Chronic Kidney Disease Severity Is Associated With Selective Expansion of a Distinctive Intermediate Monocyte Subpopulation

Chronic kidney disease (CKD) affects 11–13% of the world's population and greatly increases risk of atherosclerotic cardiovascular disease (ASCVD) and death. It is characterized by systemic inflammation and disturbances in the blood leukocytes that remain incompletely understood. In particular, abnormalities in the numbers and relative proportions of the three major monocyte subsets—classical, intermediate, and non-classical—are described in CKD and end-stage renal disease. In this study, we characterized absolute numbers of blood leukocyte subtypes in adults with renal function varying from normal to advanced CKD. The primary aim was to identify monocyte subpopulations that associated most closely with current estimated glomerular filtration rate (eGFR) and subsequent rate of eGFR decline. Leucocyte and monocyte populations were enumerated by multi-color flow cytometry of whole blood and peripheral blood mononuclear cell (PBMC) samples from adults with CKD stage 1–5 (n = 154) and healthy adults (n = 33). Multiple-linear regression analyses were performed to identify associations between numbers of leucocyte and monocyte populations and clinical characteristics including eGFR and rate of eGFR decline with adjustment for age and gender. In whole blood, total monocyte and neutrophil, but not lymphocyte, numbers were higher in adults with CKD 1-5 compared to no CKD and were significantly associated with current eGFR even following correction for age. In PBMC, classical and intermediate monocyte numbers were higher in CKD 1-5 but only intermediate monocyte numbers were significantly associated with current eGFR in an age-corrected analysis. When intermediate monocytes were further sub-divided into those with mid- and high-level expression of class II MHC (HLA-DRmid and HLA-DRhi intermediate monocytes) it was found that only DRhi intermediate monocytes were increased in number in CKD 1-5 compared to no CKD and were significantly associated with eGFR independently of age among the total (No CKD + CKD 1-5) study cohort as well as those with established CKD (CKD 1-5 only). Furthermore, blood number of DRhi intermediate monocytes alone proved to be significantly associated with subsequent rate of renal functional decline. Together, our data confirm neutrophil and monocyte subset dysregulation in CKD and identify a distinct subpopulation of intermediate monocytes that is associated with higher rate of loss of kidney function

UK's Association of British Clinical Diabetologist's Diabetes Technology Network (ABCD-DTN): Best practice guide for hybrid closed-loop therapy

This best practice guide is written with the aim of providing an overview of current hybrid closed-loop (HCL) systems in use within the United Kingdom's (UK) National Health Service (NHS) and to provide education and advice for their management on both an individual and clinical service level. The environment of diabetes technology, and particularly HCL systems, is rapidly evolving. The past decade has seen unprecedented advances in the development of HCL systems. These systems improve glycaemic outcomes and reduce the burden of treatment for people with type 1 diabetes (pwT1D). It is anticipated that access to these systems will increase in England as a result of updates in National Institute of Health and Care Excellence (NICE) guidance providing broader support for the use of real-time continuous glucose monitoring (CGM) for pwT1D. NICE are currently undertaking multiple-technology appraisal into HCL systems. Based on experience from centres involved in supporting advanced technologies as well as from the recent NHS HCL pilot, this guide is intended to provide healthcare professionals (HCPs) with UK expert consensus on the best practice for initiation, optimization and ongoing management of HCL therapy. [Abstract copyright: This article is protected by copyright. All rights reserved.

A core outcome set for studies of gestational diabetes mellitus prevention and treatment

AIMS/HYPOTHESIS: The aim of this systematic review was to develop core outcome sets (COSs) for trials evaluating interventions for the prevention or treatment of gestational diabetes mellitus (GDM). METHODS: We identified previously reported outcomes through a systematic review of the literature. These outcomes were presented to key stakeholders (including patient representatives, researchers and clinicians) for prioritisation using a three-round, e-Delphi study. A priori consensus criteria informed which outcomes were brought forward for discussion at a face-to-face consensus meeting where the COS was finalised. RESULTS: Our review identified 74 GDM prevention and 116 GDM treatment outcomes, which were presented to stakeholders in round 1 of the e-Delphi study. Round 1 was completed by 173 stakeholders, 70% (121/173) of whom went on to complete round 2; 84% (102/121) of round 2 responders completed round 3. Twenty-two GDM prevention outcomes and 30 GDM treatment outcomes were discussed at the consensus meeting. Owing to significant overlap between included prevention and treatment outcomes, consensus meeting stakeholders agreed to develop a single prevention/treatment COS. Fourteen outcomes were included in the final COS. These consisted of six maternal outcomes (GDM diagnosis, adherence to the intervention, hypertensive disorders of pregnancy, requirement and type of pharmacological therapy for hyperglycaemia, gestational weight gain and mode of birth) and eight neonatal outcomes (birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, neonatal hypoglycaemia, neonatal death and stillbirth). CONCLUSIONS/INTERPRETATION: This COS will enable future GDM prevention and treatment trials to measure similar outcomes that matter to stakeholders and facilitate comparison and combination of these studies. TRIAL REGISTRATION: This study was registered prospectively with the Core Outcome Measures in Effectiveness Trials (COMET) database: http://www.comet-initiative.org/studies/details/686/

