| 1. |
- Ip, H. F., et al.
(författare)
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Genetic association study of childhood aggression across raters, instruments, and age
- 2021
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Ingår i: Translational Psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGG(overall). The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (rg) among rater-specific assessment of AGG ranged from r(g)= 0.46 between self- and teacher-assessment to r(g)d= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range r(g): 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r(g)=-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |r(g)| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.
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| 2. |
- Castro-Tirado, A. J., et al.
(författare)
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GRB 030227 : The first multiwavelength afterglow of an INTEGRAL GRB
- 2003
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Ingår i: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 411:1, s. 315-319
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Tidskriftsartikel (refereegranskat)abstract
- We present multiwavelength observations of a gamma-ray burst detected byINTEGRAL (GRB 030227) between 5.3 hours and ~ 1.7days after the event. Here we report the discovery of a dim opticalafterglow (OA) that would not have been detected by many previoussearches due to its faintess (R ~ 23). This OA was seen to declinefollowing a power law decay with index alpha R = -0.95 +/-0.16. The spectral index beta_ opt/NIR yielded -1.25 +/- 0.14. Thesevalues may be explained by a relativistic expansion of a fireball (withp = 2.0) in the cooling regime. We also find evidence for inverseCompton scattering in X-rays.Based on observations with INTEGRAL, an ESA project with instruments andscience data centre funded by ESA member states (especially the PIcountries: Denmark, France, Germany, Italy, Switzerland, Spain), CzechRepublic and Poland, and with the participation of Russia and the USA.Also partially based on observations collected by the Gamma-Ray BurstCollaboration at ESO (GRACE) at the European Southern Observatory, Chile(ESO Large Programme 165.H-0464).
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| 3. |
- Ganna, A., et al.
(författare)
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Large-scale GWAS reveals insights into the genetic architecture of same-sex sexual behavior
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 365:6456
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Tidskriftsartikel (refereegranskat)abstract
- Twin and family studies have shown that same-sex sexual behavior is partly genetically influenced, but previous searches for specific genes involved have been underpowered. We performed a genome-wide association study (GWAS) on 477,522 individuals, revealing five loci significantly associated with same-sex sexual behavior. In aggregate, all tested genetic variants accounted for 8 to 25% of variation in same-sex sexual behavior, only partially overlapped between males and females, and do not allow meaningful prediction of an individual's sexual behavior. Comparing these GWAS results with those for the proportion of same-sex to total number of sexual partners among nonheterosexuals suggests that there is no single continuum from opposite-sex to same-sex sexual behavior. Overall, our findings provide insights into the genetics underlying same-sex sexual behavior and underscore the complexity of sexuality.
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| 4. |
- Jami, E. S., et al.
(författare)
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Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms
- 2022
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Ingår i: Journal of the American Academy of Child and Adolescent Psychiatry. - : Elsevier BV. - 0890-8567 .- 1527-5418. ; 61:7, s. 934-945
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n(effective) = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (vertical bar r(g)vertical bar > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range vertical bar r(g)vertical bar = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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| 5. |
- Gerkin, RC, et al.
(författare)
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The best COVID-19 predictor is recent smell loss: a cross-sectional study
- 2020
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Ingår i: medRxiv : the preprint server for health sciences. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundCOVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19.MethodsThis preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery.ResultsBoth C19+ and C19-groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ∼50% of participants and was best predicted by time since illness onset.ConclusionsAs smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4<OR<10), which can be deployed when viral lab tests are impractical or unavailable.
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| 6. |
- Marcos, S., et al.
(författare)
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Vision science and adaptive optics, the state of the field
- 2017
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Ingår i: Vision Research. - : Elsevier BV. - 0042-6989 .- 1878-5646. ; 132, s. 3-33
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Tidskriftsartikel (refereegranskat)abstract
- Adaptive optics is a relatively new field, yet it is spreading rapidly and allows new questions to be asked about how the visual system is organized. The editors of this feature issue have posed a series of question to scientists involved in using adaptive optics in vision science. The questions are focused on three main areas. In the first we investigate the use of adaptive optics for psychophysical measurements of visual system function and for improving the optics of the eye. In the second, we look at the applications and impact of adaptive optics on retinal imaging and its promise for basic and applied research. In the third, we explore how adaptive optics is being used to improve our understanding of the neurophysiology of the visual system.
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| 7. |
- Fuxe, K., et al.
(författare)
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Intramembrane receptor-receptor interactions: a novel principle in molecular medicine
- 2007
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Ingår i: Journal of neural transmission. - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 114:1, s. 49-75
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Tidskriftsartikel (refereegranskat)abstract
- In 1980/81 Agnati and Fuxe introduced the concept of intramembrane receptor-receptor interactions and presented the first experimental observations for their existence in crude membrane preparations. The second step was their introduction of the receptor mosaic hypothesis of the engram in 1982. The third step was their proposal that the existence of intramembrane receptor-receptor interactions made possible the integration of synaptic (WT) and extrasynaptic (VT) signals. With the discovery of the intramembrane receptor-receptor interactions with the likely formation of receptor aggregates of multiple receptors, so called receptor mosaics, the entire decoding process becomes a branched process already at the receptor level in the surface membrane. Recent developments indicate the relevance of cooperativity in intramembrane receptor-receptor interactions namely the presence of regulated cooperativity via receptor-receptor interactions in receptor mosaics (RM) built up of the same type of receptor (homo-oligomers) or of subtypes of the same receptor (RM type1). The receptor-receptor interactions will to a large extent determine the various conformational states of the receptors and their operation will be dependent on the receptor composition (stoichiometry), the spatial organization (topography) and order of receptor activation in the RM. The biochemical and functional integrative implications of the receptor-receptor interactions are outlined and long-lived heteromeric receptor complexes with frozen RM in various nerve cell systems may play an essential role in learning, memory and retrieval processes. Intramembrane receptor-receptor interactions in the brain have given rise to novel strategies for treatment of Parkinson's disease (A2A and mGluR5 receptor antagonists), schizophrenia (A2A and mGluR5 agonists) and depression (galanin receptor antagonists). The A2A/D2, A2A/D3 and A2A/mGluR5 heteromers and heteromeric complexes with their possible participation in different types of RM are described in detail, especially in the cortico-striatal glutamate synapse and its extrasynaptic components, together with a postulated existence of A2A/D4 heteromers. Finally, the impact of intramembrane receptor-receptor interactions in molecular medicine is discussed outside the brain with focus on the endocrine, the cardiovascular and the immune systems.
