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  • Schael, S, et al. (author)
  • Precision electroweak measurements on the Z resonance
  • 2006
  • In: Physics Reports. - : Elsevier BV. - 0370-1573 .- 1873-6270. ; 427:5-6, s. 257-454
  • Research review (peer-reviewed)abstract
    • We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron-positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLID experiment using a polarised beam at SLC. The measurements include cross-sections, forward-backward asymmetries and polarised asymmetries. The mass and width of the Z boson, m(Z) and Gamma(Z), and its couplings to fermions, for example the p parameter and the effective electroweak mixing angle for leptons, are precisely measured: m(Z) = 91.1875 +/- 0.0021 GeV, Gamma(Z) = 2.4952 +/- 0.0023 GeV, rho(l) = 1.0050 +/- 0.0010, sin(2)theta(eff)(lept) = 0.23153 +/- 0.00016. The number of light neutrino species is determined to be 2.9840 +/- 0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward-backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, m(t) = 173(+10)(+13) GeV, and the mass of the W boson, m(W) = 80.363 +/- 0.032 GeV. These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of m(t) and m(W), the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than 285 GeV at 95% confidence level. (c) 2006 Elsevier B.V. All rights reserved.
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  • 2021
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  • Kanai, M, et al. (author)
  • 2023
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  • Glasbey, JC, et al. (author)
  • 2021
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  • Niemi, MEK, et al. (author)
  • 2021
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  • 2021
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  • Abel, I, et al. (author)
  • Overview of the JET results with the ITER-like wall
  • 2013
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 53:10, s. 104002-
  • Journal article (peer-reviewed)abstract
    • Following the completion in May 2011 of the shutdown for the installation of the beryllium wall and the tungsten divertor, the first set of JET campaigns have addressed the investigation of the retention properties and the development of operational scenarios with the new plasma-facing materials. The large reduction in the carbon content (more than a factor ten) led to a much lower Z(eff) (1.2-1.4) during L- and H-mode plasmas, and radiation during the burn-through phase of the plasma initiation with the consequence that breakdown failures are almost absent. Gas balance experiments have shown that the fuel retention rate with the new wall is substantially reduced with respect to the C wall. The re-establishment of the baseline H-mode and hybrid scenarios compatible with the new wall has required an optimization of the control of metallic impurity sources and heat loads. Stable type-I ELMy H-mode regimes with H-98,H-y2 close to 1 and beta(N) similar to 1.6 have been achieved using gas injection. ELM frequency is a key factor for the control of the metallic impurity accumulation. Pedestal temperatures tend to be lower with the new wall, leading to reduced confinement, but nitrogen seeding restores high pedestal temperatures and confinement. Compared with the carbon wall, major disruptions with the new wall show a lower radiated power and a slower current quench. The higher heat loads on Be wall plasma-facing components due to lower radiation made the routine use of massive gas injection for disruption mitigation essential.
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  • Forrest, ARR, et al. (author)
  • A promoter-level mammalian expression atlas
  • 2014
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 507:7493, s. 462-
  • Journal article (peer-reviewed)
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  • Romanelli, F, et al. (author)
  • Overview of the JET results
  • 2011
  • In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 51:9
  • Journal article (peer-reviewed)abstract
    • Since the last IAEA Conference JET has been in operation for one year with a programmatic focus on the qualification of ITER operating scenarios, the consolidation of ITER design choices and preparation for plasma operation with the ITER-like wall presently being installed in JET. Good progress has been achieved, including stationary ELMy H-mode operation at 4.5 MA. The high confinement hybrid scenario has been extended to high triangularity, lower ρ*and to pulse lengths comparable to the resistive time. The steady-state scenario has also been extended to lower ρ*and ν*and optimized to simultaneously achieve, under stationary conditions, ITER-like values of all other relevant normalized parameters. A dedicated helium campaign has allowed key aspects of plasma control and H-mode operation for the ITER non-activated phase to be evaluated. Effective sawtooth control by fast ions has been demonstrated with3He minority ICRH, a scenario with negligible minority current drive. Edge localized mode (ELM) control studies using external n = 1 and n = 2 perturbation fields have found a resonance effect in ELM frequency for specific q95values. Complete ELM suppression has, however, not been observed, even with an edge Chirikov parameter larger than 1. Pellet ELM pacing has been demonstrated and the minimum pellet size needed to trigger an ELM has been estimated. For both natural and mitigated ELMs a broadening of the divertor ELM-wetted area with increasing ELM size has been found. In disruption studies with massive gas injection up to 50% of the thermal energy could be radiated before, and 20% during, the thermal quench. Halo currents could be reduced by 60% and, using argon/deuterium and neon/deuterium gas mixtures, runaway electron generation could be avoided. Most objectives of the ITER-like ICRH antenna have been demonstrated; matching with closely packed straps, ELM resilience, scattering matrix arc detection and operation at high power density (6.2 MW m-2) and antenna strap voltages (42 kV). Coupling measurements are in very good agreement with TOPICA modelling. © 2011 IAEA, Vienna.
