Background There is growing evidence that sleep duration and quality may be associated with cardiovascular harm and mortality. Methods and Results We conducted a systematic review, meta-analysis, and ...spline analysis of prospective cohort studies that evaluate the association between sleep duration and quality and cardiovascular outcomes. We searched MEDLINE and EMBASE for these studies and extracted data from identified studies. We utilized linear and nonlinear dose-response meta-analysis models and used DerSimonian-Laird random-effects meta-analysis models of risk ratios, with inverse variance weighting, and the I
statistic to quantify heterogeneity. Seventy-four studies including 3 340 684 participants with 242 240 deaths among 2 564 029 participants who reported death events were reviewed. Findings were broadly similar across both linear and nonlinear dose-response models in 30 studies with >1 000 000 participants, and we report results from the linear model. Self-reported duration of sleep >8 hours was associated with a moderate increased risk of all-cause mortality, with risk ratio , 1.14 (1.05-1.25) for 9 hours, risk ratio, 1.30 (1.19-1.42) for 10 hours, and risk ratio, 1.47 (1.33-1.64) for 11 hours. No significant difference was identified for periods of self-reported sleep <7 hours, whereas similar patterns were observed for stroke and cardiovascular disease mortality. Subjective poor sleep quality was associated with coronary heart disease (risk ratio , 1.44; 95% confidence interval, 1.09-1.90), but no difference in mortality and other outcomes. Conclusions Divergence from the recommended 7 to 8 hours of sleep is associated with a higher risk of mortality and cardiovascular events. Longer duration of sleep may be more associated with adverse outcomes compared with shorter sleep durations.
AOT reverse micelles are a common and convenient model system for studying the effects of nanoconfinement on aqueous solutions. The reverse micelle shape is important to understanding how the ...constituent components come together to form the coherent whole and the unique properties observed there. The shape of reverse micelles impacts the amount of interface present and the distance of the solute from the interface and is therefore vital to understanding interfacial properties and the behavior of solutes in the polar core. In this work, we use previously introduced measures of shape, the coordinate-pair eccentricity (CPE) and convexity, and apply them to a series of simulations of AOT reverse micelles. We simulate the most commonly used force field for AOT reverse micelles, the CHARMM force field, but we also adapt the OPLS force field for use with AOT, the first work to do so, in addition to using both 3- and 4-site water models. Altogether, these simulations are designed to examine the impact of the force field on the shape of the reverse micelles in detail. We also study the time autocorrelation of shape, the water rotational anisotropy decay, and how the CPE changes between the water pool and AOT tail groups. We find that although the force field changes the shape noticeably, AOT reverse micelles are always amorphous particles. The shape of the micelles changes on the order of 10 ns. The water rotational dynamics observed match the experiment and demonstrate slower dynamics relative to bulk water, suggesting a two-population model that fits a core/shell hypothesis. Taken together, our results indicate that it is likely not possible to create a perfect force field that can reproduce every aspect of the AOT reverse micelle accurately. However, the magnitude of the differences between simulations appears relatively small, suggesting that any reasonably derived force field should provide an acceptable model for most work on AOT reverse micelles.
The core–shell assembly motif is ubiquitous in chemistry. While the most obvious examples are core/shell-type nanoparticles, many other examples exist. The shape of the core/shell constructs is ...poorly understood, making it impossible to separate chemical effects from geometric effects. Here, we create a model for the core/shell construct and develop proof for how the eccentricity is expected to change as a function of the shell. We find that the addition of a constant thickness shell always creates a relatively more spherical shape for all shapes covered by our model unless the shape is already spherical or has some underlying radial symmetry. We apply this work to simulated AOT reverse micelles and demonstrate that it is remarkably successful at explaining the observed shapes of the chemical systems. We identify the three specific cases where the model breaks down and how this impacts eccentricity.
There is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, ...characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2.
We conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9-2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1-1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39-2.48) and aOR 2.07 (1.53-2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93-9.90), aOR 4.36, (3.19-5.95) and aOR 12.95, (4.93-34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32-2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80-426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97-3.42) and aOR 3.08, (1.99-4.77); asymptomatic aOR 2.02, (1.52-2.70) and aOR 1.84, (1.12-3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status.
We have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the majority of women do not experience severe complications of SARS-CoV-2 in pregnancy.
