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Sökning: WFRF:(Dick Florian)

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  • Adams, Hieab H. H., et al. (författare)
  • Novel genetic loci underlying human intracranial volume identified through genome-wide association
  • 2016
  • Ingår i: Nature Neuroscience. - 1097-6256 .- 1546-1726. ; 19:12, s. 1569-1582
  • Tidskriftsartikel (refereegranskat)abstract
    • Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.
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  • Behrendt, Christian-Alexander, et al. (författare)
  • Editor's Choice - Recommendations for Registry Data Collection for Revascularisations of Acute Limb Ischaemia : A Delphi Consensus from the International Consortium of Vascular Registries
  • 2019
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 57:6, s. 816-821
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To develop a minimum core data set for evaluation of acute limb ischaemia (ALI) revascularisation treatment and outcomes that would enable collaboration among international registries. Methods: A modified Delphi approach was used to achieve consensus among international multidisciplinary vascular specialists and registry members of the International Consortium of Vascular Registries (ICVR). Variables identified in the literature or suggested by the expert panel, and variables, including definitions, currently used in 15 countries in the ICVR, were assessed to define both a minimum core and an optimum data set to register ALI treatment. Clinical relevance and practicability were both assessed, and consensus was defined as >= 80% agreement among participants. Results: Of 40 invited experts, 37 completed a preliminary survey and 31 completed the two subsequent Delphi rounds via internet exchange and face to face discussions. In total, 117 different items were generated from the various registry data forms, an extensive review of the literature, and additional suggestions from the experts, for potential inclusion in the data set. Ultimately, 35 items were recommended for inclusion in the minimum core data set, including 23 core items important for all registries, and an additional 12 more specific items for registries capable of capturing more detail. These 35 items supplement previous data elements recommended for registering chronic peripheral arterial occlusive disease treatment. Conclusion: A modified Delphi study allowed 37 international vascular registry experts to achieve a consensus recommendation for a minimum core and an optimum data set for registries covering patients who undergo ALI revascularisation. Continued global harmonisation of registry infrastructure and definition of items allows international comparisons and global quality improvement. Furthermore, it can help to define and monitor standards of care and enable international research collaboration.
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  • Conte, Michael S., et al. (författare)
  • Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia
  • 2019
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : Saunders Elsevier. - 1078-5884 .- 1532-2165. ; 69:6S, s. 3S-125S.e40
  • Tidskriftsartikel (refereegranskat)abstract
    • Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum. CLTI is a clinical syndrome defined by the presence of peripheral artery disease (PAD) in combination with rest pain, gangrene, or a lower limb ulceration >2 weeks duration. Venous, traumatic, embolic, and nonatherosclerotic etiologies are excluded. All patients with suspected CLTI should be referred urgently to a vascular specialist. Accurately staging the severity of limb threat is fundamental, and the Society for Vascular Surgery Threatened Limb Classification system, based on grading of Wounds, Ischemia, and foot Infection (WIfI) is endorsed. Objective hemodynamic testing, including toe pressures as the preferred measure, is required to assess CLTI. Evidence-based revascularization (EBR) hinges on three independent axes: Patient risk, Limb severity, and ANatomic complexity (PLAN). Average-risk and high-risk patients are defined by estimated procedural and 2-year all-cause mortality. The GVG proposes a new Global Anatomic Staging System (GLASS), which involves defining a preferred target artery path (TAP) and then estimating limb-based patency (LBP), resulting in three stages of complexity for intervention. The optimal revascularization strategy is also influenced by the availability of autogenous vein for open bypass surgery. Recommendations for EBR are based on best available data, pending level 1 evidence from ongoing trials. Vein bypass may be preferred for average-risk patients with advanced limb threat and high complexity disease, while those with less complex anatomy, intermediate severity limb threat, or high patient risk may be favored for endovascular intervention. All patients with CLTI should be afforded best medical therapy including the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control agents, as well as counseling on smoking cessation, diet, exercise, and preventive foot care. Following EBR, long-term limb surveillance is advised. The effectiveness of nonrevascularization therapies (eg, spinal stimulation, pneumatic compression, prostanoids, and hyperbaric oxygen) has not been established. Regenerative medicine approaches (eg, cell, gene therapies) for CLTI should be restricted to rigorously conducted randomizsed clinical trials. The GVG promotes standardization of study designs and end points for clinical trials in CLTI. The importance of multidisciplinary teams and centers of excellence for amputation prevention is stressed as a key health system initiative.
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  • Dick, Florian, et al. (författare)
  • The EJVES is Taking the Next Step Anew
  • 2020
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : W B SAUNDERS CO LTD. - 1078-5884 .- 1532-2165. ; 59:1, s. 1-2
  • Tidskriftsartikel (övrigt vetenskapligt)
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  • Gmeiner, Florian, et al. (författare)
  • GABA(B) receptors play an essential role in maintaining sleep during the second half of the night in Drosophila melanogaster
  • 2013
  • Ingår i: Journal of Experimental Biology. - 0022-0949 .- 1477-9145. ; 216:20, s. 3837-3843
  • Tidskriftsartikel (refereegranskat)abstract
    • GABAergic signalling is important for normal sleep in humans and flies. Here we advance the current understanding of GABAergic modulation of daily sleep patterns by focusing on the role of slow metabotropic GABA(B) receptors in the fruit fly Drosophila melanogaster. We asked whether GABA(B)-R2 receptors are regulatory elements in sleep regulation in addition to the already identified fast ionotropic Rdl GABA(A) receptors. By immunocytochemical and reporter-based techniques we show that the pigment dispersing factor (PDF)-positive ventrolateral clock neurons (LNv) express GABA(B)-R2 receptors. Downregulation of GABA(B)-R2 receptors in the large PDF neurons (l-LNv) by RNAi reduced sleep maintenance in the second half of the night, whereas sleep latency at the beginning of the night that was previously shown to depend on ionotropic Rdl GABA(A) receptors remained unaltered. Our results confirm the role of the l-LNv neurons as an important part of the sleep circuit in D. melanogaster and also identify the GABA(B)-R2 receptors as the thus far missing component in GABA-signalling that is essential for sleep maintenance. Despite the significant effects on sleep, we did not observe any changes in circadian behaviour in flies with downregulated GABA(B)-R2 receptors, indicating that the regulation of sleep maintenance via l-LNv neurons is independent of their function in the circadian clock circuit.
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  • Grasby, Katrina L., et al. (författare)
  • The genetic architecture of the human cerebral cortex
  • 2020
  • Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 367:6484, s. 1340-
  • Tidskriftsartikel (refereegranskat)abstract
    • The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder.
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