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- Kaufmann, Tobias, et al.
(författare)
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Common brain disorders are associated with heritable patterns of apparent aging of the brain
- 2019
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Ingår i: Nature Neuroscience. - : Nature Publishing Group. - 1097-6256 .- 1546-1726. ; 22:10, s. 1617-
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Tidskriftsartikel (refereegranskat)abstract
- Common risk factors for psychiatric and other brain disorders are likely to converge on biological pathways influencing the development and maintenance of brain structure and function across life. Using structural MRI data from 45,615 individuals aged 3-96 years, we demonstrate distinct patterns of apparent brain aging in several brain disorders and reveal genetic pleiotropy between apparent brain aging in healthy individuals and common brain disorders.
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| 2. |
- Alnaes, Dag, et al.
(författare)
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Brain Heterogeneity in Schizophrenia and Its Association With Polygenic Risk
- 2019
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Ingår i: JAMA psychiatry. - : AMER MEDICAL ASSOC. - 2168-6238 .- 2168-622X. ; 76:7, s. 739-748
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Tidskriftsartikel (refereegranskat)abstract
- ImportanceBetween-individual variability in brain structure is determined by gene-environment interactions, possibly reflecting differential sensitivity to environmental and genetic perturbations. Magnetic resonance imaging (MRI) studies have revealed thinner cortices and smaller subcortical volumes in patients with schizophrenia. However, group-level comparisons may mask considerable within-group heterogeneity, which has largely remained unnoticed in the literature. ObjectivesTo compare brain structural variability between individuals with schizophrenia and healthy controls and to test whether respective variability reflects the polygenic risk score (PRS) for schizophrenia in an independent sample of healthy controls. Design, Setting, and ParticipantsThis case-control and polygenic risk analysis compared MRI-derived cortical thickness and subcortical volumes between healthy controls and patients with schizophrenia across 16 cohorts and tested for associations between PRS and MRI features in a control cohort from the UK Biobank. Data were collected from October 27, 2004, through April 12, 2018, and analyzed from December 3, 2017, through August 1, 2018. Main Outcomes and MeasuresMean and dispersion parameters were estimated using double generalized linear models. Vertex-wise analysis was used to assess cortical thickness, and regions-of-interest analyses were used to assess total cortical volume, total surface area, and white matter, subcortical, and hippocampal subfield volumes. Follow-up analyses included within-sample analysis, test of robustness of the PRS threshold, population covariates, outlier removal, and control for image quality. ResultsA comparison of 1151 patients with schizophrenia (mean [SD] age,33.8[10.6] years; 68.6% male [n=790] and 31.4% female [n=361]) with 2010 healthy controls (mean [SD] age,32.6[10.4] years; 56.0% male [n=1126] and 44.0% female [n=884]) revealed higher heterogeneity in schizophrenia for cortical thickness and area (t = 3.34), cortical (t=3.24) and ventricle (t range, 3.15-5.78) volumes, and hippocampal subfields (t range, 2.32-3.55). In the UK Biobank sample of 12 490 participants (mean [SD] age,55.9 [7.5] years; 48.2% male [n=6025] and 51.8% female [n=6465]), higher PRS was associated with thinner frontal and temporal cortices and smaller left CA2/3 (t=-3.00) but was not significantly associated with dispersion. Conclusions and RelevanceThis study suggests that schizophrenia is associated with substantial brain structural heterogeneity beyond the mean differences. These findings may reflect higher sensitivity to environmental and genetic perturbations in patients, supporting the heterogeneous nature of schizophrenia. A higher PRS was associated with thinner frontotemporal cortices and smaller hippocampal subfield volume, but not heterogeneity. This finding suggests that brain variability in schizophrenia results from interactions between environmental and genetic factors that are not captured by the PRS. Factors contributing to heterogeneity in frontotemporal cortices and hippocampus are key to furthering our understanding of how genetic and environmental factors shape brain biology in schizophrenia.
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| 4. |
- Makubi, Abel, et al.
