α-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic Population

Background: Insulin resistance is a risk factor for type 2 diabetes and cardiovascular disease progression. Current diagnostic tests, such as glycemic indicators, have limitations in the early detection of insulin resistant individuals. We searched for novel biomarkers identifying these at-risk subjects. Methods: Using mass spectrometry, non-targeted biochemical profiling was conducted in a cohort of 399 nondiabetic subjects representing a broad spectrum of insulin sensitivity and glucose tolerance (based on the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing, respectively). Results: Random forest statistical analysis selected alpha-hydroxybutyrate (alpha-HB) as the top-ranked biochemical for separating insulin resistant (lower third of the clamp-derived M(FFM) = 33 [12] mu mol.min(-1).kg(FFM)(-1), median [interquartile range], n = 140) from insulin sensitive subjects (M(FFM) = 66 [23] mu mol.min(-1).kg(FFM)(-1)) with a 76% accuracy. By targeted isotope dilution assay, plasma alpha-HB concentrations were reciprocally related to M(FFM); and by partition analysis, an alpha-HB value of 5 mu g/ml was found to best separate insulin resistant from insulin sensitive subjects. alpha-HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of, and in an additive fashion to, insulin resistance. These associations were also independent of sex, age and BMI. Other metabolites from this global analysis that significantly correlated to insulin sensitivity included certain organic acid, amino acid, lysophospholipid, acylcarnitine and fatty acid species. Several metabolites are intermediates related to alpha-HB metabolism and biosynthesis. Conclusions: alpha-hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation. The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress

Future Directions for Cardiovascular Disease Comparative Effectiveness Research Report of a Workshop Sponsored by the National Heart, Lung, and Blood Institute

Comparative effectiveness research (CER) aims to provide decision makers with the evidence needed to evaluate the benefits and harms of alternative clinical management strategies. CER has become a national priority, with considerable new research funding allocated. Cardiovascular disease is a priority area for CER. This workshop report provides an overview of CER methods, with an emphasis on practical clinical trials and observational treatment comparisons. The report also details recommendations to the National Heart, Lung, and Blood Institute for a new framework for evidence development to foster cardiovascular CER, and specific studies to address 8 clinical issues identified by the Institute of Medicine as high priorities for cardiovascular CER

Virtual Reality, 360⁰ Video, and Journalism Studies: Conceptual Approaches to Immersive Technologies

A growing number of newsrooms are experimenting with Virtual Reality (VR) and other immersive storytelling techniques, typically supported by technology companies that see journalism as a potential vehicle for taking VR mainstream. The resulting pieces have been wide-ranging in topic, style, and scope, but all introduce new complexities to journalistic norms and practices. To date, however, journalism studies scholars have conducted relatively little research into these immersive technologies. This essay proposes three conceptual approaches to examining VR journalism: Actor-Network Theory, normative theory, and a sociological perspective on journalistic work

JWST MIRI/MRS in-flight absolute flux calibration and tailored fringe correction for unresolved sources

Context. The Medium Resolution Spectrometer (MRS) is one of the four observing modes of JWST/MIRI. Using JWST in-flight data of unresolved (point) sources, we can derive the MRS absolute spectral response function (ASRF) starting from raw data. Spectral fringing, caused by coherent reflections inside the detector arrays, plays a critical role in the derivation and interpretation of the MRS ASRF. The fringe corrections implemented in the current pipeline are not optimal for non-extended sources, and a high density of molecular features particularly inhibits an accurate correction. Aims. In this paper, we present an alternative way to calibrate the MIRI/MRS data. Firstly, we derive a fringe correction that accounts for the dependence of the fringe properties on the MIRI/MRS pupil illumination and detector pixel sampling of the point spread function. Secondly, we derive the MRS ASRF using an absolute flux calibrator observed across the full 5- 28 \ub5m wavelength range of the MRS. Thirdly, we apply the new ASRF to the spectrum of a G dwarf and compare it with the output of the JWST/MIRI default data reduction pipeline. Finally, we examine the impact of the different fringe corrections on the detectability of molecular features in the G dwarf and K giant. Methods. The absolute flux calibrator HD 163466 (A-star) was used to derive tailored point source fringe flats at each of the default dither locations of the MRS. The fringe-corrected point source integrated spectrum of HD 163466 was used to derive the MRS ASRF using a theoretical model for the stellar continuum. A cross-correlation was run to quantify the uncertainty on the detection of CO, SiO, and OH in the K giant and CO in the G dwarf for different fringe corrections. Results. The point-source-tailored fringe correction and ASRF are found to perform at the same level as the current corrections, beating down the fringe contrast to the sub-percent level in the G dwarf in the longer wavelengths, whilst mitigating the alteration of real molecular features. The same tailored solutions can be applied to other MRS unresolved targets. Target acquisition is required to ensure the pointing is accurate enough to apply this method. A pointing repeatability issue in the MRS limits the effectiveness of the tailored fringe flats is at short wavelengths. Finally, resulting spectra require no scaling to make the sub-bands match, and a dichroic spectral leak at 12.2 \ub5m is removed

