XMM-Newton X-ray Observations of the Wolf-Rayet Binary System WR 147

We present results of a 20 ksec X-ray observation of the Wolf-Rayet (WR) binary system WR 147 obtained with XMM-Newton. Previous studies have shown that this system consists of a nitrogen-type WN8 star plus an OB companion whose winds are interacting to produce a colliding wind shock. X-ray spectra from the pn and MOS detectors confirm the high extinction reported from IR studies and reveal hot plasma including the first detection of the Fe K-alpha line complex at 6.67 keV. Spectral fits with a constant-temperature plane-parallel shock model give a shock temperature kT(shock) = 2.7 keV [T(shock) ~ 31 MK], close to but slightly hotter than the maximum temperature predicted for a colliding wind shock. Optically thin plasma models suggest even higher temperatures, which are not yet ruled out. The X-ray spectra are harder than can be accounted for using 2D numerical colliding wind shock models based on nominal mass-loss parameters. Possible explanations include: (i) underestimates of the terminal wind speeds or wind abundances, (ii) overly simplistic colliding wind models, or (iii) the presence of other X-ray emission mechanisms besides colliding wind shocks. Further improvement of the numerical models to include potentially important physics such as non-equilibrium ionization will be needed to rigorously test the colliding wind interpretation.Comment: 8 pages, 7 figure

The Universal Stellar Mass-Stellar Metallicity Relation for Dwarf Galaxies

We present spectroscopic metallicities of individual stars in seven gas-rich dwarf irregular galaxies (dIrrs), and we show that dIrrs obey the same mass-metallicity relation as the dwarf spheroidal (dSph) satellites of both the Milky Way and M31: Z_* ∝ M_*^(0.30±0.02). The uniformity of the relation is in contradiction to previous estimates of metallicity based on photometry. This relationship is roughly continuous with the stellar mass-stellar metallicity relation for galaxies as massive as M_* = 10^(12) M_☉. Although the average metallicities of dwarf galaxies depend only on stellar mass, the shapes of their metallicity distributions depend on galaxy type. The metallicity distributions of dIrrs resemble simple, leaky box chemical evolution models, whereas dSphs require an additional parameter, such as gas accretion, to explain the shapes of their metallicity distributions. Furthermore, the metallicity distributions of the more luminous dSphs have sharp, metal-rich cut-offs that are consistent with the sudden truncation of star formation due to ram pressure stripping

Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury.

Background:Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods:Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results:Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion:In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence:III. Study type:Prognostic/epidemiological

Mass loss from inhomogeneous hot star winds II. Constraints from a combined optical/UV study

Mass-loss rates currently in use for hot, massive stars have recently been seriously questioned, mainly because of the effects of wind clumping. We investigate the impact of clumping on diagnostic ultraviolet resonance and optical recombination lines. Optically thick clumps, a non-void interclump medium, and a non-monotonic velocity field are all accounted for in a single model. We used 2D and 3D stochastic and radiation-hydrodynamic (RH) wind models, constructed by assembling 1D snapshots in radially independent slices. To compute synthetic spectra, we developed and used detailed radiative transfer codes for both recombination lines (solving the "formal integral") and resonance lines (using a Monte-Carlo approach). In addition, we propose an analytic method to model these lines in clumpy winds, which does not rely on optically thin clumping. Results: Synthetic spectra calculated directly from current RH wind models of the line-driven instability are unable to in parallel reproduce strategic optical and ultraviolet lines for the Galactic O-supergiant LCep. Using our stochastic wind models, we obtain consistent fits essentially by increasing the clumping in the inner wind. A mass-loss rate is derived that is approximately two times lower than predicted by the line-driven wind theory, but much higher than the corresponding rate derived from spectra when assuming optically thin clumps. Our analytic formulation for line formation is used to demonstrate the potential impact of optically thick clumping in weak-winded stars and to confirm recent results that resonance doublets may be used as tracers of wind structure and optically thick clumping. (Abridged)Comment: 14 pages+1 Appendix, 8 figures, 3 tables. Accepted for publication in Astronomy and Astrophysics. One reference updated, minor typo in Appendix correcte

Detection of Drug-Induced Acute Kidney Injury in Humans Using Urinary KIM-1, miR-21,-200c, and-423

Drug-induced acute kidney injury (AKI) is often encountered in hospitalized patients. Although serum creatinine (SCr) is still routinely used for assessing AKI, it is known to be insensitive and nonspecific. Therefore, our objective was to evaluate kidney injury molecule 1 (KIM-1) in conjunction with microRNA (miR)-21, -200c, and -423 as urinary biomarkers for drug-induced AKI in humans. In a cross-sectional cohort of patients (n = 135) with acetaminophen (APAP) overdose, all 4 biomarkers were significantly (P < .004) higher not only in APAP-overdosed (OD) patients with AKI (based on SCr increase) but also in APAP-OD patients without clinical diagnosis of AKI compared with healthy volunteers. In a longitudinal cohort of patients with malignant mesothelioma receiving intraoperative cisplatin (Cp) therapy (n = 108) the 4 biomarkers increased significantly (P < .0014) over time after Cp administration, but could not be used to distinguish patients with or without AKI. Evidence for human proximal tubular epithelial cells (HPTECs) being the source of miRNAs in urine was obtained first, by in situ hybridization based confirmation of increase in miR-21 expression in the kidney sections of AKI patients and second, by increased levels of miR-21, -200c, and -423 in the medium of cultured HPTECs treated with Cp and 4-aminophenol (APAP degradation product). Target prediction analysis revealed 1102 mRNA targets of miR-21, -200c, and -423 that are associated with pathways perturbed in diverse pathological kidney conditions. In summary, we report noninvasive detection of AKI in humans by combining the sensitivity of KIM-1 along with mechanistic potentials of miR-21, -200c, and -423

