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The vulnerability, impacts, adaptation and climate services advisory board (VIACS AB v1.0) contribution to CMIP6
This paper describes the motivation for the creation of the Vulnerability, Impacts, Adaptation and Climate Services (VIACS) Advisory Board for the Sixth Phase of the Coupled Model Intercomparison Project (CMIP6), its initial activities, and its plans to serve as a bridge between climate change applications experts and climate modelers. The climate change application community comprises researchers and other specialists who use climate information (alongside socioeconomic and other environmental information) to analyze vulnerability, impacts and adaptation of natural systems and society in relation to past, ongoing and projected future climate change. Much of this activity is directed toward the co-development of information needed by decision-makers for managing projected risks. CMIP6 provides a unique opportunity to facilitate a two-way dialogue between climate modelers and VIACS experts who are looking to apply CMIP6 results for a wide array of research and climate services objectives. The VIACS Advisory Board convenes leaders of major impact sectors, international programs, and climate services to solicit community feedback that increases applications relevance of the CMIP6-Endorsed Model Intercomparison Projects (MIPs). As an illustration of its potential, the VIACS community provided CMIP6 leadership with a list of prioritized climate model variables and MIP experiments of greatest interest to the climate model applications community, indicating the applicability and societal relevance of climate model simulation outputs. The VIACS Advisory Board also recommended an impacts version of Obs4MIPs, and indicated user needs for the gridding and processing of model output
Not interesting enough to be followed by the NSA: An analysis of Dutch privacy attitudes
Open curtains and a careless attitude. The Dutch are described as holding an indifferent stance towards privacy in the aftermath of Snowden’s revelations of far-reaching government surveillance. But are Dutch reactions as aloof as often claimed? This study provides an in-depth overview of privacy attitudes in the Dutch debate about the National Security Agency (NSA) leaks, showing a greater variety of sentiments than anticipated. A qualitative frame analysis and a quantitative descriptive analysis resulted in six frames, which convey distinct privacy attitudes. Online and offline as well as professional and non-journalistic content in the debate displays a different distribution of frames. The frames, ranging from an “End justifies the means” attitude to an anxious fear of an “Orwellian dystopia”, are placed in a larger framework as the research demonstrates the connection to existing theories about privacy and surveillance. Dutch discussions about the NSA revelations often display a trade-off narrative balancing safety against privacy, and include (de)legitimisation strategies. These outcomes are in line with previous studies about mediated surveillance debates, which indicates that privacy attitudes transcend national boundaries. However, the inclusion of user-generated content adds an individual dimension to the existing body of research and reveals a personal perspective on surveillance issues
Identification of germline monoallelic mutations in IKZF2 in patients with immune dysregulation
Helios, encoded by IKZF2, is a member of the Ikaros family of transcription factors with pivotal roles in T-follicular helper, NK- and T-regulatory cell physiology. Somatic IKZF2 mutations are frequently found in lymphoid malignancies. Although germline mutations in IKZF1 and IKZF3 encoding Ikaros and Aiolos have recently been identified in patients with phenotypically similar immunodeficiency syndromes, the effect of germline mutations in IKZF2 on human hematopoiesis and immunity remains enigmatic. We identified germline IKZF2 mutations (one nonsense (p.R291X)- and 4 distinct missense variants) in six patients with systemic lupus erythematosus, immune thrombocytopenia or EBV-associated hemophagocytic lymphohistiocytosis. Patients exhibited hypogammaglobulinemia, decreased number of T-follicular helper and NK cells. Single-cell RNA sequencing of PBMCs from the patient carrying the R291X variant revealed upregulation of proinflammatory genes associated with T-cell receptor activation and T-cell exhaustion. Functional assays revealed the inability of HeliosR291X to homodimerize and bind target DNA as dimers. Moreover, proteomic analysis by proximity-dependent Biotin Identification revealed aberrant interaction of 3/5 Helios mutants with core components of the NuRD complex conveying HELIOS-mediated epigenetic and transcriptional dysregulation.Peer reviewe
Serum prolactin concentrations as risk factor of metabolic syndrome or type 2 diabetes?
BMPR2 mutations and survival in pulmonary arterial hypertension: an individual participant data meta-analysis.
