198 research outputs found
Genotoxic stresses promote clonal expansion of hematopoietic stem cells expressing mutant p53
Poorly Controlled HIV Infection: An Independent Risk Factor for Liver Fibrosis
Liver disease is a major cause of mortality among HIV-infected persons. There is limited information about the extent to which HIV disease severity impacts liver disease progression
Transmitted Drug Resistance in the CFAR Network of Integrated Clinical Systems Cohort: Prevalence and Effects on Pre-Therapy CD4 and Viral Load
Human immunodeficiency virus type 1 (HIV-1) genomes often carry one or more mutations associated with drug resistance upon transmission into a therapy-naïve individual. We assessed the prevalence and clinical significance of transmitted drug resistance (TDR) in chronically-infected therapy-naïve patients enrolled in a multi-center cohort in North America. Pre-therapy clinical significance was quantified by plasma viral load (pVL) and CD4+ cell count (CD4) at baseline. Naïve bulk sequences of HIV-1 protease and reverse transcriptase (RT) were screened for resistance mutations as defined by the World Health Organization surveillance list. The overall prevalence of TDR was 14.2%. We used a Bayesian network to identify co-transmission of TDR mutations in clusters associated with specific drugs or drug classes. Aggregate effects of mutations by drug class were estimated by fitting linear models of pVL and CD4 on weighted sums over TDR mutations according to the Stanford HIV Database algorithm. Transmitted resistance to both classes of reverse transcriptase inhibitors was significantly associated with lower CD4, but had opposing effects on pVL. In contrast, position-specific analyses of TDR mutations revealed substantial effects on CD4 and pVL at several residue positions that were being masked in the aggregate analyses, and significant interaction effects as well. Residue positions in RT with predominant effects on CD4 or pVL (D67 and M184) were re-evaluated in causal models using an inverse probability-weighting scheme to address the problem of confounding by other mutations and demographic or risk factors. We found that causal effect estimates of mutations M184V/I ( pVL) and D67N/G ( and pVL) were compensated by K103N/S and K219Q/E/N/R. As TDR becomes an increasing dilemma in this modern era of highly-active antiretroviral therapy, these results have immediate significance for the clinical management of HIV-1 infections and our understanding of the ongoing adaptation of HIV-1 to human populations
Identification, isolation, and characterization of a novel type of Fukushima-derived microparticle
In the course of the Fukushima nuclear accident, radionuclides were released in various forms, including so-called radiocesium-bearing microparticles (CsMP). So far, four types of CsMP were described: Type A is smaller in size ( 100 μm). In this work, we present a novel type of CsMP (proclaimed Type E). Three particles of Type E were extracted from a contaminated blade of grass that was sampled 1.5 km from the Fukushima Daiichi nuclear power plant in late 2011. They were located using autoradiography, isolated using an optical microscope and micromanipulator, and characterized using scanning electron microscopy, energy dispersive x-ray spectroscopy, and low-level gamma-ray spectrometry. Type E CsMPs are 10–20 μm in size and exhibit an unusually low and barely detectable 137Cs activity of only ≤ 10 mBq per particle. Their brittle and fragile character may indicate a high surface tension
Multiple Imputation to Account for Measurement Error in Marginal Structural Models
Marginal structural models are an important tool for observational studies. These models typically assume that variables are measured without error. We describe a method to account for differential and non-differential measurement error in a marginal structural model
HIV primary care providers—Screening, knowledge, attitudes and behaviors related to alcohol interventions
Alcohol has particularly harmful health effects in HIV-infected patients; therefore, HIV clinics are an important setting for integration of brief alcohol intervention and alcohol pharmacotherapy to improve patient outcomes. Current practices of alcohol screening, counseling, and prescription of pharmacotherapy by HIV providers are unknown
Large-Scale Variation in Wave Attenuation of Oyster Reef Living Shorelines and the Influence of Inundation Duration
One of the paramount goals of oyster reef living shorelines is to achieve sustained and adaptive coastal protection, which requires meeting ecological (i.e., develop a self-sustaining oyster population) and engineering (i.e., provide coastal defense) targets. In a large-scale comparison along the Atlantic and Gulf coasts of the United States, the efficacy of various designs of oyster reef living shorelines at providing wave attenuation was evaluated accounting for the ecological limitations of oysters with regards to inundation duration. A critical threshold for intertidal oyster reef establishment is 50% inundation duration. Living shorelines that spent less than half of the time (\u3c 50%) inundated were not considered suitable habitat for oysters, however, were effective at wave attenuation (68% reduction in wave height). Reefs that experienced \u3e 50% inundation were considered suitable habitat for oysters, but wave attenuation was similar to controls (no reef; ~5% reduction in wave height). Many of the oyster reef living shoreline approaches therefore failed to optimize the ecological and engineering goals. In both inundation regimes, wave transmission decreased with an increasing freeboard (difference between reef crest elevation and water level), supporting its importance in the wave attenuation capacity of oyster reef living shorelines. However, given that the reef crest elevation (and thus freeboard) should be determined by the inundation duration requirements of oysters, research needs to be re-focused on understanding the implications of other reef parameters (e.g. width) for optimising wave attenuation. A broader understanding of the reef characteristics and seascape contexts that result in effective coastal defense by oyster reefs is needed to inform appropriate design and implementation of oyster-based living shorelines globally
High Levels of Antiretroviral Use and Viral Suppression Among Persons in HIV Care in the United States, 2010
Contemporary data on patterns of antiretroviral therapy (ART) use in the U.S. are needed to inform efforts to improve the HIV care cascade
Design and Implementation of a Facility for Discovering New Scintillator Materials
We describe the design and operation of a high-throughput facility for synthesizing thousands of inorganic crystalline samples per year and evaluating them as potential scintillation detector materials. This facility includes a robotic dispenser, arrays of automated furnaces, a dual-beam X-ray generator for diffractometery and luminescence spectroscopy, a pulsed X-ray generator for time response measurements, computer-controlled sample changers, an optical spectrometer, and a network-accessible database management system that captures all synthesis and measurement data
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