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| 8. |
- Hankey, Graeme J., et al.
(författare)
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Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration
- 2021
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Ingår i: Stroke. - : Lippincott Williams & Wilkins. - 0039-2499 .- 1524-4628. ; 52:8, s. 2502-2509
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. METHODS: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. RESULTS: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76-1.14]; P=0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P=0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P=0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P=0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P=0.64) at 12 months. CONCLUSIONS: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding.
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| 9. |
- Myslivets, E., et al.
(författare)
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Dispersion Fluctuation Equalization Nonlinear Fibers by Spatially Controlled Tension
- 2010
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Ingår i: Optical Fiber Communication Conference, OFC 2010; San Diego, CA; United States; 21 March 2010 through 25 March 2010. - 2162-2701. - 9781557528841
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Konferensbidrag (refereegranskat)abstract
- We experimentally verified that spatial dispersive fluctuations in nonlinear fiber can be effectively suppressedby inverting precisely mapped zero-dispersion wavelength via application of longitudinally controlled stretching.
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| 10. |
- Myslivets, E., et al.
(författare)
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Spatial Equalization of Zero-Dispersion Wavelength Profiles in Nonlinear Fibers
- 2009
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Ingår i: IEEE Photonics Technology Letters. - 1041-1135 .- 1941-0174. ; 21:24, s. 1807-1809
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Tidskriftsartikel (refereegranskat)abstract
- Longitudinal zero-dispersion wavelength (ZDW) fluctuations in long waveguides impose a fundamental limit on the achievable parametric mixer bandwidth. We demonstrate for the first time that the precisely measured ZDW profile can be taken advantage of by applying spatially controlled tension along the fiber length for fluctuation reduction and synthesis of a wide mixer response. The technique was experimentally validated by measuring local dispersion and tension maps and synthesizing a 145-nm-wide fiber parametric amplifier.
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| 11. |
- Notarnicola, A., et al.
(författare)
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Serum and balf-derived anti-JO1 autoantibodies exhibit high reactivity to distinct HISRS domains and associate with lung and joint involvement in patients with IIM/ASS
- 2020
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ Publishing Group. - 0003-4967 .- 1468-2060. ; 79, s. 1109-1110
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Autoantibodies that target aminoacyl transfer(t) RNA synthetases (aaRS) represent the serological marker of the anti-synthetase syndrome (ASS), a major subgroup of the idiopathic inflammatory myopathies (IIM) (1). Among the anti-aaRS, anti-histidyl tRNA synthetase (HisRS) autoantibodies (anti-Jo1) are the most common. Up to 90% of IIM/ASS patients diagnosed with interstitial lung disease (ILD) harbor anti-Jo1 autoantibodies (2).Objectives:Reactivity and affinity of anti-Jo1 autoantibodies from serum and broncheoalveolar lavage fluid (BALF) were investigated against HisRS autoantigen. Associations with clinical data from patients IIM/ASS were addressed.Methods:Total IgGs were purified by affinity chromatography. Samples and clinical data were obtained from: i) 26 anti-Jo1+patients (19 at diagnosis, 16/19 at follow-up, 7 BALF/matching serum at baseline; ii) 29 anti-Jo1-(25 serum at diagnosis, 4 BALF/matching serum at baseline); iii) 24 age/gender matched healthy controls. Anti-Jo1 IgG and IgA response against HisRS was evaluated by ELISA and western blot. Affinity was measured by surface plasmon resonance. HisRS full-length (HisRS-FL), two HisRS domains (ABD and CD), and two HisRS splice variants (WHEP and WHEP + ABD splice variant (SV)) were tested. Correlations between autoantibody reactivity and clinical data, at baseline and over disease course, were evaluated.Results:Anti-Jo1 autoantibodies from serum and lung bound HisRS-FL, WHEP and SV with high reactivity and affinity already at diagnosis and recognized both conformational and linear HisRS epitopes (Fig. 1). Levels of autoantibodies (against HisRS-FL, -domains and -splice variants) varied among patients and overtime. Patients with ILD, arthritis and less skin involvement presented higher anti-Jo1 titers compared to those with lower anti-Jo1 titers and to the anti-Jo1 negative group (Fig. 2). Anti-WHEP reactivity in BALF strongly correlated with poor pulmonary function.Conclusion:High reactivity and affinity at time of diagnosis indicates that autoimmunity against HisRS is most likely initiated before IIM/ASS diagnosis. Reactivity to specific splice variants of HisRS may be employed as diagnostic and prognostic markers.References:[1]Marguerie C, Bunn CC, Beynon HL, Bernstein RM, Hughes JM, So AK, Walport MJ: Polymyositis, pulmonary fibrosis and autoantibodies to aminoacyl-tRNA synthetase enzymes. Q J Med 1990, 77(282):1019-1038[2]Richards TJ, Eggebeen A, Gibson K, Yousem S, Fuhrman C, Gochuico BR, Fertig N, Oddis CV, Kaminski N, Rosas IO et al: Characterization and peripheral blood biomarker assessment of anti-Jo-1 antibody-positive interstitial lung disease. Arthritis Rheum 2009, 60(7):2183-2192.Fig. 1.Anti-Jo1 reactivity in total IgG purified from the first available serum sampleFig. 2.Reactivity of total anti-Jo1+ IgG purified from the first available serum close to IIM/ASS diagnosis in relation to clinical dataDisclosure of Interests:Antonella Notarnicola: None declared, Charlotta Preger: None declared, Susanna Lundström: None declared, Nuria Renard: None declared, Edvard Wigren: None declared, Eveline Van Gompel: None declared, Angeles Shunashy Galindo-Feria: None declared, Helena Persson: None declared, Maryam Fathi: None declared, Johan Grunewald: None declared, Per-Johan Jakobsson Shareholder of: Gesynta Pharma, Grant/research support from: Gesynta Pharma, AstraZeneca,, Susanne Gräslund: None declared, Ingrid E. Lundberg Grant/research support from: Bristol Meyer Squibb, Corbus Pharmaceuticals, Inc and Astra Zeneca, Catia Cerqueira: None declared
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| 12. |
- Wolffsohn, James S., et al.
