| 1. |
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| 2. |
- Landén, Mikael, 1966, et al.
(författare)
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Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5124-5139
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Tidskriftsartikel (refereegranskat)abstract
- Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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| 3. |
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| 4. |
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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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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| 10. |
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| 11. |
- Stampalija, T., et al.
(författare)
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Fetal cerebral Doppler changes and outcome in late preterm fetal growth restriction : prospective cohort study
- 2020
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Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 56:2, s. 173-181
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. Methods This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32+ 0 to 36+ 6weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th percentile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 percentile points from the 20-week scan. Composite adverse outcome comprised both immediate adverse birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. Results The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n= 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th percentile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33weeks and 1.0 at 34-36weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a stronger association. Conclusion In this prospective multicenter study, signs of cerebral blood flow redistribution were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. (C) 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.
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| 12. |
- Thompson, PM, et al.
(författare)
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
- 2020
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 100-
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Tidskriftsartikel (refereegranskat)abstract
- This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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| 13. |
- Mylrea-Foley, Bronacha, et al.
(författare)
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Longitudinal Doppler Assessments in Late Preterm Fetal Growth Restriction
- 2023
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Ingår i: Ultraschall in der Medizin. - : Georg Thieme Verlag KG. - 0172-4614. ; 44:1, s. 56-67
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Tidskriftsartikel (refereegranskat)abstract
- Purpose To assess the longitudinal variation of the ratio of umbilical and cerebral artery pulsatility index (UCR) in late preterm fetal growth restriction (FGR). Materials and Methods A prospective European multicenter observational study included women with a singleton pregnancy, 32 +0-36 +6, at risk of FGR (estimated fetal weight [EFW] or abdominal circumference [AC] <10 th percentile, abnormal arterial Doppler or fall in AC from 20-week scan of >40 percentile points). The primary outcome was a composite of abnormal condition at birth or major neonatal morbidity. UCR was categorized as normal (<0.9) or abnormal (≥0.9). UCR was assessed by gestational age at measurement interval to delivery, and by individual linear regression coefficient in women with two or more measurements. Results 856 women had 2770 measurements; 696 (81%) had more than one measurement (median 3 (IQR 2-4). At inclusion, 63 (7%) a UCR ≥0.9. These delivered earlier and had a lower birth weight and higher incidence of adverse outcome (30% vs. 9%, relative risk 3.2; 95%CI 2.1-5.0) than women with a normal UCR at inclusion. Repeated measurements after an abnormal UCR at inclusion were abnormal again in 67% (95%CI 55-80), but after a normal UCR the chance of finding an abnormal UCR was 6% (95%CI 5-7%). The risk of composite adverse outcome was similar using the first or subsequent UCR values. Conclusion An abnormal UCR is likely to be abnormal again at a later measurement, while after a normal UCR the chance of an abnormal UCR is 5-7% when repeated weekly. Repeated measurements do not predict outcome better than the first measurement, most likely due to the most compromised fetuses being delivered after an abnormal UCR.
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| 14. |
- Pham, M. K., et al.
(författare)
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A new Certified Reference Material for radionuclides in Irish sea sediment (IAEA-385)
- 2008
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Ingår i: APPLIED RADIATION AND ISOTOPES. - : Elsevier BV. - 1872-9800 .- 0969-8043. ; 66:11, s. 1711-1717
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Konferensbidrag (refereegranskat)abstract
- A new Certified Reference Material (CRM) for radionuclides in sediment (IAEA-385) is described and the results of the certification process are presented. Eleven radionuclides (K-40, Cs-137, Ra-226, Ra-228, Th-230, Th-232, U-234, U-238, Pu-238, Pu239+240 and Am-241) have been certified and information mass activities with 95% confidence intervals are given for seven other radionuclides (Sr-90, Pb-210(Po-210), U-235, Pu-239, Pu-240 and Pu-241). Results for less frequently reported radionuclides (Co-60, Tc-99, Cs-134, Eu-155, Ra-224 and Np-239) and information on some activity and mass ratios are also reported. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in sediment samples, for the development and validation of analytical methods and for training purposes. (C) 2008 IAEA. Published by Elsevier Ltd. All rights reserved.
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| 15. |
- Schumann, G, et al.
(författare)
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Stratified medicine for mental disorders
- 2014
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Ingår i: European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. - : Elsevier BV. - 1873-7862. ; 24:1, s. 5-50
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Tidskriftsartikel (refereegranskat)
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| 16. |
- Baldwin, DS, et al.
