| 1. |
- Kanai, M, et al.
(author)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(author)
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- 2021
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swepub:Mat__t
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| 3. |
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| 4. |
- Kanoni, Stavroula, et al.
(author)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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In: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Journal article (peer-reviewed)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 5. |
- Mahajan, Anubha, et al.
(author)
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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
- 2022
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 54:5, s. 560-572
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Journal article (peer-reviewed)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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| 6. |
- Sumaila, U. Rashid, et al.
(author)
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WTO must ban harmful fisheries subsidies
- 2021
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In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 374:6567, s. 544-544
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Journal article (other academic/artistic)
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| 7. |
- Bousquet, Jean, et al.
(author)
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ARIA digital anamorphosis : Digital transformation of health and care in airway diseases from research to practice
- 2021
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 76:1, s. 168-190
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Research review (peer-reviewed)abstract
- Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.
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| 8. |
- Surendran, Praveen, et al.
(author)
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Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
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Journal article (peer-reviewed)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
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| 9. |
- Attia, Zachi I., et al.
(author)
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Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram
- 2021
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In: Mayo Clinic proceedings. - : ELSEVIER SCIENCE INC. - 0025-6196 .- 1942-5546. ; 96:8, s. 2081-2094
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Journal article (peer-reviewed)abstract
- Objective: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). Methods: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. Results: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. Conclusion: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control. (C) 2021 Mayo Foundation Medical Education and Research
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| 10. |
- Carrick, Richard T., et al.
(author)
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Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe
- 2024
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In: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645.
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Journal article (peer-reviewed)abstract
- Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC.Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed.Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans.Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.
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| 11. |
- G., Aad, et al.
(author)
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Measurement of soft-drop jet observables in pp collisions with the ATLAS detector at s =13 TeV
- 2020
-
In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 101:5
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Journal article (peer-reviewed)abstract
- Jet substructure quantities are measured using jets groomed with the soft-drop grooming procedure in dijet events from 32.9 fb-1 of pp collisions collected with the ATLAS detector at s=13 TeV. These observables are sensitive to a wide range of QCD phenomena. Some observables, such as the jet mass and opening angle between the two subjets which pass the soft-drop condition, can be described by a high-order (resummed) series in the strong coupling constant αS. Other observables, such as the momentum sharing between the two subjets, are nearly independent of αS. These observables can be constructed using all interacting particles or using only charged particles reconstructed in the inner tracking detectors. Track-based versions of these observables are not collinear safe, but are measured more precisely, and universal nonperturbative functions can absorb the collinear singularities. The unfolded data are directly compared with QCD calculations and hadron-level Monte Carlo simulations. The measurements are performed in different pseudorapidity regions, which are then used to extract quark and gluon jet shapes using the predicted quark and gluon fractions in each region. All of the parton shower and analytical calculations provide an excellent description of the data in most regions of phase space. © 2020 CERN.
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| 12. |
- G., Aad, et al.
(author)
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Measurement of the tt¯ production cross-section and lepton differential distributions in eμ dilepton events from pp collisions at √s=13TeV with the ATLAS detector
- 2020
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In: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:6
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Journal article (peer-reviewed)abstract
- The inclusive top quark pair (tt¯) production cross-section σtt¯ has been measured in proton–proton collisions at s=13TeV, using 36.1 fb- 1 of data collected in 2015–2016 by the ATLAS experiment at the LHC. Using events with an opposite-charge eμ pair and b-tagged jets, the cross-section is measured to be: σtt¯=826.4±3.6(stat)±11.5(syst)±15.7(lumi)±1.9(beam)pb,where the uncertainties reflect the limited size of the data sample, experimental and theoretical systematic effects, the integrated luminosity, and the LHC beam energy, giving a total uncertainty of 2.4%. The result is consistent with theoretical QCD calculations at next-to-next-to-leading order. It is used to determine the top quark pole mass via the dependence of the predicted cross-section on mtpole, giving mtpole=173.1-2.1+2.0GeV. It is also combined with measurements at s=7TeV and s=8TeV to derive ratios and double ratios of tt¯ and Z cross-sections at different energies. The same event sample is used to measure absolute and normalised differential cross-sections as functions of single-lepton and dilepton kinematic variables, and the results are compared with predictions from various Monte Carlo event generators. © 2020, CERN for the benefit of the ATLAS collaboration.
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| 13. |
- G., Aad, et al.
(author)
-
Search for heavy neutral Higgs bosons produced in association with b-quarks and decaying into b-quarks at s =13 TeV with the ATLAS detector
- 2020
-
In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 1550-7998 .- 1550-2368. ; 102:3
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Journal article (peer-reviewed)abstract
- A search for heavy neutral Higgs bosons produced in association with one or two b-quarks and decaying to b-quark pairs is presented using 27.8 fb-1 of s=13 TeV proton-proton collision data recorded by the ATLAS detector at the Large Hadron Collider during 2015 and 2016. No evidence of a signal is found. Upper limits on the heavy neutral Higgs boson production cross section times its branching ratio to bb¯ are set, ranging from 4.0 to 0.6 pb at 95% confidence level over a Higgs boson mass range of 450 to 1400 GeV. Results are interpreted within the two-Higgs-doublet model and the minimal supersymmetric Standard Model. © 2020 American Physical Society. All rights reserved.
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| 14. |
- G., Aad, et al.
