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Sökning: WFRF:(Tadic V)

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  • Joffrin, E., et al. (författare)
  • Overview of the JET preparation for deuterium-tritium operation with the ITER like-wall
  • 2019
  • Ingår i: Nuclear Fusion. - : IOP PUBLISHING LTD. - 0029-5515 .- 1741-4326. ; 59:11
  • Forskningsöversikt (refereegranskat)abstract
    • For the past several years, the JET scientific programme (Pamela et al 2007 Fusion Eng. Des. 82 590) has been engaged in a multi-campaign effort, including experiments in D, H and T, leading up to 2020 and the first experiments with 50%/50% D-T mixtures since 1997 and the first ever D-T plasmas with the ITER mix of plasma-facing component materials. For this purpose, a concerted physics and technology programme was launched with a view to prepare the D-T campaign (DTE2). This paper addresses the key elements developed by the JET programme directly contributing to the D-T preparation. This intense preparation includes the review of the physics basis for the D-T operational scenarios, including the fusion power predictions through first principle and integrated modelling, and the impact of isotopes in the operation and physics of D-T plasmas (thermal and particle transport, high confinement mode (H-mode) access, Be and W erosion, fuel recovery, etc). This effort also requires improving several aspects of plasma operation for DTE2, such as real time control schemes, heat load control, disruption avoidance and a mitigation system (including the installation of a new shattered pellet injector), novel ion cyclotron resonance heating schemes (such as the three-ions scheme), new diagnostics (neutron camera and spectrometer, active Alfven eigenmode antennas, neutral gauges, radiation hard imaging systems...) and the calibration of the JET neutron diagnostics at 14 MeV for accurate fusion power measurement. The active preparation of JET for the 2020 D-T campaign provides an incomparable source of information and a basis for the future D-T operation of ITER, and it is also foreseen that a large number of key physics issues will be addressed in support of burning plasmas.
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  • Heckman, Michael G., et al. (författare)
  • Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
  • 2013
  • Ingår i: Movement Disorders. - : John Wiley and Sons. - 0885-3185. ; 28:12, s. 1740-1744
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
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  • Ross, Owen A., et al. (författare)
  • Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
  • 2011
  • Ingår i: Lancet Neurology. - : Lancet Ltd. - 1474-4465. ; 10:10, s. 898-908
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
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  • Stevanovic, D., et al. (författare)
  • Assessing the symptoms of Internet Gaming Disorder among college/university students: An international validation study of a self-report
  • 2020
  • Ingår i: Psihologija. - 0048-5705. ; 53:1, s. 43-63
  • Tidskriftsartikel (refereegranskat)abstract
    • The present study evaluated the psychometric properties of a self-report scale for assessing Internet Gaming Disorder (IGD) symptoms according to the DSM-5 and ICD-11 among 3270 college/university students (2095 [64.1%] females; age mean 21.6 [3.1] years) from different countries worldwide. Croatian, English, Polish, Portuguese, Serbian, Turkish, and Vietnamese versions of the scale were tested. The study showed that symptoms of IGD could be measured as a single underlying factor among college/university students. A nine item-symptom scale following DSM-5, and a short four-item scale representing the main ICD-11 symptoms, had sound internal consistency and construct validity. Three symptom-items were found non-invariant across the language samples (i.e., preoccupation with on-line gaming, loss of interests in previous hobbies and entertainment, and the use of gaming to relieve negative moods). This study provides initial evidence for assessing IGD symptoms among college/university students and will hopefully foster further research into gaming addiction in this population worldwide especially with taking into account language/cultural differences.
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  • Witt, S. H., et al. (författare)
  • Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia
  • 2017
  • Ingår i: Translational Psychiatry. - : Nature Publishing Group. - 2158-3188. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P = 4.42 x 10(-7)) and PKP4 (P = 8.67 x 10(-7)); and gene-set analysis yielded a significant finding for exocytosis (GO: 0006887, PFDR = 0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r(g) = 0.28 [P = 2.99 x 10(-3)]), SCZ (r(g) = 0.34 [P = 4.37 x 10(-5)]) and MDD (r(g) = 0.57 [P = 1.04 x 10(-3)]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
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