| 1. |
- 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.
|
|
| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 3. |
|
|
| 4. |
- Sønderby, Ida E., et al.
(författare)
-
1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans
- 2021
-
Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.
|
|
| 5. |
- Taylor, M. J., et al.
(författare)
-
Isospin symmetry in the odd-odd mirror nuclei (44)V/(44)Sc
- 2011
-
Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 84:6
-
Tidskriftsartikel (refereegranskat)abstract
- Excited states in the N = Z - 2 nucleus (44)V have been observed for the first time. The states have been identified through particle-gamma-gamma coincidence relationships and comparison with analog states in themirror nucleus (44)Sc. Mirror energy differences have been extracted and compared to state-of-the-art shell-model calculations which include charge-symmetry-breaking forces. Observed decay pattern asymmetries between the mirror pair are discussed in terms of core excitations, electromagnetic spin-orbit effects and isospin mixing.
|
|
| 6. |
- van der Meer, Dennis, et al.
(författare)
-
Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
- 2020
-
Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
|
|
| 7. |
- Brodin, N., et al.
(författare)
-
Coaching patients with early rheumatoid arthritis to healthy physical activity : A multicenter, randomized, controlled study
- 2008
-
Ingår i: Arthritis and Rheumatism. - Hoboken, NJ : Wiley. - 0004-3591 .- 1529-0131. ; 59:3, s. 325-331
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To investigate the effect of a 1-year coaching program for healthy physical activity on perceived health status, body function, and activity limitation in patients with early rheumatoid arthritis. Methods. A total of 228 patients (169 women, 59 men, mean age 55 years, mean time since diagnosis 21 months) were randomized to 2 groups after assessments with the EuroQol visual analog scale (VAS), Grippit, Timed-Stands Test, Escola Paulista de Medicina Range of Motion scale, walking in a figure-of-8, a visual analog scale for pain, the Health Assessment Questionnaire disability index, a self-reported physical activity questionnaire, and the Disease Activity Score in 28 joints. All patients were regularly seen by rheumatologists and underwent rehabilitation as prescribed. Those in the intervention group were further individually coached by a physical therapist to reach or maintain healthy physical activity (=30 minutes, moderately intensive activity, most days of the week). Results. The retention rates after 1 year were 82% in the intervention group and 85% in the control group. The percentages of individuals in the intervention and control groups fulfilling the requirements for healthy physical activity were similar before (47% versus 51%, P > 0.05) and after (54% versus 44%, P > 0.05) the intervention. Analyses of outcome variables indicated improvements in the intervention group over the control group in the EuroQol VAS (P = 0.025) and muscle strength (Timed-Stands Test, P = 0.000) (Grippit, P = 0.003), but not in any other variables assessed. Conclusion. A 1-year coaching program for healthy physical activity resulted in improved perceived health status and muscle strength, but the mechanisms remain unclear, as self-reported physical activity at healthy level did not change. © 2008, American College of Rheumatology.
|
|
| 8. |
- Doornenbal, P., et al.
(författare)
-
RISING: Gamma‐ray Spectroscopy with Radioactive Beams at GSI
- 2007
-
Ingår i: AIP Conference Proceedings. - : AIP. - 0094-243X. - 9780735413283 ; 891, s. 99-107
-
Konferensbidrag (refereegranskat)abstract
- The Rare Isotope Spectroscopic INvestigation at GSI (RISING) project is a major pan‐European collaboration. Its physics aims are the studies of exotic nuclear matter with abnormal proton‐to‐neutron ratios compared with naturally occurring isotopes. RISING combines the FRagment Separator (FRS) which allows relativistic energies and projectile fragmentation reactions with EUROBALL Ge Cluster detectors for γ spectroscopic research. The RISING setup can be used in two different configurations. Either the nuclei of interest are investigated after being stopped or the heavy ions hit a secondary target at relativistic energies and the thereby occurring excitations are studied. For the latter case, MINIBALL Ge detectors and the HECTOR array are used in addition. Example achievements of the Fast Beam setup are presented and compared to various shell model calculations, while for the Stopped Beam setup initial results are shown.
|
|
| 9. |
- Hildebrandt, Franziska, 1994-, et al.
(författare)
-
Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Reconstruction of heterogeneity through single cell transcriptional profiling has greatly advanced our understanding of the spatial liver transcriptome in recent years. However, global transcriptional differences across lobular units remain elusive in physical space. Here, we apply Spatial Transcriptomics to perform transcriptomic analysis across sectioned liver tissue. We confirm that the heterogeneity in this complex tissue is predominantly determined by lobular zonation. By introducing novel computational approaches, we enable transcriptional gradient measurements between tissue structures, including several lobules in a variety of orientations. Further, our data suggests the presence of previously transcriptionally uncharacterized structures within liver tissue, contributing to the overall spatial heterogeneity of the organ. This study demonstrates how comprehensive spatial transcriptomic technologies can be used to delineate extensive spatial gene expression patterns in the liver, indicating its future impact for studies of liver function, development and regeneration as well as its potential in pre-clinical and clinical pathology. Global transcriptional differences across lobular units in the liver remain unknown. Here the authors perform spatial transcriptomics of liver tissue to delineate transcriptional differences in physical space, confirm lobular zonation along transcriptional gradients and suggest the presence of previously uncharacterized structures within liver tissue.
|
|
| 10. |
- McPhearson, Timon, et al.
(författare)
-
A social-ecological-technological systems framework for urban ecosystem services
- 2022
-
Ingår i: One Earth. - : Elsevier BV. - 2590-3330 .- 2590-3322. ; 5:5, s. 505-518
-
Tidskriftsartikel (refereegranskat)abstract
- As rates of urbanization and climatic change soar, decision-makers are increasingly challenged to provide innovative solutions that simultaneously address climate change impacts and risks and inclusively ensure quality of life for urban residents. Cities have turned to nature-based solutions to help address these challenges. Nature-based solutions, through the provision of ecosystem services, can yield numerous benefits for people and address multiple challenges simultaneously. Yet, efforts to mainstream nature-based solutions are impaired by the complexity of the interacting social, ecological, and technological dimensions of urban systems. This complexity must be understood and managed to ensure ecosystem-service provisioning is effective, equitable, and resilient. Here, we provide a social-ecological-technological system (SETS) framework that builds on decades of urban ecosystem services research to better understand four core challenges associated with urban nature-based solutions: multi-functionality, systemic valuation, scale mismatch of ecosystem services, and inequity and injustice. The framework illustrates the importance of coordinating natural, technological, and socio-economic systems when designing, planning, and managing urban nature-based solutions to enable optimal social-ecological outcomes.
|
|