(författare)
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Heart failure in Tanzania and Sweden: Comparative characterization and prognosis in the Tanzania Heart Failure (TaHeF) study and the Swedish Heart Failure Registry (SwedeHF)
- 2016
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 220, s. 750-758
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Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) in developing countries is poorly described. We compare characteristics and prognosis of HF in Tanzania vs. Sweden. Methods: A prospective cohort study was conducted from the Tanzania HF study (TaHeF) and the Swedish HF Registry (SwedeHF). Patients were compared overall (n 427 vs. 51,060) and after matching 1: 3 by gender and age +/- 5 years (n 411 vs. 1232). The association between cohort and all-cause mortality was assessed with multivariable Cox regression. Results: In the unmatched cohorts, TaHeF (as compared to SwedeHF) patients were younger (median age [inter-quartile range] 55 [40-68] vs. 77 [64-84] years, p amp;lt; 0.001) and more commonly women (51% vs. 40%, p amp;lt; 0.001). The three-year survival was 61% in both cohorts. In the matched cohorts, TaHeF patients had more hypertension (47% vs. 37%, p amp;lt; 0.001), more anemia (57% vs. 9%), more preserved EF, more advanced HF, longer duration of HF, and less use of beta-blockers. Crude mortality was worse in TaHeF (HR 2.25 [95% CI 1.78-2.85], p amp;lt; 0.001), with three-year survival 61% vs. 83%. However, covariate-adjusted risk was similar (HR 1.07, 95% CI 0.69-1.66; p = 0.760). In both cohorts, preserved EF was associated with higher mortality in crude but not adjusted analysis. Conclusions: Compared to in Sweden, HF patients in Tanzania were younger and more commonly female, and after age and gender matching, had more frequent hypertension and anemia, more severe HF despite higher EF, and worse crude but similar adjusted prognosis. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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| 5. |
- Mortensen, Mike A., et al.
(författare)
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Artificial intelligence-based versus manual assessment of prostate cancer in the prostate gland: a method comparison study
- 2019
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 39:6, s. 399-406
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Tidskriftsartikel (refereegranskat)abstract
- Aim : To test the feasibility of a fully automated artificial intelligence-based method providing PET measures of prostate cancer (PCa). Methods : A convolutional neural network (CNN) was trained for automated measurements in 18F-choline (FCH) PET/CT scans obtained prior to radical prostatectomy (RP) in 45 patients with newly diagnosed PCa. Automated values were obtained for prostate volume, maximal standardized uptake value (SUVmax), mean standardized uptake value of voxels considered abnormal (SUVmean) and volume of abnormal voxels (Volabn). The product SUVmean × Volabn was calculated to reflect total lesion uptake (TLU). Corresponding manual measurements were performed. CNN-estimated data were compared with the weighted surgically removed tissue specimens and manually derived data and related to clinical parameters assuming that 1 g ≈ 1 ml of tissue. Results : The mean (range) weight of the prostate specimens was 44 g (20–109), while CNN-estimated volume was 62 ml (31–108) with a mean difference of 13·5 g or ml (95% CI: 9·78–17·32). The two measures were significantly correlated (r = 0·77, P<0·001). Mean differences (95% CI) between CNN-based and manually derived PET measures of SUVmax, SUVmean, Volabn (ml) and TLU were 0·37 (−0·01 to 0·75), −0·08 (−0·30 to 0·14), 1·40 (−2·26 to 5·06) and 9·61 (−3·95 to 23·17), respectively. PET findings Volabn and TLU correlated with PSA (P<0·05), but not with Gleason score or stage. Conclusion : Automated CNN segmentation provided in seconds volume and simple PET measures similar to manually derived ones. Further studies on automated CNN segmentation with newer tracers such as radiolabelled prostate-specific membrane antigen are warranted.
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| 7. |
- Pennells, Lisa, et al.
(författare)
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Equalization of four cardiovascular risk algorithms after systematic recalibration : individual-participant meta-analysis of 86 prospective studies
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:7, s. 621-
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Tidskriftsartikel (refereegranskat)abstract
- Aims: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after ‘recalibration’, a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Methods and results: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at ‘high’ 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29–39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22–24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44–51 such individuals using original algorithms, in contrast to 37–39 individuals with recalibrated algorithms.Conclusion: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.
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| 10. |
- Ahmad, Tariq, et al.
(författare)
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Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients
- 2018
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Ingår i: Journal of the American Heart Association. - : WILEY. - 2047-9980. ; 7:8
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Tidskriftsartikel (refereegranskat)abstract
- Background-Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. Methods and Results-The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, )i-blockers, and nitrates, Pamp;lt;0.001, all). Conclusions-Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics. Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.
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