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| 2. |
- Mishra, A., et al.
(författare)
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Stroke genetics informs drug discovery and risk prediction across ancestries
- 2022
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 611, s. 115-123
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Tidskriftsartikel (refereegranskat)abstract
- Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry(1,2). Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30% non-European) and 1,013,843 control individuals, 87% of the primary stroke risk loci and 60% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis(3), and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach(4), we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry(5). Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.
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| 3. |
- Jaworek, T., et al.
(författare)
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Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke
- 2022
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 99:16
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
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| 6. |
- Qvarford, M, et al.
(författare)
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Photoemission and x-ray absorption study of superconducting and semiconducting Ba1-xKxBiO3 single crystals
- 1996
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 54:9, s. 6700-6707
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Tidskriftsartikel (refereegranskat)abstract
- Semiconducting Ba0.9K0.1BiO3 and superconducting Ba0.6K0.4BiO3 single crystals cleaved in situ have been studied by core level and valence band photoelectron spectroscopy and O K edge x-ray absorption spectroscopy. It was found that the general shape of the valence band spectrum agrees with the shape predicted by band structure calculations, but the intensity near the Fermi level, was lower in the experimental spectrum as compared to the calculated. The O K edge spectra showed that the metallic phase is not related to the presence of doping inducted O 2p holes. This property of Ba1-xKxBiO3 shows that the semiconductor-metal transition of this system is of a different nature than that of the hole doped cuprate high-T-c superconductors. The core level photoemission spectra of the cations showed a small asymmetry for Ba0.9K0.1BiO3. Corresponding spectra for Ba0.6K0.4BiO3 showed a larger asymmetry resulting in a resolved high binding energy shoulder in the Bi 4f spectrum. The origin of this feature is discussed.
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| 9. |
- Bonkhoff, A. K., et al.
(författare)
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Sex-specific lesion pattern of functional outcomes after stroke
- 2022
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Relying on neuroimaging and clinical data of 822 acute stroke patients, Bonkhoff et al. report substantially more detrimental effects of lesions in left-hemispheric posterior circulation regions on functional outcomes in women compared to men. These findings may motivate a sex-specific clinical stroke management to improve outcomes in the longer term. Stroke represents a considerable burden of disease for both men and women. However, a growing body of literature suggests clinically relevant sex differences in the underlying causes, presentations and outcomes of acute ischaemic stroke. In a recent study, we reported sex divergences in lesion topographies: specific to women, acute stroke severity was linked to lesions in the left-hemispheric posterior circulation. We here determined whether these sex-specific brain manifestations also affect long-term outcomes. We relied on 822 acute ischaemic patients [age: 64.7 (15.0) years, 39% women] originating from the multi-centre MRI-GENIE study to model unfavourable outcomes (modified Rankin Scale >2) based on acute neuroimaging data in a Bayesian hierarchical framework. Lesions encompassing bilateral subcortical nuclei and left-lateralized regions in proximity to the insula explained outcomes across men and women (area under the curve = 0.81). A pattern of left-hemispheric posterior circulation brain regions, combining left hippocampus, precuneus, fusiform and lingual gyrus, occipital pole and latero-occipital cortex, showed a substantially higher relevance in explaining functional outcomes in women compared to men [mean difference of Bayesian posterior distributions (men - women) = -0.295 (90% highest posterior density interval = -0.556 to -0.068)]. Once validated in prospective studies, our findings may motivate a sex-specific approach to clinical stroke management and hold the promise of enhancing outcomes on a population level.
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| 12. |
- Girard, R T, et al.
