The Detection of Crystalline Silicates in Ultra-Luminous Infrared Galaxies

Silicates are an important component of interstellar dust and the structure of these grains -- amorphous versus crystalline -- is sensitive to the local physical conditions. We have studied the infrared spectra of a sample of ultra-luminous infrared galaxies. Here, we report the discovery of weak, narrow absorption features at 11, 16, 19, 23, and 28 microns, characteristic of crystalline silicates, superimposed on the broad absorption bands at 10 and 18 microns due to amorphous silicates in a subset of this sample. These features betray the presence of forsterite (Mg_2SiO_4), the magnesium-rich end member of the olivines. Previously, crystalline silicates have only been observed in circumstellar environments. The derived fraction of forsterite to amorphous silicates is typically 0.1 in these ULIRGs. This is much larger than the upper limit for this ratio in the interstellar medium of the Milky Way, 0.01. These results suggest that the timescale for injection of crystalline silicates into the ISM is short in a merger-driven starburst environment (e.g., as compared to the total time to dissipate the gas), pointing towards massive stars as a prominent source of crystalline silicates. Furthermore, amorphization due to cosmic rays, which is thought to be of prime importance for the local ISM, lags in vigorous starburst environments.Comment: 7 pages, 5 figures, accepted for publication in Ap

Mid-Infrared interferometry of dust around massive evolved stars

We report long-baseline interferometric measurements of circumstellar dust around massive evolved stars with the MIDI instrument on the Very Large Telescope Interferometer and provide spectrally dispersed visibilities in the 8-13 micron wavelength band. We also present diffraction-limited observations at 10.7 micron on the Keck Telescope with baselines up to 8.7 m which explore larger scale structure. We have resolved the dust shells around the late type WC stars WR 106 and WR 95, and the enigmatic NaSt1 (formerly WR 122), suspected to have recently evolved from a Luminous Blue Variable (LBV) stage. For AG Car, the protoypical LBV in our sample, we marginally resolve structure close to the star, distinct from the well-studied detached nebula. The dust shells around the two WC stars show fairly constant size in the 8-13 micron MIDI band, with gaussian half-widths of ~ 25 to 40 mas. The compact dust we detect around NaSt1 and AG Car favors recent or ongoing dust formation. Using the measured visibilities, we build spherically symmetric radiative transfer models of the WC dust shells which enable detailed comparison with existing SED-based models. Our results indicate that the inner radii of the shells are within a few tens of AU from the stars. In addition, our models favor grain size distributions with large (~ 1 micron) dust grains. This proximity of the inner dust to the hot central star emphasizes the difficulty faced by current theories in forming dust in the hostile environment around WR stars. Although we detect no direct evidence for binarity for these objects, dust production in a colliding-wind interface in a binary system is a feasible mechanism in WR systems under these conditions.Comment: 21 pages, 4 tables, 13 figures. Accepted for publication in the Astrophysical Journa

The dusty Nebula surrounding HR Car: a Spitzer view

We present mid-IR observations of the Galactic Luminous Blue Variable (LBV) HR Car and its associated nebula carried out with the Spitzer Space Telescope using both IRAC and IRS, as part of a GTO program aimed to study stellar ejecta from evolved stars. Our observations reveal a rich mid-IR spectrum of the inner nebula showing both solid state and atomic gas signatures. Strong low-excitation atomic fine structure lines such as $26.0 \mu$m [\ion{Fe}{2}] and $34.8 \mu$m [\ion{Si}{2}], indicate, for the first time, the presence of a PDR in this object class. While the physics and chemistry of the low-excitation gas appears to be dominated by photodissociation, a possible contribution due to shocks can be inferred from the evidence of gas phase Fe abundance enhancement. The presence of amorphous silicates, inferred from the observed characteristic broad feature at $10 \mu$m located in the inner nebula, suggests that dust has formed during the LBV outburst. This is in contrast with the detection of crystalline dust in other probably more evolved Galactic LBVs, which is similar to the crystalline dust observed in red supergiants. This has been considered to be evidence of dust production during evolutionary phases prior to the outburst.Comment: 27 pages, 6 figures. accepted by Ap

Rolofylline, an adenosine A1−receptor antagonist, in acute heart failure

Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1−receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure. Methods: We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient’s clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes. Results: Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A1-receptor antagonists. Conclusions: Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.

On the role of continuum-driven eruptions in the evolution of very massive stars and Population III stars

We suggest that the mass lost during the evolution of very massive stars may be dominated by optically thick, continuum-driven outbursts or explosions, instead of by steady line-driven winds. In order for a massive star to become a WR star, it must shed its H envelope, but new estimates of the effects of clumping in winds indicate that line driving is vastly insufficient. We discuss massive stars above roughly 40-50 Msun, for which the best alternative is mass loss during brief eruptions of luminous blue variables (LBVs). Our clearest example of this phenomenon is the 19th century outburst of eta Car, when the star shed 12-20 Msun or more in less than a decade. Other examples are circumstellar nebulae of LBVs, extragalactic eta Car analogs (``supernova impostors''), and massive shells around SNe and GRBs. We do not yet fully understand what triggers LBV outbursts, but they occur nonetheless, and present a fundamental mystery in stellar astrophysics. Since line opacity from metals becomes too saturated, the extreme mass loss probably arises from a continuum-driven wind or a hydrodynamic explosion, both of which are insensitive to metallicity. As such, eruptive mass loss could have played a pivotal role in the evolution and fate of massive metal-poor stars in the early universe. If they occur in these Population III stars, such eruptions would profoundly affect the chemical yield and types of remnants from early SNe and hypernovae.Comment: 4 pages, 1 figure, accepted by ApJ Letter

