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.

Galaxy Counterparts of metal-rich Damped Lyman-alpha Absorbers - I: The case of the z=2.35 DLA towards Q2222-0946

We have initiated a survey using the newly commissioned X-shooter spectrograph to target candidate relatively metal-rich damped Lyman-alpha absorbers (DLAs). The spectral coverage of X-shooter allows us to search for not only Lyman-alpha emission, but also rest-frame optical emission lines. We have chosen DLAs where the strongest rest-frame optical lines ([OII], [OIII], Hbeta and Halpha) fall in the NIR atmospheric transmission bands. In this first paper resulting from the survey, we report on the discovery of the galaxy counterpart of the z_abs = 2.354 DLA towards the z=2.926 quasar Q2222$-0946. This DLA is amongst the most metal-rich z>2 DLAs studied so far at comparable redshifts and there is evidence for substantial depletion of refractory elements onto dust grains. We measure metallicities from ZnII, SiII, NiII, MnII and FeII of -0.46+/-0.07, -0.51+/-0.06, -0.85+/-0.06, -1.23+/-0.06, and -0.99+/-0.06, respectively. The galaxy is detected in the Lyman-alpha, [OIII] lambda4959,5007 Halpha emission lines at an impact parameter of about 0.8 arcsec (6 kpc at z_abs = 2.354). We infer a star-formation rate of 10 M_sun yr^-1, which is a lower limit due to the possibility of slit-loss. Compared to the recently determined Halpha luminosity function for z=2.2 galaxies the DLA-galaxy counterpart has a luminosity of L~0.1L^*_Halpha. The emission-line ratios are 4.0 (Lyalpha/Halpha) and 1.2 ([OIII]/Halpha). The Lyalpha line shows clear evidence for resonant scattering effects, namely an asymmetric, redshifted (relative to the systemic redshift) component and a much weaker blueshifted component. The fact that the blueshifted component is relatively weak indicates the presence of a galactic wind. The properties of the galaxy counterpart of this DLA is consistent with the prediction that metal-rich DLAs are associated with the most luminous of the DLA-galaxy counterparts.Comment: 9 pages, 7 figures. Accepted for publication in MNRA

Searching for Dust Reddening in SDSS Spectra with Damped Lyman α\alpha{} Systems

We searched for evidence of reddening of background SDSS QSO spectra due to dust in intervening DLA systems. We utilise the Data Releases 5 and 7 to arrive at sample sizes of 475 (DR5) and 676 (DR7) absorbers, based on two different published lists of SDSS DLAs. Both samples span roughly the redshift range of 2.2 < z_abs < 5.2, with a mean of z~3.0, and the majority of the DLAs (75%) below z=3.3. We construct geometric mean spectra in the absorber restframes ranging from 1240 to ~2800 A, and composite spectra of samples matching the 'DLA' QSOs in i band magnitude and emission redshift z_em, but without absorption lines. By comparing the slopes of these composite spectra with their matched counterparts, we find no sign of reddening in the ensemble of the absorbers from these samples. Owing to both the unprecedently large sizes of the DLA samples themselves and the non-DLA SDSS QSO sample, from which we can draw our matching spectra, we can place very tight limits for this non-detection ( =-0.0013+-0.0025 (DR5) and =-0.0017+-0.0022 (DR7). Interestingly, when applying our technique to the samples of York et. al. (2006), vandenBerk et al. (2008) (intervening and intrinsic MgII absorbers) and the smaller DLA-subsample and pool of comparison QSOs of Vladilo et al. (2008), we do recover their results, i.e. detect the same amount of reddening as these authors do. Furthermore, we have tested whether subsamples of our large sample in categories involving the absorbers (HI column densities, presence or absence of accompanying metal absorption, absorber redshift) or the background quasars (emission redshift, brightness) do reveal dust extinction, but found no trends. These results are at odds with both detections of dust reddening from previous studies, and also with expectations from observations of high-redshift galaxies. (abridged)Comment: 16 pages, 12 figures, accepted for publication in MNRA

On the sizes of z>2 Damped Lyman-alpha Absorbing Galaxies

Recently, the number of detected galaxy counterparts of z > 2 Damped Lyman-alpha Absorbers in QSO spectra has increased substantially so that we today have a sample of 10 detections. M{\o}ller et al. in 2004 made the prediction, based on a hint of a luminosity-metallicity relation for DLAs, that HI size should increase with increasing metallicity. In this paper we investigate the distribution of impact parameter and metallicity that would result from the correlation between galaxy size and metallicity. We compare our observations with simulated data sets given the relation of size and metallicity. The observed sample presented here supports the metallicity-size prediction: The present sample of DLA galaxies is consistent with the model distribution. Our data also show a strong relation between impact parameter and column density of HI. We furthermore compare the observations with several numerical simulations and demonstrate that the observations support a scenario where the relation between size and metallicity is driven by feedback mechanisms controlling the star-formation efficiency and outflow of enriched gas.Comment: Accepted for publishing in MNRAS lette

Velocity-Metallicity Correlation for high-z DLA Galaxies: Evidence for a Mass-Metallicity Relation?

