| 1. |
- Glasbey, JC, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
- de Rojas, I., et al.
(author)
-
Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- 2021
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
-
Journal article (peer-reviewed)abstract
- Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Fomalont, E. B., et al.
(author)
-
THE 2014 ALMA LONG BASELINE CAMPAIGN: AN OVERVIEW
- 2015
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 808:1
-
Journal article (peer-reviewed)abstract
- A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to similar to 15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried out from 2014 September to late November, culminating in end-to-end observations, calibrations, and imaging of selected Science Verification (SV) targets. This paper presents an overview of the campaign and its main results, including an investigation of the short-term coherence properties and systematic phase errors over the long baselines at the ALMA site, a summary of the SV targets and observations, and recommendations for science observing strategies at long baselines. Deep ALMA images of the quasar 3C 138 at 97 and 241 GHz are also compared to VLA 43 GHz results, demonstrating an agreement at a level of a few percent. As a result of the extensive program of LBC testing, the highly successful SV imaging at long baselines achieved angular resolutions as fine as 19 mas at similar to 350 GHz. Observing with ALMA on baselines of up to 15 km is now possible, and opens up new parameter space for submm astronomy.
|
|
| 7. |
- Bellenguez, C, et al.
(author)
-
New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
-
In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
-
Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Hudson, Lawrence N, et al.
(author)
-
The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
-
In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
-
Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Thompson, B.A., et al.
(author)
-
Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
- 2014
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
-
Journal article (peer-reviewed)abstract
- The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Eron, Joseph J., et al.
(author)
-
Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
- 2019
-
In: Antiviral Research. - : Elsevier BV. - 0166-3542 .- 1872-9096. ; 170
-
Journal article (peer-reviewed)abstract
- © 2019 The Authors Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
|
|
| 19. |
- Ching, C. R. K., et al.
(author)
-
What we learn about bipolar disorder from large-scale neuroimaging: Findings and future directions from the ENIGMA Bipolar Disorder Working Group
- 2022
-
In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 56-82
-
Journal article (peer-reviewed)abstract
- MRI-derived brain measures offer a link between genes, the environment and behavior and have been widely studied in bipolar disorder (BD). However, many neuroimaging studies of BD have been underpowered, leading to varied results and uncertainty regarding effects. The Enhancing Neuro Imaging Genetics through Meta-Analysis (ENIGMA) Bipolar Disorder Working Group was formed in 2012 to empower discoveries, generate consensus findings and inform future hypothesis-driven studies of BD. Through this effort, over 150 researchers from 20 countries and 55 institutions pool data and resources to produce the largest neuroimaging studies of BD ever conducted. The ENIGMA Bipolar Disorder Working Group applies standardized processing and analysis techniques to empower large-scale meta- and mega-analyses of multimodal brain MRI and improve the replicability of studies relating brain variation to clinical and genetic data. Initial BD Working Group studies reveal widespread patterns of lower cortical thickness, subcortical volume and disrupted white matter integrity associated with BD. Findings also include mapping brain alterations of common medications like lithium, symptom patterns and clinical risk profiles and have provided further insights into the pathophysiological mechanisms of BD. Here we discuss key findings from the BD working group, its ongoing projects and future directions for large-scale, collaborative studies of mental illness.
|
|
| 20. |
- Chelban, V., et al.
(author)
-
PDXK mutations cause polyneuropathy responsive to pyridoxal 5′-phosphate supplementation
- 2019
-
In: Annals of Neurology. - : Wiley. - 0364-5134 .- 1531-8249. ; 86:2, s. 225-240
-
Journal article (peer-reviewed)abstract
- Objective: To identify disease-causing variants in autosomal recessive axonal polyneuropathy with optic atrophy and provide targeted replacement therapy. Methods: We performed genome-wide sequencing, homozygosity mapping, and segregation analysis for novel disease-causing gene discovery. We used circular dichroism to show secondary structure changes and isothermal titration calorimetry to investigate the impact of variants on adenosine triphosphate (ATP) binding. Pathogenicity was further supported by enzymatic assays and mass spectroscopy on recombinant protein, patient-derived fibroblasts, plasma, and erythrocytes. Response to supplementation was measured with clinical validated rating scales, electrophysiology, and biochemical quantification. Results: We identified biallelic mutations in PDXK in 5 individuals from 2 unrelated families with primary axonal polyneuropathy and optic atrophy. The natural history of this disorder suggests that untreated, affected individuals become wheelchair-bound and blind. We identified conformational rearrangement in the mutant enzyme around the ATP-binding pocket. Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5′-phosphate (PLP) concentrations. We rescued the clinical and biochemical profile with PLP supplementation in 1 family, improvement in power, pain, and fatigue contributing to patients regaining their ability to walk independently during the first year of PLP normalization. Interpretation: We show that mutations in PDXK cause autosomal recessive axonal peripheral polyneuropathy leading to disease via reduced PDXK enzymatic activity and low PLP. We show that the biochemical profile can be rescued with PLP supplementation associated with clinical improvement. As B6 is a cofactor in diverse essential biological pathways, our findings may have direct implications for neuropathies of unknown etiology characterized by reduced PLP levels. ANN NEUROL 2019;86:225–240. © 2019 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Bursill, D., et al.