Luminous Type II Short-Plateau Supernovae 2006Y, 2006ai, and 2016egz: A Transitional Class from Stripped Massive Red Supergiants

The diversity of Type II supernovae (SNe II) is thought to be driven mainly by differences in their progenitor's hydrogen-rich (H-rich) envelope mass, with SNe IIP having long plateaus ($\sim100$ days) and the most massive H-rich envelopes. However, it is an ongoing mystery why SNe II with short plateaus (tens of days) are rarely seen. Here we present optical/near-infrared photometric and spectroscopic observations of luminous Type II short-plateau SNe 2006Y, 2006ai, and 2016egz. Their plateaus of about $50$--$70$ days and luminous optical peaks ($\lesssim-18.4$ mag) indicate significant pre-explosion mass loss resulting in partially-stripped H-rich envelopes and early circumstellar material (CSM) interaction. We compute a large grid of MESA+STELLA single-star progenitor and light-curve models with various progenitor zero-age main-sequence (ZAMS) masses, mass-loss efficiencies, explosion energies, $^{56}$Ni masses, and CSM densities. Our model grid shows a continuous population of SNe IIP--IIL--IIb-like light-curve morphology in descending order of H-rich envelope mass. With large $^{56}$Ni masses ($\gtrsim0.05\,M_\odot$), short-plateau SNe II lie in a confined parameter space as a transitional class between SNe IIL and IIb. For SNe 2006Y, 2006ai, and 2016egz, our findings suggest high-mass red supergiant (RSG) progenitors ($M_{\rm ZAMS} \simeq 18$--$22\,M_{\odot}$) with small H-rich envelope masses ($M_{\rm H_{\rm env}} \simeq 1.7\,M_{\odot}$) that experience enhanced mass loss ($\dot{M} \simeq 10^{-2}\,M_{\odot}\,{\rm yr}^{-1}$) for the last few decades before the explosion. If high-mass RSGs result in rare short-plateau SNe II, then these events might ease some of the apparent under-representation of higher-luminosity RSGs in observed SN II progenitor samples.Comment: 26 pages, 16 figures, submitted to Ap

Luminous Type II Short-Plateau Supernovae 2006Y, 2006ai, and 2016egz: A Transitional Class from Stripped Massive Red Supergiants

The diversity of Type II supernovae (SNe II) is thought to be driven mainly by differences in their progenitor's hydrogen-rich (H-rich) envelope mass, with SNe IIP having long plateaus (similar to 100 days) and the most massive H-rich envelopes. However, it is an ongoing mystery why SNe II with short plateaus (tens of days) are rarely seen. Here, we present optical/near-infrared photometric and spectroscopic observations of luminous Type II short-plateau SNe 2006Y, 2006ai, and 2016egz. Their plateaus of about 50-70 days and luminous optical peaks (less than or similar to-18.4 mag) indicate significant pre-explosion mass loss resulting in partially stripped H-rich envelopes and early circumstellar material (CSM) interaction. We compute a large grid of MESA+STELLA single-star progenitor and light-curve models with various progenitor zero-age main-sequence (ZAMS) masses, mass-loss efficiencies, explosion energies, Ni-56 masses, and CSM densities. Our model grid shows a continuous population of SNe IIP-IIL-IIb-like light-curve morphology in descending order of H-rich envelope mass. With large Ni-56 masses (greater than or similar to 0.05M(circle dot)), short-plateau SNe II lie in a confined parameter space as a transitional class between SNe IIL and IIb. For SNe 2006Y, 2006ai, and 2016egz, our findings suggest high-mass red supergiant (RSG) progenitors (M-ZAMS similar or equal to 18-22M(circle dot)) with small H-rich envelope masses (M-Henv similar or equal to 1.7 M-circle dot) that have experienced enhanced mass loss (M similar or equal to 10(-2) M-circle dot yr(-1)) for the last few decades before the explosion. If high-mass RSGs result in rare short-plateau SNe II, then these events might ease some of the apparent underrepresentation of higher-luminosity RSGs in observed SN II progenitor samples

SN 2019ehk: A Double-peaked Ca-rich Transient with Luminous X-Ray Emission and Shock-ionized Spectral Features

