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1.
  • Falster, Daniel, et al. (author)
  • AusTraits, a curated plant trait database for the Australian flora
  • 2021
  • In: Scientific Data. - : Nature Portfolio. - 2052-4463. ; 8:1
  • Journal article (peer-reviewed)abstract
    • We introduce the AusTraits database - a compilation of values of plant traits for taxa in the Australian flora (hereafter AusTraits). AusTraits synthesises data on 448 traits across 28,640 taxa from field campaigns, published literature, taxonomic monographs, and individual taxon descriptions. Traits vary in scope from physiological measures of performance (e.g. photosynthetic gas exchange, water-use efficiency) to morphological attributes (e.g. leaf area, seed mass, plant height) which link to aspects of ecological variation. AusTraits contains curated and harmonised individual- and species-level measurements coupled to, where available, contextual information on site properties and experimental conditions. This article provides information on version 3.0.2 of AusTraits which contains data for 997,808 trait-by-taxon combinations. We envision AusTraits as an ongoing collaborative initiative for easily archiving and sharing trait data, which also provides a template for other national or regional initiatives globally to fill persistent gaps in trait knowledge.
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2.
  • Kattge, Jens, et al. (author)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Journal article (peer-reviewed)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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3.
  • Kim, Jae-Young, et al. (author)
  • Event Horizon Telescope imaging of the archetypal blazar 3C 279 at an extreme 20 microarcsecond resolution
  • 2020
  • In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 640
  • Journal article (peer-reviewed)abstract
    • 3C 279 is an archetypal blazar with a prominent radio jet that show broadband flux density variability across the entire electromagnetic spectrum. We use an ultra-high angular resolution technique - global Very Long Baseline Interferometry (VLBI) at 1.3mm (230 GHz) - to resolve the innermost jet of 3C 279 in order to study its fine-scale morphology close to the jet base where highly variable-ray emission is thought to originate, according to various models. The source was observed during four days in April 2017 with the Event Horizon Telescope at 230 GHz, including the phased Atacama Large Millimeter/submillimeter Array, at an angular resolution of ∼20 μas (at a redshift of z = 0:536 this corresponds to ∼0:13 pc ∼ 1700 Schwarzschild radii with a black hole mass MBH = 8 × 108 M⊙). Imaging and model-fitting techniques were applied to the data to parameterize the fine-scale source structure and its variation.We find a multicomponent inner jet morphology with the northernmost component elongated perpendicular to the direction of the jet, as imaged at longer wavelengths. The elongated nuclear structure is consistent on all four observing days and across diffierent imaging methods and model-fitting techniques, and therefore appears robust. Owing to its compactness and brightness, we associate the northern nuclear structure as the VLBI "core". This morphology can be interpreted as either a broad resolved jet base or a spatially bent jet.We also find significant day-to-day variations in the closure phases, which appear most pronounced on the triangles with the longest baselines. Our analysis shows that this variation is related to a systematic change of the source structure. Two inner jet components move non-radially at apparent speeds of ∼15 c and ∼20 c (∼1:3 and ∼1:7 μas day-1, respectively), which more strongly supports the scenario of traveling shocks or instabilities in a bent, possibly rotating jet. The observed apparent speeds are also coincident with the 3C 279 large-scale jet kinematics observed at longer (cm) wavelengths, suggesting no significant jet acceleration between the 1.3mm core and the outer jet. The intrinsic brightness temperature of the jet components are ≤1010 K, a magnitude or more lower than typical values seen at ≥7mm wavelengths. The low brightness temperature and morphological complexity suggest that the core region of 3C 279 becomes optically thin at short (mm) wavelengths.
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4.
  • Kanai, M, et al. (author)
  • 2023
  • swepub:Mat__t
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5.
  • Wielgus, Maciek, et al. (author)
  • Monitoring the Morphology of M87* in 2009-2017 with the Event Horizon Telescope
  • 2020
  • In: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 901:1
  • Journal article (peer-reviewed)abstract
    • The Event Horizon Telescope (EHT) has recently delivered the first resolved images of M87*, the supermassive black hole in the center of the M87 galaxy. These images were produced using 230 GHz observations performed in 2017 April. Additional observations are required to investigate the persistence of the primary image feature-a ring with azimuthal brightness asymmetry-and to quantify the image variability on event horizon scales. To address this need, we analyze M87* data collected with prototype EHT arrays in 2009, 2011, 2012, and 2013. While these observations do not contain enough information to produce images, they are sufficient to constrain simple geometric models. We develop a modeling approach based on the framework utilized for the 2017 EHT data analysis and validate our procedures using synthetic data. Applying the same approach to the observational data sets, we find the M87* morphology in 2009-2017 to be consistent with a persistent asymmetric ring of similar to 40 mu as diameter. The position angle of the peak intensity varies in time. In particular, we find a significant difference between the position angle measured in 2013 and 2017. These variations are in broad agreement with predictions of a subset of general relativistic magnetohydrodynamic simulations. We show that quantifying the variability across multiple observational epochs has the potential to constrain the physical properties of the source, such as the accretion state or the black hole spin.
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6.
  • 2021
  • swepub:Mat__t
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7.
  • Glasbey, JC, et al. (author)
  • 2021
  • swepub:Mat__t
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8.
  • 2021
  • swepub:Mat__t
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9.
  • Dima, Danai, et al. (author)
  • Subcortical volumes across the lifespan : Data from 18,605 healthy individuals aged 3-90 years.
  • 2022
  • In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 43:1, s. 452-469
  • Journal article (peer-reviewed)abstract
    • Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to examine age-related trajectories inferred from cross-sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3-90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter-individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age-related morphometric patterns.
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10.
  • Fazey, Ioan, et al. (author)
  • Transforming knowledge systems for life on Earth : Visions of future systems and how to get there
  • 2020
  • In: Energy Research & Social Science. - : Elsevier. - 2214-6296 .- 2214-6326. ; 70
  • Journal article (peer-reviewed)abstract
    • Formalised knowledge systems, including universities and research institutes, are important for contemporary societies. They are, however, also arguably failing humanity when their impact is measured against the level of progress being made in stimulating the societal changes needed to address challenges like climate change. In this research we used a novel futures-oriented and participatory approach that asked what future envisioned knowledge systems might need to look like and how we might get there. Findings suggest that envisioned future systems will need to be much more collaborative, open, diverse, egalitarian, and able to work with values and systemic issues. They will also need to go beyond producing knowledge about our world to generating wisdom about how to act within it. To get to envisioned systems we will need to rapidly scale methodological innovations, connect innovators, and creatively accelerate learning about working with intractable challenges. We will also need to create new funding schemes, a global knowledge commons, and challenge deeply held assumptions. To genuinely be a creative force in supporting longevity of human and non-human life on our planet, the shift in knowledge systems will probably need to be at the scale of the enlightenment and speed of the scientific and technological revolution accompanying the second World War. This will require bold and strategic action from governments, scientists, civic society and sustained transformational intent.
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11.
  • Frangou, Sophia, et al. (author)
  • Cortical thickness across the lifespan : Data from 17,075 healthy individuals aged 3-90 years
  • 2022
  • In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 431-451
  • Journal article (peer-reviewed)abstract
    • Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3-90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes.