(author)
-
Gout, Hyperuricaemia and Crystal-Associated Disease Network (G-CAN) consensus statement regarding labels and definitions of disease states of gout
- 2019
-
In: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 78:11, s. 1592-1600
-
Journal article (peer-reviewed)abstract
- Objective There is a lack of standardisation in the terminology used to describe gout. The aim of this project was to develop a consensus statement describing the recommended nomenclature for disease states of gout. Methods A content analysis of gout-related articles from rheumatology and general internal medicine journals published over a 5-year period identified potential disease states and the labels commonly assigned to them. Based on these findings, experts in gout were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach agreement on disease state labels and definitions. Results The content analysis identified 13 unique disease states and a total of 63 unique labels. The Delphi exercise (n=76 respondents) and face-to-face meeting (n=35 attendees) established consensus agreement for eight disease state labels and definitions. The agreed labels were as follows: 'asymptomatic hyperuricaemia', 'asymptomatic monosodium urate crystal deposition', 'asymptomatic hyperuricaemia with monosodium urate crystal deposition', 'gout', 'tophaceous gout', 'erosive gout', 'first gout flare' and 'recurrent gout flares'. There was consensus agreement that the label 'gout' should be restricted to current or prior clinically evident disease caused by monosodium urate crystal deposition (gout flare, chronic gouty arthritis or subcutaneous tophus). Conclusion Consensus agreement has been established for the labels and definitions of eight gout disease states, including 'gout' itself. The Gout, Hyperuricaemia and Crystal-Associated Disease Network recommends the use of these labels when describing disease states of gout in research and clinical practice.
|
|
| 24. |
- Zhou, Wei, et al.
(author)
-
Global Biobank Meta-analysis Initiative : Powering genetic discovery across human disease
- 2022
-
In: Cell Genomics. - : Elsevier. - 2666-979X. ; 2:10
-
Journal article (peer-reviewed)abstract
- Biobanks facilitate genome-wide association studies (GWASs), which have mapped genomic loci across a range of human diseases and traits. However, most biobanks are primarily composed of individuals of European ancestry. We introduce the Global Biobank Meta-analysis Initiative (GBMI)-a collaborative network of 23 biobanks from 4 continents representing more than 2.2 million consented individuals with genetic data linked to electronic health records. GBMI meta-analyzes summary statistics from GWASs generated using harmonized genotypes and phenotypes from member biobanks for 14 exemplar diseases and endpoints. This strategy validates that GWASs conducted in diverse biobanks can be integrated despite heterogeneity in case definitions, recruitment strategies, and baseline characteristics. This collaborative effort improves GWAS power for diseases, benefits understudied diseases, and improves risk prediction while also enabling the nomination of disease genes and drug candidates by incorporating gene and protein expression data and providing insight into the underlying biology of human diseases and traits.
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
- Stanke, T., et al.
(author)
-
The APEX Large CO Heterodyne Orion Legacy Survey (ALCOHOLS): I. Survey overview
- 2022
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
-
Journal article (peer-reviewed)abstract
- Context. The Orion molecular cloud complex harbours the nearest Giant Molecular Clouds (GMCs) and the nearest site of high-mass star formation. Its young star and protostar populations are thoroughly characterized. The region is therefore a prime target for the study of star formation. Aims. Here, we verify the performance of the SuperCAM 64 pixel heterodyne array on the Atacama Pathfinder Experiment (APEX). We give a descriptive overview of a set of wide-field CO(32) spectral line cubes obtained towards the Orion GMC complex, aimed at characterizing the dynamics and structure of the extended molecular gas in diverse regions of the clouds, ranging from very active sites of clustered star formation in Orion B to comparatively quiet regions in southern Orion A. In a future publication, we will characterize the full population of protostellar outflows and their feedback over an entire GMC. Methods. We present a 2.7 square degree (130 pc2) mapping survey in the 12CO(32) transition, obtained using SuperCAM on APEX at an angular resolution of 19 (7600 AU or 0.037 pc at a distance of 400 pc), covering the main sites of star formation in the Orion B cloud (L 1622, NGC 2071, NGC 2068, Ori B9, NGC 2024, and NGC 2023), and a large patch in the southern part of the L 1641 cloud in Orion A. Results. We describe CO integrated line emission and line moment maps and position-velocity diagrams for all survey fields and discuss a few sub-regions in some detail. Evidence for expanding bubbles is seen with lines splitting into double components, often in areas of optical nebulosities, most prominently in the NGC 2024 H II region, where we argue that the bulk of the molecular gas is in the foreground of the H II region. High CO(32)/CO(10) line ratios reveal warm CO along the western edge of the Orion B cloud in the NGC 2023 & NGC 2024 region facing the IC 434 H II region. We see multiple, well separated radial velocity cloud components towards several fields and propose that L 1641-S consists of a sequence of clouds at increasingly larger distances. We find a small, seemingly spherical cloud, which we term Cow Nebula globule, north of NGC 2071. We confirm that we can trace high velocity line wings out to the extremely high velocity regime in protostellar molecular outflows for the NGC 2071-IR outflow and the NGC 2024 CO jet, and identify the protostellar dust core FIR4 (rather than FIR5) as the true driving source of the NGC 2024 monopolar outflow.