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  • Baldwin, H, et al. (author)
  • Neuroanatomical heterogeneity and homogeneity in individuals at clinical high risk for psychosis
  • 2022
  • In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 12:1, s. 297-
  • Journal article (peer-reviewed)abstract
    • Individuals at Clinical High Risk for Psychosis (CHR-P) demonstrate heterogeneity in clinical profiles and outcome features. However, the extent of neuroanatomical heterogeneity in the CHR-P state is largely undetermined. We aimed to quantify the neuroanatomical heterogeneity in structural magnetic resonance imaging measures of cortical surface area (SA), cortical thickness (CT), subcortical volume (SV), and intracranial volume (ICV) in CHR-P individuals compared with healthy controls (HC), and in relation to subsequent transition to a first episode of psychosis. The ENIGMA CHR-P consortium applied a harmonised analysis to neuroimaging data across 29 international sites, including 1579 CHR-P individuals and 1243 HC, offering the largest pooled CHR-P neuroimaging dataset to date. Regional heterogeneity was indexed with the Variability Ratio (VR) and Coefficient of Variation (CV) ratio applied at the group level. Personalised estimates of heterogeneity of SA, CT and SV brain profiles were indexed with the novel Person-Based Similarity Index (PBSI), with two complementary applications. First, to assess the extent of within-diagnosis similarity or divergence of neuroanatomical profiles between individuals. Second, using a normative modelling approach, to assess the ‘normativeness’ of neuroanatomical profiles in individuals at CHR-P. CHR-P individuals demonstrated no greater regional heterogeneity after applying FDR corrections. However, PBSI scores indicated significantly greater neuroanatomical divergence in global SA, CT and SV profiles in CHR-P individuals compared with HC. Normative PBSI analysis identified 11 CHR-P individuals (0.70%) with marked deviation (>1.5 SD) in SA, 118 (7.47%) in CT and 161 (10.20%) in SV. Psychosis transition was not significantly associated with any measure of heterogeneity. Overall, our examination of neuroanatomical heterogeneity within the CHR-P state indicated greater divergence in neuroanatomical profiles at an individual level, irrespective of psychosis conversion. Further large-scale investigations are required of those who demonstrate marked deviation.
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  • Dork, T, et al. (author)
  • Two truncating variants in FANCC and breast cancer risk
  • 2019
  • In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 12524-
  • Journal article (peer-reviewed)abstract
    • Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
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  • Haas, SS, et al. (author)
  • Normative modeling of brain morphometry in Clinical High-Risk for Psychosis
  • 2023
  • In: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
  • Journal article (other academic/artistic)abstract
    • ImportanceThe lack of robust neuroanatomical markers of psychosis risk has been traditionally attributed to heterogeneity. A complementary hypothesis is that variation in neuroanatomical measures in the majority of individuals at psychosis risk may be nested within the range observed in healthy individuals.ObjectiveTo quantify deviations from the normative range of neuroanatomical variation in individuals at clinical high-risk for psychosis (CHR-P) and evaluate their overlap with healthy variation and their association with positive symptoms, cognition, and conversion to a psychotic disorder.Design, Setting, and ParticipantsClinical, IQ and FreeSurfer-derived regional measures of cortical thickness (CT), cortical surface area (SA), and subcortical volume (SV) from 1,340 CHR-P individuals [47.09% female; mean age: 20.75 (4.74) years] and 1,237 healthy individuals [44.70% female; mean age: 22.32 (4.95) years] from 29 international sites participating in the ENIGMA Clinical High Risk for Psychosis Working Group.Main Outcomes and MeasuresFor each regional morphometric measure, z-scores were computed that index the degree of deviation from the normative means of that measure in a healthy reference population (N=37,407). Average deviation scores (ADS) for CT, SA, SV, and globally across all measures (G) were generated by averaging the respective regional z-scores. Regression analyses were used to quantify the association of deviation scores with clinical severity and cognition and two-proportion z-tests to identify case-control differences in the proportion of individuals with infranormal (z<-1.96) or supranormal (z>1.96) scores.ResultsCHR-P and healthy individuals overlapped in the distributions of the observed values, regional z-scores, and all ADS vales. The proportion of CHR-P individuals with infranormal or supranormal values in any metric was low (<12%) and similar to that of healthy individuals. CHR-P individuals who converted to psychosis compared to those who did not convert had a higher percentage of infranormal values in temporal regions (5-7% vs 0.9-1.4%). In the CHR-P group, only the ADSSAshowed significant but weak associations (|β|<0.09; PFDR<0.05) with positive symptoms and IQ.Conclusions and RelevanceThe study findings challenge the usefulness of macroscale neuromorphometric measures as diagnostic biomarkers of psychosis risk and suggest that such measures do not provide an adequate explanation for psychosis risk.Key pointsQuestionIs the risk of psychosis associated with brain morphometric changes that deviate significantly from healthy variation?FindingsIn this study of 1340 individuals high-risk for psychosis (CHR-P) and 1237 healthy participants, individual-level variation in macroscale neuromorphometric measures of the CHR-P group was largely nested within healthy variation and was not associated with the severity of positive psychotic symptoms or conversion to a psychotic disorder.MeaningThe findings suggest the macroscale neuromorphometric measures have limited utility as diagnostic biomarkers of psychosis risk.
