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Sökning: WFRF:(Rose Matthias)

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1.
  • Pattaro, Cristian, et al. (författare)
  • Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways.
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2.
  • Shungin, Dmitry, et al. (författare)
  • New genetic loci link adipose and insulin biology to body fat distribution.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
  • Tidskriftsartikel (refereegranskat)abstract
    • Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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3.
  • Wheeler, Eleanor, et al. (författare)
  • Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations : A transethnic genome-wide meta-analysis
  • 2017
  • Ingår i: PLoS Medicine. - : PUBLIC LIBRARY SCIENCE. - 1549-1277 .- 1549-1676. ; 14:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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4.
  • Aguado, D. S., et al. (författare)
  • The Fifteenth Data Release of the Sloan Digital Sky Surveys : First Release of MaNGA-derived Quantities, Data Visualization Tools, and Stellar Library
  • 2019
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics Publishing (IOPP). - 0067-0049 .- 1538-4365. ; 240:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Twenty years have passed since first light for the Sloan Digital Sky Survey (SDSS). Here, we release data taken by the fourth phase of SDSS (SDSS-IV) across its first three years of operation (2014 July-2017 July). This is the third data release for SDSS-IV, and the 15th from SDSS (Data Release Fifteen; DR15). New data come from MaNGA-we release 4824 data cubes, as well as the first stellar spectra in the MaNGA Stellar Library (MaStar), the first set of survey-supported analysis products (e.g., stellar and gas kinematics, emission-line and other maps) from the MaNGA Data Analysis Pipeline, and a new data visualization and access tool we call "Marvin." The next data release, DR16, will include new data from both APOGEE-2 and eBOSS; those surveys release no new data here, but we document updates and corrections to their data processing pipelines. The release is cumulative; it also includes the most recent reductions and calibrations of all data taken by SDSS since first light. In this paper, we describe the location and format of the data and tools and cite technical references describing how it was obtained and processed. The SDSS website (www.sdss.org) has also been updated, providing links to data downloads, tutorials, and examples of data use. Although SDSS-IV will continue to collect astronomical data until 2020, and will be followed by SDSS-V (2020-2025), we end this paper by describing plans to ensure the sustainability of the SDSS data archive for many years beyond the collection of data.
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5.
  • Alonso, Jordi, et al. (författare)
  • The case for an international patient-reported outcomes measurement information system (PROMIS®) initiative.
  • 2013
  • Ingår i: Health and quality of life outcomes. - : Springer Science and Business Media LLC. - 1477-7525. ; 11
  • Tidskriftsartikel (refereegranskat)abstract
    • Patient-reported outcomes (PROs) play an increasingly important role in clinical practice and research. Modern psychometric methods such as item response theory (IRT) enable the creation of item banks that support fixed-length forms as well as computerized adaptive testing (CAT), often resulting in improved measurement precision and responsiveness. Here we describe and discuss the case for developing an international core set of PROs building from the US PROMIS® network.PROMIS is a U.S.-based cooperative group of research sites and centers of excellence convened to develop and standardize PRO measures across studies and settings. If extended to a global collaboration, PROMIS has the potential to transform PRO measurement by creating a shared, unifying terminology and metric for reporting of common symptoms and functional life domains. Extending a common set of standardized PRO measures to the international community offers great potential for improving patient-centered research, clinical trials reporting, population monitoring, and health care worldwide. Benefits of such standardization include the possibility of: international syntheses (such as meta-analyses) of research findings; international population monitoring and policy development; health services administrators and planners access to relevant information on the populations they serve; better assessment and monitoring of patients by providers; and improved shared decision making.The goal of the current PROMIS International initiative is to ensure that item banks are translated and culturally adapted for use in adults and children in as many countries as possible. The process includes 3 key steps: translation/cultural adaptation, calibration, and validation. A universal translation, an approach focusing on commonalities, rather than differences across versions developed in regions or countries speaking the same language, is proposed to ensure conceptual equivalence for all items. International item calibration using nationally representative samples of adults and children within countries is essential to demonstrate that all items possess expected strong measurement properties. Finally, it is important to demonstrate that the PROMIS measures are valid, reliable and responsive to change when used in an international context.IRT item banking will allow for tailoring within countries and facilitate growth and evolution of PROs through contributions from the international measurement community. A number of opportunities and challenges of international development of PROs item banks are discussed.
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6.
  • Andersen, Casper W., et al. (författare)
  • OPTIMADE, an API for exchanging materials data
  • 2021
  • Ingår i: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The Open Databases Integration for Materials Design (OPTIMADE) consortium has designed a universal application programming interface (API) to make materials databases accessible and interoperable. We outline the first stable release of the specification, v1.0, which is already supported by many leading databases and several software packages. We illustrate the advantages of the OPTIMADE API through worked examples on each of the public materials databases that support the full API specification.
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7.
  • Atkins, Isabelle, et al. (författare)
  • Transcriptome-Wide Association Study Identifies New Candidate Susceptibility Genes for Glioma
  • 2019
  • Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 79:8, s. 2065-2071
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in noncoding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM and 5,820 non-GBM) and 18,169 controls. Imposing a Bonferroni-corrected significance level of P < 5.69 x 10(-6), candidate novel risk locus for GBM (mean Z = 4.43; P = 5.68 x 10(-6)). GALNT6 resides at least 55 Mb away from any previously identified glioma risk variant, while all other 30 significantly associated genes were located within 1 Mb of known GWAS-identified loci and were not significant after conditioning on the known GWAS-identified variants. These data identify a novel locus (GALNT6 at 12q13.33) and 30 genes at 12 known glioma risk loci associated with glioma risk, providing further insights into glioma tumorigenesis.Significance: This study identifies new genes associated with glioma risk, increasing understanding of how these tumors develop.
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8.
  • Bauckneht, Matteo, et al. (författare)
  • Associations among education, age, and the dementia with Lewy bodies (DLB) metabolic pattern: A European-DLB consortium project
  • 2021
  • Ingår i: Alzheimer's & Dementia. - : WILEY. - 1552-5260 .- 1552-5279. ; 17:8, s. 1277-1286
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction We assessed the influence of education as a proxy of cognitive reserve and age on the dementia with Lewy bodies (DLB) metabolic pattern. Methods Brain 18F-fluorodeoxyglucose positron emission tomography and clinical/demographic information were available in 169 probable DLB patients included in the European DLB-consortium database. Principal component analysis identified brain regions relevant to local data variance. A linear regression model was applied to generate age- and education-sensitive maps corrected for Mini-Mental State Examination score, sex (and either education or age). Results Age negatively covaried with metabolism in bilateral middle and superior frontal cortex, anterior and posterior cingulate, reducing the expression of the DLB-typical cingulate island sign (CIS). Education negatively covaried with metabolism in the left inferior parietal cortex and precuneus (making the CIS more prominent). Discussion These findings point out the importance of tailoring interpretation of DLB biomarkers considering the concomitant effect of individual, non-disease-related variables such as age and cognitive reserve.