(author)
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Search for long-lived neutral particles produced in pp collisions at s =13 TeV decaying into displaced hadronic jets in the ATLAS inner detector and muon spectrometer
- 2020
-
In: Physical Review D. - : AMER PHYSICAL SOC. - 2470-0010 .- 2470-0029. ; 101:5
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Journal article (peer-reviewed)abstract
- A search is presented for pair production of long-lived neutral particles using 33 fb-1 of s=13 TeV proton-proton collision data, collected during 2016 by the ATLAS detector at the LHC. This search focuses on a topology in which one long-lived particle decays in the ATLAS inner detector and the other decays in the muon spectrometer. Special techniques are employed to reconstruct the displaced tracks and vertices in the inner detector and in the muon spectrometer. One event is observed that passes the full event selection, which is consistent with the estimated background. Limits are placed on scalar boson propagators with masses from 125 GeV to 1000 GeV decaying into pairs of long-lived hidden-sector scalars with masses from 8 GeV to 400 GeV. The limits placed on several low-mass scalars extend previous exclusion limits in the range of proper lifetimes cτ from 5 cm to 1 m. © 2020 CERN.
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| 15. |
- G., Aad, et al.
(author)
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Search for Magnetic Monopoles and Stable High-Electric-Charge Objects in 13 Tev Proton-Proton Collisions with the ATLAS Detector
- 2020
-
In: Physical Review Letters. - : American Physical Society. - 0031-9007 .- 1079-7114. ; 124:3
-
Journal article (peer-reviewed)abstract
- A search for magnetic monopoles and high-electric-charge objects is presented using 34.4 fb-1 of 13 TeV pp collision data collected by the ATLAS detector at the LHC during 2015 and 2016. The considered signature is based upon high ionization in the transition radiation tracker of the inner detector associated with a pencil-shape energy deposit in the electromagnetic calorimeter. The data were collected by a dedicated trigger based on the tracker high-threshold hit capability. The results are interpreted in models of Drell-Yan pair production of stable particles with two spin hypotheses (0 and 1/2) and masses ranging from 200 to 4000 GeV. The search improves by approximately a factor of 5 the constraints on the direct production of magnetic monopoles carrying one or two Dirac magnetic charges and stable objects with electric charge in the range 20≤|z|≤60 and extends the charge range to 60
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| 16. |
- Geerts, Bart, et al.
(author)
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The COMBLE Campaign : A Study of Marine Boundary Layer Clouds in Arctic Cold-Air Outbreaks
- 2022
-
In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 103:5, s. E1371-E1389
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Journal article (peer-reviewed)abstract
- One of the most intense air mass transformations on Earth happens when cold air flows from frozen surfaces to much warmer open water in cold-air outbreaks (CAOs), a process captured beautifully in satellite imagery. Despite the ubiquity of the CAO cloud regime over high-latitude oceans, we have a rather poor understanding of its properties, its role in energy and water cycles, and its treatment in weather and climate models. The Cold-Air Outbreaks in the Marine Boundary Layer Experiment (COMBLE) was conducted to better understand this regime and its representation in models. COMBLE aimed to examine the relations between surface fluxes, boundary layer structure, aerosol, cloud, and precipitation properties, and mesoscale circulations in marine CAOs. Processes affecting these properties largely fall in a range of scales where boundary layer processes, convection, and precipitation are tightly coupled, which makes accurate representation of the CAO cloud regime in numerical weather prediction and global climate models most challenging. COMBLE deployed an Atmospheric Radiation Measurement Mobile Facility at a coastal site in northern Scandinavia (69°N), with additional instruments on Bear Island (75°N), from December 2019 to May 2020. CAO conditions were experienced 19% (21%) of the time at the main site (on Bear Island). A comprehensive suite of continuous in situ and remote sensing observations of atmospheric conditions, clouds, precipitation, and aerosol were collected. Because of the clouds’ well-defined origin, their shallow depth, and the broad range of observed temperature and aerosol concentrations, the COMBLE dataset provides a powerful modeling testbed for improving the representation of mixed-phase cloud processes in large-eddy simulations and large-scale models.
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| 17. |
- Hawthorn, F., et al.
(author)
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TOI-836: A super-Earth and mini-Neptune transiting a nearby K-dwarf
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 520:3, s. 3649-3668
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Journal article (peer-reviewed)abstract
- We present the discovery of two exoplanets transiting TOI-836 (TIC 440887364) using data from TESS Sector 11 and Sector 38. TOI-836 is a bright (T = 8.5 mag), high proper motion (∼200 mas yr−1), low metallicity ([Fe/H]≈−0.28) K-dwarf with a mass of 0.68 ± 0.05 M and a radius of 0.67 ± 0.01 R. We obtain photometric follow-up observations with a variety of facilities, and we use these data sets to determine that the inner planet, TOI-836 b, is a 1.70 ± 0.07 R super-Earth in a 3.82-d orbit, placing it directly within the so-called ‘radius valley’. The outer planet, TOI-836 c, is a 2.59 ± 0.09 R mini-Neptune in an 8.60-d orbit. Radial velocity measurements reveal that TOI-836 b has a mass of 4.5 ± 0.9 M, while TOI-836 c has a mass of 9.6 ± 2.6 M. Photometric observations show Transit Timing Variations (TTVs) on the order of 20 min for TOI-836 c, although there are no detectable TTVs for TOI-836 b. The TTVs of planet TOI-836 c may be caused by an undetected exterior planet.
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| 18. |
- Maxwell, Tania L., et al.
