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- 2019
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Journal article (peer-reviewed)
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- Ederle, Joerg, et al.
(author)
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Carotid artery stenting compared with endarterectomy in patients with symptomatic carotid stenosis (International Carotid Stenting Study): an interim analysis of a randomised controlled trial
- 2010
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In: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Journal article (peer-reviewed)abstract
- Background Stents are an alternative treatment to carotid endarterectomy for symptomatic carotid stenosis, but previous trials have not established equivalent safety and efficacy. We compared the safety of carotid artery stenting with that of carotid endarterectomy. Methods The International Carotid Stenting Study (ICSS) is a multicentre, international, randomised controlled trial with blinded adjudication of outcomes. Patients with recently symptomatic carotid artery stenosis were randomly assigned in a 1:1 ratio to receive carotid artery stenting or carotid endarterectomy. Randomisation was by telephone call or fax to a central computerised service and was stratified by centre with minimisation for sex, age, contralateral occlusion, and side of the randomised artery. Patients and investigators were not masked to treatment assignment. Patients were followed up by independent clinicians not directly involved in delivering the randomised treatment. The primary outcome measure of the trial is the 3-year rate of fatal or disabling stroke in any territory, which has not been analysed yet. The main outcome measure for the interim safety analysis was the 120-day rate of stroke, death, or procedural myocardial infarction. Analysis was by intention to treat (ITT). This study is registered, number ISRCTN25337470. Findings The trial enrolled 1713 patients (stenting group, n=855; endarterectomy group, n=858). Two patients in the stenting group and one in the endarterectomy group withdrew immediately after randomisation, and were not included in the ITT analysis. Between randomisation and 120 days, there were 34 (Kaplan-Meier estimate 4.0%) events of disabling stroke or death in the stenting group compared with 27 (3.2%) events in the endarterectomy group (hazard ratio [HR] 1.28, 95% CI 0.77-2.11). The incidence of stroke, death, or procedural myocardial infarction was 8.5% in the stenting group compared with 5.2% in the endarterectomy group (72 vs 44 events; HR 1.69, 1.16-2.45, p=0.006), Risks of any stroke (65 vs 35 events; HR 1.92, 1.27-2.89) and all-cause death (19 vs seven events; HR 2.76, 1.16-6.56) were higher in the stenting group than in the endarterectomy group. Three procedural myocardial infarctions were recorded in the stenting group, all of which were fatal, compared with four, all non-fatal, in the endarterectomy group. There was one event of cranial nerve palsy in the stenting group compared with 45 in the endarterectomy group. There were also fewer haematomas of any severity in the stenting group than in the endarterectomy group (31 vs 50 events; p=0.0197). Interpretation Completion of long-term follow-up is needed to establish the efficacy of carotid artery stenting compared with endarterectomy. In the meantime, carotid endarterectomy should remain the treatment of choice for patients suitable for surgery.
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| 5. |
- Bui, T. P. N., et al.
(author)
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Conversion of dietary inositol into propionate and acetate by commensal Anaerostipes associates with host health
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Here, the authors report an anaerobic metabolic pathway from the dominant gut butyrogen Anaerostipes, showing several strains of this genus to be capable of producing propionate from dietary myo-inositol that associates with reduced fasting-glucose levels in mice. We describe the anaerobic conversion of inositol stereoisomers to propionate and acetate by the abundant intestinal genus Anaerostipes. A inositol pathway was elucidated by nuclear magnetic resonance using [C-13]-inositols, mass spectrometry and proteogenomic analyses in A. rhamnosivorans, identifying 3-oxoacid CoA transferase as a key enzyme involved in both 3-oxopropionyl-CoA and propionate formation. This pathway also allowed conversion of phytate-derived inositol into propionate as shown with [C-13]-phytate in fecal samples amended with A. rhamnosivorans. Metabolic and (meta)genomic analyses explained the adaptation of Anaerostipes spp. to inositol-containing substrates and identified a propionate-production gene cluster to be inversely associated with metabolic biomarkers in (pre)diabetes cohorts. Co-administration of myo-inositol with live A. rhamnosivorans in western-diet fed mice reduced fasting-glucose levels comparing to heat-killed A. rhamnosivorans after 6-weeks treatment. Altogether, these data suggest a potential beneficial role for intestinal Anaerostipes spp. in promoting host health.