(författare)
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Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology
- 2014
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Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 28:5, s. 403-439
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Tidskriftsartikel (refereegranskat)abstract
- This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.
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| 17. |
- Belov, Vladimir, et al.
(författare)
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Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures
- 2024
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Ingår i: Scientific Reports. - : NATURE PORTFOLIO. - 2045-2322. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.
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| 18. |
- Groenewold, Nynke A., et al.
(författare)
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Volume of subcortical brain regions in social anxiety disorder : mega-analytic results from 37 samples in the ENIGMA-Anxiety Working Group
- 2023
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 28:3, s. 1079-1089
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Tidskriftsartikel (refereegranskat)abstract
- There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = −0.077, pFWE = 0.037; right: d = −0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = −0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = −0.141, pFWE < 0.001; right: d = −0.158, pFWE < 0.001) and larger bilateral pallidum volumes (left: d = 0.129, pFWE = 0.006; right: d = 0.099, pFWE = 0.046) were detected in adult SAD patients relative to controls, but no volumetric differences were apparent in adolescent SAD patients relative to controls. Comorbid anxiety disorders and age of SAD onset were additional determinants of SAD-related volumetric differences in subcortical regions. To conclude, subtle volumetric alterations in subcortical regions in SAD were detected. Heterogeneity in age and clinical characteristics may partly explain inconsistencies in previous findings. The association between alterations in subcortical volumes and SAD illness progression deserves further investigation, especially from adolescence into adulthood.
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| 19. |
- Pham, M. K., et al.
(författare)
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Certified reference material for radionuclides in fish flesh sample IAEA-414 (mixed fish from the Irish Sea and North Sea)
- 2006
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Ingår i: Proceedings of the 15th International Conference on Radionuclide Metrology and its Applications (Applied Radiation and Isotopes). - Amsterdam : Elsevier BV. - 0969-8043 .- 1872-9800. ; 64:10-11, s. 1253-1259
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Konferensbidrag (refereegranskat)abstract
- A certified reference material (CRM) for radionuclides in fish sample IAEA-414 (mixed fish from the Irish Sea and North Seas) is described and the results of the certification process are presented. Nine radionuclides (K-40, Cs-137, Th-232, U-234, U-235, U-238, Pu-238, Pu239+240 and Am-241) were certified for this material. Information on massic activities with 95% confidence intervals is given for six other radionuclides (Sr-90, Pb-210(Po-210), Ra-226, Pu-239, Pu-240 Pu-241). Less frequently reported radionuclides (Tc-99, I-129, Th-228, Th-230 and Np-217) and information on some activity and mass ratios are also included. The CRM can be used for quality assurance/quality control of the analysis of radionuclides in fish sample, for the development and validation of analytical methods and for training purposes. The material is available from IAEA, Vienna, in 100 g units.
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| 20. |
- Povinec, Pavel, et al.
(författare)
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Reference material for radionuclides in sediment. IAEA-384 (Fangataufa lagoon sediment).
- 2007
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Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - Dordrecht : Springer. - 0236-5731 .- 1588-2780. ; 273:2, s. 383-393
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Tidskriftsartikel (refereegranskat)abstract
- A reference material designed for the determination of anthropogenic and natural radionuclides in sediment, IAEA-384 (Fangataufa Lagoon sediment), is described and the results of certification are presented. The material has been certified for 8 radionuclides (40K, 60Co, 155Eu, 230Th, 238U, 238Pu, 239+240Pu and 241Am). Information values are given for 12 radionuclides (90Sr, 137Cs, 210Pb (210Po), 226Ra, 228Ra, 232Th, 234U, 235U, 239Pu, 240Pu and 241Pu). Less reported radionuclides include 228Th, 236U, 239Np and 242Pu. The reference material may be used for quality management of radioanalytical laboratories engaged in the analysis of radionuclides in the environment, as well as for the development and validation of analytical methods and for training purposes. The material is available from IAEA in 100 g units.
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| 21. |
- Unelius, C. Rikard, et al.