(author)
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Global dataset of soil organic carbon in tidal marshes
- 2023
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In: Scientific Data. - : Springer Nature. - 2052-4463. ; 10:1
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Journal article (peer-reviewed)abstract
- Tidal marshes store large amounts of organic carbon in their soils. Field data quantifying soil organic carbon (SOC) stocks provide an important resource for researchers, natural resource managers, and policy-makers working towards the protection, restoration, and valuation of these ecosystems. We collated a global dataset of tidal marsh soil organic carbon (MarSOC) from 99 studies that includes location, soil depth, site name, dry bulk density, SOC, and/or soil organic matter (SOM). The MarSOC dataset includes 17,454 data points from 2,329 unique locations, and 29 countries. We generated a general transfer function for the conversion of SOM to SOC. Using this data we estimated a median (± median absolute deviation) value of 79.2 ± 38.1 Mg SOC ha−1 in the top 30 cm and 231 ± 134 Mg SOC ha−1 in the top 1 m of tidal marsh soils globally. This data can serve as a basis for future work, and may contribute to incorporation of tidal marsh ecosystems into climate change mitigation and adaptation strategies and policies.
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| 19. |
- Osborn, H. P., et al.
(author)
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Two warm Neptunes transiting HIP 9618 revealed by TESS and Cheops
- 2023
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In: Monthly Notices of the Royal Astronomical Society. - 0035-8711 .- 1365-2966. ; 523:2, s. 3069-3089
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Journal article (peer-reviewed)abstract
- HIP 9618 (HD 12572, TOI-1471, TIC 306263608) is a bright (G = 9.0 mag) solar analogue. TESS photometry revealed the star to have two candidate planets with radii of 3.9 ± 0.044 R (HIP 9618 b) and 3.343 ± 0.039 R (HIP 9618 c). While the 20.77291 d period of HIP 9618 b was measured unambiguously, HIP 9618 c showed only two transits separated by a 680-d gap in the time series, leaving many possibilities for the period. To solve this issue, CHEOPS performed targeted photometry of period aliases to attempt to recover the true period of planet c, and successfully determined the true period to be 52.56349 d. High-resolution spectroscopy with HARPS-N, SOPHIE, and CAFE revealed a mass of 10.0 ± 3.1M for HIP 9618 b, which, according to our interior structure models, corresponds to a 6.8 ± 1.4 per cent gas fraction. HIP 9618 c appears to have a lower mass than HIP 9618 b, with a 3-sigma upper limit of <18M. Follow-up and archival RV measurements also reveal a clear long-term trend which, when combined with imaging and astrometric information, reveal a low-mass companion (0.08+−000512M☉) orbiting at 26.0+−111900 au. This detection makes HIP 9618 one of only five bright (K < 8 mag) transiting multiplanet systems known to host a planet with P > 50 d, opening the door for the atmospheric characterization of warm (Teq < 750 K) sub-Neptunes.
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| 20. |
- Abildgaard, Amanda B., et al.
(author)
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HSP70-binding motifs function as protein quality control degrons
- 2023
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In: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 80:1
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Journal article (peer-reviewed)abstract
- Protein quality control (PQC) degrons are short protein segments that target misfolded proteins for proteasomal degradation, and thus protect cells against the accumulation of potentially toxic non-native proteins. Studies have shown that PQC degrons are hydrophobic and rarely contain negatively charged residues, features which are shared with chaperone-binding regions. Here we explore the notion that chaperone-binding regions may function as PQC degrons. When directly tested, we found that a canonical Hsp70-binding motif (the APPY peptide) functioned as a dose-dependent PQC degron both in yeast and in human cells. In yeast, Hsp70, Hsp110, Fes1, and the E3 Ubr1 target the APPY degron. Screening revealed that the sequence space within the chaperone-binding region of APPY that is compatible with degron function is vast. We find that the number of exposed Hsp70-binding sites in the yeast proteome correlates with a reduced protein abundance and half-life. Our results suggest that when protein folding fails, chaperone-binding sites may operate as PQC degrons, and that the sequence properties leading to PQC-linked degradation therefore overlap with those of chaperone binding.
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| 21. |
- Alexander, Stephen P. H., et al.
(author)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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In: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180
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Journal article (peer-reviewed)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 22. |
- Andrean, Stefio Y., 1991-, et al.
(author)
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Search for heavy particles in the b-tagged dijet mass distribution with additional b-tagged jets in proton-proton collisions at √s=13 TeV with the ATLAS experiment
- 2022
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In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 105:1
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Journal article (peer-reviewed)abstract
- A search optimized for new heavy particles decaying to two b-quarks and produced in association with additional b-quarks is reported. The sensitivity is improved by b-tagging at least one lower-pT jet in addition to the two highest-pT jets. The data used in this search correspond to an integrated luminosity of 103 fb−1 collected with a dedicated trijet trigger during the 2017 and 2018 √s=13 TeV proton-proton collision runs with the ATLAS detector at the LHC. The search looks for resonant peaks in the b-tagged dijet invariant mass spectrum over a smoothly falling background. The background is estimated with an innovative data-driven method based on orthonormal functions. The observed b-tagged dijet invariant mass spectrum is compatible with the background-only hypothesis. Upper limits at 95% confidence level on a heavy vector-boson production cross section times branching ratio to a pair of b-quarks are derived.
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| 23. |
- Biurrun, Idoia, et al.
