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

Archaeological cooperation in the Soviet Union and Russia from the 1950s to the early 2020s at the University of Helsinki

‘East archaeology’, research cooperation in the areas of present-day Russia, has been one part of the research activities of the Department of Archaeology at the University of Helsinki in the post-war era. The first steps were taken as part of the state-controlled Finnish-Soviet scientific cooperation between the 1950s and 1970s, but Glasnost and Perestroika opened up a whole new range of opportunities in the 1980s and 1990s. Initially, the collaboration focused primarily on the Karelian Iron Age, but soon expanded to the other periods of prehistory, the Stone Age and the Early Metal Period. A significant part of the research has been conducted in areas near Finland – the Karelian Isthmus and Ingria, the Karelian Republic, and the Kola Peninsula – but several other parts of Russia have also attracted attention over the years. The purpose of this article is to present the history of these ‘eastern’ studies from the beginning to the early 2020s; cooperation has currently been stopped as a consequence of Russian politics, which culminated in the war in Ukraine in 2022

Specifics of Asbestos Utilization in the Second Half of the 4th Millenium Bc in the Eastern Fennoscandia (on the materials of lithic workshop Fofanovo XIII)

The authors analys the cultural phenomenon of asbestos ware in the forest zone of North-eastern Europe in the second half of the 4th millennium BC. The dynamic of this phenomenon is studied on the materials of the site Fofanovo XIII, which combines characteristics of metatuff adze and axe workshop, asbestos ware workshop, and interregional center for social communication. Typological and spatial analysis of the ware collections allows us to distinguish two periods of asbestos ware distribution in the late Neolithic-Eneolithic. During the first period (3500–3300 BC), asbestos ware (type Voinavolok) had high social status and was distributed far from the zone of natural deposits of this mineral. Distribution of asbestos ware at this stage fits the model of prestige economy. During the second period (3300–3100 BC), asbestos ware (type Orovnavolok) lost its interregional status. The distribution zone of the asbestos ware had decreased and took its place in linear economic connections. Statistical comparison of the metric parameters of pieces of asbestos collected on the site, as well as phase and chemical analysis show that changes in the social role of asbestos correlated with the downgrade of the mineral raw material quality, and increase of its variability. The authors suggest that this dynamic could be explained in the context of the change in the role of the social centers on the western shore of lake Onega, presented by site Fofanovo XIII

Evidence for polarization-induced phase transformations and degradation in CH3_3NH3_3PbI3_3

In solar cells, hybrid halide perovskites operate under constant bias, thus their stability towards electric field-induced degradation is of key importance. Here we report on evidence of previously unidentified electric field-induced transitions and degradation path of CH$_3$NH$_3$PbI$_3$ (MAPbI$_3$) using elemental and phase mapping. Thin films of MAPbI$_3$ were deposited onto 1–2 µm-pitch interdigitated electrodes and subjected to direct current (DC)-polarization. The MAPbI$_3$ layer polarized with < 0.8 V/µm DC electric field undergoes pronounced ion redistribution to methylammonium-rich MAPbI$_{3−y}$ (y < 0.6) and iodine-rich MA$_{1−x}$PbI$_3$ (x < 0.3) regions. Polarization-induced loss of both methylammonium and iodine provokes degradation of MAPbI$_3$. Using nanofocus grazing-incidence wide-angle X-ray scattering (GIWAXS), we unambiguously showed that the bias voltage induces the transformation of β-MAPbI$_3$ to metastable δ-MAPbI$_3$ polymorph via alignment of polar organic cation with the electric field. This transformation is partially reversible upon field removal. However, once formed, δ-MAPbI$_3$ disrupts the morphology of pristine film and undergoes decomposition to β-MAPbI$_3$ (β-MAPI) and PbI$_2$. With the aforementioned compositional and phase changes, only MA-rich part serves as the charge separation layer, while the I-rich excitation is blocked with the PbI$_2$ barrier serving as holes trapping layer. These observations reveal the intermediate steps in electric-field-driven degradation of halide perovskites and show the role of polar cations in the process, which is instructive for further material design with higher stability metrics

New Insight into the Formation of Hybrid Perovskite Nanowires via Structure Directing Adducts

We report a facile preparation approach of MAPbBr(3), MAPbCl(3), or FAPbBr(3) (where MA = CH3NH3+ and FA = CH(NH2)(2)(+)) perovskite nanowires via sequential synthesis of MAPbI(3) and FAPbI(3) nanowires with chemically controlled composition and morphologies followed by an exchange of halide anions. The nanowires formation sequence includes intermediate phases such as MAI-PbI2-DMF and FAIPbIrDMF (DMF = dimethylformamide) acting as structure directing agent. The 1D shape of the adduct is preserved during the conversion to perovskite. The adducts play the role of key precursors controlling the final product morphology. Systematic investigations of the observed phase transformations and morphology features on multiple length scales revealed the effectiveness of the suggested synthetic route utilizing an original pseudomorph formation mechanism of the 1D structures to produce partly oriented films and textured layers of the nanowires via only a few experimental steps

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.)