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9.
  • Berner, Logan T., et al. (författare)
  • The Arctic plant aboveground biomass synthesis dataset
  • 2024
  • Ingår i: Scientific Data. - : Springer Nature. - 2052-4463. ; 11:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant biomass is a fundamental ecosystem attribute that is sensitive to rapid climatic changes occurring in the Arctic. Nevertheless, measuring plant biomass in the Arctic is logistically challenging and resource intensive. Lack of accessible field data hinders efforts to understand the amount, composition, distribution, and changes in plant biomass in these northern ecosystems. Here, we present The Arctic plant aboveground biomass synthesis dataset, which includes field measurements of lichen, bryophyte, herb, shrub, and/or tree aboveground biomass (g m−2) on 2,327 sample plots from 636 field sites in seven countries. We created the synthesis dataset by assembling and harmonizing 32 individual datasets. Aboveground biomass was primarily quantified by harvesting sample plots during mid- to late-summer, though tree and often tall shrub biomass were quantified using surveys and allometric models. Each biomass measurement is associated with metadata including sample date, location, method, data source, and other information. This unique dataset can be leveraged to monitor, map, and model plant biomass across the rapidly warming Arctic.
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10.
  • Blankestijn, Peter J., et al. (författare)
  • Benefits and harms of high-dose haemodiafiltration versus high-flux haemodialysis : The comparison of high-dose haemodiafiltration with high-flux haemodialysis (CONVINCE) trial protocol
  • 2020
  • Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 10:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction End-stage kidney disease (ESKD) is a major public health problem affecting more than 2 million people worldwide. It is one of the most severe chronic non-communicable diseases. Haemodialysis (HD) is the most common therapeutic option but is also associated with a risk of cardiovascular events, hospitalisation and suboptimal quality of life. Over the past decades, haemodiafiltration (HDF) has become available. Although high-dose HDF has shown some promising survival advantage compared to conventional HD, the evidence remains controversial. A Cochrane systematic review found, in low-quality trials, with various convective forms of dialysis, a reduction in cardiovascular, but not all-cause mortality and the effects on non-fatal cardiovascular events and hospitalisation were uncertain. In contrast, an individual patient data analysis suggested that high-dose HDF reduced both all-cause and cardiovascular mortality compared to HD. In view of these discrepant results, a definitive trial is required to determine whether high-dose HDF is preferable to high-flux HD. The comparison of high-dose HDF with high-flux HD (CONVINCE) study will assess the benefits and harms of high-dose HDF versus a conventional high-flux HD in adults with ESKD. Methods and analysis This international, prospective, open label, randomised controlled trial aims to recruit 1800 ESKD adults treated with HD in nine European countries. Patients will be randomised 1:1 to high-dose HDF versus continuation of conventional high-flux HD. The primary outcome will be all-cause mortality at 3 years' follow-up. Secondary outcomes will include cause-specific mortality, cardiovascular events, all-cause and infection-related hospitalisations, patient-reported outcomes (eg, health-related quality of life) and cost-effectiveness. Ethics and dissemination The CONVINCE study will address the question of benefits and harms of high-dose HDF compared to high-flux HD for kidney replacement therapy in patients with ESKD with a focus on survival, patient perspectives and cost-effectiveness. Trial registration number Netherlands National Trial Register (NTR 7138).
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11.
  • Cattaruzza, S, et al. (författare)
  • Distribution of PG-M/versican variants in human tissues and de novo expression of isoform V3 upon endothelial cell activation, migration, and neoangiogenesis in vitro
  • 2002
  • Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 277:49, s. 47626-47635
  • Tidskriftsartikel (refereegranskat)abstract
    • We have carried out a comprehensive molecular mapping of PG-M/versican isoforms V0-V3 in adult human tissues and have specifically investigated how the expression of these isoforms is regulated in endothelial cells in vitro. A survey of 21 representative tissues highlighted a prevalence of V1 mRNA, demonstrated that the relative frequency of expression was V1>V2>V3greater than or equal toV2; and showed that <15% of the tissues transcribed significant levels of all four isoforms. By employing novel and previously described anti-versican antibodies we verified a ubiquitous versican deposition in normal and tumor-associated vascular structures and disclosed differences in the glycanation profiles of versicans produced in different vascular beds. Resting endothelial cells isolated from different tissue sources transcribed several of the versican isoforms but consistently failed to translate these mRNAs into detectable proteoglycans. However, if stimulated with tumor necrosis factor-α or vascular endothelial growth factor, they altered their versican expression by de novo transcribing the V3 isoform and by exhibiting a moderate V1/V2 production. Induced versican synthesis and de novo V3 expression was also observed in endothelial cells elicited to migrate in a wound-healing model in vitro and in angiogenic endothelial cells forming tubule-like structures in Matrigel or fibrin clots. The results suggest that, independent of the degree of vascularization, human adult tissues show a limited expression of versican isoforms V0, V2, and V3 and that endothelial cells may contribute to the deposition of versican in vascular structures, but only following proper stimulation.
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12.
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13.
  • de Vries, Paul S., et al. (författare)
  • Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
  • 2019
  • Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
  • Tidskriftsartikel (refereegranskat)abstract
    • A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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14.
  • Disney-Hogg, Linden, et al. (författare)
  • Impact of atopy on risk of glioma : a Mendelian randomisation study
  • 2018
  • Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 16
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: An inverse relationship between allergies with glioma risk has been reported in several but not all epidemiological observational studies. We performed an analysis of genetic variants associated with atopy to assess the relationship with glioma risk using Mendelian randomisation (MR), an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations.Methods: Two-sample MR was undertaken using genome-wide association study data. We used single nucleotide polymorphisms (SNPs) associated with atopic dermatitis, asthma and hay fever, IgE levels, and self-reported allergy as instrumental variables. We calculated MR estimates for the odds ratio (OR) for each risk factor with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighting (IVW), maximum likelihood estimation (MLE), weighted median estimate (WME) and mode-based estimate (MBE) methods. Violation of MR assumptions due to directional pleiotropy were sought using MR-Egger regression and HEIDI-outlier analysis.Results: Under IVW, MLE, WME and MBE methods, associations between glioma risk with asthma and hay fever, self-reported allergy and IgE levels were non-significant. An inverse relationship between atopic dermatitis and glioma risk was found by IVW (OR 0.96, 95% confidence interval (CI) 0.93-1.00, P = 0.041) and MLE (OR 0.96, 95% CI 0.94-0.99, P = 0.003), but not by WME (OR 0.96, 95% CI 0.91-1.01, P = 0.114) or MBE (OR 0.97, 95% CI 0.92-1.02, P = 0.194).Conclusions: Our investigation does not provide strong evidence for relationship between atopy and the risk of developing glioma, but findings do not preclude a small effect in relation to atopic dermatitis. Our analysis also serves to illustrate the value of using several MR methods to derive robust conclusions.
