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- Pulit, SL, et al.
(author)
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Loci associated with ischaemic stroke and its subtypes (SiGN): a genome-wide association study.
- 2016
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In: The Lancet. Neurology. - 1474-4465. ; 15:2, s. 174-84
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Journal article (peer-reviewed)abstract
- The discovery of disease-associated loci through genome-wide association studies (GWAS) is the leading genetic approach to the identification of novel biological pathways underlying diseases in humans. Until recently, GWAS in ischaemic stroke have been limited by small sample sizes and have yielded few loci associated with ischaemic stroke. We did a large-scale GWAS to identify additional susceptibility genes for stroke and its subtypes.To identify genetic loci associated with ischaemic stroke, we did a two-stage GWAS. In the first stage, we included 16851 cases with state-of-the-art phenotyping data and 32473 stroke-free controls. Cases were aged 16 to 104 years, recruited between 1989 and 2012, and subtypes of ischaemic stroke were recorded by centrally trained and certified investigators who used the web-based protocol, Causative Classification of Stroke (CCS). We constructed case-control strata by identifying samples that were genotyped on nearly identical arrays and were of similar genetic ancestral background. We cleaned and imputed data by use of dense imputation reference panels generated from whole-genome sequence data. We did genome-wide testing to identify stroke-associated loci within each stratum for each available phenotype, and we combined summary-level results using inverse variance-weighted fixed-effects meta-analysis. In the second stage, we did in-silico lookups of 1372 single nucleotide polymorphisms identified from the first stage GWAS in 20941 cases and 364736 unique stroke-free controls. The ischaemic stroke subtypes of these cases had previously been established with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification system, in accordance with local standards. Results from the two stages were then jointly analysed in a final meta-analysis.We identified a novel locus (G allele at rs12122341) at 1p13.2 near TSPAN2 that was associated with large artery atherosclerosis-related stroke (first stage odds ratio [OR] 1·21, 95% CI 1·13-1·30, p=4·50×10(-8); joint OR 1·19, 1·12-1·26, p=1·30×10(-9)). Our results also supported robust associations with ischaemic stroke for four other loci that have been reported in previous studies, including PITX2 (first stage OR 1·39, 1·29-1·49, p=3·26×10(-19); joint OR 1·37, 1·30-1·45, p=2·79×10(-32)) and ZFHX3 (first stage OR 1·19, 1·11-1·27, p=2·93×10(-7); joint OR 1·17, 1·11-1·23, p=2·29×10(-10)) for cardioembolic stroke, and HDAC9 (first stage OR 1·29, 1·18-1·42, p=3·50×10(-8); joint OR 1·24, 1·15-1·33, p=4·52×10(-9)) for large artery atherosclerosis stroke. The 12q24 locus near ALDH2, which has previously been associated with all ischaemic stroke but not with any specific subtype, exceeded genome-wide significance in the meta-analysis of small artery stroke (first stage OR 1·20, 1·12-1·28, p=6·82×10(-8); joint OR 1·17, 1·11-1·23, p=2·92×10(-9)). Other loci associated with stroke in previous studies, including NINJ2, were not confirmed.Our results suggest that all ischaemic stroke-related loci previously implicated by GWAS are subtype specific. We identified a novel gene associated with large artery atherosclerosis stroke susceptibility. Follow-up studies will be necessary to establish whether the locus near TSPAN2 can be a target for a novel therapeutic approach to stroke prevention. In view of the subtype-specificity of the associations detected, the rich phenotyping data available in the Stroke Genetics Network (SiGN) are likely to be crucial for further genetic discoveries related to ischaemic stroke.US National Institute of Neurological Disorders and Stroke, National Institutes of Health.
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| 3. |
- Hansson, Lena, et al.
