Racial discrimination in medical care settings and opioid pain reliever misuse in a U.S. cohort: 1992 to 2015

BACKGROUND: In the United States whites are more likely to misuse opioid pain relievers (OPRs) than blacks, and blacks are less likely to be prescribed OPRs than whites. Our objective is to determine whether racial discrimination in medical settings is protective for blacks against OPR misuse, thus mediating the black-white disparities in OPR misuse. METHODS: We used data from 3528 black and white adults in the Coronary Artery Risk Development in Young Adults (CARDIA) study, an ongoing multi-site cohort. We employ causal mediation methods, with race (black vs white) as the exposure, lifetime discrimination in medical settings prior to year 2000 as the mediator, and OPR misuse after 2000 as the outcome. RESULTS: We found black participants were more likely to report discrimination in a medical setting (20.3% vs 0.9%) and less likely to report OPR misuse (5.8% vs 8.0%, OR = 0.71, 95% CI = 0.55, 0.93, adjusted for covariates). Our mediation models suggest that when everyone is not discriminated against, the disparity is wider with black persons having even lower odds of reporting OPR misuse (OR = 0.63, 95% CI = 0.45, 0.89) compared to their white counterparts, suggesting racial discrimination in medical settings is a risk factor for OPR misuse rather than protective. CONCLUSIONS: These results suggest that racial discrimination in a medical setting is a risk factor for OPR misuse rather than being protective, and thus could not explain the seen black-white disparity in OPR misuse

First radial velocity results from the MINiature Exoplanet Radial Velocity Array (MINERVA)

The MINiature Exoplanet Radial Velocity Array (MINERVA) is a dedicated observatory of four 0.7m robotic telescopes fiber-fed to a KiwiSpec spectrograph. The MINERVA mission is to discover super-Earths in the habitable zones of nearby stars. This can be accomplished with MINERVA's unique combination of high precision and high cadence over long time periods. In this work, we detail changes to the MINERVA facility that have occurred since our previous paper. We then describe MINERVA's robotic control software, the process by which we perform 1D spectral extraction, and our forward modeling Doppler pipeline. In the process of improving our forward modeling procedure, we found that our spectrograph's intrinsic instrumental profile is stable for at least nine months. Because of that, we characterized our instrumental profile with a time-independent, cubic spline function based on the profile in the cross dispersion direction, with which we achieved a radial velocity precision similar to using a conventional "sum-of-Gaussians" instrumental profile: 1.8 m s$^{-1}$ over 1.5 months on the RV standard star HD 122064. Therefore, we conclude that the instrumental profile need not be perfectly accurate as long as it is stable. In addition, we observed 51 Peg and our results are consistent with the literature, confirming our spectrograph and Doppler pipeline are producing accurate and precise radial velocities.Comment: 22 pages, 9 figures, submitted to PASP, Peer-Reviewed and Accepte

Early Markers of Glycaemic Control in Children with Type 1 Diabetes Mellitus

Background: Type 1 diabetes mellitus (T1DM) may lead to severe long-term health consequences. In a longitudinal study, we aimed to identify factors present at diagnosis and 6 months later that were associated with glycosylated haemoglobin (HbA 1c) levels at 24 months after T1DM diagnosis, so that diabetic children at risk of poor glycaemic control may be identified. Methods: 229 children,15 years of age diagnosed with T1DM in the Auckland region were studied. Data collected at diagnosis were: age, sex, weight, height, ethnicity, family living arrangement, socio-economic status (SES), T1DM antibody titre, venous pH and bicarbonate. At 6 and 24 months after diagnosis we collected data on weight, height, HbA 1c level, and insulin dose. Results: Factors at diagnosis that were associated with higher HbA1c levels at 6 months: female sex (p,0.05), lower SES (p,0.01), non-European ethnicity (p,0.01) and younger age (p,0.05). At 24 months, higher HbA1c was associated with lower SES (p,0.001), Pacific Island ethnicity (p,0.001), not living with both biological parents (p,0.05), and greater BMI SDS (p,0.05). A regression equation to predict HbA1c at 24 months was consequently developed. Conclusions: Deterioration in glycaemic control shortly after diagnosis in diabetic children is particularly marked in Pacific Island children and in those not living with both biological parents. Clinicians need to be aware of factors associated wit

