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In patients with heart failure with preserved ejection fraction and obesity, treatment with tirzepatide led to a lower risk of death from cardiovascular causes or worsening heart-failure events than placebo.

The authors report 12-year follow-up results of Roux-en-Y gastric bypass versus no surgery. The results show long-term durability of weight loss and effective remission and prevention of type 2 diabetes, hypertension, and dyslipidemia after Roux-en-Y gastric bypass.

Patients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular–kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide ( n  = 364, 200 women) or placebo ( n  = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure. Here, in this mechanistic secondary analysis of the SUMMIT trial, tirzepatide treatment at 52 weeks, as compared with placebo, reduced systolic blood pressure (estimated treatment difference (ETD) −5 mmHg, 95% confidence interval (CI) −7 to −3; P  < 0.001), decreased estimated blood volume (ETD −0.58 l, 95% CI −0.63 to −0.52; P  < 0.001) and reduced C-reactive protein levels (ETD −37.2%, 95% CI −45.7 to −27.3; P  < 0.001). These changes were coupled with an increase in estimated glomerular filtration rate (ETD 2.90 ml min −1  1.73 m −2  yr −1 , 95% CI 0.94 to 4.86; P  = 0.004), a decrease in urine albumin–creatinine ratio (ETD 24 weeks, −25.0%, 95% CI −36 to −13%; P  < 0.001; 52 weeks, −15%, 95% CI −28 to 0.1; P  = 0.051), a reduction in N-terminal prohormone B-type natriuretic peptide levels (ETD 52 weeks −10.5%, 95% CI −20.7 to 1.0%; P  = 0.07) and a reduction in troponin T levels (ETD 52 weeks −10.4%, 95% CI −16.7 to −3.6; P  = 0.003). In post hoc exploratory analyses, decreased estimated blood volume with tirzepatide treatment was significantly correlated with decreased blood pressure, reduced microalbuminuria, improved Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and increased 6-min walk distance. Moreover, decreased C-reactive protein levels were correlated with reduced troponin T levels and improved 6-min walk distance. In conclusion, tirzepatide reduced circulatory volume–pressure overload and systemic inflammation and mitigated cardiovascular–kidney end-organ injury in patients with HFpEF and obesity, providing new insights into the mechanisms of benefit from tirzepatide. ClinicalTrials.gov registration: NCT04847557 . In a mechanistic analysis of the SUMMIT trial that tested tirzepatide in patients with heart failure with preserved ejection fraction and obesity, treatment with this dual glucagon-like peptide-1 receptor and gastric inhibitory polypeptide agonist, as compared with placebo, reduced blood pressure and estimated circulatory volume–pressure overload, reduced systemic inflammation and mitigated cardiovascular and kidney injury.

The Dark Energy Survey (DES) is a five-year optical imaging campaign with the goal of understanding the origin of cosmic acceleration. DES performs a ∼5000 deg2 survey of the southern sky in five optical bands (g, r, i, z, Y) to a depth of ∼24th magnitude. Contemporaneously, DES performs a deep, time-domain survey in four optical bands (g, r, i, z) over ∼27 deg2. DES exposures are processed nightly with an evolving data reduction pipeline and evaluated for image quality to determine if they need to be retaken. Difference imaging and transient source detection are also performed in the time domain component nightly. On a bi-annual basis, DES exposures are reprocessed with a refined pipeline and coadded to maximize imaging depth. Here we describe the DES image processing pipeline in support of DES science, as a reference for users of archival DES data, and as a guide for future astronomical surveys.

Mechanistic target of rapamycin (Mtor) is required for embryonic inner cell mass proliferation during early development. However, Mtor expression levels are very low in the mouse heart during embryogenesis. To determine if Mtor plays a role during mouse cardiac development, cardiomyocyte specific Mtor deletion was achieved using α myosin heavy chain (α-MHC) driven Cre recombinase. Initial mosaic expression of Cre between embryonic day (E) 10.5 and E11.5 eliminated a subset of cardiomyocytes with high Cre activity by apoptosis and reduced overall cardiac proliferative capacity. The remaining cardiomyocytes proliferated and expanded normally. However loss of 50% of cardiomyocytes defined a threshold that impairs the ability of the embryonic heart to sustain the embryo's circulatory requirements. As a result 92% of embryos with cardiomyocyte Mtor deficiency died by the end of gestation. Thus Mtor is required for survival and proliferation of cardiomyocytes in the developing heart.

SGLT-2 inhibitors show promise for treatment of heart failure with preserved ejection fraction, but clinical data are nuanced. Appropriate endpoint selection will be key to deciphering their benefits.

Photogenerated charge in thick, back-illuminated, fully-depleted CCDs is transported by electric fields from the silicon substrate to the collecting well at the front gate of the CCDs. However, electric fields transverse to the surface of the CCD-with diverse origins such as doping gradients, guard rings around the imaging area of the sensor, and physical stresses on the silicon lattice-displace this charge, effectively modifying the pixel area and producing noticeable signals in astrometric and photometric measurements. We use data from the science verification period of the Dark Energy Survey (DES) to characterize these effects in the Dark Energy Camera (DECam) CCDs. The transverse fields mainly manifest as concentric rings (''tree rings'') and bright stripes near the boundaries of the detectors (''edge distortions'') with relative amplitudes of about 1% and 10% in the flat-field images, respectively. Their nature as pixel size variations is confirmed by comparing their photometric and astrometric signatures. Using flat-field images from DECam, we derive templates in the five DES photometric bands (grizY) for the tree rings and the edge distortions as a function of their position in each DECam detector. These templates can be directly incorporated into the derivation of photometric and astrometric solutions, helping to meet the DES photometric and astrometric requirements.