We used our database of VLT-UVES quasar spectra to build up a sample of 70 Damped Lyman-alpha (DLA) or strong sub-DLA systems with total neutral hydrogen column densities of log N(HI)>20 and redshifts in the range 1.7<z_abs<4.3. For each of the systems, we measured in an homogeneous manner the metallicities relative to Solar, [X/H] (with X=Zn, or S or Si), and the velocity widths of low-ionization line profiles, Delta V. We provide for the first time evidence for a correlation between DLA metallicity and line profile velocity width, which is detected at the 6.1sigma significance level. This confirms the trend previously observed in a much smaller sample by Wolfe & Prochaska (1998). The best-fit linear relation is [X/H]=1.55(\pm 0.12) log Delta V -4.33(\pm 0.23) with Delta V expressed in km/s. The slope of the DLA velocity-metallicity relation is the same within uncertainties between the higher (z_abs>2.43) and the lower (z_abs<2.43) redshift halves of our sample. However, the two populations of systems are statistically different. There is a strong redshift evolution in the sense that the mean metallicity and mean velocity width increase with decreasing redshift. We argue that the existence of a DLA velocity-metallicity correlation, over more than a factor of 100 spread in metallicity, is probably the consequence of an underlying mass-metallicity relation for the galaxies responsible for DLA absorption lines. Assuming a simple linear scaling of the galaxy luminosity with the mass of the dark-matter halo, we find that the slope of the DLA velocity-metallicity relation is consistent with that of the luminosity-metallicity relation derived for local galaxies. [...] abridged.Comment: 10 pages, 4 figures, A&A in pres

Optical and structural properties of dislocations in InGaN

Threading dislocations in thick layers of InxGa1−xN (5% &amp;lt; x &amp;lt; 15%) have been investigated by means of cathodoluminescence, time-resolved cathodoluminescence, and molecular dynamics. We show that indium atoms segregate near dislocations in all the samples. This promotes the formation of In-N-In chains and atomic condensates, which localize carriers and hinder nonradiative recombination at dislocations. We note, however, that the dark halo surrounding the dislocations in the cathodoluminescence image becomes increasingly pronounced as the indium fraction of the sample increases. Using transmission electron microscopy, we attribute the dark halo to a region of lower indium content formed below the facet of the V-shaped pit that terminates the dislocation in low composition samples (x &amp;lt; 12%). For x &amp;gt; 12%, the facets of the V-defect featured dislocation bundles instead of the low indium fraction region. In this sample, the origin of the dark halo may relate to a compound effect of the dislocation bundles, of a variation of surface potential, and perhaps, of an increase in carrier diffusion length.ER-C Lindemann Trust Fellowshi

Uncovering strong MgII absorbing galaxies: Imaging below the Lyman limit

The nature of the galaxies that give rise to absorption lines, such as damped Lyman-alpha systems (DLAs) or strong MgII lines, in quasar spectra is difficult to investigate in emission. Taking advantage of the total absorption of the QSO light bluewards of the Lyman limit of two DLAs at z>3.4, we look for the continuum emission from intervening galaxies at z~2 that are identified via strong metal absorption lines. The MgII absorbers have equivalent width large enough to be potential DLA systems. Deep images are obtained with the FOcal Reducer and Spectrograph (FORS1) on the Very Large Telescope for the fields towards SDSS J110855+120953 and SDSS J140850+020522. These quasars have MgII absorption lines at z=1.87 (W_r(MgII)=2.46 A) and z=1.98 (W_r(MgII)=1.89 A), respectively, and each QSO has two intervening higher redshift DLAs at z>3. The U and R bands of FORS1 lie blue and redwards of the Lyman limit of the background DLAs, allowing us to search for emission from the foreground galaxies directly along the lines of sight to the QSOs. No galaxies are found close to the sight line of the QSO to a point source limit of U_AB=28.0. In both fields, the closest objects lie at an impact parameter of 5 arcsec corresponding to 40 kpc in projection at z=2, and have typical colours of star forming galaxies at that redshift. However, the currently available data do not allow us to confirm if the galaxies lie at the same redshifts as the absorption systems. A more extended structure is visible in the SDSS J14085+020522 field at an impact parameter of 0.8 arcsec or 7 kpc. If these objects are at z~2 their luminosities are 0.03-0.04 L* in both fields. The star formation rates estimated from the UV flux are 0.5-0.6 M_sun yr^-1. (Abbreviated).Comment: 10 pages, Accepted for publication in A&