(författare)
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IMI - Clinical Myopia Control Trials and Instrumentation Report
- 2019
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Ingår i: Investigative Ophthalmology and Visual Science. - : ASSOC RESEARCH VISION OPHTHALMOLOGY INC. - 0146-0404 .- 1552-5783. ; 60:3, s. M132-M160
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Tidskriftsartikel (refereegranskat)abstract
- The evidence-basis based on existing myopia control trials along with the supporting academic literature were reviewed; this informed recommendations on the outcomes suggested from clinical trials aimed at slowing myopia progression to show the effectiveness of treatments and the impact on patients. These outcomes were classified as primary (refractive error and/or axial length), secondary (patient reported outcomes and treatment compliance), and exploratory (peripheral refraction, accommodative changes, ocular alignment, pupil size, outdoor activity/lighting levels, anterior and posterior segment imaging, and tissue biomechanics). The currently available instrumentation, which the literature has shown to best achieve the primary and secondary outcomes, was reviewed and critiqued. Issues relating to study design and patient selection were also identified. These findings and consensus from the International Myopia Institute members led to final recommendations to inform future instrumentation development and to guide clinical trial protocols.
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| 13. |
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| 14. |
- Bach, Anders, et al.
(författare)
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A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage
- 2012
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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. ; 109:9, s. 3317-3322
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Tidskriftsartikel (refereegranskat)abstract
- Inhibition of the ternary protein complex of the synaptic scaffolding protein postsynaptic density protein-95 (PSD-95), neuronal nitric oxide synthase (nNOS), and the N-methyl-D-aspartate (NMDA) receptor is a potential strategy for treating ischemic brain damage, but high-affinity inhibitors are lacking. Here we report the design and synthesis of a novel dimeric inhibitor, Tat-NPEG4(IETDV)(2) (Tat-N-dimer), which binds the tandem PDZ1-2 domain of PSD-95 with an unprecedented high affinity of 4.6 nM, and displays extensive protease-resistance as evaluated in vitro by stability-measurements in human blood plasma. X-ray crystallography, NMR, and small-angle X-ray scattering (SAXS) deduced a true bivalent interaction between dimeric inhibitor and PDZ1-2, and also provided a dynamic model of the conformational changes of PDZ1-2 induced by the dimeric inhibitor. A single intravenous injection of Tat-N-dimer (3 nmol/g) to mice subjected to focal cerebral ischemia reduces infarct volume with 40% and restores motor functions. Thus, Tat-N-dimer is a highly efficacious neuroprotective agent with therapeutic potential in stroke.
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| 15. |
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| 16. |
- Gopalakrishnan, Shyam, et al.
(författare)
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The population genomic legacy of the second plague pandemic
- 2022
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Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 32:21, s. 4743-4751.e6
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Tidskriftsartikel (refereegranskat)abstract
- Human populations have been shaped by catastrophes that may have left long-lasting signatures in their genomes. One notable example is the second plague pandemic that entered Europe in ca. 1,347 CE and repeatedly returned for over 300 years, with typical village and town mortality estimated at 10%–40%.1 It is assumed that this high mortality affected the gene pools of these populations. First, local population crashes reduced genetic diversity. Second, a change in frequency is expected for sequence variants that may have affected survival or susceptibility to the etiologic agent (Yersinia pestis).2 Third, mass mortality might alter the local gene pools through its impact on subsequent migration patterns. We explored these factors using the Norwegian city of Trondheim as a model, by sequencing 54 genomes spanning three time periods: (1) prior to the plague striking Trondheim in 1,349 CE, (2) the 17th–19th century, and (3) the present. We find that the pandemic period shaped the gene pool by reducing long distance immigration, in particular from the British Isles, and inducing a bottleneck that reduced genetic diversity. Although we also observe an excess of large FST values at multiple loci in the genome, these are shaped by reference biases introduced by mapping our relatively low genome coverage degraded DNA to the reference genome. This implies that attempts to detect selection using ancient DNA (aDNA) datasets that vary by read length and depth of sequencing coverage may be particularly challenging until methods have been developed to account for the impact of differential reference bias on test statistics.
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| 17. |
- Graham, C., et al.
(författare)
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The FOCUS, AFFINITY and EFFECTS trials studying the effect(s) of fluoxetine in patients with a recent stroke : Statistical and health economic analysis plan for the trials and for the individual patient data meta-analysis
- 2017
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Ingår i: Trials. - : BioMed Central Ltd.. - 1745-6215. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Small trials have suggested that fluoxetine may improve neurological recovery from stroke. FOCUS, AFFINITY and EFFECTS are a family of investigator-led, multicentre, parallel group, randomised, placebo-controlled trials which aim to determine whether the routine administration of fluoxetine (20 mg daily) for six months after an acute stroke improves patients' functional outcome. Methods/Design: The core protocol for the three trials has been published (Mead et al., Trials 20:369, 2015). The trials include patients aged 18 years and older with a clinical diagnosis of stroke and persisting focal neurological deficits at randomisation 2-15 days after stroke onset. Patients are randomised centrally via each trials' web-based randomisation system using a common minimisation algorithm. Patients are allocated fluoxetine 20 mg once daily or matching placebo capsules for six months. The primary outcome measure is the modified Rankin scale (mRS) at six months. Secondary outcomes include: living circumstances; the Stroke Impact Scale; EuroQol (EQ5D-5 L); the vitality subscale of the 36-Item Short Form Health Survey (SF36); diagnosis of depression; adherence to medication; serious adverse events including death and recurrent stroke; and resource use at six and 12 months and the mRS at 12 months. Discussion: Minor variations have been tailored to the national setting in the UK (FOCUS), Australia, New Zealand and Vietnam (AFFINITY) and Sweden (EFFECTS). Each trial is run and funded independently and will report its own results. A prospectively planned individual patient data meta-analysis of all three trials will provide the most precise estimate of the overall effect and establish whether any effects differ between trials or subgroups. This statistical analysis plan describes the core analyses for all three trials and that for the individual patient data meta-analysis. Recruitment and follow-up in the FOCUS trial is expected to be completed by the end of 2018. AFFINITY and EFFECTS are likely to complete follow-up in 2020.
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| 18. |
- Gruner-Nielsen, Lars, et al.