Clinical Determinants and Prognostic Implications of Renin and Aldosterone in Patients with Symptomatic Heart Failure

Aims Activation of the renin-angiotensin-aldosterone system plays an important role in the pathophysiology of heart failure (HF) and has been associated with poor prognosis. There are limited data on the associations of renin and aldosterone levels with clinical profiles, treatment response, and study outcomes in patients with HF. Methods and results We analysed 2,039 patients with available baseline renin and aldosterone levels in BIOSTAT-CHF (a systems BIOlogy study to Tailored Treatment in Chronic Heart Failure). The primary outcome was the composite of all-cause mortality or HF hospitalization. We also investigated changes in renin and aldosterone levels after administration of mineralocorticoid receptor antagonists (MRAs) in a subset of the EPHESUS trial and in an acute HF cohort (PORTO). In BIOSTAT-CHF study, median renin and aldosterone levels were 85.3 (percentile(25-75) = 28-247) mu IU/mL and 9.4 (percentile(25-75) = 4.4-19.8) ng/dL, respectively. Prior HF admission, lower blood pressure, sodium, poorer renal function, and MRA treatment were associated with higher renin and aldosterone. Higher renin was associated with an increased rate of the primary outcome [highest vs. lowest renin tertile: adjusted-HR (95% CI) = 1.47 (1.16-1.86), P = 0.002], whereas higher aldosterone was not [highest vs. lowest aldosterone tertile: adjusted-HR (95% CI) = 1.16 (0.93-1.44), P = 0.19]. Renin and/or aldosterone did not improve the BIOSTAT-CHF prognostic models. The rise in aldosterone with the use of MRAs was observed in EPHESUS and PORTO studies. Conclusions Circulating levels of renin and aldosterone were associated with both the disease severity and use of MRAs. By reflecting both the disease and its treatments, the prognostic discrimination of these biomarkers was poor. Our data suggest that the "point" measurement of renin and aldosterone in HF is of limited clinical utility

A combined clinical and biomarker approach to predict diuretic response in acute heart failure

Background: Poor diuretic response in acute heart failure is related to poor clinical outcome. The underlying mechanisms and pathophysiology behind diuretic resistance are incompletely understood. We evaluated a combined approach using clinical characteristics and biomarkers to predict diuretic response in acute heart failure (AHF). Methods and results: We investigated explanatory and predictive models for diuretic response—weight loss at day 4 per 40 mg of furosemide—in 974 patients with AHF included in the PROTECT trial. Biomarkers, addressing multiple pathophysiological pathways, were determined at baseline and after 24 h. An explanatory baseline biomarker model of a poor diuretic response included low potassium, chloride, hemoglobin, myeloperoxidase, and high blood urea nitrogen, albumin, triglycerides, ST2 and neutrophil gelatinase-associated lipocalin (r2 = 0.086). Diuretic response after 24 h (early diuretic response) was a strong predictor of diuretic response (β = 0.467, P < 0.001; r2 = 0.523). Addition of diuretic response after 24 h to biomarkers and clinical characteristics significantly improved the predictive model (r2 = 0.586, P < 0.001). Conclusions: Biomarkers indicate that diuretic unresponsiveness is associated with an atherosclerotic profile with abnormal renal function and electrolytes. However, predicting diuretic response is difficult and biomarkers have limited additive value. Patients at risk of poor diuretic response can be identified by measuring early diuretic response after 24 h

Biomarker profiles of acute heart failure patients with a mid-range ejection fraction

OBJECTIVES: In this study, the authors used biomarker profiles to characterize differences between patients with acute heart failure with a midrange ejection fraction (HFmrEF) and compare them with patients with a reduced (heart failure with a reduced ejection fraction [HFrEF]) and preserved (heart failure with a preserved ejection fraction [HFpEF]) ejection fraction. BACKGROUND: Limited data are available on biomarker profiles in acute HFmrEF. METHODS: A panel of 37 biomarkers from different pathophysiological domains (e.g., myocardial stretch, inflammation, angiogenesis, oxidative stress, hematopoiesis) were measured at admission and after 24 h in 843 acute heart failure patients from the PROTECT trial. HFpEF was defined as left ventricular ejection fraction (LVEF) of ≥50% (n = 108), HFrEF as LVEF of <40% (n = 607), and HFmrEF as LVEF of 40% to 49% (n = 128). RESULTS: Hemoglobin and brain natriuretic peptide levels (300 pg/ml [HFpEF]; 397 pg/ml [HFmrEF]; 521 pg/ml [HFrEF]; ptrend <0.001) showed an upward trend with decreasing LVEF. Network analysis showed that in HFrEF interactions between biomarkers were mostly related to cardiac stretch, whereas in HFpEF, biomarker interactions were mostly related to inflammation. In HFmrEF, biomarker interactions were both related to inflammation and cardiac stretch. In HFpEF and HFmrEF (but not in HFrEF), remodeling markers at admission and changes in levels of inflammatory markers across the first 24 h were predictive for all-cause mortality and rehospitalization at 60 days (pinteraction <0.05). CONCLUSIONS: Biomarker profiles in patients with acute HFrEF were mainly related to cardiac stretch and in HFpEF related to inflammation. Patients with HFmrEF showed an intermediate biomarker profile with biomarker interactions between both cardiac stretch and inflammation markers. (PROTECT-1: A Study of the Selective A1 Adenosine Receptor Antagonist KW-3902 for Patients Hospitalized With Acute HF and Volume Overload to Assess Treatment Effect on Congestion and Renal Function; NCT00328692)