3,129 research outputs found

    Bringing scientific rigor to community-developed programs in Hong Kong

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    BACKGROUND: This paper describes efforts to generate evidence for community-developed programs to enhance family relationships in the Chinese culture of Hong Kong, within the framework of community-based participatory research (CBPR). METHODS: The CBPR framework was applied to help maximize the development of the intervention and the public health impact of the studies, while enhancing the capabilities of the social service sector partners. RESULTS: Four academic-community research teams explored the process of designing and implementing randomized controlled trials in the community. In addition to the expected cultural barriers between teams of academics and community practitioners, with their different outlooks, concerns and languages, the team navigated issues in utilizing the principles of CBPR unique to this Chinese culture. Eventually the team developed tools for adaptation, such as an emphasis on building the relationship while respecting role delineation and an iterative process of defining the non-negotiable parameters of research design while maintaining scientific rigor. Lessons learned include the risk of underemphasizing the size of the operational and skills shift between usual agency practices and research studies, the importance of minimizing non-negotiable parameters in implementing rigorous research designs in the community, and the need to view community capacity enhancement as a long term process. CONCLUSIONS: The four pilot studies under the FAMILY Project demonstrated that nuanced design adaptations, such as wait list controls and shorter assessments, better served the needs of the community and led to the successful development and vigorous evaluation of a series of preventive, family-oriented interventions in the Chinese culture of Hong Kong

    Inflammation, organomegaly, and muscle wasting despite hyperphagia in a mouse model of burn cachexia.

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    BACKGROUND: Burn injury results in a chronic inflammatory, hypermetabolic, and hypercatabolic state persisting long after initial injury and wound healing. Burn survivors experience a profound and prolonged loss of lean body mass, fat mass, and bone mineral density, associated with significant morbidity and reduced quality of life. Understanding the mechanisms responsible is essential for developing therapies. A complete characterization of the pathophysiology of burn cachexia in a reproducible mouse model was lacking. METHODS: Young adult (12-16 weeks of age) male C57BL/6J mice were given full thickness burns using heated brass plates or sham injury. Food and water intake, organ and muscle weights, and muscle fiber diameters were measured. Body composition was determined by Piximus. Plasma analyte levels were determined by bead array assay. RESULTS: Survival and weight loss were dependent upon burn size. The body weight nadir in burned mice was 14 days, at which time we observed reductions in total body mass, lean carcass mass, individual muscle weights, and muscle fiber cross-sectional area. Muscle loss was associated with increased expression of the muscle ubiquitin ligase, MuRF1. Burned mice also exhibited reduced fat mass and bone mineral density, concomitant with increased liver, spleen, and heart mass. Recovery of initial body weight occurred at 35 days; however, burned mice exhibited hyperphagia and polydipsia out to 80 days. Burned mice had significant increases in serum cytokine, chemokine, and acute phase proteins, consistent with findings in human burn subjects. CONCLUSIONS: This study describes a mouse model that largely mimics human pathophysiology following severe burn injury. These baseline data provide a framework for mouse-based pharmacological and genetic investigation of burn-injury-associated cachexia

    High Energy Physics in the Atmosphere: Phenomenology of Cosmic Ray Air Showers

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    The properties of cosmic rays with energies above 10**6 GeV have to be deduced from the spacetime structure and particle content of the air showers which they initiate. In this review we summarize the phenomenology of these giant air showers. We describe the hadronic interaction models used to extrapolate results from collider data to ultra high energies, and discuss the prospects for insights into forward physics at the LHC. We also describe the main electromagnetic processes that govern the longitudinal shower evolution, as well as the lateral spread of particles. Armed with these two principal shower ingredients and motivation from the underlying physics, we provide an overview of some of the different methods proposed to distinguish primary species. The properties of neutrino interactions and the potential of forthcoming experiments to isolate deeply penetrating showers from baryonic cascades are also discussed. We finally venture into a terra incognita endowed with TeV-scale gravity and explore anomalous neutrino-induced showers.Comment: Typo in caption of Fig. 8 corrected, references adde

