| 1. |
- 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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| 2. |
- 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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| 3. |
- Mauritsen, Thorsten, et al.
(författare)
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Developments in the MPI-M Earth System Model version 1.2 (MPI-ESM1.2) and Its Response to Increasing CO2
- 2019
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Ingår i: Journal of Advances in Modeling Earth Systems. - 1942-2466. ; 11:4, s. 998-1038
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Tidskriftsartikel (refereegranskat)abstract
- A new release of the Max Planck Institute for Meteorology Earth System Model version 1.2 (MPI-ESM1.2) is presented. The development focused on correcting errors in and improving the physical processes representation, as well as improving the computational performance, versatility, and overall user friendliness. In addition to new radiation and aerosol parameterizations of the atmosphere, several relatively large, but partly compensating, coding errors in the model's cloud, convection, and turbulence parameterizations were corrected. The representation of land processes was refined by introducing a multilayer soil hydrology scheme, extending the land biogeochemistry to include the nitrogen cycle, replacing the soil and litter decomposition model and improving the representation of wildfires. The ocean biogeochemistry now represents cyanobacteria prognostically in order to capture the response of nitrogen fixation to changing climate conditions and further includes improved detritus settling and numerous other refinements. As something new, in addition to limiting drift and minimizing certain biases, the instrumental record warming was explicitly taken into account during the tuning process. To this end, a very high climate sensitivity of around 7 K caused by low-level clouds in the tropics as found in an intermediate model version was addressed, as it was not deemed possible to match observed warming otherwise. As a result, the model has a climate sensitivity to a doubling of CO2 over preindustrial conditions of 2.77 K, maintaining the previously identified highly nonlinear global mean response to increasing CO2 forcing, which nonetheless can be represented by a simple two-layer model.
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| 4. |
- Oettl, Felix C., et al.
(författare)
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A practical guide to the implementation of AI in orthopaedic research, Part 6: How to evaluate the performance of AI research?
- 2024
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Ingår i: Journal of Experimental Orthopaedics. - 2197-1153. ; 11:3
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Forskningsöversikt (refereegranskat)abstract
- Artificial intelligence's (AI) accelerating progress demands rigorous evaluation standards to ensure safe, effective integration into healthcare's high-stakes decisions. As AI increasingly enables prediction, analysis and judgement capabilities relevant to medicine, proper evaluation and interpretation are indispensable. Erroneous AI could endanger patients; thus, developing, validating and deploying medical AI demands adhering to strict, transparent standards centred on safety, ethics and responsible oversight. Core considerations include assessing performance on diverse real-world data, collaborating with domain experts, confirming model reliability and limitations, and advancing interpretability. Thoughtful selection of evaluation metrics suited to the clinical context along with testing on diverse data sets representing different populations improves generalisability. Partnering software engineers, data scientists and medical practitioners ground assessment in real needs. Journals must uphold reporting standards matching AI's societal impacts. With rigorous, holistic evaluation frameworks, AI can progress towards expanding healthcare access and quality. Level of Evidence: Level V.
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| 5. |
- Winkler, Philipp W, et al.
(författare)
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Sports activity and quality of life improve after isolated ACL, isolated PCL, and combined ACL/PCL reconstruction.
- 2023
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Ingår i: Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA. - : Springer Science and Business Media LLC. - 1433-7347. ; 31:5, s. 1781-1789
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Tidskriftsartikel (refereegranskat)abstract
- To compare patient-reported outcomes following isolated anterior cruciate ligament reconstruction (ACL-R), isolated posterior cruciate ligament reconstruction (PCL-R), and combined ACL-R and PCL-R (ACL/PCL-R), at a minimum follow-up of 2years.This was a prospective observational registry cohort study based on the Swedish National Knee Ligament Registry. Patients undergoing isolated ACL-R, isolated PCL-R, and combined ACL/PCL-R between 2005 and 2019 were eligible for inclusion. Demographic characteristics as well as injury- and surgery-related data were queried from the SNKLR. To evaluate functional outcomes, the Knee Injury and Osteoarthritis Outcome Score (KOOS) was collected preoperatively and at 1- and 2-year follow-ups and compared between the treatment groups.In total, 45,169 patients underwent isolated ACL-R, 192 patients isolated PCL-R, and 203 patients combined ACL/PCL-R. Preoperatively, and at the 1- and 2-year follow-ups, KOOS subscales were highest for the isolated ACL-R group, followed by the isolated PCL-R, and lowest for the combined ACL/PCL-R groups. Significant improvements were observed across all treatment groups in the majority of KOOS subscales between the preoperative, and 1- and 2-year follow-ups. All treatment groups showed the greatest improvements between the preoperative and 2-year follow-ups in the knee-related quality of life (mean improvement: isolated ACL-R,+28 points; isolated PCL-R,+23 points; combined ACL/PCL-R,+21 points) and the function in sport and recreation (mean improvement: isolated ACL-R,+26 points; isolated PCL-R,+20 points; combined ACL/PCL-R,+19 points) subscales.Clinically relevant improvements in knee function can be expected after isolated ACL-R, isolated PCL-R, and combined ACL/PCL-R. Functional improvements were particularly pronounced in the KOOS function in sport and recreation subscale, indicating the importance of knee stability for sports activity. This study facilitates more comprehensive patient education about functional expectations after surgical treatment of isolated and combined ACL and PCL injuries.Level 2.
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