(författare)
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Electronic structure of ZnO(0001) studied by angle-resolved photoelectron spectroscopy
- 1997
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Ingår i: Surface Science. - 0039-6028 .- 1879-2758. ; 373:2-3, s. 409-417
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of the ZnO(0001) surface was studied by angle-resolved photoelectron spectroscopy. The recorded normal emission spectra give information about the Valence band states as well as the Zn 3d states. The dispersions of the four valence bands observed in the (0001) direction were compared with theory and are in good agreement with recent calculations which consider the Zn 3d electrons as part of the valence band. The Zn 3d states are seen to separate into two groups of four and six bands, which show dispersion with k(perpendicular to). This is in agreement with theoretical results but the location of these states were not accurately predicted. The present photoemission results show that they lie around 10.5 eV below E(F). Two surface states were observed on the (0001) surface. One, at 7.5 eV binding energy, was predicted by theory and is interpreted as arising from the ''back-bondings'' of the Zn 4s-O 2p mixed bulk states. The other one at 4.5 eV below E(F), most likely Zn 4p-0 2p derived, was not predicted by theoretical calculations and this is discussed further in the text. (C) 1997 Elsevier Science B.V.
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| 13. |
- Hirschauer, B, et al.
(författare)
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Highly oriented alpha-alumina films grown by pulsed laser deposition
- 1997
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Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 305:1-2, s. 243-247
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Tidskriftsartikel (refereegranskat)abstract
- Highly oriented thin films of alpha-alumina have been grown by pulsed laser deposition on Si(lll). The influence of the substrate temperature on the film growth was studied by X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (MID). Ablation at temperatures between room temperature and 850 degrees C gave rise to incorporated crystalline aluminium (Al), while the stoichiometric and highly oriented alpha-Al2O3 films were obtained only at 850 degrees C. The XRD rocking curve measurements of the ablated films showed the full-width-at-half-maximum (FWHM) Of 0.2 degrees. Further annealing at 1000 degrees C in air for 26 h slightly improved out-of-plane orientation. (C) 1997 Elsevier Science S.A.
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| 14. |
- Qvarford, M, et al.
(författare)
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Doping dependence of the O 1s is core-level photoemission in bi-Sr-Ca-Cu-O superconductors
- 1996
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 53:22, s. 14753-14756
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Tidskriftsartikel (refereegranskat)abstract
- The O 1s core level of three different Bi-Sr-Ca-Cu-O superconductors has been studied by means of high-resolution x-ray-photoelectron spectroscopy (XPS) and x-ray absorption spectroscopy (XAS). The O 1a XPS spectra could be decomposed into three components that were unambiguously assigned to the emission from the three different oxide layers in the crystal structure. These are, in order of increasing binding energy, Cu-O-2, Sr-O, and Bi-O. Furthermore, the component assigned to the Cu-O-2 layers exhibits a shift which depends on the hole doping as monitored by the XAS spectra.
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| 15. |
- Qvarford, M, et al.
(författare)
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Doping dependence of the O 1s is core-level photoemission in bi-Sr-Ca-Cu-O superconductors
- 1996
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Ingår i: PHYSICAL REVIEW B-CONDENSED MATTER. - : AMER INST PHYSICS. - 0163-1829. ; 53:22, s. 14753-14756
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The O 1s core level of three different Bi-Sr-Ca-Cu-O superconductors has been studied by means of high-resolution x-ray-photoelectron spectroscopy (XPS) and x-ray absorption spectroscopy (XAS). The O 1a XPS spectra could be decomposed into three component
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| 20. |
- Soderholm, M., et al.
