| 1. |
- Holmes, Michael V., et al.
(författare)
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Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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| 2. |
- Thiel, U, et al.
(författare)
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Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: a retrospective assessment
- 2013
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Ingår i: British Journal of Cancer. - : Cancer Research UK. - 0007-0920 .- 1532-1827. ; 109:10, s. 2523-2532
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. less thanbrgreater than less thanbrgreater thanMethods: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. less thanbrgreater than less thanbrgreater thanResults: Three-year OS was 20% (s. e.+/- 8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s. e.+/- 10%) and 11% (s. e.+/- 6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. less thanbrgreater than less thanbrgreater thanConclusion: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials.
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| 3. |
- Ballantyne, Kaye N., et al.
(författare)
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Toward Male Individualization with Rapidly Mutating Y-Chromosomal Short Tandem Repeats
- 2014
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Ingår i: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 35:8, s. 1021-1032
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Tidskriftsartikel (refereegranskat)abstract
- Relevant for various areas of human genetics, Y-chromosomal short tandem repeats (Y-STRs) are commonly used for testing close paternal relationships among individuals and populations, and for male lineage identification. However, even the widely used 17-loci Yfiler set cannot resolve individuals and populations completely. Here, 52 centers generated quality-controlled data of 13 rapidly mutating (RM) Y-STRs in 14,644 related and unrelated males from 111 worldwide populations. Strikingly, greater than99% of the 12,272 unrelated males were completely individualized. Haplotype diversity was extremely high (global: 0.9999985, regional: 0.99836-0.9999988). Haplotype sharing between populations was almost absent except for six (0.05%) of the 12,156 haplotypes. Haplotype sharing within populations was generally rare (0.8% nonunique haplotypes), significantly lower in urban (0.9%) than rural (2.1%) and highest in endogamous groups (14.3%). Analysis of molecular variance revealed 99.98% of variation within populations, 0.018% among populations within groups, and 0.002% among groups. Of the 2,372 newly and 156 previously typed male relative pairs, 29% were differentiated including 27% of the 2,378 father-son pairs. Relative to Yfiler, haplotype diversity was increased in 86% of the populations tested and overall male relative differentiation was raised by 23.5%. Our study demonstrates the value of RMY-STRs in identifying and separating unrelated and related males and provides a reference database.
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| 4. |
- Ludewig, Kristin, et al.
(författare)
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Phenology and morphology of the invasive legume Lupinus polyphyllus along a latitudinal gradient in Europe
- 2022
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Ingår i: NeoBiota. - : Pensoft Publishers. - 1619-0033 .- 1314-2488. ; 78
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Tidskriftsartikel (refereegranskat)abstract
- Plant phenology, i. e. the timing of life cycle events, is related to individual fitness and species distributionranges. Temperature is one of the most important drivers of plant phenology together with day length.The adaptation of their phenology may be important for the success of invasive plant species. The presentstudy aims at understanding how the performance and the phenology of the invasive legume Lupinuspolyphyllus vary with latitude. We sampled data across a >2000 km latitudinal gradient from Centralto Northern Europe. We quantified variation in phenology of flowering and fruiting of L. polyphyllususing >1600 digital photos of inflorescences from 220 individual plants observed weekly at 22 sites. Theday of the year at which different phenological phases were reached, increased 1.3–1.8 days per degreelatitude, whereas the growing degree days (gdd) required for these phenological phases decreased 5–16 gddper degree latitude. However, this difference disappeared, when the day length of each day included inthe calculation of gdd was considered. The day of the year of the earliest and the latest climatic zone toreach any of the three studied phenological phases differed by 23–30 days and temperature requirementsto reach these stages differed between 62 and 236 gdd. Probably, the invasion of this species will furtherincrease in the northern part of Europe over the next decades due to climate warming. For invasive speciescontrol, our results suggest that in countries with a large latitudinal extent, the mowing date should shiftby ca. one week per 500 km at sites with similar elevations.
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| 5. |
- Ludewig, Kristin, et al.
