• Scarborough Tobin posted an update 2 days, 12 hours ago

    This finding reduces the subjectivity of the choice of t empirically. The proposal is illustrated with the survival data from a primary biliary cirrhosis study, and its finite sample properties are investigated via an extensive simulation study. © 2020 The International Biometric Society.BACKGROUND Kawasaki disease (KD) is an acute, self-limited vasculitis. Coronary artery aneurysm (CAA) serves as a major contributor to the long-term prognosis of KD. In addition, acute KD usually also leads to several kinds of noncoronary cardiac abnormalities (NCA) involving the pericardium, myocardium and endocardium. MATERIALS AND METHODS A total of 142 Chinese children with KD were recruited from July 2015 to April 2018. Blood samples were collected at 24 h pre-Intravenous immunoglobulin (IVIG) therapy. Several inflammatory mediators and biomarkers for acute myocardial infarction were detected. Echocardiography and electrocardiography (ECG) were performed. RESULTS Plasma white blood cells counts (WBC) was significantly increased in patients with IVIG-nonresponsive KD when compared with their IVIG-responsive counterparts. Selleckchem BIX 02189 A total of 106 children (74.65%) suffered from NCA, including 8 patients (5.63%) with pericardial effusion, 23 patients (16.20%) with acute myocarditis, 101 patients (71.13%) with valvular regurgitation, and 8 patients (5.63%) with abnormal ECG. No significant differences were observed in the distribution of clinical classification and the response to IVIG therapy regardless of NCA exhibited or not. CONCLUSIONS NCA is almost universal in acute KD and mainly manifests as valvular regurgitation. However, it has no influence on clinical classification and the response to IVIG therapy. This article is protected by copyright. All rights reserved.Under the condition of LPS/IFN-γ activation, macrophage metabolism is conversed from oxidative phosphorylation to glycolysis. In the present work, we analyzed whether glycolysis could affect IL-1β expression through altering histone acetylation level in mouse bone marrow-derived macrophages. Immunocytochemistry and Western blot analysis are used to characterize histone acetylation in macrophages stimulated by LPS/IFN-γ. RT-PCR and ELISA were used to determine IL-1β production. Macrophages’ metabolism was monitored in real time by Seahorse test. Our results showed that glycolytic metabolism could enhance the histone acetylation and promote the IL-1β production in LPS/IFN-γ activated macrophage. Moreover, increased production of IL-1β by glycolysis was mediated through enhanced H3K9 acetylation. Importantly, it is found that high-dose of HDAC inhibitor could also significantly increase the expression of IL-1β in the absence of glycolytic metabolism. In conclusion, this study demonstrates that glycolytic metabolism could regulate IL-1β expression by increasing histone acetylation levels in LPS/IFN-γ stimulated macrophages. This article is protected by copyright. All rights reserved.It has been an unsolved question how cardiac mitochondrial energetics is regulated during working transition. Mathematical modelling is a powerful tool for exploring the complicated networks of mitochondrial metabolism. We summarize the recent progress and remaining questions about mitochondrial energetics in heart, especially focusing on approaches utilizing mathematical modelling. Feedback activation by ADP and/or inorganic phosphate is an old but still attractive hypothesis for explaining the regulation mechanisms of cardiac mitochondrial energetics. However, this hypothesis has not been fully validated by experiments because rises of ADP and/or inorganic phosphate concentrations during cardiac workload increase have not been detected in many experiments. The hypothesis of intracellular energetic units is an extended version of feedback activation, which has a similar problem. The each-step activation hypothesis beautifully reproduces metabolite constancy, although such master regulators have not been identified yet. Ca2+ has been the most plausible candidate because some of the mitochondrial dehydrogenases are activated by it. Recent experimental and simulation studies, however, throw doubt on its physiological relevance. Finally, we discuss issues to be solved to obtain a better view of cardiac mitochondrial energetics. © 2020 The Authors. The Journal of Physiology © 2020 The Physiological Society.PURPOSE To assess a quality improvement initiative aimed at improving clinic utilization and encounter and intervention workload capture for clinical pharmacy specialists. This initiative aided in justification of clinical pharmacy services, identification of clinical areas for intervention, and incorporation of all modalities to appropriately document clinical care. METHODS In order to objectively demonstrate clinical pharmacy service value to stakeholders, pharmacy administrators and clinical pharmacy specialists at the North Florida/South Georgia Veterans Health System performed clinic scheduling and profile reviews using data extracted from the Veterans Health Administration electronic health record and analytic software. Outpatient clinical pharmacy specialty practice areas were primarily investigated; the specialty areas included are as follows cardiology, infectious disease, mental health, oncology, pain management/palliative care, and specialty clinics (a collection of medical and surgical subspecialtntions observed for the clinical pharmacy specialists suggest the beneficial role of pharmacy administrators’ collaboration with clinical pharmacy specialists to improve workload capture and access to quality care, to justify clinical pharmacy services, and to identify opportunities for pharmacy clinical intervention. © American Society of Health-System Pharmacists 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.A basket trial in oncology encompasses multiple “baskets” that simultaneously assess one treatment in multiple cancer types or subtypes. It is well-recognized that hierarchical modeling methods, which adaptively borrow strength across baskets, can improve over simple pooling and stratification. We propose a novel Bayesian method, RoBoT (Robust Bayesian Hypothesis Testing), for the data analysis and decision-making in phase II basket trials. In contrast to most existing methods that use posterior credible intervals to determine the efficacy of the new treatment, RoBoT builds upon a formal Bayesian hypothesis testing framework that leads to interpretable and robust inference. Specifically, we assume that the baskets belong to several latent subgroups, and within each subgroup, the treatment has similar probabilities of being more efficacious than controls, historical, or concurrent. The number of latent subgroups and subgroup memberships are inferred by the data through a Dirichlet process mixture model. Such model specification helps avoid type I error inflation caused by excessive shrinkage under typical hierarchical models.