Current approaches used in epidemiologic studies to examine short-term multipollutant air pollution exposures

Air pollution epidemiology traditionally focuses on the relationship between individual air pollutants and health outcomes (e.g., mortality). To account for potential copollutant confounding, individual pollutant associations are often estimated by adjusting or controlling for other pollutants in the mixture. Recently, the need to characterize the relationship between health outcomes and the larger multipollutant mixture has been emphasized in an attempt to better protect public health and inform more sustainable air quality management decisions

Fatal progression of experimental visceral leishmaniasis is associated with intestinal parasitism and secondary infection by commensal bacteria, and is delayed by antibiotic prophylaxis.

Leishmania donovani causes visceral leishmaniasis (VL), which is typically fatal without treatment. There is substantial variation between individuals in rates of disease progression, response to treatment and incidence of post-treatment sequelae, specifically post-kala-azar dermal leishmaniasis (PKDL). Nevertheless, the majority of infected people are asymptomatic carriers. Hamsters and mice are commonly used as models of fatal and non-fatal VL, respectively. Host and parasite genetics are likely to be important factors, but in general the reasons for heterogeneous disease presentation in humans and animal models are poorly understood. Host microbiota has become established as a factor in cutaneous forms of leishmaniasis but this has not been studied in VL. We induced intestinal dysbiosis in mice and hamsters by long-term treatment with broad-spectrum antibiotics in their drinking water. There were no significant differences in disease presentation in dysbiotic mice. In contrast, dysbiotic hamsters infected with L. donovani had delayed onset and progression of weight loss. Half of control hamsters had a rapid progression phenotype compared with none of the ABX-treated animals and the nine-month survival rate was significantly improved compared to untreated controls (40% vs. 10%). Antibiotic-treated hamsters also had significantly less severe hepatosplenomegaly, which was accompanied by a distinct cytokine gene expression profile. The protective effect was not explained by differences in parasite loads or haematological profiles. We further found evidence that the gut-liver axis is a key aspect of fatal VL progression in hamsters, including intestinal parasitism, bacterial translocation to the liver, malakoplakia and iron sequestration, none of which occurred in non-progressing murine VL. Diverse bacterial genera were cultured from VL affected livers, of which Rodentibacter was specifically absent from ABX-treated hamsters, indicating this pathobiont may play a role in promoting disease progression. The results provide experimental support for antibiotic prophylaxis against secondary bacterial infections as an adjunct therapy in human VL patients

Influence of Urbanicity and County Characteristics on the Association between Ozone and Asthma Emergency Department Visits in North Carolina

Background: Air pollution epidemiologic studies, often conducted in large metropolitan areas because of proximity to regulatory monitors, are limited in their ability to examine potential associations between air pollution exposures and health effects in rural locations

Preliminary Jitter Stability Results for the Large UV/Optical/Infrared (LUVOIR) Surveyor Concept Using a Non-Contact Vibration Isolation and Precision Pointing System

The need for high payload dynamic stability and ultra-stable mechanical systems is an overarching technology need for large space telescopes such as the Large Ultraviolet / Optical / Infrared (LUVOIR) Surveyor concept. The LUVOIR concept includes a 15-meter-diameter segmented-aperture telescope with a suite of serviceable instruments operating over a range of wavelengths between 100nm to 2.5 um. Wavefront error (WFE) stability of less than 10 picometers RMS of uncorrected system WFE per wavefront control step represents a drastic performance improvement over current space-based telescopes being fielded. Through the utilization of an isolation architecture that involves no mechanical contact between the telescope and the host spacecraft structure, a system design is realized that maximizes the telescope dynamic stability performance without driving stringent technology requirements on spacecraft structure, sensors or actuators. Through analysis of the LUVOIR finite element model and linear optical model, the wavefront error and Line-Of-Sight (LOS) jitter performance is discussed in this paper when using the Vibration Isolation and Precision Pointing System (VIPPS) being developed cooperatively with Lockheed Martin in addition to a multi-loop control architecture. The multi-loop control architecture consists of the spacecraft Attitude Control System (ACS), VIPPS, and a Fast Steering Mirror on the instrument. While the baseline attitude control device for LUVOIR is a set of Control Moment Gyroscopes (CMGs), Reaction Wheel Assembly (RWA) disturbance contribution to wavefront error stability and LOS stability are presented to give preliminary results in this paper. CMG disturbance will be explored in further work to be completed

The Large UV/Optical/Infrared Surveyor (LUVOIR): Decadal Mission Concept Design Update