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15.
  • Disney-Hogg, Linden, et al. (författare)
  • Influence of obesity-related risk factors in the aetiology of glioma
  • 2018
  • Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 118:7, s. 1020-1027
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Obesity and related factors have been implicated as possible aetiological factors for the development of glioma in epidemiological observation studies. We used genetic markers in a Mendelian randomisation framework to examine whether obesity-related traits influence glioma risk. This methodology reduces bias from confounding and is not affected by reverse causation. METHODS: Genetic instruments were identified for 10 key obesity-related risk factors, and their association with glioma risk was evaluated using data from a genome-wide association study of 12,488 glioma patients and 18,169 controls. The estimated odds ratio of glioma associated with each of the genetically defined obesity-related traits was used to infer evidence for a causal relationship. RESULTS: No convincing association with glioma risk was seen for genetic instruments for body mass index, waist-to-hip ratio, lipids, type-2 diabetes, hyperglycaemia or insulin resistance. Similarly, we found no evidence to support a relationship between obesity-related traits with subtypes of glioma-glioblastoma (GBM) or non-GBM tumours. CONCLUSIONS: This study provides no evidence to implicate obesity-related factors as causes of glioma.
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16.
  • Etminani, Kobra, 1984-, et al. (författare)
  • A 3D deep learning model to predict the diagnosis of dementia with Lewy bodies, Alzheimers disease, and mild cognitive impairment using brain 18F-FDG PET
  • 2022
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - New York : Springer. - 1619-7070 .- 1619-7089. ; 49, s. 563-584
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose The purpose of this study is to develop and validate a 3D deep learning model that predicts the final clinical diagnosis of Alzheimers disease (AD), dementia with Lewy bodies (DLB), mild cognitive impairment due to Alzheimers disease (MCI-AD), and cognitively normal (CN) using fluorine 18 fluorodeoxyglucose PET (18F-FDG PET) and compare models performance to that of multiple expert nuclear medicine physicians readers. Materials and methods Retrospective 18F-FDG PET scans for AD, MCI-AD, and CN were collected from Alzheimers disease neuroimaging initiative (556 patients from 2005 to 2020), and CN and DLB cases were from European DLB Consortium (201 patients from 2005 to 2018). The introduced 3D convolutional neural network was trained using 90% of the data and externally tested using 10% as well as comparison to human readers on the same independent test set. The models performance was analyzed with sensitivity, specificity, precision, F1 score, receiver operating characteristic (ROC). The regional metabolic changes driving classification were visualized using uniform manifold approximation and projection (UMAP) and network attention. Results The proposed model achieved area under the ROC curve of 96.2% (95% confidence interval: 90.6-100) on predicting the final diagnosis of DLB in the independent test set, 96.4% (92.7-100) in AD, 71.4% (51.6-91.2) in MCI-AD, and 94.7% (90-99.5) in CN, which in ROC space outperformed human readers performance. The network attention depicted the posterior cingulate cortex is important for each neurodegenerative disease, and the UMAP visualization of the extracted features by the proposed model demonstrates the reality of development of the given disorders. Conclusion Using only 18F-FDG PET of the brain, a 3D deep learning model could predict the final diagnosis of the most common neurodegenerative disorders which achieved a competitive performance compared to the human readers as well as their consensus.
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17.
  • Fazey, Ioan, et al. (författare)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • Ingår i: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Tidskriftsartikel (refereegranskat)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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18.
  • Goddi, Ciriaco, et al. (författare)
  • Polarimetric Properties of Event Horizon Telescope Targets from ALMA
  • 2021
  • Ingår i: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 910:1
  • Tidskriftsartikel (refereegranskat)abstract
    • We present the results from a full polarization study carried out with the Atacama Large Millimeter/submillimeter Array (ALMA) during the first Very Long Baseline Interferometry (VLBI) campaign, which was conducted in 2017 April in the lambda 3 mm and lambda 1.3 mm bands, in concert with the Global mm-VLBI Array (GMVA) and the Event Horizon Telescope (EHT), respectively. We determine the polarization and Faraday properties of all VLBI targets, including Sgr A*, M87, and a dozen radio-loud active galactic nuclei (AGNs), in the two bands at several epochs in a time window of 10 days. We detect high linear polarization fractions (2%-15%) and large rotation measures (RM > 10(3.3)-10(5.5) rad m(-2)), confirming the trends of previous AGN studies at millimeter wavelengths. We find that blazars are more strongly polarized than other AGNs in the sample, while exhibiting (on average) order-of-magnitude lower RM values, consistent with the AGN viewing angle unification scheme. For Sgr A* we report a mean RM of (-4.2 0.3) x 10(5) rad m(-2) at 1.3 mm, consistent with measurements over the past decade and, for the first time, an RM of (-2.1 0.1) x 10(5) rad m(-2) at 3 mm, suggesting that about half of the Faraday rotation at 1.3 mm may occur between the 3 mm photosphere and the 1.3 mm source. We also report the first unambiguous measurement of RM toward the M87 nucleus at millimeter wavelengths, which undergoes significant changes in magnitude and sign reversals on a one year timescale, spanning the range from -1.2 to 0.3 x 10(5) rad m(-2) at 3 mm and -4.1 to 1.5 x 10(5) rad m(-2) at 1.3 mm. Given this time variability, we argue that, unlike the case of Sgr A*, the RM in M87 does not provide an accurate estimate of the mass accretion rate onto the black hole. We put forward a two-component model, comprised of a variable compact region and a static extended region, that can simultaneously explain the polarimetric properties observed by both the EHT (on horizon scales) and ALMA (which observes the combined emission from both components). These measurements provide critical constraints for the calibration, analysis, and interpretation of simultaneously obtained VLBI data with the EHT and GMVA.
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19.
  • Graña-González, A., et al. (författare)
  • Quasi-free (p,2p) reactions in inverse kinematics for studying the fission yield dependence on temperature
  • 2023
  • Ingår i: FAIR next generation scientists - 7th Edition Workshop : FAIRness2022 - FAIRness2022. - 1824-8039. ; 419
  • Konferensbidrag (refereegranskat)abstract
    • Despite the recent experimental and theoretical progress in the investigation of the nuclear fission process, a complete description still represents a challenge in nuclear physics because it is a very complex dynamical process, whose description involves the coupling between intrinsic and collective degrees of freedom, as well as different quantum-mechanical phenomena. To improve on the existing data on nuclear fission, we produce fission reactions of heavy nuclei in inverse kinematics by using quasi-free (p,2p) scattering, which induce fission through particle-hole excitations that can range from few to ten's of MeV. The measurement of the four-momenta of the two outgoing protons allows to reconstruct the excitation energy of the fissioning compound nucleus and therefore to study the evolution of the fission yields with temperature. The realization of this kind of experiment requires a complex experimental setup, providing full isotopic identification of both fission fragments and an accurate measurement of the momenta of the two outgoing protons. This was realized recently at the GSI/FAIR facility and here some preliminary results are presented.