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  • Kim, Myung Ja, et al. (author)
  • Effects of Value-Belief-Norm Theory, ESG, and AI on Space Tourist Behavior for Sustainability With Three Types of Space Tourism
  • 2024
  • In: Journal of Travel Research. - : Sage Publications. - 0047-2875 .- 1552-6763. ; 63:6, s. 1395-1410
  • Journal article (peer-reviewed)abstract
    • Since reusable launch vehicles have revolutionized access to space, space tourism has received enormous policy and research attention. However, such growth is occurring within a wider context of concerns over climate change, emissions, and space debris. Although the space industries have enormous environmental impacts, few studies have been undertaken on the sustainability of space tourism. Therefore, we aim to create and assess an extended value-beliefs-norms theory with environmental, social, and governance (ESG) factors, trust in artificial intelligence (AI), and the benefits of AI, in comparing three types of space tourism (Earth, suborbital, and orbital). To achieve the goals, multi-method analyses of 1,000 respondents were applied, including partial least squares-structural equation modeling, multi-group analysis, fuzzy-set Qualitative Comparative Analysis, and deep learning. Results revealed that the extended value-belief-norm model well explains space tourist behavior, ESG also has significant roles on the research model, and the three types have unique characteristics.
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  • Kim, Myung Ja, et al. (author)
  • Orbital and sub-orbital space tourism : motivation, constraint and artificial intelligence
  • 2024
  • In: Tourism Review. - : Emerald Group Publishing Limited. - 1660-5373 .- 1759-8451. ; 79:2, s. 392-407
  • Journal article (peer-reviewed)abstract
    • PurposeThere is limited research on the behavior of different categories of space tourists as identified by different types of space tourism. To address this deficiency, the purpose of this study is to examine what factors make consumers participate in orbital and/or suborbital space tourism, along with three dimensions of motivation, constraint and artificial intelligence. To achieve this study's goals, a comprehensive research model was developed that included three dimensions of intrinsic and extrinsic motivation, intrapersonal and interpersonal constraint and awareness of and trust in artificial intelligence, in comparing orbital and suborbital space tourism groups. Design/methodology/approachA questionnaire was carried out with respondents who wanted to participate in orbital (n = 332) and suborbital (n = 332) space tourism in the future. Partial least squares-structural equation modeling, fuzzy-set qualitative comparative analysis, multi-group analysis and deep learning were used to understand potential space tourist behavior. FindingsExtrinsic motivation has the greatest positive impact on behavioral intention, followed by awareness of and trust in artificial intelligence, while intrapersonal constraint strongly negatively affects behavioral intention. Surprisingly, interpersonal constraint is insignificant by partial least squares-structural equation modeling but is still one of sufficient causal configurations by fuzzy-set qualitative comparative analysis. Interestingly, the two types of space tourism have very distinct characteristics. Originality/valueThis study created a comprehensive integrated research model with three dimensions of motivation, constraint and artificial intelligence, along with potential orbital and suborbital space tourist groups, to identify future consumer behavior. Importantly, this study used multi-analysis methods using four different approaches to better shed light on potential orbital and suborbital space tourists.
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  • Kim, Myung Ja, et al. (author)
  • Space tourism : Do age and gender make a difference in risk perception?
  • 2023
  • In: Journal of Hospitality and Tourism Management. - : Elsevier. - 1447-6770 .- 1839-5260. ; 57, s. 13-17
  • Journal article (peer-reviewed)abstract
    • Space tourism is an industry with risks including health and safety, space debris, biological hazards, and sustainability concerns. However, there is limited research on the perceived risk of participation in space tourism, particularly regarding age and gender differences. An integrated research model was created and tested with four perceived risk dimensions using fuzzy-set Qualitative Comparative Analysis. A survey of 1000 South Korean residents over 18 who wanted to participate in space tourism was conducted. Results show significant differences in perceived risks between senior and younger groups, as well as male and female respondents. These findings offer valuable insights for space tourism stakeholders.
