Caltech Core-Collapse Project (CCCP) observations of type IIn supernovae: typical properties and implications for their progenitor stars

Type IIn Supernovae (SNe IIn) are rare events, constituting only a few percent of all core-collapse SNe, and the current sample of well observed SNe IIn is small. Here, we study the four SNe IIn observed by the Caltech Core-Collapse Project (CCCP). The CCCP SN sample is unbiased to the extent that object selection was not influenced by target SN properties. Therefore, these events are representative of the observed population of SNe IIn. We find that a narrow P-Cygni profile in the hydrogen Balmer lines appears to be a ubiquitous feature of SNe IIn. Our light curves show a relatively long rise time (>20 days) followed by a slow decline stage (0.01 to 0.15 mag/day), and a typical V-band peak magnitude of M_V=-18.4 +/- 1.0 mag. We measure the progenitor star wind velocities (600 - 1400 km/s) for the SNe in our sample and derive pre-explosion mass loss rates (0.026 - 0.12 solar masses per year). We compile similar data for SNe IIn from the literature, and discuss our results in the context of this larger sample. Our results indicate that typical SNe IIn arise from progenitor stars that undergo LBV-like mass-loss shortly before they explode.Comment: ApJ, submitte

The Unique Type Ia Supernova 2000cx in NGC 524

We present extensive photometric and spectroscopic observations of the Type Ia supernova (SN Ia) 2000cx in the S0 galaxy NGC 524, which reveal it to be peculiar. Photometrically, SN 2000cx is different from all known SNe Ia, and its light curves cannot be fit well by the fitting techniques currently available. There is an apparent asymmetry in the $B$-band peak, in which the premaximum brightening is relatively fast (similar to that of the normal SN 1994D), but the postmaximum decline is relatively slow (similar to that of the overluminous SN 1991T). The color evolution of SN 2000cx is also peculiar: the $(B - V)_0$ color has a unique plateau phase and the $(V - R)_0$ and $(V - I)_0$ colors are very blue. Although the premaximum spectra of SN 2000cx are similar to those of SN 1991T-like objects (with weak Si II lines), its overall spectral evolution is quite different. The Si II lines that emerged near maximum $B$-band brightness stay strong in SN 2000cx until about three weeks past maximum. The change in the excitation stages of iron-peak elements is slow. Both the iron-peak and the intermediate-mass elements are found to be moving at very high expansion velocities in the ejecta of SN 2000cx. We discuss theoretical models for SN 2000cx. SN 2000cx may be an overluminous object like SN 1991T, but with a larger yield of $^{56}$Ni and a higher kinetic energy in the ejecta. We also briefly discuss the implications of our observations for the luminosity vs. light-curve width relation.Comment: Accepted to be published in the Oct issue of PAS

Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

Baseline population health conditions ahead of a health system strengthening program in rural Madagascar

Background: A model health district was initiated through a program of health system strengthening (HSS) in Ifanadiana District of southeastern Madagascar in 2014. We report population health indicators prior to initiation of the program. Methods: A representative household survey based on the Demographic Health Survey was conducted using a two-stage cluster sampling design in two strata – the initial program catchment area and the future catchment area. Chi-squared and t-tests were used to compare data by stratum, using appropriate sampling weights. Madagascar data for comparison were taken from a 2013 national study. Results: 1522 households were surveyed, representing 8310 individuals including 1635 women ages 15–49, 1685 men ages 15–59 and 1251 children under age 5. Maternal mortality rates in the district are 1044/100,000. 81% of women’s last childbirth deliveries were in the home; only 20% of deliveries were attended by a doctor or nurse/midwife (not different by stratum). 9.3% of women had their first birth by age 15, and 29.5% by age 18. Under-5 mortality rate is high: 145/1000 live births vs. 62/1000 nationally. 34.6% of children received all recommended vaccines by age 12 months (compared to 51.5% in Madagascar overall). In the 2 weeks prior to interview, approximately 28% of children under age 5 had acute respiratory infections of whom 34.7% were taken for care, and 14% of children had diarrhea of whom 56.6% were taken for care. Under-5 mortality, illness, care-seeking and vaccination rates were not significantly different between strata. Conclusions: Indicators of population health and health care-seeking reveal low use of the formal health system, which could benefit from HSS. Data from this survey and from a longitudinal follow-up study will be used to target needed interventions, to assess change in the district and the impact of HSS on individual households and the population of the district

Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loc

Exponential growth, high prevalence of SARS-CoV-2, and vaccine effectiveness associated with the Delta variant

SARS-CoV-2 infections were rising during early summer 2021 in many countries associated with the Delta variant. We assessed RT-PCR swab-positivity in the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. We observed sustained exponential growth with average doubling time (June-July 2021) of 25 days driven by complete replacement of Alpha variant by Delta, and by high prevalence at younger less-vaccinated ages. Unvaccinated people were three times more likely than double-vaccinated people to test positive. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p