Evidence for a Chandrasekhar-mass explosion in the Ca-strong 1991bg-like type la supernova 2016hnk

Aims. We present a comprehensive dataset of optical and near-infrared photometry and spectroscopy of type Ia supernova (SN) 2016hnk, combined with integral field spectroscopy (IFS) of its host galaxy, MCG-01-06-070, and nearby environment. Our goal with this complete dataset is to understand the nature of this peculiar object. Methods. Properties of the SN local environment are characterized by means of single stellar population synthesis applied to IFS observations taken two years after the SN exploded. We performed detailed analyses of SN photometric data by studying its peculiar light and color curves. SN 2016hnk spectra were compared to other 1991bg-like SNe Ia, 2002es-like SNe Ia, and Ca-rich transients. In addition, we used abundance stratification modeling to identify the various spectral features in the early phase spectral sequence and also compared the dataset to a modified non-LTE model previously produced for the sublumnious SN 1999by. Results. SN 2016hnk is consistent with being a subluminous (MB = -16.7 mag, sBV=0.43 ± 0.03), highly reddened object. The IFS of its host galaxy reveals both a significant amount of dust at the SN location, residual star formation, and a high proportion of old stellar populations in the local environment compared to other locations in the galaxy, which favors an old progenitor for SN 2016hnk. Inspection of a nebular spectrum obtained one year after maximum contains two narrow emission lines attributed to the forbidden [Ca ii] λλ7291,7324 doublet with a Doppler shift of 700 km s-1. Based on various observational diagnostics, we argue that the progenitor of SN 2016hnk was likely a near Chandrasekhar-mass (MCh) carbon-oxygen white dwarf that produced 0.108 M of 56Ni. Our modeling suggests that the narrow [Ca ii] features observed in the nebular spectrum are associated with 48Ca from electron capture during the explosion, which is expected to occur only in white dwarfs that explode near or at the MCh limit

Evidence for a Chandrasekhar-mass explosion in the Ca-strong 1991bg-like type Ia supernova 2016hnk

Aims. We present a comprehensive dataset of optical and near-infrared photometry and spectroscopy of type Ia supernova (SN) 2016hnk, combined with integral field spectroscopy (IFS) of its host galaxy, MCG -01-06-070, and nearby environment. Our goal with this complete dataset is to understand the nature of this peculiar object. Methods. Properties of the SN local environment are characterized by means of single stellar population synthesis applied to IFS observations taken two years after the SN exploded. We performed detailed analyses of SN photometric data by studying its peculiar light and color curves. SN 2016hnk spectra were compared to other 1991bg-like SNe Ia, 2002es-like SNe Ia, and Ca-rich transients. In addition, we used abundance stratification modeling to identify the various spectral features in the early phase spectral sequence and also compared the dataset to a modified non-LTE model previously produced for the sublumnious SN 1999by. Results. SN 2016hnk is consistent with being a subluminous (MB = −16.7 mag, sBV=0.43 ± 0.03), highly reddened object. The IFS of its host galaxy reveals both a significant amount of dust at the SN location, residual star formation, and a high proportion of old stellar populations in the local environment compared to other locations in the galaxy, which favors an old progenitor for SN 2016hnk. Inspection of a nebular spectrum obtained one year after maximum contains two narrow emission lines attributed to the forbidden [Ca II] λλ7291,7324 doublet with a Doppler shift of 700 km s−1. Based on various observational diagnostics, we argue that the progenitor of SN 2016hnk was likely a near Chandrasekhar-mass (MCh) carbon-oxygen white dwarf that produced 0.108 M⊙ of 56Ni. Our modeling suggests that the narrow [Ca II] features observed in the nebular spectrum are associated with 48Ca from electron capture during the explosion, which is expected to occur only in white dwarfs that explode near or at the MCh limit

Evidence for a Chandrasekhar-mass explosion in the Ca-strong 1991bg-like type la supernova 2016hnk

Aims. We present a comprehensive dataset of optical and near-infrared photometry and spectroscopy of type Ia supernova (SN) 2016hnk, combined with integral field spectroscopy (IFS) of its host galaxy, MCG -01-06-070, and nearby environment. Our goal with this complete dataset is to understand the nature of this peculiar object.Methods. Properties of the SN local environment are characterized by means of single stellar population synthesis applied to IFS observations taken two years after the SN exploded. We performed detailed analyses of SN photometric data by studying its peculiar light and color curves. SN 2016hnk spectra were compared to other 1991bg-like SNe Ia, 2002es-like SNe Ia, and Ca-rich transients. In addition, we used abundance stratification modeling to identify the various spectral features in the early phase spectral sequence and also compared the dataset to a modified non-LTE model previously produced for the sublumnious SN 1999by.Results. SN 2016hnk is consistent with being a subluminous (M-B = -16.7 mag, S-BV =0.43 +/- 0.03), highly reddened object. The IFS of its host galaxy reveals both a significant amount of dust at the SN location, residual star formation, and a high proportion of old stellar populations in the local environment compared to other locations in the galaxy, which favors an old progenitor for SN 2016hnk. Inspection of a nebular spectrum obtained one year after maximum contains two narrow emission lines attributed to the forbidden [Ca II] lambda lambda 7291,7324 doublet with a Doppler shift of 700 km s(-1). Based on various observational diagnostics, we argue that the progenitor of SN 2016hnk was likely a near Chandrasekhar-mass (M-Ch) carbon-oxygen white dwarf that produced 0.108 M-circle dot of Ni-56. Our modeling suggests that the narrow [Ca II] features observed in the nebular spectrum are associated with Ca-48 from electron capture during the explosion, which is expected to occur only in white dwarfs that explode near or at the M-Ch limit.</p