|
|
| 29. |
|
|
| 30. |
- Schijven, Dick, et al.
(author)
-
Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium
- 2023
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:14
-
Journal article (peer-reviewed)abstract
- Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, with MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macrostructural asymmetry may reflect differences at the molecular, cytoarchitectonic, or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia.
|
|
| 31. |
- Taquet, V, et al.
(author)
-
Seeds of Life in Space (SOLIS) VI. Chemical evolution of sulfuretted species along the outflows driven by the low-mass protostellar binary NGC1333-IRAS4A
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 637
-
Journal article (peer-reviewed)abstract
- Context. Low-mass protostars drive powerful molecular outflows that can be observed with millimetre and submillimetre telescopes. Various sulfuretted species are known to be bright in shocks and could be used to infer the physical and chemical conditions throughout the observed outflows. Aims. The evolution of sulfur chemistry is studied along the outflows driven by the NGC1333-IRAS4A protobinary system located in the Perseus cloud to constrain the physical and chemical processes at work in shocks. Methods. We observed various transitions from OCS, CS, SO, and SO2 towards NGC1333-IRAS4A in the 1.3, 2, and 3mm bands using the IRAM NOrthern Extended Millimeter Array and we interpreted the observations through the use of the Paris-Durham shock model. Results. The targeted species clearly show different spatial emission along the two outflows driven by IRAS4A. OCS is brighter on small and large scales along the south outflow driven by IRAS4A1, whereas SO2 is detected rather along the outflow driven by IRAS4A2 that is extended along the north east-south west direction. SO is detected at extremely high radial velocity up to +25 km s 1 relative to the source velocity, clearly allowing us to distinguish the two outflows on small scales. Column density ratio maps estimated from a rotational diagram analysis allowed us to confirm a clear gradient of the OCS/SO2 column density ratio between the IRAS4A1 and IRAS4A2 outflows. Analysis assuming non Local Thermodynamic Equilibrium of four SO2 transitions towards several SiO emission peaks suggests that the observed gas should be associated with densities higher than 105 cm 3 and relatively warm (T > 100 K) temperatures in most cases. Conclusions. The observed chemical differentiation between the two outflows of the IRAS4A system could be explained by a different chemical history. The outflow driven by IRAS4A1 is likely younger and more enriched in species initially formed in interstellar ices, such as OCS, and recently sputtered into the shock gas. In contrast, the longer and likely older outflow triggered by IRAS4A2 is more enriched in species that have a gas phase origin, such as SO2.
|
|
| 32. |
- Bursill, D., et al.
(author)
-
Gout, Hyperuricemia, and Crystal-Associated Disease Network Consensus Statement Regarding Labels and Definitions for Disease Elements in Gout
- 2019
-
In: Arthritis Care & Research. - : Wiley. - 2151-464X. ; 71:3, s. 427-434
-
Journal article (peer-reviewed)abstract
- Objective The language currently used to describe gout lacks standardization. The aim of this project was to develop a consensus statement on the labels and definitions used to describe the basic disease elements of gout. Methods Experts in gout (n = 130) were invited to participate in a Delphi exercise and face-to-face consensus meeting to reach consensus on the labeling and definitions for the basic disease elements of gout. Disease elements and labels in current use were derived from a content analysis of the contemporary medical literature, and the results of this analysis were used for item selection in the Delphi exercise and face-to-face consensus meeting. Results There were 51 respondents to the Delphi exercise and 30 attendees at the face-to-face meeting. Consensus agreement (>= 80%) was achieved for the labels of 8 disease elements through the Delphi exercise; the remaining 3 labels reached consensus agreement through the face-to-face consensus meeting. The agreed labels were monosodium urate crystals, urate, hyperuric(a)emia, tophus, subcutaneous tophus, gout flare, intercritical gout, chronic gouty arthritis, imaging evidence of monosodium urate crystal deposition, gouty bone erosion, and podagra. Participants at the face-to-face meeting achieved consensus agreement for the definitions of all 11 elements and a recommendation that the label "chronic gout" should not be used. Conclusion Consensus agreement was achieved for the labels and definitions of 11 elements representing the fundamental components of gout etiology, pathophysiology, and clinical presentation. The Gout, Hyperuricemia, and Crystal-Associated Disease Network recommends the use of these labels when describing the basic disease elements of gout.
