The K2 Mission: Characterization and Early results

The K2 mission will make use of the Kepler spacecraft and its assets to expand upon Kepler's groundbreaking discoveries in the fields of exoplanets and astrophysics through new and exciting observations. K2 will use an innovative way of operating the spacecraft to observe target fields along the ecliptic for the next 2-3 years. Early science commissioning observations have shown an estimated photometric precision near 400 ppm in a single 30 minute observation, and a 6-hour photometric precision of 80 ppm (both at V=12). The K2 mission offers long-term, simultaneous optical observation of thousands of objects at a precision far better than is achievable from ground-based telescopes. Ecliptic fields will be observed for approximately 75-days enabling a unique exoplanet survey which fills the gaps in duration and sensitivity between the Kepler and TESS missions, and offers pre-launch exoplanet target identification for JWST transit spectroscopy. Astrophysics observations with K2 will include studies of young open clusters, bright stars, galaxies, supernovae, and asteroseismology.Comment: 25 pages, 11 figures, Accepted to PAS

Predicted chance that global warming will temporarily exceed 1.5 °C

The Paris Agreement calls for efforts to limit anthropogenic global warming to less than 1.5 °C above preindustrial levels. However, natural internal variability may exacerbate anthropogenic warming to produce temporary excursions above 1.5 °C. Such excursions would not necessarily exceed the Paris Agreement, but would provide a warning that the threshold is being approached. Here we develop a new capability to predict the probability that global temperature will exceed 1.5 °C above preindustrial levels in the coming 5 years. For the period 2017 to 2021 we predict a 38% and 10% chance, respectively, of monthly or yearly temperatures exceeding 1.5 °C, with virtually no chance of the 5‐year mean being above the threshold. Our forecasts will be updated annually to provide policy makers with advanced warning of the evolving probability and duration of future warming events

Recent applications and potential of near-term (interannual to decadal) climate predictions

Following efforts from leading centres for climate forecasting, sustained routine operational near-term climate predictions (NTCP) are now produced that bridge the gap between seasonal forecasts and climate change projections offering the prospect of seamless climate services. Though NTCP is a new area of climate science and active research is taking place to increase understanding of the processes and mechanisms required to produce skillful predictions, this significant technical achievement combines advances in initialisation with ensemble prediction of future climate up to a decade ahead. With a growing NTCP database, the predictability of the evolving externally-forced and internally-generated components of the climate system can now be quantified. Decision-makers in key sectors of the economy can now begin to assess the utility of these products for informing climate risk and for planning adaptation and resilience strategies up to a decade into the future. Here, case studies are presented from finance and economics, water management, agriculture and fisheries management demonstrating the emerging utility and potential of operational NTCP to inform strategic planning across a broad range of applications in key sectors of the global economy

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Pubertal development and prostate cancer risk: Mendelian randomization study in a population-based cohort.

BACKGROUND: Epidemiological studies have observed a positive association between an earlier age at sexual development and prostate cancer, but markers of sexual maturation in boys are imprecise and observational estimates are likely to suffer from a degree of uncontrolled confounding. To obtain causal estimates, we examined the role of pubertal development in prostate cancer using genetic polymorphisms associated with Tanner stage in adolescent boys in a Mendelian randomization (MR) approach. METHODS: We derived a weighted genetic risk score for pubertal development, combining 13 SNPs associated with male Tanner stage. A higher score indicated a later puberty onset. We examined the association of this score with prostate cancer risk, stage and grade in the UK-based ProtecT case-control study (n = 2,927), and used the PRACTICAL consortium (n = 43,737) as a replication sample. RESULTS: In ProtecT, the puberty genetic score was inversely associated with prostate cancer grade (odds ratio (OR) of high- vs. low-grade cancer, per tertile of the score: 0.76; 95 % CI, 0.64-0.89). In an instrumental variable estimation of the causal OR, later physical development in adolescence (equivalent to a difference of one Tanner stage between pubertal boys of the same age) was associated with a 77 % (95 % CI, 43-91 %) reduced odds of high Gleason prostate cancer. In PRACTICAL, the puberty genetic score was associated with prostate cancer stage (OR of advanced vs. localized cancer, per tertile: 0.95; 95 % CI, 0.91-1.00) and prostate cancer-specific mortality (hazard ratio amongst cases, per tertile: 0.94; 95 % CI, 0.90-0.98), but not with disease grade. CONCLUSIONS: Older age at sexual maturation is causally linked to a reduced risk of later prostate cancer, especially aggressive disease.This work was supported by the World Cancer Research Fund (2011/419) and Cancer Research UK (C18281/A19169). The Integrative Epidemiology Unit (IEU) is supported by the MRC and the University of Bristol (G0600705, MC_UU_12013/19), and the Integrative Cancer Epidemiology Programme is supported by Cancer Research UK programme grant C18281/A19169. The National Institute for Health Research (NIHR) Bristol Nutrition Biomedical Research Unit is funded by the NIHR and is a partnership between University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The ProtecT study is supported by the UK NIHR Health Technology Assessment (HTA) Programme (HTA 96/20/99; ISRCTN20141297). Funding for PRACTICAL and the iCOGS infrastructure came from: the European Community’s Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/ A16565), the National Institutes of Health (CA128978), and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112 – the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. We acknowledge support from the NIHR to the Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s12916-016-0602-

