Gamma-ray Observations Under Bright Moonlight with VERITAS

Imaging atmospheric Cherenkov telescopes (IACTs) are equipped with sensitive photomultiplier tube (PMT) cameras. Exposure to high levels of background illumination degrades the efficiency of and potentially destroys these photo-detectors over time, so IACTs cannot be operated in the same configuration in the presence of bright moonlight as under dark skies. Since September 2012, observations have been carried out with the VERITAS IACTs under bright moonlight (defined as about three times the night-sky-background (NSB) of a dark extragalactic field, typically occurring when Moon illumination > 35%) in two observing modes, firstly by reducing the voltage applied to the PMTs and, secondly, with the addition of ultra-violet (UV) bandpass filters to the cameras. This has allowed observations at up to about 30 times previous NSB levels (around 80% Moon illumination), resulting in 30% more observing time between the two modes over the course of a year. These additional observations have already allowed for the detection of a flare from the 1ES 1727+502 and for an observing program targeting a measurement of the cosmic-ray positron fraction. We provide details of these new observing modes and their performance relative to the standard VERITAS observations

Upper limits from five years of blazar observations with the VERITAS Cherenkov telescopes

Between the beginning of its full-scale scientific operations in 2007 and 2012, the VERITAS Cherenkov telescope array observed more than 130 blazars; of these, 26 were detected as very-high-energy (VHE; E > 100 GeV) γ-ray sources. In this work, we present the analysis results of a sample of 114 undetected objects. The observations constitute a total live-time of ~570 hr. The sample includes several unidentified Fermi-Large Area Telescope (LAT) sources (located at high Galactic latitude) as well as all the sources from the second Fermi-LAT catalog that are contained within the field of view of the VERITAS observations. We have also performed optical spectroscopy measurements in order to estimate the redshift of some of these blazars that do not have spectroscopic distance estimates. We present new optical spectra from the Kast instrument on the Shane telescope at the Lick observatory for 18 blazars included in this work, which allowed for the successful measurement or constraint on the redshift of four of them. For each of the blazars included in our sample, we provide the flux upper limit in the VERITAS energy band. We also study the properties of the significance distributions and we present the result of a stacked analysis of the data set, which shows a 4σ excess

Oncogenic Signaling Pathways in The Cancer Genome Atlas

Genetic alterations in signaling pathways that control cell-cycle progression, apoptosis, and cell growth are common hallmarks of cancer, but the extent, mechanisms, and co-occurrence of alterations in these pathways differ between individual tumors and tumor types. Using mutations, copy-number changes, mRNA expression, gene fusions and DNA methylation in 9,125 tumors profiled by The Cancer Genome Atlas (TCGA), we analyzed the mechanisms and patterns of somatic alterations in ten canonical pathways: cell cycle, Hippo, Myc, Notch, Nrf2, PI-3-Kinase/Akt, RTK-RAS, TGFb signaling, p53 and beta-catenin/Wnt. We charted the detailed landscape of pathway alterations in 33 cancer types, stratified into 64 subtypes, and identified patterns of co-occurrence and mutual exclusivity. Eighty-nine percent of tumors had at least one driver alteration in these one alteration potentially targetable by currently available drugs. Thirty percent of tumors had multiple targetable alterations, indicating opportunities for combination therapy

Electrical cardioversion for atrial fibrillation: outcomes in 'real-life' clinical practice

Background: There is currently considerable debate with regard to the optimal management of atrial fibrillation/flutter (AF), including the long-term success of electrical cardioversion and the duration of anti-coagulation thereafter. The aim of this study was to investigate the current management and outcomes of electrical cardioversion in unselected patients in ordinary clinical practice. Methods: A prospective, observational study of 111 consecutive patients with AF who had been referred for electrical cardioversion was undertaken in a large teaching hospital. After cardioversion, patients were followed-up for 12 months or until death if this occurred earlier. Results: Sinus rhythm was restored immediately in 96 of 111 (86%) patients. Only 54 of 88 (61%) patients in sinus rhythm at discharge remained in this rhythm at 1 month. Of these 54, a further 21 (39%) had relapsed into AF by 12 months. Independent predictors of sinus rhythm at discharge were younger age (for a difference of 5 years, odds ratio=1.54; 95% confidence interval 1.04 to 1.16; P=0.002) and absence of hypertension (1.73, 1.22–1.91; P=0.015). The presence of sinus rhythm at discharge (6.4, 1.6–25.3; P=0.007) was an independent predictor of sinus rhythm at 1 month, whereas older age was a negative predictor (0.96, 0.92–1.0; P=0.05). Health-related quality of life improved at 1 and 12 months in those patients who remained in sinus rhythm compared to those who remained in AF. Conclusions: Though electrical cardioversion for AF has a high initial success rate only a minority of patients remained in sinus rhythm 1 year. The common practice of discontinuing anticoagulant treatment in patients in sinus rhythm at 1 month may be unsafe. Long-term maintenance of sinus rhythm is, however, associated with better health-related quality of life

