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Sökning: WFRF:(Nicolas Aude)

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1.
  • Jones, Geraint H., et al. (författare)
  • The Comet Interceptor Mission
  • 2024
  • Ingår i: Space Science Reviews. - : Springer Nature. - 0038-6308 .- 1572-9672. ; 220:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Here we describe the novel, multi-point Comet Interceptor mission. It is dedicated to the exploration of a little-processed long-period comet, possibly entering the inner Solar System for the first time, or to encounter an interstellar object originating at another star. The objectives of the mission are to address the following questions: What are the surface composition, shape, morphology, and structure of the target object? What is the composition of the gas and dust in the coma, its connection to the nucleus, and the nature of its interaction with the solar wind? The mission was proposed to the European Space Agency in 2018, and formally adopted by the agency in June 2022, for launch in 2029 together with the Ariel mission. Comet Interceptor will take advantage of the opportunity presented by ESA’s F-Class call for fast, flexible, low-cost missions to which it was proposed. The call required a launch to a halo orbit around the Sun-Earth L2 point. The mission can take advantage of this placement to wait for the discovery of a suitable comet reachable with its minimum Δ V capability of 600 ms − 1 . Comet Interceptor will be unique in encountering and studying, at a nominal closest approach distance of 1000 km, a comet that represents a near-pristine sample of material from the formation of the Solar System. It will also add a capability that no previous cometary mission has had, which is to deploy two sub-probes – B1, provided by the Japanese space agency, JAXA, and B2 – that will follow different trajectories through the coma. While the main probe passes at a nominal 1000 km distance, probes B1 and B2 will follow different chords through the coma at distances of 850 km and 400 km, respectively. The result will be unique, simultaneous, spatially resolved information of the 3-dimensional properties of the target comet and its interaction with the space environment. We present the mission’s science background leading to these objectives, as well as an overview of the scientific instruments, mission design, and schedule.
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2.
  • Le Guen, Yann, et al. (författare)
  • Multiancestry analysis of the HLA locus in Alzheimer's and Parkinson's diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes.
  • 2023
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 1091-6490 .- 0027-8424. ; 120:36
  • Tidskriftsartikel (refereegranskat)abstract
    • Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson's disease (PD) and Alzheimer's disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues.
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3.
  • Luo, Jiao, et al. (författare)
  • Genetic Associations Between Modifiable Risk Factors and Alzheimer Disease
  • 2023
  • Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 6:5
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.OBJECTIVE To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.DESIGN, SETTING, AND PARTICIPANTS This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for AD were obtained from the European Alzheimer & Dementia Biobank (EADB), generated on August 31, 2021. Main analyses were conducted using the EADB clinically diagnosed end point data. All analyses were performed between April 12 and October 27, 2022.EXPOSURES Genetically determined modifiable risk factors. MAIN OUTCOMES AND MEASURES Odds ratios (ORs) and 95% CIs for AD were calculated per 1-unit change of genetically determined risk factors.RESULTS The EADB-diagnosed cohort included 39106 participants with clinically diagnosed AD and 401577 control participants without AD. The mean age ranged from 72 to 83 years for participants with AD and 51 to 80 years for control participants. Among participants with AD, 54% to 75% were female, and among control participants, 48% to 60% were female. Genetically determined high-density lipoprotein (HDL) cholesterol concentrations were associated with increased odds of AD (OR per 1-SD increase, 1.10 [95% CI, 1.05-1.16]). Genetically determined high systolic blood pressure was associated with increased risk of AD after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.22 [95% CI, 1.02-1.46]). In a second analysis to minimize bias due to sample overlap, the entire UK Biobank was excluded from the EADB consortium; odds for AD were similar for HDL cholesterol (OR per 1-SD unit increase, 1.08 [95% CI, 1.02-1.15]) and systolic blood pressure after adjusting for diastolic blood pressure (OR per 10-mm Hg increase, 1.23 [95% CI, 1.01-1.50]).CONCLUSIONS AND RELEVANCE This genetic association study found novel genetic associations between high HDL cholesterol concentrations and high systolic blood pressure with higher risk of AD. These findings may inspire new drug targeting and improved prevention implementation.
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4.
  • Alignier, Audrey, et al. (författare)
  • Configurational crop heterogeneity increases within-field plant diversity
  • 2020
  • Ingår i: Journal of Applied Ecology. - : Wiley. - 0021-8901 .- 1365-2664. ; 57:4, s. 654-663
  • Tidskriftsartikel (refereegranskat)abstract
    • Increasing landscape heterogeneity by restoring semi-natural elements to reverse farmland biodiversity declines is not always economically feasible or acceptable to farmers due to competition for land. We hypothesized that increasing the heterogeneity of the crop mosaic itself, hereafter referred to as crop heterogeneity, can have beneficial effects on within-field plant diversity. Using a unique multi-country dataset from a cross-continent collaborative project covering 1,451 agricultural fields within 432 landscapes in Europe and Canada, we assessed the relative effects of compositional and configurational crop heterogeneity on within-field plant diversity components. We also examined how these relationships were modulated by the position within the field. We found strong positive effects of configurational crop heterogeneity on within-field plant alpha and gamma diversity in field interiors. These effects were as high as the effect of semi-natural cover. In field borders, effects of crop heterogeneity were limited to alpha diversity. We suggest that a heterogeneous crop mosaic may overcome the high negative impact of management practices on plant diversity in field interiors, whereas in field borders, where plant diversity is already high, landscape effects are more limited. Synthesis and applications. Our study shows that increasing configurational crop heterogeneity is beneficial to within-field plant diversity. It opens up a new effective and complementary way to promote farmland biodiversity without taking land out of agricultural production. We therefore recommend adopting manipulation of crop heterogeneity as a specific, effective management option in future policy measures, perhaps adding to agri-environment schemes, to contribute to the conservation of farmland plant diversity.