    Atovaquone Compared with Dapsone for the Prevention of Pneumocystis carinii Pneumonia in Patients with HIV Infection Who Cannot Tolerate Trimethoprim, Sulfonamides, or Both

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    BACKGROUND Although trimethoprim–sulfamethoxazole is the drug of choice for the prevention of Pneumocystis carinii pneumonia, many patients cannot tolerate it and must switch to an alternative agent. METHODS We conducted a multicenter, open-label, randomized trial comparing daily atovaquone (1500-mg suspension) with daily dapsone (100 mg) for the prevention of P. carinii pneumonia among patients infected with the human immunodeficiency virus who could not tolerate trimethoprim–sulfamethoxazole. The median follow-up period was 27 months. RESULTS Of 1057 patients enrolled, 298 had a history of P. carinii pneumonia.P. cariniipneumonia developed in 122 of 536 patients assigned to atovaquone (15.7 cases per 100 person-years), as compared with 135 of 521 in the dapsone group (18.4 cases per 100 person-years; relative risk for atovaquone vs. dapsone, 0.85; 95 percent confidence interval, 0.67 to 1.09; P=0.20). The relative risk of death was 1.07 (95 percent confidence interval, 0.89 to 1.30; P=0.45), and the relative risk of discontinuation of the assigned medication because of adverse events was 0.94 (95 percent confidence interval, 0.74 to 1.19; P=0.59). Among the 546 patients who were receiving dapsone at base line, the relative risk of discontinuation because of adverse events was 3.78 for atovaquone as compared with dapsone (95 percent confidence interval, 2.37 to 6.01; P CONCLUSIONS Among patients who cannot tolerate trimethoprim–sulfamethoxazole, atovaquone and dapsone are similarly effective for the prevention ofP. carinii pneumonia. Our results support the continuation of dapsone prophylaxis among patients who are already receiving it. However, among those not receiving dapsone, atovaquone is better tolerated and may be the preferred choice for prophylaxis against P. cariniipneumonia

    De novo mutations in histone modifying genes in congenital heart disease

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    Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD

    A breakthrough on Amanita phalloides poisoning: an effective antidotal effect by polymyxin B

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    Amanita phalloides is responsible for more than 90 % of mushroom-related fatalities, and no effective antidote is available. a-Amanitin, the main toxin of A. phalloides, inhibits RNA polymerase II (RNAP II), causing hepatic and kidney failure. In silico studies included docking and molecular dynamics simulation coupled to molecular mechanics with generalized Born and surface area method energy decomposition on RNAP II. They were performed with a clinical drug that shares chemical similarities to a-amanitin, polymyxin B. The results show that polymyxin B potentially binds to RNAP II in the same interface of a-amanitin, preventing the toxin from binding to RNAP II. In vivo, the inhibition of the mRNA transcripts elicited by a-amanitin was efficiently reverted by polymyxin B in the kidneys. Moreover, polymyxin B significantly decreased the hepatic and renal a-amanitin-induced injury as seen by the histology and hepatic aminotransferases plasma data. In the survival assay, all animals exposed to a-amanitin died within 5 days, whereas 50 % survived up to 30 days when polymyxin B was administered 4, 8, and 12 h post-a-amanitin. Moreover, a single dose of polymyxin B administered concomitantly with a-amanitin was able to guarantee 100 % survival. Polymyxin B protects RNAP II from inactivation leading to an effective prevention of organ damage and increasing survival in a-amanitin-treated animals. The present use of clinically relevant concentrations of an already human-use-approved drug prompts the use of polymyxin B as an antidote for A. phalloides poisoning in humans.Juliana Garcia, Vera Marisa Costa, Ricardo Dinis-Oliveira and Ricardo Silvestre thank FCT-Foundation for Science and Technology-for their PhD grant (SFRH/BD/74979/2010), Post-doc grants (SFRH/BPD/63746/2009 and SFRH/BPD/110001/2015) and Investigator grants (IF/01147/2013) and (IF/00021/2014), respectively. This work was supported by the Fundacao para a Ciencia e Tecnologia (FCT) - project PTDC/DTPFTO/4973/2014 - and the European Union (FEDER funds through COMPETE) and National Funds (FCT, Fundacao para a Ciencia e Tecnologia) through project Pest-C/EQB/LA0006/2013

