| 1. |
- Gialluisi, A, et al.
(författare)
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Genome-wide association scan identifies new variants associated with a cognitive predictor of dyslexia
- 2019
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Ingår i: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 77-
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Tidskriftsartikel (refereegranskat)abstract
- Developmental dyslexia (DD) is one of the most prevalent learning disorders, with high impact on school and psychosocial development and high comorbidity with conditions like attention-deficit hyperactivity disorder (ADHD), depression, and anxiety. DD is characterized by deficits in different cognitive skills, including word reading, spelling, rapid naming, and phonology. To investigate the genetic basis of DD, we conducted a genome-wide association study (GWAS) of these skills within one of the largest studies available, including nine cohorts of reading-impaired and typically developing children of European ancestry (N = 2562–3468). We observed a genome-wide significant effect (p < 1 × 10−8) on rapid automatized naming of letters (RANlet) for variants on 18q12.2, within MIR924HG (micro-RNA 924 host gene; rs17663182 p = 4.73 × 10−9), and a suggestive association on 8q12.3 within NKAIN3 (encoding a cation transporter; rs16928927, p = 2.25 × 10−8). rs17663182 (18q12.2) also showed genome-wide significant multivariate associations with RAN measures (p = 1.15 × 10−8) and with all the cognitive traits tested (p = 3.07 × 10−8), suggesting (relational) pleiotropic effects of this variant. A polygenic risk score (PRS) analysis revealed significant genetic overlaps of some of the DD-related traits with educational attainment (EDUyears) and ADHD. Reading and spelling abilities were positively associated with EDUyears (p ~ [10−5–10−7]) and negatively associated with ADHD PRS (p ~ [10−8−10−17]). This corroborates a long-standing hypothesis on the partly shared genetic etiology of DD and ADHD, at the genome-wide level. Our findings suggest new candidate DD susceptibility genes and provide new insights into the genetics of dyslexia and its comorbities.
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| 2. |
- Gialluisi, A, et al.
(författare)
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Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
- 2021
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Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:7, s. 3004-3017
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Tidskriftsartikel (refereegranskat)abstract
- Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atpT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63];p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45];p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 × 10−4), educational attainment (0.86[0.82; 0.91];p = 2 × 10−7), and intelligence (0.72[0.68; 0.76];p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
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| 3. |
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| 4. |
- Abbasloo, A., et al.
(författare)
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Interactive formation of statistical hypotheses in diffusion tensor imaging
- 2019
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Ingår i: Eurographics Workshop on Visual Computing for Biology and Medicine, VCBM 2019. - 9783038680819 ; , s. 33-43
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Konferensbidrag (refereegranskat)abstract
- When Diffusion Tensor Imaging (DTI) is used in clinical studies, statistical hypothesis testing is the standard approach to establish significant differences between groups, such as patients and healthy controls. However, diffusion tensors contain six degrees of freedom, and the most commonly used univariate tests reduce them to a single scalar, such as Fractional Anisotropy. Multivariate tests that account for the full tensor information have been developed, but have not been widely adopted in practice. Based on analyzing the limitations of existing univariate and multivariate tests, we argue that it is beneficial to use a more flexible, steerable test. Therefore, we introduce a test that can be customized to include any subset of tensor attributes that are relevant to the analysis task at hand. We also present a visual analytics system that supports the exploratory task of customizing it to a specific scenario. Our system closely integrates quantitative analysis with suitable visualizations. It links spatial and abstract views to reveal clusters of strong differences, to relate them to the affected anatomical structures, and to visually compare the results of different tests. A use case is presented in which our system leads to the formation of several new hypotheses about the effects of systemic lupus erythematosus on water diffusion in the brain.
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| 5. |
- Foerster, Bradley R., et al.