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  • Kim, Myung Ja, et al. (author)
  • Space tourism : Value-attitude-behavior theory, artificial intelligence, and sustainability
  • 2024
  • In: Journal of Retailing and Consumer Services. - 0969-6989. ; 77
  • Journal article (peer-reviewed)abstract
    • Despite concerns over its sustainability, space tourism is an emerging luxury consumer service which is promoted to participants as providing a new connection to Earth and humanity. However, little research examines the potential connectivity between sustainability and space tourism, especially given the strong technological dimensions of space tourism. The purpose of this study is to explore an extended value-attitude-behavior theory with AI awareness and social and personal norms to examine space tourism's alignment with the UN's 17 Sustainable Development Goals. Through 664 potential space tourism consumers and applying PLS-SEM, multi-group analysis, fsQCA, and deep learning methods, findings revealed the significant influence of value and AI awareness on attitude and social and personal norms leading to sustainable behaviors. Findings provide insights into space tourism's sustainability, emphasizing environmental considerations and AI awareness in shaping luxury travel consumer services.
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  • Kim, Myung Ja, et al. (author)
  • The effects of individual and organizational interventions on space tourism : applying EMGB and fsQCA
  • 2023
  • In: Current Issues in Tourism. - : Informa UK Limited. - 1368-3500 .- 1747-7603. ; 26:9, s. 1389-1393
  • Journal article (peer-reviewed)abstract
    • There is limited theoretically informed research on sustainability in the space tourism market. An extended model of goal-directed behaviour (EMGB) is created and verified with individual and organizational interventions, comparing space tourism experienced and non-experienced travellers. Results revealed that individual intervention has fully significant effects on all MGB constructs, while organizational intervention has partially significant impacts, which in turn influence desire relevant to behavioural intention. The findings from fsQCA showed the different profiles of experienced and non-experienced tourists.
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  • Kroes, JA, et al. (author)
  • Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
  • 2023
  • In: ERJ open research. - : European Respiratory Society (ERS). - 2312-0541. ; 9:2
  • Journal article (peer-reviewed)abstract
    • An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking non-standardized, patient-level registry-data. Mepolizumab has shown clinical efficacy in RCTs and prospective real-world studies and could therefore serve as a proof of principle for this novel approach.AimTo harmonize data from 10 national severe asthma registries and characterize patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns.MethodsIn this observational cohort study, registry data (5871 patients) were extracted for harmonization. Where harmonization was possible, patients who initiated mepolizumab between 1-1-2016 and 31-12-2021 were examined. Changes of a 12 (range 11–18) months period in frequent (≥2) exacerbations, maintenance OCS use and dose were analyzed in a privacy-preserving manner using meta-analysis of generalized estimating equation parameters. Periods before and during the COVID-19 pandemic were analyzed separately.ResultsIn 912 patients who fulfilled selection criteria mepolizumab significantly reduced frequent exacerbations (OR;95%CI: 0.18;0.13–0.25), maintenance OCS use (OR;95%CI: 0.75;0.61–0.92) and dose (mean; 95%CI: −3.93 mg·day−1; −5.24–2.62) in the Pre-Pandemic group, with similar trends in the Pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns.ConclusionsBy harmonizing patient-level registry data and applying federated analysis, SHARP demonstrated the real-wold effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.
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  • Menden, MP, et al. (author)
  • Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen
  • 2019
  • In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 2674-
  • Journal article (peer-reviewed)abstract
    • The effectiveness of most cancer targeted therapies is short-lived. Tumors often develop resistance that might be overcome with drug combinations. However, the number of possible combinations is vast, necessitating data-driven approaches to find optimal patient-specific treatments. Here we report AstraZeneca’s large drug combination dataset, consisting of 11,576 experiments from 910 combinations across 85 molecularly characterized cancer cell lines, and results of a DREAM Challenge to evaluate computational strategies for predicting synergistic drug pairs and biomarkers. 160 teams participated to provide a comprehensive methodological development and benchmarking. Winning methods incorporate prior knowledge of drug-target interactions. Synergy is predicted with an accuracy matching biological replicates for >60% of combinations. However, 20% of drug combinations are poorly predicted by all methods. Genomic rationale for synergy predictions are identified, including ADAM17 inhibitor antagonism when combined with PIK3CB/D inhibition contrasting to synergy when combined with other PI3K-pathway inhibitors in PIK3CA mutant cells.
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  • Ramilowski, JA, et al. (author)
  • Functional annotation of human long noncoding RNAs via molecular phenotyping
  • 2020
  • In: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 30:7, s. 1060-1072
  • Journal article (peer-reviewed)abstract
    • Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-to-date lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.
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  • Thompson, PM, et al. (author)
  • ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
  • 2020
  • In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 100-
  • Journal article (peer-reviewed)abstract
    • This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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