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

The Gut Microbiome of an Indigenous Agropastoralist Population in a Remote Area of Colombia with High Rates of Gastrointestinal Infections and Dysbiosis

An Indigenous agropastoralist population called the Wiwa from the Sierra Nevada de Santa Marta, in North-East Colombia, shows high rates of gastrointestinal infections. Chronic gut inflammatory processes and dysbiosis could be a reason, suggesting an influence or predisposing potential of the gut microbiome composition. The latter was analyzed by 16S rRNA gene amplicon next generation sequencing from stool samples. Results of the Wiwa population microbiomes were associated with available epidemiological and morphometric data and compared to control samples from a local urban population. Indeed, locational-, age-, and gender-specific differences in the Firmicutes/Bacteriodetes ratio, core microbiome, and overall genera-level microbiome composition were shown. Alpha- and ß-diversity separated the urban site from the Indigenous locations. Urban microbiomes were dominated by Bacteriodetes, whereas Indigenous samples revealed a four times higher abundance of Proteobacteria. Even differences among the two Indigenous villages were noted. PICRUSt analysis identified several enriched location-specific bacterial pathways. Moreover, on a general comparative scale and with a high predictive accuracy, we found Sutterella associated with the abundance of enterohemorrhagic Escherichia coli (EHEC), Faecalibacteria associated with enteropathogenic Escherichia coli (EPEC) and helminth species Hymenolepsis nana and Enterobius vermicularis. Parabacteroides, Prevotella, and Butyrivibrio are enriched in cases of salmonellosis, EPEC, and helminth infections. Presence of Dialister was associated with gastrointestinal symptoms, whereas Clostridia were exclusively found in children under the age of 5 years. Odoribacter and Parabacteroides were exclusively identified in the microbiomes of the urban population of Valledupar. In summary, dysbiotic alterations in the gut microbiome in the Indigenous population with frequent episodes of self-reported gastrointestinal infections were confirmed with epidemiological and pathogen-specific associations. Our data provide strong hints of microbiome alterations associated with the clinical conditions of the Indigenous population

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA

Chasing Gravitational Waves with the Chereknov Telescope Array

Presented at the 38th International Cosmic Ray Conference (ICRC 2023), 2023 (arXiv:2309.08219)2310.07413International audienceThe detection of gravitational waves from a binary neutron star merger by Advanced LIGO and Advanced Virgo (GW170817), along with the discovery of the electromagnetic counterparts of this gravitational wave event, ushered in a new era of multimessenger astronomy, providing the first direct evidence that BNS mergers are progenitors of short gamma-ray bursts (GRBs). Such events may also produce very-high-energy (VHE, > 100GeV) photons which have yet to be detected in coincidence with a gravitational wave signal. The Cherenkov Telescope Array (CTA) is a next-generation VHE observatory which aims to be indispensable in this search, with an unparalleled sensitivity and ability to slew anywhere on the sky within a few tens of seconds. New observing modes and follow-up strategies are being developed for CTA to rapidly cover localization areas of gravitational wave events that are typically larger than the CTA field of view. This work will evaluate and provide estimations on the expected number of of gravitational wave events that will be observable with CTA, considering both on- and off-axis emission. In addition, we will present and discuss the prospects of potential follow-up strategies with CTA