Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype

Background: The majority of patients with heart failure with preserved ejection fraction (HFpEF) have the obesity phenotype, but no therapies specifically targeting obesity in HFpEF exist. Objectives: The aim of this study was to describe the design and baseline characteristics of 2 trials of semaglutide, a glucagon-like peptide-1 receptor agonist, in patients with the obesity HFpEF phenotype: STEP-HFpEF (Semaglutide Treatment Effect in People with obesity and HFpEF; NCT04788511) and STEP-HFpEF DM (Semaglutide Treatment Effect in People with obesity and HFpEF and type 2 diabetes; NCT04916470). Methods: Both STEP-HFpEF and STEP-HFpEF DM are international multicenter, double-blind, placebo-controlled trials that randomized adults with HFpEF and a body mass index ≥30 kg/m2 to once-weekly semaglutide at a dose of 2.4 mg or placebo. Participants were eligible if they had a left ventricular ejection fraction (LVEF) ≥45%; New York Heart Association (NYHA) functional class II to IV; a Kansas City Cardiomyopathy Questionnaire (KCCQ)–Clinical Summary Score (CSS) <90 points; and ≥1 of the following: elevated filling pressures, elevated natriuretic peptides plus structural echocardiographic abnormalities, recent heart failure hospitalization plus ongoing diuretic use, and/or structural abnormalities. The dual primary endpoints are the 52-week change in the KCCQ-CSS and body weight. Results: In STEP-HFpEF and STEP-HFpEF DM (N = 529 and N = 617, respectively), nearly half were women, and most had severe obesity (median body mass index of 37 kg/m2) with typical features of HFpEF (median LVEF of 57%, frequent comorbidities, and elevated natriuretic peptides). Most participants received diuretic agents and renin-angiotensin blockers at baseline, and approximately one-third were on mineralocorticoid receptor antagonists. Sodium-glucose cotransporter-2 inhibitor use was rare in STEP-HFpEF but not in STEP HFpEF DM (32%). Patients in both trials had marked symptomatic and functional impairments (KCCQ-CSS ∼59 points, 6-minute walking distance ∼300 m). Conclusions: In total, STEP-HFpEF program randomized 1,146 participants with the obesity phenotype of HFpEF and will determine whether semaglutide improves symptoms, physical limitations, and exercise function in addition to weight loss in this vulnerable group

Infrared molecular hydrogen lines in GRB host galaxies

Molecular species, most frequently H2, are present in a small, but growing, number of gammaray burst (GRB) afterglow spectra at redshifts z ∼ 2−3, detected through their rest-frame UV absorption lines. In rare cases, lines of vibrationally excited states of H2 can be detected in the same spectra. The connection between afterglow line-of-sight absorption properties of molecular (and atomic) gas, and the observed behaviour in emission of similar sources at low redshift, is an important test of the suitability of GRB afterglows as general probes of conditions in star formation regions at high redshift. Recently, emission lines of carbon monoxide have been detected in a small sample of GRB host galaxies, at sub-mm wavelengths, but no searches for H2 in emission have been reported yet. In this paper we perform an exploratory search for rest-frame K band rotation-vibrational transitions of H2 in emission, observable only in the lowest redshift GRB hosts (z 0.22). Searching the data of four host galaxies, we detect a single significant rotation-vibrational H2 line candidate, in the host of GRB 031203. Reanalysis of Spitzer mid-infrared spectra of the same GRB host gives a single low significance rotational line candidate. The (limits on) line flux ratios are consistent with those of blue compact dwarf galaxies in the literature. New instrumentation, in particular on the JWST and the ELT, can facilitate a major increase in our understanding of the H2 properties of nearby GRB hosts, and the relation to H2 absorption in GRBs at higher redshift

A search for the afterglows, kilonovae, and host galaxies of two short GRBs: GRB 211106A and GRB 211227A

