| 1. |
- Aad, G, et al.
(author)
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- 2015
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swepub:Mat__t
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| 2. |
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| 3. |
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| 4. |
- Ruilope, LM, et al.
(author)
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Design and Baseline Characteristics of the Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease Trial
- 2019
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In: American journal of nephrology. - : S. Karger AG. - 1421-9670 .- 0250-8095. ; 50:5, s. 345-356
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. <b><i>Patients and</i></b> <b><i>Methods:</i></b> The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m<sup>2</sup> and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. <b><i>Conclusions:</i></b> FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.
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| 5. |
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| 6. |
- Mishra, A, et al.
(author)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Journal article (peer-reviewed)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 7. |
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| 8. |
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| 9. |
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| 10. |
- Barausse, Enrico, et al.
(author)
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Prospects for fundamental physics with LISA
- 2020
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In: General Relativity and Gravitation. - : SPRINGER/PLENUM PUBLISHERS. - 0001-7701 .- 1572-9532. ; 52:8
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Journal article (other academic/artistic)abstract
- In this paper, which is of programmatic rather than quantitative nature, we aim to further delineate and sharpen the future potential of the LISA mission in the area of fundamental physics. Given the very broad range of topics that might be relevant to LISA,we present here a sample of what we view as particularly promising fundamental physics directions. We organize these directions through a "science-first" approach that allows us to classify how LISA data can inform theoretical physics in a variety of areas. For each of these theoretical physics classes, we identify the sources that are currently expected to provide the principal contribution to our knowledge, and the areas that need further development. The classification presented here should not be thought of as cast in stone, but rather as a fluid framework that is amenable to change with the flow of new insights in theoretical physics.
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| 11. |
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| 12. |
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| 13. |
- Poyatos, R., et al.
(author)
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Global transpiration data from sap flow measurements: the SAPFLUXNET database
- 2021
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In: Earth System Science Data. - : Copernicus GmbH. - 1866-3508 .- 1866-3516. ; 13:6, s. 2607-2649
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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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| 14. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 15. |
- Arheimer, Berit, et al.
(author)
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The IAHS Science for Solutions decade, with Hydrology Engaging Local People IN a Global world (HELPING)
- 2024
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In: Hydrological Sciences Journal. - 0262-6667 .- 2150-3435.
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Journal article (peer-reviewed)abstract
- The new scientific decade (2023-2032) of the International Association of Hydrological Sciences (IAHS) aims at searching for sustainable solutions to undesired water conditions - may it be too little, too much or too polluted. Many of the current issues originate from global change, while solutions to problems must embrace local understanding and context. The decade will explore the current water crises by searching for actionable knowledge within three themes: global and local interactions, sustainable solutions and innovative cross-cutting methods. We capitalise on previous IAHS Scientific Decades shaping a trilogy; from Hydrological Predictions (PUB) to Change and Interdisciplinarity (Panta Rhei) to Solutions (HELPING). The vision is to solve fundamental water-related environmental and societal problems by engaging with other disciplines and local stakeholders. The decade endorses mutual learning and co-creation to progress towards UN sustainable development goals. Hence, HELPING is a vehicle for putting science in action, driven by scientists working on local hydrology in coordination with local, regional, and global processes.
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| 16. |
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| 17. |
- Bergemann, M., et al.
(author)
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The Gaia-ESO Survey : radial metallicity gradients and age-metallicity relation of stars in the Milky Way disk
- 2014
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 565, s. A89-
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Journal article (peer-reviewed)abstract
- We study the relationship between age, metallicity, and alpha-enhancement of FGK stars in the Galactic disk. The results are based upon the analysis of high-resolution UVES spectra from the Gaia-ESO large stellar survey. We explore the limitations of the observed dataset, i.e. the accuracy of stellar parameters and the selection effects that are caused by the photometric target preselection. We find that the colour and magnitude cuts in the survey suppress old metal-rich stars and young metal-poor stars. This suppression may be as high as 97% in some regions of the age-metallicity relationship. The dataset consists of 144 stars with a wide range of ages from 0.5 Gyr to 13.5 Gyr, Galactocentric distances from 6 kpc to 9.5 kpc, and vertical distances from the plane 0 < vertical bar Z vertical bar < 1.5 kpc. On this basis, we find that i) the observed age-metallicity relation is nearly flat in the range of ages between 0 Gyr and 8 Gyr; ii) at ages older than 9 Gyr, we see a decrease in [Fe/H] and a clear absence of metal-rich stars; this cannot be explained by the survey selection functions; iii) there is a significant scatter of [Fe/H] at any age; and iv) [Mg/Fe] increases with age, but the dispersion of [Mg/Fe] at ages > 9 Gyr is not as small as advocated by some other studies. In agreement with earlier work, we find that radial abundance gradients change as a function of vertical distance from the plane. The [Mg/Fe] gradient steepens and becomes negative. In addition, we show that the inner disk is not only more alpha-rich compared to the outer disk, but also older, as traced independently by the ages and Mg abundances of stars.
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| 18. |
- Feigin, Valery L., et al.
(author)
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Global, regional, and national burden of neurological disorders, 1990–2016 : a systematic analysis for the Global Burden of Disease Study 2016
- 2019
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In: Lancet Neurology. - : Elsevier. - 1474-4422 .- 1474-4465. ; 18:5, s. 459-480
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Journal article (peer-reviewed)abstract
- Background: Neurological disorders are increasingly recognised as major causes of death and disability worldwide. The aim of this analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2016 is to provide the most comprehensive and up-to-date estimates of the global, regional, and national burden from neurological disorders.Methods: We estimated prevalence, incidence, deaths, and disability-adjusted life-years (DALYs; the sum of years of life lost [YLLs] and years lived with disability [YLDs]) by age and sex for 15 neurological disorder categories (tetanus, meningitis, encephalitis, stroke, brain and other CNS cancers, traumatic brain injury, spinal cord injury, Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis, motor neuron diseases, idiopathic epilepsy, migraine, tension-type headache, and a residual category for other less common neurological disorders) in 195 countries from 1990 to 2016. DisMod-MR 2.1, a Bayesian meta-regression tool, was the main method of estimation of prevalence and incidence, and the Cause of Death Ensemble model (CODEm) was used for mortality estimation. We quantified the contribution of 84 risks and combinations of risk to the disease estimates for the 15 neurological disorder categories using the GBD comparative risk assessment approach.Findings: Globally, in 2016, neurological disorders were the leading cause of DALYs (276 million [95% UI 247–308]) and second leading cause of deaths (9·0 million [8·8–9·4]). The absolute number of deaths and DALYs from all neurological disorders combined increased (deaths by 39% [34–44] and DALYs by 15% [9–21]) whereas their age-standardised rates decreased (deaths by 28% [26–30] and DALYs by 27% [24–31]) between 1990 and 2016. The only neurological disorders that had a decrease in rates and absolute numbers of deaths and DALYs were tetanus, meningitis, and encephalitis. The four largest contributors of neurological DALYs were stroke (42·2% [38·6–46·1]), migraine (16·3% [11·7–20·8]), Alzheimer's and other dementias (10·4% [9·0–12·1]), and meningitis (7·9% [6·6–10·4]). For the combined neurological disorders, age-standardised DALY rates were significantly higher in males than in females (male-to-female ratio 1·12 [1·05–1·20]), but migraine, multiple sclerosis, and tension-type headache were more common and caused more burden in females, with male-to-female ratios of less than 0·7. The 84 risks quantified in GBD explain less than 10% of neurological disorder DALY burdens, except stroke, for which 88·8% (86·5–90·9) of DALYs are attributable to risk factors, and to a lesser extent Alzheimer's disease and other dementias (22·3% [11·8–35·1] of DALYs are risk attributable) and idiopathic epilepsy (14·1% [10·8–17·5] of DALYs are risk attributable).Interpretation: Globally, the burden of neurological disorders, as measured by the absolute number of DALYs, continues to increase. As populations are growing and ageing, and the prevalence of major disabling neurological disorders steeply increases with age, governments will face increasing demand for treatment, rehabilitation, and support services for neurological disorders. The scarcity of established modifiable risks for most of the neurological burden demonstrates that new knowledge is required to develop effective prevention and treatment strategies.Funding: Bill & Melinda Gates Foundation.
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| 19. |
- Garcia-Garcia, A, et al.
(author)
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Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia
- 2023
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In: The Journal of experimental medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 220:5
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Journal article (peer-reviewed)abstract
- X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia.
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| 20. |
- Hudson, Lawrence N., et al.
(author)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Journal article (peer-reviewed)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 21. |
- Lind, Karin, et al.
