Randomized Polypill Crossover Trial in People Aged 50 and Over

PMCID: PMC3399742This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Synthesis of Chiral Nonracemic Tertiary α-Thio and α-Sulfonyl Acetic Esters via SN2 Reactions of Tertiary Mesylates

Syntheses of enantioenriched sulfides and sulfones via substitution of tertiary mesylate with thiolate nucleophile were achieved with modest to excellent success

Reconciling the Evidence on Serum Homocysteine and Ischaemic Heart Disease: A Meta-Analysis

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Toughened graphite-epoxy composites exposed in near-Earth orbit for 5.8 years

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77202/1/AIAA-26612-927.pd

Simulations and cosmological inference: A statistical model for power spectra means and covariances

We describe an approximate statistical model for the sample variance distribution of the non-linear matter power spectrum that can be calibrated from limited numbers of simulations. Our model retains the common assumption of a multivariate Normal distribution for the power spectrum band powers, but takes full account of the (parameter dependent) power spectrum covariance. The model is calibrated using an extension of the framework in Habib et al. (2007) to train Gaussian processes for the power spectrum mean and covariance given a set of simulation runs over a hypercube in parameter space. We demonstrate the performance of this machinery by estimating the parameters of a power-law model for the power spectrum. Within this framework, our calibrated sample variance distribution is robust to errors in the estimated covariance and shows rapid convergence of the posterior parameter constraints with the number of training simulations.Comment: 14 pages, 3 figures, matches final version published in PR

Longitudinal Study of the Transition From Healthy Aging to Alzheimer Disease

BACKGROUND: Detection of the earliest cognitive changes signifying Alzheimer disease is difficult. OBJECTIVE: To model the cognitive decline in preclinical Alzheimer disease. DESIGN: Longitudinal archival study comparing individuals who became demented during follow-up and people who remained nondemented on each of 4 cognitive factors: global, verbal memory, visuospatial, and working memory. SETTING: Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri. PARTICIPANTS: One hundred thirty-four individuals who became demented during follow-up and 310 who remained nondemented. MAIN OUTCOME MEASURES: Inflection point in longitudinal cognitive performance. RESULTS: The best-fitting model for each of the 4 factors in the stable group was linear, with a very slight downward trend on all but the Visuospatial factor. In contrast, a piecewise model with accelerated slope after a sharp inflection point provided the best fit for the group that progressed. The optimal inflection point for all 4 factors was prior to diagnosis of dementia: Global, 2 years; Verbal and Working Memory, 1 year; and Visuospatial, 3 years. These results were also obtained when data were limited to the subset (n = 44) with autopsy-confirmed Alzheimer disease. CONCLUSIONS: There is a sharp inflection point followed by accelerating decline in multiple domains of cognition, not just memory, in the preclinical period in Alzheimer disease when there is insufficient cognitive decline to warrant clinical diagnosis using conventional criteria. Early change was seen in tests of visuospatial ability, most of which were speeded. Research into early detection of cognitive disorders using only episodic memory tasks may not be sensitive to all of the early manifestations of disease

Optimizing astrophotonic spatial reformatters using simulated on-sky performance

One of the most useful techniques in astronomical instrumentation is image slicing. It enables a spectrograph to have a more compact angular slit, whilst retaining throughput and increasing resolving power. Astrophotonic components like the photonic lanterns and photonic reformatters can be used to replace bulk optics used so far. This study investigates the performance of such devices using end-to-end simulations to approximate realistic on-sky conditions. It investigates existing components, tries to optimize their performance and aims to understand better how best to design instruments to maximize their performance. This work complements the recent work in the field and provides an estimation for the performance of the new components.Comment: Conference proceedings in SPIE 2018 Austin Texa

Blood pressure intervention levels in preterm infants : pilot randomised trial

OBJECTIVE: To examine the feasibility of a trial allocating different blood pressure (BP) intervention levels for treatment in extremely preterm infants. DESIGN: Three-arm open randomised controlled trial performed between February 2013 and April 2015. SETTING: Single tertiary level neonatal intensive care unit. PATIENTS: Infants born <29 weeks' gestation were eligible to participate, if parents consented and they did not have a major congenital malformation. INTERVENTIONS: Infants were randomised to different levels of mean arterial BP at which they received cardiovascular support: active (<30 mm Hg), moderate (<gestational age mm Hg) or permissive (signs of poor perfusion or <19 mm Hg). Once this threshold was breached, all were managed using the same treatment guideline. BP profiles were downloaded continuously; cardiac output and carotid blood flow were measured at 1 day and 3 days, and amplitude integrated EEG was recorded during the first week. Cranial ultrasound scans were reviewed blind to study allocation. MAIN OUTCOME MEASURE: Inotrope usage and achieved BP. RESULTS: Of 134 cases screened, 60 were enrolled, with mean gestation 25.8 weeks (SD 1.5) and birth weight 817 g (SD 190). Invasively measured BP on the first day and inotrope usage were highest in the active and lowest in the permissive arms. There were no differences in haemodynamic or EEG variables or in clinical complications. Predefined cranial ultrasound findings did not differ significantly; no infants in the active arm had parenchymal brain lesions. CONCLUSION: The BP threshold used to trigger treatment affects the achieved BP and inotrope usage, and it was possible to explore these effects using this study design. TRIAL REGISTRATION NUMBER: ISRCTN83507686

Face and content validity of a novel, web-based otoscopy simulator for medical education.

BACKGROUND: Despite the fact that otoscopy is a widely used and taught diagnostic tool during medical training, errors in diagnosis are common. Physical otoscopy simulators have high fidelity, but they can be expensive and only a limited number of students can use them at a given time. OBJECTIVES: 1) To develop a purely web-based otoscopy simulator that can easily be distributed to students over the internet. 2) To assess face and content validity of the simulator by surveying experts in otoscopy. METHODS: An otoscopy simulator, OtoTrain™, was developed at Western University using web-based programming and Unity 3D. Eleven experts from academic institutions in North America were recruited to test the simulator and respond to an online questionnaire. A 7-point Likert scale was used to answer questions related to face validity (realism of the simulator), content validity (expert evaluation of subject matter and test items), and applicability to medical training. RESULTS: The mean responses for the face validity, content validity, and applicability to medical training portions of the questionnaire were all ≤3, falling between the Agree , Mostly Agree , and Strongly Agree categories. The responses suggest good face and content validity of the simulator. Open-ended questions revealed that the primary drawbacks of the simulator were the lack of a haptic arm for force feedback, a need for increased focus on pneumatic otoscopy, and few rare disorders shown on otoscopy. CONCLUSION: OtoTrain™ is a novel, web-based otoscopy simulator that can be easily distributed and used by students on a variety of platforms. Initial face and content validity was encouraging, and a skills transference study is planned following further modifications and improvements to the simulator