Search for jet extinction in the inclusive jet-pT spectrum from proton-proton collisions at s=8 TeV

Published by the American Physical Society under the terms of the Creative Commons Attribution 3.0 License. Further distribution of this work must maintain attribution to the author(s) and the published articles title, journal citation, and DOI.The first search at the LHC for the extinction of QCD jet production is presented, using data collected with the CMS detector corresponding to an integrated luminosity of 10.7  fb−1 of proton-proton collisions at a center-of-mass energy of 8 TeV. The extinction model studied in this analysis is motivated by the search for signatures of strong gravity at the TeV scale (terascale gravity) and assumes the existence of string couplings in the strong-coupling limit. In this limit, the string model predicts the suppression of all high-transverse-momentum standard model processes, including jet production, beyond a certain energy scale. To test this prediction, the measured transverse-momentum spectrum is compared to the theoretical prediction of the standard model. No significant deficit of events is found at high transverse momentum. A 95% confidence level lower limit of 3.3 TeV is set on the extinction mass scale

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Searches for electroweak neutralino and chargino production in channels with Higgs, Z, and W bosons in pp collisions at 8 TeV

Searches for supersymmetry (SUSY) are presented based on the electroweak pair production of neutralinos and charginos, leading to decay channels with Higgs, Z, and W bosons and undetected lightest SUSY particles (LSPs). The data sample corresponds to an integrated luminosity of about 19.5 fb(-1) of proton-proton collisions at a center-of-mass energy of 8 TeV collected in 2012 with the CMS detector at the LHC. The main emphasis is neutralino pair production in which each neutralino decays either to a Higgs boson (h) and an LSP or to a Z boson and an LSP, leading to hh, hZ, and ZZ states with missing transverse energy (E-T(miss)). A second aspect is chargino-neutralino pair production, leading to hW states with E-T(miss). The decays of a Higgs boson to a bottom-quark pair, to a photon pair, and to final states with leptons are considered in conjunction with hadronic and leptonic decay modes of the Z and W bosons. No evidence is found for supersymmetric particles, and 95% confidence level upper limits are evaluated for the respective pair production cross sections and for neutralino and chargino mass values

The effect of duration of follow-up and presence of competing risk on lifespan-gain from implantable cardioverter defibrillator therapy: who benefits the most?

Background: In at-risk patients with left ventricular dysfunction, implantable cardioverter defibrillators (ICDs) prolong life. Implantable cardioverter defibrillators are increasingly implanted for primary prevention and therefore into lower risk patients. Trial data have demonstrated the benefit of these devices but does not provide an estimate of potential lifespan-gain over longer time periods, e.g. a patient's lifespan. Methods: Using data from landmark ICD trials, lifespan-gain was plotted against baseline annual mortality in the individual trials. Lifespan-gain was then extrapolated to a time-horizon of >20 years while adjusting for increasing ‘competing’ risk from ageing and non-sudden cardiac death (pump failure). Results: At 3 years, directly observed lifespan-gain was strongly dependent on baseline event rate (r = 0.94, P < 0.001). However, projecting beyond the duration of the trial, lifespan-gain increases rapidly and non-linearly with time. At 3 years, it averages 1.7 months, but by 10 years up to 9-fold more. Lifespan-gain over time horizons >20 years were greatest in lower risk patients (∼5 life-years for 5% baseline mortality, ∼2 life-years for 15% baseline mortality). Increased competing risks significantly reduce lifespan-gain from ICD implantation. Conclusion: While high-risk patients may show the greatest short-term gain, the dramatic growth of lifespan-gain over time means that it is the lower risk patients, e.g. primary prevention ICD implantation, who gain the most life-years over their lifetime. Benefit is underestimated when only trial data are assessed as trials can only maintain randomization over limited periods. Lifespan-gain may be further increased through advances in ICD device programming

The effect of duration of follow-up and presence of competing risk on lifespan-gain from implantable cardioverter defibrillator therapy: who benefits the most?

Background: In at-risk patients with left ventricular dysfunction, implantable cardioverter defibrillators (ICDs) prolong life. Implantable cardioverter defibrillators are increasingly implanted for primary prevention and therefore into lower risk patients. Trial data have demonstrated the benefit of these devices but does not provide an estimate of potential lifespan-gain over longer time periods, e.g. a patient's lifespan. Methods: Using data from landmark ICD trials, lifespan-gain was plotted against baseline annual mortality in the individual trials. Lifespan-gain was then extrapolated to a time-horizon of >20 years while adjusting for increasing ‘competing’ risk from ageing and non-sudden cardiac death (pump failure). Results: At 3 years, directly observed lifespan-gain was strongly dependent on baseline event rate (r = 0.94, P < 0.001). However, projecting beyond the duration of the trial, lifespan-gain increases rapidly and non-linearly with time. At 3 years, it averages 1.7 months, but by 10 years up to 9-fold more. Lifespan-gain over time horizons >20 years were greatest in lower risk patients (∼5 life-years for 5% baseline mortality, ∼2 life-years for 15% baseline mortality). Increased competing risks significantly reduce lifespan-gain from ICD implantation. Conclusion: While high-risk patients may show the greatest short-term gain, the dramatic growth of lifespan-gain over time means that it is the lower risk patients, e.g. primary prevention ICD implantation, who gain the most life-years over their lifetime. Benefit is underestimated when only trial data are assessed as trials can only maintain randomization over limited periods. Lifespan-gain may be further increased through advances in ICD device programming

A novel method to predict the proportional risk of sudden cardiac death in heart failure: derivation of the Seattle Proportional Risk Model

Background: Patients with heart failure are at increased risk of both sudden death and pump failure death. Strategies to better identify those who have greatest net benefit from implantable cardioverter-defibrillator (ICD) implantation could reduce morbidity and maximize cost-effectiveness of ICDs. Objective: We aimed to identify baseline variables in patients with cardiomyopathy that are independently associated with a disproportionate fraction of mortality risk attributable to sudden death vs nonsudden death. Methods: We used data from 9885 patients with heart failure without ICDs, of whom 2552 died during an average follow-up of 2.3 years. Using commonly available baseline clinical and demographic variables, we developed a multivariate regression model to identify variables associated with a disproportionate risk of sudden death. Results: We confirmed that lower ejection fraction and better functional class were associated with a greater proportion of mortality due to sudden death. Younger age, male sex, and higher body mass index were independently associated with a greater proportional risk of sudden death, while diabetes mellitus, hyper/hypotension, higher creatinine level, and hyponatremia were associated with a disproportionately lower risk of sudden death. The use of several heart failure medications, left ventricular end-diastolic dimension, or NT-pro brain natriuretic peptide concentrations were not associated with a disproportionate risk of sudden death. Conclusion: Several easily obtained baseline demographic and clinical variables, beyond ejection fraction and New York Heart Association functional class, are independently associated with a disproportionately increased risk of sudden death. Further investigation is needed to assess whether this novel predictive method can be used to target the use of lifesaving therapies to populations who will derive greatest mortality benefit