(author)
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Benchmarking plant diversity of Palaearctic grasslands and other open habitats
- 2021
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In: Journal of Vegetation Science. - Oxford : John Wiley & Sons. - 1100-9233 .- 1654-1103. ; 32:4
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Journal article (peer-reviewed)abstract
- Journal of Vegetation Science published by John Wiley & Sons Ltd on behalf of International Association for Vegetation Science.Aims: Understanding fine-grain diversity patterns across large spatial extents is fundamental for macroecological research and biodiversity conservation. Using the GrassPlot database, we provide benchmarks of fine-grain richness values of Palaearctic open habitats for vascular plants, bryophytes, lichens and complete vegetation (i.e., the sum of the former three groups). Location: Palaearctic biogeographic realm. Methods: We used 126,524 plots of eight standard grain sizes from the GrassPlot database: 0.0001, 0.001, 0.01, 0.1, 1, 10, 100 and 1,000 m2 and calculated the mean richness and standard deviations, as well as maximum, minimum, median, and first and third quartiles for each combination of grain size, taxonomic group, biome, region, vegetation type and phytosociological class. Results: Patterns of plant diversity in vegetation types and biomes differ across grain sizes and taxonomic groups. Overall, secondary (mostly semi-natural) grasslands and natural grasslands are the richest vegetation type. The open-access file ”GrassPlot Diversity Benchmarks” and the web tool “GrassPlot Diversity Explorer” are now available online (https://edgg.org/databases/GrasslandDiversityExplorer) and provide more insights into species richness patterns in the Palaearctic open habitats. Conclusions: The GrassPlot Diversity Benchmarks provide high-quality data on species richness in open habitat types across the Palaearctic. These benchmark data can be used in vegetation ecology, macroecology, biodiversity conservation and data quality checking. While the amount of data in the underlying GrassPlot database and their spatial coverage are smaller than in other extensive vegetation-plot databases, species recordings in GrassPlot are on average more complete, making it a valuable complementary data source in macroecology. © 2021 The Authors.
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| 24. |
- Ekström, Magnus, et al.
(author)
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Normative Reference Equations for Breathlessness Intensity during Incremental Cardiopulmonary Cycle Exercise Testing
- 2024
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In: Annals of the American Thoracic Society. - 2329-6933 .- 2325-6621. ; 21:1, s. 56-67
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Journal article (peer-reviewed)abstract
- Rationale: Cardiopulmonary exercise testing (CPET) is the gold standard to evaluate exertional breathlessness, a common and disabling symptom. However, the interpretation of breathlessness responses to CPET is limited by a scarcity of normative data. Objectives: We aimed to develop normative reference equations for breathlessness intensity (Borg 0–10 category ratio) response in men and women aged >40 years during CPET, in relation to power output (watts), oxygen uptake, and minute ventilation. Methods: Analysis of ostensibly healthy people aged >40 years undergoing symptom-limited incremental cycle CPET (10 W/ min) in the CanCOLD (Canadian Cohort Obstructive Lung Disease) study. Participants had smoking histories ,5 pack-years and normal lung function and exercise capacity. The probability of each Borg 0–10 category ratio breathlessness intensity rating by power output, oxygen uptake, and minute ventilation (as an absolute or a relative value [percentage of predicted maximum]) was predicted using ordinal multinomial logistic regression.Model performance was evaluated by fit, calibration, and discrimination (C statistic) and externally validated in an independent sample (n = 86) of healthy Canadian adults. Results: We included 156 participants (43% women) from CanCOLD; the mean age was 65 (range, 42–91) years, and the mean body mass index was 26.3 (standard deviation, 3.8) kg/m2. Reference equations were developed for women and men separately, accounting for age and/or body mass. Model performance was high across all equations, including in the validation sample (C statistic for men = 0.81–0.92, C statistic for women = 0.81–0.96). Conclusions: Normative reference equations are provided to compare exertional breathlessness intensity ratings among individuals or groups and to identify and quantify abnormal breathlessness responses (scores greater than the upper limit of normal) during CPET.
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| 25. |
- Gyldenkerne, Christine, et al.
(author)
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Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
- 2023
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In: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
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Journal article (peer-reviewed)abstract
- BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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| 26. |
- Hansen, Aleksander L., et al.
(author)
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Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes
- 2023
-
In: Diabetologia. - 0012-186X. ; 66:9, s. 1680-1692
-
Journal article (peer-reviewed)abstract
- Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes but it is unknown whether low birthweight is associated with distinct clinical characteristics at disease onset. We examined whether a lower or higher birthweight in type 2 diabetes is associated with clinically relevant characteristics at disease onset. Methods: Midwife records were traced for 6866 individuals with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Using a cross-sectional design, we assessed age at diagnosis, anthropomorphic measures, comorbidities, medications, metabolic variables and family history of type 2 diabetes in individuals with the lowest 25% of birthweight (<3000 g) and highest 25% of birthweight (>3700 g), compared with a birthweight of 3000–3700 g as reference, using log-binomial and Poisson regression. Continuous relationships across the entire birthweight spectrum were assessed with linear and restricted cubic spline regression. Weighted polygenic scores (PS) for type 2 diabetes and birthweight were calculated to assess the impact of genetic predispositions. Results: Each 1000 g decrease in birthweight was associated with a 3.3 year (95% CI 2.9, 3.8) younger age of diabetes onset, 1.5 kg/m2 (95% CI 1.2, 1.7) lower BMI and 3.9 cm (95% CI 3.3, 4.5) smaller waist circumference. Compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity (prevalence ratio [PR] for Charlson Comorbidity Index Score ≥3 was 1.36 [95% CI 1.07, 1.73]), having a systolic BP ≥155 mmHg (PR 1.26 [95% CI 0.99, 1.59]), lower prevalence of diabetes-associated neurological disease, less likelihood of family history of type 2 diabetes, use of three or more glucose-lowering drugs (PR 1.33 [95% CI 1.06, 1.65]) and use of three or more antihypertensive drugs (PR 1.09 [95% CI 0.99, 1.20]). Clinically defined low birthweight (<2500 g) yielded stronger associations. Most associations between birthweight and clinical characteristics appeared linear, and a higher birthweight was associated with characteristics mirroring lower birthweight in opposite directions. Results were robust to adjustments for PS representing weighted genetic predisposition for type 2 diabetes and birthweight. Conclusion/interpretation: Despite younger age at diagnosis, and fewer individuals with obesity and family history of type 2 diabetes, a birthweight <3000 g was associated with more comorbidities, including a higher systolic BP, as well as with greater use of glucose-lowering and antihypertensive medications, in individuals with recently diagnosed type 2 diabetes.
