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Sökning: WFRF:(Soderman E)

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  • Ederle, Joerg, et al. (författare)
  • 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
  • Ingår i: The Lancet. - Elsevier. - 1474-547X. ; 375:9719, s. 985-997
  • 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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  • Huckins, Laura M., et al. (författare)
  • Gene expression imputation across multiple brain regions provides insights into schizophrenia risk
  • 2019
  • Ingår i: Nature genetics. - 1546-1718. ; 51:4, s. 659-
  • Tidskriftsartikel (refereegranskat)abstract
    • Transcriptomic imputation approaches combine eQTL reference panels with large-scale genotype data in order to test associations between disease and gene expression. These genic associations could elucidate signals in complex genome-wide association study (GWAS) loci and may disentangle the role of different tissues in disease development. We used the largest eQTL reference panel for the dorso-lateral prefrontal cortex (DLPFC) to create a set of gene expression predictors and demonstrate their utility. We applied DLPFC and 12 GTEx-brain predictors to 40,299 schizophrenia cases and 65,264 matched controls for a large transcriptomic imputation study of schizophrenia. We identified 413 genic associations across 13 brain regions. Stepwise conditioning identified 67 non-MHC genes, of which 14 did not fall within previous GWAS loci. We identified 36 significantly enriched pathways, including hexosaminidase-A deficiency, and multiple porphyric disorder pathways. We investigated developmental expression patterns among the 67 non-MHC genes and identified specific groups of pre- and postnatal expression.
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  • Marshall, Christian R., et al. (författare)
  • Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects
  • 2017
  • Ingår i: Nature Genetics. - 1061-4036. ; 49:1, s. 27-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 x 10(-15)), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 x 10(-6)). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 x 10(-11)) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 x 10(-5)). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.
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  • Ripke, Stephan, et al. (författare)
  • Biological insights from 108 schizophrenia-associated genetic loci
  • 2014
  • Ingår i: Nature. - 0028-0836. ; 511:7510, s. 421-427
  • Tidskriftsartikel (refereegranskat)abstract
    • Schizophrenia is a highly heritable disorder. Genetic risk is conferred by a large number of alleles, including common alleles of small effect that might be detected by genome-wide association studies. Here we report a multi-stage schizophrenia genome-wide association study of up to 36,989 cases and 113,075 controls. We identify 128 independent associations spanning 108 conservatively defined loci that meet genome-wide significance, 83 of which have not been previously reported. Associations were enriched among genes expressed in brain, providing biological plausibility for the findings. Many findings have the potential to provide entirely new insights into aetiology, but associations at DRD2 and several genes involved in glutamatergic neurotransmission highlight molecules of known and potential therapeutic relevance to schizophrenia, and are consistent with leading pathophysiological hypotheses. Independent of genes expressed in brain, associations were enriched among genes expressed in tissues that have important roles in immunity, providing support for the speculated link between the immune system and schizophrenia.
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  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
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  • Finnbogason, T., et al. (författare)
  • Anterior dynamic ultrasound and Graf's examination in neonatal hip instability
  • 2008
  • Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - 1600-0455. ; 49:2, s. 204-11
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Discrepancy between neonatal hip morphology and stability has been reported in the literature. Comparative ultrasound studies on this issue are limited. PURPOSE: To compare neonatal hip instability, as assessed by dynamic ultrasound and clinical examination, with acetabular morphology, as assessed by Graf's method. MATERIAL AND METHODS: 536 newborn infants with clinical signs of hip instability, ambiguous findings at clinical hip examination, or positive risk factors for DDH were investigated with two ultrasound methods, the Graf method and anterior dynamic ultrasound, at an average age of 12 days. The hips were allocated to three groups according to the Graf result: A, normal (type Ia and b); B, borderline or immature (type IIa); and C, pathologic (type IIc and worse). Graf examination was compared with two diagnostic tests for instability, namely clinical examination by senior pediatric orthopedists and anterior dynamic ultrasound. RESULTS: According to Graf's method, 77% of the hips were normal, 20% borderline/immature, and 3% pathologic. On clinical hip examination, 82% were stable, 14% unstable, and 4% dislocatable. The dynamic ultrasound outcome was 88% stable hips, 10% unstable, and 2% dislocatable. Of the hips considered unstable or dislocatable on dynamic ultrasound, 21% had normal (type I) and 66% immature acetabular morphology according to the Graf method. Of the hips that were stable on dynamic ultrasound, only one (0.1%) was dysplastic according to the Graf method. Graf's examination showed the smallest number of normal hips, but also the fewest pathologic hips, with many indeterminate results that needed follow-up. CONCLUSION: Acetabular morphology correlated better to stability as assessed by dynamic ultrasound than to the clinical examination results, with fair to moderate agreement. Graf's examination resulted in a large number of indeterminate results that needed follow-up, but when used as the sole criterion for deciding treatment did not lead to a higher treatment rate than when the decision was based on clinical hip examination.
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  • Finnbogason, T., et al. (författare)
  • Neonatal hip instability : a prospective comparison of clinical examination and anterior dynamic ultrasound
  • 2008
  • Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - 1600-0455. ; 49:2, s. 212-9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Ultrasound is increasingly being used to complement the clinical examination in assessing neonatal hip instability. The clinical examination, although highly sensitive in detecting hip instability, can lead to considerable overtreatment. PURPOSE: To compare anterior dynamic ultrasound and clinical examination in the assessment of neonatal hip instability and regarding treatment rates. MATERIAL AND METHODS: 536 newborn infants (out of a population of 18,031) were selected, on the basis of a combination of risk factors, clinical signs of hip instability or ambiguous clinical findings, to undergo an anterior dynamic ultrasound examination of the hip, by a method developed by our group. This examination, performed by one out of seven experienced examiners, was compared with the standard clinical hip examination conducted by one of four pediatric orthopedic surgeons. The clinical examination was carried out both prior to and within a few hours after the ultrasound examination. RESULTS: The clinical examination diagnosed 81.7% of the hips as normal, 14.5% as unstable, and 3.8% as dislocatable or dislocated. With the dynamic ultrasound method, the corresponding figures were 87.8%, 10.4%, and 1.8%, respectively. Use of the criteria of the clinical examination resulted in treatment of 147 infants. Using the dynamic ultrasound examination as a criterion meant that 87 infants would receive treatment. The calculated treatment rate was 0.85% when based on the clinical stress test and 0.49% when based on the dynamic ultrasound. CONCLUSION: The dynamic ultrasound results reduced the treatment rate by over 40% when used as a basis for the decision regarding treatment.
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