In preparation for the 2020 Astrophysics Decadal Survey, NASA has commissioned the study of four large mission concepts, including the Large Ultraviolet / Optical / Infrared (LUVOIR) Surveyor. The LUVOIR Science and Technology Definition Team (STDT) has identified a broad range of science objectives including the direct imaging and spectral characterization of habitable exoplanets around sun-like stars, the study of galaxy formation and evolution, the epoch of reionization, star and planet formation, and the remote sensing of Solar System bodies. NASAs Goddard Space Flight Center (GSFC) is providing the design and engineering support to develop executable and feasible mission concepts that are capable of the identified science objectives. We present an update on the first of two architectures being studied: a 15-meter-diameter segmented-aperture telescope with a suite of serviceable instruments operating over a range of wavelengths between 100 nm to 2.5 microns. Four instruments are being developed for this architecture: an optical / near-infrared coronagraph capable of 10(exp -10) contrast at inner working angles as small as 2 lambda/D; the LUVOIR UV Multi-object Spectrograph (LUMOS), which will provide low- and medium-resolution UV (100 400 nm) multi-object imaging spectroscopy in addition to far-UV imaging; the High Definition Imager (HDI), a high-resolution wide-field-of-view NUV-Optical-IR imager; and a UV spectro-polarimeter being contributed by Centre National dEtudes Spatiales (CNES). A fifth instrument, a multi-resolution optical-NIR spectrograph, is planned as part of a second architecture to be studied in late 2017

Strategies for Treating Latent Multiple-Drug Resistant Tuberculosis: A Decision Analysis

BACKGROUND: The optimal treatment for latent multiple-drug resistant tuberculosis infection remains unclear. In anticipation of future clinical trials, we modeled the expected performance of six potential regimens for treatment of latent multiple-drug resistant tuberculosis. METHODS: A computerized Markov model to analyze the total cost of treatment for six different regimens: Pyrazinamide/ethambutol, moxifloxacin monotherapy, moxifloxacin/pyrazinamide, moxifloxacin/ethambutol, moxifloxacin/ethionamide, and moxifloxacin/PA-824. Efficacy estimates were extrapolated from mouse models and examined over a wide range of assumptions. RESULTS: In the base-case, moxifloxacin monotherapy was the lowest cost strategy, but moxifloxacin/ethambutol was cost-effective at an incremental cost-effectiveness ratio of $21,252 per quality-adjusted life-year. Both pyrazinamide-containing regimens were dominated due to their toxicity. A hypothetical regimen of low toxicity and even modest efficacy was cost-effective compared to "no treatment." CONCLUSION: In our model, moxifloxacin/ethambutol was the preferred treatment strategy under a wide range of assumptions; pyrazinamide-containing regimens fared poorly because of high rates of toxicity. Although more data are needed on efficacy of treatments for latent MDR-TB infection, data on toxicity and treatment discontinuation, which are easier to obtain, could have a substantial impact on public health practice

Next Generation Mapping of Enological Traits in an F2 Interspecific Grapevine Hybrid Family

In winegrapes (Vitis spp.), fruit quality traits such as berry color, total soluble solids content (SS), malic acid content (MA), and yeast assimilable nitrogen (YAN) affect fermentation or wine quality, and are important traits in selecting new hybrid winegrape cultivars. Given the high genetic diversity and heterozygosity of Vitis species and their tendency to exhibit inbreeding depression, linkage map construction and quantitative trait locus (QTL) mapping has relied on F1 families with the use of simple sequence repeat (SSR) and other markers. This study presents the construction of a genetic map by single nucleotide polymorphisms identified through genotyping-by-sequencing (GBS) technology in an F2 mapping family of 424 progeny derived from a cross between the wild species V. riparia Michx. and the interspecific hybrid winegrape cultivar, ‘Seyval’. The resulting map has 1449 markers spanning 2424 cM in genetic length across 19 linkage groups, covering 95% of the genome with an average distance between markers of 1.67 cM. Compared to an SSR map previously developed for this F2 family, these results represent an improved map covering a greater portion of the genome with higher marker density. The accuracy of the map was validated using the well-studied trait berry color. QTL affecting YAN, MA and SS related traits were detected. A joint MA and SS QTL spans a region with candidate genes involved in the malate metabolism pathway. We present an analytical pipeline for calling intercross GBS markers and a high-density linkage map for a large F2 family of the highly heterozygous Vitis genus. This study serves as a model for further genetic investigations of the molecular basis of additional unique characters of North American hybrid wine cultivars and to enhance the breeding process by marker-assisted selection. The GBS protocols for identifying intercross markers developed in this study can be adapted for other heterozygous species

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]