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| 27. |
- Hohenschurz-Schmidt, David, et al.
(author)
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Recommendations for the development, implementation, and reporting of control interventions in efficacy and mechanistic trials of physical, psychological, and self-management therapies : the CoPPS Statement
- 2023
-
In: BMJ. British Medical Journal. - : BMJ Publishing Group Ltd. - 0959-8146 .- 0959-535X. ; 381, s. e072108-
-
Journal article (peer-reviewed)abstract
- Control interventions (often called "sham," "placebo," or "attention controls") are essential for studying the efficacy or mechanism of physical, psychological, and self-management interventions in clinical trials. This article presents core recommendations for designing, conducting, and reporting control interventions to establish a quality standard in non-pharmacological intervention research. A framework of additional considerations supports researchers' decision making in this context. We also provide a reporting checklist for control interventions to enhance research transparency, usefulness, and rigour.
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| 28. |
- Huang, Chelsea X., et al.
(author)
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TESS Spots a Hot Jupiter with an Inner Transiting Neptune
- 2020
-
In: Astrophysical Journal Letters. - : American Astronomical Society. - 2041-8213 .- 2041-8205. ; 892:1
-
Journal article (peer-reviewed)abstract
- Hot Jupiters are rarely accompanied by other planets within a factor of a few in orbital distance. Previously, only two such systems have been found. Here, we report the discovery of a third system using data from the Transiting Exoplanet Survey Satellite (TESS). The host star, TOI-1130, is an eleventh magnitude K-dwarf in Gaia G-band. It has two transiting planets: a Neptune-sized planet (3.65 ± 0.10 R\oplus) with a 4.1 days period, and a hot Jupiter (1.50-0.22+0.27 RJ) with an 8.4 days period. Precise radial-velocity observations show that the mass of the hot Jupiter is 0.974-0.044+0.043 MJ. For the inner Neptune, the data provide only an upper limit on the mass of 0.17 MJ (3σ). Nevertheless, we are confident that the inner planet is real, based on follow-up ground-based photometry and adaptive-optics imaging that rule out other plausible sources of the TESS transit signal. The unusual planetary architecture of and the brightness of the host star make TOI-1130 a good test case for planet formation theories, and an attractive target for future spectroscopic observations.
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| 29. |
- Jensen, Marie Louise, et al.
(author)
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Implant migration and functional outcome of Reverse Shoulder Lateralized Glenosphere Line Extension System : a study protocol for a randomized controlled trial
- 2022
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 23:1
-
Journal article (peer-reviewed)abstract
- Background: Inferior scapular notching is a complication unique to reverse shoulder arthroplasty. The most efficient technique to avoid inferior scapular notching has been reported to be lateralization of the glenoid offset. This study aims to compare radiological and functional outcomes of the DELTA Xtend® Reverse Shoulder System Lateralized Glenosphere Line Extension (intervention group) with the Standard DELTA Xtend® Reverse Shoulder System (control group). We hypothesize that the lateralization improves the patient outcome by decreasing the risk of inferior scapular notching without increasing the risk of migration and loosening of glenoid component. Methods: In this randomized controlled trial, all Danish citizens with rotator cuff arthropathy or degeneration of the glenohumeral joint with severe posterior wear and allocated for a reverse total shoulder arthroplasty at the department of orthopaedic surgery at Herlev and Gentofte Hospital, Copenhagen University Hospital, will be considered for participation. The exclusion criteria are as follows: below 50 years of age, cognitive or linguistic impairment, insufficient glenoid bone stock, previous fracture in the upper extremity and autoimmune-mediated inflammatory arthritis. There will be included a total of 122 patients of which 56 will participate in the radiostereometric analysis. This number of patients allows 20% to drop out. The co-primary outcomes are the pattern and magnitude of the migration of the glenoid component assessed by radiostereometric analysis and the Western Ontario Osteoarthritis of the Shoulder index. The secondary outcomes are inferior scapular notching, patient-reported and functional outcomes (Oxford shoulder score, Constant-Murley score and pain), side effects and complications, changes in bone mineral density and economy. The included patients will be examined before the surgery, within 1 week and 3, 6, 12 and 24 months after. Discussion: No previous studies have compared the conventional reverse shoulder arthroplasty with the lateralized reverse shoulder arthroplasty in a randomized controlled trial regarding migration and functional outcome. Furthermore, radiostereometric analysis has not been used to evaluate the migration of reverse shoulder arthroplasty in a randomized controlled trial. This study intends to determine which treatment has the most optimal outcome for the benefit of future patients with an indication for reverse shoulder arthroplasty. Trial registration: The study has been notified to Pactius and has approval number P-2021-231. Furthermore, the study will be registered on Clinicaltrials.gov before starting the inclusion.
