| 1. |
- Ederle, Joerg, et al.
(författare)
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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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Ingår i: The Lancet. - 1474-547X. ; 375:9719, s. 985-997
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Hladyz, Sally, et al.
(författare)
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Stream ecosystem functioning in an agricultural landscape : the importance of terrestrial-aquatic linkages
- 2011
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Ingår i: Ecosystems in a human-modified landscape. - San Diego : Academic Press. - 9780123747945 ; 44, s. 211-276
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Bokkapitel (refereegranskat)abstract
- The loss of native riparian vegetation and its replacement with non-native species or grazing land for agriculture is a worldwide phenomenon, but one that is prevalent in Europe, reflecting the heavily-modified nature of the continent's landscape. The consequences of these riparian alterations for freshwater ecosystems remain largely unknown, largely because bioassessment has traditionally focused on the impacts of organic pollution on community structure. We addressed the need for a broader perspective, which encompasses changes at the catchment scale, by comparing ecosystem processes in woodland reference sites with those with altered riparian zones. We assessed a range of riparian modifications, including clearance for pasture and replacement of woodland with a range of low diversity plantations, in 100 streams to obtain a continental-scale perspective of the major types of alterations across Europe. Subsequently, we focused on pasture streams, as an especially prevalent widespread riparian alteration, by characterising their structural (e.g. invertebrate and fish communities) and functional (e.g. litter decomposition, algal production, herbivory) attributes in a country (Ireland) dominated by this type of landscape modification, via field and laboratory experiments. We found that microbes became increasingly important as agents of decomposition relative to macrofauna (invertebrates) in impacted sites in general and in pasture streams in particular. Resource quality of grass litter (e.g., carbon : nutrient ratios, lignin and cellulose content) was a key driver of decomposition rates in pasture streams. These systems also relied more heavily on autochthonous algal production than was the case in woodland streams, which were more detrital based. These findings suggest that these pasture streams might be fundamentally different from their native, ancestral woodland state, with a shift towards greater reliance on autochthonous-based processes. This could have a destabilizing effect on the dynamics of the food web relative to the slower, detrital-based pathways that dominate in woodland streams.
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| 3. |
- Johnson, Toby, et al.
(författare)
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Blood Pressure Loci Identified with a Gene-Centric Array.
- 2011
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 1537-6605 .- 0002-9297. ; 89:6, s. 688-700
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Gallagher, Michael D., et al.
(författare)
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TMEM106B is a genetic modifier of frontotemporal lobar degeneration with C9orf72 hexanucleotide repeat expansions
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 127:3, s. 407-418
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Tidskriftsartikel (refereegranskat)abstract
- Hexanucleotide repeat expansions in chromosome 9 open reading frame 72 (C9orf72) have recently been linked to frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis, and may be the most common genetic cause of both neurodegenerative diseases. Genetic variants at TMEM106B influence risk for the most common neuropathological subtype of FTLD, characterized by inclusions of TAR DNA-binding protein of 43 kDa (FTLD-TDP). Previous reports have shown that TMEM106B is a genetic modifier of FTLD-TDP caused by progranulin (GRN) mutations, with the major (risk) allele of rs1990622 associating with earlier age at onset of disease. Here, we report that rs1990622 genotype affects age at death in a single-site discovery cohort of FTLD patients with C9orf72 expansions (n = 14), with the major allele correlated with later age at death (p = 0.024). We replicate this modifier effect in a 30-site international neuropathological cohort of FTLD-TDP patients with C9orf72 expansions (n = 75), again finding that the major allele associates with later age at death (p = 0.016), as well as later age at onset (p = 0.019). In contrast, TMEM106B genotype does not affect age at onset or death in 241 FTLD-TDP cases negative for GRN mutations or C9orf72 expansions. Thus, TMEM106B is a genetic modifier of FTLD with C9orf72 expansions. Intriguingly, the genotype that confers increased risk for developing FTLD-TDP (major, or T, allele of rs1990622) is associated with later age at onset and death in C9orf72 expansion carriers, providing an example of sign epistasis in human neurodegenerative disease.
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| 5. |
- Hladyz, Sally, et al.
(författare)
-
Stream ecosystem functioning in an agricultural landscape : the importance of terrestrial-aquatic linkages
- 2011
-
Ingår i: Ecosystems in a human-modified landscape. - San Diego : Academic Press. - 9780123747945 ; 44, s. 211-276
-
Bokkapitel (populärvet., debatt m.m.)abstract
- The loss of native riparian vegetation and its replacement with non-native species or grazing land for agriculture is a worldwide phenomenon, but one that is prevalent in Europe, reflecting the heavily-modified nature of the continent's landscape. The consequences of these riparian alterations for freshwater ecosystems remain largely unknown, largely because bioassessment has traditionally focused on the impacts of organic pollution on community structure. We addressed the need for a broader perspective, which encompasses changes at the catchment scale, by comparing ecosystem processes in woodland reference sites with those with altered riparian zones. We assessed a range of riparian modifications, including clearance for pasture and replacement of woodland with a range of low diversity plantations, in 100 streams to obtain a continental-scale perspective of the major types of alterations across Europe. Subsequently, we focused on pasture streams, as an especially prevalent widespread riparian alteration, by characterising their structural (e.g. invertebrate and fish communities) and functional (e.g. litter decomposition, algal production, herbivory) attributes in a country (Ireland) dominated by this type of landscape modification, via field and laboratory experiments. We found that microbes became increasingly important as agents of decomposition relative to macrofauna (invertebrates) in impacted sites in general and in pasture streams in particular. Resource quality of grass litter (e.g., carbon : nutrient ratios, lignin and cellulose content) was a key driver of decomposition rates in pasture streams. These systems also relied more heavily on autochthonous algal production than was the case in woodland streams, which were more detrital based. These findings suggest that these pasture streams might be fundamentally different from their native, ancestral woodland state, with a shift towards greater reliance on autochthonous-based processes. This could have a destabilizing effect on the dynamics of the food web relative to the slower, detrital-based pathways that dominate in woodland streams.
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| 6. |
- Woodward, Guy, et al.
(författare)
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Continental-scale effects of nutrient pollution on stream ecosystem functioning
- 2012
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Ingår i: Science. - : American Association for the Advancement of Science. - 0036-8075 .- 1095-9203. ; 336:6087, s. 1438-1440
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Tidskriftsartikel (refereegranskat)abstract
- Excessive nutrient loading is a major threat to aquatic ecosystems worldwide that leads to profound changes in aquatic biodiversity and biogeochemical processes. Systematic quantitative assessment of functional ecosystem measures for river networks is, however, lacking, especially at continental scales. Here, we narrow this gap by means of a pan-European field experiment on a fundamental ecosystem process—leaf-litter breakdown—in 100 streams across a greater than 1000-fold nutrient gradient. Dramatically slowed breakdown at both extremes of the gradient indicated strong nutrient limitation in unaffected systems, potential for strong stimulation in moderately altered systems, and inhibition in highly polluted streams. This large-scale response pattern emphasizes the need to complement established structural approaches (such as water chemistry, hydrogeomorphology, and biological diversity metrics) with functional measures (such as litter-breakdown rate, whole-system metabolism, and nutrient spiraling) for assessing ecosystem health.
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