226 research outputs found

    The Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial

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    Previous trials (Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure [MERIT-HF], Cardiac Insufficiency Bisoprolol Study [CIBIS] II) have demonstrated a mortality benefit of β-adrenergic blockade in patients with mild to moderate heart failure. The recent Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial has extended these results to a more advanced patient population. This trial did not, however, include patients who could not reach compensation, patients with far advanced heart failure symptoms, or a significant number of black patients. Future studies of β-blockade may focus on these patients or patients with asymptomatic left ventricular dysfunction

    Mechanism of action of carvedilol in human ventricular myocardium

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    The Opacity of the Lyman Alpha Forest and Implications for Omega_{baryon} and the Ionizing Background

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    We have measured the distribution function of the flux decrement caused by Lyman alpha forest absorption in a new sample of high resolution QSO spectra. The observations are compared to the results from two simulations of the Lya forest: an Eulerian Lambda-CDM model, and an SPH standard CDM model. Good agreement between the shapes of simulated and observed distributions is achieved by globally scaling the optical depth to match the mean flux decrements. This procedure amounts to a measurement of the parameter Omega_b^2 h^3 / Gamma (where Omega_b is the baryonic matter density and Gamma is the HI ionization rate). Estimating a lower limit Gamma > 7 10^{-13} s^{-1} from the abundance of known QSOs, we derive a lower limit to the baryon density, Omega_b h^2>0.021(0.017) for the Lambda-CDM (SCDM) model. In both cases the large values are inconsistent with some recent D/H determinations (Rugers & Hogan 1996a,b), favoring a low deuterium abundance as reported by Tytler, Fan & Burles (1996). Adopting a fixed Omega_b, we can determine the evolution of the ionizing radiation field. Our models predict the intensity to be approximately constant with redshift, consistent with the assumption that the ionizing background is produced by known quasars for z < 3. However, additional sources of ionizing photons are required at higher redshift.Comment: 35 pages latex (uses aaspp4 and psfig.sty), 10 postscript figures; submitted to ApJ. The complete paper can also be retrieved at http://astro.caltech.edu/~mr/preprints/fluxdec.ps.g

    Dose-limiting, adverse event-associated bradycardia with β-blocker treatment of atrial fibrillation in the GENETIC-AF trial

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    Background: Heart failure (HF) patients with atrial fibrillation (AF) often have conduction system disorders, which may be worsened by β-blocker therapy.Objective: In a post hoc analysis we examined the prevalence of bradycardia and its association with adverse events (AEs) and failure to achieve target dose in the GENETIC-AF trial.Methods: Patients randomized to metoprolol (n = 125) or bucindolol (n = 131) entering 24-week efficacy follow-up and receiving study medication were evaluated. Bradycardia was defined as an electrocardiogram (ECG) heart rate (HR) &lt;60 beats per minute (bpm) and severe bradycardia &lt;50 bpm.Results: Mean HR in sinus rhythm (SR) was 62.6 ± 12.5 bpm for metoprolol and 68.3 ± 11.1 bpm for bucindolol (P &lt; .0001), but in AF HRs were not different (87.5 bpm vs 89.7 bpm, respectively). Episodes per patient for bucindolol vs metoprolol were 0.82 vs 2.08 (P &lt; .001) for bradycardia and 0.24 vs 0.57 for severe bradycardia (P &lt; .001), with 98.9% of the episodes occurring in SR. Patients experiencing bradycardia had a 4.15-fold higher prevalence of study medication dose reduction (P &lt;.0001) compared to patients without bradycardia. Fewer patients receiving metoprolol were at target dose (61.7% vs 74.9% for bucindolol, P &lt; .0001) at ECG recordings, and bradycardia AEs were more prevalent in the metoprolol group (13 vs 1 for bucindolol, P = .001). On multivariate analysis of 21 candidate bradycardia predictors including presence of a device with pacing capability, bucindolol treatment was associated with the greatest degree of prevention (Zodds ratio -4.24, P &lt; .0001).Conclusion: In AF-prone HF patients bradycardia may limit the effectiveness of β blockers, and this property is agent-dependent.</p

    Two warm, low-density sub-Jovian planets orbiting bright stars in K2 campaigns 13 and 14

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    We report the discovery of two planets transiting the bright stars HD 89345 (EPIC 248777106, V=9.376V=9.376, K=7.721K=7.721) in K2 Campaign 14 and HD 286123 (EPIC 247098361, V=9.822V=9.822, K=8.434K=8.434) in K2 Campaign 13. Both stars are G-type stars, one of which is at or near the end of its main sequence lifetime, and the other that is just over halfway through its main sequence lifetime. HD 89345 hosts a warm sub-Saturn (0.66 RJR_J, 0.11 MJM_J, Teq=1100T_\mathrm{eq}=1100 K) in an 11.81-day orbit. The planet is similar in size to WASP-107b, which falls in the transition region between ice giants and gas giants. HD 286123 hosts a Jupiter-sized, low-mass planet (1.06 RJR_J, 0.39 MJM_J, Teq=1000T_\mathrm{eq}=1000 K) in an 11.17-day, mildly eccentric orbit, with e=0.255±0.035e=0.255\pm0.035. Given that they orbit relatively evolved main-sequence stars and have orbital periods longer than 10 days, these planets are interesting candidates for studies of gas planet evolution, migration, and (potentially) re-inflation. Both planets have spent their entire lifetimes near the proposed stellar irradiation threshold at which giant planets become inflated, and neither shows any sign of radius inflation. They probe the regime where inflation begins to become noticeable and are valuable in constraining planet inflation models. In addition, the brightness of the host stars, combined with large atmospheric scale heights of the planets, makes these two systems favorable targets for transit spectroscopy to study their atmospheres and perhaps provide insight into the physical mechanisms that lead to inflated hot Jupiters.Comment: 16 pages, 12 figures; accepted for publication in A

    Identification of functional elements and regulatory circuits by Drosophila modENCODE

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    To gain insight into how genomic information is translated into cellular and developmental programs, the Drosophila model organism Encyclopedia of DNA Elements (modENCODE) project is comprehensively mapping transcripts, histone modifications, chromosomal proteins, transcription factors, replication proteins and intermediates, and nucleosome properties across a developmental time course and in multiple cell lines. We have generated more than 700 data sets and discovered protein-coding, noncoding, RNA regulatory, replication, and chromatin elements, more than tripling the annotated portion of the Drosophila genome. Correlated activity patterns of these elements reveal a functional regulatory network, which predicts putative new functions for genes, reveals stage- and tissue-specific regulators, and enables gene-expression prediction. Our results provide a foundation for directed experimental and computational studies in Drosophila and related species and also a model for systematic data integration toward comprehensive genomic and functional annotation