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12.
  • Frier, Emily M, et al. (author)
  • Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids.
  • 2023
  • In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 18:3
  • Journal article (peer-reviewed)abstract
    • Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure.The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records.The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS.
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14.
  • Khatri, C, et al. (author)
  • Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
  • 2021
  • In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
  • Journal article (peer-reviewed)abstract
    • Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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15.
  • Sonderby, Ida E., et al. (author)
  • Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia
  • 2020
  • In: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:3, s. 584-602
  • Journal article (peer-reviewed)abstract
    • Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = −0.71 to −1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = −0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10−6, 1.7 × 10−9, 3.5 × 10−12 and 1.0 × 10−4, respectively). Full scale IQ was lower in both deletion and duplication carriers compared to non-carriers. This is the first brain MRI study of the impact of the 16p11.2 distal CNV, and we demonstrate a specific effect on subcortical brain structures, suggesting a neuropathological pattern underlying the neurodevelopmental syndromes.
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16.
  • Tapia-Ruiz, Nuria, et al. (author)
  • 2021 roadmap for sodium-ion batteries
  • 2021
  • In: Journal of Physics. - : Institute of Physics Publishing (IOPP). - 2515-7655. ; 3:3
  • Journal article (peer-reviewed)abstract
    • Increasing concerns regarding the sustainability of lithium sources, due to their limited availability and consequent expected price increase, have raised awareness of the importance of developing alternative energy-storage candidates that can sustain the ever-growing energy demand. Furthermore, limitations on the availability of the transition metals used in the manufacturing of cathode materials, together with questionable mining practices, are driving development towards more sustainable elements. Given the uniformly high abundance and cost-effectiveness of sodium, as well as its very suitable redox potential (close to that of lithium), sodium-ion battery technology offers tremendous potential to be a counterpart to lithium-ion batteries (LIBs) in different application scenarios, such as stationary energy storage and low-cost vehicles. This potential is reflected by the major investments that are being made by industry in a wide variety of markets and in diverse material combinations. Despite the associated advantages of being a drop-in replacement for LIBs, there are remarkable differences in the physicochemical properties between sodium and lithium that give rise to different behaviours, for example, different coordination preferences in compounds, desolvation energies, or solubility of the solid-electrolyte interphase inorganic salt components. This demands a more detailed study of the underlying physical and chemical processes occurring in sodium-ion batteries and allows great scope for groundbreaking advances in the field, from lab-scale to scale-up. This roadmap provides an extensive review by experts in academia and industry of the current state of the art in 2021 and the different research directions and strategies currently underway to improve the performance of sodium-ion batteries. The aim is to provide an opinion with respect to the current challenges and opportunities, from the fundamental properties to the practical applications of this technology.
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17.
  • van der Meer, Dennis, et al. (author)
  • Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition
  • 2020
  • In: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 77:4, s. 420-430
  • Journal article (peer-reviewed)abstract
    • Importance: Recurrent microdeletions and duplications in the genomic region 15q11.2 between breakpoints 1 (BP1) and 2 (BP2) are associated with neurodevelopmental disorders. These structural variants are present in 0.5% to 1.0% of the population, making 15q11.2 BP1-BP2 the site of the most prevalent known pathogenic copy number variation (CNV). It is unknown to what extent this CNV influences brain structure and affects cognitive abilities.Objective: To determine the association of the 15q11.2 BP1-BP2 deletion and duplication CNVs with cortical and subcortical brain morphology and cognitive task performance.Design, Setting, and Participants: In this genetic association study, T1-weighted brain magnetic resonance imaging were combined with genetic data from the ENIGMA-CNV consortium and the UK Biobank, with a replication cohort from Iceland. In total, 203 deletion carriers, 45 247 noncarriers, and 306 duplication carriers were included. Data were collected from August 2015 to April 2019, and data were analyzed from September 2018 to September 2019.Main Outcomes and Measures: The associations of the CNV with global and regional measures of surface area and cortical thickness as well as subcortical volumes were investigated, correcting for age, age2, sex, scanner, and intracranial volume. Additionally, measures of cognitive ability were analyzed in the full UK Biobank cohort.Results: Of 45 756 included individuals, the mean (SD) age was 55.8 (18.3) years, and 23 754 (51.9%) were female. Compared with noncarriers, deletion carriers had a lower surface area (Cohen d = -0.41; SE, 0.08; P = 4.9 × 10-8), thicker cortex (Cohen d = 0.36; SE, 0.07; P = 1.3 × 10-7), and a smaller nucleus accumbens (Cohen d = -0.27; SE, 0.07; P = 7.3 × 10-5). There was also a significant negative dose response on cortical thickness (β = -0.24; SE, 0.05; P = 6.8 × 10-7). Regional cortical analyses showed a localization of the effects to the frontal, cingulate, and parietal lobes. Further, cognitive ability was lower for deletion carriers compared with noncarriers on 5 of 7 tasks.Conclusions and Relevance: These findings, from the largest CNV neuroimaging study to date, provide evidence that 15q11.2 BP1-BP2 structural variation is associated with brain morphology and cognition, with deletion carriers being particularly affected. The pattern of results fits with known molecular functions of genes in the 15q11.2 BP1-BP2 region and suggests involvement of these genes in neuronal plasticity. These neurobiological effects likely contribute to the association of this CNV with neurodevelopmental disorders.
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18.
  • van Meel, Evelien R., et al. (author)
  • Early-life respiratory tract infections and the risk of school-age lower lung function and asthma: a meta-analysis of 150 000 European children
  • 2022
  • In: European Respiratory Journal. - : EUROPEAN RESPIRATORY SOC JOURNALS LTD. - 0903-1936 .- 1399-3003. ; 60:4
  • Journal article (peer-reviewed)abstract
    • Background Early-life respiratory tract infections might affect chronic obstructive respiratory diseases, but conclusive studies from general populations are lacking. Our objective was to examine if children with early-life respiratory tract infections had increased risks of lower lung function and asthma at school age. Methods We used individual participant data of 150 090 children primarily from the EU Child Cohort Network to examine the associations of upper and lower respiratory tract infections from age 6 months to 5 years with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), FEV1/FVC, forced expiratory flow at 75% of FVC (FEF75%) and asthma at a median (range) age of 7 (4-15) years. Results Children with early-life lower, not upper, respiratory tract infections had a lower school-age FEV1, FEV1/FVC and FEF75% (z-score range: -0.09 (95% CI -0.14- -0.04) to -0.30 (95% CI -0.36- -0.24)). Children with early-life lower respiratory tract infections had a higher increased risk of school-age asthma than those with upper respiratory tract infections (OR range: 2.10 (95% CI 1.98-2.22) to 6.30 (95% CI 5.64-7.04) and 1.25 (95% CI 1.18-1.32) to 1.55 (95% CI 1.47-1.65), respectively). Adjustment for preceding respiratory tract infections slightly decreased the strength of the effects. Observed associations were similar for those with and without early-life wheezing as a proxy for early-life asthma. Conclusions Our findings suggest that early-life respiratory tract infections affect development of chronic obstructive respiratory diseases in later life, with the strongest effects for lower respiratory tract infections.
