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Background: Insufficient sleep is associated with cardiometabolic disease and poor health. However, few studies have assessed its determinants in a nationally-representative sample. Methods: Data from the 2009 Behavioral Risk Factor Surveillance System (BRFSS) was used (N=323,047 adults). Insufficient sleep was assessed as insufficient rest/sleep over 30 days. This was evaluated relative to sociodemographics (age, sex, race/ethnicity, marital status, region), socioeconomics (education, income, employment, insurance), health behaviors (diet, exercise, smoking, alcohol), and health/functioning (emotional support, BMI, mental/physical health). Results: Overall, insufficient sleep was associated with being female, White or Black/African-American, unemployed, without health insurance, and not married; decreased age, income, education, physical activity; worse diet and overall health; and increased household size, alcohol, and smoking. Conclusion: These factors should be considered risk factors for insufficient sleep.

This review introduces a conceptual framework for understanding stakeholder management in the clinical and community-based research environment. In recent years, an evolution in practice has occurred in which many applicants for public and non-governmental funding of public health research in hospital settings. Community health research projects are inherently complex, have sought to involve patients and other stakeholders in the center of the research process. Substantial evidence has now been provided that stakeholder involvement is essential for management effectiveness in clinical research. Feedback from stakeholders has critical value for research managers inasmuch as it alerts them to the social, environmental and ethical implications of research activities. Additionally those who are directly affected by program development and clinical research, the patients, their families, and others, almost universally have a strong motivation to be involved in the planning and execution of new program changes. The current overview introduces a conceptual framework for stakeholder management in the clinical research environment and offers practical suggestions for fostering meaningful stakeholder engagement. The fifth edition of PMBOK® of the Project Management Institute (PMI), has served as basis for many of the suggested guidelines that are put forward in this article.

Nucleotide-binding domain and leucine-rich repeat containing (NLR) family are intracellular sentinels of cytosolic homeostasis that orchestrate immune and inflammatory responses in infectious and immune-mediated diseases. NLRX1 is a mitochondrial-associated NOD-like receptor involved in the modulation of immune and metabolic responses. This study utilizes molecular docking approaches to investigate the structure of NLRX1 and experimentally assesses binding to naturally occurring compounds from several natural product and lipid databases. Screening of compound libraries predicts targeting of NLRX1 by conjugated trienes, polyketides, prenol lipids, sterol lipids, and coenzyme A-containing fatty acids for activating the NLRX1 pathway. The ligands of NLRX1 were identified by docking punicic acid (PUA), eleostearic acid (ESA), and docosahexaenoic acid (DHA) to the C-terminal fragment of the human NLRX1 (cNLRX1). Their binding and that of positive control RNA to cNLRX1 were experimentally determined by surface plasmon resonance (SPR) spectroscopy. In addition, the ligand binding sites of cNLRX1 were predicted in silico and validated experimentally. Target mutagenesis studies demonstrate that mutation of 4 critical residues ASP677, PHE680, PHE681, and GLU684 to alanine resulted in diminished affinity of PUA, ESA, and DHA to NLRX1. Consistent with the regulatory actions of NLRX1 on the NF-κB pathway, treatment of bone marrow derived macrophages (BMDM)s with PUA and DHA suppressed NF-κB activity in a NLRX1 dependent mechanism. In addition, a series of pre-clinical efficacy studies were performed using a mouse model of dextran sodium sulfate (DSS)-induced colitis. Our findings showed that the regulatory function of PUA on colitis is NLRX1 dependent. Thus, we identified novel small molecules that bind to NLRX1 and exert anti-inflammatory actions.

