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Sökning: WFRF:(Dudley M)

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1.
  • 2019
  • Tidskriftsartikel (refereegranskat)
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2.
  • Lumbers, R. T., et al. (författare)
  • The genomics of heart failure: design and rationale of the HERMES consortium
  • 2021
  • Ingår i: Esc Heart Failure. - : Wiley. - 2055-5822. ; 8:6, s. 5531-5541
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims The HERMES (HEart failure Molecular Epidemiology for Therapeutic targets) consortium aims to identify the genomic and molecular basis of heart failure. Methods and results The consortium currently includes 51 studies from 11 countries, including 68 157 heart failure cases and 949 888 controls, with data on heart failure events and prognosis. All studies collected biological samples and performed genome-wide genotyping of common genetic variants. The enrolment of subjects into participating studies ranged from 1948 to the present day, and the median follow-up following heart failure diagnosis ranged from 2 to 116 months. Forty-nine of 51 individual studies enrolled participants of both sexes; in these studies, participants with heart failure were predominantly male (34-90%). The mean age at diagnosis or ascertainment across all studies ranged from 54 to 84 years. Based on the aggregate sample, we estimated 80% power to genetic variant associations with risk of heart failure with an odds ratio of >1.10 for common variants (allele frequency > 0.05) and >1.20 for low-frequency variants (allele frequency 0.01-0.05) at P < 5 x 10(-8) under an additive genetic model. Conclusions HERMES is a global collaboration aiming to (i) identify the genetic determinants of heart failure; (ii) generate insights into the causal pathways leading to heart failure and enable genetic approaches to target prioritization; and (iii) develop genomic tools for disease stratification and risk prediction.
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3.
  • Roselli, Carolina, et al. (författare)
  • Multi-ethnic genome-wide association study for atrial fibrillation
  • 2018
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
  • Tidskriftsartikel (refereegranskat)abstract
    • Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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4.
  • Shah, S, et al. (författare)
  • Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure
  • 2020
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 163-
  • Tidskriftsartikel (refereegranskat)abstract
    • Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.
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5.
  • Nowak-Sliwinska, Patrycja, et al. (författare)
  • Consensus guidelines for the use and interpretation of angiogenesis assays
  • 2018
  • Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
  • Forskningsöversikt (refereegranskat)abstract
    • The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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6.
  • Menkveld, Albert J., et al. (författare)
  • Nonstandard Errors
  • 2024
  • Ingår i: JOURNAL OF FINANCE. - : Wiley-Blackwell. - 0022-1082 .- 1540-6261. ; 79:3, s. 2339-2390
  • Tidskriftsartikel (refereegranskat)abstract
    • In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty-nonstandard errors (NSEs). We study NSEs by letting 164 teams test the same hypotheses on the same data. NSEs turn out to be sizable, but smaller for more reproducible or higher rated research. Adding peer-review stages reduces NSEs. We further find that this type of uncertainty is underestimated by participants.
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7.
  • Sunguc, Ceren, et al. (författare)
  • Risk of subsequent primary oral cancer in a cohort of 69,460 5-year survivors of childhood and adolescent cancer in Europe : the PanCareSurFup study
  • 2023
  • Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 128:1, s. 80-90
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Survivors of childhood cancer are at risk of subsequent primary malignant neoplasms (SPNs), but the risk for rarer types of SPNs, such as oral cancer, is uncertain. Previous studies included few oral SPNs, hence large-scale cohorts are required to identify groups at risks. Methods: The PanCareSurFup cohort includes 69,460 5-year survivors of childhood cancer across Europe. Risks of oral SPNs were defined by standardised incidence ratios (SIRs), absolute excess risks and cumulative incidence. Results: One hundred and forty-five oral SPNs (64 salivary gland, 38 tongue, 20 pharynx, 2 lip, and 21 other) were ascertained among 143 survivors. Survivors were at 5-fold risk of an oral SPN (95% CI: 4.4–5.6). Survivors of leukaemia were at greatest risk (SIR = 19.2; 95% CI: 14.6–25.2) followed by bone sarcoma (SIR = 6.4, 95% CI: 3.7–11.0), Hodgkin lymphoma (SIR = 6.2, 95% CI: 3.9–9.9) and soft-tissue sarcoma (SIR = 5.0, 95% CI: 3.0–8.5). Survivors treated with radiotherapy were at 33-fold risk of salivary gland SPNs (95% CI: 25.3–44.5), particularly Hodgkin lymphoma (SIR = 66.2, 95% CI: 43.6–100.5) and leukaemia (SIR = 50.5, 95% CI: 36.1–70.7) survivors. Survivors treated with chemotherapy had a substantially increased risk of a tongue SPN (SIR = 15.9, 95% CI: 10.6–23.7). Conclusions: Previous radiotherapy increases the risk of salivary gland SPNs considerably, while chemotherapy increases the risk of tongue SPNs substantially. Awareness of these risks among both health-care professionals and survivors could play a crucial role in detecting oral SPNs early.