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19.
  • Vandenput, Liesbeth, et al. (author)
  • A meta-analysis of previous falls and subsequent fracture risk in cohort studies
  • 2024
  • In: Osteoporosis International. - : Springer. - 0937-941X .- 1433-2965. ; 35:3, s. 469-494
  • Journal article (peer-reviewed)abstract
    • SummaryThe relationship between self-reported falls and fracture risk was estimated in an international meta-analysis of individual-level data from 46 prospective cohorts. Previous falls were associated with an increased fracture risk in women and men and should be considered as an additional risk factor in the FRAX® algorithm.IntroductionPrevious falls are a well-documented risk factor for subsequent fracture but have not yet been incorporated into the FRAX algorithm. The aim of this study was to evaluate, in an international meta-analysis, the association between previous falls and subsequent fracture risk and its relation to sex, age, duration of follow-up, and bone mineral density (BMD).MethodsThe resource comprised 906,359 women and men (66.9% female) from 46 prospective cohorts. Previous falls were uniformly defined as any fall occurring during the previous year in 43 cohorts; the remaining three cohorts had a different question construct. The association between previous falls and fracture risk (any clinical fracture, osteoporotic fracture, major osteoporotic fracture, and hip fracture) was examined using an extension of the Poisson regression model in each cohort and each sex, followed by random-effects meta-analyses of the weighted beta coefficients.ResultsFalls in the past year were reported in 21.4% of individuals. During a follow-up of 9,102,207 person-years, 87,352 fractures occurred of which 19,509 were hip fractures. A previous fall was associated with a significantly increased risk of any clinical fracture both in women (hazard ratio (HR) 1.42, 95% confidence interval (CI) 1.33–1.51) and men (HR 1.53, 95% CI 1.41–1.67). The HRs were of similar magnitude for osteoporotic, major osteoporotic fracture, and hip fracture. Sex significantly modified the association between previous fall and fracture risk, with predictive values being higher in men than in women (e.g., for major osteoporotic fracture, HR 1.53 (95% CI 1.27–1.84) in men vs. HR 1.32 (95% CI 1.20–1.45) in women, P for interaction = 0.013). The HRs associated with previous falls decreased with age in women and with duration of follow-up in men and women for most fracture outcomes. There was no evidence of an interaction between falls and BMD for fracture risk. Subsequent risk for a major osteoporotic fracture increased with each additional previous fall in women and men.ConclusionsA previous self-reported fall confers an increased risk of fracture that is largely independent of BMD. Previous falls should be considered as an additional risk factor in future iterations of FRAX to improve fracture risk prediction.
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20.
  • Wierenga, Lara M., et al. (author)
  • Greater male than female variability in regional brain structure across the lifespan
  • 2022
  • In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 470-499
  • Journal article (peer-reviewed)abstract
    • For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.
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21.
  • Yeung, Edwina, et al. (author)
  • Maternal age is related to offspring DNA methylation : a meta-analysis of results from the pace consortium
  • 2024
  • In: Aging Cell. - : John Wiley & Sons. - 1474-9718 .- 1474-9726. ; 23:8
  • Journal article (peer-reviewed)abstract
    • Worldwide trends to delay childbearing have increased parental ages at birth. Older parental age may harm offspring health, but mechanisms remain unclear. Alterations in offspring DNA methylation (DNAm) patterns could play a role as aging has been associated with methylation changes in gametes of older individuals. We meta-analyzed epigenome-wide associations of parental age with offspring blood DNAm of over 9500 newborns and 2000 children (5–10 years old) from the Pregnancy and Childhood Epigenetics consortium. In newborns, we identified 33 CpG sites in 13 loci with DNAm associated with maternal age (PFDR < 0.05). Eight of these CpGs were located near/in the MTNR1B gene, coding for a melatonin receptor. Regional analysis identified them together as a differentially methylated region consisting of 9 CpGs in/near MTNR1B, at which higher DNAm was associated with greater maternal age (PFDR = 6.92 × 10−8) in newborns. In childhood blood samples, these differences in blood DNAm of MTNR1B CpGs were nominally significant (p < 0.05) and retained the same positive direction, suggesting persistence of associations. Maternal age was also positively associated with higher DNA methylation at three CpGs in RTEL1-TNFRSF6B at birth (PFDR < 0.05) and nominally in childhood (p < 0.0001). Of the remaining 10 CpGs also persistent in childhood, methylation at cg26709300 in YPEL3/BOLA2B in external data was associated with expression of ITGAL, an immune regulator. While further study is needed to establish causality, particularly due to the small effect sizes observed, our results potentially support offspring DNAm as a mechanism underlying associations of maternal age with child health.
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22.
  • Bravo, L, et al. (author)
  • 2021
  • swepub:Mat__t
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23.
  • Tabiri, S, et al. (author)
  • 2021
  • swepub:Mat__t
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24.
  • Adesiyun, Adewole, et al. (author)
  • Digital Road Operations : Deliverable D4
  • 2023
  • Reports (other academic/artistic)abstract
    • The DiREC CAV-Readiness Framework (CRF) is a framework that aims to help an NRA assess their capability with respect to the deployment of Connected and Automated Driving (CAD) solutions, their ability to influence the use of CAD on their network via investment in digital and physical infrastructure, and the impacts and outcomes of any investment decision.DiREC structured the CRF around C-ITS Services and Use Cases as defined under the C-ROADS project. C-ROADS is a joint initiative of European Member States and road operators for testing and implementing C-ITS services, with a desire for cross-border harmonisation and interoperability.The CRF is thus a framework which can be used by NRAs to help assess their aspirations and readiness to support CAD, and to implement individual C-ITS services and use cases. It does this by:Defining the C-ITS services to be providedBreaking those services down into use cases and enablersScoring the NRAs readiness, aspirations and high-level assessment of costs and impacts of each enabler to help plan and prioritise the NRA support for CAD.
  •  
25.
  • Adesiyun, Adewole, et al. (author)
  • Final Report
  • 2023
  • Reports (other academic/artistic)abstract
    • The 2020 CEDR Research Call on the Impact of CAD on Safe Smart Roads had as its aim to “prepare the national road authorities on future challenges of connectivity, digitalization and automation to get to an autonomously well-managed traffic flow.” CEDR cautioned that “ If NRAs do not act proactively, the vehicle manufacturers will determine the automation of traffic flow alone, the NRAs will fall behind and huge investment will be needed to safeguard NRAs’ objectives. NRAs’ goals and roles in the Cooperative, Connected and Automated Mobility of the future must be clear…NRAs need to determine and act before other parties decide in our place where we need to invest.”.The Digital Road for Evolving Connected and Automated Driving (DiREC) project set out to develop a toolkit for NRAs to use in their assessment and development of their capabilities as digital road operators. This toolkit, referred to as the CAV Readiness Framework (CRF), focuses on five key areasof provision that are central to the development of connected and automated driving capabilities. Those areas being:Physical infrastructureDigital infrastructureCommunications infrastructureStandards and regulationOperational supportDiREC focused on technologies, services and regulatory infrastructure for which NRAs might either have direct responsibility or at least significant influence. Development led by vehicle manufacturers or the regulations governing them were considered to be outside the scope of influence of the NRAs, for the moment at least. Instead, attention was given to those technologies and services that are likely to be generically useful to most or all future CAD solutions. We identified that there is still a considerable diversity of approaches amongst the developers of automated vehicles, with no single technical strategy yet close to being dominant.
