2681. |
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2682. |
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2683. |
- Sharma, M, et al.
(författare)
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Rationale, design, and baseline participant characteristics in the MRI and cognitive substudy of the cardiovascular outcomes for people using anticoagulation strategies trial
- 2019
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Ingår i: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 14:3, s. 270-281
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Tidskriftsartikel (refereegranskat)abstract
- Covert vascular disease of the brain manifests as infarcts, white matter hyperintensities, and microbleeds on MRI. Their cumulative effect is often a decline in cognition, motor impairment, and psychiatric disorders. Preventive therapies for covert brain ischemia have not been established but represent a huge unmet clinical need. Aims The MRI substudy examines the effects of the antithrombotic regimens in COMPASS on incident covert brain infarcts (the primary outcome), white matter hyperintensities, and cognitive and functional status in a sample of consenting COMPASS participants without contraindications to MRI. Methods COMPASS is a randomized superiority trial testing rivaroxaban 2.5 mg bid plus acetylsalicylic acid 100 mg and rivaroxaban 5 mg bid against acetylsalicylic acid 100 mg per day for the combined endpoint of MI, stroke, and cardiovascular death in individuals with stable coronary artery disease or peripheral artery disease. T1-weighted, T2-weighted, T2*-weighted, and FLAIR images were obtained close to randomization and near the termination of assigned antithrombotic therapy; biomarker and genetic samples at randomization and one month, and cognitive and functional assessment at randomization, after two years and at the end of study. Results Between March 2013 and May 2016, 1905 participants were recruited from 86 centers in 16 countries. Of these participants, 1760 underwent baseline MRI scans that were deemed technically adequate for interpretation. The mean age at entry of participants with interpretable MRI was 71 years and 23.5% were women. Coronary artery disease was present in 90.4% and 28.1% had peripheral artery disease. Brain infarcts were present in 34.8%, 29.3% had cerebral microbleeds, and 93.0% had white matter hyperintensities. The median Montreal Cognitive Assessment score was 26 (interquartile range 23–28). Conclusions The COMPASS MRI substudy will examine the effect of the antithrombotic interventions on MRI-determined covert brain infarcts and cognition. Demonstration of a therapeutic effect of the antithrombotic regimens on brain infarcts would have implications for prevention of cognitive decline and provide insight into the pathogenesis of vascular cognitive decline.
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2684. |
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2685. |
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2686. |
- Shrivastava, Manish, et al.
(författare)
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Recent advances in understanding secondary organic aerosol : Implications for global climate forcing
- 2017
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Ingår i: Reviews of Geophysics. - 8755-1209. ; 55:2, s. 509-559
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Tidskriftsartikel (refereegranskat)abstract
- Anthropogenic emissions and land use changes have modified atmospheric aerosol concentrations and size distributions over time. Understanding preindustrial conditions and changes in organic aerosol due to anthropogenic activities is important because these features (1) influence estimates of aerosol radiative forcing and (2) can confound estimates of the historical response of climate to increases in greenhouse gases. Secondary organic aerosol (SOA), formed in the atmosphere by oxidation of organic gases, represents a major fraction of global submicron-sized atmospheric organic aerosol. Over the past decade, significant advances in understanding SOA properties and formation mechanisms have occurred through measurements, yet current climate models typically do not comprehensively include all important processes. This review summarizes some of the important developments during the past decade in understanding SOA formation. We highlight the importance of some processes that influence the growth of SOA particles to sizes relevant for clouds and radiative forcing, including formation of extremely low volatility organics in the gas phase, acid-catalyzed multiphase chemistry of isoprene epoxydiols, particle-phase oligomerization, and physical properties such as volatility and viscosity. Several SOA processes highlighted in this review are complex and interdependent and have nonlinear effects on the properties, formation, and evolution of SOA. Current global models neglect this complexity and nonlinearity and thus are less likely to accurately predict the climate forcing of SOA and project future climate sensitivity to greenhouse gases. Efforts are also needed to rank the most influential processes and nonlinear process-related interactions, so that these processes can be accurately represented in atmospheric chemistry-climate models.
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2687. |
- Singleton, Ellen, et al.