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20.
  • Hibar, Derrek P., et al. (författare)
  • Novel genetic loci associated with hippocampal volume
  • 2017
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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21.
  • Huber, Maria, et al. (författare)
  • Metabolic correlates of dopaminergic loss in dementia with lewy bodies
  • 2020
  • Ingår i: Movement Disorders. - : WILEY. - 0885-3185 .- 1531-8257. ; 35, s. 595-605
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Striatal dopamine deficiency and metabolic changes are well-known phenomena in dementia with Lewy bodies and can be quantified in vivo by I-123-Ioflupane brain single-photon emission computed tomography of dopamine transporter and F-18-fluorodesoxyglucose PET. However, the linkage between both biomarkers is ill-understood. Objective We used the hitherto largest study cohort of combined imaging from the European consortium to elucidate the role of both biomarkers in the pathophysiological course of dementia with Lewy bodies. Methods We compared striatal dopamine deficiency and glucose metabolism of 84 dementia with Lewy body patients and comparable healthy controls. After normalization of data, we tested their correlation by region-of-interest-based and voxel-based methods, controlled for study center, age, sex, education, and current cognitive impairment. Metabolic connectivity was analyzed by inter-region coefficients stratified by dopamine deficiency and compared to healthy controls. Results There was an inverse relationship between striatal dopamine availability and relative glucose hypermetabolism, pronounced in the basal ganglia and in limbic regions. With increasing dopamine deficiency, metabolic connectivity showed strong deteriorations in distinct brain regions implicated in disease symptoms, with greatest disruptions in the basal ganglia and limbic system, coincident with the pattern of relative hypermetabolism. Conclusions Relative glucose hypermetabolism and disturbed metabolic connectivity of limbic and basal ganglia circuits are metabolic correlates of dopamine deficiency in dementia with Lewy bodies. Identification of specific metabolic network alterations in patients with early dopamine deficiency may serve as an additional supporting biomarker for timely diagnosis of dementia with Lewy bodies. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
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22.
  • Klein, Jan Philipp, et al. (författare)
  • The EVIDENT-trial: protocol and rationale of a multicenter randomized controlled trial testing the effectiveness of an online-based psychological intervention
  • 2013
  • Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundDepressive disorders are among the leading causes of worldwide disability with mild to moderate forms of depression being particularly common. Low-intensity treatments such as online psychological treatments may be an effective way to treat mild to moderate depressive symptoms and prevent the emergence or relapse of major depression.Methods/DesignThis study is a currently recruiting multicentre parallel-groups pragmatic randomized-controlled single-blind trial. A total of 1000 participants with mild to moderate symptoms of depression from various settings including in- and outpatient services will be randomized to an online psychological treatment or care as usual (CAU). We hypothesize that the intervention will be superior to CAU in reducing depressive symptoms assessed with the Personal Health Questionnaire (PHQ-9, primary outcome measure) following the intervention (12 wks) and at follow-up (24 and 48 wks). Further outcome parameters include quality of life, use of health care resources and attitude towards online psychological treatments.DiscussionThe study will yield meaningful answers to the question of whether online psychological treatment can contribute to the effective and efficient prevention and treatment of mild to moderate depression on a population level with a low barrier to entry.
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23.
  • Koettgen, Anna, et al. (författare)
  • Genome-wide association analyses identify 18 new loci associated with serum urate concentrations
  • 2013
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:2, s. 145-154
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SEMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout.
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24.
  • Leo, Isabelle Rose, et al. (författare)
  • Integrative multi-omics and drug response profiling of childhood acute lymphoblastic leukemia cell lines
  • 2022
  • Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Although standard-of-care chemotherapeutics are sufficient for most ALL cases, there are subsets of patients with poor response who relapse in disease. The biology underlying differences between subtypes and their response to therapy has only partially been explained by genetic and transcriptomic profiling. Here, we perform comprehensive multi-omic analyses of 49 readily available childhood ALL cell lines, using proteomics, transcriptomics, and pharmacoproteomic characterization. We connect the molecular phenotypes with drug responses to 528 oncology drugs, identifying drug correlations as well as lineage-dependent correlations. We also identify the diacylglycerol-analog bryostatin-1 as a therapeutic candidate in the MEF2D-HNRNPUL1 fusion high-risk subtype, for which this drug activates pro-apoptotic ERK signaling associated with molecular mediators of pre-B cell negative selection. Our data is the foundation for the interactive online Functional Omics Resource of ALL (FORALL) with navigable proteomics, transcriptomics, and drug sensitivity profiles at https://proteomics.se/fora.
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25.
  • Li, Haoyuan, et al. (författare)
  • Diffraction data from aerosolized Coliphage PR772 virus particles imaged with the Linac Coherent Light Source
  • 2020
  • Ingår i: Scientific Data. - : NATURE RESEARCH. - 2052-4463. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Single Particle Imaging (SPI) with intense coherent X-ray pulses from X-ray free-electron lasers (XFELs) has the potential to produce molecular structures without the need for crystallization or freezing. Here we present a dataset of 285,944 diffraction patterns from aerosolized Coliphage PR772 virus particles injected into the femtosecond X-ray pulses of the Linac Coherent Light Source (LCLS). Additional exposures with background information are also deposited. The diffraction data were collected at the Atomic, Molecular and Optical Science Instrument (AMO) of the LCLS in 4 experimental beam times during a period of four years. The photon energy was either 1.2 or 1.7keV and the pulse energy was between 2 and 4 mJ in a focal spot of about 1.3 mu m x 1.7 mu m full width at half maximum (FWHM). The X-ray laser pulses captured the particles in random orientations. The data offer insight into aerosolised virus particles in the gas phase, contain information relevant to improving experimental parameters, and provide a basis for developing algorithms for image analysis and reconstruction.
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26.
  • Liegl, Gregor, et al. (författare)
  • Physical performance tasks were linked to the PROMIS physical function metric in patients undergoing hemodialysis
  • 2023
  • Ingår i: Journal of Clinical Epidemiology. - 0895-4356. ; 159, s. 128-138
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: To investigate whether a multi-item performance outcome measure, the physical performance test (PPT), can be calibrated to a common scale with patient-reported outcome measures, using the Patient-Reported Outcomes Measurement Information System (PROMIS) physical function (PF) metric. Study Design and Setting: We analyzed baseline data (N = 1,113) from the CONVINCE study, an international trial in end-stage kidney disease patients comparing high-dose hemodiafiltration with high-flux hemodialysis. Assumptions of item response theory (IRT) modelling were investigated for the combined set of the nine-item PPT and a four-item PROMIS PF short form (PROMIS-PF4a). We applied unidimensional IRT linking for calibrating the PPT to the PROMIS PF metric. Results: Although some evidence for multidimensionality was found, classical test statistics (Cronbach's Alpha = 0.93), Mokken (Loevinger's H = 0.50), and bifactor analysis (explained common variance = 0.65) indicated that PPT and PROMIS-PF4a items can be used to assess a common PF construct. On the group level, the agreement between PROMIS-PF4a and linked PPT scores was stable across several subsamples. On the individual level, scores differed considerably. Conclusion: We found preliminary evidence that the PPT can be linked to the PROMIS PF metric in hemodialysis patients, enabling group comparisons across patient-reported outcome and performance outcome measures. Alternative linking methods should be applied in future studies using a more comprehensive PROMIS PF item set.