  •  
26.
  • Adesiyun, Adewole, et al. (author)
  • Level of Service Definitions : Deliverable D3
  • 2023
  • Reports (other academic/artistic)abstract
    • The Level of Service (LoS) is a widely employed metric that quantifies the performance and quality of a provided service, utilizing a predetermined scale. In the transportation domain, road capacity (i.e., maximum throughput in a given road section) is the most widely used performance indicator, where the LoS is applied. In road capacity studies, the LoS definition is dependent upon the specific context and facility under examination, such as urban areas or motorways. In urban settings, the criteria typically employed for determining LoS include average travel speed, average travel time, frequency of stops, and delays. Conversely, on motorways, LoS is determined by factors such as vehicle density, traffic speed, and frequency of lane changes (HCM, 2016). Upon specifying the context, the chosen criteria are applied, and threshold requirements are established to categorize the performance and quality under the appropriate LoS. The LoS scale can range from binary levels (e.g., acceptable or unacceptable) to more nuanced scales. For instance, the HCM (2016) employs a six-point scale (A = very good; B = good; C = acceptable; D = bad; E = very bad; F = system breakdown).For C-ITS services (i.e., information provision), however, the aim is to provide information that are, among other things, accurate and timely to the road users, connected and autonomous vehicles, so they can react accordingly to events on the road network. The CAV-ready framework (CRF) developed in WP3 aims to illustrate the progress of National Road Authorities (NRAs) towards becoming a digital authority, meaning that the NRAs should provide traffic related information (data provision) to its users (connected and autonomous vehicles) that are precise, accurate, and timely. As such, we have defined three distinct LoS categories:Basic: Minimum acceptable performance/qualityEnhanced: Not optimal but sufficient performance/qualityAdvanced: Ideal or best performance/quality
  •  
27.
  • Adesiyun, Adewole, et al. (author)
  • Review and Evaluation of NRAs : Deliverable D2
  • 2023
  • Reports (other academic/artistic)abstract
    • Connected and Automated Driving (CAD) is an important area of digital technology that will bring disruption to individuals, economies, and societies. Most forms of CAD require some level of infrastructure support for their safe operation. Additional infrastructure and services to support CAD have the potential to improve safety even further, and to bring other benefits such as increased efficiency or reduced congestion. However, the infrastructure requirements from Original Equipment Manufacturer (OEMs) are not always clear, and it is difficult for National Road Authorities (NRAs) to predict and plan for the future levels of support needed for CAD given rapidly evolving technology and uncertain projections of future CAD demand. In addition, there is also a need for better dialogue among NRAs, OEMs and service providers to articulate those requirements and to define a roadmap and responsibilities for achieving safe and smart roads through CAD.The aim of DiREC is to establish a CAV Readiness Framework and a set of toolkits dedicated to CAVs (Connected and Autonomous Vehicles) that incorporates a wide range of components that affect CAD and the ability of highway infrastructure to support it. These components include machine readability of physical infrastructure, digital services, connectivity, in addition to aspects such as governance of the infrastructure and services, and legal and regulatory requirements. Together these components influence the ability of the NRA to become a digital road operator. The DiREC project will thus provide a framework for NRAs, service providers and OEMs to support CAD. It will consolidate and combine standards, research, and recommendations from other projects and extend research into new areas such as creating a common vision for digital twins among NRAs, understanding connectivity and connectivity requirements to support digital services and analysing how these can be met, reviewing the quality management processes around digital data, and documenting existing legal and regulatory frameworks in all areas relating to CAD.
  •  
28.
  • Adesiyun, Adewole, et al. (author)
  • Stakeholder Engagement Report : Deliverable D1
  • 2023
  • Reports (other academic/artistic)abstract
    • The main aim of the DiREC project is developing a common framework to support National Road Authorities (NRAs) to provide better engagement with Original Equipment Manufacturers (OEM) and service providers, identify clearer responsibilities and liabilities, and include tools to calculate the costs and benefits of providing different levels of support to Connected and Automated Vehicles (CAVs). Greater engagement and dialogue are key. By understanding the infrastructure and communications requirements of automated vehicles, and the challenges faced by CAVs in an operational environment, NRAs will be able to strategically plan their networks to support Connected and Automated Driving (CAD) and place themselves in a much stronger position to influence how traffic operates on the network.A proactive approach to liaising with vehicle manufacturers and service providers will also promote NRA involvement in the services that are developing around digital mapping, localisation, navigation and traffic management. By aligning the digital strategies and plans of the NRAs with the requirements of OEMs and CAVs, and by giving direction to service providers, a common framework for CAD will help achieve major cost efficiencies and facilitate economic transformation. It will help optimise the delivery of infrastructure and communications systems on national road networks in support of CAD implementation whilst helping NRAs maintain their influence over CAD activity. In order to facilitate productive interactions with various stakeholders involved with CAVs, WP1 within the DiREC project is dedicated to stakeholder engagement activities. This will ensure that input from different stakeholder categories will be collected and utilized for CAV-ready framework development.
  •  
29.
  • Amare, Azmeraw, et al. (author)
  • Association of Polygenic Score and the involvement of Cholinergic and Glutamatergic Pathways with Lithium Treatment Response in Patients with Bipolar Disorder.
  • 2023
  • In: Research square. - : Research Square Platform LLC.
  • Journal article (peer-reviewed)abstract
    • Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2,367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������.
  •  
30.
  • Amare, Azmeraw T, et al. (author)
  • Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.
  • 2023
  • In: Molecular psychiatry. - 1476-5578. ; 28, s. 5251-5261
  • Journal article (peer-reviewed)abstract
    • Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental healthdisorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N=2367) and replicated in the combined PsyCourse (N=89) and BipoLife (N=102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P<0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P=9.8×10-12, R2=1.9%) and continuous (P=6.4×10-9, R2=2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P=3.9×10-4, R2=0.9%), but not for the continuous outcome (P=0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.
  •  
31.
  • Anthon, Carl Thomas, et al. (author)
  • Thrombocytopenia and platelet transfusions in ICU patients : an international inception cohort study (PLOT-ICU)
  • 2023
  • In: Intensive Care Medicine. - 0342-4642. ; 49:11, s. 1327-1338
  • Journal article (peer-reviewed)abstract
    • PURPOSE: Thrombocytopenia (platelet count < 150 × 10 9/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses.RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42).CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.
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32.