Aerosol-OT reverse micelles represent a chemical construct where surfactant molecules self-assemble to stabilize water nanodroplets 1–10 nm in diameter. Although commonly assumed to adopt a spherical ...shape, all-atom molecular dynamics simulations and some experimental studies predict a nonspherical shape. If these aggregates are not spherical, then what shape do they take? Because the tools needed to evaluate the shape of something that lacks regular structure, order, or symmetry are not well developed, we present a set of three intuitive metricscoordinate-pair eccentricity, convexity, and the curvature distributionthat estimate the shape of an amorphous object, and we demonstrate their use on a simulated aerosol-OT reverse micelle. These metrics are all well-established methods and principles in mathematics, and each provides unique information about the shape. Together, these metrics provide intuitive descriptions of amorphous shapes, facilitate ways to quantify those shapes, and follow their changes over time.
The epidermal growth factor receptor (EGFR) kinase inhibitors gefitinib and erlotinib are effective treatments for lung cancers with EGFR activating mutations, but these tumors invariably develop ...drug resistance. Here, we describe a gefitinib-sensitive lung cancer cell line that developed resistance to gefitinib as a result of focal amplification of the MET proto-oncogene. inhibition of MET signaling in these cells restored their sensitivity to gefitinib. MET amplification was detected in 4 of 18 (22%) lung cancer specimens that had developed resistance to gefitinib or erlotinib. We find that amplification of MET causes gefitinib resistance by driving ERBB3 (HER3)-dependent activation of PI3K, a pathway thought to be specific to EGFR/ERBB family receptors. Thus, we propose that MET amplification may promote drug resistance in other ERBB-driven cancers as well.
Objective To investigate dietary fibre intake and any potential dose-response association with coronary heart disease and cardiovascular disease.Design Systematic review of available literature and ...dose-response meta-analysis of cohort studies using random effects models.Data sources The Cochrane Library, Medline, Medline in-process, Embase, CAB Abstracts, ISI Web of Science, BIOSIS, and hand searching.Eligibility criteria for studies Prospective studies reporting associations between fibre intake and coronary heart disease or cardiovascular disease, with a minimum follow-up of three years and published in English between 1 January 1990 and 6 August 2013.Results 22 cohort study publications met inclusion criteria and reported total dietary fibre intake, fibre subtypes, or fibre from food sources and primary events of cardiovascular disease or coronary heart disease. Total dietary fibre intake was inversely associated with risk of cardiovascular disease (risk ratio 0.91 per 7 g/day (95% confidence intervals 0.88 to 0.94)) and coronary heart disease (0.91 (0.87 to 0.94)). There was evidence of some heterogeneity between pooled studies for cardiovascular disease (I2=45% (0% to 74%)) and coronary heart disease (I2=33% (0% to 66%)). Insoluble fibre and fibre from cereal and vegetable sources were inversely associated with risk of coronary heart disease and cardiovascular disease. Fruit fibre intake was inversely associated with risk of cardiovascular disease.Conclusions Greater dietary fibre intake is associated with a lower risk of both cardiovascular disease and coronary heart disease. Findings are aligned with general recommendations to increase fibre intake. The differing strengths of association by fibre type or source highlight the need for a better understanding of the mode of action of fibre components.
The aim of this study was to determine if earlier administration of oral β blocker therapy in patients with acute coronary syndromes (ACSs) is associated with an increased short-term survival rate ...and improved left ventricular (LV) function. We studied 11,581 patients enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries registry from January 2010 to June 2014. Of these patients, 6,117 were excluded as they received intravenous β blockers or remained free of any β blocker treatment during hospital stay, 23 as timing of oral β blocker administration was unknown, and 182 patients because they died before oral β blockers could be given. The final study population comprised 5,259 patients. The primary outcome was the incidence of in-hospital mortality. The secondary outcome was the incidence of severe LV dysfunction defined as an ejection fraction <40% at hospital discharge. Oral β blockers were administered soon (≤24 hours) after hospital admission in 1,377 patients and later (>24 hours) during hospital stay in the remaining 3,882 patients. Early β blocker therapy was significantly associated with reduced in-hospital mortality (odds ratio 0.41, 95% CI 0.21 to 0.80) and reduced incidence of severe LV dysfunction (odds ratio 0.57, 95% CI 0.42 to 0.78). Significant mortality benefits with early β blocker therapy disappeared when patients with Killip class III/IV were included as dummy variables. The results were confirmed by propensity score–matched analyses. In conclusion, in patients with ACSs, earlier administration of oral β blocker therapy should be a priority with a greater probability of improving LV function and in-hospital survival rate. Patients presenting with acute pulmonary edema or cardiogenic shock should be excluded from this early treatment regimen.