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8.
  • Borregales, L. D., et al. (författare)
  • Grade Migration of Prostate Cancer in the United States During the Last Decade
  • 2022
  • Ingår i: Jnci-Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 114:7, s. 1012-1019
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Prostate cancer (PC) screening guidelines have changed over the last decade to reduce overdiagnosis and overtreatment of low-grade disease. We sought to examine and attempt to explain how changes in screening strategies have impacted temporal trends in Gleason grade group (GG) PC at diagnosis and radical prostatectomy pathology. Methods Using the Surveillance, Epidemiology, and End Results Registry database, we identified 438 432 men with newly diagnosed PC during 2010-2018. Temporal trends in incidence of GG at biopsy, radical prostatectomy pathology, prostate-specific antigen (PSA) level, and metastasis at diagnosis were examined. The National Health Interview Survey database was examined to evaluate trends in PSA-screening rates, and a literature review evaluating magnetic resonance imaging and biomarkers utilization during this period was performed. Results Between 2010 and 2018, the incidence of low-grade PC (GG1) decreased from 52 to 26 cases per 100 000 (P < .001). The incidence of GG1 as a proportion of all PC decreased from 47% to 32%, and the proportion of GG1 at radical prostatectomy pathology decreased from 32% to 10% (P < .001). However, metastases at diagnosis increased from 3.0% to 5.2% (P < .001). During 2010-2013, PSA screening rates in men aged 50-74 years declined from 39 to 32 per 100 men and remained stable. Utilization rates of magnetic resonance imaging and biomarkers modestly increased from 7.2% in 2012 to 17% in 2019 and 1.3% in 2012 to 13% in 2019, respectively. Conclusions We found a significant decrease in the diagnosis and treatment of GG1 PC between 2010 and 2018. Changes in PSA screening practices appear as the primary contributor. Public health efforts should be directed toward addressing the increase in the diagnoses of metastatic PC.
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10.
  • Vetter, W.M., et al. (författare)
  • Dislocation loops formed during the degradation of forward-biased 4H-SiC p-n junctions
  • 2003
  • Ingår i: Materials Science & Engineering. - 0921-5107 .- 1873-4944. ; 98:3, s. 220-224
  • Tidskriftsartikel (refereegranskat)abstract
    • The partial dislocations that border triangle or parallelogram-shaped stacking faults formed during the degradation of p-n diodes fabricated on 4H-SiC wafers were determined by transmission X-ray topography to be dislocation loops of Burgers vector 1/3<101¯0>, the Shockley partial type, consistent with previously reported TEM results. Some were separated from axial screw dislocations also present in the sample, indicating that the axial dislocations were not involved in the loops' nucleation, while others were seen to have interacted during their growth with the axial screw dislocations, distorting their shapes from those of ideal parallelograms. © 2003 Elsevier Science B.V. All rights reserved.
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11.
  • Blösch, Günter, et al. (författare)
  • Twenty-three unsolved problems in hydrology (UPH) - a community perspective
  • 2019
  • Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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12.
  • Cox, E., et al. (författare)
  • The Intriguing Interaction of Escherichia coli with the Host Environment and Innovative Strategies To Interfere with Colonization: a Summary of the 2019 E. coli and the Mucosal Immune System Meeting
  • 2020
  • Ingår i: Applied and environmental microbiology. - : American Society for Microbiology. - 0099-2240 .- 1098-5336. ; 86:24
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • The third E. coli and the Mucosal Immune System (ECMIS) meeting was held at Ghent University in Belgium from 2 to 5 June 2019. It brought together an international group of scientists interested in mechanisms of colonization, host response, and vaccine development. ECMIS distinguishes itself from related meetings on these enteropathogens by providing a greater emphasis on animal health and disease and covering a broad range of pathotypes, including enterohemorrhagic, enteropathogenic, enterotoxigenic, enteroaggregative, and extraintestinal pathogenic Escherichia coli. As it is well established that the genus Shigella represents a subspecies of E. coli, these organisms along with related enteroinvasive E. coli are also included. In addition, Tannerella forsythia, a periodontal pathogen, was presented as an example of a pathogen which uses its surface glycans for mucosal interaction. This review summarizes several highlights from the 2019 meeting and major advances to our understanding of the biology of these pathogens and their impact on the host.