Context. GRB 211106A and GRB 211227A are two recent gamma-ray bursts (GRBs) whose initial X-ray position enabled us to possibly associate them with bright, low-redshift galaxies (z < 0.7). The prompt emission properties suggest that GRB 211106A is a genuine short-duration GRB and GRB 211227A is a short GRB with extended emission. Therefore, they are likely to be produced by a compact binary merger. However, a classification based solely on the prompt emission properties can be misleading. Aims. The possibility of having two short GRBs occurring in the local Universe makes them ideal targets for the search of associated kilonova (KN) emission and for detailed studies of the host galaxy properties. Methods. We carried out deep optical and near-infrared (NIR) follow-up with the ESO-VLT FORS2, HAWK-I, and MUSE instruments for GRB 211106A and with ESO-VLT FORS2 and X-shooter for GRB 211227A, starting from hours after the X-ray afterglow discovery up to days later. We performed photometric analysis to look for afterglow and KN emissions associated with the bursts, together with imaging and spectroscopic observations of the host galaxy candidates. We compared the results obtained from the optical/NIR observations with the available Swift X-Ray Telescope (XRT) and others high-energy data of both events. Results. For both GRBs we placed deep limits to the optical/NIR afterglow and KN emission. We identified their associated host galaxies, GRB 211106A at a photometric redshift z = 0.64, GRB 211227A at a spectroscopic z = 0.228. From MUSE and X-shooter spectra we derived the host galaxy properties, which turned out to be consistent with short GRBs typical hosts. We also compared the properties of GRB 211106A and GRB 211227A with those of the short GRBs belonging to the S-BAT4 sample, here extended up to December 2021, in order to further investigate the nature of these two bursts. Conclusions. Our study of the prompt and afterglow phase of the two GRBs, together with the analysis of their associated host galaxies, allows us to confirm the classification of GRB 211106A as a short GRB, and GRB 211227A as a short GRB with extended emission. The absence of an optical/NIR counterpart down to deep magnitude limits is likely due to high local extinction for GRB 211106A and a peculiarly faint kilonova for GRB 211227A.</p

Synergies of THESEUS with the large facilities of the '30s and GO opportunities

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multimessenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities.We discuss here a number of these powerful synergies and guest observer opportunities.</p

Correction to: Comparing emission- and absorption-based gas-phase metallicities in GRB host galaxies at <i>z</i> = 2−4 using JWST

This is a correction to: P. Schady and others, Comparing emission- and absorption-based gas-phase metallicities in GRB host galaxies at z = 2−4 using JWST, Monthly Notices of the Royal Astronomical Society, Volume 529, Issue 3, April 2024, Pages 2807–2831, https://doi.org/10.1093/mnras/stae677.We found a mistake in our abstract where we accidentally wrote that the host galaxy of GRB 090323 was at z = 4.7 whereas it is in fact at redshift z = 3.58 based on the NIRSpec emission line spectrum of the host galaxy. The redshift of this GRB host galaxy is correctly reported in the rest of the paper. We also found a bug in our code that produces the [O III] λ5007 surface brightness maps of the host galaxies of GRB 050820A and GRB 150403A (figs 1 and 2 of the original paper) that caused the labelled physical pixel scale to be too small by a factor of ∼1.4. This error only affected the axes shown in the figures and has no implications for the rest of the paper. The corresponding pixel-to-kpc conversions have now been corrected and the updated maps are shown in Figs 1 and 2.</p

Comparing emission- and absorption-based gas-phase metallicities in GRB host galaxies at <i>z</i> = 2 − 4 using JWST

Much of what is known of the chemical composition of the universe is based on emission line spectra from star forming galaxies. Emission-based inferences are, nevertheless, model-dependent and they are dominated by light from luminous star forming regions. An alternative and sensitive probe of the metallicity of galaxies is through absorption lines imprinted on the luminous afterglow spectra of long gamma ray bursts (GRBs) from neutral material within their host galaxy. We present results from a JWST/NIRSpec programme to investigate for the first time the relation between the metallicity of neutral gas probed in absorption by GRB afterglows and the metallicity of the star forming regions for the same host galaxy sample. Using an initial sample of eight GRB host galaxies at z = 2.1 − 4.7, we find a tight relation between absorption and emission line metallicities when using the recently proposed $\hat{R}$ metallicity diagnostic (±0.2 dex). This agreement implies a relatively chemically-homogeneous multi-phase interstellar medium, and indicates that absorption and emission line probes can be directly compared. However, the relation is less clear when using other diagnostics, such as R23 and R3. We also find possible evidence of an elevated N/O ratio in the host galaxy of GRB 090323 at z = 4.7, consistent with what has been seen in other z > 4 galaxies. Ultimate confirmation of an enhanced N/O ratio and of the relation between absorption and emission line metallicities will require a more direct determination of the emission line metallicity via the detection of temperature-sensitive auroral lines in our GRB host galaxy sample.</p