Comparing open-source DEM frameworks for simulations of common bulk processes

Multiple software frameworks based on the Discrete Element Method (DEM) are available for simulating granular materials. All of them employ the same principles of explicit time integration, with each time step consisting of three main steps: contact detection, calculation of interactions, and integration of the equations of motion. However, there exist significant algorithmic differences, such as the choice of contact models, particle and wall shapes, and data analysis methods. Further differences can be observed in the practical implementation, including data structures, architecture, parallelization and domain decomposition techniques, user interaction, and the documentation of resources. This study compares, verifies, and benchmarks nine widely-used software frameworks. Only open-source packages were considered, as these are freely available and their underlying algorithms can be reviewed, edited, and tested. The benchmark consists of three common bulk processes: silo emptying, drum mixing, and particle impact. To keep it simple and comparable, only standard features were used, such as spherical particles and the Hertz-Mindlin model for dry contacts. Scripts for running the benchmarks in each software are provided as a dataset.</p

Comparing open-source DEM frameworks for simulations of common bulk processes

Multiple software frameworks based on the Discrete Element Method (DEM) are available for simulating granular materials. All of them employ the same principles of explicit time integration, with each time step consisting of three main steps: contact detection, calculation of interactions, and integration of the equations of motion. However, there exist significant algorithmic differences, such as the choice of contact models, particle and wall shapes, and data analysis methods. Further differences can be observed in the practical implementation, including data structures, architecture, parallelization and domain decomposition techniques, user interaction, and the documentation of resources.This study compares, verifies, and benchmarks nine widely-used software frameworks. Only open-source packages were considered, as these are freely available and their underlying algorithms can be reviewed, edited, and tested. The benchmark consists of three common bulk processes: silo emptying, drum mixing, and particle impact. To keep it simple and comparable, only standard features were used, such as spherical particles and the Hertz-Mindlin model for dry contacts. Scripts for running the benchmarks in each software are provided as a dataset

Explanations for the Lower Rates of Diabetic Neuropathy in Indian Asians Versus Europeans

OBJECTIVE - Risks of diabetes and cardiovascular disease are elevated worldwide in Indian Asians. However, risks of other diabetes-related complications, i.e., foot ulceration and amputation, also with a vascular basis, are substantially lower in Asians than in white Europeans in the U.K., possibly due to less neuropathy. We therefore compared signs, symptoms, and objective quantitative measures of diabetic neuropathy and their risk factors in Indian Asians and Europeans. RESEARCH DESIGN AND METHODS - This was a cross-sectional study of a population-based sample of age- and sex-matched adults with type 2 diabetes of European (95 male and 85 female) and Asian (96 male and 84 female) descent in the U.K. Patients were assessed for neuropathic symptoms, signs, nerve conduction, autonomic function, and quantitative sensory testing. Peripheral vascular function and other potential risk factors for neuropathy were measured. RESULTS - Mean nerve conduction velocity Z scores were better in Asians (mean ± SD 0.07 ± 0.62) than in Europeans (-0.11 ± 0.60; P = 0.007) and were explained by the shorter height, fewer pack-years smoked, and higher transcutaneous oxygen levels (TCpO2) in Indian Asians (P value for ethnic comparison attenuated to 0.2). Small fiber neuropathy was less prevalent in Indian Asians compared with Europeans (odds ratio 0.58 [95% CI 0.37-0.93]; P = 0.02) and was primarily accounted for by better TCpO2 (0.70 [0.40-1.21]; P = 0.2). CONCLUSIONS - Asians with diabetes have substantially less large and small fiber neuropathy than Europeans, despite comparable traditional risk factors. Independent from smoking, the lower risk of neuropathy in Asians is due to better skin microvascularization and may help explain the substantially reduced Asian foot ulcer risk. © 2010 by the American Diabetes Association