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27.
  • Locke, Adam E, et al. (författare)
  • Genetic studies of body mass index yield new insights for obesity biology.
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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28.
  • Melin, Beatrice S., et al. (författare)
  • Genome-wide association study of glioma subtypes identifies specific differences in genetic susceptibility to glioblastoma and non-glioblastoma tumors
  • 2017
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 789-794
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have transformed our understanding of glioma susceptibility, but individual studies have had limited power to identify risk loci. We performed a meta-analysis of existing GWAS and two new GWAS, which totaled 12,496 cases and 18,190 controls. We identified five new loci for glioblastoma (GBM) at 1p31.3 (rs12752552; P = 2.04 x 10(-9), odds ratio (OR) = 1.22), 11q14.1 (rs11233250; P = 9.95 x 10(-10), OR = 1.24), 16p13.3 (rs2562152; P = 1.93 x 10-8, OR = 1.21), 16q12.1 (rs10852606; P = 1.29 x 10(-11), OR = 1.18) and 22q13.1 (rs2235573; P = 1.76 x 10(-10), OR = 1.15), as well as eight loci for non-GBM tumors at 1q32.1 (rs4252707; P = 3.34 x 10(-9), OR = 1.19), 1q44 (rs12076373; P = 2.63 x 10(-10), OR = 1.23), 2q33.3 (rs7572263; P = 2.18 x 10(-10), OR = 1.20), 3p14.1 (rs11706832; P = 7.66 x 10(-9), OR = 1.15), 10q24.33 (rs11598018; P = 3.39 x 10-8, OR = 1.14), 11q21 (rs7107785; P = 3.87 x 10(-10), OR = 1.16), 14q12 (rs10131032; P = 5.07 x 10(-11), OR = 1.33) and 16p13.3 (rs3751667; P = 2.61 x 10(-9), OR = 1.18). These data substantiate that genetic susceptibility to GBM and non-GBM tumors are highly distinct, which likely reflects different etiology.
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29.
  • Meyer, Björn, et al. (författare)
  • Effects of an Internet intervention (Deprexis) on severe depression symptoms : Randomized controlled trial
  • 2015
  • Ingår i: Internet Interventions. - : Elsevier. - 2214-7829. ; 2:1, s. 48-59
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundStudies have shown that certain Internet interventions can help alleviate depression. However, many such interventions contain personal support elements, making it difficult to ascertain whether the program or the support drives the effects. Studies are needed to investigate whether Internet interventions contribute to symptom reduction even when they are delivered without personal support, and even among severely depressed individuals who often receive other forms of treatment.ObjectiveThis randomized controlled trial aimed to examine the effect of an Internet intervention that was deployed without personal support (“Deprexis”) among adults with initially severe depression symptoms.MethodsAdults recruited from a range of sources who had exceeded the threshold for severe depression (PHQ-9 ≥ 15) in a pre-screening assessment and met inclusion criteria were randomized (N = 163) to the intervention (3 months program access; n = 78) or care-as-usual/waitlist control (n = 85). A diagnostic screening interview was administered by telephone at baseline to all participants. Online assessments were administered at baseline, 3 months (post-treatment), and 6 months (follow-up). The main outcome was the Patient Health Questionnaire (PHQ-9) between baseline and post-treatment.ResultsEighty-two percent of randomized participants were reached for the post-treatment assessment. Results for the intention-to-treat (ITT) sample showed significant intervention effects on depression reduction between baseline and post-treatment (linear mixed model [MM], F1,155.6 = 9.00, p < .01, for the time by condition interaction), with a medium between-group effect size, Cohen's d = 0.57 (95% CI: 0.22–0.92). Group differences in depression severity at follow-up were marginally significant in the ITT sample, t (119) = 1.83, p = 0.07, and smaller than at post-treatment (PHQ-9, d = 0.33, 95% CI: − 0.03–0.69). The number needed to treat (NNT) at post-treatment was 5, with 38% of participants in the intervention group achieving response (at least 50% PHQ-9 symptom change, plus post-treatment score < 10), compared to 17% in the control group, p < 0.01. Effects on secondary outcomes, including anxiety, health-related quality of life, and somatic symptoms, were not significant, with the exception of significant effects on anxiety reduction in PP analyses. Early ratings of program helpfulness/alliance (after 3 weeks) predicted pre–post depression reduction, controlling for baseline severity and early symptom change.ConclusionsThese results replicate and extend previous findings by showing that Deprexis can facilitate symptomatic improvement over 3 months and, perhaps to a lesser degree, up until 6 months among adults with initially severe depression.
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30.
  • Morbelli, Silvia, et al. (författare)
  • Metabolic patterns across core features in dementia with lewy bodies
  • 2019
  • Ingår i: Annals of Neurology. - : John Wiley & Sons. - 0364-5134 .- 1531-8249. ; 85:5, s. 715-725
  • Tidskriftsartikel (refereegranskat)abstract
    • ObjectiveTo identify brain regions whose metabolic impairment contributes to dementia with Lewy bodies (DLB) clinical core features expression and to assess the influence of severity of global cognitive impairment on the DLB hypometabolic pattern.MethodsBrain fluorodeoxyglucose positron emission tomography and information on core features were available in 171 patients belonging to the imaging repository of the European DLB Consortium. Principal component analysis was applied to identify brain regions relevant to the local data variance. A linear regression model was applied to generate core‐feature–specific patterns controlling for the main confounding variables (Mini‐Mental State Examination [MMSE], age, education, gender, and center). Regression analysis to the locally normalized intensities was performed to generate an MMSE‐sensitive map.ResultsParkinsonism negatively covaried with bilateral parietal, precuneus, and anterior cingulate metabolism; visual hallucinations (VH) with bilateral dorsolateral–frontal cortex, posterior cingulate, and parietal metabolism; and rapid eye movement sleep behavior disorder (RBD) with bilateral parieto‐occipital cortex, precuneus, and ventrolateral–frontal metabolism. VH and RBD shared a positive covariance with metabolism in the medial temporal lobe, cerebellum, brainstem, basal ganglia, thalami, and orbitofrontal and sensorimotor cortex. Cognitive fluctuations negatively covaried with occipital metabolism and positively with parietal lobe metabolism. MMSE positively covaried with metabolism in the left superior frontal gyrus, bilateral–parietal cortex, and left precuneus, and negatively with metabolism in the insula, medial frontal gyrus, hippocampus in the left hemisphere, and right cerebellum.InterpretationRegions of more preserved metabolism are relatively consistent across the variegate DLB spectrum. By contrast, core features were associated with more prominent hypometabolism in specific regions, thus suggesting a close clinical–imaging correlation, reflecting the interplay between topography of neurodegeneration and clinical presentation in DLB patients. Ann Neurol 2019;85:715–725
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31.
