Enabling Exploration Missions Now: Applications of On-orbit Staging

Future NASA Exploration goals are difficult to meet using current launch vehicle implementations and techniques. We introduce a concept of On-Orbit Staging (OOS) using multiple launches into a Low Earth orbit (LEO) staging area to increase payload mass and reduce overall cost for exploration initiative missions. This concept is a forward-looking implementation of ideas put forth by Oberth and Von Braun to address the total mission design. Applying staging throughout the mission and utilizing technological advances in propulsion efficiency and architecture enable us to show that exploration goals can be met in the next decade. As part of this architecture, we assume the readiness of automated rendezvous, docking, and assembly technology

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

Maximum rooting depth of vegetation types at the global scale

The depth at which plants are able to grow roots has important implications for the whole ecosystem hydrological balance, as well as for carbon and nutrient cycling. Here we summarize maximum rooting depth of species belonging to the major terrestrial biomes. We found 290 observations of maximum rooting depth in the literature which covered 255 woody and herbaceous species. Maximum rooting depth ranged from 0.3 m for some tundra species to 68 m for Boscia albitrunca in the central Kalahari; 196 species had roots at least 2 m deep, 50 species had roots at a depth of 5 m or more, and 22 species had roots as deep as 10 m or more. The average for the globe was 4.6 +0.5 m. Maximum root depth by biome was 2.0 m for boreal forest, 2.1 m for cropland, 9.5 m for desert, 5.2 m for sclerophyllous shrubland and forest, 3.9 m for temperate coniferous forest, 2.9 m for temperate deciduous forest, 2.6 m for temperate grassland, 3.7 m for tropical deciduous forest, 7.3 m for tropical evergreen forest, 15.0 m for tropical grassland/savanna, and 0.5 m for tundra. Grouping all species across biomes (except croplands) by three basic functional groups (trees, shrubs, and herbaceous plants), the average maximum rooting depth was 7.0 m for trees, 5.1 m for shrubs, and 2.6 m for herbaceous plants

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.)