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| 30. |
- Kumsars, Indulis, et al.
(author)
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Randomised comparison of provisional side branch stenting versus a two-stent strategy for treatment of true coronary bifurcation lesions involving a large side branch : the Nordic-Baltic Bifurcation Study IV
- 2020
-
In: Open heart. - : BMJ Publishing Group Ltd. - 2053-3624. ; 7:1
-
Journal article (peer-reviewed)abstract
- Background: It is still uncertain whether coronary bifurcations with lesions involving a large side branch (SB) should be treated by stenting the main vessel and provisional stenting of the SB (simple) or by routine two-stent techniques (complex). We aimed to compare clinical outcome after treatment of lesions in large bifurcations by simple or complex stent implantation.Methods: The study was a randomised, superiority trial. Enrolment required a SB >= 2.75 mm, >= 50% diameter stenosis in both vessels, and allowed SB lesion length up to 15 mm. The primary endpoint was a composite of cardiac death, non-procedural myocardial infarction and target lesion revascularisation at 6 months. Two-year clinical follow-up was included in this primary reporting due to lower than expected event rates.Results: A total of 450 patients were assigned to simple stenting (n = 221) or complex stenting (n=229) in 14 Nordic and Baltic centres. Two-year follow-up was available in 218 (98.6%) and 228 (99.5%) patients, respectively. The primary endpoint of major adverse cardiac events (MACE) at 6 months was 5.5% vs 2.2% (risk differences 3.2%, 95% CI -0.2 to 6.8, p=0.07) and at 2 years 12.9% vs 8.4% (HR 0.63, 95% CI 0.35 to 1.13, p = 0.12) after simple versus complex treatment. In the subgroup treated by newer generation drug-eluting stents, MACE was 12.0% vs 5.6% (HR 0.45, 95% CI 0.17 to 1.17, p = 0.10) after simple versus complex treatment.Conclusion: In the treatment of bifurcation lesions involving a large SB with ostial stenosis, routine two-stent techniques did not improve outcome significantly compared with treatment by the simpler main vessel stenting technique after 2 years.
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| 31. |
- Mullier, G.A., et al.
(author)
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Measurement of the nuclear modification factor for muons from charm and bottom hadrons in Pb+Pb collisions at 5.02 TeV with the ATLAS detector
- 2022
-
In: Physics Letters B. - : Elsevier BV. - 0370-2693 .- 1873-2445. ; 829
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Journal article (peer-reviewed)abstract
- Heavy-flavour hadron production provides information about the transport properties and microscopic structure of the quark–gluon plasma created in ultra-relativistic heavy-ion collisions. A measurement of the muons from semileptonic decays of charm and bottom hadrons produced in Pb+Pb and pp collisions at a nucleon–nucleon centre-of-mass energy of 5.02 TeV with the ATLAS detector at the Large Hadron Collider is presented. The Pb+Pb data were collected in 2015 and 2018 with sampled integrated luminosities of 208μb−1 and 38μb−1, respectively, and pp data with a sampled integrated luminosity of 1.17pb−1 were collected in 2017. Muons from heavy-flavour semileptonic decays are separated from the light-flavour hadronic background using the momentum imbalance between the inner detector and muon spectrometer measurements, and muons originating from charm and bottom decays are further separated via the muon track's transverse impact parameter. Differential yields in Pb+Pb collisions and differential cross sections in pp collisions for such muons are measured as a function of muon transverse momentum from 4 GeV to 30 GeV in the absolute pseudorapidity interval |η|<2. Nuclear modification factors for charm and bottom muons are presented as a function of muon transverse momentum in intervals of Pb+Pb collision centrality. The bottom muon results are the most precise measurement of b quark nuclear modification at low transverse momentum where reconstruction of B hadrons is challenging. The measured nuclear modification factors quantify a significant suppression of the yields of muons from decays of charm and bottom hadrons, with stronger effects for muons from charm hadron decays.
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| 32. |
- Mullier, G.A., et al.
(author)
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Search for Higgs boson pair production in the two bottom quarks plus two photons final state in pp collisions at √s=13 TeV with the ATLAS detector
- 2022
-
In: Physical Review D. - : American Physical Society (APS). - 2470-0010 .- 2470-0029. ; 106:5
-
Journal article (peer-reviewed)abstract
- Searches are performed for nonresonant and resonant di-Higgs boson production in the b¯bγγ final state. The dataset used corresponds to an integrated luminosity of 139 fb−1 of proton–proton collisions at a center-of-mass energy of 13 TeV recorded by the ATLAS detector at the CERN Large Hadron Collider. No excess above the expected background is found and upper limits on the di-Higgs boson production cross sections are set. A 95% confidence-level upper limit of 4.2 times the cross section predicted by the Standard Model is set on pp→HH nonresonant production, where the expected limit is 5.7 times the Standard Model predicted value. The expected constraints are obtained for a background hypothesis excluding pp→HH production. The observed (expected) constraints on the Higgs boson trilinear coupling modifier κλ are determined to be [−1.5,6.7] ([−2.4,7.7]) at 95% confidence level, where the expected constraints on κλ are obtained excluding pp→HH production from the background hypothesis. For resonant production of a new hypothetical scalar particle X (X→HH→b¯bγγ), limits on the cross section for pp→X→HH are presented in the narrow-width approximation as a function of mX in the range 251 GeV≤mX≤1000 GeV. The observed (expected) limits on the cross section for pp→X→HH range from 640 fb to 44 fb (391 fb to 46 fb) over the considered mass range.
