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- Franceschini, N., et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
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Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
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- Franceschini, N, et al.
(author)
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GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 5141-
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Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
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- Perner, Anders, et al.
(author)
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Hydroxyethyl Starch 130/0.4 versus Ringer's Acetate in Severe Sepsis
- 2012
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In: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 367:2, s. 124-134
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Journal article (peer-reviewed)abstract
- BACKGROUND Hydroxyethyl starch (HES) 130/0.4 is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. METHODS In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.4 or Ringer's acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modified intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.4 had died, as compared with 172 of 400 patients (43%) assigned to Ringer's acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P=0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.4 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer's acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P=0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P=0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.4 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.
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- Hübers, M, et al.
(author)
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A reappraisal of Mississippian (Tournaisian and Visean) adpression floras from central and northwestern Europe
- 2014
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In: Zitteliana, Series A. - München. - 1612-412X. ; 54, s. 39-52
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Journal article (peer-reviewed)abstract
- Mississippian plant fossils are generally rare, and in central and northwestern Europe especially Tournaisian to middle Visean fossil floras are restricted to isolated occurrences. While sphenophytes and lycophytes generally are represented by only a few widespread and long-ranging taxa such as Archaeocalamites radiatus, Sphenophyllum tenerrimum and several species of Lepidodendropsis and Lepidodendron, Visean floras in particular show a remarkably high diversity of fern-like foliage, including filiform types (Rhodea, Diplotmema), forms with bipartite fronds (Sphenopteridium, Diplopteridium, Spathulopteris, Archaeopteridium), others with monopodial, pinnate fronds (Anisopteris, Fryopsis) and still others characterized by several-times pinnate fronds (e.g., Adiantites, Triphyllopteris, Sphenopteris, Neuropteris). Most of these leaf types have been interpreted as belonging to early seed ferns, whereas true ferns seem to have been rare or lacking in impression/compression floras. In the upper Visean, two types of plant assemblages can be distinguished, i.e., the northern Kohlenkalk-type and the south-eastern Kulm-type assemblage. Although several compression/impression taxa have been revised in recent years to provide a more uniform classification, additional parameters such as different modes of preservation and imprecise information on stratigraphic age hamper detailed interregional comparisons of Mississippian floras.
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