  • Axelsson, John, et al. (author)
  • Sleepiness as motivation : a potential mechanism for how sleep deprivation affects behavior
  • 2020
  • In: Sleep. - : Oxford University Press (OUP). - 0161-8105 .- 1550-9109. ; 43:6
  • Journal article (peer-reviewed)abstract
    • STUDY OBJECTIVES: To determine how sleepiness and sleep deprivation drive the motivation to engage in different behaviors.METHODS: We studied the sleepiness of 123 participants who had been randomized to sleep deprivation or normal sleep, and their willingness to engage in a range of everyday behaviors.RESULTS: Self-reported sleepiness was a strong predictor of the motivation to engage in sleep-preparatory behaviors such as shutting one's eyes (OR=2.78, 95%CI: 2.19-3.52 for each step up on the Karolinska Sleepiness Scale) and resting (OR=3.20, CI: 2.46-4.16). Sleepiness was also related to the desire to be cared for by a loved one (OR=1.49, CI: 1.22-1.82), and preparedness to utilize monetary and energy resources to get to sleep. Conversely, increased sleepiness was associated with a decreased motivation for social and physical activities (e.g., be with friends OR=0.71, CI: 0.61-0.82; exercise OR=0.65, CI: 0.56-0.76). Sleep deprivation had similar effects as sleepiness on these behaviors. Neither sleepiness nor sleep deprivation had strong associations with hunger, thirst, or food preferences.CONCLUSIONS: Our findings indicate that sleepiness is a dynamic motivational drive that promotes sleep-preparatory behaviors and competes with other drives and desired outcomes. Consequently, sleepiness may be a central mechanism by which impaired alertness, e.g., due to insufficient sleep, contributes to poor quality of life and adverse health. We propose that sleepiness helps organize behaviors toward the specific goal of assuring sufficient sleep, in competition with other needs and incentives. A theoretical framework on sleepiness and its behavioral consequences are likely to improve our understanding of several disease mechanisms.
  •  
33.
  • Barrado, David, et al. (author)
  • 15NH3 in the atmosphere of a cool brown dwarf
  • 2023
  • In: Nature. - 0028-0836 .- 1476-4687. ; 624:7991, s. 263-266
  • Journal article (peer-reviewed)abstract
    • Brown dwarfs serve as ideal laboratories for studying the atmospheres of giant exoplanets on wide orbits, as the governing physical and chemical processes within them are nearly identical. Understanding the formation of gas-giant planets is challenging, often involving the endeavour to link atmospheric abundance ratios, such as the carbon-to-oxygen (C/O) ratio, to formation scenarios. However, the complexity of planet formation requires further tracers, as the unambiguous interpretation of the measured C/O ratio is fraught with complexity. Isotope ratios, such as deuterium to hydrogen and 14N/15N, offer a promising avenue to gain further insight into this formation process, mirroring their use within the Solar System. For exoplanets, only a handful of constraints on 12C/13C exist, pointing to the accretion of 13C-rich ice from beyond the CO iceline of the disks. Here we report on the mid-infrared detection of the 14NH3 and 15NH3 isotopologues in the atmosphere of a cool brown dwarf with an effective temperature of 380 K in a spectrum taken with the Mid-Infrared Instrument (MIRI) of JWST. As expected, our results reveal a 14N/15N value consistent with star-like formation by gravitational collapse, demonstrating that this ratio can be accurately constrained. Because young stars and their planets should be more strongly enriched in the 15N isotope, we expect that 15NH3 will be detectable in several cold, wide-separation exoplanets. 
  •  
34.
  • Bridges, Hannah R., et al. (author)
  • Structure of inhibitor-bound mammalian complex I
  • 2020
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
  • Journal article (peer-reviewed)abstract
    • Respiratory complex I (NADH:ubiquinone oxidoreductase) captures the free energy from oxidising NADH and reducing ubiquinone to drive protons across the mitochondrial inner membrane and power oxidative phosphorylation. Recent cryo-EM analyses have produced near-complete models of the mammalian complex, but leave the molecular principles of its long-range energy coupling mechanism open to debate. Here, we describe the 3.0-Ao resolution cryo-EM structure of complex I from mouse heart mitochondria with a substrate-like inhibitor, piericidin A, bound in the ubiquinone-binding active site. We combine our structural analyses with both functional and computational studies to demonstrate competitive inhibitor binding poses and provide evidence that two inhibitor molecules bind end-to-end in the long substrate binding channel. Our findings reveal information about the mechanisms of inhibition and substrate reduction that are central for understanding the principles of energy transduction in mammalian complex I. The respiratory complex I (NADH:ubiquinone oxidoreductase) is a large redox-driven proton pump that initiates respiration in mitochondria. Here, the authors present the 3.0 angstrom cryo-EM structure of complex I from mouse heart mitochondria with the ubiquinone-analogue inhibitor piericidin A bound in the active site and with kinetic measurements and MD simulations they further show that this inhibitor acts competitively against the native ubiquinone-10 substrate.
  •  
35.
  • Burris, William A., et al. (author)
  • IRAS 00450+7401 and the Mid-infrared Fade/Burst Cycle of R Coronae Borealis-type Stars
  • 2023
  • In: Astronomical Journal. - 1538-3881 .- 0004-6256. ; 166:2
  • Journal article (peer-reviewed)abstract
    • We present optical and infrared imaging and spectroscopy of the R Coronae Borealis-type (R Cor Bor) star IRAS 00450+7401. Optical spectra further confirm its classification as a cool R Cor Bor system, having a hydrogen-deficient carbon star spectral subclass of HdC5 or later. Mid-infrared spectroscopy reveals the typical ∼8 μm “hump” seen in other R Cor Bor stars and no other features. A modern-epoch spectral energy distribution shows bright emission from hot dust having T dust > 600 K. Historical infrared data reveal generally cooler dust color temperatures combined with long-term fading trends, but provide no discernible correlation between flux level and temperature. Investigating the most mid-infrared variable R Cor Bor stars found in IRAS, AKARI, and WISE data reveals similar fading trends, bursts that can show a factor of up to 10 change in flux density between epochs, and blackbody-fit dust color temperatures that span 400-1300 K. While some R Cor Bor stars such as IRAS 00450+7401 appear to undergo fade/burst cycles in the mid-infrared, significant gaps in temporal coverage prevent conclusively identifying any preferred timescale for their mid-infrared variability and circumstellar dust temperature changes.
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36.
  • Cornille, Amandine, et al. (author)
  • The relative role of plasticity and demographic history in Capsella bursa-pastoris : a common garden experiment in Asia and Europe
  • 2022
  • In: AoB Plants. - : Oxford University Press (OUP). - 2041-2851. ; 14:3
  • Journal article (peer-reviewed)abstract
    • The respective role of demography, plasticity and adaptation in the colonization success of plant species remains an intense topic of investigation in evolutionary ecology and genomics. A screening of phenotypic traits of hundreds of genotypes in large-scale common garden experiments in Eastern Asia and Europe shows that both demography and a high phenotypic plasticity underlie the success of the tetraploid and self-fertilizing species, Capsella bursa-pastoris, the shepherd's purse, at different stages of expansion. This study provides insight into the causes of the ecological success of a plant species during range expansion. The colonization success of a species depends on the interplay between its phenotypic plasticity, adaptive potential and demographic history. Assessing their relative contributions during the different phases of a species range expansion is challenging, and requires large-scale experiments. Here, we investigated the relative contributions of plasticity, performance and demographic history to the worldwide expansion of the shepherd's purse, Capsella bursa-pastoris. We installed two large common gardens of the shepherd's purse, a young, self-fertilizing, allopolyploid weed with a worldwide distribution. One common garden was located in Europe, the other in Asia. We used accessions from three distinct genetic clusters (Middle East, Europe and Asia) that reflect the demographic history of the species. Several life-history traits were measured. To explain the phenotypic variation between and within genetic clusters, we analysed the effects of (i) the genetic clusters, (ii) the phenotypic plasticity and its association to fitness and (iii) the distance in terms of bioclimatic variables between the sampling site of an accession and the common garden, i.e. the environmental distance. Our experiment showed that (i) the performance of C. bursa-pastoris is closely related to its high phenotypic plasticity; (ii) within a common garden, genetic cluster was a main determinant of phenotypic differences; and (iii) at the scale of the experiment, the effect of environmental distance to the common garden could not be distinguished from that of genetic clusters. Phenotypic plasticity and demographic history both play important role at different stages of range expansion. The success of the worldwide expansion of C. bursa-pastoris was undoubtedly influenced by its strong phenotypic plasticity.