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17.
  • Jenkin, M. E., et al. (författare)
  • The CRI v2.2 reduced degradation scheme for isoprene
  • 2019
  • Ingår i: Atmospheric Environment. - : Elsevier BV. - 1873-2844 .- 1352-2310. ; 212:1 Sept., s. 172-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The reduced representation of isoprene degradation in the Common Representative Intermediates (CRI)mechanism has been systematically updated, using the Master Chemical Mechanism (MCM v3.3.1)as a reference benchmark, with the updated mechanism being released as CRI v2.2. The complete isoprene degradation mechanism in CRI v2.2 consists of 186 reactions of 56 closed shell and free radical species, this being an order of magnitude reduction in size compared with MCM v3.3.1. The chemistry initiated by reaction with OH radicals, NO3 radicals and ozone (O3)is treated. An overview of the updates is provided, within the context of reported kinetic and mechanistic information. The revisions mainly relate to the OH-initiated chemistry, which tends to dominate under atmospheric conditions, although these include updates to the chemistry of products that are also generated from the O3- and NO3-initiated oxidation. The revisions have impacts in a number of key areas, including recycling of HOx and NOx. The performance of the CRI v2.2 isoprene mechanism has been compared with those of the preceding version (CRI v2.1)and the reference MCM v3.3.1 over a range of relevant conditions, using a box model of the tropical forested boundary layer. In addition, tests are carried out to ensure that the performance of MCM v3.3.1 remains robust to more recently reported information. CRI v2.2 has also been implemented into the STOCHEM chemistry-transport model, with a customized close-variant of CRI v2.2 implemented into the EMEP MSC-W chemistry-transport model. The results of these studies are presented and used to illustrate the global-scale impacts of the mechanistic updates on HOx radical concentrations.
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18.
  • Penning, W.E., et al. (författare)
  • Classifying aquatic macrophytes as indicators of eutrophication in European lakes
  • 2008
  • Ingår i: Aquatic Ecology. - : Springer Science and Business Media LLC. - 1386-2588 .- 1573-5125. ; 42:2, s. 237-251
  • Tidskriftsartikel (refereegranskat)abstract
    • Aquatic macrophytes are one of the biological quality elements in the Water Framework Directive (WFD) for which status assessments must be defined. We tested two methods to classify macrophyte species and their response to eutrophication pressure: one based on percentiles of occurrence along a phosphorous gradient and another based on trophic ranking of species using Canonical Correspondence Analyses in the ranking procedure. The methods were tested at Europe-wide, regional and national scale as well as by alkalinity category, using 1,147 lakes from 12 European states. The grouping of species as sensitive, tolerant or indifferent to eutrophication was evaluated for some taxa, such as the sensitive Chara spp. and the large isoetids, by analysing the (non-linear) response curve along a phosphorous gradient. These thresholds revealed in these response curves can be used to set boundaries among different ecological status classes. In total 48 taxa out of 114 taxa were classified identically regardless of dataset or classification method. These taxa can be considered the most consistent and reliable indicators of sensitivity or tolerance to eutrophication at European scale. Although the general response of well known indicator species seems to hold, there are many species that were evaluated differently according to the database selection and classification methods. This hampers a Europe-wide comparison of classified species lists as used for the status assessment within the WFD implementation process.
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19.
  • Penning, W. Ellis, et al. (författare)
  • Using aquatic macrophyte community indices to define the ecological status of European lakes
  • 2008
  • Ingår i: Aquatic Ecology. - : Springer Science and Business Media LLC. - 1386-2588 .- 1573-5125. ; 42:2, s. 253-264
  • Tidskriftsartikel (refereegranskat)abstract
    • Defining the overall ecological status of lakes according to the Water Framework Directive (WFD) is to be partially based on the species composition of the aquatic macrophyte community. We tested three assessment methods to define the ecological status of the macrophyte community in response to a eutrophication pressure as reflected by total phosphorus concentrations in lake water. An absolute species richness, a trophic index (TI) and a lake trophic ranking (LTR) method were tested at Europe-wide, regional and national scales as well as by alkalinity category, using data from 1,147 lakes from 12 European states. Total phosphorus data were used to represent the trophic status of individual samples and were plotted against the calculated TI and LTR values. Additionally, the LTR method was tested in some individual lakes with a relatively long time series of monitoring data. The TI correlated well with total P in the Northern European lake types, whereas the relationship in the Central European lake types was less clear. The relationship between total P and light extinction is often very good in the Northern European lake types compared to the Central European lake types. This can be one of the reasons for a better agreement between the indices and eutrophication pressure in the Northern European lake types. The response of individual lakes to changes in the abiotic environment was sometimes represented incorrectly by the indices used, which is a cause of concern for the use of single indices in status assessments in practice.
