Sleep duration, baseline cardiovascular risk, inflammation and incident cardiovascular mortality in ambulatory U.S. Adults: National health and nutrition examination survey

Introduction: The interplay between sleep duration and inflammation on the baseline and incident cardiovascular (CV) risk is unknown. We sought to evaluate the association between sleep duration, C-reactive protein (CRP), baseline CV risk, and incident CV mortality. Methods: We used data from the National Health and Nutrition Examination Survey 2005-2010 linked with the cause of death data from the National Center for Health Statistics for adults aged ≥18 years. The associations between self-reported sleep duration and CRP, 10-year atherosclerotic CV disease risk score (ASCVD) and CV mortality were assessed using Linear, Poisson and Cox proportional hazard modeling as appropriate. Results: There were 17,635 eligible participants with a median age of 46 years (interquartile range [IQR] 31, 63). Among them, 51.3% were women and 46.9% were non-Hispanic Whites. Over a median follow-up of 7.5 years (IQR 6.0, 9.1), 350 CV deaths occurred at an incident rate of 2.7 per 1000-person years (IQR 2.4, 3.0). We observed a U-shaped associations between sleep duration and incident CV mortality rate (P-trend=0.011), sleep duration and 10-year ASCVD risk (P-trend \u3c0.001), as well as sleep duration and CRP (P-trend \u3c0.001). A self-reported sleep duration of 6-7 hours appeared most optimal. We observed that those participants who reported \u3c6 or \u3e7 hours of sleep had higher risk of CV death attributable to inflammation after accounting for confounders. Conclusions: There was a U-shaped relationship of incident CV mortality, 10-year ASCVD risk, and CRP with sleep duration. These findings suggest an interplay between sleep duration, inflammation, and CV risk

Clinical outcomes in high-hypoglycaemia-risk patients with type 2 diabetes switching to insulin glargine 300 U/mL versus a first-generation basal insulin analogue in the United States: Results from the DELIVER High Risk real-world study

Aims: To compare 12-month clinical effectiveness of insulin glargine 300 units/mL (Gla-300) versus first-generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla-100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla-300 or Gla-100/IDet) in a real-world setting. // Methods: DELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla-300 (Gla-300 switchers) and were propensity score-matched (1:1) to patients who switched to Gla-100 or IDet (Gla-100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all-hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact). // Results: HbA1c reductions were similar following switching to Gla-300 or Gla-100/IDet (−0.51% vs. −0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all-hypoglycaemia incidence and event rates. However, the Gla-300 switcher cohort had a significantly lower risk of inpatient/ED-associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60–0.89; p = .002) and experienced significantly fewer inpatient/ED-associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001). // Conclusion: In patients with T2D at high risk of hypoglycaemia, switching to Gla-300 or Gla-100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla-300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching

Genome-Wide Association Studies of Schizophrenia and Bipolar Disorder in a Diverse Cohort of US Veterans

Background: Schizophrenia (SCZ) and bipolar disorder (BIP) are debilitating neuropsychiatric disorders, collectively affecting 2% of the world\u27s population. Recognizing the major impact of these psychiatric disorders on the psychosocial function of more than 200 000 US Veterans, the Department of Veterans Affairs (VA) recently completed genotyping of more than 8000 veterans with SCZ and BIP in the Cooperative Studies Program (CSP) #572. Methods: We performed genome-wide association studies (GWAS) in CSP #572 and benchmarked the predictive value of polygenic risk scores (PRS) constructed from published findings. We combined our results with available summary statistics from several recent GWAS, realizing the largest and most diverse studies of these disorders to date. Results: Our primary GWAS uncovered new associations between CHD7 variants and SCZ, and novel BIP associations with variants in Sortilin Related VPS10 Domain Containing Receptor 3 (SORCS3) and downstream of PCDH11X. Combining our results with published summary statistics for SCZ yielded 39 novel susceptibility loci including CRHR1, and we identified 10 additional findings for BIP (28 326 cases and 90 570 controls). PRS trained on published GWAS were significantly associated with case-control status among European American (P \u3c 10-30) and African American (P \u3c .0005) participants in CSP #572. Conclusions: We have demonstrated that published findings for SCZ and BIP are robustly generalizable to a diverse cohort of US veterans. Leveraging available summary statistics from GWAS of global populations, we report 52 new susceptibility loci and improved fine-mapping resolution for dozens of previously reported associations

Multinational Comparative Cross-Sectional Survey of Views of medical students about Acceptable Terminology and Subgroups in Schizophrenia

