158 research outputs found

    From Instantons to Sphalerons: Time-Dependent Periodic Solutions of SU(2)-Higgs Theory

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    We solve numerically for periodic, spherically symmetric, classical solutions of SU(2)-Higgs theory in four-dimensional Euclidean space. In the limit of short periods the solutions approach tiny instanton-anti-instanton superpositions while, for longer periods, the solutions merge with the static sphaleron. A previously predicted bifurcation point, where two branches of periodic solutions meet, appears for Higgs boson masses larger than 3.091MW3.091 M_W.Comment: 14 pages, RevTeX with eps figure

    Ecological enhancement techniques to improve habitat heterogeneity on coastal defence structures

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    Sea level rise and higher storm frequency are increasing the need for the placement of hard coastal defences worldwide. The majority of these defences lack optimal habitats for intertidal species, resulting in low diversity and abundance. The construction of coastal defences within marine protected areas (MPA) is also increasing and this study investigates ways to limit the loss of species diversity and intertidal habitat caused by installing rock armour defence structures and other coastal developments. Arrays of holes and grooves were created on granite rock armour in the north of England at Runswick Bay, N. Yorkshire and limestone rock groynes in southern England at Boscombe, Poole Bay, Dorset. Runswick Bay is a Marine Conservation Zone (MCZ) designated for its intertidal habitat and Boscombe is located in close proximity to a Special Area of Conservation (SAC). After 12 months, the treatments had attracted new species to the defence structures and increased the overall diversity and abundance of organisms compared to control areas. Mobile fauna including crabs and fish were also recorded utilising the holes and grooves at Boscombe. Non-native species were recorded in grooves at one site however their abundance was not significantly different to that of control areas. At the southern site, species known to be spreading in response to climate change were found in treatments but not in control areas. The cost of the installation of these enhancement techniques was low in relation to that of the defence scheme and could be easily incorporated before, during or after construction. Through evaluation of the use of these ecological enhancement techniques on coastal structures, it is suggested that they have considerable potential to increase biodiversity on artificial structures, particularly when used within large-scale coastal engineering defence projects

    Associations between statins and COPD: a systematic review

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    <p>Abstract</p> <p>Background</p> <p>Statins have anti-inflammatory and immunomodulating properties which could possibly influence inflammatory airways disease. We assessed evidence for disease modifying effects of statin treatment in patients with chronic obstructive pulmonary disease (COPD).</p> <p>Methods</p> <p>A systematic review was conducted of studies which reported effects of statin treatment in COPD. Data sources searched included MEDLINE, EMBASE and reference lists.</p> <p>Results</p> <p>Eight papers reporting nine original studies met the selection criteria. One was a randomized controlled trial (RCT), one a retrospective nested case-control study, five were retrospective cohort studies of which one was linked with a case-control study, and one was a retrospective population-based analysis. Outcomes associated with treatment with statins included decreased all-cause mortality in three out of four studies (OR/HR 0.48–0.67 in three studies, OR 0.99 in one study), decreased COPD-related mortality (OR 0.19–0.29), reduction in incidence of respiratory-related urgent care (OR 0.74), fewer COPD exacerbations (OR 0.43), fewer intubations for COPD exacerbations (OR 0.1) and attenuated decline in pulmonary function. The RCT reported improvement in exercise capacity and dyspnea after exercise associated with decreased levels of C-reactive protein and Interleukin-6 in statin users, but no improvement of lung function.</p> <p>Conclusion</p> <p>There is evidence from observational studies and one RCT that statins may reduce morbidity and/or mortality in COPD patients. Further interventional studies are required to confirm these findings.</p

    Roadmap on Photovoltaic Absorber Materials for Sustainable Energy Conversion

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    Photovoltaics (PVs) are a critical technology for curbing growing levels of anthropogenic greenhouse gas emissions, and meeting increases in future demand for low-carbon electricity. In order to fulfil ambitions for net-zero carbon dioxide equivalent (CO2eq) emissions worldwide, the global cumulative capacity of solar PVs must increase by an order of magnitude from 0.9 TWp in 2021 to 8.5 TWp by 2050 according to the International Renewable Energy Agency, which is considered to be a highly conservative estimate. In 2020, the Henry Royce Institute brought together the UK PV community to discuss the critical technological and infrastructure challenges that need to be overcome to address the vast challenges in accelerating PV deployment. Herein, we examine the key developments in the global community, especially the progress made in the field since this earlier roadmap, bringing together experts primarily from the UK across the breadth of the photovoltaics community. The focus is both on the challenges in improving the efficiency, stability and levelized cost of electricity of current technologies for utility-scale PVs, as well as the fundamental questions in novel technologies that can have a significant impact on emerging markets, such as indoor PVs, space PVs, and agrivoltaics. We discuss challenges in advanced metrology and computational tools, as well as the growing synergies between PVs and solar fuels, and offer a perspective on the environmental sustainability of the PV industry. Through this roadmap, we emphasize promising pathways forward in both the short- and long-term, and for communities working on technologies across a range of maturity levels to learn from each other.Comment: 160 pages, 21 figure

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

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    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer

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    Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10−8) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for ∼11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction

    Transcriptome-wide association study of breast cancer risk by estrogen-receptor status

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    Previous transcriptome-wide association studies (TWAS) have identified breast cancer risk genes by integrating data from expression quantitative loci and genome-wide association studies (GWAS), but analyses of breast cancer subtype-specific associations have been limited. In this study, we conducted a TWAS using gene expression data from GTEx and summary statistics from the hitherto largest GWAS meta-analysis conducted for breast cancer overall, and by estrogen receptor subtypes (ER+ and ER-). We further compared associations with ER+ and ER- subtypes, using a case-only TWAS approach. We also conducted multigene conditional analyses in regions with multiple TWAS associations. Two genes, STXBP4 and HIST2H2BA, were specifically associated with ER+ but not with ER- breast cancer. We further identified 30 TWAS-significant genes associated with overall breast cancer risk, including four that were not identified in previous studies. Conditional analyses identified single independent breast-cancer gene in three of six regions harboring multiple TWAS-significant genes. Our study provides new information on breast cancer genetics and biology, particularly about genomic differences between ER+ and ER- breast cancer.Peer reviewe
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