78 research outputs found

    Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

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    Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

    The first 20 months of the COVID-19 pandemic: Mortality, intubation and ICU rates among 104,590 patients hospitalized at 21 United States health systems

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    Main objective There is limited information on how patient outcomes have changed during the COVID-19 pandemic. This study characterizes changes in mortality, intubation, and ICU admission rates during the first 20 months of the pandemic. Study design and methods University of Wisconsin researchers collected and harmonized electronic health record data from 1.1 million COVID-19 patients across 21 United States health systems from February 2020 through September 2021. The analysis comprised data from 104,590 adult hospitalized COVID-19 patients. Inclusion criteria for the analysis were: (1) age 18 years or older; (2) COVID-19 ICD-10 diagnosis during hospitalization and/or a positive COVID-19 PCR test in a 14-day window (+/- 7 days of hospital admission); and (3) health system contact prior to COVID-19 hospitalization. Outcomes assessed were: (1) mortality (primary), (2) endotracheal intubation, and (3) ICU admission. Results and significance The 104,590 hospitalized participants had a mean age of 61.7 years and were 50.4% female, 24% Black, and 56.8% White. Overall risk-standardized mortality (adjusted for age, sex, race, ethnicity, body mass index, insurance status and medical comorbidities) declined from 16% of hospitalized COVID-19 patients (95% CI: 16% to 17%) early in the pandemic (February-April 2020) to 9% (CI: 9% to 10%) later (July-September 2021). Among subpopulations, males (vs. females), those on Medicare (vs. those on commercial insurance), the severely obese (vs. normal weight), and those aged 60 and older (vs. younger individuals) had especially high mortality rates both early and late in the pandemic. ICU admission and intubation rates also declined across these 20 months. Conclusions Mortality, intubation, and ICU admission rates improved markedly over the first 20 months of the pandemic among adult hospitalized COVID-19 patients although gains varied by subpopulation. These data provide important information on the course of COVID-19 and identify hospitalized patient groups at heightened risk for negative outcomes. Trial registration ClinicalTrials.gov Identifier: NCT04506528 (https://clinicaltrials.gov/ct2/show/NCT04506528)

    Assimilation and partial melting of continental crust: evidence from the mineralogy and geochemistry of autoliths and xenoliths

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    This paper presents a model for the partial melting of quartz diorite and greywacke in the upper crust based on the mineralogy and geochemistry of enclaves within the Loch Doon granitic intrusion of southern Scotland. The melting of quartz diorite was modelled using autoliths, which represent fragments of cogenetic igneous rocks that became incorporated in the fractionating magma. Compared to their quartz diorite parents, the autoliths are enriched to varying degrees in some elements (notably Rb, Nb, Ta, Sm, Y, Yb) and depleted in others (Sr, and Ba); Eu and P are also depleted in the more assimitated autoliths. The compositions of melts that could be derived from assimilation of the autoliths have also been calculated: their REE patterns reveal a light REE enrichment, low concentrations of heavy REEs (1–3 x chondrite) and a positive Eu anomaly. The calculated degrees of melting vary from 35% in the least assimilated to 84% in the most assimilated autolith (assuming a bulk distribution coefficient of 10 for the most compatible element). Results from modelling of xenolith compositions (derived from metasediments) are also reported, but because of uncertainties in the composition of the parental sediment, these data are subject to larger errors. They do, however, indicate that resultant partial melts are distinctly different from those derived by partial melting of autoliths. In particular, the REE pattern of a greywacke-derived melt shows a slight enrichment in light REEs, greater concentrations of heavy REEs (10 x chondrite) and a small negative Eu anomaly. The calculated degrees of melting of the xenoliths fall in the range of 66–88% (assuming a bulk distribution coefficient of 10 for the most compatible element). The results have direct implications for assimilation and melting of the upper crust. By taking into account how the nature of residual phases is likely to change with depth, it can be demonstrated that some Archaean tonalite gneisses could represent liquids derived by partial melting of igneous material

    Petrogenetic modelling of in situ fractional crystallization in the zoned Loch Doon pluton, Scotland

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    The late Caledonian Loch Doon granitic intrusion ranges in composition from hypersthene diorite at the margin, through quartz diorite, granodiorite and granite to cordierite microgranite at its core. Petrogenetic modelling of trace element variations and least squares analysis of major elements indicate that two distinct magmas are involved, each magma controlled by crystallization of plag-opx-cpx-bio. Late stage rocks related to the second magma include the cordierite microgranites and aplites, which are interpreted as the final residue which crystallized rapidly after a build up and loss of volatiles. Analyses of whole rocks and minerals for REE's and other elements of moderate-high ionic potential indicate that these elements are strongly controlled by minor phase crystallization; apatite, zircon, sphene and allanite are dominant at intermediate compositions but other accessory minerals such as monazite and xenotime may also become important at acid compositions. It is probable that within each magma the mechanisms of crystal settling and filter pressing operated, the former being initially dominant, and the latter becoming more important with increasing degree of fractional crystallization
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