Short-term haemodynamic effects of BQ-123, a selective endothelin ETA-receptor antagonist, in chronic heart failure

No abstract available

Pulmonary and systemic responses to exogenous endothelin-1 in patients with left ventricular dysfunction

lasma levels of immunoreactive endothelin-1 (ET-1) are elevated in chronic heart failure(CHF) and have been reported to correlate closely with pulmonary hemodynamic measurements. We investigated the effects of exogenous ET-1 on the pulmonary vasculature in patients with left ventricular systolic dysfunction (LVD), with or without overt heart failure. ET-1 was infused at 1, 5, and 15 pmol/min into a distal pulmonary artery of 10 patients with LVD. Hemodynamics were measured by a thermodilution catheter and arterial line. Intravascular Doppler and local pulmonary angiography were used to assess local pulmonary blood flow in the first four patients. Systemic hemodynamic changes occurred with ET-1 infusion in a dose-dependent fashion. Mean arterial pressure (100 ± 8-107± 11 mm Hg; p < 0.01) and systemic vascular resistance (1,699± 375-2,033 ± 427 dynes/s/cm-5; p < 0.001) rose, whereas the cardiac index fell from 2.43 ± 0.53 to 2.20 ± 0.491/min/m2(p < 0.002). However, mean pulmonary artery pressure (21 ± 7 mm Hg) and pulmonary vascular resistance (151 ± 43-147 ± 43 dynes/s/cm-5) did not change. Exogenous ET-1, when infused into patients with LVD, causes systemic but not pulmonary vasoconstriction

EndothelinB receptors are functionally important in mediating vasoconstriction in the systemic circulation in patients with left ventricular systolic dysfunction

OBJECTIVES: This study was designed to assess the functional importance of endothelin (ET)B receptors in patients with left ventricular systolic dysfunction (LVSD) by comparing the hemodynamic effects of ET-1, a nonselective ETA and ETB agonist, with ET-3, a selective ETB receptor agonist.<p></p> BACKGROUND: Knowledge of the functional importance of ETB receptors in mediating vasoconstriction in chronic heart failure will help determine whether antagonists at both ETA and ETB receptors are required to fully prevent vasoconstriction to endogenously produced ET-1.<p></p> METHODS: We infused ET-1 (5 and 15 pmol/min) and ET-3 (5 and 15 pmol/min) into two separate groups of eight patients with LVSD with similar baseline hemodynamic indices. Hemodynamics were measured using a pulmonary thermodilution catheter and an arterial line.<p></p> RESULTS: Endothelin-1 infusion led to systemic vasoconstriction, with a rise in mean arterial pressure (mean ± SEM 100 ± 3 to 105 ± 3 mm Hg, p < 0.02) and systemic vascular resistance (1,727 ± 142 to 2,055 ± 164 dyn/s/cm−5, p < 0.001) and a fall in cardiac index (2.44 ± 0.21 to 2.22 ± 0.20 liters/min/m2, p < 0.01). Endothelin-3 infusion also led to systemic vasoconstriction, with a rise in mean arterial pressure (99 ± 6 to 105 ± 6 mm Hg, p < 0.01) and systemic vascular resistance (1,639 ± 210 to 1,918 ± 245 dyn/s/cm−5, p < 0.01) and a fall in cardiac index (2.66 ± 0.28 to 2.42 ± 0.24 liters/min/m2, p < 0.05). Pulmonary hemodynamic measurements did not change significantly in either group.<p></p> CONCLUSIONS: Both ET-1 and ET-3 infusions led to systemic vasoconstriction; the hemodynamic changes observed were of a similar magnitude at the same molar concentration. This suggests that ETB receptors are functionally important in mediating vasoconstriction, at least in the systemic circulation, in patients with LVSD