WMO Global Annual to Decadal Climate Update A Prediction for 2021-25

Under embargo until: 2022-10-01As climate change accelerates, societies and climate-sensitive socioeconomic sectors cannot continue to rely on the past as a guide to possible future climate hazards. Operational decadal predictions offer the potential to inform current adaptation and increase resilience by filling the important gap between seasonal forecasts and climate projections. The World Meteorological Organization (WMO) has recognized this and in 2017 established the WMO Lead Centre for Annual to Decadal Climate Predictions (shortened to “Lead Centre” below), which annually provides a large multimodel ensemble of predictions covering the next 5 years. This international collaboration produces a prediction that is more skillful and useful than any single center can achieve. One of the main outputs of the Lead Centre is the Global Annual to Decadal Climate Update (GADCU), a consensus forecast based on these predictions. This update includes maps showing key variables, discussion on forecast skill, and predictions of climate indices such as the global mean near-surface temperature and Atlantic multidecadal variability. it also estimates the probability of the global mean temperature exceeding 1.5°C above preindustrial levels for at least 1 year in the next 5 years, which helps policy-makers understand how closely the world is approaching this goal of the Paris Agreement. This paper, written by the authors of the GADCU, introduces the GADCU, presents its key outputs, and briefly discusses its role in providing vital climate information for society now and in the future.publishedVersio

The effects of height and BMI on prostate cancer incidence and mortality:a Mendelian randomization study in 20,848 cases and 20,214 controls from the PRACTICAL consortium

Background\ud \ud Epidemiological studies suggest a potential role for obesity and determinants of adult stature in prostate cancer risk and mortality, but the relationships described in the literature are complex. To address uncertainty over the causal nature of previous observational findings, we investigated associations of height- and adiposity-related genetic variants with prostate cancer risk and mortality.\ud \ud Methods\ud \ud We conducted a case–control study based on 20,848 prostate cancers and 20,214 controls of European ancestry from 22 studies in the PRACTICAL consortium. We constructed genetic risk scores that summed each man’s number of height and BMI increasing alleles across multiple single nucleotide polymorphisms robustly associated with each phenotype from published genome-wide association studies.\ud \ud Results\ud \ud The genetic risk scores explained 6.31 and 1.46 % of the variability in height and BMI, respectively. There was only weak evidence that genetic variants previously associated with increased BMI were associated with a lower prostate cancer risk (odds ratio per standard deviation increase in BMI genetic score 0.98; 95 % CI 0.96, 1.00; p = 0.07). Genetic variants associated with increased height were not associated with prostate cancer incidence (OR 0.99; 95 % CI 0.97, 1.01; p = 0.23), but were associated with an increase (OR 1.13; 95 % CI 1.08, 1.20) in prostate cancer mortality among low-grade disease (p heterogeneity, low vs. high grade <0.001). Genetic variants associated with increased BMI were associated with an increase (OR 1.08; 95 % CI 1.03, 1.14) in all-cause mortality among men with low-grade disease (p heterogeneity = 0.03).\ud \ud Conclusions\ud \ud We found little evidence of a substantial effect of genetically elevated height or BMI on prostate cancer risk, suggesting that previously reported observational associations may reflect common environmental determinants of height or BMI and prostate cancer risk. Genetically elevated height and BMI were associated with increased mortality (prostate cancer-specific and all-cause, respectively) in men with low-grade disease, a potentially informative but novel finding that requires replication

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin