Antineutrinos from Earth: A reference model and its uncertainties

We predict geoneutrino fluxes in a reference model based on a detailed description of Earth's crust and mantle and using the best available information on the abundances of uranium, thorium, and potassium inside Earth's layers. We estimate the uncertainties of fluxes corresponding to the uncertainties of the element abundances. In addition to distance integrated fluxes, we also provide the differential fluxes as a function of distance from several sites of experimental interest. Event yields at several locations are estimated and their dependence on the neutrino oscillation parameters is discussed. At Kamioka we predict N(U+Th)=35 +- 6 events for 10^{32} proton yr and 100% efficiency assuming sin^2(2theta)=0.863 and delta m^2 = 7.3 X 10^{-5} eV^2. The maximal prediction is 55 events, obtained in a model with fully radiogenic production of the terrestrial heat flow.Comment: 24 pages, ReVTeX4, plus 7 postscript figures; minor formal changes to match version to be published in PR

The Role of Tobacco Smoke in Bladder and Kidney Carcinogenesis: A Comparison of Exposures and Meta-analysis of Incidence and Mortality Risks.

Context Tobacco smoke includes a mix of carcinogens implicated in the etiology of bladder cancer (BC) and renal cell cancer (RCC). Objective We reviewed the impact of tobacco exposure on BCC and RCC incidence and mortality, and whether smoking cessation decreases the risk. Evidence acquisition A systematic review of original articles in English was performed in August 2013. Meta-analysis of risks was performed using adjusted risk ratios where available. Publication bias was assessed using Begg and Egger tests. Evidence synthesis We identified 2683 papers, of which 114 fulfilled our inclusion criteria, of which 90 studies investigated BC and 24 investigated RCC. The pooled relative risk (RR) of BC incidence was 2.57 (95% confidence interval [CI] 2.37–2.78) for all smokers, 3.37 (3.01–3.78) for current smokers, and 1.98 (1.76–2.22) for former smokers. The corresponding pooled RR of BC disease-specific mortality (DSM) was 1.79 (1.40–2.29), 1.89 (1.29–2.78) and 1.66 (1.10–2.52). The pooled RR of RCC incidence was 1.27 (1.18–135) for all smokers, 1.29 (1.14–1.46) for current smokers, and 1.14 (1.06–1.22) for former smokers. The corresponding RCC DSM risk was 1.20 (1.02–1.41), 1.32 (1.08–1.62), and 1.01 (0.85–1.18). Conclusions We present an up-to-date review of tobacco smoking and BC and RCC incidence and mortality. Tobacco smoking significantly increases the risk of BC and RCC incidence. BC incidence and DSM risk are greatest in current smokers and lowest in former smokers, indicating that smoking cessation confers benefit. We found that secondhand smoke exposure is associated with a significant increase in BC risk. Patient summary Tobacco smoking affects the development and progression of bladder cancer and renal cell cancer. Smoking cessation reduces the risks of developing and dying from these common cancers. We quantify these risks using the most up-to-date results published in the literature

Urban hedges: a review of plant species and cultivars for ecosystem service delivery in north-west Europe

Urban hedges provide a number of important ecosystem services (ESs) including microclimate alteration, flood and pollution mitigation, and biodiversity provision, along with some disservices (DSs, e.g. invasiveness, allergenicity). However, hedge plant species differ in their capacity to promote different services, so it is important that the decision to plant hedges is evidence-based. The objectives of this study were thus to (i) to review the role of urban hedges within NW Europe; (ii) review the available literature detailing the ESs and DSs provided by different plant species and cultivars when used as hedge plants; (iii) identify where there is a lack of evidence for certain species or ESs/DSs; and (iv) develop a starting point for a discussion about appropriate species/cultivar selection to deliver multiple ESs, and avoid DSs. Many studies consider biodiversity and air quality ESs. There are significant gaps in the literature relating to rainfall mitigation/flood protection, but also CO2 sequestration, allergenicity and human psychological well-being impact of different species. Additionally, for noise and pollution mitigation studies, a range of methodologies and units are used, making comparisons between hedge species difficult/impossible. A number of common hedge species demonstrated high levels of ESs delivery, including Fagus sylvatica, Crataegus monogyna, Ilex aquifolium and Rosa rugosa. No species surveyed had an entirely negative association with ESs, and most provide at least some benefits in supporting ESs provision (e.g. Viburnum tinus, Laurus nobilis). We created a matrix, in a table form, linking plant species, key plant traits and ESs/DSs, which should make it easier for professionals to choose species best suited to provide multiple benefits, whilst minimising the drawbacks. Our review suggests that the relative contribution of urban hedges to ESs delivery may be under-valued currently, and calls for more research

Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10−9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies. Delineation of the genetic architecture of hematological traits in a multi-ethnic dataset allows identification of rare variants with strong effects specific to non-European populations and improved fine mapping of GWAS variants using the trans-ethnic approach

Functional and quality of life outcomes of localised prostate cancer treatments (prostate testing for cancer and treatment [ProtecT] study)

Objective To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making. Patients and Methods Men aged 50–69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores. Results Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL. Conclusion Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes

Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Funding Information: GMP, PN, and CW are supported by NHLBI R01HL127564. GMP and PN are supported by R01HL142711. AG acknowledge support from the Wellcome Trust (201543/B/16/Z), European Union Seventh Framework Programme FP7/2007–2013 under grant agreement no. HEALTH-F2-2013–601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. JMM is supported by American Diabetes Association Innovative and Clinical Translational Award 1–19-ICTS-068. SR was supported by the Academy of Finland Center of Excellence in Complex Disease Genetics (Grant No 312062), the Finnish Foundation for Cardiovascular Research, the Sigrid Juselius Foundation, and University of Helsinki HiLIFE Fellow and Grand Challenge grants. EW was supported by the Finnish innovation fund Sitra (EW) and Finska Läkaresällskapet. CNS was supported by American Heart Association Postdoctoral Fellowships 15POST24470131 and 17POST33650016. Charles N Rotimi is supported by Z01HG200362. Zhe Wang, Michael H Preuss, and Ruth JF Loos are supported by R01HL142302. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 217065/Z/19/Z), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215–2001) and the MRC Integrative Epidemiology Unit (MC_UU_00011), and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). Ruth E Mitchell is a member of the MRC Integrative Epidemiology Unit at the University of Bristol funded by the MRC (MC_UU_00011/1). Simon Haworth is supported by the UK National Institute for Health Research Academic Clinical Fellowship. Paul S. de Vries was supported by American Heart Association grant number 18CDA34110116. Julia Ramierz acknowledges support by the People Programme of the European Union’s Seventh Framework Programme grant n° 608765 and Marie Sklodowska-Curie grant n° 786833. Maria Sabater-Lleal is supported by a Miguel Servet contract from the ISCIII Spanish Health Institute (CP17/00142) and co-financed by the European Social Fund. Jian Yang is funded by the Westlake Education Foundation. Olga Giannakopoulou has received funding from the British Heart Foundation (BHF) (FS/14/66/3129). CHARGE Consortium cohorts were supported by R01HL105756. Study-specific acknowledgements are available in the Additional file : Supplementary Note. The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services. Publisher Copyright: © 2022, The Author(s).Background: Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery. Results: To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3–5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism. Conclusions: Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.Peer reviewe