    Preuve de la validité du score de la qualité de l’évaluation pour l’apprentissage : une mesure de qualité pour les commentaires des superviseurs dans la formation médicale fondée sur les compétences

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    Background: Competency based medical education (CBME) relies on supervisor narrative comments contained within entrustable professional activities (EPA) for programmatic assessment, but the quality of these supervisor comments is unassessed. There is validity evidence supporting the QuAL (Quality of Assessment for Learning) score for rating the usefulness of short narrative comments in direct observation. Objective: We sought to establish validity evidence for the QuAL score to rate the quality of supervisor narrative comments contained within an EPA by surveying the key end-users of EPA narrative comments: residents, academic advisors, and competence committee members. Methods: In 2020, the authors randomly selected 52 de-identified narrative comments from two emergency medicine EPA databases using purposeful sampling. Six collaborators (two residents, two academic advisors, and two competence committee members) were recruited from each of four EM Residency Programs (Saskatchewan, McMaster, Ottawa, and Calgary) to rate these comments with a utility score and the QuAL score.  Correlation between utility and QuAL score were calculated using Pearson’s correlation coefficient. Sources of variance and reliability were calculated using a generalizability study. Results: All collaborators (n = 24) completed the full study.  The QuAL score had a high positive correlation with the utility score amongst the residents (r = 0.80) and academic advisors (r = 0.75) and a moderately high correlation amongst competence committee members (r = 0.68).  The generalizability study found that the major source of variance was the comment indicating the tool performs well across raters. Conclusion: The QuAL score may serve as an outcome measure for program evaluation of supervisors, and as a resource for faculty development.Contexte : Dans la formation médicale fondée sur les compétences (FMFC), l’évaluation programmatique s’appuie sur les commentaires narratifs des superviseurs en lien avec les activités professionnelles confiables (EPA). En revanche, la qualité de ces commentaires n’est pas évaluée. Il existe des preuves de la validité du score QuAL (qualité de l’évaluation pour l’apprentissage, Quality of Assessment for Learning en anglais) pour l’évaluation de l’utilité des commentaires de rétroaction courts lors de la supervision par observation directe. Objectif : Nous avons tenté de démontrer la validité du score QuAL aux fins de l’évaluation de la qualité des commentaires narratifs des superviseurs pour une APC en interrogeant les principaux utilisateurs finaux des rétroactions : les résidents, les conseillers pédagogiques et les membres du comité de compétence. Méthodes : En 2020, les auteurs ont sélectionné au hasard 52 commentaires narratifs anonymisés dans deux bases de données d’APC en médecine d’urgence au moyen d’un échantillonnage intentionnel. Six collaborateurs (deux résidents, deux conseillers pédagogiques et deux membres de comités de compétence) ont été recrutés dans chacun des quatre programmes de résidence en médecine d’urgence (Saskatchewan, McMaster, Ottawa et Calgary) pour évaluer ces commentaires à l’aide d’un score d’utilité et du score QuAL.  La corrélation entre l’utilité et le score QuAL a été calculée à l’aide du coefficient de corrélation de Pearson. Les sources de variance et la fiabilité ont été calculées à l’aide d’une étude de généralisabilité. Résultats : Tous les collaborateurs (n=24) ont réalisé l’étude complète.  Le score QuAL présentait une corrélation positive élevée avec le score d’utilité parmi les résidents (r=0,80) et les conseillers pédagogiques (r=0,75) et une corrélation modérément élevée parmi les membres du comité de compétence (r=0,68).  L’étude de généralisation a révélé que la principale source de variance était le commentaire, ce qui indique que l’outil a fonctionné avec une efficacité égale pour tous les évaluateurs. Conclusion : Le score QuAL peut servir de mesure des résultats pour l’évaluation des superviseurs par les programmes, et de ressource pour le perfectionnement du corps professoral
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