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| 33. |
- Murgas, F., et al.
(author)
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TOI-674b: An oasis in the desert of exo-Neptunes transiting a nearby M dwarf
- 2021
-
In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
-
Journal article (peer-reviewed)abstract
- Context. The NASA mission TESS is currently doing an all-sky survey from space to detect transiting planets around bright stars. As part of the validation process, the most promising planet candidates need to be confirmed and characterized using follow-up observations. Aims. In this article, our aim is to confirm the planetary nature of the transiting planet candidate TOI-674b using spectroscopic and photometric observations. Methods. We use TESS, Spitzer, ground-based light curves, and HARPS spectrograph radial velocity measurements to establish the physical properties of the transiting exoplanet candidate TOI-674b. We perform a joint fit of the light curves and radial velocity time series to measure the mass, radius, and orbital parameters of the candidate. Results. We confirm and characterize TOI-674b, a low-density super-Neptune transiting a nearby M dwarf. The host star (TIC 158588995, V = 14.2 mag, J = 10.3 mag) is characterized by its M2V spectral type with M = 0.420 ± 0.010 M , R = 0.420 ± 0.013 R , and Teff = 3514 ± 57 K; it is located at a distance d = 46.16 ± 0.03 pc. Combining the available transit light curves plus radial velocity measurements and jointly fitting a circular orbit model, we find an orbital period of 1.977143 ± 3 × 10-6 days, a planetary radius of 5.25 ± 0.17 R , and a mass of 23.6 ± 3.3 M implying a mean density of ρp =0.91 ± 0.15 g cm-3. A non-circular orbit model fit delivers similar planetary mass and radius values within the uncertainties. Given the measured planetary radius and mass, TOI-674b is one of the largest and most massive super-Neptune class planets discovered around an M-type star to date. It is found in the Neptunian desert, and is a promising candidate for atmospheric characterization using the James Webb Space Telescope.
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| 34. |
- Qian, Frank, et al.
(author)
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Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation
- 2023
-
In: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 82:4, s. 336-349
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial.OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosa-pentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF.METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and sub-groups. Associations were pooled using inverse-variance weighted meta-analysis.RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively.CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.
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| 35. |
- Serrano, L. M., et al.
(author)
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A low-eccentricity migration pathway for a 13-h-period Earth analogue in a four-planet system
- 2022
-
In: Nature Astronomy. - : Springer Science and Business Media LLC. - 2397-3366. ; 6:6, s. 736-750
-
Journal article (peer-reviewed)abstract
- It is commonly accepted that exoplanets with orbital periods shorter than one day, also known as ultra-short-period (USP) planets, formed further out within their natal protoplanetary disks before migrating to their current-day orbits via dynamical interactions. One of the most accepted theories suggests a violent scenario involving high-eccentricity migration followed by tidal circularization. Here we present the discovery of a four-planet system orbiting the bright (V = 10.5) K6 dwarf star TOI-500. The innermost planet is a transiting, Earth-sized USP planet with an orbital period of ~13 hours, a mass of 1.42 ± 0.18 M⊕, a radius of 1.166−0.058+0.061R⊕ and a mean density of 4.89−0.88+1.03gcm−3. Via Doppler spectroscopy, we discovered that the system hosts 3 outer planets on nearly circular orbits with periods of 6.6, 26.2 and 61.3 days and minimum masses of 5.03 ± 0.41 M⊕, 33.12 ± 0.88 M⊕ and 15.05−1.11+1.12M⊕, respectively. The presence of both a USP planet and a low-mass object on a 6.6-day orbit indicates that the architecture of this system can be explained via a scenario in which the planets started on low-eccentricity orbits then moved inwards through a quasi-static secular migration. Our numerical simulations show that this migration channel can bring TOI-500 b to its current location in 2 Gyr, starting from an initial orbit of 0.02 au. TOI-500 is the first four-planet system known to host a USP Earth analogue whose current architecture can be explained via a non-violent migration scenario.
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| 36. |
- Van den Bulcke, Bo, et al.
(author)
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Ethical climate and intention to leave among critical care clinicians: an observational study in 68 intensive care units across Europe and the United States.
- 2020
-
In: Intensive care medicine. - 1432-1238. ; 46:1, s. 46-56
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Journal article (peer-reviewed)abstract
- Apart from organizational issues, quality of inter-professional collaboration during ethical decision-making may affect the intention to leave one's job. To determine whether ethical climate is associated with the intention to leave after adjustment for country, ICU and clinicians characteristics.Perceptions of the ethical climate among clinicians working in 68 adult ICUs in 12 European countries and the US were measured using a self-assessment questionnaire, together with job characteristics and intent to leave as a sub-analysis of the Dispropricus study. The validated ethical decision-making climate questionnaire included seven factors: not avoiding decision-making at end-of-life (EOL), mutual respect within the interdisciplinary team, open interdisciplinary reflection, ethical awareness, self-reflective physician leadership, active decision-making at end-of-life by physicians, and involvement of nurses in EOL. Hierarchical mixed effect models were used to assess associations between these factors, and the intent to leave in clinicians within ICUs, within the different countries.Of 3610 nurses and 1137 physicians providing ICU bedside care, 63.1% and 62.9% participated, respectively. Of 2992 participating clinicians, 782 (26.1%) had intent to leave, of which 27% nurses, 24% junior and 22.7% senior physicians. After adjustment for country, ICU and clinicians characteristics, mutual respect OR 0.77 (95% CI 0.66- 0.90), open interdisciplinary reflection (OR 0.73 [95% CI 0.62-0.86]) and not avoiding EOL decisions (OR 0.87 [95% CI 0.77-0.98]) were all associated with a lower intent to leave.This is the first large multicenter study showing an independent association between clinicians' intent to leave and the quality of the ethical climate in the ICU. Interventions to reduce intent to leave may be most effective when they focus on improving mutual respect, interdisciplinary reflection and active decision-making at EOL.
