7 research outputs found

    Dynamic sea-level changes and potential implications for storm surges in the UK: a storylines perspective

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    Global sea-level rise caused by a warming climate increases flood risk from storm surge events for those who live in coastal and low-lying areas. Estimates of global thermosteric sea-level rises are well constrained by model projections, but local variability in dynamic sea-level arising from seasonal and interannual changes is less well characterised. In this paper we use satellite altimetry observations coupled with CMIP6 model projections to understand drivers of change in dynamic sea-level over the UK shelf seas. We find a northward shift in the atmospheric jet stream and a weakening of the Atlantic meridional overturning circulation to be the key drivers of local dynamic sea-level variability. Using a storyline approach to constrain climate system responses to changes in atmospheric greenhouse gas concentrations, we find that dynamic sea-level is predicted to rise between 15–39 cm by 2080–2099 along the east coast of England (ECE). Under a worst-case scenario, assuming maximum variability as seen in the CMIP6 projections, ECE dynamic sea-level rise could reach 58 cm by 2100. We illustrate the impact of this dynamic sea-level rise in addition to non-dynamic components on the risks posed by storm surge events in ECE using an idealised example. If a storm surge event of the magnitude of the one experienced in ECE on the 5th of December 2013 was to occur in 2100, an additional 1414 km2 of land would potentially be affected in our worst-case idealised example, 22.4% of which can be attributed to dynamic sea-level rise

    A map of human genome variation from population-scale sequencing

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    The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic researc

    Empagliflozin in Patients with Chronic Kidney Disease

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    Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m(2) of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m(2) with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to < 10 ml per minute per 1.73 m(2), a sustained decrease in eGFR of & GE;40% from baseline, or death from renal causes) or death from cardiovascular causes. Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P < 0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups. Conclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo
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