(författare)
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Identification and electrophysiological studies of (4S,5S)-5-hydroxy-4-methyl-3-heptanone and 4-methyl-3,5-heptanedione in male lucerne weevils
- 2013
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Ingår i: The Science of Nature. - : Springer Science and Business Media LLC. - 0028-1042 .- 1432-1904. ; 100:2, s. 135-143
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Tidskriftsartikel (refereegranskat)abstract
- An investigation to identify a sex or aggregation pheromone of Sitona discoideus GyllenhAyenl (Coleoptera: Curculionidae) is presented. Antenna flicking and attraction behaviors evoked by conspecifics of both sexes were recorded in arena bioassays, where attraction of females to males was observed. Air entrainment of both males and females was conducted in separate chambers. Gas chromatographic-mass spectrometric analysis of headspace volatiles revealed that two male-specific compounds, 4-methyl-3,5-heptanedione (major) and (4S,5S)-5-hydroxy-4-methyl-3-heptanone (minor), were emitted during the autumnal post-aestivatory flight period. The stereoisomers of the minor component were separated by enantioselective gas chromatography and their absolute configurations assigned by NMR (diastereomers) and the known preference of enantioselective transesterification reactions catalyzed by Candida antarctica lipase B. Electroantennogram and single sensillum recording studies indicate that 4-methyl-3,5-heptanedione as well as all individual stereoisomers of 5-hydroxy-4-methyl-3-heptanone are detected by the antennae of male and female S. discoideus. Further, single sensillum recordings suggest that both sexes of S. discoideus have specialized olfactory receptor neurons (ORNs) for detecting 4-methyl-3,5-heptanedione and different populations of stereoselective ORNs for detecting the stereoisomers of 5-hydroxy-4-methyl-3-heptanone. Some of these stereoselective ORNs appear to be sex-specific in S. discoideus.
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| 22. |
- Andela, C. D., et al.
(författare)
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MECHANISMS IN ENDOCRINOLOGY Cushing's syndrome causes irreversible effects on the human brain: a systematic review of structural and functional magnetic resonance imaging studies
- 2015
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Ingår i: European Journal of Endocrinology. - : Oxford University Press (OUP). - 0804-4643 .- 1479-683X. ; 173:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cushing's syndrome (CS) is characterized by excessive exposure to cortisol, and is associated with both metabolic and behavioral abnormalities. Symptoms improve substantially after biochemical cure, but may persist during long-term remission. The causes for persistent morbidity are probably multi-factorial, including a profound effect of cortisol excess on the brain, a major target area for glucocorticoids. Objective: To review publications evaluating brain characteristics in patients with CS using magnetic resonance imaging (MRI). Methods: Systematic review of literature published in PubMed, Embase, Web of Knowledge, and Cochrane databases. Results: Nineteen studies using MRI in patients with CS were selected, including studies in patients with active disease, patients in long-term remission, and longitudinal studies, covering a total of 339 unique patients. Patients with active disease showed smaller hippocampal volumes, enlarged ventricles, and cerebral atrophy as well as alterations in neurochemical concentrations and functional activity. After abrogation of cortisol excess, the reversibility of structural and neurochemical alterations was incomplete after long-term remission. MRI findings were related to clinical characteristics (i.e., cortisol levels, duration of exposure to hypercortisolism, current age, age at diagnosis, and triglyceride levels) and behavioral outcome (i.e., cognitive and emotional functioning, mood, and quality of life). Conclusion: Patients with active CS demonstrate brain abnormalities, which only partly recover after biochemical cure, because these still occur even after long-term remission. CS might be considered as a human model of nature that provides a keyhole perspective of the neurotoxic effects of exogenous glucocorticoids on the brain.
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| 26. |
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| 29. |
- Gregoire, V, et al.
(författare)
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Delineation of the primary tumour Clinical Target Volumes (CTV-P) in laryngeal, hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, SOMERA, SRO, SSHNO, TROG consensus guidelines
- 2018
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Ingår i: Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. - : Elsevier BV. - 1879-0887. ; 126:1, s. 3-24
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Tidskriftsartikel (refereegranskat)
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| 30. |
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| 31. |
- Hultquist, Gunnar, et al.