  • Moritz, Steffen, et al. (författare)
  • Beyond words : Sensory properties of depressive thoughts
  • 2014
  • Ingår i: Cognition & Emotion. - : ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD. - 0269-9931 .- 1464-0600. ; 28:6, s. 1047-1056
  • Tidskriftsartikel (refereegranskat)abstract
    • Verbal thoughts (such as negative cognitions) and sensory phenomena (such as visual mental imagery) are usually conceptualised as distinct mental experiences. The present study examined to what extent depressive thoughts are accompanied by sensory experiences and how this is associated with symptom severity, insight of illness and quality of life. A large sample of mildly to moderately depressed patients (N = 356) was recruited from multiple sources and asked about sensory properties of their depressive thoughts in an online study. Diagnostic status and symptom severity were established over a telephone interview with trained raters. Sensory properties of negative thoughts were reported by 56.5% of the sample (i.e., sensation in at least one sensory modality). The highest prevalence was seen for bodily (39.6%) followed by auditory (30.6%) and visual (27.2%) sensations. Patients reporting sensory properties of thoughts showed more severe psychopathological symptoms than those who did not. The degree of perceptuality was marginally associated with quality of life. The findings support the notion that depressive thoughts are not only verbal but commonly accompanied by sensory experiences. The perceptuality of depressive thoughts and the resulting sense of authenticity may contribute to the emotional impact and pervasiveness of such thoughts, making them difficult to dismiss for their holder.
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32.
  • Petropoulos, Fotios, et al. (författare)
  • Operational Research : methods and applications
  • 2024
  • Ingår i: Journal of the Operational Research Society. - : Taylor & Francis Group. - 0160-5682 .- 1476-9360. ; 75:3, s. 423-617
  • Forskningsöversikt (refereegranskat)abstract
    • Throughout its history, Operational Research has evolved to include methods, models and algorithms that have been applied to a wide range of contexts. This encyclopedic article consists of two main sections: methods and applications. The first summarises the up-to-date knowledge and provides an overview of the state-of-the-art methods and key developments in the various subdomains of the field. The second offers a wide-ranging list of areas where Operational Research has been applied. The article is meant to be read in a nonlinear fashion and used as a point of reference by a diverse pool of readers: academics, researchers, students, and practitioners. The entries within the methods and applications sections are presented in alphabetical order. The authors dedicate this paper to the 2023 Turkey/Syria earthquake victims. We sincerely hope that advances in OR will play a role towards minimising the pain and suffering caused by this and future catastrophes.
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33.
  • Philipp Klein, Jan, et al. (författare)
  • Effects of a Psychological Internet Intervention in the Treatment of Mild to Moderate Depressive Symptoms: Results of the EVIDENT Study, a Randomized Controlled Trial
  • 2016
  • Ingår i: Psychotherapy and Psychosomatics. - : KARGER. - 0033-3190 .- 1423-0348. ; 85:4, s. 218-228
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Mild to moderate depressive symptoms are common but often remain unrecognized and treated inadequately. We hypothesized that an Internet intervention in addition to usual care is superior to care as usual alone (CAU) in the treatment of mild to moderate depressive symptoms in adults. Methods: This trial was controlled, randomized and assessor-blinded. Participants with mild to moderate depressive symptoms (Patient Health Questionnaire, PHQ-9, score 5-14) were recruited from clinical and non-clinical set-tings and randomized to either CAU or a 12-week Internet intervention (Deprexis) adjunctive to usual care. Outcomes were assessed at baseline, 3 months (post-assessment) and 6 months (follow-up). The primary outcome measure was self-rated depression severity (PHQ-9). The main analysis was based on the intention-to-treat principle and used linear mixed models. Results: A total of 1,013 participants were randomized. Changes in PHQ-9 from baseline differed significantly between groups (t(825) = 6.12, p amp;lt; 0.001 for the main effect of group). The post-assessment between-group effect size in favour of the intervention was d = 0.39 (95% CI: 0.13-0.64). It was stable at follow-up, with d = 0.32 (95% CI: 0.06-0.69). The rate of participants experiencing at least minimally clinically important PHQ-9 change at the post-assessment was higher in the intervention group (35.6 vs. 20.2%) with a number needed to treat of 7 (95% CI: 5-10). Conclusions: The Internet intervention examined in this trial was superior to CAU alone in reducing mild to moderate depressive symptoms. The magnitude of the effect is clinically important and has public health implications. (C) 2016 S. Karger AG, Basel
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34.
  • Ried, Janina S., et al. (författare)
  • A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
  • 2016
  • Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
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35.
  • Salyers, Michelle P, et al. (författare)
  • A coding system to measure elements of shared decision making during psychiatric visits
  • 2012
  • Ingår i: Psychiatric Services. - : American Psychiatric Association Publishing. - 1075-2730 .- 1557-9700. ; 63:8, s. 779-784
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Shared decision making is widely recognized to facilitate effective health care. The purpose of this study was to assess the applicability and usefulness of a scale to measure the presence and extent of shared decision making in clinical decisions in psychiatric practice. Methods: A coding scheme assessing shared decision making in general medical settings was adapted to mental health settings, and a manual for using the scheme was created. Trained raters used the adapted scale to analyze 170 audio-recordings of medication check-up visits with either psychiatrists or nurse practitioners. The scale assessed the level of shared decision making based on the presence of nine specific elements. Interrater reliability was examined, and the frequency with which elements of shared decision making were observed was documented. The association between visit length and extent of shared decision making was also examined. Results: Interrater reliability among three raters on a subset of 20 recordings ranged from 67% to 100% agreement for the presence of each of the nine elements of shared decision making and 100% for the agreement between provider and consumer on decisions made. Of the 170 sessions, 128 (75%) included a clinical decision. Just over half of the decisions (53%) met minimum criteria for shared decision making. Shared decision making was not related to visit length after the analysis controlled for the complexity of the decision. Conclusions: The rating scale appears to reliably assess shared decision making in psychiatric practice and could be helpful for future research, training, and implementation efforts.
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36.