(författare)
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Heterogeneous distribution of tau pathology in the behavioural variant of Alzheimer's disease
- 2021
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 92:8, s. 872-880
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The clinical phenotype of the rare behavioural variant of Alzheimer's disease (bvAD) is insufficiently understood. Given the strong clinico-anatomical correlations of tau pathology in AD, we investigated the distribution of tau deposits in bvAD, in-vivo and ex-vivo, using positron emission tomography (PET) and postmortem examination. Methods: For the tau PET study, seven amyloid-β positive bvAD patients underwent [18F]flortaucipir or [18F]RO948 PET. We converted tau PET uptake values into standardised (W-)scores, adjusting for age, sex and mini mental state examination in a 'typical' memory-predominant AD (n=205) group. W-scores were computed within entorhinal, temporoparietal, medial and lateral prefrontal, insular and whole-brain regions-of-interest, frontal-to-entorhinal and frontal-to-parietal ratios and within intrinsic functional connectivity network templates. For the postmortem study, the percentage of AT8 (tau)-positive area in hippocampus CA1, temporal, parietal, frontal and insular cortices were compared between autopsy-confirmed patients with bvAD (n=8) and typical AD (tAD;n=7). Results: Individual regional W-scores ≥1.96 (corresponding to p<0.05) were observed in three cases, that is, case #5: medial prefrontal cortex (W=2.13) and anterior default mode network (W=3.79), case #2: lateral prefrontal cortex (W=2.79) and salience network (W=2.77), and case #7: frontal-to-entorhinal ratio (W=2.04). The remaining four cases fell within the normal distributions of the tAD group. Postmortem AT8 staining indicated no group-level regional differences in phosphorylated tau levels between bvAD and tAD (all p>0.05). Conclusions: Both in-vivo and ex-vivo, patients with bvAD showed heterogeneous distributions of tau pathology. Since key regions involved in behavioural regulation were not consistently disproportionally affected by tau pathology, other factors are more likely driving the clinical phenotype in bvAD.
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2688. |
- Smith, C.A., et al.
(författare)
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A simplified assay for the arylamine N-acetyltransferase 2 polymorphism validated by phenotyping with isoniazid
- 1997
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 34:9, s. 758-60
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Tidskriftsartikel (refereegranskat)abstract
- Human arylamine N-acetyltransferase (NAT) activity is determined by two distinct genes, NAT1 and NAT2, and the classical acetylation polymorphism in NAT2 has been associated with a variety of disorders, including lupus erythematosus and arylamine induced cancers. Over 50% of the white population exhibit a slow acetylator phenotype. The genetic basis of the defect has been identified and several DNA based assays are available for genotyping studies. We present here a simplified, rapid PCR based assay for the identification of the major slow acetylator genotypes and validate it using isoniazid as probe drug. This assay was 100% predictive of phenotype. The three genotypes (homozygous mutated, heterozygous, and homozygous rapid) corresponded to a trimodal distribution of Ac-INH/INH metabolic ratios (slow, intermediate, and rapid) without overlapping.
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2689. |
- Smith, K. A., et al.
(författare)
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Burden of comorbid diseases among MS patients in Sweden
- 2019
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Ingår i: Multiple Sclerosis Journal. - : Sage Publications. - 1352-4585 .- 1477-0970. ; 25:Suppl. 2, s. 646-646
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: A raised risk for several comorbid diseases among MS patients has been identified. Most previous studies examined diseases separately rather than considering the overall burden of comorbidity. Multiple comorbidities may have important implica-tions for clinicians managing MS patients.Aims: To describe the lifetime burden of comorbid diseases among MS patients and the rate of these diseases compared with the general population in Sweden.Methods: MS patients identified using the MS Register and the Patient Register (PR) between 1964-2012 (n=25476) were matched by sex, age and county of residence with up to 10 general population comparators (n=251170). Prevalent and incident diag-noses of diseases other than MS for seven diseases categories were identified using the PR between 1987-2012. The total num-ber of comorbid diseases were compared using chi-square tests and prevalence rate ratios (PRR) were calculated. Hazard ratios (HR) were estimated using Cox regression and flexible non-para-metric survival models with age as the underlying time scale, MS as exposure, an additional comorbid disease as the outcome, adjusted for matching variables, education, number of previous comorbid diseases, and duration since study entry.Results: The proportion of MS patients with 1,2 or 3+ comorbid disease diagnoses was greater than in the comparison cohort across all age groups (p< 0.001). The largest PRR (range 1.22-9.99) were among younger age groups (6-18,19-40,41-60 years) in autoim-mune, cardiovascular, diabetes and seizure disease categories. Additionally, PRR were elevated in depression and respiratory dis-eases, but not for renal diseases. PRR between 61-80 and 81-100 years were reduced compared to younger groups across all comorbid diseases, but remained elevated for respiratory, seizure and renal dis-eases. The adjusted HR for an additional diagnosis in MS patients was 1.7 (95% CI 1.66-1.75). Flexible modelling showed signifi-cantly higher risk for all ages of an additional disease diagnosis in MS patients; twice the risk (95% CI 1.8-2.2) up to age 35 years and decreasing with age to 1.3 (95% CI 1.5-1.25) over age 80 years.Conclusions: MS patients in Sweden experience an increased burden of comorbidity and tend to be diagnosed with these dis-eases at an earlier age than the general population. This increased disease burden demonstrates the clinical reality of treating MS, indicating the need for integrated treatment approaches over sev-eral medical specialties.
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