AIM: The aim of this study was to inform thinking around the terminology for \u27schizophrenia\u27 in different countries. OBJECTIVES: The objective of this study was to investigate: (1) whether medical students view alternative terminology (psychosis subgroups), derived from vulnerability-stress models of schizophrenia, as acceptable and less stigmatising than the term schizophrenia; (2) if there are differences in attitudes to the different terminology across countries with different cultures and (3) whether clinical training has an impact in reducing stigma. DESIGN: This is a cross-sectional survey that examined the attitudes of medical students towards schizophrenia and the alternative subgroups. SETTING: The study was conducted across eight sites: (1) University of Southampton, UK; (2) All India Institute of Medical Science, India; (3) Rowan University, USA; (4) Peshawar Medical College, Pakistan; (5) Capital Medical University, China; (6) College of Medicine and Medical sciences, Bahrain; (7) Queens University, Kingston, Canada and (8) University of Cape Town, South Africa. METHOD: This study extended an initial pilot conducted by the Royal College of Psychiatrists on the term schizophrenia and psychosis subgroups to assess whether the subgroup terminology might have an effect on the attitudes of a convenience sample of medical students from eight different countries and potentially play a role in reducing stigmatisation. RESULTS: 1873 medical students completed a questionnaire recording their attitudes to schizophrenia and the psychosis subgroups. A reduction in negative perceptions were found for the psychosis subgroups, especially for the stress sensitivity psychosis and anxiety psychosis subgroups. Negative perceptions were found for drug-related psychosis. Participants who had undergone clinical training had overall positive attitudes. Differences across different countries were found. CONCLUSION: The attitudes towards psychosis subgroups used in this study have shown mixed results and variation across countries. Further research is warranted to investigate acceptability of terminology. Methods of reducing stigma are discussed in line with the findings. ETHICS: The study received ethical approval from ERGO (Ethics and Research Governance Online; ID: 15972) and subsequently from the ethics committee at each site

Quantum cosmic fluids in the early universe

We present a new framework to study the early universe by replacing the classical perfect fluid background with a quantum fluid. The widely accepted idea that the universe is fundamentally quantum in nature, favours the argument that the energy-momentum tensor for the matter source, in the Einstein field equations, should show inherent quantum behaviour. Our approach tries to implement this perspective by considering the early universe as a quantum microcanonical ensemble of energy states, for a non-interacting scalar field. Building upon its partition function, a detailed calculation for deriving an expression for a propagator in this ensemble has been performed. Furthermore, to model the accelerated expanding universe, we re-derive the expression for the propagator in the conformally flat Friedmann–Lemaître–Robertson–Walker (FLRW) universe under the de Sitter space approximations. The motivation is to set a stage to perform calculations with regard to quantum backgrounds in physical cosmology

The relationship between political risk insurance policies and international investment agreements

This thesis analyses the relationship between political risk insurance ("PRI") policies issued by public providers such as the Overseas Private Investment Corporation ("OPIC") and international investment agreements ("IIAs"). The analysis proceeds in three parts. Part I explains the basic features of the PRI industry and compares IIAs with PRI policies. Generally speaking, IIAs provide broad protections that are available to investors for free, whereas PRI policies provide specific and narrower protections, which are more effective and easier to enforce. Ultimately, both PRI policies and IIAs are risk-mitigation tools that should be evaluated together by investors at the time of making foreign investments. Part II explores the impact of PRI policies on the development of international law. Of particular importance are subrogation provisions found in most IIAs, which allow PRI providers to 'step into the shoes' of the investors and seek recovery from the host State. PRI providers should therefore take account of rights available to them under IIAs when assessing their recovery options. Further, as public insurers are government owned agencies, their actions give rise to State practice that may be relevant for interpretation of treaties in accordance with Articles 31(3)(a) and 31(3)(b) of the Vienna Convention on the Law of Treaties. Finally, Part III illustrates the contribution that OPIC jurisprudence can make to international law by studying specific determinations made by OPIC. Two OPIC determinations are particularly revealing: the Mid-American Holding/Indonesia Determination and the BoA/India Determination. In both cases, OPIC applied international law to determine whether the host State’s actions breached protections contained in the policies and, upon making payment to the investor, OPIC relied on international law to seek recovery fom the host States. Finallly, Part III analyses OPIC jurisprudence in the areas of attribution under international law and quantification of compensation – the analysis shows there is substantial scope for cross-fertilisation between OPIC’s jurisprudence and that of investment treaty tribunals.</p

The relationship between political risk insurance policies and international investment agreements

This thesis analyses the relationship between political risk insurance ("PRI") policies issued by public providers such as the Overseas Private Investment Corporation ("OPIC") and international investment agreements ("IIAs"). The analysis proceeds in three parts. Part I explains the basic features of the PRI industry and compares IIAs with PRI policies. Generally speaking, IIAs provide broad protections that are available to investors for free, whereas PRI policies provide specific and narrower protections, which are more effective and easier to enforce. Ultimately, both PRI policies and IIAs are risk-mitigation tools that should be evaluated together by investors at the time of making foreign investments. Part II explores the impact of PRI policies on the development of international law. Of particular importance are subrogation provisions found in most IIAs, which allow PRI providers to 'step into the shoes' of the investors and seek recovery from the host State. PRI providers should therefore take account of rights available to them under IIAs when assessing their recovery options. Further, as public insurers are government owned agencies, their actions give rise to State practice that may be relevant for interpretation of treaties in accordance with Articles 31(3)(a) and 31(3)(b) of the Vienna Convention on the Law of Treaties. Finally, Part III illustrates the contribution that OPIC jurisprudence can make to international law by studying specific determinations made by OPIC. Two OPIC determinations are particularly revealing: the Mid-American Holding/Indonesia Determination and the BoA/India Determination. In both cases, OPIC applied international law to determine whether the host Stateâs actions breached protections contained in the policies and, upon making payment to the investor, OPIC relied on international law to seek recovery fom the host States. Finallly, Part III analyses OPIC jurisprudence in the areas of attribution under international law and quantification of compensation â the analysis shows there is substantial scope for cross-fertilisation between OPICâs jurisprudence and that of investment treaty tribunals.</p