The Most Slowly Declining Type Ia Supernova 2001ay

We present optical and near-infrared photometry, as well as ground-based optical spectra and Hubble Space Telescope ultraviolet spectra, of the Type Ia supernova (SN) 2001ay. At maximum light the Si II and Mg II lines indicated expansion velocities of 14,000 km/sec, while Si III and S II showed velocities of 9,000 km/sec There is also evidence for some unburned carbon at 12,000 km/sec. SN 2001ay exhibited a decline-rate parameter Delta m_15(B) = 0.68 \pm 0.05 mag; this and the B-band photometry at t > +25 d past maximum make it the most slowly declining Type Ia SN yet discovered. Three of four super-Chandrasekhar-mass candidates have decline rates almost as slow as this. After correction for Galactic and host-galaxy extinction, SN 2001ay had M_B = -19.19 and M_V = -19.17 mag at maximum light; thus, it was not overluminous in optical bands. In near-infrared bands it was overluminous only at the 2-sigma level at most. For a rise time of 18 d (explosion to bolometric maximum) the implied Ni-56 yield was (0.58 \pm 0.15)/alpha M_Sun, with alpha = L_max/E_Ni probably in the range 1.0 to 1.2. The Ni-56 yield is comparable to that of many Type Ia supernovae. The "normal" Ni-56 yield and the typical peak optical brightness suggest that the very broad optical light curve is explained by the trapping of the gamma rays in the inner regions.Comment: 57 pages, 22 figures. To be published in the Astronomical Journal (September 2011

Evidence from diatom-bound nitrogen isotopes for subarctic Pacific stratification during the last ice age and a link to North Pacific denitrification changes

Author Posting. © American Geophysical Union, 2007. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Paleoceanography 22 (2007): PA1215, doi:10.1029/2005PA001205.In a piston core from the central Bering Sea, diatom microfossil-bound N isotopes and the concentrations of opal, biogenic barium, calcium carbonate, and organic N are measured over the last glacial/interglacial cycle. Compared to the interglacial sections of the core, the sediments of the last ice age are characterized by 3‰ higher diatom-bound δ 15N, 70 wt % lower opal content and 1200 ppm lower biogenic barium. Taken together and with constraints on sediment accumulation rate, these results suggest a reduced supply of nitrate to the surface due to stronger stratification of the upper water column of the Bering Sea during glacial times, with more complete nitrate consumption resulting from continued iron supply through atmospheric deposition. This finding extends the body of evidence for a pervasive link between cold climates and polar ocean stratification. In addition, we hypothesize that more complete nutrient consumption in the glacial age subarctic Pacific contributed to the previously observed ice age reduction in suboxia and denitrification in the eastern tropical North Pacific by lowering the nutrient content of the intermediate-depth water formed in the subpolar North Pacific. In the deglacial interval of the Bering Sea record, two apparent peaks in export productivity are associated with maxima in diatom-bound and bulk sediment δ 15N. The high δ 15N in these intervals may have resulted from greater surface nutrient consumption during this period. However, the synchroneity of the deglacial peaks in the Bering Sea with similar bulk sediment δ 15N changes in the eastern Pacific margin and the presence of sediment lamination within the Bering Sea during the deposition of the productivity peaks raise the possibility that both regional and local denitrification worked to raise the δ 15N of the nitrate feeding Bering Sea surface waters at these times.Financial support for this work was provided by NSF grants OCE-0136449, OCE-9981479, ANT-0453680, by BP and Ford Motor Company through the Princeton Carbon Migration Initiative, and by a NDSEG fellowship to B.G.B. Work conducted aboard the USCG Healy (Healy 0202) was funded by grant OPP-9912122

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to ~192,000 individuals, and used ~155,063 samples for independent replication. We identified 31 novel blood pressure or hypertension associated genetic regions in the general population, including three rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5mmHg/allele) than common variants. Multiple rare, nonsense and missense variant associations were found in A2ML1 and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

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

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Dimethyl fumarate (DMF) inhibits inflammasome-mediated inflammation and has been proposed as a treatment for patients hospitalised with COVID-19. This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple treatments in patients hospitalised for COVID-19 (NCT04381936, ISRCTN50189673). In this assessment of DMF performed at 27 UK hospitals, adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. Between 2 March 2021 and 18 November 2021, 713 patients were enroled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients received corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.86-1.47; p = 0.40). There was no significant effect of DMF on any secondary outcome