|
|
| 33. |
- Nguyen, Thanh N, et al.
(author)
-
Global Impact of the COVID-19 Pandemic on Stroke Volumes and Cerebrovascular Events: A 1-Year Follow-up.
- 2023
-
In: Neurology. - 1526-632X. ; 100:4
-
Journal article (peer-reviewed)abstract
- Declines in stroke admission, IV thrombolysis (IVT), and mechanical thrombectomy volumes were reported during the first wave of the COVID-19 pandemic. There is a paucity of data on the longer-term effect of the pandemic on stroke volumes over the course of a year and through the second wave of the pandemic. We sought to measure the effect of the COVID-19 pandemic on the volumes of stroke admissions, intracranial hemorrhage (ICH), IVT, and mechanical thrombectomy over a 1-year period at the onset of the pandemic (March 1, 2020, to February 28, 2021) compared with the immediately preceding year (March 1, 2019, to February 29, 2020).We conducted a longitudinal retrospective study across 6 continents, 56 countries, and 275 stroke centers. We collected volume data for COVID-19 admissions and 4 stroke metrics: ischemic stroke admissions, ICH admissions, IVT treatments, and mechanical thrombectomy procedures. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.There were 148,895 stroke admissions in the 1 year immediately before compared with 138,453 admissions during the 1-year pandemic, representing a 7% decline (95% CI [95% CI 7.1-6.9]; p < 0.0001). ICH volumes declined from 29,585 to 28,156 (4.8% [5.1-4.6]; p < 0.0001) and IVT volume from 24,584 to 23,077 (6.1% [6.4-5.8]; p < 0.0001). Larger declines were observed at high-volume compared with low-volume centers (all p < 0.0001). There was no significant change in mechanical thrombectomy volumes (0.7% [0.6-0.9]; p = 0.49). Stroke was diagnosed in 1.3% [1.31-1.38] of 406,792 COVID-19 hospitalizations. SARS-CoV-2 infection was present in 2.9% ([2.82-2.97], 5,656/195,539) of all stroke hospitalizations.There was a global decline and shift to lower-volume centers of stroke admission volumes, ICH volumes, and IVT volumes during the 1st year of the COVID-19 pandemic compared with the prior year. Mechanical thrombectomy volumes were preserved. These results suggest preservation in the stroke care of higher severity of disease through the first pandemic year.This study is registered under NCT04934020.
|
|
| 34. |
- Bulut, N., et al.
(author)
-
Gas phase Elemental abundances in Molecular cloudS (GEMS): III. Unlocking the CS chemistry: The CS+O reaction
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 646
-
Journal article (peer-reviewed)abstract
- Context. Carbon monosulphide (CS) is among the most abundant gas-phase S-bearing molecules in cold dark molecular clouds. It is easily observable with several transitions in the millimeter wavelength range, and has been widely used as a tracer of the gas density in the interstellar medium in our Galaxy and external galaxies. However, chemical models fail to account for the observed CS abundances when assuming the cosmic value for the elemental abundance of sulfur. Aims. The CS+O → CO + S reaction has been proposed as a relevant CS destruction mechanism at low temperatures, and could explain the discrepancy between models and observations. Its reaction rate has been experimentally measured at temperatures of 150-400 K, but the extrapolation to lower temperatures is doubtful. Our goal is to calculate the CS+O reaction rate at temperatures <150 K which are prevailing in the interstellar medium. Methods. We performed ab initio calculations to obtain the three lowest potential energy surfaces (PES) of the CS+O system. These PESs are used to study the reaction dynamics, using several methods (classical, quantum, and semiclassical) to eventually calculate the CS + O thermal reaction rates. In order to check the accuracy of our calculations, we compare the results of our theoretical calculations for T ~ 150-400 K with those obtained in the laboratory. Results. Our detailed theoretical study on the CS+O reaction, which is in agreement with the experimental data obtained at 150-400 K, demonstrates the reliability of our approach. After a careful analysis at lower temperatures, we find that the rate constant at 10 K is negligible, below 10-15 cm s-1, which is consistent with the extrapolation of experimental data using the Arrhenius expression. Conclusions. We use the updated chemical network to model the sulfur chemistry in Taurus Molecular Cloud 1 (TMC 1) based on molecular abundances determined from Gas phase Elemental abundances in Molecular CloudS (GEMS) project observations. In our model, we take into account the expected decrease of the cosmic ray ionization rate, ζH2, along the cloud. The abundance of CS is still overestimated when assuming the cosmic value for the sulfur abundance.