IMPORTANCE:Sudden cardiac death is a leading cause of mortality in psychiatric patients. Long QT (LQT) is common in this population and predisposes to Torsades-de-Pointes (TdP) and subsequent mortality. OBJECTIVE:To estimate the cost-effectiveness of electrocardiographic screening to detect LQT in psychiatric inpatients. DESIGN, SETTING, AND PARTICIPANTS:We built a decision analytic model based on a decision tree to evaluate the cost-effectiveness and utility of LQT screening from a health care perspective. LQT proportion parameters were derived from an in-hospital cross-sectional study. We performed experts' elicitation to estimate the risk of TdP, given extent of QT prolongation. A TdP reduction of 65% after LQT detection was based on positive drug dechallenge rate and through adequate treatment and electrolyte adjustments. The base-case model uncertainty was assessed with one-way and probabilistic sensitivity analyses. Finally, the TdP related mortality and TdP avoidance parameters were varied in a two-way sensitivity analysis to assess their effect on the Incremental Cost-Effectiveness Ratio (ICER). MAIN OUTCOMES AND MEASURES:Costs, Quality Ajusted Life Year (QALY), ICER, and probability of cost effectiveness thresholds ($ 10,000, $25,000, and $50,000 per QALY). RESULTS:In the base-case scenario, the numbers of patients needed to screen were 1128 and 2817 to avoid one TdP and one death, respectively. The ICER of systematic ECG screening was $8644 (95%CI, 3144-82 498) per QALY. The probability of cost-effectiveness was 96% at a willingness-to-pay of $50,000 for one QALY. In sensitivity analyses, results were sensitive to the case-fatality of TdP episodes and to the TdP reduction following the diagnosis of LQT. CONCLUSION AND RELEVANCE:In psychiatric hospitals, performing systematic ECG screening at admission help reduce the number of sudden cardiac deaths in a cost-effective fashion.

Traditional beta is only a linear measure of overall market risk and places equal emphasis on upside and downside risks, but actually the latter is always much stronger probably due to the trading mechanism like short-sale constraints. Therefore, this paper employs the nonlinear measure, tail dependence, to measure the extreme downside risks that individual stocks crash together with the whole market and investigates whether such tail dependence risks will affect stock returns. Our empirical evidence based on Shanghai A shares confirms that most stocks display nonnegligible tail dependence with the whole market, and, more importantly, such tail dependence risks can indeed provide additional information beyond beta and other factors for asset pricing. In cross-sectional regression, it is proved that this tail dependence does help to explain monthly returns on Shanghai A shares, whereas the time-series regression further indicates that mimicking portfolio returns for tail dependence can capture strong common variation of Shanghai A stock returns.

Helicobacter pylori colonizes half of the world's population as the dominant member of the gastric microbiota resulting in a lifelong chronic infection. Host responses toward the bacterium can result in asymptomatic, pathogenic or even favorable health outcomes; however, mechanisms underlying the dual role of H. pylori as a commensal versus pathogenic organism are not well characterized. Recent evidence suggests mononuclear phagocytes are largely involved in shaping dominant immunity during infection mediating the balance between host tolerance and succumbing to overt disease. We combined computational modeling, bioinformatics and experimental validation in order to investigate interactions between macrophages and intracellular H. pylori. Global transcriptomic analysis on bone marrow-derived macrophages (BMDM) in a gentamycin protection assay at six time points unveiled the presence of three sequential host response waves: an early transient regulatory gene module followed by sustained and late effector responses. Kinetic behaviors of pattern recognition receptors (PRRs) are linked to differential expression of spatiotemporal response waves and function to induce effector immunity through extracellular and intracellular detection of H. pylori. We report that bacterial interaction with the host intracellular environment caused significant suppression of regulatory NLRC3 and NLRX1 in a pattern inverse to early regulatory responses. To further delineate complex immune responses and pathway crosstalk between effector and regulatory PRRs, we built a computational model calibrated using time-series RNAseq data. Our validated computational hypotheses are that: 1) NLRX1 expression regulates bacterial burden in macrophages; and 2) early host response cytokines down-regulate NLRX1 expression through a negative feedback circuit. This paper applies modeling approaches to characterize the regulatory role of NLRX1 in mechanisms of host tolerance employed by macrophages to respond to and/or to co-exist with intracellular H. pylori.

