The first high-resolution observations of 37.7-, 38.3- and 38.5-GHz methanol masers

We have used the Australia Telescope Compact Array (ATCA) to undertake the first high angular resolution observations of 37.7-GHz ($7_{-2} - 8_{-1}E$) methanol masers towards a sample of eleven high-mass star formation regions which host strong 6.7-GHz methanol masers. The 37.7-GHz methanol sites are coincident to within the astrometric uncertainty (0.4 arcseconds) with the 6.7-GHz methanol masers associated with the same star formation region. However, spatial and spectral comparison of the 6.7- and 37.7-GHz maser emission within individual sources shows that the 37.7-GHz masers are less often, or to a lesser degree co-spatial than are the 12.2-GHz and 6.7-GHz masers. We also made sensitive, high angular resolution observations of the 38.3- and 38.5-GHz class II methanol transitions ($6_{2} - 5_{3}A^{-}$ and $6_{2} - 5_{3}A^{+}$, respectively) and the 36.2-GHz ($4_{-1} - 3_{0}E$) class I methanol transition towards the same sample of eleven sources. The 37.7-, 38.3- and 38.5-GHz methanol masers are unresolved in the current observations, which implies a lower limit on the brightness temperature of the strongest masers of more than $10^6$K. We detected the 38.3-GHz methanol transition towards 7 sources, 5 of which are new detections and detected the 38.5-GHz transition towards 6 sources, 4 of which are new detections. We detected 36.2-GHz class I methanol masers towards all eleven sources, 6 of these are new detections for this transition, of which 4 sources do not have previously reported class I methanol masers from any transition.Comment: Accepted for publication in MNRAS, 34 pages, 20 figure

Maser action in methanol transitions

We report the detection with the ATCA of 6.7 GHz methanol emission towards OMC-1. The source has a size between 40'' and 90'', is located to the south-east of Ori-KL and may coincide in position with the 25 GHz masers. The source may be an example of an interesting case recently predicted in theory where the transitions of traditionally different methanol maser classes show maser activity simultaneously. In addition, results of recent search for methanol masers from the 25 and 104.3 GHz transitions are reported.Comment: To appear in the Proceedings of the 2004 European Workshop: "Dense Molecular Gas around Protostars and in Galactic Nuclei", Eds. Y.Hagiwara, W.A.Baan, H.J. van Langevelde, 2004, a special issue of ApSS, Kluwer; author list has been corrected, text is unchange

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

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)