|
|
| 35. |
|
|
| 36. |
|
|
| 37. |
- Dominguez-Valentin, M, et al.
(author)
-
No Difference in Penetrance between Truncating and Missense/Aberrant Splicing Pathogenic Variants in MLH1 and MSH2: A Prospective Lynch Syndrome Database Study
- 2021
-
In: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 10:13
-
Journal article (peer-reviewed)abstract
- Background. Lynch syndrome is the most common genetic predisposition for hereditary cancer. Carriers of pathogenic changes in mismatch repair (MMR) genes have an increased risk of developing colorectal (CRC), endometrial, ovarian, urinary tract, prostate, and other cancers, depending on which gene is malfunctioning. In Lynch syndrome, differences in cancer incidence (penetrance) according to the gene involved have led to the stratification of cancer surveillance. By contrast, any differences in penetrance determined by the type of pathogenic variant remain unknown. Objective. To determine cumulative incidences of cancer in carriers of truncating and missense or aberrant splicing pathogenic variants of the MLH1 and MSH2 genes. Methods. Carriers of pathogenic variants of MLH1 (path_MLH1) and MSH2 (path_MSH2) genes filed in the Prospective Lynch Syndrome Database (PLSD) were categorized as truncating or missense/aberrant splicing according to the InSiGHT criteria for pathogenicity. Results. Among 5199 carriers, 1045 had missense or aberrant splicing variants, and 3930 had truncating variants. Prospective observation years for the two groups were 8205 and 34,141 years, respectively, after which there were no significant differences in incidences for cancer overall or for colorectal cancer or endometrial cancers separately. Conclusion. Truncating and missense or aberrant splicing pathogenic variants were associated with similar average cumulative incidences of cancer in carriers of path MLH1 and path_MSH2.
|
|
| 38. |
- Navarro-Almaida, D., et al.
(author)
-
Gas phase Elemental abundances in Molecular cloudS (GEMS): II. On the quest for the sulphur reservoir in molecular clouds: the H2S case
- 2020
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 637
-
Journal article (peer-reviewed)abstract
- Context. Sulphur is one of the most abundant elements in the Universe. Surprisingly, sulphuretted molecules are not as abundant as expected in the interstellar medium and the identity of the main sulphur reservoir is still an open question. Aims. Our goal is to investigate the H2S chemistry in dark clouds, as this stable molecule is a potential sulphur reservoir. Methods. Using millimeter observations of CS, SO, H2S, and their isotopologues, we determine the physical conditions and H2S abundances along the cores TMC 1-C, TMC 1-CP, and Barnard 1b. The gas-grain model NAUTILUS is used to model the sulphur chemistry and explore the impact of photo-desorption and chemical desorption on the H2S abundance. Results. Our modeling shows that chemical desorption is the main source of gas-phase H2S in dark cores. The measured H2S abundance can only be fitted if we assume that the chemical desorption rate decreases by more than a factor of 10 when n(H) > 2 x 10(4). This change in the desorption rate is consistent with the formation of thick H2O and CO ice mantles on grain surfaces. The observed SO and H2S abundances are in good agreement with our predictions adopting an undepleted value of the sulphur abundance. However, the CS abundance is overestimated by a factor of 5-10. Along the three cores, atomic S is predicted to be the main sulphur reservoir. Conclusions. The gaseous H2S abundance is well reproduced, assuming undepleted sulphur abundance and chemical desorption as the main source of H2S. The behavior of the observed H2S abundance suggests a changing desorption efficiency, which would probe the snowline in these cold cores. Our model, however, highly overestimates the observed gas-phase CS abundance. Given the uncertainty in the sulphur chemistry, we can only conclude that our data are consistent with a cosmic elemental S abundance with an uncertainty of a factor of 10.
|
|
| 39. |
- Rodríguez-Baras, M., et al.