(författare)
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Phenology of Lupinus polyphyllus from Central to Northern Europe
- 2022
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Annan publikationabstract
- Plant phenology, i. e. the timing of life cycle events, is related to individual fitness and species distribution ranges. Among the environmental factors, phenology is mostly driven by temperature and day length. Rapid adaptation of their phenology may also be important for the success of invasive plant species. Our main aim was to understand how the performance, timing, and temperature dependence of the phenology of the invasive legume Lupinus polyphyllus varies with latitude. L. polyphyllus is one of the most frequent invasive species in Europe, and the gained information may help to make management more effective by adjustments to latitude and phenology.Methods:We quantified variation in phenology across a >2000 km latitudinal gradient from Central to Northern Europe. We sampled data of flowering and fruiting of L. polyphyllus using >1600 digital photos of inflorescences from 220 individual plants observed weekly at 22 locations. We calculated the accumulated growing degree days for each observation date at each site from the temperature data of the meteorological stations, which are listed in the metadata of the dataset.
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| 6. |
- Wittchen, Hans-Ulrich, et al.
(författare)
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The need for a behavioural science focus in research on mental health and mental disorders
- 2014
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Ingår i: International Journal of Methods in Psychiatric Research. - : Wiley-Blackwell. - 1049-8931 .- 1557-0657. ; 23, s. 28-40
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Tidskriftsartikel (refereegranskat)abstract
- Psychology as a science offers an enormous diversity of theories, principles, and methodological approaches to understand mental health, abnormal functions and behaviours and mental disorders. A selected overview of the scope, current topics as well as strength and gaps in Psychological Science may help to depict the advances needed to inform future research agendas specifically on mental health and mental disorders. From an integrative psychological perspective, most maladaptive health behaviours and mental disorders can be conceptualized as the result of developmental dysfunctions of psychological functions and processes as well as neurobiological and genetic processes that interact with the environment. The paper presents and discusses an integrative translational model, linking basic and experimental research with clinical research as well as population-based prospective-longitudinal studies. This model provides a conceptual framework to identify how individual vulnerabilities interact with environment over time, and promote critical behaviours that might act as proximal risk factors for ill-health and mental disorders. Within the models framework, such improved knowledge is also expected to better delineate targeted preventive and therapeutic interventions that prevent further escalation in early stages before the full disorder and further complications thereof develop. In contrast to conventional personalized medicine that typically targets individual (genetic) variation of patients who already have developed a disease to improve medical treatment, the proposed framework model, linked to a concerted funding programme of the Science of Behaviour Change, carries the promise of improved diagnosis, treatment and prevention of health-risk behaviour constellations as well as mental disorders.
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| 7. |
- Emmelkamp, Paul M.G., et al.
(författare)
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Advancing psychotherapy and evidence-based psychological interventions
- 2014
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Ingår i: International Journal of Methods in Psychiatric Research. - : John Wiley & Sons. - 1049-8931 .- 1557-0657. ; 23:S1, s. 58-91
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Tidskriftsartikel (refereegranskat)abstract
- Psychological models of mental disorders guide research into psychological and environmental factors that elicit and maintain mental disorders as well as interventions to reduce them. This paper addresses four areas. (1) Psychological models of mental disorders have become increasingly transdiagnostic, focusing on core cognitive endophenotypes of psychopathology from an integrative cognitive psychology perspective rather than offering explanations for unitary mental disorders. It is argued that psychological interventions for mental disorders will increasingly target specific cognitive dysfunctions rather than symptom-based mental disorders as a result. (2) Psychotherapy research still lacks a comprehensive conceptual framework that brings together the wide variety of findings, models and perspectives. Analysing the state-of-the-art in psychotherapy treatment research, “component analyses” aiming at an optimal identification of core ingredients and the mechanisms of change is highlighted as the core need towards improved efficacy and effectiveness of psychotherapy, and improved translation to routine care. (3) In order to provide more effective psychological interventions to children and adolescents, there is a need to develop new and/or improved psychotherapeutic interventions on the basis of developmental psychopathology research taking into account knowledge of mediators and moderators. Developmental neuroscience research might be instrumental to uncover associated aberrant brain processes in children and adolescents with mental health problems and to better examine mechanisms of their correction by means of psychotherapy and psychological interventions. (4) Psychotherapy research needs to broaden in terms of adoption of large-scale public health strategies and treatments that can be applied to more patients in a simpler and cost-effective way. Increased research on efficacy and moderators of Internet-based treatments and e-mental health tools (e.g. to support “real time” clinical decision-making to prevent treatment failure or relapse) might be one promising way forward.