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| 7. |
- Johnson, Toby, et al.
(author)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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In: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Journal article (peer-reviewed)abstract
- Raised blood pressure (BP) is a major risk factor for cardiovascular disease. Previous studies have identified 47 distinct genetic variants robustly associated with BP, but collectively these explain only a few percent of the heritability for BP phenotypes. To find additional BP loci, we used a bespoke gene-centric array to genotype an independent discovery sample of 25,118 individuals that combined hypertensive case-control and general population samples. We followed up four SNPs associated with BP at our p < 8.56× 10(-7) study-specific significance threshold and six suggestively associated SNPs in a further 59,349 individuals. We identified and replicated a SNP at LSP1/TNNT3, a SNP at MTHFR-NPPB independent (r(2) = 0.33) of previous reports, and replicated SNPs at AGT and ATP2B1 reported previously. An analysis of combined discovery and follow-up data identified SNPs significantly associated with BP at p < 8.56× 10(-7) at four further loci (NPR3, HFE, NOS3, and SOX6). The high number of discoveries made with modest genotyping effort can be attributed to using a large-scale yet targeted genotyping array and to the development of a weighting scheme that maximized power when meta-analyzing results from samples ascertained with extreme phenotypes, in combination with results from nonascertained or population samples. Chromatin immunoprecipitation and transcript expression data highlight potential gene regulatory mechanisms at the MTHFR and NOS3 loci. These results provide candidates for further study to help dissect mechanisms affecting BP and highlight the utility of studying SNPs and samples that are independent of those studied previously even when the sample size is smaller than that in previous studies.
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| 8. |
- Pavon-Jordan, Diego, et al.
(author)
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Climate-driven changes in winter abundance of a migratory waterbird in relation to EU protected areas
- 2015
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In: Diversity and Distributions. - : Wiley. - 1366-9516. ; 21:5, s. 571-582
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Journal article (peer-reviewed)abstract
- AimSpecies are responding to climate change by changing their distributions, creating debate about the effectiveness of existing networks of protected areas. As a contribution to this debate, we assess whether regional winter abundances and distribution of the Smew Mergellus albellus, a migratory waterbird species listed on Annex I (EU Birds Directive) that overwinters exclusively in European wetlands, changed during 1990-2011, the role of global warming in driving distributional changes and the effectiveness of the network of Special Protection Areas (SPAs, EU Birds Directive) in the context of climate change. LocationEurope. MethodsWe used site-specific counts (6,883 sites) from 16 countries covering the entire flyway to estimate annual abundance indices and trends at country, region (north-eastern, central and south-western) and flyway scales, inside and outside SPAs. We fitted autoregressive models to assess the effect of winter temperature on the annual abundance indices whilst accounting for autocorrelation. ResultsThe Smew wintering distribution shifted north-eastwards in Europe in accordance with the predictions of global warming, with increasing numbers in the north-eastern region and declines in the central region. Trends in wintering numbers were more positive in SPAs on the north-eastern and south-western part of the flyway. However, a large proportion of the wintering population remains unprotected in north-eastern areas outside of the existing SPA network. Main conclusionsSPAs accommodated climate-driven abundance changes in the north-eastern region of the wintering distribution by supporting increasing numbers of Smew in traditional and newly colonized areas. However, we highlight gaps in the current network, suggesting that urgent policy responses are needed. Given rapid changes in species distributions, we urge regular national and international assessments of the adequacy of the EU Natura 2000 network to ensure coherence in site-safeguard networks for this and other species.