(författare)
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Brillouin Suppressed Highly Nonlinear Fibers
- 2012
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Ingår i: European Conference and Exhibition on Optical Communication, ECEOC 2012; Amsterdam; Netherlands; 16 September 2012 through 20 September 2012. - 9781557529503 ; , s. We.1.F.1-
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Konferensbidrag (refereegranskat)abstract
- Methods for suppression of stimulated Brillouin scattering in highly nonlinear fibers are reviewed. Emphasis is paid to SBS suppression by aluminum doping of the core. New results for a HNLF with an aluminum doped core and reduced loss are presented.
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| 19. |
- Gruner-Nielsen, Lars, et al.
(författare)
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Silica-based highly nonlinear fibers with a high SBS threshold
- 2011
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Ingår i: 2011 IEEE Winter Topicals, WTM 2011. - 9781424484287 ; , s. 171-172
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Results on the suppression of stimulated Brillouin scattering in highly non linear fibers with both germanium- and aluminum-doped cores based on spooling the fiber with a linear strain gradient are compared and presented.
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| 20. |
- Herlitz, Johan, et al.
(författare)
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A comparison between patients suffering in-hospital and out-of-hospital cardiac arrest in terms of treatment and outcome
- 2000
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Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell Publishing Ltd.. - 0954-6820 .- 1365-2796. ; 248:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To compare treatment and outcome amongst patients suffering in-hospital and out-of-hospital cardiac arrest in the same community. PATIENTS: All patients suffering in-hospital cardiac arrest in Sahlgrenska University Hospital covering half the catchment area of the community of Göteborg (500 000 inhabitants) and all patients suffering out-of-hospital cardiac arrest in the community of Göteborg. Criteria for inclusion were that resuscitation efforts should have been attempted. TIME OF SURVEY: From 1 November 1994 to 1 November 1997. METHODS: Data were recorded both prospectively and retrospectively. RESULTS: In total, 422 patients suffered in-hospital cardiac arrest and 778 patients suffered out-of-hospital cardiac arrest. Patients with in-hospital cardiac arrest included more women and were more frequently found in ventricular fibrillation. The median interval between collapse and defibrillation was 2 min in in-hospital cardiac arrest compared with 7 min in out-of-hospital cardiac arrest (< 0.001). The proportion of patients being discharged from hospital was 37.5% after in-hospital cardiac arrest, compared with 8.7% after out-of-hospital cardiac arrest (P < 0.001). Corresponding figures for patients found in ventricular fibrillation were 56.9 vs. 19.7% (P < 0.001) and for patients found in asystole 25.2 vs. 1.8% (P < 0.001). CONCLUSION: In a survey evaluating patients with in-hospital and out-of-hospital cardiac arrest in whom resuscitation efforts were attempted, we found that the former group had a survival rate more than four times higher than the latter. Possible strong contributing factors to this observation are: (i) shorter time interval to start of treatment, and (ii) a prepared selection for resuscitation efforts.
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| 21. |
- Herlitz, Johan, et al.
(författare)
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Characteristics and outcome among patients suffering in hospital cardiac arrest in monitored and non monitored areas
- 2001
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Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 48:2, s. 125-135
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe the characteristics and outcome among patients suffering in-hospital cardiac arrest in relation to whether the arrest took place in a ward with monitoring facilities. METHODS: All patients who suffered an in-hospital cardiac arrest during a 4-year period in Sahlgrenska Hospital, Göteborg, Sweden and in whom resuscitative efforts were attempted, were prospectively recorded and described in terms of characteristics and outcome. RESULTS: Among 557 patients, 292 (53%) had a cardiac arrest in wards with monitoring facilities. Those in a monitored location more frequently had a confirmed or possible acute myocardial infarction (AMI) as judged to be the cause of arrest (P < 0.0001), and the arrest was witnessed more frequently (96 vs. 79%; P < 0.0001). Ventricular fibrillation/tachycardia was observed more often as initial arrhythmia in monitored wards (56 vs. 44%; P = 0.006). The median interval between collapse and first defibrillation was 1 min in monitored wards and 5 min in non-monitored wards (P < 0.0001). Among patients with arrest in monitored wards 43.2% were discharged alive compared with 31.1% of patients in non-monitored wards (P = 0.004). Cerebral performance category (CPC-score) at discharge was somewhat better among survivors in monitored wards. CONCLUSION: In a Swedish University Hospital 47% of in-hospital cardiac arrests in which resuscitation was attempted took place in wards without monitoring facilities. These patients differed markedly from those having arrest in wards with monitoring facilities in terms of characteristics, interval to defibrillation and outcome. A shortening of the interval between collapse and defibrillation in these patients might increase survival even further.
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| 22. |
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| 23. |
- Lundström, Torbjörn S, et al.
(författare)
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Caries in the infundibulum of the second upper premolar tooth in the horse.
- 2007
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Ingår i: Acta veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 1751-0147. ; 49:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Swedish equine dental practices have empirically found that the prevalence of infundibular caries as a primary disorder in the first permanent premolar teeth (P2) of the horse upper jaw has increased during the last 10 years. A previously unknown bacterial species, Streptococcus devriesei (CCUG 47155T), which is related to Streptococcus mutans, has recently been isolated from these carious lesions. To understand the aetiology of caries in horses, it is essential to elucidate the relationship between S. devriesei and P2 infundibular caries. METHODS: The anterior infundibulum of maxillary P2, or the occlusal surface at the site of the infundibulum, in 117 horses and ponies, 77 with and 40 without caries in this tooth, was sampled for bacteriological analyses between 1990 and 2004. Samples were transported in VMGA III medium and then inoculated onto MSB agar. The approximate number of bacteria was counted in each sample and the isolates were characterised biochemically, using a commercial kit. RESULTS: All 50 samples taken from carious lesions after 2002 were positive for an S. mutans-like strain, i.e. S. devriesei. The bacteria were also found in four of the control animals, but were much less numerous than in samples from caries-affected horses. None of the swabs taken prior to 2002 were positive for this bacteria. CONCLUSION: Our results demonstrate that S. devriesei can colonise the infundibulum of P2 of the horse upper jaw, which can be fatal for the dental tissue. We conclude that S. devriesei is strongly associated with P2 caries in horses.
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| 24. |
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| 25. |
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| 26. |
- Nakagomi, S, et al.