(author)
-
Gas phase Elemental abundances in Molecular cloudS (GEMS): IV. Observational results and statistical trends
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 648
-
Journal article (peer-reviewed)abstract
- Gas phase Elemental abundances in Molecular CloudS (GEMS) is an IRAM 30 m Large Program designed to provide estimates of the S, C, N, and O depletions and gas ionization degree, X(e-), in a selected set of star-forming filaments of Taurus, Perseus, and Orion. Our immediate goal is to build up a complete and large database of molecular abundances that can serve as an observational basis for estimating X(e-) and the C, O, N, and S depletions through chemical modeling. We observed and derived the abundances of 14 species (13CO, C18O, HCO+, H13CO+, HC18O+, HCN, H13CN, HNC, HCS+, CS, SO, 34SO, H2S, and OCS) in 244 positions, covering the AV ~3 to ~100 mag, n(H2) ~ a few 103 to 106 cm-3, and Tk ~10 to ~30 K ranges in these clouds, and avoiding protostars, HII regions, and bipolar outflows. A statistical analysis is carried out in order to identify general trends between different species and with physical parameters. Relations between molecules reveal strong linear correlations which define three different families of species: (1) 13CO and C18O isotopologs; (2) H13CO+, HC18O+, H13 CN, and HNC; and (3) the S-bearing molecules. The abundances of the CO isotopologs increase with the gas kinetic temperature until TK ~ 15 K. For higher temperatures, the abundance remains constant with a scatter of a factor of ~3. The abundances of H13 CO+, HC18 O+, H13 CN, and HNC are well correlated with each other, and all of them decrease with molecular hydrogen density, following the law ∝ n(H2)-0.8 ± 0.2. The abundances of S-bearing species also decrease with molecular hydrogen density at a rate of (S-bearing/H)gas ∝ n(H2)-0.6 ± 0.1. The abundances of molecules belonging to groups 2 and 3 do not present any clear trend with gas temperature. At scales of molecular clouds, the C18O abundance is the quantity that better correlates with the cloud mass. We discuss the utility of the 13CO/C18O, HCO+/H13CO+, and H13 CO+/H13CN abundance ratios as chemical diagnostics of star formation in external galaxies.
|
|
| 40. |
|
|
| 41. |
- Fuente, A., et al.
(author)
-
Gas phase Elemental abundances in Molecular cloudS (GEMS) I. The prototypical dark cloud TMC 1
- 2019
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 624
-
Journal article (peer-reviewed)abstract
- GEMS is an IRAM 30 m Large Program whose aim is determining the elemental depletions and the ionization fraction in a set of prototypical star-forming regions. This paper presents the first results from the prototypical dark cloud Taurus molecular cloud (TMC) 1. Extensive millimeter observations have been carried out with the IRAM 30 m telescope (3 and 2mm) and the 40 m Yebes telescope (1.3 cm and 7 mm) to determine the fractional abundances of CO, HCO+, HCN, CS, SO, HCS+, and N2H+ in three cuts which intersect the dense filament at the well-known positions TMC 1-CP, TMC 1-NH3, and TMC 1-C, covering a visual extinction range from A(v) similar to 3 to similar to 20 mag. Two phases with differentiated chemistry can be distinguished: (i) the translucent envelope with molecular hydrogen densities of 1-5 x 10(3) cm(-3); and (ii) the dense phase, located at A(v) > 10 mag, with molecular hydrogen densities >10(4) cm(-3). Observations and modeling show that the gas phase abundances of C and O progressively decrease along the C+/C/CO transition zone (A(v) similar to 3 mag) where C/H similar to 8 x 10(-5) and C/O similar to 0.8-1, until the beginning of the dense phase at A(v) similar to 10 mag. This is consistent with the grain temperatures being below the CO evaporation temperature in this region. In the case of sulfur, a strong depletion should occur before the translucent phase where we estimate an S/H similar to (0.4-2.2) x 10(-6), an abundance similar to 7-40 times lower than the solar value. A second strong depletion must be present during the formation of the thick icy mantles to achieve the values of S/H measured in the dense cold cores (S/H similar to 8 x 10(-8)). Based on our chemical modeling, we constrain the value of zeta(H2) to similar to(0.5-1.8) x 10(-16) s(-1) in the translucent cloud.
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
- McWhinney, Sean R, et al.
(author)
-
Diagnosis of bipolar disorders and body mass index predict clustering based on similarities in cortical thickness-ENIGMA study in 2436 individuals.