  • Soliman, Amira, 1980-, et al. (författare)
  • Adopting transfer learning for neuroimaging : a comparative analysis with a custom 3D convolution neural network model
  • 2022
  • Ingår i: BMC Medical Informatics and Decision Making. - London : BioMed Central (BMC). - 1472-6947. ; 22, s. 1-15
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: In recent years, neuroimaging with deep learning (DL) algorithms have made remarkable advances in the diagnosis of neurodegenerative disorders. However, applying DL in different medical domains is usually challenged by lack of labeled data. To address this challenge, transfer learning (TL) has been applied to use state-of-the-art convolution neural networks pre-trained on natural images. Yet, there are differences in characteristics between medical and natural images, also image classification and targeted medical diagnosis tasks. The purpose of this study is to investigate the performance of specialized and TL in the classification of neurodegenerative disorders using 3D volumes of 18F-FDG-PET brain scans. Results: Results show that TL models are suboptimal for classification of neurodegenerative disorders, especially when the objective is to separate more than two disorders. Additionally, specialized CNN model provides better interpretations of predicted diagnosis. Conclusions: TL can indeed lead to superior performance on binary classification in timely and data efficient manner, yet for detecting more than a single disorder, TL models do not perform well. Additionally, custom 3D model performs comparably to TL models for binary classification, and interestingly perform better for diagnosis of multiple disorders. The results confirm the superiority of the custom 3D-CNN in providing better explainable model compared to TL adopted ones. © 2022, The Author(s).
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37.
  • Stevens, Kristen N, et al. (författare)
  • 19p13.1 is a triple negative-specific breast cancer susceptibility locus
  • 2012
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 72, s. 1795-
  • Tidskriftsartikel (refereegranskat)abstract
    • The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with risk of ovarian cancer. Here we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly associated with ER-negative breast cancer risk [rs8170 Odds Ratio (OR)=1.10, 95% Confidence Interval (CI) 1.05 - 1.15, p=3.49 x 10-5] and triple negative (TN) (ER, PR and HER2 negative) breast cancer [rs8170 OR=1.22, 95% CI 1.13 - 1.31, p=2.22 x 10-7]. However, rs8170 was no longer associated with ER-negative breast cancer risk when TN cases were excluded [OR=0.98, 95% CI 0.89 - 1.07, p=0.62]. In addition, a combined analysis of TN cases from BCAC and the Triple Negative Breast Cancer Consortium (TNBCC) (n=3,566) identified a genome-wide significant association between rs8170 and TN breast cancer risk [OR=1.25, 95% CI 1.18 - 1.33, p=3.31 x 10-13]. Thus, 19p13.1 is the first triple negative-specific breast cancer risk locus and the first locus specific to a histological subtype defined by ER, PR, and HER2 to be identified. These findings provide convincing evidence that genetic susceptibility to breast cancer varies by tumor subtype and that triple negative tumors and other subtypes likely arise through distinct etiologic pathways.
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38.
  • Stockbauer, Anna, et al. (författare)
  • Metabolic network alterations as a supportive biomarker in dementia with Lewy bodies with preserved dopamine transmission
  • 2024
  • Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : SPRINGER. - 1619-7070 .- 1619-7089. ; 51:4, s. 1023-1034
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Metabolic network analysis of FDG-PET utilizes an index of inter-regional correlation of resting state glucose metabolism and has been proven to provide complementary information regarding the disease process in parkinsonian syndromes. The goals of this study were (i) to evaluate pattern similarities of glucose metabolism and network connectivity in dementia with Lewy bodies (DLB) subjects with subthreshold dopaminergic loss compared to advanced disease stages and to (ii) investigate metabolic network alterations of FDG-PET for discrimination of patients with early DLB from other neurodegenerative disorders (Alzheimer's disease, Parkinson's disease, multiple system atrophy) at individual patient level via principal component analysis (PCA).Methods FDG-PETs of subjects with probable or possible DLB (n = 22) without significant dopamine deficiency (z-score < 2 in putamen binding loss on DaT-SPECT compared to healthy controls (HC)) were scaled by global-mean, prior to volume-of-interest-based analyses of relative glucose metabolism. Single region metabolic changes and network connectivity changes were compared against HC (n = 23) and against DLB subjects with significant dopamine deficiency (n = 86). PCA was applied to test discrimination of patients with DLB from disease controls (n = 101) at individual patient level.Results Similar patterns of hypo- (parietal- and occipital cortex) and hypermetabolism (basal ganglia, limbic system, motor cortices) were observed in DLB patients with and without significant dopamine deficiency when compared to HC. Metabolic connectivity alterations correlated between DLB patients with and without significant dopamine deficiency (R2 = 0.597, p < 0.01). A PCA trained by DLB patients with dopamine deficiency and HC discriminated DLB patients without significant dopaminergic loss from other neurodegenerative parkinsonian disorders at individual patient level (area-under-the-curve (AUC): 0.912).Conclusion Disease-specific patterns of altered glucose metabolism and altered metabolic networks are present in DLB subjects without significant dopaminergic loss. Metabolic network alterations in FDG-PET can act as a supporting biomarker in the subgroup of DLB patients without significant dopaminergic loss at symptoms onset.
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39.
  • Takahashi, Hannah, et al. (författare)
  • Mendelian randomisation study of the relationship between vitamin D and risk of glioma
  • 2018
  • Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • To examine for a causal relationship between vitamin D and glioma risk we performed an analysis of genetic variants associated with serum 25-hydroxyvitamin D (25(OH) D) levels using Mendelian randomisation (MR), an approach unaffected by biases from confounding. Two-sample MR was undertaken using genome-wide association study data. Single nucleotide polymorphisms (SNPs) associated with 25(OH) D levels were used as instrumental variables (IVs). We calculated MR estimates for the odds ratio (OR) for 25(OH) D levels with glioma using SNP-glioma estimates from 12,488 cases and 18,169 controls, using inverse-variance weighted (IVW) and maximum likelihood estimation (MLE) methods. A non-significant association between 25(OH) D levels and glioma risk was shown using both the IVW (OR = 1.21, 95% confidence interval [CI] = 0.90-1.62, P = 0.201) and MLE (OR = 1.20, 95% CI = 0.98-1.48, P = 0.083) methods. In an exploratory analysis of tumour subtype, an inverse relationship between 25(OH)D levels and glioblastoma (GBM) risk was identified using the MLE method (OR = 0.62, 95% CI = 0.43-0.89, P = 0.010), but not the IVW method (OR = 0.62, 95% CI = 0.37-1.04, P = 0.070). No statistically significant association was shown between 25(OH) D levels and non-GBM glioma. Our results do not provide evidence for a causal relationship between 25(OH) D levels and all forms of glioma risk. More evidence is required to explore the relationship between 25(OH) D levels and risk of GBM.
  •  
40.