International studies report a decline in mortality following non-ST-elevation myocardial infarction (NSTEMI). Whether this is due to lower baseline risk or increased utilization of ...guideline-indicated treatments is unknown.
To determine whether changes in characteristics of patients with NSTEMI are associated with improvements in outcomes.
Data on patients with NSTEMI in 247 hospitals in England and Wales were obtained from the Myocardial Ischaemia National Audit Project between January 1, 2003, and June 30, 2013 (final follow-up, December 31, 2013).
Baseline demographics, clinical risk (GRACE risk score), and pharmacological and invasive coronary treatments.
Adjusted all-cause 180-day postdischarge mortality time trends estimated using flexible parametric survival modeling.
Among 389 057 patients with NSTEMI (median age, 72.7 years IQR, 61.7-81.2 years; 63.1% men), there were 113 586 deaths (29.2%). From 2003-2004 to 2012-2013, proportions with intermediate to high GRACE risk decreased (87.2% vs 82.0%); proportions with lowest risk increased (4.2% vs 7.6%; P= .01 for trend). The prevalence of diabetes, hypertension, cerebrovascular disease, chronic obstructive pulmonary disease, chronic renal failure, previous invasive coronary strategy, and current or ex-smoking status increased (all P < .001). Unadjusted all-cause mortality rates at 180 days decreased from 10.8% to 7.6% (unadjusted hazard ratio HR, 0.968 95% CI, 0.966-0.971; difference in absolute mortality rate per 100 patients AMR/100, -1.81 95% CI, -1.95 to -1.67). These findings were not substantially changed when adjusted additively by baseline GRACE risk score (HR, 0.975 95% CI, 0.972-0.977; AMR/100, -0.18 95% CI, -0.21 to -0.16), sex and socioeconomic status (HR, 0.975 95% CI, 0.973-0.978; difference in AMR/100, -0.24 95% CI, -0.27 to -0.21), comorbidities (HR, 0.973 95% CI, 0.970-0.976; difference in AMR/100, -0.44 95% CI, -0.49 to -0.39), and pharmacological therapies (HR, 0.972 95% CI, 0.964-0.980; difference in AMR/100, -0.53 95% CI, -0.70 to -0.36). However, the direction of association was reversed after further adjustment for use of an invasive coronary strategy (HR, 1.02 95% CI, 1.01-1.03; difference in AMR/100, 0.59 95% CI, 0.33-0.86), which was associated with a relative decrease in mortality of 46.1% (95% CI, 38.9%-52.0%).
Among patients hospitalized with NSTEMI in England and Wales, improvements in all-cause mortality were observed between 2003 and 2013. This was significantly associated with use of an invasive coronary strategy and not entirely related to a decline in baseline clinical risk or increased use of pharmacological therapies.
To determine the effect of different types of dietary fibre on SBP and DBP.
A systematic review of the literature and a meta-analysis of randomized controlled trials using random-effects models. ...Eligibility criteria for studies included randomized controlled trials of at least 6 weeks duration, testing a fibre isolate or fibre-rich diet against a control or placebo published between 1 January 1990 and 1 December 2013.
Twenty-eight trials met the inclusion criteria and reported fibre intake and SBP and/or DBP. Eighteen trials were included in a meta-analysis. Studies were categorized into 1 of 12 fibre-type categories. The pooled estimates for all fibre types were -0.9 mmHg 95% confidence interval (CI) -2.5 to 0.6 mmHg and -0.7 mmHg (95% CI -1.9 to 0.5 mmHg) for SBP and DBP, respectively. The median difference in total fibre was 6 g. Analyses of specific fibre types concluded that diets rich in beta-glucans reduce SBP by 2.9 mmHg (95% CI 0.9 to 4.9 mmHg) and DBP by 1.5 mmHg (95% CI 0.2 to 2.7 mmHg) for a median difference in beta-glucans of 4 g. Heterogeneity for individual fibre types was generally low.
Higher consumption of beta-glucan fibre is associated with lower SBP and DBP. The results of this review are consistent with recommendations to increase consumption of foods rich in dietary fibre, but some additional emphasis on sources of beta-glucans, such as oats and barley, may be warranted.
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