(författare)
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Substrate bias amplification of a SiC junction field effect transistor with a catalytic gate electrode
- 2004
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Ingår i: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 457-460, s. 1507-1510
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Tidskriftsartikel (refereegranskat)abstract
- The drain current-voltage (I-d-V-D) characteristics of a chemical gas sensor based on a catalytic metal insulator silicon carbide field effect transistor (SiC-FET) were measured in H-2 or O-2 ambient while applying negative substrate bias, V-sub, at temperatures up to 600degreesC. An increase in the negative V-sub gives rise to an increase of the drain voltage at a given drain current level, which can be used to adjust the device baseline. In addition, we found that the difference in drain voltage between H-2 and O-2 ambient at a given drain current level (the gas response to H-2) increases for an increased negative substrate bias. By modifying an equation for the drain current in a SIT (static induction transistor), the influence of substrate bias on the amplification factors, mu and eta, was estimated using the temperature dependence of the I-d-V-D characteristics. From this, the effect of substrate bias on the gas response to hydrogen was calculated. It was clarified that the increase in the gas response caused by the negative substrate bias is due to a substrate bias dependence of the amplification factor of the short channel device.
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| 27. |
- Nambu, Kei, et al.
(författare)
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Composition of organic solutes and respiration in soils derived from alkaline and non-alkaline parent materials
- 2008
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Ingår i: Geoderma. - : Elsevier. - 0016-7061 .- 1872-6259. ; 144:3-4, s. 468-477
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Tidskriftsartikel (refereegranskat)abstract
- Parent material greatly influences pedogenesis and soil nutrient availability and consequently we hypothesized that it would significantly affect the amount of organic solutes in soil, many of which have been implicated in rhizosphere processes linked to plant nutrient uptake. Consequently, we investigated the influence of two contrasting parent materials in which calcite was present or absent (alkaline and non-alkaline soils) on the concentrations of dissolved organic carbon (DOC), low-molecular weight organic acids (LMWOA) and glucose in soil solution. Both soils were under Norway spruce. The dynamics of LMWOAs in soil were also investigated using 14C-labelled citrate and oxalate. Some of the mineral horizons of the alkaline soils showed significantly higher concentrations of DOC, phenolics, and fumarate in soil solution and also a higher basal respiration. No major differences were seen in organic solute status in the organic horizons of the two soil types. LMWOAs were present at low concentrations in soil solution (< 1 to 25 ΌM). Their mineralization rate significantly decreased with soil depth, however, overall neither their concentration or half-life in soil was markedly affected by parent material. The alkaline soils had significantly higher CO2-to-soil organic C (SOC) ratios, and consequently SOC in the alkaline soils did not seem more chemically stable against mineralization. Considering possible DOC and CO2 efflux rates it was suggested that the equal or larger SOC stocks in alkaline mineral soils were most likely linked to a higher net primary productivity. In conclusion, our study found that parent material exerted only a small effect on the concentration and dynamics of organic solutes in soil solution. This suggests that in comparison to other factors (e.g. vegetation cover, climate etc) parent material may not be a major regulator of the organic solute pool in soil. © 2008 Elsevier B.V. All rights reserved.
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| 28. |
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| 29. |
- Osswald, S., et al.
(författare)
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EVIS 2014 : 3rd Workshop on Electric Vehicle Information Systems
- 2014
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Ingår i: AutomotiveUI 2014 - 6th International Conference on Automotive User Interfaces and Interactive Vehicular Applications, in Cooperation with ACM SIGCHI - Adjunct Proceedings. - New York, NY, USA : ACM. - 9781450307253 ; , s. 93-98
-
Konferensbidrag (refereegranskat)abstract
- The effort to push the electric vehicle development worldwide is continuously rising. Production sites for electric vehicle components are built, billions are invested to create new battery electric vehicle concepts (BEV) and new players are entering the market. The information systems of electric vehicles (EVIS) need to cope with a variety of new features that are related to changes of vehicle components and driving behavior, but also with changes and new systems that are silently introduced into the vehicles. Sustainability, mobility concepts and smart mobility are just a few points out of many that can be attributed to the "silent" category. With this workshop, we continue to bring together researchers, designers and practitioners to explore the related field and generate a state of the art perspective on EVIS.
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| 30. |
- Parmigiani, Francesca, et al.
(författare)
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All-Optical Phase Regeneration of 40Gbit/s DPSK Signals in a Black‐Box Phase Sensitive Amplifier
- 2010
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Ingår i: 2010 Conference on Optical Fiber Communication, Collocated National Fiber Optic Engineers Conference, OFC/NFOEC 2010; San Diego, CA; United States; 21 March 2010 through 25 March 2010. - 9781557528841 ; , s. PDPC3-
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Konferensbidrag (refereegranskat)abstract
- We present a black‐box four wave mixingbased bit‐rate‐flexible phase sensitive amplifier and use it in the first demonstration of 40 Gbit/s DPSK phaseregeneration.
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| 31. |
- Rudberg, A. -S, et al.
(författare)
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Stroke survivors’ priorities for research related to life after stroke
- 2020
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Ingår i: Topics in Stroke Rehabilitation. - : Taylor & Francis. - 1074-9357 .- 1945-5119. ; , s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Stroke has transitioned from an untreatable, unpreventable disease to a highly treatable and preventable disease over recent decades, and the number of stroke survivors is expected to increase. The number is also foreseen to grow larger as a result of an aging population. With an escalating number of stroke survivors, research on how to improve life after stroke is needed. Aims: The primary aim was to determine which area of research related to life after stroke that stroke patients and their informal carers prioritized as being relevant and valuable. Methods: A cross-sectional study of all patients who had completed the 12 months of follow-up in the EFFECTS trial. In the questionnaire the stroke patients and their informal carers were asked to prioritize areas of research they considered important and valuable with respect to their life after stroke. Results: Of the 731 patients who were still alive after the 12 months-follow-up, 589 responded. The most prioritized areas of research were Balance and walking difficulties (290 (49%) responders) and Post-stroke fatigue (173 (29%) responders). Women answered the undefined alternative “other” more often than men (43 women (11%) versus 11 men (6%), p = .04). Younger patients prioritized Post-stroke fatigue to a higher extent (88 (45%) versus (22%), p < .001), and elderly prioritized Balance and walking difficulties (214 (54%) versus 76 (40%), p = .002) and Speech difficulties (38 (10%) versus 9 (5%), p = .045). Conclusions: Life after stroke is perceived differentely with aging. Future research should address strategies to face challenges such as imbalance and walking difficulties and post-stroke-fatigue.
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| 32. |
- Salomonsson, S., et al.
