| 1. |
- Dima, Danai, et al.
(författare)
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Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
- 2022
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
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Tidskriftsartikel (refereegranskat)abstract
- Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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| 2. |
- Frangou, Sophia, et al.
(författare)
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Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
- 2022
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Ingår i: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
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Tidskriftsartikel (refereegranskat)abstract
- Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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| 3. |
- Breznau, Nate, et al.
(författare)
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Observing many researchers using the same data and hypothesis reveals a hidden universe of uncertainty
- 2022
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 119:44
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Tidskriftsartikel (refereegranskat)abstract
- This study explores how researchers analytical choices affect the reliability of scientific findings. Most discussions of reliability problems in science focus on systematic biases. We broaden the lens to emphasize the idiosyncrasy of conscious and unconscious decisions that researchers make during data analysis. We coordinated 161 researchers in 73 research teams and observed their research decisions as they used the same data to independently test the same prominent social science hypothesis: that greater immigration reduces support for social policies among the public. In this typical case of social science research, research teams reported both widely diverging numerical findings and substantive conclusions despite identical start conditions. Researchers expertise, prior beliefs, and expectations barely predict the wide variation in research outcomes. More than 95% of the total variance in numerical results remains unexplained even after qualitative coding of all identifiable decisions in each teams workflow. This reveals a universe of uncertainty that remains hidden when considering a single study in isolation. The idiosyncratic nature of how researchers results and conclusions varied is a previously underappreciated explanation for why many scientific hypotheses remain contested. These results call for greater epistemic humility and clarity in reporting scientific findings.
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| 4. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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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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| 5. |
- Satizabal, Claudia L., et al.
(författare)
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Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
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Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
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| 6. |
- Thompson, Paul M., et al.
(författare)
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The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
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Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
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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.
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| 7. |
- Backé, Eva-Maria, et al.
(författare)
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The role of psychosocial stress at work for the development of cardiovascular diseases : a systematic review.
- 2012
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Ingår i: International Archives of Occupational and Environmental Health. - Berlin : Springer Berlin/Heidelberg. - 0340-0131 .- 1432-1246. ; 85:1, s. 67-79
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: A systematic review was carried out to assess evidence for the association between different models of stress at work, and cardiovascular morbidity and mortality. METHODS: A literature search was conducted using five databases (MEDLINE, Cochrane Library, EMBASE, PSYNDEX and PsycINFO). Inclusion criteria for studies were the following: self-reported stress for individual workplaces, prospective study design and incident disease (myocardial infarction, stroke, angina pectoris, high blood pressure). Evaluation, according to the criteria of the Scottish Intercollegiate Guidelines Network, was done by two readers. In case of disagreement, a third reader was involved. RESULTS: Twenty-six publications were included, describing 40 analyses out of 20 cohorts. The risk estimates for work stress were associated with a statistically significant increased risk of cardiovascular disease in 13 out of the 20 cohorts. Associations were significant for 7 out of 13 cohorts applying the demand-control model, all three cohorts using the effort-reward model and 3 out of 6 cohorts investigating other models. Most significant results came from analyses considering only men. Results for the association between job stress and cardiovascular diseases in women were not clear. Associations were weaker in participants above the age of 55. CONCLUSIONS: In accordance with other systematic reviews, this review stresses the importance of psychosocial factors at work in the aetiology of cardiovascular diseases. Besides individual measures to manage stress and to cope with demanding work situations, organisational changes at the workplace need to be considered to find options to reduce occupational risk factors for cardiovascular diseases.
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| 8. |
- Bauer, Friederike U., et al.
