24 research outputs found

    Towards an integrated set of surface meteorological observations for climate science and applications

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    Observations are the foundation for understanding the climate system. Yet, currently available land meteorological data are highly fractured into various global, regional and national holdings for different variables and timescales, from a variety of sources, and in a mixture of formats. Added to this, many data are still inaccessible for analysis and usage. To meet modern scientific and societal demands as well as emerging needs such as the provision of climate services, it is essential that we improve the management and curation of available land-based meteorological holdings. We need a comprehensive global set of data holdings, of known provenance, that is truly integrated both across Essential Climate Variables (ECVs) and across timescales to meet the broad range of stakeholder needs. These holdings must be easily discoverable, made available in accessible formats, and backed up by multi-tiered user support. The present paper provides a high level overview, based upon broad community input, of the steps that are required to bring about this integration. The significant challenge is to find a sustained means to realize this vision. This requires a long-term international program. The database that results will transform our collective ability to provide societally relevant research, analysis and predictions in many weather and climate related application areas across much of the globe

    Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

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    Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

    Universal DNA methylation age across mammalian tissues

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    DATA AVAILABILITY STATEMENT : The individual-level data from the Mammalian Methylation Consortium can be accessed from several online locations. All data from the Mammalian Methylation Consortium are posted on Gene Expression Omnibus (complete dataset, GSE223748). Subsets of the datasets can also be downloaded from accession numbers GSE174758, GSE184211, GSE184213, GSE184215, GSE184216, GSE184218, GSE184220, GSE184221, GSE184224, GSE190660, GSE190661, GSE190662, GSE190663, GSE190664, GSE174544, GSE190665, GSE174767, GSE184222, GSE184223, GSE174777, GSE174778, GSE173330, GSE164127, GSE147002, GSE147003, GSE147004, GSE223943 and GSE223944. Additional details can be found in Supplementary Note 2. The mammalian data can also be downloaded from the Clock Foundation webpage: https://clockfoundation.org/MammalianMethylationConsortium. The mammalian methylation array is available through the non-profit Epigenetic Clock Development Foundation (https://clockfoundation.org/). The manifest file of the mammalian array and genome annotations of CpG sites can be found on Zenodo (10.5281/zenodo.7574747). All other data supporting the findings of this study are available from the corresponding author upon reasonable request. The chip manifest files, genome annotations of CpG sites and the software code for universal pan-mammalian clocks can be found on GitHub95 at https://github.com/shorvath/MammalianMethylationConsortium/tree/v2.0.0. The individual R code for the universal pan-mammalian clocks, EWAS analysis and functional enrichment studies can be also found in the Supplementary Code.SUPPLEMENTARY MATERIAL 1 : Supplementary Tables 1–3 and Notes 1–6.SUPPLEMENTARY MATERIAL 2 : Reporting SummarySUPPLEMENTARY MATERIAL 3 : Supplementary Data 1–14.SUPPLEMENTARY MATERIAL 4 : Supplementary Code.Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.https://www.nature.com/nataginghj2024Zoology and EntomologySDG-15:Life on lan

    Recherche de l'influence des conditions de milieu sur la fixation des bacteries pathogenes aux surfaces solides, leur survie et leur maintien dans les eaux continentales superficielles

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    Comite: Milieux physiques - EauSIGLEAvailable from Centre de Documentation Scientifique et Technique, CNRS, 26 rue Boyer, 75971 Paris Cedex 20 (France) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

    Biomonitoring of the genotoxic potential of draining water from dredged sediments, using the comet and micronucleus tests on amphibian (Xenopus laevis) larvae and bacterial assays (Mutatox (R) and Ames tests)

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    International audienceManagement of contaminated dredged sediments is a matter of great human concern. The present investigation evaluates the genotoxic potential of aqueous extracts of five sediments from French channels (draining water from dredged sediments), using larvae of the frog Xenopus laevis. Two genotoxic endpoints were analyzed in larvae: clastogenic and/or aneugenic effects (micronucleus induction after 12 d of exposure) and DNA-strand breaking potency (comet assay after 1 and 12 d of exposure) in the circulating blood. Additionally, in vitro bacterial assays (Microtox and Ames tests) were carried out and the results were compared with those obtained with larvae. Physicochemical analyses were also taken into account. Analytical analyses highlighted in the five draining waters a heavy load of contaminants such as metals and hydrocarbons. The results obtained with the micronucleus test established the genotoxicity of three draining waters. The comet assay showed that all 5 draining waters were genotoxic after 1 d of exposure. Although 3 of them were still genotoxic after 12 d of exposure, DNA damage globally decreased between d 1 and 12. The comet assay can be considered as a genotoxicity-screening tool. Data indicate that both tests should be used in conjunction in Xenopus. Bacterial tests (Ames) revealed genotoxicity for only one draining water. The results confirm the relevance of the amphibian model and the need to resort to bioassays in vivo such as the Xenopus micronucleus and comet assays for evaluation of the ecotoxicological impact, an essential complement to the physicochemical data

    European low-dose radiation risk research strategy: Future of research on biological effects at low doses.

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    In 2009, the European High Level and Expert Group identified key policy and scientific questions to be addressed through a strategic research agenda for low-dose radiation risk. This initiated the establishment of a European Research Platform, called MELODI (Multidisciplinary European Low Dose Research Initiative). In 2010, the DoReMi Network of Excellence was launched in the Euratom 7th Framework Programme. DoReMi has acted as an operational tool for the sustained development of the MELODI platform during its early years. A long-term Strategic Research Agenda for European low-dose radiation risk research has been developed by MELODI. Strategic planning of DoReMi research activities is carried out in close collaboration with MELODI. The research priorities for DoReMi are designed to focus on objectives that are achievable within the 6-y lifetime of the project and that are in areas where stimulus and support can help progress towards the longer-term strategic objectives
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