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1.
  • Abe, H., et al. (author)
  • Gamma-ray observations of MAXI J1820+070 during the 2018 outburst
  • 2022
  • In: Monthly notices of the Royal Astronomical Society. - : Oxford University Press. - 0035-8711 .- 1365-2966. ; 517:4, s. 4736-4751
  • Journal article (peer-reviewed)abstract
    • MAXIJ1820+070 is a low-mass X-ray binary with a black hole (BH) as a compact object. This binary underwent an exceptionally bright X-ray outburst from 2018 March to October, showing evidence of a non-thermal particle population through its radio emission during this whole period. The combined results of 59.5 h of observations of the MAXI J1820+070 outburst with the H.E.S.S., MAGIC and VERITAS experiments at energies above 200 GeV are presented, together with Fermi-LAT data between 0.1 and 500 GeV, and multiwavelength observations from radio to X-rays. Gamma-ray emission is not detected from MAXI J1820+070, but the obtained upper limits and the multiwavelength data allow us to put meaningful constraints on the source properties under reasonable assumptions regarding the non-thermal particle population and the jet synchrotron spectrum. In particular, it is possible to show that, if a high-energy (HE) gamma-ray emitting region is present during the hard state of the source, its predicted flux should be at most a factor of 20 below the obtained Fermi-LAT upper limits, and closer to them for magnetic fields significantly below equipartition. During the state transitions, under the plausible assumption that electrons are accelerated up to similar to 500 GeV, the multiwavelength data and the gamma-ray upper limits lead consistently to the conclusion that a potential HE and very-HE gamma-ray emitting region should be located at a distance from the BH ranging between 10(11) and 10(13) cm. Similar outbursts from low-mass X-ray binaries might be detectable in the near future with upcoming instruments such as CTA.
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  • De Angelis, A., et al. (author)
  • Science with e-ASTROGAM A space mission for MeV-GeV gamma-ray astrophysics
  • 2018
  • In: Journal of High Energy Astrophysics. - : Elsevier. - 2214-4048 .- 2214-4056. ; 19, s. 1-106
  • Journal article (peer-reviewed)abstract
    • e-ASTROGAM ('enhanced ASTROGAM') is a breakthrough Observatory space mission, with a detector composed by a Silicon tracker, a calorimeter, and an anticoincidence system, dedicated to the study of the non-thermal Universe in the photon energy range from 0.3 MeV to 3 GeV - the lower energy limit can be pushed to energies as low as 150 keV for the tracker, and to 30 keV for calorimetric detection. The mission is based on an advanced space-proven detector technology, with unprecedented sensitivity, angular and energy resolution, combined with polarimetric capability. Thanks to its performance in the MeV-GeV domain, substantially improving its predecessors, e-ASTROGAM will open a new window on the non-thermal Universe, making pioneering observations of the most powerful Galactic and extragalactic sources, elucidating the nature of their relativistic outflows and their effects on the surroundings. With a line sensitivity in the MeV energy range one to two orders of magnitude better than previous generation instruments, e-ASTROGAM will determine the origin of key isotopes fundamental for the understanding of supernova explosion and the chemical evolution of our Galaxy. The mission will provide unique data of significant interest to a broad astronomical community, complementary to powerful observatories such as LIGO-Virgo-GEO600-KAGRA, SKA, ALMA, E-ELT, TMT, LSST, JWST, Athena, CTA, IceCube, KM3NeT, and LISA.
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  • Correa, D. F., et al. (author)
  • Geographic patterns of tree dispersal modes in Amazonia and their ecological correlates
  • 2023
  • In: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 32:1, s. 49-69
  • Journal article (peer-reviewed)abstract
    • Aim To investigate the geographic patterns and ecological correlates in the geographic distribution of the most common tree dispersal modes in Amazonia (endozoochory, synzoochory, anemochory and hydrochory). We examined if the proportional abundance of these dispersal modes could be explained by the availability of dispersal agents (disperser-availability hypothesis) and/or the availability of resources for constructing zoochorous fruits (resource-availability hypothesis). Time period Tree-inventory plots established between 1934 and 2019. Major taxa studied Trees with a diameter at breast height (DBH) >= 9.55 cm. Location Amazonia, here defined as the lowland rain forests of the Amazon River basin and the Guiana Shield. Methods We assigned dispersal modes to a total of 5433 species and morphospecies within 1877 tree-inventory plots across terra-firme, seasonally flooded, and permanently flooded forests. We investigated geographic patterns in the proportional abundance of dispersal modes. We performed an abundance-weighted mean pairwise distance (MPD) test and fit generalized linear models (GLMs) to explain the geographic distribution of dispersal modes. Results Anemochory was significantly, positively associated with mean annual wind speed, and hydrochory was significantly higher in flooded forests. Dispersal modes did not consistently show significant associations with the availability of resources for constructing zoochorous fruits. A lower dissimilarity in dispersal modes, resulting from a higher dominance of endozoochory, occurred in terra-firme forests (excluding podzols) compared to flooded forests. Main conclusions The disperser-availability hypothesis was well supported for abiotic dispersal modes (anemochory and hydrochory). The availability of resources for constructing zoochorous fruits seems an unlikely explanation for the distribution of dispersal modes in Amazonia. The association between frugivores and the proportional abundance of zoochory requires further research, as tree recruitment not only depends on dispersal vectors but also on conditions that favour or limit seedling recruitment across forest types.
