Optimization and first electronic implementation of the Constant-Fraction Time-Over-Threshold pulse shape discrimination method

In this contribution we report on further investigations of the recently-evaluated Constant-Fraction Time-over-Threshold (CF-ToT) method for neutron/gamma-ray pulse shape discrimination (PSD). The superiority of the CF-ToT PSD method over the constant-threshold (CT-ToT) method was previously demonstrated, down to low neutron energy thresholds of 100 keVee. Here, we report on a quantitative comparison between the traditionally used Charge Comparison (CC) method and the CF-ToT method using a stilbene scintillator coupled to a silicon photomultiplier, implementing an offline analysis of recorded fast-neutron and gamma-ray waveforms. An optimization of the constant fraction value indicates that a 20%-fraction yields the optimum figure-of-merit (FOM) and gamma-ray peak-to-valley (P/V) ratio. The results obtained for a particle energy threshold of 100 keVee show that the FOM and P/V values achieved with the CF-ToT method are superior to those obtained using the standard CC method. In addition, a first electronic implementation of the CF-ToT method was performed using simple circuitry suitable for multichannel architecture. Initial results obtained with this circuit prototype are presented.Comment: 10 pages, 8 figures. To be submitted to JINS

The BEAUTIFUL study: randomized trial of ivabradine in patients with stable coronary artery disease and left ventricular systolic dysfunction – baseline characteristics of the study population

<p>Objectives: Ivabradine is a selective heart rate-lowering agent that acts by inhibiting the pacemaker current If in sinoatrial node cells. Patients with coronary artery disease and left ventricular dysfunction are at high risk of death and cardiac events, and the BEAUTIFUL study was designed to evaluate the effects of ivabradine on outcome in such patients receiving optimal medical therapy. This report describes the study population at baseline.</p> <p>Methods: BEAUTIFUL is an international, multicentre, randomized, double-blind trial to compare ivabradine with placebo in reducing mortality and cardiovascular events in patients with stable coronary artery disease and left ventricular systolic dysfunction (ejection fraction <40%).</p> <p>Results: A total of 10,917 patients were randomized. At baseline, their mean age was 65 years, 83% were male, 98% Caucasian, 88% had previous myocardial infarction, 37% had diabetes, and 40% had metabolic syndrome. Mean ejection fraction was 32% and resting heart rate was 71.6 bpm. Concomitant medications included beta-blockers (87%), renin-angiotensin system agents (89%), antithrombotic agents (94%), and lipid-lowering agents (76%).</p> <p>Conclusions: Main results from BEAUTIFUL are expected in 2008, and should show whether ivabradine, on top of optimal medical treatment, reduces mortality and cardiovascular events in this population of high-risk patients.</p&gt

Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial

<p><b>Background</b> Ivabradine specifically inhibits the I-f current in the sinoatrial node to lower heart rate, without affecting other aspects of cardiac function. We aimed to test whether lowering the heart rate with ivabradine reduces cardiovascular death and morbidity in patients with coronary artery disease and left-ventricular systolic dysfunction.</p> <p><b>Methods</b> Between December, 2004, and December, 2006, we screened 12473 patients at 781 centres in 33 countries. We enrolled 10 917 eligible patients who had coronary artery disease and a left-ventricular ejection fraction of less than 40% in a randomised, double-blind, placebo-controlled, parallel-group trial. 5479 patients received 5 mg ivabradine, with the intention of increasing to the target dose of 7.5 mg twice a day, and 5438 received matched placebo in addition to appropriate cardiovascular medication. The primary endpoint was a composite of cardiovascular death admission to hospital for acute myocardial infarction, and admission to hospital for new onset or worsening heart failure. We analysed patients by intention to treat. The study is registered with ClinicalTrials.gov, number NCT00143507.</p> <p><b>Findings</b> Mean heart rate at baseline was 71.6 (SD 9.9) beats per minute (bpm). Median follow-tip was 19 months (IQR 16-24). Ivabradine reduced heart rate by 6 bpm (S E 0.2) at 12 months, corrected for placebo. Most (87%) patients were receiving beta blockers in addition to study drugs, and no safety concerns were identified. Ivabradine did not affect the primary composite endpoint (hazard ratio 1. 00, 95% CI 0 . 91-1. 1, p=0 . 94). 1233 (22 . 5%) patients in the ivabradine group had serious adverse events, compared with 1239 (22.8%) controls (p=0.70). In a prespecified subgroup of patients with heart rate of 70 bpm or greater, ivabradine treatment did not affect the primary composite outcome (hazard ratio 0 . 91, 95% CI 0 . 81-1.04, p=0.17), cardiovascular death, or admission to hospital for new-onset or worsening heart failure. However, it did reduce secondary endpoints: admission to hospital for fatal and non-fatal myocardial infarction (0 . 64, 95% CI 0 . 49-0 . 84, p=0 . 001) and coronary revascularisation (0. 70, 95% CI 0 . 52-0.93, p=0 .016).</p> <p><b>Interpretation</b> Reduction in heart rate with ivabradine does not improve cardiac outcomes in all patients with stable coronary artery disease and left-ventricular systolic dysfunction, but could be used to reduce the incidence of coronary artery disease outcomes in a subgroup of patients who have heart rates of 70 bprn or greater.</p&gt