(författare)
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A Population-based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block
- 2011
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Ingår i: Scandinavian Journal of Immunology. - Oxford : Blackwell Publishing. - 0300-9475 .- 1365-3083. ; 74:5, s. 511-517
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.
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| 33. |
- Smits, Mark M, et al.
(författare)
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The fungal-mineral interface: Challanges and considerations of micro-analytical developments
- 2009
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Ingår i: Fungal Biology Reviews. - : Elsevier BV. - 1749-4613 .- 1878-0253. ; 23:4, s. 122-131
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Tidskriftsartikel (refereegranskat)abstract
- Over recent years, the role of fungi, especially mycorrhizal fungi, in the weathering of rock-forming minerals has been increasingly recognised. Much of our understanding of the effects of fungi on mineral weathering is based on macroscopic studies. However, the ability of fungi to translocate materials, including organic acids and siderophores, to specific areas of a mineral surface leads to significant spatial heterogeneity in the weathering process. Thus, geomycologists are confronted with unique challenges of how to comprehend and quantify such a high degree of diversity and complicated arrays of interactions. Recent advances in experimental and analytical techniques have increased our ability to probe the fungal-mineral interface at the resolution necessary to decouple significant biogeochemical processes. Modern microscopy, spectroscopy, mass spectrometry, wet chemistry, and scattering techniques allow for the selective extraction of physical, chemical, and structural data at the micro- to nano-scale. These techniques offer exciting possibilities to study fungal-mineral interactions at the scale of individual hyphae. In this review, we give an overview of some of these techniques with their characteristics, advantages and limitations, and how they can be used to further our understanding of biotic mineral weathering.
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| 34. |
- Sygletos, S., et al.
(författare)
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Phase locking and carrier extraction schemes for phase sensitive amplification
- 2010
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Ingår i: 2010 12th International Conference on Transparent Optical Networks, ICTON 2010. - 9781424477975
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- We demonstrate two schemes which enable simultaneous phase locking, carrier extraction and frequency shifting for use in stand-alone phase sensitive amplifiers. The schemes provide phase locked pumps at appropriate frequency spacing for a number of non-degenerate PSA configurations. © 2010 IEEE.
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| 35. |
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| 36. |
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| 37. |
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| 38. |
- Aifa, Sami, et al.
(författare)
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Phosphorylation of Thr654 but not Thr669 within the juxtamembrane domain of the EGF receptor inhibits calmodulin binding
- 2006
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Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 347:2, s. 381-387
-
Tidskriftsartikel (refereegranskat)abstract
- Calcium-calmodulin (CaM) binding to the epidermal growth factor receptor (EGFR) has been shown to both inhibit and stimulate receptor activity. CaM binds to the intracellular juxtamembrane (JM) domain (Met645-Phe688) of EGFR. Protein kinase C (PKC) mediated phosphorylation of Thr654 occurs within this domain. CaM binding to the JM domain inhibits PKC phosphorylation and conversely PKC mediated phosphorylation of Thr654 or Glu substitution of Thr654 inhibits CaM binding. A second threonine residue (Thr669) within the JM domain is phosphorylated by the mitogen-activated protein kinase (MAPK). Previous results have shown that CaM interferes with EGFR-induced MAPK activation. If and how phosphorylation of Thr669 affects CaM-EGFR interaction is however not known.In the present study we have used surface plasmon resonance (BIAcore) to study the influence of Thr669 phosphorylation on real time interactions between the intracellular juxtamembrane (JM) domain of EGFR and CaM. The EGFR-JM was expressed as GST fusion proteins in Escherichia coli and phosphorylation was mimicked by generating Glu substitutions of either Thr654 or Thr669. Purified proteins were coupled to immobilized anti-GST antibodies at the sensor surface and increasing concentration of CaM was applied. When mutating Thr654 to Glu654 no specific CaM binding could be detected. However, neither single substitutions of Thr669 (Gly669 or Glu669) nor double mutants Gly654/Gly669 or Gly654/Glu669 influenced the binding of CaM to the EGFR-JM. This clearly shows that PKC may regulate EGF-mediated CaM signalling through phosphorylation of Thr654 whereas phosphorylation of Thr669 seems to play a CaM independent regulatory role. The role of both residues in the EGFR-calmodulin interaction was also studied in silico. Our modelling work supports a scenario where Thr654 from the JM domain interacts with Glu120 in the calmodulin molecule. Phosphorylation of Thr654 or Glu654 substitution creates a repulsive electrostatic force that would diminish CaM binding to the JM domain. These results are in line with the Biacore experiments showing a weak binding of the CaM to the JM domain with Thr654 mutated to Glu. Furthermore, these results provide a hypothesis to how CaM binding to EGFR might both positively and negatively interfere with EGFR-activity. © 2006 Elsevier Inc. All rights reserved.
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| 39. |
- Akingbuwa, W. A., et al.
(författare)
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Genetic Associations between Childhood Psychopathology and Adult Depression and Associated Traits in 42998 Individuals: A Meta-Analysis
- 2020
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Ingår i: JAMA Psychiatry. - : American Medical Association (AMA). - 2168-622X .- 2168-6238. ; 77:7, s. 715-728
-
Tidskriftsartikel (refereegranskat)abstract
- Importance: Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits. Objective: To investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders. Design, Setting, and Participants: This meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019. Exposures: Individual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI). Main Outcomes and Measures: Regression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater. Results: The sample included 42998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (β estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (β, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (Δβ, 0.0561 [Δ95% CI, 0.0318-0.0804]; ΔSE, 0.0124) and social problems (Δβ, 0.0528 [Δ95% CI, 0.0282-0.0775]; ΔSE, 0.0126), and between BMI PGS and ADHD and social problems (Δβ, -0.0001 [Δ95% CI, -0.0102 to 0.0100]; ΔSE, 0.0052), compared with internalizing problems (Δβ, -0.0310 [Δ95% CI, -0.0456 to -0.0164]; ΔSE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (Δβ, -0.0032 [Δ 95% CI, -0.0048 to -0.0017]; ΔSE, 0.0008). Conclusions and Relevance: Results from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.. © 2020 Lippincott Williams and Wilkins. All rights reserved.
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| 40. |
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| 41. |
- Andersson, L-O, et al.
(författare)
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A new neutron beam facility
- 2004
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Ingår i: Proc. of the 9th European Particle Accelerator Conference.