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37.
  • Dyrek, Achrène, et al. (author)
  • SO2, silicate clouds, but no CH4 detected in a warm Neptune
  • 2024
  • In: Nature. - 0028-0836 .- 1476-4687. ; 625, s. 51-54
  • Journal article (peer-reviewed)abstract
    • WASP-107b is a warm (approximately 740 K) transiting planet with a Neptune-like mass of roughly 30.5 M⊕ and Jupiter-like radius of about 0.94 RJ (refs. 1,2), whose extended atmosphere is eroding3. Previous observations showed evidence for water vapour and a thick, high-altitude condensate layer in the atmosphere of WASP-107b (refs. 4,5). Recently, photochemically produced sulfur dioxide (SO2) was detected in the atmosphere of a hot (about 1,200 K) Saturn-mass planet from transmission spectroscopy near 4.05 μm (refs. 6,7), but for temperatures below about 1,000 K, sulfur is predicted to preferably form sulfur allotropes instead of SO2 (refs. 8,9,10). Here we report the 9σ detection of two fundamental vibration bands of SO2, at 7.35 μm and 8.69 μm, in the transmission spectrum of WASP-107b using the Mid-Infrared Instrument (MIRI) of JWST. This discovery establishes WASP-107b as the second irradiated exoplanet with confirmed photochemistry, extending the temperature range of exoplanets exhibiting detected photochemistry from about 1,200 K down to about 740 K. Furthermore, our spectral analysis reveals the presence of silicate clouds, which are strongly favoured (around 7σ) over simpler cloud set-ups. Furthermore, water is detected (around 12σ) but methane is not. These findings provide evidence of disequilibrium chemistry and indicate a dynamically active atmosphere with a super-solar metallicity.
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38.
  • Gilmour, Kathleen M., et al. (author)
  • Through the looking glass : attempting to predict future opportunities and challenges in experimental biology
  • 2023
  • In: The Journal of experimental biology. - 1477-9145. ; 226:24
  • Journal article (peer-reviewed)abstract
    • To celebrate its centenary year, Journal of Experimental Biology (JEB) commissioned a collection of articles examining the past, present and future of experimental biology. This Commentary closes the collection by considering the important research opportunities and challenges that await us in the future. We expect that researchers will harness the power of technological advances, such as '-omics' and gene editing, to probe resistance and resilience to environmental change as well as other organismal responses. The capacity to handle large data sets will allow high-resolution data to be collected for individual animals and to understand population, species and community responses. The availability of large data sets will also place greater emphasis on approaches such as modeling and simulations. Finally, the increasing sophistication of biologgers will allow more comprehensive data to be collected for individual animals in the wild. Collectively, these approaches will provide an unprecedented understanding of 'how animals work' as well as keys to safeguarding animals at a time when anthropogenic activities are degrading the natural environment.
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39.
  • Gumz, Michelle L, et al. (author)
  • Toward Precision Medicine : Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report
  • 2023
  • In: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 80:3, s. 503-522
  • Journal article (peer-reviewed)abstract
    • Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure. Sleep patterns, hormone release, eating habits, digestion, body temperature, renal and cardiovascular function, and other important host functions as well as gut microbiota exhibit circadian rhythms, and influence circadian rhythms of blood pressure. Potential benefits of nonpharmacologic interventions such as meal timing, and pharmacologic chronotherapeutic interventions, such as the bedtime administration of antihypertensive medications, have recently been suggested in some studies. However, the mechanisms underlying circadian rhythm-mediated blood pressure regulation and the efficacy of chronotherapy in hypertension remain unclear. This review summarizes the results of the National Heart, Lung, and Blood Institute workshop convened on October 27 to 29, 2021 to assess knowledge gaps and research opportunities in the study of circadian rhythm of blood pressure and chronotherapy for hypertension.
  •  
40.
  • Gutman, Boris A, et al. (author)
  • A meta-analysis of deep brain structural shape and asymmetry abnormalities in 2,833 individuals with schizophrenia compared with 3,929 healthy volunteers via the ENIGMA Consortium
  • 2022
  • In: Human Brain Mapping. - : John Wiley & Sons. - 1065-9471 .- 1097-0193. ; 43:1, s. 352-372
  • Journal article (peer-reviewed)abstract
    • Schizophrenia is associated with widespread alterations in subcortical brain structure. While analytic methods have enabled more detailed morphometric characterization, findings are often equivocal. In this meta-analysis, we employed the harmonized ENIGMA shape analysis protocols to collaboratively investigate subcortical brain structure shape differences between individuals with schizophrenia and healthy control participants. The study analyzed data from 2,833 individuals with schizophrenia and 3,929 healthy control participants contributed by 21 worldwide research groups participating in the ENIGMA Schizophrenia Working Group. Harmonized shape analysis protocols were applied to each site's data independently for bilateral hippocampus, amygdala, caudate, accumbens, putamen, pallidum, and thalamus obtained from T1-weighted structural MRI scans. Mass univariate meta-analyses revealed more-concave-than-convex shape differences in the hippocampus, amygdala, accumbens, and thalamus in individuals with schizophrenia compared with control participants, more-convex-than-concave shape differences in the putamen and pallidum, and both concave and convex shape differences in the caudate. Patterns of exaggerated asymmetry were observed across the hippocampus, amygdala, and thalamus in individuals with schizophrenia compared to control participants, while diminished asymmetry encompassed ventral striatum and ventral and dorsal thalamus. Our analyses also revealed that higher chlorpromazine dose equivalents and increased positive symptom levels were associated with patterns of contiguous convex shape differences across multiple subcortical structures. Findings from our shape meta-analysis suggest that common neurobiological mechanisms may contribute to gray matter reduction across multiple subcortical regions, thus enhancing our understanding of the nature of network disorganization in schizophrenia.
  •  
41.