(författare)
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Reduced insular gamma-aminobutyric acid in fibromyalgia
- 2012
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 64:2, s. 579-583
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Tidskriftsartikel (refereegranskat)abstract
- Objective Recent scientific findings have reinvigorated interest in examining the role of gamma-aminobutyric acid (GABA), the major inhibitory central nervous system neurotransmitter, in chronic pain conditions. Decreased inhibitory neurotransmission is a proposed mechanism in the pathophysiology of chronic pain syndromes such as fibromyalgia (FM). The purpose of this study was to test the hypothesis that decreased levels of insular and anterior cingulate GABA would be present in FM patients, and that the concentration of this neurotransmitter would be correlated with pressurepain thresholds. Methods. Sixteen FM patients and 17 age-and sex-matched healthy controls underwent pressure-pain testing and a 3T proton magnetic resonance spectroscopy session in which the right anterior insula, right posterior insula, anterior cingulate, and occipital cortex were examined in subjects at rest. Results. GABA levels in the right anterior insula were significantly lower in FM patients compared with healthy controls (mean +/- SD 1.17 +/- 0.24 arbitrary institutional units versus 1.42 +/- 0.32 arbitrary institutional units; P = 0.016). There was a trend toward increased GABA levels in the anterior cingulate of FM patients compared with healthy controls (P = 0.06). No significant differences between groups were detected in the posterior insula or occipital cortex (P > 0.05 for all comparisons). Within the right posterior insula, higher levels of GABA were positively correlated with pressurepain thresholds in the FM patients (Spearman's rho = 0.63; P = 0.02). Conclusion. Diminished inhibitory neurotransmission resulting from lower concentrations of GABA within the right anterior insula may play a role in the pathophysiology of FM and other central pain syndromes.
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| 6. |
- Kamstrup, P, et al.
(författare)
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Biomarkers of Clot Activation and Degradation and Risk of Future Major Cardiovascular Events in Acute Exacerbation of COPD: A Cohort Sub-Study in a Randomized Trial Population
- 2022
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 10:8
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Tidskriftsartikel (refereegranskat)abstract
- Cardiovascular diseases are common in patients with chronic obstructive pulmonary disease (COPD). Clot formation and resolution secondary to systemic inflammation may be a part of the explanation. The aim was to determine whether biomarkers of clot formation (products of von Willebrand Factor formation and activation) and clot resolution (product of fibrin degeneration) during COPD exacerbation predicted major cardiovascular events (MACE). The cohort was based on clinical data and biobank plasma samples from a trial including patients admitted with an acute exacerbation of COPD (CORTICO-COP). Neo-epitope biomarkers of formation and the activation of von Willebrand factor (VWF-N and V-WFA, respectively) and cross-linked fibrin degradation (X-FIB) were assessed using ELISAs in EDTA plasma at the time of acute admission, and analyzed for time-to-first MACE within 36 months, using multivariable Cox proportional hazards models. In total, 299/318 participants had samples available for analysis. The risk of MACE for patients in the upper quartile of each biomarker versus the lower quartile was: X-FIB: HR 0.98 (95% CI 0.65–1.48), VWF-N: HR 1.56 (95% CI 1.07–2.27), and VWF-A: HR 0.78 (95% CI 0.52–1.16). Thus, in COPD patients with an acute exacerbation, VWF-N was associated with future MACE and warrants further studies in a larger population.
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| 7. |
- Larsson Ivanov, Oskar, et al.
(författare)
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Climate change impact on snow loads in northern Europe
- 2022
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Ingår i: Structural Safety. - : Elsevier BV. - 0167-4730. ; 97
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Tidskriftsartikel (refereegranskat)abstract
- Ongoing and future climate change will affect our built environment. It will have an impact on how we should design our structures to withstand the future environment. One important load when designing buildings in high latitudes and high elevations is the snow load, which in many countries is the governing load for roofs and other structural parts. A warmer climate may lead to a reduction in snow cover. How this reduction relates to extreme values that occur very seldom, however, is unclear. For some regions an increase in precipitation may lead to an increase in snow fall over the winter, and thus to higher snow loads even in a warmer climate. The annual maximum snow water equivalents available from an ensemble of regional climate projections representing the three emission scenarios, RCP 2.6, RCP 4.5, and RCP 8.5, were used to project how the snow load will change in northern Europe until the end of the century. The variability between the different models is studied by analyzing results for individual cities as well as the overall regional variation. The results show that the spatial difference is large, where the mountainous and colder areas may experience an increase in extreme snow loads in the future for all climate scenarios, while the warmer parts of the region may have a significant decrease. The study shows that it is possible to project future snow loads with reasonable accuracy. The variability is still large, though, and must be considered when using climate projections for structural design.
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| 8. |
- Lin, Changgui, 1985, et al.