- 2022
-
In: Bipolar disorders. - : Wiley. - 1399-5618 .- 1398-5647. ; 24:5, s. 509-520
-
Journal article (peer-reviewed)abstract
- Rates of obesity have reached epidemic proportions, especially among people with psychiatric disorders. While the effects of obesity on the brain are of major interest in medicine, they remain markedly under-researched in psychiatry.We obtained body mass index (BMI) and magnetic resonance imaging-derived regional cortical thickness, surface area from 836 bipolar disorders (BD) and 1600 control individuals from 14sites within the ENIGMA-BD Working Group. We identified regionally specific profiles of cortical thickness using K-means clustering and studied clinical characteristics associated with individual cortical profiles.We detected two clusters based on similarities among participants in cortical thickness. The lower thickness cluster (46.8% of the sample) showed thinner cortex, especially in the frontal and temporal lobes and was associated with diagnosis of BD, higher BMI, and older age. BD individuals in the low thickness cluster were more likely to have the diagnosis of bipolar disorder I and less likely to be treated with lithium. In contrast, clustering based on similarities in the cortical surface area was unrelated to BD or BMI and only tracked age and sex.We provide evidence that both BD and obesity are associated with similar alterations in cortical thickness, but not surface area. The fact that obesity increased the chance of having low cortical thickness could explain differences in cortical measures among people with BD. The thinner cortex in individuals with higher BMI, which was additive and similar to the BD-associated alterations, may suggest that treating obesity could lower the extent of cortical thinning in BD.
|
|
| 45. |
- McWhinney, Sean R, et al.
(author)
-
Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants.
- 2023
-
In: Psychological medicine. - 1469-8978. ; 53:14, s. 6743-6753
-
Journal article (peer-reviewed)abstract
- Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain is a target organ for both obesity and BD. Yet, we do not understand how cortical brain alterations in BD and obesity interact.We obtained body mass index (BMI) and MRI-derived regional cortical thickness, surface area from 1231 BD and 1601 control individuals from 13 countries within the ENIGMA-BD Working Group. We jointly modeled the statistical effects of BD and BMI on brain structure using mixed effects and tested for interaction and mediation. We also investigated the impact of medications on the BMI-related associations.BMI and BD additively impacted the structure of many of the same brain regions. Both BMI and BD were negatively associated with cortical thickness, but not surface area. In most regions the number of jointly used psychiatric medication classes remained associated with lower cortical thickness when controlling for BMI. In a single region, fusiform gyrus, about a third of the negative association between number of jointly used psychiatric medications and cortical thickness was mediated by association between the number of medications and higher BMI.We confirmed consistent associations between higher BMI and lower cortical thickness, but not surface area, across the cerebral mantle, in regions which were also associated with BD. Higher BMI in people with BD indicated more pronounced brain alterations. BMI is important for understanding the neuroanatomical changes in BD and the effects of psychiatric medications on the brain.
|
|
| 46. |
|
|
| 47. |
- Barnes, A. T., et al.
(author)
-
ALMA-IRDC: dense gas mass distribution from cloud to core scales
- 2021
-
In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 503:3, s. 4601-4626
-
Journal article (peer-reviewed)abstract
- Infrared dark clouds (IRDCs) are potential hosts of the elusive early phases of high mass star formation (HMSF). Here, we conduct an in-depth analysis of the fragmentation properties of a sample of 10 IRDCs, which have been highlighted as some of the best candidates to study HMSF within the Milky Way. To do so, we have obtained a set of large mosaics covering these IRDCs with Atacama Large Millimeter/submillimeter Array (ALMA) at Band 3 (or 3 mm). These observations have a high angular resolution (similar to 3 arcsec; similar to 0.05 pc), and high continuum and spectral line sensitivity (similar to 0.15 mJy beam(-1) and similar to 0.2 K per 0.1 km s(-1) channel at the N2H+ (1 - 0) transition). From the dust continuum emission, we identify 96 cores ranging from low to high mass (M = 3.4-50.9M(circle dot)) that are gravitationally bound (alpha(vir) = 0.3-1.3) and which would require magnetic field strengths of B = 0.3-1.0 mG to be in virial equilibrium. We combine these results with a homogenized catalogue of literature cores to recover the hierarchical structure within these clouds over four orders of magnitude in spatial scale (0.01-10 pc). Using supplementary observations at an even higher angular resolution, we find that the smallest fragments (<0.02 pc) within this hierarchy do not currently have the mass and/or the density required to form high-mass stars. None the less, the new ALMA observations presented in this paper have facilitated the identification of 19 (6 quiescent and 13 star-forming) cores that retain >16M(circle dot) without further fragmentation. These high-mass cores contain trans-sonic non-thermal motions, are kinematically sub-virial, and require moderate magnetic field strengths for support against collapse. The identification of these potential sites of HMSF represents a key step in allowing us to test the predictions from high-mass star and cluster formation theories.
|
|
| 48. |
- McWhinney, Sean R, et al.