  • Horton, Megan K., et al. (author)
  • Using the delayed spatial alternation task to assess environmentally associated changes in working memory in very young children
  • 2020
  • In: Neurotoxicology. - : Elsevier. - 0161-813X .- 1872-9711. ; 77, s. 71-79
  • Journal article (peer-reviewed)abstract
    • Background: Working memory (WM) is critical for problem solving and reasoning. Beginning in infancy, children show WM capacity increasing with age but there are few validated tests of WM in very young children. Because rapid brain development may increase susceptibility to adverse impacts of prenatal neurotoxicant exposure, such as lead, tests of WM in very young children would help to delineate onset of developmental problems and windows of susceptibility. Purpose: Our objective was to assess the feasibility of administering a Delayed Spatial Alternation Task (DSAT) to measure WM among 18- and 24-month old children enrolled in an ongoing longitudinal birth cohort study and compare DSAT performance with age and general cognitive development. We further explored whether prenatal lead exposure impacted DSAT performance. Methods: We assessed 457 mother-child pairs participating in the Programming Research in Obesity, GRowth, Environment and Social Stressors (PROGRESS) Study in Mexico City. The DSAT and Bayley Scales of Infant Development (BSID-III) were administered at 18- and 24-months. Lead was measured in maternal blood collected during pregnancy (MBPb) and in a subsample of children at 24-months (CBPb). We regressed DSAT measures on MBPb and CBPb, child sex, and maternal age, education, socioeconomic status, and household smoking. We compared DSAT performance to BSID-III performance with adjusted residuals. Results: 24-month children perform better on the DSAT than 18-month children; 24-month subjects reached a higher level on the DSAT (3.3 (0.86) vs. 2.4 (0.97), p < 0.01), and had a higher number of correct responses (20.3 vs. 17.2, p < 0.01). In all DSAT parameters, females performed better than males. Maternal education predicted better DSAT performance; household smoking predicted worse DSAT performance. A higher number of correct responses was associated with higher BSID-III Cognitive scales at 18 months (r = 0.20, p < 0.01) and 24 months (r = 0.27, p < 0.01). MBPb and CPBb did not significantly predict DSAT performance. Conclusion: Improved performance on the DSAT with increasing age, the positive correlation with the BSID-III cognitive and language scales and the correlation with common sociodemographic predictors of neurodevelopment demonstrate the validity of the DSAT as a test of infant development.
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42.
  • Horvath, Robert, et al. (author)
  • Selection on Accessible Chromatin Regions in Capsella grandiflora
  • 2021
  • In: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 38:12, s. 5563-5575
  • Journal article (peer-reviewed)abstract
    • Accurate estimates of genome-wide rates and fitness effects of new mutations are essential for an improved understanding of molecular evolutionary processes. Although eukaryotic genomes generally contain a large noncoding fraction, functional noncoding regions and fitness effects of mutations in such regions are still incompletely characterized. A promising approach to characterize functional noncoding regions relies on identifying accessible chromatin regions (ACRs) tightly associated with regulatory DNA. Here, we applied this approach to identify and estimate selection on ACRs in Capsella grandiflora, a crucifer species ideal for population genomic quantification of selection due to its favorable population demography. We describe a population-wide ACR distribution based on ATAC-seq data for leaf samples of 16 individuals from a natural population. We use population genomic methods to estimate fitness effects and proportions of positively selected fixations (alpha) in ACRs and find that intergenic ACRs harbor a considerable fraction of weakly deleterious new mutations, as well as a significantly higher proportion of strongly deleterious mutations than comparable inaccessible intergenic regions. ACRs are enriched for expression quantitative trait loci (eQTL) and depleted of transposable element insertions, as expected if intergenic ACRs are under selection because they harbor regulatory regions. By integrating empirical identification of intergenic ACRs with analyses of eQTL and population genomic analyses of selection, we demonstrate that intergenic regulatory regions are an important source of nearly neutral mutations. These results improve our understanding of selection on noncoding regions and the role of nearly neutral mutations for evolutionary processes in outcrossing Brassicaceae species.
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43.
  • Hoshino, Ayuko, et al. (author)
  • Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers
  • 2020
  • In: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 182:4, s. 1044-
  • Journal article (peer-reviewed)abstract
    • There is an unmet clinical need for improved tissue and liquid biopsy tools for cancer detection. We investigated the proteomic profile of extracellular vesicles and particles (EVPs) in 426 human samples from tissue explants (TEs), plasma, and other bodily fluids. Among traditional exosome markers, CD9, HSPA8, ALIX, and HSP90AB1 represent pan-EVP markers, while ACTB, MSN, and RAP1B are novel pan-EVP markers. To confirm that EVPs are ideal diagnostic tools, we analyzed proteomes of TE- (n =151) and plasma-derived (n =120) EVPs. Comparison of TE EVPs identified proteins (e.g., VCAN, TNC, and THBS2) that distinguish tumors from normal tissues with 90% sensitivity/94% specificity. Machine-learning classification of plasma-derived EVP cargo, including immunoglobulins, revealed 95% sensitivity/90% specificity in detecting cancer Finally, we defined a panel of tumor-type-specific EVP proteins in TEs and plasma, which can classify tumors of unknown primary origin. Thus, EVP proteins can serve as reliable biomarkers for cancer detection and determining cancer type.
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44.
  • Iani, Edoardo, et al. (author)
  • MIDIS : JWST NIRCam and MIRI Unveil the Stellar Population Properties of Lyα Emitters and Lyman-break Galaxies at z ≃ 3–7
  • 2024
  • In: Astrophysical Journal. - 0004-637X .- 1538-4357. ; 963:2
  • Journal article (peer-reviewed)abstract
    • We study the stellar population properties of 182 spectroscopically confirmed (MUSE/VLT) Lyα emitters (LAEs) and 450 photometrically selected Lyman-break galaxies (LBGs) at z = 2.8–6.7 in the Hubble Extreme Deep Field. Leveraging the combined power of Hubble Space Telescope and JWST NIRCam and MIRI observations, we analyze their rest-frame UV-through-near-IR spectral energy distributions, with MIRI playing a crucial role in robustly assessing the LAEs' stellar masses and ages. Our LAEs are low-mass objects (log10(M⋆/M⊙)≃7.5) with little or no dust extinction (E(B − V) ≃ 0.1) and a blue UV continuum slope (β ≃ −2.2). While 75% of our LAEs are young (<100 Myr), the remaining 25% have significantly older stellar populations (≥100 Myr). These old LAEs are statistically more massive, less extinct, and have lower specific star formation rate than young LAEs. Besides, they populate the plane of M⋆ versus star formation rate along the main sequence of star-forming galaxies, while young LAEs populate the starburst region. The comparison between the LAEs' properties and those of a stellar-mass-matched sample of LBGs shows no statistical difference between these objects, except for the LBGs' redder UV continuum slope and marginally larger E(B − V) values. Interestingly, 48% of the LBGs have ages <10 Myr and are classified as starbursts, but lack detectable Lyα emission. This is likely due to H i resonant scattering and/or dust-selective extinction. Overall, we find that JWST observations are crucial in determining the properties of LAEs and shedding light on their comparison with LBGs.
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45.
  • Ingelhag, Karin, et al. (author)
  • The future of sustainability projects: Flights of fancy or a threnody to a lost age?