(författare)
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Genome-wide association meta-analysis of functional outcome after ischemic stroke
- 2019
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Ingår i: Neurology. - : Ovid Technologies (Wolters Kluwer Health). - 0028-3878 .- 1526-632X. ; 92:12
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Tidskriftsartikel (refereegranskat)abstract
- Objective To discover common genetic variants associated with poststroke outcomes using a genome-wide association (GWA) study. Methods The study comprised 6,165 patients with ischemic stroke from 12 studies in Europe, the United States, and Australia included in the GISCOME (Genetics of Ischaemic Stroke Functional Outcome) network. The primary outcome was modified Rankin Scale score after 60 to 190 days, evaluated as 2 dichotomous variables (0-2 vs 3-6 and 0-1 vs 2-6) and subsequently as an ordinal variable. GWA analyses were performed in each study independently and results were meta-analyzed. Analyses were adjusted for age, sex, stroke severity (baseline NIH Stroke Scale score), and ancestry. The significance level was p < 5 x 10(-8). Results We identified one genetic variant associated with functional outcome with genome-wide significance (modified Rankin Scale scores 0-2 vs 3-6, p = 5.3 x 10(-9)). This intronic variant (rs1842681) in the LOC105372028 gene is a previously reported trans-expression quantitative trait locus for PPP1R21, which encodes a regulatory subunit of protein phosphatase 1. This ubiquitous phosphatase is implicated in brain functions such as brain plasticity. Several variants detected in this study demonstrated suggestive association with outcome (p < 10(-5)), some of which are within or near genes with experimental evidence of influence on ischemic stroke volume and/or brain recovery (e.g., NTN4, TEK, and PTCH1). Conclusions In this large GWA study on functional outcome after ischemic stroke, we report one significant variant and several variants with suggestive association to outcome 3 months after stroke onset with plausible mechanistic links to poststroke recovery. Future replication studies and exploration of potential functional mechanisms for identified genetic variants are warranted.
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| 21. |
- Tjernberg, O, et al.
(författare)
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Evidence of pseudogap related core level shifts in Bi2Sr2Ca1-xYxCu2O8+delta
- 1997
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 79:3, s. 499-502
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Tidskriftsartikel (refereegranskat)abstract
- Photoelectron spectroscopy data from Bi2Sr2Ca1-xYxCu2O8+delta Single crystals, for x = 0, 0.16, and 0.55, are presented. It is shown that there are core level shifts related to the opening of a pseudogap and that similar shifts are observed at the opening of the superconducting gap in optimally doped samples. This result is in agreement with pair formation above T-c as suggested by V.J. Emery and S.A. Kivelson [Nature (London) 374, 434 (1995)].
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| 22. |
- Tjernberg, O, et al.
(författare)
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Evidence of pseudogap related core level shifts in Bi2Sr2Ca1-xYxCu2O8+delta
- 1997
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Ingår i: PHYSICAL REVIEW LETTERS. - : AMER INST PHYSICS. - 0031-9007. ; 79:3, s. 499-502
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Photoelectron spectroscopy data from Bi2Sr2Ca1-xYxCu2O8+delta Single crystals, for x = 0, 0.16, and 0.55, are presented. It is shown that there are core level shifts related to the opening of a pseudogap and that similar shifts are observed at the opening
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| 23. |
- Tjernberg, O, et al.
(författare)
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Influence of magnetic ordering on the NiO valence band
- 1996
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Ingår i: Physical Review B Condensed Matter. - 0163-1829 .- 1095-3795. ; 54:15, s. 10245-10248
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Tidskriftsartikel (refereegranskat)abstract
- The influence of magnetic ordering on the NiO valence band has been studied by angle resolved photoelectron spectroscopy. Measurements have been performed at temperatures above and below the Neel temperature (T-N), as well as at room. temperature. The results show temperature dependence but no significant changes in the valence band structure are detected in connection to the passing of T-N. The reported data suggest that the magnetic phase transition does not influence the valence band structure significantly.
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| 24. |
- Tjernberg, O, et al.
(författare)
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Resonant photoelectron spectroscopy on NiO
- 1996
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 53:15, s. 10372-10376
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Tidskriftsartikel (refereegranskat)abstract
- Resonant photoelectron spectroscopy studies have been performed on the NiO valence band at photon energies corresponding to the Ni 2p, 3p, and O 1s absorption thresholds. Strong resonances are seen in the vicinity of the Ni 2P threshold, which confirm earlier conclusions from the weaker resonances seen at the Ni 3p threshold. No valence-band resonance is observed at the O 1s threshold. The analysis of this data confirms the picture of NiO as a strongly correlated charge-transfer insulator by identifying the highest-lying states as being of mainly 3d(8)L final-state character. The existence of localized excited Ni states, as well as the delocalized nature of the O states, are confirmed. Comparisons with the configuration-interaction model and quasiparticle calculations are also made.
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