(författare)
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Tracing the exhumation history of the Rwenzori Mountains, Albertine Rift, Uganda, using low-temperature thermochronology
- 2013
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Ingår i: Tectonophysics. - : Elsevier BV. - 0040-1951 .- 1879-3266. ; 599, s. 8-28
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Tidskriftsartikel (refereegranskat)abstract
- The Rwenzori Mtns form a striking feature within the Albertine Rift of the East African Rift System. They are made up of a dissected Precambrian metamorphic basement block reaching heights of more than 5 km. Applying low-temperature therrnochronology a complex exhumation history becomes evident, where rock and surface uplift can be traced from Palaeozoic to Neogene times. Fission-track and (U-Th-Sm)/He cooling ages and derived cooling histories allow distinguishing different blocks in the Rwenzori Mtns. In the central part a northern and a southern block are separated by a putative NW-SE trending fault; with the northern block showing distinctly younger apatite fission-track ages (similar to 130 Ma) than the southern block (similar to 300 Ma). Cooling ages in both blocks do not vary significantly with elevation, despite considerable differences in elevation. Thermal history modelling reflects protracted cooling histories. Modelled t-T paths show decoupled blocks that were relocated separately along distinct fault planes, which reactivated pre-existing structures, inherited from Palaeozoic folding and thrusting. Initial cooling affected the Rwenzori area in Silurian to Devonian times, followed by Mesozoic and Cainozoic cooling events. Pre-Neogene evolution seems to be triggered by tectonic processes like the opening of the Indian Ocean and the south Atlantic. From thermochronological data the formation of a Mesozoic Albertine high is conceivable. In Cainozoic times the area was affected by rifting, resulting in differentiated surface uplift. Along the western flank of the Rwenzori Mtns, surface uplift was more pronounced. This is also reflected in their recent topography, formed by accelerated rock uplift in the near past (Pliocene to Pleistocene). Erosion could not compensate for this most recent uplift, resulting in apatite He ages of Oligocene to Miocene age or even older.
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| 9. |
- Bergmann, Annekatrin, et al.
(författare)
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Do occupational risks for low back pain differ from risks for specific lumbar disc diseases? : Results of the German Lumbar Spine Study (EPILIFT)
- 2017
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Ingår i: Spine. - 0362-2436 .- 1528-1159. ; 42:20, s. E1204-E1211
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Tidskriftsartikel (refereegranskat)abstract
- Study design: A multicenter, population based, case-control study.Objective: The aim of the present analysis is to clarify potential differences in the "occupational risk profiles" of structural lumbar disc diseases on the one hand, and low back pain (LBP) on the other hand.Summary of background data: Physical workplace factors seem to play an important etiological role.Methods: We recruited 901 patients with structural lumbar disc diseases (disc herniation or severe disc space narrowing) and 233 control subjects with "low-back-pain." Both groups were compared with 422 "low-back pain free" control subjects. Case history, pain data, neurological deficits, and movement restrictions were documented. LBP was recorded by the Nordic questionnaire on musculoskeletal symptoms. All magnetic resonance imaging, computed tomography, and X-rays were inspected by an independent study radiologist. The calculation of cumulative physical workload was based on a computer-assisted interview and a biomechanical analysis by 3-D-dynamic simulation tool. Occupational exposures were documented for the whole working life.Results: We found a positive dose-response relationship between cumulative lumbar load and LBP among men, but not among women. Physical occupational risks for structural lumbar disc diseases [odds ratio (OR) 3.7; 95% confidence interval (95% CI) 2.3-6.0] are higher than for LBP (OR 1.9; 95% CI 1.0-3.5).Conclusion: Our finding points to potentially different etiological pathways in the heterogeneous disease group of LBP. Results suggest that not all of the structural disc damage arising from physical workload leads to LBP.
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| 10. |
- Blösch, Günter, et al.
(författare)
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Twenty-three unsolved problems in hydrology (UPH) - a community perspective
- 2019
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Ingår i: Hydrological Sciences Journal. - : Informa UK Limited. - 0262-6667 .- 2150-3435. ; 64:10, s. 1141-1158
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the outcome of a community initiative to identify major unsolved scientific problems in hydrology motivated by a need for stronger harmonisation of research efforts. The procedure involved a public consultation through online media, followed by two workshops through which a large number of potential science questions were collated, prioritised, and synthesised. In spite of the diversity of the participants (230 scientists in total), the process revealed much about community priorities and the state of our science: a preference for continuity in research questions rather than radical departures or redirections from past and current work. Questions remain focused on the process-based understanding of hydrological variability and causality at all space and time scales. Increased attention to environmental change drives a new emphasis on understanding how change propagates across interfaces within the hydrological system and across disciplinary boundaries. In particular, the expansion of the human footprint raises a new set of questions related to human interactions with nature and water cycle feedbacks in the context of complex water management problems. We hope that this reflection and synthesis of the 23 unsolved problems in hydrology will help guide research efforts for some years to come.
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