(författare)
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Present and future European heat wave magnitudes: climatologies, trends, and their associated uncertainties in GCM-RCM model chains
- 2022
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Ingår i: Earth System Dynamics. - : Copernicus GmbH. - 2190-4979 .- 2190-4987. ; 13:3, s. 1197-1214
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates present and future European heat wave magnitudes, represented by the Heat Wave Magnitude Index-daily (HWMId), for regional climate models (RCMs) and the driving global climate models (GCMs) over Europe. A subset of the large EURO-CORDEX ensemble is employed to study sources of uncertainties related to the choice of GCMs, RCMs, and their combinations. We initially compare the evaluation runs of the RCMs driven by ERA-interim reanalysis to E-OBS (observation-based estimates), finding that the RCMs can capture most of the observed spatial and temporal features of HWMId. With their higher resolution compared to GCMs, RCMs can reveal spatial features of HWMId associated with small-scale processes (e.g., orographic effects); moreover, RCMs represent large-scale features of HWMId satisfactorily (e.g., by reproducing the general pattern revealed by E-OBS with high values at western coastal regions and low values at the eastern part). Our results indicate a clear added value of the RCMs compared to the driving GCMs. Forced with the emission scenario RCP8.5, all the GCM and RCM simulations consistently project a rise in HWMId at an exponential rate. However, the climate change signals projected by the GCMs are generally attenuated when downscaled by the RCMs, with the spatial pattern also altered. The uncertainty in a simulated future change of heat wave magnitudes following global warming can be attributed almost equally to the difference in model physics (as represented by different RCMs) and to the driving data associated with different GCMs. Regarding the uncertainty associated with RCM choice, a major factor is the different representation of the orographic effects. No consistent spatial pattern in the ensemble spread associated with different GCMs is observed between the RCMs, suggesting GCM uncertainties are transformed by RCMs in a complex manner due to the nonlinear nature of model dynamics and physics. In summary, our results support the use of dynamical downscaling for deriving regional climate realization regarding heat wave magnitudes. © Author(s) 2022.
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| 9. |
- Lundstedt, Staffan, et al.
(författare)
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First intercomparison study on the analysis of oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) in contaminated soil
- 2014
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Ingår i: TrAC. Trends in analytical chemistry. - : Elsevier. - 0165-9936 .- 1879-3142. ; 57, s. 83-92
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Forskningsöversikt (refereegranskat)abstract
- Oxygenated polycyclic aromatic hydrocarbons (oxy-PAHs) and nitrogen heterocyclic polycyclic aromatic compounds (N-PACs) are toxic, highly leachable and often abundant at sites that are also contaminated with PAHs. However, due to lack of regulations and standardized methods for their analysis, they are seldom included in monitoring and risk-assessment programs. This intercomparison study constitutes an important step in the harmonization of the analytical methods currently used, and may also be considered a first step towards the certification of reference materials for these compounds. The results showed that the participants were able to determine oxy-PAHs with accuracy similar to PAHs, with average determined mass fractions agreeing well with the known levels in a spiked soil and acceptable inter- and intra-laboratory precisions for all soils analyzed. For the N-PACs, the results were less satisfactory, and have to be improved by using analytical methods more specifically optimized for these compounds.
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| 10. |
- Pulatov, Bakhtiyor, et al.
(författare)
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Evaluation of the phenological synchrony between potato crop and Colorado potato beetle under future climate in Europe
- 2016
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Ingår i: Agriculture, Ecosystems & Environment. - : Elsevier BV. - 0167-8809. ; 224, s. 39-49
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Tidskriftsartikel (refereegranskat)abstract
- Europe is one of the world's largest food producers, and climate change may pose a serious threat to food security in the region. In the present study, we assess the potential impact of climate change on the Colorado Potato Beetle (CPB), Leptinotarsa decemlineata (Say)-a severe pest of potato (Solanum tuberosum, L.). We also investigate the possible impact of climate change on the phenological development of potato. The main focus is on factors that may limit the northward expansion of the CPB, and the number of generations per year in areas where the insect pest is already present. These factors include lack of temperature sum for completed development before winter, and lack of food (i.e. potato) due to mismatches in insect-host plant phenological synchrony.We use a gridded observational dataset and an ensemble of bias corrected regional climate model data for the period of 1981-2099, representing RCP8.5, as input to a potato and CPB phenological model. The results show that in the future, CPB individuals with a low developmental threshold (+10 °C) can complete maturity of two generations per year before potato is harvested in most parts of Europe. A third generation of CPB may not be able to complete maturation due to lack of food in south and central Europe, while temperature becomes a limiting factor further north. In north-eastern Europe, the initiation of a first generation may be delayed due to lack of food in spring. CPBs with a high developmental threshold (+12 °C) will emerge later from winter hibernation, and food availability will therefore not be a problem in spring. However, individuals with a high developmental threshold face a greater risk of regeneration failure caused by harvesting of potato in autumn. The potential lack of food in autumn may also increase the strength of selection towards a low developmental threshold in northern populations. The combined analysis of CPB and potato phenology indicated that climate change can lead to increased pressure from the CPB in most potato growing areas.
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