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

Wpływ korozji ciernej na wytrzymałość zmęczeniową materiału części silnika turbiny gazowej

The paper presents the results of a study on the fretting corrosion effect on strength as per the diagrams of material fatigue of low-cycle and high-cycle loading. An experimental study of the effect of fretting corrosion on fatigue of a titanium alloy VT3-1 showed that, when choosing a particular technological method to increase fatigue resistance of gas turbine engine parts operating under fretting corrosion conditions, it is necessary to take into account the fact that fretting itself is intensive strengthening and at the same time a softening factor affecting the surface layers of the material. Technological methods of surface plastic deformation treatment result in a significant change in the parameters of metal surface layer state, which depends on both the type and duration of treatment. If the power and time parameters of processing are too high, the surface may be re-cold worked and the surface layer of the material almost completely exhausts the reserve of plasticity, as a result dangerous microcracks occur, and the formation of particles of flaking metal emerge. Possible ways using technological methods have been suggested by the authors to improve fretting strength of part surfaces operating under fretting corrosion conditions.W artykule przedstawiono wyniki badań wpływu korozji ciernej na wytrzymałość zmęczeniową przy niskiej i wysokiej częstotliwości obciążania. Eksperymentalne badania wpływu korozji ciernej na zmęczenie stopu tytanu VT3-1 wykazały, że wybierając metodę technologicznego zwiększania odporności zmęczeniowej części silników turbogazowych pracujących w warunkach korozji ciernej, należy wziąć pod uwagę fakt, że sam fretting jest czynnikiem wzmacniającym i jednocześnie osłabiającym warstwy wierzchnie materiału. Technologiczne metody powierzchniowej obróbki plastycznej powodują istotną zmianę parametrów stanu warstwy metalu w zależności zarówno od rodzaju, jak i czasu trwania obróbki. Gdy parametry obróbki (moc i czas) są zbyt duże, powierzchnia zostaje poddana obróbce na zimno, warstwa wierzchnia materiału nie jest podatna na odkształcenie plastyczne, wobec czego powstają niebezpieczne mikropęknięcia oraz tworzą się odpryski. Wskazano potencjalne zabiegi technologiczne rekomendowane do zwiększenia odporności elementów maszyn pracujących w warunkach występowania korozji ciernej

Morphology, structure, and optical properties of semiconductor films with GeSiSn nanoislands and strained layers

The dependences of the two-dimensional to three-dimensional growth (2D-3D) critical transition thickness on the composition for GeSiSn films with a fixed Ge content and Sn content from 0 to 16% at the growth temperature of 150 °С have been obtained. The phase diagrams of the superstructure change during the epitaxial growth of Sn on Si and on Ge(100) have been built. Using the phase diagram data, it becomes possible to identify the Sn cover on the Si surface and to control the Sn segregation on the superstructure observed on the reflection high-energy electron diffraction (RHEED) pattern. The multilayer structures with the GeSiSn pseudomorphic layers and island array of a density up to 1.8 × 1012 cm−2 have been grown with the considering of the Sn segregation suppression by the decrease of GeSiSn and Si growth temperature. The double-domain (10 × 1) superstructure related to the presence of Sn on the surface was first observed in the multilayer periodic structures during Si growth on the GeSiSn layer. The periodical GeSiSn/Si structures demonstrated the photoluminescence in the range of 0.6–0.85 eV corresponding to the wavelength range of 1.45–2 μm. The calculation of the band diagram for the structure with the pseudomorphic Ge0.315Si0.65Sn0.035 layers allows assuming that photoluminescence peaks correspond to the interband transitions between the X valley in Si or the Δ4-valley in GeSiSn and the subband of heavy holes in the GeSiSn layer

Formation of SnO and SnO2 phases during the annealing of SnO(x) films obtained by molecular beam epitaxy

SnO and SnO2 films were obtained on the SiO2 surface by the molecular-beam epitaxy method. The initial film

Effect of Sn for the dislocation-free SiSn nanostructure formation on the vapor-liquid-crystal mechanism

Structures with tin-rich island arrays on silicon pedestals were obtained by molecular beam epitaxy using Sn as a catalyst for the growth of nanostructures. A tin island array was used further to study the growth of nanostructures in the process of Si deposition on the surface with Sn islands. It was established that, during the growth on the vapor-liquid-crystal mechanism, tin-rich islands are formed on faceted pedestals. A nanostructured cellular surface was formed between the islands on pedestals. The analysis of the elemental composition of the obtained nanostructures was performed by the methods of energy dispersive X-ray spectroscopy and photoelectron spectroscopy. It is shown that tin-rich islands can contain up to 90% tin, whereas the pedestal consists of silicon. The transmission electron microscopy data demonstrated a distinct crystal structure of tin-rich islands and silicon pedestals, as well as the absence of dislocations in the structures with island arrays on the faceted pedestals. The facet tilt angle is 19° and corresponds to the (311) plane. The photoluminescence signal was observed with a photoluminescence maximum near the wavelength of 1.55 μm

Effect of annealing temperature on the morphology, structure, and optical properties of nanostructured SnO(x) films

Fabrication and characterization of titanium dioxide (TiO2) thin film on Al/TiO2/SiO2/p-Si MIS structure for the study of morphology, optical and electrical properties were reported. A transparent and high crystallinity of TiO2 thin films were prepared at room temperature (~25 °C) by sol–gel route. TiO2 sol suspension were prepared at molar ratio of TTIP:EtOH:AA = 2:15:1 using titanium tetra-isopropoxide (TTIP) and a mixture of absolute ethanol (EtOH) and acetic acid (AA) which used as a precursor and catalyst for the peptization, respectively. The TiO2 thin films were deposited on a thermally grown SiO2 layer of p-type silicon (100) substrates and were thermally treated at different annealing temperatures of 300, 500, 700 and 900 °C. For study of optical properties, the TiO2 thin films were deposited on a glass slides substrate and were annealed from 200 to 700 °C. The XRD results show that the presence of an amorphous TiO2 phases were transformed into the polycrystalline (anatase or rutile) with good crystallinity after treated at higher annealing temperatures. Besides, the surface roughness of TiO2 thin films increased with increasing annealing temperatures. In addition, the resistivity of the thin films decreased from 2.5751E+8 to 6.714E+7 Ω cm with the increasing temperatures. Moreover, the optical absorbance of TiO2 thin films exhibited high UV–visible light absorption with band gap energy shifted to the higher wavelength (low energy photons). The band gap energy (Eg) of the films decreased from 3.79 to 3.16 eV and from 3.95 to 3.75 eV significantly for direct band allowed and indirect band allowed, respectively, with the increasing annealing temperatures

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.)