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20.
  • Petersen, Steffen E, et al. (författare)
  • Cardiovascular Magnetic Resonance for Patients With COVID-19
  • 2022
  • Ingår i: JACC: Cardiovascular Imaging. - : Elsevier BV. - 1876-7591 .- 1936-878X. ; 15:4, s. 685-699
  • Forskningsöversikt (refereegranskat)abstract
    • COVID-19 is associated with myocardial injury caused by ischemia, inflammation, or myocarditis. Cardiovascular magnetic resonance (CMR) is the noninvasive reference standard for cardiac function, structure, and tissue composition. CMR is a potentially valuable diagnostic tool in patients with COVID-19 presenting with myocardial injury and evidence of cardiac dysfunction. Although COVID-19-related myocarditis is likely infrequent, COVID-19-related cardiovascular histopathology findings have been reported in up to 48% of patients, raising the concern for long-term myocardial injury. Studies to date report CMR abnormalities in 26% to 60% of hospitalized patients who have recovered from COVID-19, including functional impairment, myocardial tissue abnormalities, late gadolinium enhancement, or pericardial abnormalities. In athletes post-COVID-19, CMR has detected myocarditis-like abnormalities. In children, multisystem inflammatory syndrome may occur 2 to 6 weeks after infection; associated myocarditis and coronary artery aneurysms are evaluable by CMR. At this time, our understanding of COVID-19-related cardiovascular involvement is incomplete, and multiple studies are planned to evaluate patients with COVID-19 using CMR. In this review, we summarize existing studies of CMR for patients with COVID-19 and present ongoing research. We also provide recommendations for clinical use of CMR for patients with acute symptoms or who are recovering from COVID-19.
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21.
  • Ruban, V., et al. (författare)
  • Rogue waves - towards a unifying concept?: Discussions and debates
  • 2010
  • Ingår i: The European Physical Journal. Special Topics. - : Springer Science and Business Media LLC. - 1951-6355 .- 1951-6401. ; 185:1, s. 5-15
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper contains the discussion inputs by the contributors of the special issue on the subject of rogue waves.
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23.
  • Zimmermann, U., et al. (författare)
  • Material defects in 4H-silicon carbide diodes
  • 2003
  • Ingår i: Journal of Applied Physics. - : AIP Publishing. - 0021-8979 .- 1089-7550. ; 93:1, s. 611-618
  • Tidskriftsartikel (refereegranskat)abstract
    • Crystallographic defects revealed by synchrotron white beam x-ray topography, electron beam induced current, optical microscopy, and electroluminescence are correlated with the electrical characteristics of medium-voltage epitaxial 4H-silicon carbide diodes. Diodes that include macroscopic crystallographic defects show a significantly reduced reverse breakdown voltage with typical microplasma current fluctuations under reverse bias. Microplasma current paths are revealed by increased electroluminescence both under forward and reverse bias of the diodes and coincide with the locations of screw dislocations in the epitaxial layers of the diodes. The role of crystallographic imperfections on the formation of stacking faults responsible for the degradation of bipolar silicon carbide components is discussed.
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  • Arnold, Cord, et al. (författare)
  • Nonlinear Bessel vortex beams for applications
  • 2015
  • Ingår i: Journal of Physics B: Atomic, Molecular and Optical Physics. - : IOP Publishing. - 0953-4075 .- 1361-6455. ; 48:9
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigate experimentally and numerically the nonlinear propagation of intense BesselGauss vortices in transparent solids. We show that nonlinear Bessel-Gauss vortices preserve all properties of nonlinear Bessel-Gauss beams while their helicity provides an additional control parameter for single-shot precision micro structuring of transparent solids. For sufficiently large cone angle, a stable hollow tube of intense light is formed, generating a plasma channel whose radius and density are increasing with helicity and cone angle, respectively. We assess the potential of intense Bessel vortices for applications based on the generation of hollow plasma channels.
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