Boston University

About: Boston University is a education organization based out in Boston, Massachusetts, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 48688 authors who have published 119622 publications receiving 6276020 citations. The organization is also known as: BU & Boston U.

Dose-response associations between accelerometry measured physical activity and sedentary time and all cause mortality: systematic review and harmonised meta-analysis

Abstract: Objective To examine the dose-response associations between accelerometer assessed total physical activity, different intensities of physical activity, and sedentary time and all cause mortality. Design Systematic review and harmonised meta-analysis. Data sources PubMed, PsycINFO, Embase, Web of Science, Sport Discus from inception to 31 July 2018. Eligibility criteria Prospective cohort studies assessing physical activity and sedentary time by accelerometry and associations with all cause mortality and reported effect estimates as hazard ratios, odds ratios, or relative risks with 95% confidence intervals. Data extraction and analysis Guidelines for meta-analyses and systematic reviews for observational studies and PRISMA guidelines were followed. Two authors independently screened the titles and abstracts. One author performed a full text review and another extracted the data. Two authors independently assessed the risk of bias. Individual level participant data were harmonised and analysed at study level. Data on physical activity were categorised by quarters at study level, and study specific associations with all cause mortality were analysed using Cox proportional hazards regression analyses. Study specific results were summarised using random effects meta-analysis. Main outcome measure All cause mortality. Results 39 studies were retrieved for full text review; 10 were eligible for inclusion, three were excluded owing to harmonisation challenges (eg, wrist placement of the accelerometer), and one study did not participate. Two additional studies with unpublished mortality data were also included. Thus, individual level data from eight studies (n=36 383; mean age 62.6 years; 72.8% women), with median follow-up of 5.8 years (range 3.0-14.5 years) and 2149 (5.9%) deaths were analysed. Any physical activity, regardless of intensity, was associated with lower risk of mortality, with a non-linear dose-response. Hazards ratios for mortality were 1.00 (referent) in the first quarter (least active), 0.48 (95% confidence interval 0.43 to 0.54) in the second quarter, 0.34 (0.26 to 0.45) in the third quarter, and 0.27 (0.23 to 0.32) in the fourth quarter (most active). Corresponding hazards ratios for light physical activity were 1.00, 0.60 (0.54 to 0.68), 0.44 (0.38 to 0.51), and 0.38 (0.28 to 0.51), and for moderate-to-vigorous physical activity were 1.00, 0.64 (0.55 to 0.74), 0.55 (0.40 to 0.74), and 0.52 (0.43 to 0.61). For sedentary time, hazards ratios were 1.00 (referent; least sedentary), 1.28 (1.09 to 1.51), 1.71 (1.36 to 2.15), and 2.63 (1.94 to 3.56). Conclusion Higher levels of total physical activity, at any intensity, and less time spent sedentary, are associated with substantially reduced risk for premature mortality, with evidence of a non-linear dose-response pattern in middle aged and older adults. Systematic review registration PROSPERO CRD42018091808.

Genome-Wide Association Study of Retinopathy in Individuals Without Diabetes

Abstract: Background Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.

A proposed function for Hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning

Abstract: The theta rhythm appears in the rat hippocampal electroencephalogram during exploration and shows phase locking to stimulus acquisition. Lesions that block theta rhythm impair performance in tasks requiring reversal of prior learning, including reversal in a T-maze, where associations between one arm location and food reward need to be extinguished in favor of associations between the opposite arm location and food reward. Here, a hippocampal model shows how theta rhythm could be important for reversal in this task by providing separate functional phases during each 100-300 msec cycle, consistent with physiological data. In the model, effective encoding of new associations occurs in the phase when synaptic input from entorhinal cortex is strong and long-term potentiation (LTP) of excitatory connections arising from hippocampal region CA3 is strong, but synaptic currents arising from region CA3 input are weak (to prevent interference from prior learned associations). Retrieval of old associations occurs in the phase when entorhinal input is weak and synaptic input from region CA3 is strong, but when depotentiation occurs at synapses from CA3 (to allow extinction of prior learned associations that do not match current input). These phasic changes require that LTP at synapses arising from region CA3 should be strongest at the phase when synaptic transmission at these synapses is weakest. Consistent with these requirements, our recent data show that synaptic transmission in stratum radiatum is weakest at the positive peak of local theta, which is when previous data show that induction of LTP is strongest in this layer.

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program.

Abstract: The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1 In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals) These rare variants provide insights into mutational processes and recent human evolutionary history The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 001% The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history