BACKGROUND: Mutations in the gene encoding the bone morphogenetic protein receptor type II (BMPR2) are the commonest genetic cause of pulmonary arterial hypertension (PAH). However, the effect of BMPR2 mutations on clinical phenotype and outcomes remains uncertain. METHODS: We analysed individual participant data of 1550 patients with idiopathic, heritable, and anorexigen-associated PAH from eight cohorts that had been systematically tested for BMPR2 mutations. The primary outcome was the composite of death or lung transplantation. All-cause mortality was the secondary outcome. Hazard ratios (HRs) for death or transplantation and all-cause mortality associated with the presence of BMPR2 mutation were calculated using Cox proportional hazards models stratified by cohort. FINDINGS: Overall, 448 (29%) of 1550 patients had a BMPR2 mutation. Mutation carriers were younger at diagnosis (mean age 35·4 [SD 14·8] vs 42·0 [17·8] years), had a higher mean pulmonary artery pressure (60·5 [13·8] vs 56·4 [15·3] mm Hg) and pulmonary vascular resistance (16·6 [8·3] vs 12·9 [8·3] Wood units), and lower cardiac index (2·11 [0·69] vs 2·51 [0·92] L/min per m(2); all p<0·0001). Patients with BMPR2 mutations were less likely to respond to acute vasodilator testing (3% [10 of 380] vs 16% [147 of 907]; p<0·0001). Among the 1164 individuals with available survival data, age-adjusted and sex-adjusted HRs comparing BMPR2 mutation carriers with non-carriers were 1·42 (95% CI 1·15-1·75; p=0·0011) for the composite of death or lung transplantation and 1·27 (1·00-1·60; p=0·046) for all-cause mortality. These HRs were attenuated after adjustment for potential mediators including pulmonary vascular resistance, cardiac index, and vasoreactivity. HRs for death or transplantation and all-cause mortality associated with BMPR2 mutation were similar in men and women, but higher in patients with a younger age at diagnosis (p=0·0030 for death or transplantation, p=0·011 for all-cause mortality). INTERPRETATION: Patients with PAH and BMPR2 mutations present at a younger age with more severe disease, and are at increased risk of death, and death or transplantation, compared with those without BMPR2 mutations. FUNDING: Cambridge NIHR Biomedical Research Centre, Medical Research Council, British Heart Foundation, Assistance Publique-Hôpitaux de Paris, INSERM, Université Paris-Sud, Intermountain Research and Medical Foundation, Vanderbilt University, National Center for Advancing Translational Sciences, National Institutes of Health, National Natural Science Foundation of China, and Beijing Natural Science Foundation.Cambridge NIHR Biomedical Research Centre, Medical Research Council, British Heart Foundation, Assistance Publique-Hôpitaux de Paris, INSERM, Université Paris-Sud, Intermountain Research and Medical Foundation, Vanderbilt University, The National Center for Advancing Translational Sciences, The National Institutes of Health, National Natural Science Foundation of China and Beijing Natural Science Foundation.This is the final version of the article. It first appeared from Elsevier via https://doi.org/10.1016/S2213-2600(15)00544-
Health and climate related ecosystem services provided by street trees in the urban environment
Combined searches for the production of supersymmetric top quark partners in proton-proton collisions at root s=13 TeV
A combination of searches for top squark pair production using proton-proton collision data at a center-of-mass energy of 13 TeV at the CERN LHC, corresponding to an integrated luminosity of 137 fb(-1) collected by the CMS experiment, is presented. Signatures with at least 2 jets and large missing transverse momentum are categorized into events with 0, 1, or 2 leptons. New results for regions of parameter space where the kinematical properties of top squark pair production and top quark pair production are very similar are presented. Depending on themodel, the combined result excludes a top squarkmass up to 1325 GeV for amassless neutralino, and a neutralinomass up to 700 GeV for a top squarkmass of 1150 GeV. Top squarks with masses from 145 to 295 GeV, for neutralino masses from 0 to 100 GeV, with a mass difference between the top squark and the neutralino in a window of 30 GeV around the mass of the top quark, are excluded for the first time with CMS data. The results of theses searches are also interpreted in an alternative signal model of dark matter production via a spin-0 mediator in association with a top quark pair. Upper limits are set on the cross section for mediator particle masses of up to 420 GeV
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