We present panchromatic observations and modeling of the Calcium-rich supernova (SN) 2019ehk in the star-forming galaxy M100 (d ≈ 16.2 Mpc) starting 10 hr after explosion and continuing for ~300 days. SN 2019ehk shows a double-peaked optical light curve peaking at t = 3 and 15 days. The first peak is coincident with luminous, rapidly decaying Swift-XRT–discovered X-ray emission (L_x ≈ 10⁴¹ erg s⁻¹ at 3 days; L_x ∝ t⁻³), and a Shane/Kast spectral detection of narrow Hα and He II emission lines (v ≈ 500 km s⁻¹) originating from pre-existent circumstellar material (CSM). We attribute this phenomenology to radiation from shock interaction with extended, dense material surrounding the progenitor star at r (0.1–1) × 10¹⁷ cm. The photometric and spectroscopic properties during the second light-curve peak are consistent with those of Ca-rich transients (rise-time of t_r = 13.4 ± 0.210 days and a peak B-band magnitude of M_B = −15.1 ± 0.200 mag). We find that SN 2019ehk synthesized (3.1 ± 0.11) × 10⁻² M_⊙ of ⁵⁶Ni and ejected M_(ej) = (0.72 ± 0.040) M⊙ total with a kinetic energy E_k = (1.8 ± 0.10) × 10⁵⁰ erg. Finally, deep HST pre-explosion imaging at the SN site constrains the parameter space of viable stellar progenitors to massive stars in the lowest mass bin (~10 M_⊙) in binaries that lost most of their He envelope or white dwarfs (WDs). The explosion and environment properties of SN 2019ehk further restrict the potential WD progenitor systems to low-mass hybrid HeCO WD+CO WD binaries

Strong Carbon Features and a Red Early Color in the Underluminous Type Ia SN 2022xkq

We present optical, infrared, ultraviolet, and radio observations of SN 2022xkq, an underluminous fast-declining type Ia supernova (SN Ia) in NGC 1784 ($\mathrm{D}\approx31$ Mpc), from $<1$ to 180 days after explosion. The high-cadence observations of SN 2022xkq, a photometrically transitional and spectroscopically 91bg-like SN Ia, cover the first days and weeks following explosion which are critical to distinguishing between explosion scenarios. The early light curve of SN 2022xkq has a red early color and exhibits a flux excess which is more prominent in redder bands; this is the first time such a feature has been seen in a transitional/91bg-like SN Ia. We also present 92 optical and 19 near-infrared (NIR) spectra, beginning 0.4 days after explosion in the optical and 2.6 days after explosion in the NIR. SN 2022xkq exhibits a long-lived C I 1.0693 $\mu$m feature which persists until 5 days post-maximum. We also detect C II $\lambda$6580 in the pre-maximum optical spectra. These lines are evidence for unburnt carbon that is difficult to reconcile with the double detonation of a sub-Chandrasekhar mass white dwarf. No existing explosion model can fully explain the photometric and spectroscopic dataset of SN 2022xkq, but the considerable breadth of the observations is ideal for furthering our understanding of the processes which produce faint SNe Ia.Comment: 38 pages, 16 figures, accepted for publication in ApJ, the figure 15 input models and synthetic spectra are now available at https://zenodo.org/record/837925

Weak mass loss from the Red Supergiant progenitor of the type II SN 2021yja

We present high-cadence optical, ultraviolet (UV), and near-infrared data of the nearby (D ≈ 23 Mpc) Type II supernova (SN) 2021yja. Many Type II SNe show signs of interaction with circumstellar material (CSM) during the first few days after explosion, implying that their red supergiant (RSG) progenitors experience episodic or eruptive mass loss. However, because it is difficult to discover SNe early, the diversity of CSM configurations in RSGs has not been fully mapped. SN 2021yja, first detected within ≈ 5.4 hours of explosion, shows some signatures of CSM interaction (high UV luminosity and radio and x-ray emission) but without the narrow emission lines or early light-curve peak that can accompany CSM. Here we analyze the densely sampled early light curve and spectral series of this nearby SN to infer the properties of its progenitor and CSM. We find that the most likely progenitor was an RSG with an extended envelope, encompassed by low-density CSM. We also present archival Hubble Space Telescope imaging of the host galaxy of SN 2021yja, which allows us to place a stringent upper limit of ≲ 9 M ☉ on the progenitor mass. However, this is in tension with some aspects of the SN evolution, which point to a more massive progenitor. Our analysis highlights the need to consider progenitor structure when making inferences about CSM properties, and that a comprehensive view of CSM tracers should be made to give a fuller view of the last years of RSG evolution