(författare)
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Effects of O-2 dissociation on a porous platinum coating in the thermal oxidation of GaAs
- 2006
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Ingår i: Journal of the Electrochemical Society. - : The Electrochemical Society. - 0013-4651 .- 1945-7111. ; 153:2, s. G182-G186
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Tidskriftsartikel (refereegranskat)abstract
- A 20-30-nm-thick porous Pt layer has been sputter-coated on a portion of a GaAs sample and subsequently the sample was oxidized at 500 degrees C in O-16(2) followed by O-18-enriched O-2. The oxide formed was characterized by Auger electron spectroscopy, secondary ion mass spectrometry, and X-ray photoelectron spectroscopy, all with a lateral resolution of about 100 mu m. Away from the Pt area, a mm-ranged gradually decreasing degree of As oxidation was observed in the outermost oxide layer. In the Pt area, Ga was preferentially oxidized at the oxide/substrate interface producing a five to seven times thicker oxide than in an area without the influence of Pt. A strongly enhanced dissociation rate of O-2 on Pt particles and a subsequent O spillover to adjacent oxide explain the experimental observations. The mm-ranged spillover is believed to take place via fast lateral surface diffusion and results in the observed variation of oxidized As at the gas/oxide interface. In the Pt area, a high concentration gradient of dissociated oxygen across the oxide layer supplies a high flux of dissociated oxygen to the GaAs substrate where Ga is preferentially oxidized. The results clearly demonstrate that both a surface reaction and solid-state diffusion influence the oxidation rate. A localized high effective oxygen (O) activity that spills over to a nearby oxide area is believed to be a general phenomenon that is operating in oxides where a dissociating element such as Pt is present at O-2/oxide interfaces.
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| 32. |
- Jarfors, A. E. W., et al.
(författare)
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Mechanism of lubrication-induced surface cracking in hot chamber die cast thin-walled AZ91D parts
- 2003
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Ingår i: Materials and Manufacturing Processes. - 1042-6914 .- 1532-2475. ; 18:4, s. 637-641
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Tidskriftsartikel (refereegranskat)abstract
- Thin-walled hot chamber die cast parts are often used to make telephone casings and similar products having primarily requirements on weight and aesthetically satisfying surfaces. The post casting surface treatment often generates a glossy appearance. The glossy appearance makes it extremely sensitive to small-scale flaws, such as blisters, cold shuts, and cracks. Hot chamber die casting of thin-walled parts requires high filling speed and the use of lubrication because the parts have high aspect ratios. In the manufacturing of such high aspect ratio parts with a wall thickness of 0.6 mm, a new type of cold crack induced by the lubrication is observed. To some extent this defect is similar to a blister, but the characteristic bump is not formed and the actual crack is formed by thermal contraction along the high aspect ratio areas.
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| 33. |
- Jongs, N, et al.
(författare)
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A framework for assessing neuropsychiatric phenotypes by using smartphone-based location data
- 2020
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 211-
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Tidskriftsartikel (refereegranskat)abstract
- The use of smartphone-based location data to quantify behavior longitudinally and passively is rapidly gaining traction in neuropsychiatric research. However, a standardized and validated preprocessing framework for deriving behavioral phenotypes from smartphone-based location data is currently lacking. Here, we present a preprocessing framework consisting of methods that are validated in the context of geospatial data. This framework aims to generate context-enriched location data by identifying stationary, non-stationary, and recurrent stationary states in movement patterns. Subsequently, this context-enriched data is used to derive a series of behavioral phenotypes that are related to movement. By using smartphone-based location data collected from 245 subjects, including patients with schizophrenia, we show that the proposed framework is effective and accurate in generating context-enriched location data. This data was subsequently used to derive behavioral readouts that were sensitive in detecting behavioral nuances related to schizophrenia and aging, such as the time spent at home and the number of unique places visited. Overall, our results indicate that the proposed framework reliably preprocesses raw smartphone-based location data in such a manner that relevant behavioral phenotypes of interest can be derived.
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| 34. |
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| 35. |
- Lim, Yi Huey, et al.
(författare)
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Effect of optic flow on postural control in children and adults with autism spectrum disorder
- 2018
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Ingår i: Neuroscience. - : Elsevier. - 0306-4522 .- 1873-7544. ; 393, s. 138-149
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Tidskriftsartikel (refereegranskat)abstract
- Individuals with autism spectrum disorder (ASD) have been associated with sensorimotor difficulties, commonly presented by poor postural control. Postural control is necessary for all motor behaviors. However, findings concerning the effect of visual motion on postural control and the age progression of postural control in individuals with ASD are inconsistent. The aims of the present study were to examine postural responses to optic flow in children and adults with and without ASD, postural responses to optic flow in the central and peripheral visual fields, and the changes in postural responses between the child and adult groups. Thirty-three children (8–12 years old) and 33 adults (18–50 years old) with and without ASD were assessed on quiet standing for 60 seconds under conditions of varying optic flow illusions, consisting of different combinations of optic flow directions and visual field display. The results showed that postural responses to most optic flow conditions were comparable between children with and without ASD and between adults with and without ASD. However, adults with ASD appeared more responsive to forward-moving optic flow in the peripheral visual field compared with typically developed adults. The findings suggest that children and adults with ASD may not display maladaptive postural responses all the time. In addition, adults in the ASD group may have difficulties prioritizing visual information in the central visual field over visual information in the peripheral visual field when in unfamiliar environments, which may have implications in understanding their motor behaviors in new surroundings.