  • 2020
  • In: Anatomy of a 21st-century sustainability project: The untold stories. - Göteborg : Chalmers University of Technology and Mistra Urban Futures. - 9789198416633 - 9789198416633 ; , s. 236-238
  • Book chapter (peer-reviewed)abstract
    • Just like a living organism, also the project has an anatomy, a life span and a purpose. A project has its given actors, given timeframe and phases, and a given goal. Towards the project’s completion, all these factors must intertwine perfectly, otherwise the project’s success will be challenged. Uncovering how these intricacies are held in place has been the epistemological foundation of this book. However, rather than relying on formal project descriptions, reports and evaluations, we chose a different way, autoethnography. By exploring the implicit knowledge that emerges during the process of running a complex 21st-century sustainability project, we wanted to better understand what makes it tick, halt or change its course. Taking cue from the various project actors’ personal reflections on their own role within the project has helped illuminate a complex transdisciplinary co-creation process from the perspective of the individual. We conclude that if we truly want to attain sustainability transitions, then the organisation, the methods and the modes of thinking utilised in projects must differ from the traditional ones. But reaching a breakpoint for behavioural change must be rooted in interactions where the participating individuals and organisations have a common understanding of the complex challenges that are entailed in running a sustainability project in the 21st century.
  •  
46.
  • Jandrić, Petar, et al. (author)
  • Teaching in the Age of Covid-19
  • 2020
  • In: Postdigital Science and Education. - : Springer Science and Business Media LLC. - 2524-4868 .- 2524-485X. ; 2:3, s. 1069-1230
  • Journal article (other academic/artistic)abstract
    • A collection of 84 author's testimonies and workspace photographs between 18 March and 5 May 2020.
  •  
47.
  • Jandrić, Petar, et al. (author)
  • Teaching in the Age of Covid-19 : The New Normal
  • 2022
  • In: Postdigital Science and Education. - : Springer Science and Business Media LLC. - 2524-485X .- 2524-4868. ; 4:3, s. 877-1015
  • Journal article (peer-reviewed)abstract
    • On 17 March 2020, Postdigital Science and Education launched a call for testimonies about teaching and learning during very frst Covid-19 lockdowns. The resulting article, ‘Teaching in the Age of Covid-19’ (attached), presents 81 written testimonies and 80 workspace photographs submitted by 84 authors from 19 countries. On 17 March 2021, Postdigital Science and Education launched a call for a sequel article of testimonies about teaching and learning during very first Covid-19 lockdowns. The resulting article, ‘Teaching in the Age of Covid-19—1 Year Later’(attached), consists of 74 textual testimonies and 76 workspace photographs submitted by 77 authors from 20 countries.These two articles have been downloaded almost 100,000 times and have been cited more than 100 times. This shows their value as historical documents. Recent analyses, such as ‘Teaching in the Age of Covid-19—A Longitudinal Study ’(attached), also indicate their strong potential for educational research. As the Covid-19 pandemic seems to wind down, pandemic experiences have entered the mainstream. They shape all educational research of today and arguably do not require special treatment. Yet, our unique series of pandemic testimonies provides a unique opportunity to longitudinally trace what happens to the same people over the years—and this opportunity should not be missed.Today, we launch a call for fnal sequel: Teaching in the Age of Covid-19—The New Normal. In this sequel, we would like to hear about ways in which you—contributors to the previous articles—have established your own new normal. We hope that this will be the last iteration in this series of testimony articles. Unless the world faces another strong pandemic outburst, we would like to end the series with this last article.
  •  
48.
  • Jin, Shoko, et al. (author)
  • The wide-field, multiplexed, spectroscopic facility WEAVE : Survey design, overview, and simulated implementation
  • 2024
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 530:3, s. 2688-2730
  • Journal article (peer-reviewed)abstract
    • WEAVE, the new wide-field, massively multiplexed spectroscopic survey facility for the William Herschel Telescope, saw first light in late 2022. WEAVE comprises a new 2-deg field-of-view prime-focus corrector system, a nearly 1000-multiplex fibre positioner, 20 individually deployable 'mini' integral field units (IFUs), and a single large IFU. These fibre systems feed a dual-beam spectrograph covering the wavelength range 366-959nm at R similar to 5000, or two shorter ranges at . After summarizing the design and implementation of WEAVE and its data systems, we present the organization, science drivers, and design of a five- to seven-year programme of eight individual surveys to: (i) study our Galaxy's origins by completing Gaia's phase-space information, providing metallicities to its limiting magnitude for similar to 3 million stars and detailed abundances for similar to 1.5 million brighter field and open-cluster stars; (ii) survey similar to 0.4 million Galactic-plane OBA stars, young stellar objects, and nearby gas to understand the evolution of young stars and their environments; (iii) perform an extensive spectral survey of white dwarfs; (iv) survey similar to 400 neutral-hydrogen-selected galaxies with the IFUs; (v) study properties and kinematics of stellar populations and ionized gas in z < 0.5 cluster galaxies; (vi) survey stellar populations and kinematics in field galaxies at 0.3 less than or similar to z less than or similar to 0.7; (vii) study the cosmic evolution of accretion and star formation using >1 million spectra of LOFAR-selected radio sources; and (viii) trace structures using intergalactic/circumgalactic gas at z > 2. Finally, we describe the WEAVE Operational Rehearsals using the WEAVE Simulator.
  •  
49.
  • Kelsoe, John, et al. (author)
  • Lithium Response in Bipolar Disorder is Associated with Focal Adhesion and PI3K-Akt Networks: A Multi-omics Replication Study.
  • 2023
  • In: Research square.
  • Other publication (other academic/artistic)abstract
    • Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extracellular matrix (ECM), and PI3K-Akt signaling networks were associated with response to lithium. In this study, we replicated the results of our previous study using network propagation methods in a genome-wide association study of an independent sample of 2,039 patients from the International Consortium on Lithium Genetics (ConLiGen) study. We identified functional enrichment in focal adhesion and PI3K-Akt pathways, but we did not find an association with the ECM pathway. Our results suggest that deficits in the neuronal growth cone and PI3K-Akt signaling, but not in ECM proteins, may influence response to lithium in BD.
  •  
50.
  • Kreiner, Julia M., et al. (author)
  • Quantifying the role of genome size and repeat content in adaptive variation and the architecture of flowering time in Amaranthus tuberculatus
  • 2023
  • In: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 19:12
  • Journal article (peer-reviewed)abstract
    • Genome size variation, largely driven by repeat content, is poorly understood within and among populations, limiting our understanding of its significance for adaptation. Here we characterize intraspecific variation in genome size and repeat content across 186 individuals of Amaranthus tuberculatus, a ubiquitous native weed that shows flowering time adaptation to climate across its range and in response to agriculture. Sequence-based genome size estimates vary by up to 20% across individuals, consistent with the considerable variability in the abundance of transposable elements, unknown repeats, and rDNAs across individuals. The additive effect of this variation has important phenotypic consequences—individuals with more repeats, and thus larger genomes, show slower flowering times and growth rates. However, compared to newly-characterized gene copy number and polygenic nucleotide changes underlying variation in flowering time, we show that genome size is a marginal contributor. Differences in flowering time are reflected by genome size variation across sexes and marginally, habitats, while polygenic variation and a gene copy number variant within the ATP synthesis pathway show consistently stronger environmental clines than genome size. Repeat content nonetheless shows non-neutral distributions across the genome, and across latitudinal and environmental gradients, demonstrating the numerous governing processes that in turn influence quantitative genetic variation for phenotypes key to plant adaptation.
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