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  • Pfaller, M.A., et al. (author)
  • Twelve years of fluconazole in clinical practice : Global-trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida
  • 2004
  • In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
  • Journal article (peer-reviewed)abstract
    • We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C. albicans, 984 C. glabrata, 796 C. parapsilosis, 585 C. tropicalis, 153 C. krusei, 67 C. lusitaniae, 48 C. guilliermondii, 10 C. famata, 10 C. kefyr, six C. pelliculosa, five C. rugosa, four C. lipolytica, three C. dubliniensis, three C. inconspicua, two C. sake and one isolate each of C. lambica, C. norvegensis and C. zeylanoides. Minimum inhibitory concentration determinations were made using the National Committee for Clinical Laboratory Standards reference broth microdilution method. Variation in the rank order and frequency of the different species of Candida was observed over time and by geographic area. The proportion of BSI due to C. albicans and C. glabrata increased and C. parapsilosis decreased over time in Canada, the USA and Europe. C. glabrata was an infrequent cause of BSI in Latin America and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observed among isolates of C. albicans, C. tropicalis and C. parapsilosis. These species accounted for 78% of all BSI and remained highly susceptible (91-100% susceptible) to fluconazole from 1992 to 2001 irrespective of geographic origin. The prevalence of fluconazole resistance among C. glabrata isolates was variable both over time and among the various countries and regions. Resistance to fluconazole among C. glabrata isolates was greatest in the USA and varied by US census region (range 0-23%). These observations are generally encouraging relative to the sustained usefulness of fluconazole as a systemically active antifungal agent for the treatment of candida BSI. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.
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  • 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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  • Poyatos, R., et al. (author)
  • Global transpiration data from sap flow measurements: the SAPFLUXNET database
  • 2021
  • In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2607-2649
  • Journal article (peer-reviewed)abstract
    • Plant transpiration links physiological responses of vegetation to water supply and demand with hydrological, energy, and carbon budgets at the land-atmosphere interface. However, despite being the main land evaporative flux at the global scale, transpiration and its response to environmental drivers are currently not well constrained by observations. Here we introduce the first global compilation of whole-plant transpiration data from sap flow measurements (SAPFLUXNET, https://sapfluxnet.creaf.cat/, last access: 8 June 2021). We harmonized and quality-controlled individual datasets supplied by contributors worldwide in a semi-automatic data workflow implemented in the R programming language. Datasets include sub-daily time series of sap flow and hydrometeorological drivers for one or more growing seasons, as well as metadata on the stand characteristics, plant attributes, and technical details of the measurements. SAPFLUXNET contains 202 globally distributed datasets with sap flow time series for 2714 plants, mostly trees, of 174 species. SAPFLUXNET has a broad bioclimatic coverage, with woodland/shrubland and temperate forest biomes especially well represented (80 % of the datasets). The measurements cover a wide variety of stand structural characteristics and plant sizes. The datasets encompass the period between 1995 and 2018, with 50 % of the datasets being at least 3 years long. Accompanying radiation and vapour pressure deficit data are available for most of the datasets, while on-site soil water content is available for 56 % of the datasets. Many datasets contain data for species that make up 90 % or more of the total stand basal area, allowing the estimation of stand transpiration in diverse ecological settings. SAPFLUXNET adds to existing plant trait datasets, ecosystem flux networks, and remote sensing products to help increase our understanding of plant water use, plant responses to drought, and ecohydrological processes. SAPFLUXNET version 0.1.5 is freely available from the Zenodo repository (https://doi.org/10.5281/zenodo.3971689; Poyatos et al., 2020a). The "sapfluxnetr" R package - designed to access, visualize, and process SAPFLUXNET data - is available from CRAN.