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| 36. |
- Lim, Yi Huey, et al.
(författare)
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Effect of visual information on postural control in adults with autism spectrum disorder
- 2019
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Ingår i: Journal of autism and developmental disorders. - : Springer. - 0162-3257 .- 1573-3432. ; 49:12, s. 4731-4739
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Tidskriftsartikel (refereegranskat)abstract
- Sensory processing difficulties affect the development of sensorimotor skills in individuals with autism spectrum disorder (ASD). However, the effect of sensory information on postural control is unclear in the ASD adult population. The present study examined the effect of visual information on postural control as well as the attentional demands associated with postural control in fourteen adults with ASD and seventeen typically developed adults. The results showed that postural sway and attention demands of postural control were larger in adults with ASD than in typically developed adults. These findings indicate that visual processing used for postural control may be different in adults with ASD. Further research in visual field processing and visual motion processing may elucidate these sensorimotor differences.
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| 37. |
- Lim, Yi Huey, et al.
(författare)
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Effect of visual information on postural control in children with Autism Spectrum Disorder
- 2020
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Ingår i: Journal of autism and developmental disorders. - : Springer. - 0162-3257 .- 1573-3432. ; 50, s. 3320-3325
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Tidskriftsartikel (refereegranskat)abstract
- Visual information is crucial for postural control. Visual processing in children with autism spectrum disorder (ASD) was hypothesized to be less efficient and thus they would display a less stable standing posture than typically developing children. The present study compared the static standing responses and attentional demands of 15 children with ASD and 18 control participants in conditions of eyes open and eyes closed. The results showed that postural responses and attention invested in standing were similar between the participant groups in the two visual conditions. Both groups displayed a more stable posture when their eyes were open in comparison to eyes closed. The finding suggests that normal postural control development could occur in children with ASD.
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| 38. |
- Lim, Yi Huey, et al.
(författare)
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Postural control adaptation to optic flow in children and adults with autism spectrum disorder
- 2019
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Ingår i: Gait & Posture. - : Elsevier. - 0966-6362 .- 1879-2219. ; 72, s. 175-181
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Tidskriftsartikel (refereegranskat)abstract
- Background: Sensory reweighting is important for humans to flexibly up-weigh and down-weigh sensory information in dynamic environments. There is an element of time involved in the sensory reweighting process. A longer time spent on sensory reweighting may increase the destabilizing effect of postural control. Individuals with autism spectrum disorder (ASD) are reported to have poor postural control. It is uncertain if a different sensory reweighting process underlies the postural control deficit in children and adults with ASD.Research question: To explore the sensory reweighting capability in ASD, the present study examined whether the temporal domains of postural control differed in children and adults, with and without ASD under various optic flow conditions.Methods: Thirty-three children (8–12 years old) and 33 adults (18–50 years old) with and without ASD underwent quiet standing in six radial optic flow conditions. Each condition lasted for 60 s and was shown twice to all participants. For each optic flow condition, changes in postural response within-trial and between-trials were measured.Results: Under various optic flow illusions, both children with and without ASD took a longer time to restore their posture compared with adults with and without ASD. Nonetheless, all groups demonstrated comparable abilities to adjust their posture to one that is close to the baseline position after one exposure to the optic flow stimulation.Significance: The present study showed that the temporal domains of postural control under different optic flow conditions were similar between individuals with and without ASD from the same age group. The ability to down-weigh visual information efficiently comes with the developmental progression of the sensory reweighting system. These findings suggest that the sensory reweighting process does not elucidate the postural control deficits in individuals with ASD and thus alternative explanations to determine the underlying mechanism for postural instability are needed.
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| 39. |
- Marshall, D. G., et al.