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

Mid-infrared interferometry of the massive young stellar object NGC3603 - IRS 9A

We present observations and models for one of these MYSO candidates, NGC3603 IRS 9A. Our goal is to investigate with infrared interferometry the structure of IRS 9A on scales as small as 200AU, exploiting the fact that a cluster of O and B stars has blown away much of the obscuring foreground dust and gas. Observations in the N-band were carried out with the MIDI beam combiner attached to the VLTI. Additional interferometric observations which probe the structure of IRS 9A on larger scales were performed with an aperture mask installed in the T-ReCS instrument of Gemini South. The spectral energy distribution (SED) is constrained by the MIDI N-band spectrum and by data from the Spitzer Space Telescope. Our efforts to model the structure and SED of IRS 9A range from simple geometrical models of the brightness distribution to one- and two-dimensional radiative transfer computations. The target is resolved by T-ReCS, with an equivalent (elliptical) Gaussian width of 330mas by 280mas (2300 AU by 2000 AU). Despite this fact, a warm compact unresolved component was detected by MIDI which is possibly associated with the inner regions of a flattened dust distribution. Based on our interferometric data, no sign of multiplicity was found on scales between about 200AU and 700AU projected separation. A geometric model consisting of a warm (1000 K) ring (400 AU diameter) and a cool (140 K) large envelope provides a good fit to the data. No single model fitting all visibility and photometric data could be found, with disk models performing better than spherical models. While the data are clearly inconsistent with a spherical dust distribution they are insufficient to prove the existence of a disk but rather hint at a more complex dust distribution.Comment: 8 pages, 11 figures. Accepted for publication in A&

Instabilities in the Envelopes and Winds of Very Massive Stars

The high luminosity of Very Massive Stars (VMS) means that radiative forces play an important, dynamical role both in the structure and stability of their stellar envelope, and in driving strong stellar-wind mass loss. Focusing on the interplay of radiative flux and opacity, with emphasis on key distinctions between continuum vs. line opacity, this chapter reviews instabilities in the envelopes and winds of VMS. Specifically, we discuss how: 1) the iron opacity bump can induce an extensive inflation of the stellar envelope; 2) the density dependence of mean opacity leads to strange mode instabilities in the outer envelope; 3) desaturation of line-opacity by acceleration of near-surface layers initiates and sustains a line-driven stellar wind outflow; 4) an associated line-deshadowing instability leads to extensive small-scale structure in the outer regions of such line-driven winds; 5) a star with super-Eddington luminosity can develop extensive atmospheric structure from photon bubble instabilities, or from stagnation of flow that exceeds the "photon tiring" limit; 6) the associated porosity leads to a reduction in opacity that can regulate the extreme mass loss of such continuum-driven winds. Two overall themes are the potential links of such instabilities to Luminous Blue Variable (LBV) stars, and the potential role of radiation forces in establishing the upper mass limit of VMS.Comment: 44 pages, 13 figures. Chapter to appear in the book "Very Massive Stars in the Local Universe", Springer, J.S. Vink, e

Activator protein transcription factors coordinate human IL-33 expression from noncanonical promoters in chronic airway disease

IL-33 is a cytokine central to type 2 immune pathology in chronic airway disease. This cytokine is abundantly expressed in the respiratory epithelium and increased in disease, but how expression is regulated is undefined. Here we show that increased IL33 expression occurs from multiple noncanonical promoters in human chronic obstructive pulmonary disease (COPD), and it facilitates production of alternatively spliced isoforms in airway cells. We found that phorbol 12-myristate 13-acetate (PMA) can activate IL33 promoters through protein kinase C in primary airway cells and lines. Transcription factor (TF) binding arrays combined with RNA interference identified activator protein (AP) TFs as regulators of baseline and induced IL33 promoter activity. ATAC-Seq and ChIP-PCR identified chromatin accessibility and differential TF binding as additional control points for transcription from noncanonical promoters. In support of a role for these TFs in COPD pathogenesis, we found that AP-2 (TFAP2A, TFAP2C) and AP-1 (FOS and JUN) family members are upregulated in human COPD specimens. This study implicates integrative and pioneer TFs in regulating IL33 promoters and alternative splicing in human airway basal cells. Our work reveals a potentially novel approach for targeting IL-33 in development of therapeutics for COPD

Modelling the clumping-induced polarimetric variability of hot star winds

Clumping in the winds of massive stars may significantly reduce empirical mass-loss rates, and which in turn may have a large impact on our understanding of massive star evolution. Here, we investigate wind-clumping through the linear polarization induced by light scattering off the clumps. Through the use of an analytic wind clumping model, we predict the time evolution of the linear polarimetry over a large parameter space. We concentrate on the Luminous Blue Variables, which display the greatest amount of polarimetric variability and for which we recently conducted a spectropolarimetric survey. Our model results indicate that the observed level of polarimetric variability can be reproduced for two regimes of parameter space: one of a small number of massive, optically-thick clumps; and one of a very large number of low-mass clumps. Although a systematic time-resolved monitoring campaign is required to distinguish between the two scenarios, we currently favour the latter, given the short timescale of the observed polarization variability. As the polarization is predicted to scale linearly with mass-loss rate, we anticipate that all hot stars with very large mass-loss rates should display polarimetric variability. This is consistent with recent findings that intrinsic polarization is more common in stars with strong H$\alpha$ emission.Comment: 12 pages, 11 figures, accepted to A&