Impact of primary kidney disease on the effects of empagliflozin in patients with chronic kidney disease: secondary analyses of the EMPA-KIDNEY trial

Background: The EMPA KIDNEY trial showed that empagliflozin reduced the risk of the primary composite outcome of kidney disease progression or cardiovascular death in patients with chronic kidney disease mainly through slowing progression. We aimed to assess how effects of empagliflozin might differ by primary kidney disease across its broad population. Methods: EMPA-KIDNEY, a randomised, controlled, phase 3 trial, was conducted at 241 centres in eight countries (Canada, China, Germany, Italy, Japan, Malaysia, the UK, and the USA). Patients were eligible if their estimated glomerular filtration rate (eGFR) was 20 to less than 45 mL/min per 1·73 m2, or 45 to less than 90 mL/min per 1·73 m2 with a urinary albumin-to-creatinine ratio (uACR) of 200 mg/g or higher at screening. They were randomly assigned (1:1) to 10 mg oral empagliflozin once daily or matching placebo. Effects on kidney disease progression (defined as a sustained ≥40% eGFR decline from randomisation, end-stage kidney disease, a sustained eGFR below 10 mL/min per 1·73 m2, or death from kidney failure) were assessed using prespecified Cox models, and eGFR slope analyses used shared parameter models. Subgroup comparisons were performed by including relevant interaction terms in models. EMPA-KIDNEY is registered with ClinicalTrials.gov, NCT03594110. Findings: Between May 15, 2019, and April 16, 2021, 6609 participants were randomly assigned and followed up for a median of 2·0 years (IQR 1·5–2·4). Prespecified subgroupings by primary kidney disease included 2057 (31·1%) participants with diabetic kidney disease, 1669 (25·3%) with glomerular disease, 1445 (21·9%) with hypertensive or renovascular disease, and 1438 (21·8%) with other or unknown causes. Kidney disease progression occurred in 384 (11·6%) of 3304 patients in the empagliflozin group and 504 (15·2%) of 3305 patients in the placebo group (hazard ratio 0·71 [95% CI 0·62–0·81]), with no evidence that the relative effect size varied significantly by primary kidney disease (pheterogeneity=0·62). The between-group difference in chronic eGFR slopes (ie, from 2 months to final follow-up) was 1·37 mL/min per 1·73 m2 per year (95% CI 1·16–1·59), representing a 50% (42–58) reduction in the rate of chronic eGFR decline. This relative effect of empagliflozin on chronic eGFR slope was similar in analyses by different primary kidney diseases, including in explorations by type of glomerular disease and diabetes (p values for heterogeneity all &gt;0·1). Interpretation: In a broad range of patients with chronic kidney disease at risk of progression, including a wide range of non-diabetic causes of chronic kidney disease, empagliflozin reduced risk of kidney disease progression. Relative effect sizes were broadly similar irrespective of the cause of primary kidney disease, suggesting that SGLT2 inhibitors should be part of a standard of care to minimise risk of kidney failure in chronic kidney disease. Funding: Boehringer Ingelheim, Eli Lilly, and UK Medical Research Council

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2009-223175, HEALTH-F2-2009-223175Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); doi: https://doi.org/10.13039/501100000024Funder: Quebec Breast cancer Foundation Genome QuebecFunder: U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM); doi: https://doi.org/10.13039/100000092Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))Funder: European Union’s Horizon 2020Funder: Deutsche Krebshilfe (German Cancer Aid); doi: https://doi.org/10.13039/501100005972Funder: BCAST - European Union’s Horizon 2020Funder: Breast Cancer Now; doi: https://doi.org/10.13039/501100007913Abstract: Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Is widening participation still ethical?

This article comes from a joint Society for Research in Higher Education (SRHE) and University Association for Lifelong Learning (UALL) seminar in London on Widening Participation (WP) on 24 November 2010 - the day of the second major demonstration against the changes to higher education (HE) funding in England. Despite continuing public opposition and much soul-searching on the part of some politicians, on 9 December 2010 the House of Commons voted to remove the cap on tuition fees. Opposition continues and although we are writing now in January 2011 with little expectation of a speedy reversal of the policy, we aim to explore the possibilities for WP in the new policy context. We start by considering some of the broader implications of the new funding system and go on to focus on the ethical questions and dilemmas raised by the radical policy changes being imposed on HE in the United Kingdom