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| 37. |
- Warthegau, Stefan S., et al.
(author)
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Heterocyclic [9]Helicenes Exhibiting Bright Circularly Polarized Luminescence
- 2023
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In: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 29:58
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Journal article (peer-reviewed)abstract
- We describe a concise synthetic strategy for the preparation of heterocyclic [9]helicenes and a simple preparative-scale protocol for the optical resolution of the resulting M- and P-enantiomers. The helicenes were characterized by single-crystal X-ray diffraction along with a range of spectroscopic and computational techniques. A fluorescence quantum yield of up to 65 % was observed, and the chiroptical properties of both M- and P-helicenes revealed large dissymmetry factors. The circularly polarized luminescence brightness reaches up to 17 M−1 cm−1, as measured experimentally and verified computationally, which makes this the highest circularly polarized luminescence brightness among heterocyclic helicenes. We describe how chiroptical properties (both circular dichroism and circularly polarized luminescence) can be described and predicted using quantum chemical calculations. The synthetic approach also reveals by-products that originate from internal oxidation reactions, presumably mediated by the close proximity of the π-surfaces in the helicene structure.
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| 38. |
- Wulf Hanson, Sarah, et al.
(author)
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A global systematic analysis of the occurrence, severity, and recovery pattern of long COVID in 2020 and 2021
- 2022
-
Other publication (other academic/artistic)abstract
- Importance: While much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.Objective: To estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recovery.Design: We jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.Results: Analyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8-312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38-7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9-92.4), 60.4% (18.9-89.1), and 35.4% (9.4-75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84-4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10-9.78]). At twelve months, 15.1% (10.3-21.1) continued to experience long COVID symptoms.Conclusions and relevance: The occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key Points: Question: What are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?Findings: Globally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.Meaning: The substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.
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| 39. |
- Wulf Hanson, Sarah, et al.
(author)
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Estimated Global Proportions of Individuals With Persistent Fatigue, Cognitive, and Respiratory Symptom Clusters Following Symptomatic COVID-19 in 2020 and 2021
- 2022
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In: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 328:16, s. 1604-1615
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Journal article (peer-reviewed)abstract
- IMPORTANCE: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID).OBJECTIVE: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration.DESIGN, SETTING, AND PARTICIPANTS: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022.EXPOSURES: Symptomatic SARS-CoV-2 infection.MAIN OUTCOMES AND MEASURES: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age.RESULTS: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months.CONCLUSIONS AND RELEVANCE: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.
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| 40. |
- Zhang, J., et al.
(author)
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Combining mechanistic and machine learning models for predictive engineering and optimization of tryptophan metabolism
- 2020
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- Through advanced mechanistic modeling and the generation of large high-quality datasets, machine learning is becoming an integral part of understanding and engineering living systems. Here we show that mechanistic and machine learning models can be combined to enable accurate genotype-to-phenotype predictions. We use a genome-scale model to pinpoint engineering targets, efficient library construction of metabolic pathway designs, and high-throughput biosensor-enabled screening for training diverse machine learning algorithms. From a single data-generation cycle, this enables successful forward engineering of complex aromatic amino acid metabolism in yeast, with the best machine learning-guided design recommendations improving tryptophan titer and productivity by up to 74 and 43%, respectively, compared to the best designs used for algorithm training. Thus, this study highlights the power of combining mechanistic and machine learning models to effectively direct metabolic engineering efforts.
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| 41. |
- Zhao, Cheng, et al.
(author)
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Single-cell multi-omics of human preimplantation embryos shows susceptibility to glucocorticoids
- 2022
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In: Genome Research. - : Cold Spring Harbor Laboratory Press (CSHL). - 1088-9051 .- 1549-5469. ; 32:9, s. 1627-1641
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Journal article (peer-reviewed)abstract
- The preconceptual, intrauterine, and early life environments can have a profound and long-lasting impact on the developmental trajectories and health outcomes of the offspring. Given the relatively low success rates of assisted reproductive technologies (ART; similar to 25%), additives and adjuvants, such as glucocorticoids, are used to improve the success rate. Considering the dynamic developmental events that occur during this window, these exposures may alter blastocyst formation at a molecular level, and as such, affect not only the viability of the embryo and the ability of the blastocyst to implant, but also the developmental trajectory of the first three cell lineages, ultimately influencing the physiology of the embryo. In this study, we present a comprehensive single-cell transcriptome, methylome, and small RNA atlas in the day 7 human embryo. We show that, despite no change in morphology and developmental features, preimplantation glucocorticoid exposure reprograms the molecular profile of the trophectoderm (TE) lineage, and these changes are associated with an altered metabolic and inflammatory response. Our data also suggest that glucocorticoids can precociously mature the TE sublineages, supported by the presence of extravillous trophoblast markers in the polar sublineage and presence of X Chromosome dosage compensation. Further, we have elucidated that epigenetic regulation-DNA methylation and microRNAs (miRNAs)-likely underlies the transcriptional changes observed. This study suggests that exposures to exogenous compounds during preimplantation may unintentionally reprogram the human embryo, possibly leading to suboptimal development and longer-term health outcomes.
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