722 research outputs found
Altitude Effects on Thermal Ice Protection System Performance; a Study of an Alternative Approach
Research has been conducted to better understand the phenomena involved during operation of an aircraft's thermal ice protection system under running wet icing conditions. In such situations, supercooled water striking a thermally ice-protected surface does not fully evaporate but runs aft to a location where it freezes. The effects of altitude, in terms of air pressure and density, on the processes involved were of particular interest. Initial study results showed that the altitude effects on heat energy transfer were accurately modeled using existing methods, but water mass transport was not. Based upon those results, a new method to account for altitude effects on thermal ice protection system operation was proposed. The method employs a two-step process where heat energy and mass transport are sequentially matched, linked by matched surface temperatures. While not providing exact matching of heat and mass transport to reference conditions, the method produces a better simulation than other methods. Moreover, it does not rely on the application of empirical correction factors, but instead relies on the straightforward application of the primary physics involved. This report describes the method, shows results of testing the method, and discusses its limitations
Thrombolytic removal of intraventricular haemorrhage in treatment of severe stroke: results of the randomised, multicentre, multiregion, placebo-controlled CLEAR III trial
Background:
Intraventricular haemorrhage is a subtype of intracerebral haemorrhage, with 50% mortality and serious disability for survivors. We aimed to test whether attempting to remove intraventricular haemorrhage with alteplase versus saline irrigation improved functional outcome.
Methods:
In this randomised, double-blinded, placebo-controlled, multiregional trial (CLEAR III), participants with a routinely placed extraventricular drain, in the intensive care unit with stable, non-traumatic intracerebral haemorrhage volume less than 30 mL, intraventricular haemorrhage obstructing the 3rd or 4th ventricles, and no underlying pathology were adaptively randomly assigned (1:1), via a web-based system to receive up to 12 doses, 8 h apart of 1 mg of alteplase or 0·9% saline via the extraventricular drain. The treating physician, clinical research staff, and participants were masked to treatment assignment. CT scans were obtained every 24 h throughout dosing. The primary efficacy outcome was good functional outcome, defined as a modified Rankin Scale score (mRS) of 3 or less at 180 days per central adjudication by blinded evaluators. This study is registered with ClinicalTrials.gov, NCT00784134.
Findings:
Between Sept 18, 2009, and Jan 13, 2015, 500 patients were randomised: 249 to the alteplase group and 251 to the saline group. 180-day follow-up data were available for analysis from 246 of 249 participants in the alteplase group and 245 of 251 participants in the placebo group. The primary efficacy outcome was similar in each group (good outcome in alteplase group 48% vs saline 45%; risk ratio [RR] 1·06 [95% CI 0·88–1·28; p=0·554]). A difference of 3·5% (RR 1·08 [95% CI 0·90–1·29], p=0·420) was found after adjustment for intraventricular haemorrhage size and thalamic intracerebral haemorrhage. At 180 days, the treatment group had lower case fatality (46 [18%] vs saline 73 [29%], hazard ratio 0·60 [95% CI 0·41–0·86], p=0·006), but a greater proportion with mRS 5 (42 [17%] vs 21 [9%]; RR 1·99 [95% CI 1·22–3·26], p=0·007). Ventriculitis (17 [7%] alteplase vs 31 [12%] saline; RR 0·55 [95% CI 0·31–0·97], p=0·048) and serious adverse events (114 [46%] alteplase vs 151 [60%] saline; RR 0·76 [95% CI 0·64–0·90], p=0·002) were less frequent with alteplase treatment. Symptomatic bleeding (six [2%] in the alteplase group vs five [2%] in the saline group; RR 1·21 [95% CI 0·37–3·91], p=0·771) was similar.