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| 8. |
- Klein, JP, et al.
(författare)
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Time to remission from mild to moderate depressive symptoms: One year results from the EVIDENT-study, an RCT of an internet intervention for depression.
- 2017
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Ingår i: Behaviour Research and Therapy. - : Elsevier BV. - 0005-7967 .- 1873-622X. ; 97, s. 154-162
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Tidskriftsartikel (refereegranskat)abstract
- Background: Internet interventions are effective in treating depressive symptoms but few studies conducted a long-term follow-up. The aim of this study was to test the effectiveness of an internet intervention in increasing the remission rate over a twelve months period.less thanbr /greater thanMethods: A total of 1013 participants with mild to moderate depressive symptoms were randomized to either care as usual alone or a 12-week internet intervention (Deprexis) plus usual care. Self-rated depression severity (PHQ-9) was assessed regularly over twelve months.less thanbr /greater thanResults: Remission rates over time were significantly higher in the intervention group (Cox regression: hazard ratio [HR] 1.31; p = 0.009). The intervention was more effective in the subgroup not taking antidepressant medication (Cox regression: HR 1.88; p less than 0.001). PHQ-change from baseline was greater in the intervention group (linear mixed model [LMM]: p less than 0.001) with the between-group effect gradually decreasing from d = 0.36 at three months to d = 0.13 at twelve months (LMM: group by time interaction: p less than 0.001).less thanbr /greater thanConclusion: This internet intervention can contribute to achieving remission in people with mild to moderate depressive symptoms, especially if they are not on antidepressant medication (Trial Registration: NCT01636752).less thanbr /greater than (Copyright © 2017 Elsevier Ltd. All rights reserved.)
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| 9. |
- Bock, Alexander, 1985-, et al.
(författare)
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VCMass: A Framework for Verification of Coronal Mass Ejection Ensemble Simulations
- 2014
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Konferensbidrag (refereegranskat)abstract
- Supporting the growing field of space weather forecasting, we propose a framework to analyze ensemble simulations of coronal mass ejections. As the current simulation technique requires manual input, uncertainty is introduced into the simulation pipeline which leads to inaccurate predictions. Using our system, the analyst can compare ensemble members against ground truth data (arrival time and geo-effectivity) as well as information derived from satellite imagery. The simulations can be compared on a global basis, based on time-resolved quality measures, and as a 3D volumetric rendering with embedded satellite imagery in a multi-view setup. This flexible framework provides the expert with the tools to increase the knowledge about the, as of yet not fully understood, principles behind the formation of coronal mass ejections.
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| 10. |
- Bock, Alexander, 1985-, et al.
(författare)
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Visual Verification of Space Weather Ensemble Simulations
- 2015
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Ingår i: 2015 IEEE Scientific Visualization Conference (SciVis). - : IEEE. - 9781467397858 ; , s. 17-24
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Konferensbidrag (refereegranskat)abstract
- We propose a system to analyze and contextualize simulations of coronal mass ejections. As current simulation techniques require manual input, uncertainty is introduced into the simulation pipeline leading to inaccurate predictions that can be mitigated through ensemble simulations. We provide the space weather analyst with a multi-view system providing visualizations to: 1. compare ensemble members against ground truth measurements, 2. inspect time-dependent information derived from optical flow analysis of satellite images, and 3. combine satellite images with a volumetric rendering of the simulations. This three-tier workflow provides experts with tools to discover correlations between errors in predictions and simulation parameters, thus increasing knowledge about the evolution and propagation of coronal mass ejections that pose a danger to Earth and interplanetary travel
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