Outflows from the youngest stars are mostly molecular

The formation of stars and planets is accompanied not only by the build-up of matter, namely accretion, but also by its expulsion in the form of highly supersonic jets that can stretch for several parsecs 1,2. As accretion and jet activity are correlated and because young stars acquire most of their mass rapidly early on, the most powerful jets are associated with the youngest protostars 3. This period, however, coincides with the time when the protostar and its surroundings are hidden behind many magnitudes of visual extinction. Millimetre interferometers can probe this stage but only for the coolest components 3. No information is provided on the hottest (greater than 1,000 K) constituents of the jet, that is, the atomic, ionized and high-temperature molecular gases that are thought to make up the jet’s backbone. Detecting such a spine relies on observing in the infrared that can penetrate through the shroud of dust. Here we report near-infrared observations of Herbig-Haro 211 from the James Webb Space Telescope, an outflow from an analogue of our Sun when it was, at most, a few times 104 years old. These observations\ua0reveal copious emission from hot molecules, explaining the origin of the ‘green fuzzies’ 4–7 discovered nearly two decades ago by the Spitzer Space Telescope 8. This outflow is found to be propagating slowly in comparison to its more evolved counterparts and, surprisingly, almost no trace of atomic or ionized emission is seen, suggesting its spine is almost purely molecular

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure

Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte

Environmental Toxicology RISK ASSESSMENT OF GREAT HORNED OWLS (BUBO VIRGINIANUS) EXPOSED TO POLYCHLORINATED BIPHENYLS AND DDT ALONG THE KALAMAZOO RIVER, MICHIGAN, USA

Abstract-The great horned owl (GHO; Bubo virginianus) was used in a multiple lines of evidence study of polychlorinated biphenyls (PCBs) and p,pЈ-dichlorodiphenyltrichloroethane (DDT) exposures at the Kalamazoo River Superfund Site (KRSS), Kalamazoo, Michigan, USA. The study examined risks from total PCBs, including 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalents (TEQ World Health Organization [WHO]-Avian Toxicity Equivalency Factor [TEF] ), and total DDTs (sum of DDT, dichlorodiphenyldichloroethylene [DDE], and dichlorodiphenyldichloroethane [DDD]; ⌺DDT) by measuring concentrations in eggs and nestling blood plasma in two regions of the KRSS (upper, lower) and an upstream reference area (RA). An ecological risk assessment compared concentrations of the contaminants of concern (COCs) in eggs or plasma to toxicity reference values. Productivity and relative abundance measures for KRSS GHOs were compared with other GHO populations. Egg shell thickness was measured to assess effects of p,pЈ-DDE. The concentrations of PCBs in eggs were as great as 4.7 ϫ 10 2 and 4.0 ϫ 10 4 ng PCB/g, wet weight at the RA and combined KRSS sites, respectively. Egg TEQ WHO-Avian calculated from aryl hydrocarbon receptor-active PCB congeners and WHO TEFs ranged to 8.0 and 1.9 ϫ 10 2 pg TEQ WHO-Avian /g, (wet wt) at the RA and combined KRSS, respectively. Egg ⌺DDT concentrations were as great as 4.2 ϫ 10 2 and 5.0 ϫ 10 3 ng ⌺DDT/g (wet wt) at the RA and combined KRSS, respectively. Hazard quotients (HQs) for the upper 95% confidence interval (UCI) (geometric mean) and least observable adverse effect concentration (LOAEC) for COCs in eggs were Յ1.0 for all sites. Hazard quotient values based on the no observable adverse effect concentration (NOAEC) 95% UCI in eggs were Յ1.0, except at the LKRSS (PCB HQ ϭ 3.1; TEQ WHO-Avian HQ ϭ 1.3). Productivity and relative abundance measures indicated no population level effects in the UKRSS