Interpretation:
In patients with intraventricular haemorrhage and a routine extraventricular drain, irrigation with alteplase did not substantially improve functional outcomes at the mRS 3 cutoff compared with irrigation with saline. Protocol-based use of alteplase with extraventricular drain seems safe. Future investigation is needed to determine whether a greater frequency of complete intraventricular haemorrhage removal via alteplase produces gains in functional status
Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas
Neglected tropical diseases (NTDs) have\ud
been recently identified as significant public\ud
health problems in Texas and elsewhere in\ud
the American South. A one-day forum on the\ud
landscape of research and development and\ud
the hidden burden of NTDs in Texas\ud
explored the next steps to coordinate advocacy,\ud
public health, and research into a\ud
cogent health policy framework for the\ud
American NTDs. It also highlighted how\ud
U.S.-funded global health research can serve\ud
to combat these health disparities in the\ud
United States, in addition to benefiting\ud
communities abroad
Induced pseudoscalar coupling of the proton weak interaction
The induced pseudoscalar coupling is the least well known of the weak
coupling constants of the proton's charged--current interaction. Its size is
dictated by chiral symmetry arguments, and its measurement represents an
important test of quantum chromodynamics at low energies. During the past
decade a large body of new data relevant to the coupling has been
accumulated. This data includes measurements of radiative and non radiative
muon capture on targets ranging from hydrogen and few--nucleon systems to
complex nuclei. Herein the authors review the theoretical underpinnings of
, the experimental studies of , and the procedures and uncertainties
in extracting the coupling from data. Current puzzles are highlighted and
future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic
Lipidomics, atrial conduction, and body mass index: evidence from association, mediation, and Mendelian randomization models
BACKGROUND: Lipids are increasingly involved in cardiovascular risk prediction as potential proarrhythmic influencers. However, knowledge is limited about the specific mechanisms connecting lipid alterations with atrial conduction. METHODS: To shed light on this issue, we conducted a broad assessment of 151 sphingo- and phospholipids, measured using mass spectrometry, for association with atrial conduction, measured by P wave duration (PWD) from standard electrocardiograms, in the MICROS study (Microisolates in South Tyrol) (n=839). Causal pathways involving lipidomics, body mass index (BMI), and PWD were assessed using 2-sample Mendelian randomization analyses based on published genome-wide association studies of lipidomics (n=4034) and BMI (n=734 481), and genetic association analysis of PWD in 5 population-based studies (n=24 236). RESULTS: We identified an association with relative phosphatidylcholine 38:3 (%PC 38:3) concentration, which was replicated in the ORCADES (Orkney Complex Disease Study; n=951), with a pooled association across studies of 2.59 (95% CI, 1.3-3.9; P=1.1×10-4) ms PWD per mol% increase. While being independent of cholesterol, triglycerides, and glucose levels, the %PC 38:3-PWD association was mediated by BMI. Results supported a causal effect of BMI on both PWD ( P=8.3×10-5) and %PC 38:3 ( P=0.014). CONCLUSIONS: Increased %PC 38:3 levels are consistently associated with longer PWD, partly because of the confounding effect of BMI. The causal effect of BMI on PWD reinforces evidence of BMI's involvement into atrial electrical activity
Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.
Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition
Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD
Multidrug-resistant Acinetobacter Infection Mortality Rate and Length of Hospitalization
Acinetobacter infections have increased and gained attention because of the organism’s prolonged environmental survival and propensity to develop antimicrobial drug resistance. The effect of multidrug-resistant (MDR) Acinetobacter infection on clinical outcomes has not been reported. A retrospective, matched cohort investigation was performed at 2 Baltimore hospitals to examine outcomes of patients with MDR Acinetobacter infection compared with patients with susceptible Acinetobacter infections and patients without Acinetobacter infections. Multivariable analysis controlling for severity of illness and underlying disease identified an independent association between patients with MDR Acinetobacter infection (n = 96) and increased hospital and intensive care unit length of stay compared with 91 patients with susceptible Acinetobacter infection (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2–5.2 and OR 2.1, 95% CI 1.0–4.3] respectively) and 89 uninfected patients (OR 2.5, 95% CI 1.2–5.4 and OR 4.2, 95% CI 1.5–11.6] respectively). Increased hospitalization associated with MDR Acinetobacter infection emphasizes the need for infection control strategies to prevent cross-transmission in healthcare settings
Alcator C-Mod: research in support of ITER and steps beyond
This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235
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