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5.
  • Gninenko, Nicolas, et al. (författare)
  • Functional MRI Neurofeedback Outperforms Cognitive Behavioral Therapy for Reducing Tinnitus Distress : A Prospective Randomized Clinical Trial.
  • 2024
  • Ingår i: Radiology. - 0033-8419 .- 1527-1315. ; 310:2, s. e231143-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Cognitive behavioral therapy (CBT) is the current standard treatment for chronic severe tinnitus; however, preliminary evidence suggests that real-time functional MRI (fMRI) neurofeedback therapy may be more effective. Purpose To compare the efficacy of real-time fMRI neurofeedback against CBT for reducing chronic tinnitus distress. Materials and Methods In this prospective controlled trial, participants with chronic severe tinnitus were randomized from December 2017 to December 2021 to receive either CBT (CBT group) for 10 weekly group sessions or real-time fMRI neurofeedback (fMRI group) individually during 15 weekly sessions. Change in the Tinnitus Handicap Inventory (THI) score (range, 0-100) from baseline to 6 or 12 months was assessed. Secondary outcomes included four quality-of-life questionnaires (Beck Depression Inventory, Pittsburgh Sleep Quality Index, State-Trait Anxiety Inventory, and World Health Organization Disability Assessment Schedule). Questionnaire scores between treatment groups and between time points were assessed using repeated measures analysis of variance and the nonparametric Wilcoxon signed rank test. Results The fMRI group included 21 participants (mean age, 49 years ± 11.4 [SD]; 16 male participants) and the CBT group included 22 participants (mean age, 53.6 years ± 8.8; 16 male participants). The fMRI group showed a greater reduction in THI scores compared with the CBT group at both 6 months (mean score change, -28.21 points ± 18.66 vs -12.09 points ± 18.86; P = .005) and 12 months (mean score change, -30 points ± 25.44 vs -4 points ± 17.2; P = .01). Compared with baseline, the fMRI group showed improved sleep (mean score, 8.62 points ± 4.59 vs 7.25 points ± 3.61; P = .006) and trait anxiety (mean score, 44 points ± 11.5 vs 39.84 points ± 10.5; P = .02) at 1 month and improved depression (mean score, 13.71 points ± 9.27 vs 6.53 points ± 5.17; P = .01) and general functioning (mean score, 24.91 points ± 17.05 vs 13.06 points ± 10.1; P = .01) at 6 months. No difference in these metrics over time was observed for the CBT group (P value range, .14 to >.99). Conclusion Real-time fMRI neurofeedback therapy led to a greater reduction in tinnitus distress than the current standard treatment of CBT. ClinicalTrials.gov registration no.: NCT05737888; Swiss Ethics registration no.: BASEC2017-00813 © RSNA, 2024 Supplemental material is available for this article.
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6.
  • Mahajan, Anubha, et al. (författare)
  • Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
  • 2022
  • Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
  • Tidskriftsartikel (refereegranskat)abstract
    • We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 x 10(-9)), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background. Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.
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7.
  • Nicolas, Aude, et al. (författare)
  • Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
  • 2018
  • Ingår i: Neuron. - : Cell Press. - 0896-6273 .- 1097-4199. ; 97:6, s. 1268-1283.e6
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.
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8.
  • Sirami, Clélia, et al. (författare)
  • Increasing crop heterogeneity enhances multitrophic diversity across agricultural regions
  • 2019
  • Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 116:33, s. 16442-16447
  • Tidskriftsartikel (refereegranskat)abstract
    • Agricultural landscape homogenization has detrimental effects on biodiversity and key ecosystem services. Increasing agricultural landscape heterogeneity by increasing seminatural cover can help to mitigate biodiversity loss. However, the amount of seminatural cover is generally low and difficult to increase in many intensively managed agricultural landscapes. We hypothesized that increasing the heterogeneity of the crop mosaic itself (hereafter “crop heterogeneity”) can also have positive effects on biodiversity. In 8 contrasting regions of Europe and North America, we selected 435 landscapes along independent gradients of crop diversity and mean field size. Within each landscape, we selected 3 sampling sites in 1, 2, or 3 crop types. We sampled 7 taxa (plants, bees, butterflies, hoverflies, carabids, spiders, and birds) and calculated a synthetic index of multitrophic diversity at the landscape level. Increasing crop heterogeneity was more beneficial for multitrophic diversity than increasing seminatural cover. For instance, the effect of decreasing mean field size from 5 to 2.8 ha was as strong as the effect of increasing seminatural cover from 0.5 to 11%. Decreasing mean field size benefited multitrophic diversity even in the absence of seminatural vegetation between fields. Increasing the number of crop types sampled had a positive effect on landscape-level multitrophic diversity. However, the effect of increasing crop diversity in the landscape surrounding fields sampled depended on the amount of seminatural cover. Our study provides large-scale, multitrophic, cross-regional evidence that increasing crop heterogeneity can be an effective way to increase biodiversity in agricultural landscapes without taking land out of agricultural production.
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