  • Terwee, Caroline B., et al. (författare)
  • Patient-reported outcomes for people with diabetes : what and how to measure? A narrative review
  • 2023
  • Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 66:8, s. 1357-1377
  • Forskningsöversikt (refereegranskat)abstract
    • Patient-reported outcomes (PROs) are valuable for shared decision making and research. Patient-reported outcome measures (PROMs) are questionnaires used to measure PROs, such as health-related quality of life (HRQL). Although core outcome sets for trials and clinical practice have been developed separately, they, as well as other initiatives, recommend different PROs and PROMs. In research and clinical practice, different PROMs are used (some generic, some disease-specific), which measure many different things. This is a threat to the validity of research and clinical findings in the field of diabetes. In this narrative review, we aim to provide recommendations for the selection of relevant PROs and psychometrically sound PROMs for people with diabetes for use in clinical practice and research. Based on a general conceptual framework of PROs, we suggest that relevant PROs to measure in people with diabetes are: disease-specific symptoms (e.g. worries about hypoglycaemia and diabetes distress), general symptoms (e.g. fatigue and depression), functional status, general health perceptions and overall quality of life. Generic PROMs such as the 36-Item Short Form Health Survey (SF-36), WHO Disability Assessment Schedule (WHODAS 2.0), or Patient-Reported Outcomes Measurement Information System (PROMIS) measures could be considered to measure commonly relevant PROs, supplemented with disease-specific PROMs where needed. However, none of the existing diabetes-specific PROM scales has been sufficiently validated, although the Diabetes Symptom Self-Care Inventory (DSSCI) for measuring diabetes-specific symptoms and the Diabetes Distress Scale (DDS) and Problem Areas in Diabetes (PAID) for measuring distress showed sufficient content validity. Standardisation and use of relevant PROs and psychometrically sound PROMs can help inform people with diabetes about the expected course of disease and treatment, for shared decision making, to monitor outcomes and to improve healthcare. We recommend further validation studies of diabetes-specific PROMs that have sufficient content validity for measuring disease-specific symptoms and consider generic item banks developed based on item response theory for measuring commonly relevant PROs.
  •  
41.
  • The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
  • 2022
  • Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
  •  
42.
  • Thompson, Paul M., et al. (författare)
  • The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
  • 2014
  • Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
  • Tidskriftsartikel (refereegranskat)abstract
    • The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
  •  
43.
  • Wanner, Matthias, et al. (författare)
  • Towards a Cyclical Concept of Real-World Laboratories A Transdisciplinary Research Practice for Sustainability Transitions
  • 2018
  • Ingår i: DISP. - : Informa UK Limited. - 0251-3625 .- 2166-8604. ; 54:2, s. 94-114
  • Tidskriftsartikel (refereegranskat)abstract
    • The transformative research approach of Real-World Laboratories (RWL) has recently attracted attention in German sustainability science. Some definitions and understandings have been published, but guidelines and procedural quality criteria for establishing and running a RWL are still missing. To address this gap, this article has two aims. First, it aims to derive key components of RWLs from the current discourse on RWLs and similar, but more elaborated research approaches. Second, it aims to transfer these key components into a comprehensive research practice. This practice is illustrated by the RWL process in the project "Well-being Transformation Wuppertal" (WTW). Methodologically, the article builds on a review of RWL-related approaches for collaborative, intervention-oriented research. This includes transition management, transdisciplinary process models and action research. Based on this review, eight key components for RWLs are proposed. They position RWLs as a normatively framed approach that aims to contribute to local action for sustainable development and the empowerment of change agents. The approach uses transdisciplinary methods of knowledge integration and engages in cyclical real-world interventions within certain spatial and content-related boundaries. The components are transferred into a flow-chart, detailing process steps, aims, responsibilities and overall principles for putting RWLs into practice. Thus, a hitherto missing tool for designing and running RWLs is provided. Then, the RWL in the district of Mirke, Wuppertal, is used as an empirical example to illustrate the application of the flowchart and related key components. Consecutive discussions centre on the different roles of researchers and practitioners in the research process, as well as the relevance of an underlying theory of change for effective interventions. Finally, critical reflection, application and amendment of the proposed flowchart are encouraged.
  •  
44.
  • Westerlind, Helga, et al. (författare)
  • Dense genotyping of immune-related loci identifies HLA variants associated with increased risk of collagenous colitis.
  • 2017
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 66:3, s. 421-428
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: Collagenous colitis (CC) is a major cause of chronic non-bloody diarrhoea, particularly in the elderly female population. The aetiology of CC is unknown, and still poor is the understanding of its pathogenesis. This possibly involves dysregulated inflammation and immune-mediated reactions in genetically predisposed individuals, but the contribution of genetic factors to CC is underinvestigated. We systematically tested immune-related genes known to impact the risk of several autoimmune diseases for their potential CC-predisposing role.DESIGN: Three independent cohorts of histologically confirmed CC cases (N=314) and controls (N=4299) from Sweden and Germany were included in a 2-step association analysis. Immunochip and targeted single nucleotide polymorphism (SNP) genotype data were produced, respectively, for discovery and replication purposes. Classical human leucocyte antigen (HLA) variants at 2-digit and 4-digit resolution were obtained via imputation from single marker genotypes. SNPs and HLA variants passing quality control filters were tested for association with CC with logistic regression adjusting for age, sex and country of origin.RESULTS: Forty-two markers gave rise to genome-wide significant association signals, all contained within the HLA region on chromosome 6 (best p=4.2×10(-10) for SNP rs4143332). Among the HLA variants, most pronounced risk effects were observed for 8.1 haplotype alleles including DQ2.5, which was targeted and confirmed in the replication data set (p=2.3×10(-11); OR=2.06; 95% CI (1.67 to 2.55) in the combined analysis).CONCLUSIONS: HLA genotype associates with CC, thus implicating HLA-related immune mechanisms in its pathogenesis.
  •  
45.
  • Zhang, Hong, et al. (författare)
  • IL-6 trans-signaling promotes pancreatitis-associated lung injury and lethality
  • 2013
  • Ingår i: Journal of Clinical Investigation. - 0021-9738. ; 123:3, s. 1019-1031
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute lung injury (ALI) is an inflammatory disease with a high mortality rate. Although typically seen in individuals with sepsis, ALI is also a major complication in severe acute pancreatitis (SAP). The pathophysiology of SAP-associated ALI is poorly understood, but elevated serum levels of IL-6 is a reliable marker for disease severity. Here, we used a mouse model of acute pancreatitis–associated (AP-associated) ALI to determine the role of IL-6 in ALI lethality. Il6-deficient mice had a lower death rate compared with wild-type mice with AP, while mice injected with IL-6 were more likely to develop lethal ALI. We found that inflammation-associated NF-κB induced myeloid cell secretion of IL-6, and the effects of secreted IL-6 were mediated by complexation with soluble IL-6 receptor, a process known as trans-signaling. IL-6 trans-signaling stimulated phosphorylation of STAT3 and production of the neutrophil attractant CXCL1 in pancreatic acinar cells. Examination of human samples revealed expression of IL-6 in combination with soluble IL-6 receptor was a reliable predictor of ALI in SAP. These results demonstrate that IL-6 trans-signaling is an essential mediator of ALI in SAP across species and suggest that therapeutic inhibition of IL-6 may prevent SAP-associated ALI.
  •  
46.
  • 2019
  • Tidskriftsartikel (refereegranskat)
  •  
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