(author)
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A case study of the role of mathematics in physics textbooks and in associated lessons
- 2019
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In: Mathematics in physics education. - Dordrecht : Springer. ; , s. 293-316
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Book chapter (pop. science, debate, etc.)abstract
- This chapter describes a case study of the role of mathematics in physics textbooks and in associated teacher led lessons. The theoretical framework (Hansson et al. 2015) used in the analysis focuses on relations communicated between three entities: Theoretical models, Mathematics, and Reality. Previously the framework has been used for analysing classroom situations. In this chapter, the framework is further developed and refined, and for the first time used to analyse physics textbooks. The case study described here is a synchronised analysis of a physics textbook and associated classroom communication during teacher led lessons, and contributes with an in-depth description of relations made between Theoretical models, Mathematicsand Reality. With the starting point in this case we discuss future uses of the analysis framework. We also raise questions for further research concerning how physics textbooks support and not support a meaningful physics teaching with respect to the role of mathematics and how relations between Theoretical models, Mathematics, and Reality are communicated.
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- Redfors, B. Björn, et al.
(author)
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Incidence and prognosis of the takotsubo syndrome compared to acute myocardial infarction
- 2019
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In: European Journal of Heart Failure. - : John Wiley & Sons. - 1388-9842 .- 1879-0844. ; 21, s. 267-267
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Journal article (other academic/artistic)abstract
- Background: Takotsubo syndrome (TS) is a potentially life-threatening acute cardiac syndrome with a clinical presentation very similar to myocardial infarction (MI) and for which the natural history, management and outcome remain incompletely understood.Purpose: The aims of this study were to assess the relative short- and long-term mortality risk of TS , ST-elevation MI (STEMI) and non STEMI (NSTEMI) and to identify predictors of in-hospital complications and poor prognosis in patients with TS.Methods: Using the nationwide Swedish Angiography and Angioplasty Registry (SCAAR) we identified almost all (n=117,720) patients who underwent coronary angiography due to TS (N=2,898 [2.5%]), STEMI (N=48,493 [41.2%]) or NSTEMI (N=66,329 [56.3%]) in Sweden between January 2009 and February 2018.Results: Patients with TS were more often women as compared with patients with STEMI or NSTEMI. TS was associated with unadjusted and adjusted 30-day mortality risks lower than STEMI (adjusted hazard ratio [adjHR] 0.60, 95% confidence interval [CI]0.48-0.76, p<0.001), but higher than NSTEMI (adjHR 2.70, 95% CI 2.14-3.41, p<0.001). Compared to STEMI, TS was associated with similar risk of acute heart failure (adjHR 1.26, 95% CI 0.91–1.76, p=0.16) but lower risk of cardio-genic shock (adjHR 0.55, 95% CI 0.34–0.89, p=0.02). The relative 30-day mortality risk for TS versus STEMI and NSTEMI was higher for smokers than non-smokers (adjusted pinteractionSTEMI=0.01 and pinteractionNSTEMI=0.01).Conclusion: Thirty-day mortality in TS was higher than in NSTEMI but lower than STEMI, despite a similar risk of acute heart failure in TS and STEMI. Among patients with TS, smoking was an independent predictor of mortality
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- Redfors, Ylva Dahlin, et al.
(author)
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Psychometric properties of the Swedish version of the Glasgow Benefit Inventory in otosclerosis subjects
- 2019
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In: Laryngoscope Investigative Otolaryngology. - : Wiley. - 2378-8038. ; 4:6, s. 673-677
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Journal article (peer-reviewed)abstract
- Objective To evaluate the psychometric properties of the Swedish version of the Glasgow Benefit Inventory (GBI). Methods A prospective multicenter cohort study was conducted. A total of 123 otosclerosis subjects were included in the study. The subjects were divided in three groups based on the following interventions: (a) stapedotomy without any prior hearing-aid rehabilitation (n = 60); (b) hearing-aid rehabilitation without any prior stapedotomy (n = 33); and (c) stapedotomy with prior hearing-aid rehabilitation (n = 30). Pre- and post-operative pure tone audiometry were measured. The Swedish version of the GBI was completed by the subjects 6 months after the intervention. Test-retest reliability and internal consistency, factor analysis, construct validity, and criterion validity, was assessed. Results The Swedish version of the GBI was well accepted by the subjects. It showed good psychometric properties with an overall high reliability. Factor analysis resulted in a 5-factor solution explaining 66.6% of the variance where factors 1 and 2 represented the general health domain. Conclusions Overall, the Swedish version of the GBI showed good psychometric properties. Based on the factor analyses, there is the possibility that the general health domain should be divided in two separate domains: general health and psychosocial health. Level of Evidence 2c.
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