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Konferensbidrag (refereegranskat)
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| 42. |
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| 43. |
- Andersson, Tony P. M., et al.
(författare)
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Myosin V is the rate-determinative step in Xenopus melanophore aggregation
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- In Xenopus melanophores, melatonin induce melanosome aggregation via activation of its receptor Mel1c, coupled to inhibitory G proteins, adenylate cyclase deactivation, cyclic adenosine 3':5'-monophosphate (cAMP) decrease, protein kinase A inhibition, protein phophatase 2A activation, and serine/threonine dephosphorylations. Myosin V is the motor protein responsible for transporting melanosomes along actin filaments. Myosin V has been demonstrated to be necessary for melanosome dispersion and to keep the dispersed state. We have previously shown that melatonin induce activation of phosphoinositide-3 kinase, mitogen-activated protein kinase and tyrosine phosphorylation of a 280-kDa protein. Here we characterize the kinetics of latrunculin A-induced aggregation, and show that latrunculin A aggregate melanophores with the same kinetics as melatonin. This indicates that the downstream mechanisms might be similar although their primary targets in the cells are totally different. We suggest that both drugs act by inhibiting myosin V, the rate-determinative step for melanosome aggregation. Our data suggest that dynein is not up regulated during aggregation, as previously suggested by others,
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| 44. |
- Andréassob, A-Ch, et al.
(författare)
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Characteristics and outcome among patients with a suspected in hospital cardiac arrest
- 1998
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Ingår i: Resuscitation. - : Elsevier Ireland Ltd. - 0300-9572 .- 1873-1570. ; 39:1-2, s. 23-31
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To describe the characteristics and outcome among patients with a suspected in-hospital cardiac arrest. METHODS: All the patients who suffered from a suspected in-hospital cardiac arrest during a 14-months period, where the cardiopulmonary resuscitation (CPR) team was called, were recorded and described prospectively in terms of characteristics and outcome. RESULTS: There were 278 calls for the CPR team. Of these, 216 suffered a true cardiac arrest, 16 a respiratory arrest and 46 neither. The percentage of patients who were discharged alive from hospital was 42% for cardiac arrest patients, 62% for respiratory arrest and 87% for the remaining patients. Among patients with a cardiac arrest, those found in ventricular fibrillation/ventricular tachycardia had a survival rate of 64%, those found in asystole 24% and those found in pulseless electrical activity 10%. Among patients who were being monitored at the time of arrest, the survival rate was 52%, as compared with 27% for non-monitored patients (P= 0.001). Among survivors of cardiac arrest, a cerebral performance category (CPC) of 1 (no major deficit) was observed in 81% at discharge and in 82% on admission to hospital prior to the arrest. CONCLUSION: We conclude that, during a 14-month period at Sahlgrenska University Hospital in Göteborg, almost half the patients with a cardiac arrest in which the CPR team was called were discharged from hospital. Among survivors, 81% had a CPC score of 1 at hospital discharge. Survival seems to be closely related to the relative effectiveness of the resuscitation organisation in different parts of the hospital.
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| 45. |
- Andreasson, A., et al.
(författare)
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Fosfomycin versus Ciprofloxacin as transrectal prostatebiopsy antibiotic prophylaxis an open randomized controlled multicenter drug trial
- 2023
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 83:Suppl. 1, s. S180-S180
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction & Objectives: Antibiotic prophylaxis are administered as a routine to decrease the risk for septic complications following transrectal prostate biopsy. Fosfomycin administered 1 h or more prior to biopsy has equal or better infectious complication rates as compared to Ciprofloxacin in both prospective and retrospective studies from countries with high rates of antibiotic resistance. The aim of this study was to investigate if Fosfomycin administered immediately prior to prostate biopsy was as effective as Ciprofloxacin in Sweden, a country with low rates of antibiotic resistance.Materials & Methods: A randomized, controlled, open, multicenter, non-inferiority-study including men of all ages undergoing transrectal prostate biopsy was performed in the urology departments of three Swedish hospitals. The total number of patients were planned for 3448, divided into low and high infection risk groups. The low-risk group was randomized to either one dose of Fosfomycin 3g or Ciprofloxacin 750mg before biopsy. The high-risk group was randomized to either two doses of Fosfomycin 3g prior to biopsy and one more 24 h after biopsy or Ciprofloxacin 500mg once prior to biopsy and then twice daily for three days. The drugs were administered orally. All patients had a rectal swab for culture before and after biopsy. The endpoint was hospitalisation due to urinary tract infection within 14 days from biopsy, follow-up was performed with a phone interview.Results: The safety board prematurely interrupted the study after 42 included patients due to an unusual high number of hospitalisations. Four out of 20 patients (20%), three in the low-risk group and one in the high-risk group, had been hospitalised due to urosepsis in the Fosfomycin group. One further patient described fever symptoms but did not seek health care. No patient in the Ciprofloxacin group (n=21) described symptoms of infection from the urinary tract. One patient was lost to follow-up. A one-sided binomial test showed a p-value of <0.001. Two of the four hospitalised patients had a positive blood culture for Pseudomonas Aeruginosa and one had a positive rectal swab culture for Pseudomonas species both before and after biopsy.Conclusions: The study does not support the use of Fosfomycin administered immediately prior to prostate biopsy. The results may have been affected by the unexpected high number of Pseudomonas infections, a bacteria where Fosfomycin often lack effect. If Fosfomycin is to be used it should be with caution if Pseudomonas has been seen in earlier cultures
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| 46. |
- Baldwin, J. R., et al.
(författare)
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A genetically informed Registered Report on adverse childhood experiences and mental health
- 2023
-
Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 7:2, s. 269-290
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Tidskriftsartikel (refereegranskat)abstract
- Children who experience adversities have an elevated risk of mental health problems. However, the extent to which adverse childhood experiences (ACEs) cause mental health problems remains unclear, as previous associations may partly reflect genetic confounding. In this Registered Report, we used DNA from 11,407 children from the United Kingdom and the United States to investigate gene-environment correlations and genetic confounding of the associations between ACEs and mental health. Regarding gene-environment correlations, children with higher polygenic scores for mental health problems had a small increase in odds of ACEs. Regarding genetic confounding, elevated risk of mental health problems in children exposed to ACEs was at least partially due to pre-existing genetic risk. However, some ACEs (such as childhood maltreatment and parental mental illness) remained associated with mental health problems independent of genetic confounding. These findings suggest that interventions addressing heritable psychiatric vulnerabilities in children exposed to ACEs may help reduce their risk of mental health problems.