(författare)
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Morganella morganii bacteria produces phenol as the sex pheromone of the New Zealand grass grub from tyrosine in the colleterial gland
- 2016
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Ingår i: The Science of Nature. - : Springer Science and Business Media LLC. - 0028-1042 .- 1432-1904. ; 103:7-8
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Tidskriftsartikel (refereegranskat)abstract
- Costelytra zealandica (Coleoptera: Scarabeidae) is a univoltine endemic species that has colonised and become a major pest of introduced clover and ryegrass pastures that form about half of the land area of New Zealand. Female beetles were previously shown to use phenol as their sex pheromone produced by symbiotic bacteria in the accessory or colleterial gland. In this study, production of phenol was confirmed from the female beetles, while bacteria were isolated from the gland and tested for attractiveness towards grass grub males in traps in the field. The phenol-producing bacterial taxon was identified by partial sequencing of the 16SrRNA gene, as Morganella morganii. We then tested the hypothesis that the phenol sex pheromone is biosynthesized from the amino acid tyrosine by the bacteria. This was shown to be correct, by addition of isotopically labelled tyrosine (C-13) to the bacterial broth, followed by detection of the labelled phenol by SPME-GCMS. Elucidation of this pathway provides specific evidence how the phenol is produced as an insect sex pheromone by a mutualistic bacteria.
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| 40. |
- Mylrea-Foley, Bronacha, et al.
(författare)
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Perinatal and 2-year neurodevelopmental outcome in late preterm fetal compromise : the TRUFFLE 2 randomised trial protocol
- 2022
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Following the detection of fetal growth restriction, there is no consensus about the criteria that should trigger delivery in the late preterm period. The consequences of inappropriate early or late delivery are potentially important yet practice varies widely around the world, with abnormal findings from fetal heart rate monitoring invariably leading to delivery. Indices derived from fetal cerebral Doppler examination may guide such decisions although there are few studies in this area. We propose a randomised, controlled trial to establish the optimum method of timing delivery between 32 weeks and 36 weeks 6 days of gestation. We hypothesise that delivery on evidence of cerebral blood flow redistribution reduces a composite of perinatal poor outcome, death and short-term hypoxia-related morbidity, with no worsening of neurodevelopmental outcome at 2 years.Methods and analysis: Women with non-anomalous singleton pregnancies 32+0 to 36+6 weeks of gestation in whom the estimated fetal weight or abdominal circumference is <10th percentile or has decreased by 50 percentiles since 18-32 weeks will be included for observational data collection. Participants will be randomised if cerebral blood flow redistribution is identified, based on umbilical to middle cerebral artery pulsatility index ratio values. Computerised cardiotocography (cCTG) must show normal fetal heart rate short term variation (>= 4.5 msec) and absence of decelerations at randomisation. Randomisation will be 1:1 to immediate delivery or delayed delivery (based on cCTG abnormalities or other worsening fetal condition). The primary outcome is poor condition at birth and/or fetal or neonatal death and/or major neonatal morbidity, the secondary non-inferiority outcome is 2-year infant general health and neurodevelopmental outcome based on the Parent Report of Children's Abilities-Revised questionnaire.Ethics and dissemination: The Study Coordination Centre has obtained approval from London-Riverside Research Ethics Committee (REC) and Health Regulatory Authority (HRA). Publication will be in line with NIHR Open Access policy.
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| 41. |
- Niklasson, Mia, et al.
(författare)
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Membrane-Depolarizing Channel Blockers Induce Selective Glioma Cell Death by Impairing Nutrient Transport and Unfolded Protein/Amino Acid Responses
- 2017
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Ingår i: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 77:7, s. 1741-1752
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Tidskriftsartikel (refereegranskat)abstract
- Glioma-initiating cells (GIC) are considered the underlying cause of recurrences of aggressive glioblastomas, replenishing the tumor population and undermining the efficacy of conventional chemotherapy. Here we report the discovery that inhibiting T-type voltage-gated Ca2+ and KCa channels can effectively induce selective cell death of GIC and increase host survival in an orthotopic mouse model of human glioma. At present, the precise cellular pathways affected by the drugs affecting these channels are unknown. However, using cell-based assays and integrated proteomics, phosphoproteomics, and transcriptomics analyses, we identified the downstreamsignaling events these drugs affect. Changes in plasma membrane depolarization and elevated intracellular Na+, which compromised Na+-dependent nutrient transport, were documented. Deficits in nutrient deficit acted in turn to trigger the unfolded protein response and the amino acid response, leading ultimately to nutrient starvation and GIC cell death. Our results suggest new therapeutic targets to attack aggressive gliomas.