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  • Bethlehem, RAI, et al. (author)
  • Brain charts for the human lifespan
  • 2022
  • In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 604:79057906, s. 525-
  • Journal article (peer-reviewed)abstract
    • Over the past few decades, neuroimaging has become a ubiquitous tool in basic research and clinical studies of the human brain. However, no reference standards currently exist to quantify individual differences in neuroimaging metrics over time, in contrast to growth charts for anthropometric traits such as height and weight1. Here we assemble an interactive open resource to benchmark brain morphology derived from any current or future sample of MRI data (http://www.brainchart.io/). With the goal of basing these reference charts on the largest and most inclusive dataset available, acknowledging limitations due to known biases of MRI studies relative to the diversity of the global population, we aggregated 123,984 MRI scans, across more than 100 primary studies, from 101,457 human participants between 115 days post-conception to 100 years of age. MRI metrics were quantified by centile scores, relative to non-linear trajectories2 of brain structural changes, and rates of change, over the lifespan. Brain charts identified previously unreported neurodevelopmental milestones3, showed high stability of individuals across longitudinal assessments, and demonstrated robustness to technical and methodological differences between primary studies. Centile scores showed increased heritability compared with non-centiled MRI phenotypes, and provided a standardized measure of atypical brain structure that revealed patterns of neuroanatomical variation across neurological and psychiatric disorders. In summary, brain charts are an essential step towards robust quantification of individual variation benchmarked to normative trajectories in multiple, commonly used neuroimaging phenotypes.
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  • Morales, J. C., et al. (author)
  • A giant exoplanet orbiting a very-low-mass star challenges planet formation models
  • 2019
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 365:6460, s. 1441-1445
  • Journal article (peer-reviewed)abstract
    • Surveys have shown that super-Earth and Neptune-mass exoplanets are more frequent than gas giants around low-mass stars, as predicted by the core accretion theory of planet formation. We report the discovery of a giant planet around the very-low-mass star GJ 3512, as determined by optical and near-infrared radial-velocity observations. The planet has a minimum mass of 0.46 Jupiter masses, very high for such a small host star, and an eccentric 204-day orbit. Dynamical models show that the high eccentricity is most likely due to planet-planet interactions. We use simulations to demonstrate that the GJ 3512 planetary system challenges generally accepted formation theories, and that it puts constraints on the planet accretion and migration rates. Disk instabilities may be more efficient in forming planets than previously thought.
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  • Horwich, A, et al. (author)
  • EAU–ESMO consensus statements on the management of advanced and variant bladder cancer - an international collaborative multi-stakeholder effort : under the auspices of the EAU and ESMO Guidelines Committees
  • 2019
  • In: Annals of Oncology. - : Oxford University Press. - 0923-7534 .- 1569-8041. ; 30:11, s. 1697-1727
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial.OBJECTIVE: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management.DESIGN: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference.SETTING: Online Delphi survey and consensus conference.PARTICIPANTS: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), 7-9 (agree). A priori (level 1) consensus was defined as ≥70% agreement and ≤15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus).RESULTS AND LIMITATIONS: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease.CONCLUSIONS: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach.
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  • Morales, E, et al. (author)
  • Combined impact of healthy lifestyle factors on risk of asthma, rhinoconjunctivitis and eczema in school children: ISAAC phase III
  • 2019
  • In: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 74:6, s. 531-538
  • Journal article (peer-reviewed)abstract
    • Asthma is not the key focus of prevention strategies. A Healthy Lifestyle Index (HLI) was developed to examine the combined effect of modifiable lifestyle factors on asthma, rhinoconjunctivitis and eczema using data from the International Study of Asthma and Allergies in Childhood (ISAAC) phase III.MethodsInformation on symptoms of asthma, rhinoconjunctivitis, eczema and several lifestyle factors was obtained from children aged 6–7 years through written questionnaires. The HLI combined five lifestyle factors: no parental smoking, child’s adherence to Mediterranean diet, child’s healthy body mass index, high physical activity and non-sedentary behaviour. The association between the HLI and risk of asthma, rhinoconjunctivitis and eczema was evaluated using multilevel mixed-effects logistic regression models.FindingsData of 70 795 children from 37 centres in 19 countries were analysed. Each additional healthy lifestyle factor was associated with a reduced risk of current wheeze (OR 0.87, 95% CI 0.84 to 0.89), asthma ever (OR 0.89, 95% CI 0.87 to 0.92), current symptoms of rhinoconjunctivitis (OR 0.95, 95% CI 0.92 to 0.97) and current symptoms of eczema (OR 0.92, 95% CI 0.92 to 0.98). Theoretically, if associations were causal, a combination of four or five healthy lifestyle factors would result into a reduction up to 16% of asthma cases (ranging from 2.7% to 26.3 % according to region of the world).ConclusionsThese findings should be interpreted with caution given the limitations to infer causality from cross-sectional observational data. Efficacy of interventions to improve multiple modifiable lifestyle factors to reduce the burden asthma and allergy in childhood should be assessed.