Objective. The purpose of this study was to investigate whether short sleepers (

In order to analyze the steady state and transient behavior of the CROCUS reactor, several methods and models need to be developed in the areas of reactor physics, thermal-hydraulics, and multiphysics coupling. The long-term objectives of this project are to work towards the development of a modern method for the safety analysis of research reactors and to update the Final Safety Analysis Report of the CROCUS reactor. A first part of the paper deals with generation of a core simulator nuclear data library for the CROCUS reactor using the Serpent 2 Monte Carlo code and also with reactor core modeling using the PARCS code. PARCS eigenvalue, radial power distribution, and control rod reactivity worth results were benchmarked against Serpent 2 full-core model results. Using the Serpent 2 model as reference, PARCS eigenvalue predictions were within 240 pcm, radial power was within 3% in the central region of the core, and control rod reactivity worth was within 2%. A second part reviews the current methodology used for the safety analysis of the CROCUS reactor and presents the envisioned approach for the multiphysics modeling of the reactor.

Background: Nephrotic syndrome is a commonly acquired kidney disease in children that causes significant morbidity due to recurrent episodes of heavy proteinuria. The management of childhood nephrotic syndrome is known to be highly variable among physicians and care centres. Objectives: The primary objective of the study is to determine centre-, physician-, and patient-level characteristics associated with steroid exposure and length of steroid treatment. We will also determine the association of dose and duration of steroid treatment and time to first relapse as a secondary aim. An embedded qualitative study utilizing focus groups with health care providers will enrich the quantitative results by providing an understanding of the attitudes, beliefs and local contextual factors driving variation in care. Design: Mixed-methods study; prospective observational cohort (quantitative component), with additional semi-structured focus groups of healthcare professionals (qualitative component). Setting: National study, comprised of all 13 Canadian pediatric nephrology clinics. Patients: 400 patients under 18 years of age to be recruited over 2.5 years. Measurements: Steroid doses for all episodes (first presentation, first and subsequent relapses) tracked over course of the study. Physician and centre-level characteristics catalogued, with reasons for treatment preferences documented during focus groups. Methods: All patients tracked prospectively over the course of the study, with data comprising a prospective registry. One focus group at each site to enrich understanding of variation in care. Limitations: Contamination of treatment protocols between physicians may occur as a result of concurrent focus groups. Conclusions: Quantitative and qualitative results will be integrated at end of study and will collectively inform strategies for the development and implementation of standardized evidence-based protocols across centres.

Background and study aims: Upper gastrointestinal (UGI) bleeding is a frequent cause of hospitalization. Its severity may be assessed before endoscopy using the Glasgow-Blatchford Bleeding Score (GBS), a score validated to identify patients requiring clinical intervention. The aim of this study was to assess whether the GBS was effective for shortening hospital stay and reducing costs in patients with an UGI bleeding predicted at low risk of requiring clinical intervention. Patients and methods: Consecutive outpatients presenting with UGI bleeding at our hospital were prospectively included. In the observational study phase, UGI endoscopy was performed in all patients according to routine clinical practice. In the interventional study phase, patients with a GBS of 0 were discharged with an appointment for an outpatient UGI endoscopy. All patients had follow-up at 7 and 30 days. Need for clinical intervention was defined as performance of endoscopic hemostasis, blood transfusion or surgery. Results Two-hundred and eight patients were included, 104 in each study phase; complete follow-up was obtained in 201 patients. GBS varied from 0 to 18, with 15 (14 %) and 11 (11 %) patients having a GBS of 0 in the observational and interventional study phase, respectively. For patients with a GBS of 0, hospital stay was shorter (6 versus 19 h, P < 0.01), and costs were lower (845 EUR versus 1272 EUR, P = 0.002) in the interventional versus the observational study phase. For patients with a GBS > 0, hospital stay duration did not significantly differ between study phases (189 versus 207 h, P = 0.726). No adverse event was observed in the patients sent home with a GBS of 0 during the interventional study phase. Conclusions Implementing the GBS as a tool for triage of hospital outpatients who present with UGI bleeding allowed us to identify those who could safely be discharged for ambulatory management. Implementing this change in the hospital strategy significantly shortened hospital stay and decreased management costs.