired adaptive responses of the SAN to hypoxia, and this may have had long-term pathological consequences in the cKO mice. In conclusion, Kir6.1-containing KATP channels in the SAN have a role in excitability, heart rate control, and the electrophysiological adaptation of the SAN to hypoxia.
The Nexus of Ethical Leadership, Job Performance, and Turnover Intention: The Mediating Role of Job Satisfaction

This study aims to examine the impact of ethical leadership on employees' job satisfaction, job performance, and turnover intention. A conceptual framework is developed which integrates job satisfaction as a mediating mechanism in explaining the nexus among ethical leadership, employee job performance, and turnover intention. The proposed model is tested by using the data collected from a sample (n = 196) of tourist companies in Pakistan. The results reveal that ethical leadership has a positive effect on employees' job satisfaction, job performance and negative effect on employees' turnover intentions. Further, job satisfaction mediates the effect of ethical leadership on employees' job performance and turnover intentions. The findings recommend that the demonstration of ethical leadership behaviours by managers at the workplace increases the likelihood of employees' job satisfaction and performance, while reducing their intention to leave the job. This study elucidates that, in Pakistani tourism sector, ethical leadership plays a key role in achieving performance goals. Future research could analyse the said nexus in different sectors and across different cultures while considering other measures of individual performance. The originality of this study is theorizing as well as empirically testing the intervening mechanism of job satisfaction in probing the linkages among ethical leadership, job performance, and turnover intention in Pakistani workplace context.
Reducing Distress in Mothers of Children With Autism and Other Disabilities: A Randomized Trial

BACKGROUND: Compared with other parents, mothers of children with autism spectrum disorder or other neurodevelopmental disabilities experience more stress, illness, and psychiatric problems. Although the cumulative stress and disease burden of these mothers is exceptionally high, and associated with poorer outcomes in children, policies and practices primarily serve the identified child with disabilities. METHODS: A total of 243 mothers of children with disabilities were consented and randomized into either Mindfulness-Based Stress Reduction (mindfulness practice) or Positive Adult Development (positive psychology practice). Well-trained, supervised peer mentors led 6 weeks of group treatments in 1.5-hour weekly sessions, assessing mothers 6 times before, during, and up to 6 months after treatment. Mothers had children with autism (65%) or other disabilities (35%). At baseline, 85% of this community sample had significantly elevated stress, 48% were clinically depressed, and 41% had anxiety disorders. RESULTS: Using slopes-as-outcomes, mixed random effects models, both treatments led to significant reductions in stress, depression, and anxiety, and improved sleep and life satisfaction, with large effects in depression and anxiety. Mothers in Mindfulness-Based Stress Reduction versus Positive Adult Development had greater improvements in anxiety, depression, sleep, and well-being. Mothers of children with autism spectrum disorder improved less in anxiety, but did not otherwise differ from their counterparts. CONCLUSIONS: Future studies are warranted on how trained mentors and professionals can address the unmet mental health needs of mothers of children with developmental disabilities. Doing so improves maternal well-being and furthers their long-term caregiving of children with complex developmental, physical, and behavioral needs.