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  • Householder, John Ethan, et al. (author)
  • One sixth of Amazonian tree diversity is dependent on river floodplains
  • 2024
  • In: NATURE ECOLOGY & EVOLUTION. - 2397-334X.
  • Journal article (peer-reviewed)abstract
    • Amazonia's floodplain system is the largest and most biodiverse on Earth. Although forests are crucial to the ecological integrity of floodplains, our understanding of their species composition and how this may differ from surrounding forest types is still far too limited, particularly as changing inundation regimes begin to reshape floodplain tree communities and the critical ecosystem functions they underpin. Here we address this gap by taking a spatially explicit look at Amazonia-wide patterns of tree-species turnover and ecological specialization of the region's floodplain forests. We show that the majority of Amazonian tree species can inhabit floodplains, and about a sixth of Amazonian tree diversity is ecologically specialized on floodplains. The degree of specialization in floodplain communities is driven by regional flood patterns, with the most compositionally differentiated floodplain forests located centrally within the fluvial network and contingent on the most extraordinary flood magnitudes regionally. Our results provide a spatially explicit view of ecological specialization of floodplain forest communities and expose the need for whole-basin hydrological integrity to protect the Amazon's tree diversity and its function.
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  • Kayhanian, Hamzeh, et al. (author)
  • Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer
  • 2024
  • In: Nature Genetics. - 1061-4036. ; 56:7, s. 1420 -1433
  • Journal article (peer-reviewed)abstract
    • Mismatch repair (MMR)-deficient cancer evolves through the stepwise erosion of coding homopolymers in target genes. Curiously, the MMR genes MutS homolog 6 (MSH6) and MutS homolog 3 (MSH3) also contain coding homopolymers, and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient cancer evolution is unknown. Here we show that microsatellite instability modulates DNA repair by toggling hypermutable mononucleotide homopolymer runs in MSH6 and MSH3 through stochastic frameshift switching. Spontaneous mutation and reversion modulate subclonal mutation rate, mutation bias and HLA and neoantigen diversity. Patient-derived organoids corroborate these observations and show that MMR homopolymer sequences drift back into reading frame in the absence of immune selection, suggesting a fitness cost of elevated mutation rates. Combined experimental and simulation studies demonstrate that subclonal immune selection favors incremental MMR mutations. Overall, our data demonstrate that MMR-deficient colorectal cancers fuel intratumor heterogeneity by adapting subclonal mutation rate and diversity to immune selection.
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  • Laurie, Steven, et al. (author)
  • The RD-Connect Genome-Phenome Analysis Platform : Accelerating diagnosis, research, and gene discovery for rare diseases
  • 2022
  • In: Human Mutation. - : John Wiley & Sons. - 1059-7794 .- 1098-1004. ; 43:6, s. 717-733
  • Journal article (peer-reviewed)abstract
    • Rare disease patients are more likely to receive a rapid molecular diagnosis nowadays thanks to the wide adoption of next-generation sequencing. However, many cases remain undiagnosed even after exome or genome analysis, because the methods used missed the molecular cause in a known gene, or a novel causative gene could not be identified and/or confirmed. To address these challenges, the RD-Connect Genome-Phenome Analysis Platform (GPAP) facilitates the collation, discovery, sharing, and analysis of standardized genome-phenome data within a collaborative environment. Authorized clinicians and researchers submit pseudonymised phenotypic profiles encoded using the Human Phenotype Ontology, and raw genomic data which is processed through a standardized pipeline. After an optional embargo period, the data are shared with other platform users, with the objective that similar cases in the system and queries from peers may help diagnose the case. Additionally, the platform enables bidirectional discovery of similar cases in other databases from the Matchmaker Exchange network. To facilitate genome-phenome analysis and interpretation by clinical researchers, the RD-Connect GPAP provides a powerful user-friendly interface and leverages tens of information sources. As a result, the resource has already helped diagnose hundreds of rare disease patients and discover new disease causing genes.
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