(author)
-
Association between body mass index and subcortical brain volumes in bipolar disorders-ENIGMA study in 2735 individuals.
- 2021
-
In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:11, s. 6806-6819
-
Journal article (peer-reviewed)abstract
- Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediatedby BMI (Z=2.73, p=0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.
|
|
| 49. |
- McWhinney, Sean R, et al.
(author)
-
Principal component analysis as an efficient method for capturing multivariate brain signatures of complex disorders-ENIGMA study in people with bipolar disorders and obesity.
- 2024
-
In: Human brain mapping. - 1097-0193 .- 1097-0193. ; 45:8
-
Journal article (peer-reviewed)abstract
- Multivariate techniques better fit the anatomy of complex neuropsychiatric disorders which are characterized not by alterations in a single region, but rather by variations across distributed brain networks. Here, we used principal component analysis (PCA) to identify patterns of covariance across brain regions and relate them to clinical and demographic variables in a large generalizable dataset of individuals with bipolar disorders and controls. We then compared performance of PCA and clustering on identical sample to identify which methodology was better in capturing links between brain and clinical measures. Using data from the ENIGMA-BD working group, we investigated T1-weighted structural MRI data from 2436 participants with BD and healthy controls, and applied PCA to cortical thickness and surface area measures. We then studied the association of principal components with clinical and demographic variables using mixed regression models. We compared the PCA model with our prior clustering analyses of the same data and also tested it in a replication sample of 327 participants with BD or schizophrenia and healthy controls. The first principal component, which indexed a greater cortical thickness across all 68 cortical regions, was negatively associated with BD, BMI, antipsychotic medications, and age and was positively associated with Li treatment. PCA demonstrated superior goodness of fit to clustering when predicting diagnosis and BMI. Moreover, applying the PCA model to the replication sample yielded significant differences in cortical thickness between healthy controls and individuals with BD or schizophrenia. Cortical thickness in the same widespread regional network as determined by PCA was negatively associated with different clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. PCA outperformed clustering and provided an easy-to-use and interpret method to study multivariate associations between brain structure and system-level variables. PRACTITIONER POINTS: In this study of 2770 Individuals, we confirmed that cortical thickness in widespread regional networks as determined by principal component analysis (PCA) was negatively associated with relevant clinical and demographic variables, including diagnosis, age, BMI, and treatment with antipsychotic medications or lithium. Significant associations of many different system-level variables with the same brain network suggest a lack of one-to-one mapping of individual clinical and demographic factors to specific patterns of brain changes. PCA outperformed clustering analysis in the same data set when predicting group or BMI, providing a superior method for studying multivariate associations between brain structure and system-level variables.
|
|
| 50. |
- Nicholl, M., et al.
(author)
-
An outflow powers the optical rise of the nearby, fast-evolving tidal disruption event AT2019qiz
- 2020
-
In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 499:1, s. 482-504
-
Journal article (peer-reviewed)abstract
- At 66 Mpc, AT2019qiz is the closest optical tidal disruption event (TDE) to date, with a luminosity intermediate between the bulk of the population and the faint-and-fast event iPTF16fnl. Its proximity allowed a very early detection and triggering of multiwavelength and spectroscopic follow-up well before maximum light. The velocity dispersion of the host galaxy and fits to the TDE light curve indicate a black hole mass approximate to 10(6) M-circle dot, disrupting a star of approximate to 1 M-circle dot. By analysing our comprehensive UV, optical, and X-ray data, we show that the early optical emission is dominated by an outflow, with a luminosity evolution L proportional to t(2), consistent with a photosphere expanding at constant velocity (greater than or similar to 2000 km s(-1)), and a line-forming region producing initially blueshifted H and He II profiles with v = 3000-10 000 km s(-1). The fastest optical ejecta approach the velocity inferred from radio detections (modelled in a forthcoming companion paper from K. D. Alexander et al.), thus the same outflow may be responsible for both the fast optical rise and the radio emission - the first time this connection has been observed in a TDE. The light-curve rise begins 29 +/- 2 d before maximum light, peaking when the photosphere reaches the radius where optical photons can escape. The photosphere then undergoes a sudden transition, first cooling at constant radius then contracting at constant temperature. At the same time, the blueshifts disappear from the spectrum and Bowen fluorescence lines (N III) become prominent, implying a source of far-UV photons, while the X-ray light curve peaks at approximate to 10(41) erg s(-1). Assuming that these X-rays are from prompt accretion, the size and mass of the outflow are consistent with the reprocessing layer needed to explain the large optical to X-ray ratio in this and other optical TDEs, possibly favouring accretion-powered over collision-powered outflow models.
|
|