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| 47. |
- Baldwin, Jessie R., et al.
(författare)
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Adverse Childhood Experiences and Mental Health : A Genetically Informed Study
- 2021
-
Ingår i: Behavior Genetics. - : Springer. - 0001-8244 .- 1573-3297. ; 51:6, s. 691-692
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Children exposed to adverse childhood experiences (ACEs) have an elevated risk of mental health problems, but it is unclear whether these associations reflect genetic confounding. We tested (1) whether children with genetic liability to psychopathology are more likely to experience ACEs, and (2) the extent to which the associations between ACEs and mental health are genetically confounded. Par-ticipants were 6411 children from the Avon Longitudinal Study of Parents and Children (ALSPAC). ACEs (including maltreatment, domestic violence, and parental psychopathology, substance abuse, criminality, and separation) were prospectively measured through parent reports at multiple assessments between birth and age 9. Internalizing and externalizing problems at age 9 were assessed through parent reports on the Development and Wellbeing Assessment. We derived polygenic scores for a range of psychiatric disorders. Children with greater genetic liability to psychopathology had a small elevation in risk of ACEs (pooled odds ratio = 1.05, 95% CI 1.01–1.09). Measured polygenic scores accounted for a very small proportion of the associations between ACEs with internalizing problems (pooled average across ACEs = 3.6%) and externalizing problems (pooled average = 4.8%). However, latent polygenic scores capturing SNP heritability in mental health outcomes explained a larger proportion of the associations between ACEs with internalizing problems (pooled average = 63%) and externalizing problems (pooled average = 17%). Risk of mental health problems in children exposed to ACEs is partly, but not completely driven by pre-existing genetic liability to psychopathology. Assuming the absence of nongenetic confounding, these findings are consistent with a partly causal effect of ACEs on mental health.
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| 48. |
- Barbateskovic, Marija, et al.
(författare)
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A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions
- 2021
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 135, s. 29-41
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. Study design and setting: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. Results: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. Conclusion: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.
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| 49. |
- Bartels, M., et al.
(författare)
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Childhood aggression and the co-occurrence of behavioural and emotional problems: results across ages 3-16years from multiple raters in six cohorts in the EU-ACTION project
- 2018
-
Ingår i: European Child & Adolescent Psychiatry. - : Springer Science and Business Media LLC. - 1018-8827 .- 1435-165X. ; 27:9, s. 1105-1121
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Tidskriftsartikel (refereegranskat)abstract
- Childhood aggression and its resulting consequences inflict a huge burden on affected children, their relatives, teachers, peers and society as a whole. Aggression during childhood rarely occurs in isolation and is correlated with other symptoms of childhood psychopathology. In this paper, we aim to describe and improve the understanding of the co-occurrence of aggression with other forms of childhood psychopathology. We focus on the co-occurrence of aggression and other childhood behavioural and emotional problems, including other externalising problems, attention problems and anxiety-depression. The data were brought together within the EU-ACTION (Aggression in Children: unravelling gene-environment interplay to inform Treatment and InterventiON strategies) project. We analysed the co-occurrence of aggression and other childhood behavioural and emotional problems as a function of the child's age (ages 3 through 16years), gender, the person rating the behaviour (father, mother or self) and assessment instrument. The data came from six large population-based European cohort studies from the Netherlands (2x), the UK, Finland and Sweden (2x). Multiple assessment instruments, including the Child Behaviour Checklist (CBCL), the Strengths and Difficulties Questionnaire (SDQ) and Multidimensional Peer Nomination Inventory (MPNI), were used. There was a good representation of boys and girls in each age category, with data for 30,523 3- to 4-year-olds (49.5% boys), 20,958 5- to 6-year-olds (49.6% boys), 18,291 7- to 8-year-olds (49.0% boys), 27,218 9- to 10-year-olds (49.4% boys), 18,543 12- to 13-year-olds (48.9% boys) and 10,088 15- to 16-year-olds (46.6% boys). We replicated the well-established gender differences in average aggression scores at most ages for parental ratings. The gender differences decreased with age and were not present for self-reports. Aggression co-occurred with the majority of other behavioural and social problems, from both externalising and internalising domains. At each age, the co-occurrence was particularly prevalent for aggression and oppositional and ADHD-related problems, with correlations of around 0.5 in general. Aggression also showed substantial associations with anxiety-depression and other internalizing symptoms (correlations around 0.4). Co-occurrence for self-reported problems was somewhat higher than for parental reports, but we found neither rater differences, nor differences across assessment instruments in co-occurrence patterns. There were large similarities in co-occurrence patterns across the different European countries. Finally, co-occurrence was generally stable across age and sex, and if any change was observed, it indicated stronger correlations when children grew older. We present an online tool to visualise these associations as a function of rater, gender, instrument and cohort. In addition, we present a description of the full EU-ACTION projects, its first results and the future perspectives.
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- Beck, J. J., et al.
(författare)
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Genetic meta-analysis of twin birth weight shows high genetic correlation with singleton birth weight
- 2021
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:19, s. 1894-1905
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Tidskriftsartikel (refereegranskat)abstract
- Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardiometabolic disorders, autoimmune diseases and mental health. On average, twins have a lower BW than singletons as a result of a different pattern of fetal growth and shorter gestational duration. Therefore, investigations into the genetics of BW often exclude data from twins, leading to a reduction in sample size and remaining ambiguities concerning the genetic contribution to BW in twins. In this study, we carried out a genome-wide association meta-analysis of BW in 42 212 twin individuals and found a positive correlation of beta values (Pearson's r = 0.66, 95% confidence interval [CI]: 0.47-0.77) with 150 previously reported genome-wide significant variants for singleton BW. We identified strong positive genetic correlations between BW in twins and numerous anthropometric traits, most notably with BW in singletons (genetic correlation [r(g)]= 0.92, 95% CI: 0.66-1.18). Genetic correlations of BW in twins with a series of health-related traits closely resembled those previously observed for BW in singletons. Polygenic scores constructed from a genome-wide association study on BW in the UK Biobank demonstrated strong predictive power in a target sample of Dutch twins and singletons. Together, our results indicate that a similar genetic architecture underlies BW in twins and singletons and that future genome-wide studies might benefit from including data from large twin registers.
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