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| 42. |
- Perley, Daniel A., et al.
(författare)
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The fast, luminous ultraviolet transient AT2018cow : extreme supernova, or disruption of a star by an intermediate-mass black hole?
- 2019
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Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 484:1, s. 1031-1049
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Tidskriftsartikel (refereegranskat)abstract
- Wide-field optical surveys have begun to uncover large samples of fast (t(rise) less than or similar to 5 d), luminous (M-peak < 18), blue transients. While commonly attributed to the breakout of a supernova shock into a dense wind, the great distances to the transients of this class found so far have hampered detailed investigation of their properties. We present photometry and spectroscopy from a comprehensive worldwide campaign to observe AT 2018cow (ATLAS 18qqn), the first fast-luminous optical transient to be found in real time at low redshift. Our first spectra (<2 days after discovery) are entirely featureless. A very broad absorption feature suggestive of near-relativistic velocities develops between 3 and 8 days, then disappears. Broad emission features of H and He develop after >10 days. The spectrum remains extremely hot throughout its evolution, and the photospheric radius contracts with time (receding below R < 10 (14) cm after 1 month). This behaviour does not match that of any known supernova, although a relativistic jet within a fallback supernova could explain some of the observed features. Alternatively, the transient could originate from the disruption of a star by an intermediate-mass black hole, although this would require long-lasting emission of highly super-Eddington thermal radiation. In either case, AT 2018cow suggests that the population of fast luminous transients represents a new class of astrophysical event. Intensive follow-up of this event in its late phases, and of any future events found at comparable distance, will be essential to better constrain their origins.
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| 43. |
- Schmidt, Linnéa, et al.
(författare)
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Case-specific potentiation of glioblastoma drugs by pterostilbene
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:45, s. 73200-73215
-
Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma multiforme (GBM, astrocytoma grade IV) is the most common malignant primary brain tumor in adults. Addressing the shortage of effective treatment options for this cancer, we explored repurposing of existing drugs into combinations with potent activity against GBM cells. We report that the phytoalexin pterostilbene is a potentiator of two drugs with previously reported anti-GBM activity, the EGFR inhibitor gefitinib and the antidepressant sertraline. Combinations of either of these two compounds with pterostilbene suppress cell growth, viability, sphere formation and inhibit migration in tumor GBM cell (GC) cultures. The potentiating effect of pterostilbene was observed to a varying degree across a panel of 41 patient-derived GCs, and correlated in a case specific manner with the presence of missense mutation of EGFR and PIK3CA and a focal deletion of the chromosomal region 1p32. We identify pterostilbene-induced cell cycle arrest, synergistic inhibition of MAPK activity and induction of Thioredoxin interacting protein (TXNIP) as possible mechanisms behind pterostilbene's effect. Our results highlight a nontoxic stilbenoid compound as a modulator of anticancer drug response, and indicate that pterostilbene might be used to modulate two anticancer compounds in well-defined sets of GBM patients.
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| 44. |
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| 45. |
- Wee, Boyoung, et al.
(författare)
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ABCG2 regulates self-renewal and stem cell marker expression but not tumorigenicity or radiation resistance of glioma cells
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Glioma cells with stem cell traits are thought to be responsible for tumor maintenance and therapeutic failure. Such cells can be enriched based on their inherent drug efflux capability mediated by the ABC transporter ABCG2 using the side population assay, and their characteristics include increased self-renewal, high stem cell marker expression and high tumorigenic capacity in vivo. Here, we show that ABCG2 can actively drive expression of stem cell markers and self-renewal in glioma cells. Stem cell markers and self-renewal was enriched in cells with high ABCG2 activity, and could be specifically inhibited by pharmacological and genetic ABCG2 inhibition. Importantly, despite regulating these key characteristics of stem-like tumor cells, ABCG2 activity did not affect radiation resistance or tumorigenicity in vivo. ABCG2 effects were Notch-independent and mediated by diverse mechanisms including the transcription factor Mef. Our data demonstrate that characteristics of tumor stem cells are separable, and highlight ABCG2 as a potential driver of glioma stemness.
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| 46. |
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