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- Fox, Anthony D., et al.
(author)
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Recent changes in the abundance of Common Pochard Aythya ferina breeding in Europe
- 2016
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In: Wildfowl. - 0954-6324. ; 66, s. 22-40
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Research review (peer-reviewed)abstract
- National accounts suggest that the Common Pochard Aythya ferina was an uncommon breeding bird throughout western Europe before 1850. Extensions to the breeding range in the late 19th century were potentially aided by the rapid development of managed fish-ponds in eastern Europe, which provided suitable novel habitat at that time. Expansion into western Europe followed in subsequent decades. Wetland and waterbody eutrophication throughout Europe, which likely provided food and cover for the birds, may have accelerated the rapid expansion from the 1950s until the early 1980s. Widespread declines in the last 30 years, especially in eastern Europe, where breeding numbers are highest, are possibly linked to intensification and/or abandonment of freshwater fish farming and changes in water quality. Studies show that Pochard gain fitness benefits from nesting in Black-headed Gull Chroicocephalus ridibundus colonies and hence has been affected by major losses of European gull colonies in the last 30 years. The spread of alien fish species such as the Carp Cyprinus carpio, which compete with Pochard for food resources, is a problem in the Mediterranean region. Changing predation pressures (in some cases linked to invasive alien mammals) are also implicated in some areas. Relatively modest numbers breeding in the UK, France and the Netherlands have remained stable or increased over the same recent span of years, confirming that different factors currently affect Pochard breeding abundance throughout its range. We urgently need better information relating to key factors affecting Pochard breeding success and abundance, which is currently showing an unfavourable conservation status throughout much of Europe.
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| 10. |
- Fox, Anthony D., et al.
(author)
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Seeking explanations for recent changes in abundance of wintering Eurasian Wigeon (Anas penelope) in northwest Europe
- 2016
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In: Ornis Fennica. - 0030-5685. ; 93:1, s. 12-25
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Journal article (peer-reviewed)abstract
- We analysed annual changes in abundance of Eurasian Wigeon (Anas penelope) derived from mid-winter International Waterbird Census data throughout its northwest European flyway since 1988 using log-linear Poisson regression modelling. Increases in abundance in the north and east of the wintering range (Norway, Sweden, Denmark, Germany, Switzerland), stable numbers in the central range (Belgium, Netherlands, UK and France) and declining abundance in the west and south of the wintering range (Spain and Ireland) suggest a shift in wintering distribution consistent with milder winters throughout the range. However, because over 75% of the population of over 1 million individuals winters in Belgium, the Netherlands, UK and France, there was no evidence for a major movement in the centre of gravity of the wintering distribution. Between-winter changes in overall flyway abundance were highly significantly positively correlated (P = 0.003) with reproductive success measured by age ratios in Danish hunter wing surveys and less strongly and inversely correlated (P = 0.05) with mean January temperatures in the centre of the wintering range, suggesting that winter severity may also contribute to influence survival. However, adding winter severity to a model predicting population size based on annual reproductive success alone did not contribute to more effectively modelling the observed changes in population size. Patterns in annual reproductive success seem therefore to largely explain the recent dynamics in population size of northwest European Wigeon. Summer NAO significantly and positively explained 27% of variance in annual breeding success. Other local factors such as eutrophication of breeding sites and changes in predation pressure undoubtedly contribute to changes in the annual production of young and differences in hunting pressure as well as winter severity affect annual survival rates. However, it seems likely that the observed flyway population trend since 1988 has been mostly influenced by climate effects on the breeding grounds affecting reproductive success and marginally on the winter quarters affecting survival. We urge improved demographic monitoring of the population to better assess annual survival and reproductive success. We also recommend development of an adaptive management framework to remove uncertainties in our knowledge of Wigeon population dynamics as information is forthcoming to better inform management, especially to attempt to harmonise the harvest with annual changes in demography to ensure sustainable exploitation of this important quarry species now and in the future.
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