(author)
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The Gaia-ESO Survey : A globular cluster escapee in the Galactic halo
- 2015
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 575
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Journal article (peer-reviewed)abstract
- A small fraction of the halo field is made up of stars that share the light element (Z <= 13) anomalies characteristic of second generation globular cluster (GC) stars. The ejected stars shed light on the formation of the Galactic halo by tracing the dynamical history of the clusters, which are believed to have once been more massive. Some of these ejected stars are expected to show strong Al enhancement at the expense of shortage of Mg, but until now no such star has been found. We search for outliers in the Mg and Al abundances of the few hundreds of halo field stars observed in the first eighteen months of the Gaia-ESO public spectroscopic survey. One halo star at the base of the red giant branch, here referred to as 22593757-4648029 is found to have [Mg/Fe] = -0.36 +/- 0.04 and [Al/Fe] = 0.99 +/- 0.08, which is compatible with the most extreme ratios detected in GCs so far. We compare the orbit of 22593757-4648029 to GCs of similar metallicity and find it unlikely that this star has been tidally stripped with low ejection velocity from any of the clusters. However, both chemical and kinematic arguments render it plausible that the star has been ejected at high velocity from the anomalous GC omega Centauri within the last few billion years. We cannot rule out other progenitor GCs, because some may have disrupted fully, and the abundance and orbital data are inadequate for many of those that are still intact.
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| 22. |
- Arun, K. G., et al.
(author)
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New horizons for fundamental physics with LISA
- 2022
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In: Living Reviews in Relativity. - : Springer Science and Business Media LLC. - 1433-8351 .- 2367-3613. ; 25:1
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Research review (peer-reviewed)abstract
- The Laser Interferometer Space Antenna (LISA) has the potential to reveal wonders about the fundamental theory of nature at play in the extreme gravity regime, where the gravitational interaction is both strong and dynamical. In this white paper, the Fundamental Physics Working Group of the LISA Consortium summarizes the current topics in fundamental physics where LISA observations of gravitational waves can be expected to provide key input. We provide the briefest of reviews to then delineate avenues for future research directions and to discuss connections between this working group, other working groups and the consortium work package teams. These connections must be developed for LISA to live up to its science potential in these areas.
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| 23. |
- Jordanova, V. K., et al.
(author)
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Specification of the near-Earth space environment with SHIELDS
- 2018
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In: Journal of Atmospheric and Solar-Terrestrial Physics. - : PERGAMON-ELSEVIER SCIENCE LTD. - 1364-6826 .- 1879-1824. ; 177, s. 148-159
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Journal article (peer-reviewed)abstract
- Predicting variations in the near-Earth space environment that can lead to spacecraft damage and failure is one example of "space weather" and a big space physics challenge. A project recently funded through the Los Alamos National Laboratory (LANL) Directed Research and Development (LDRD) program aims at developing a new capability to understand, model, and predict Space Hazards Induced near Earth by Large Dynamic Storms, the SHIELDS framework. The project goals are to understand the dynamics of the surface charging environment (SCE), the hot (keV) electrons representing the source and seed populations for the radiation belts, on both macro and micro-scale. Important physics questions related to particle injection and acceleration associated with magnetospheric storms and substorms, as well as plasma waves, are investigated. These challenging problems are addressed using a team of world-class experts in the fields of space science and computational plasma physics, and state-of-the-art models and computational facilities. A full two-way coupling of physics-based models across multiple scales, including a global MHD (BATS-R-US) embedding a particle-in-cell (iPIC3D) and an inner magnetosphere (RAM-SCB) codes, is achieved. New data assimilation techniques employing in situ satellite data are developed; these provide an order of magnitude improvement in the accuracy in the simulation of the SCE. SHIELDS also includes a post-processing tool designed to calculate the surface charging for specific spacecraft geometry using the Curvilinear Particle-In-Cell (CPIC) code that can be used for reanalysis of satellite failures or for satellite design.
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| 24. |
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| 25. |
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| 26. |
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| 27. |
- Thompson, PM, et al.
(author)
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ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries
- 2020
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 10:1, s. 100-
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Journal article (peer-reviewed)abstract
- This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of “big data” (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA’s activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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| 28. |
- Arias, M. C., et al.
(author)
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Permanent Genetic Resources added to Molecular Ecology Resources Database 1 February 2013-31 March 2013
- 2013
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In: Molecular Ecology Resources. - : Wiley. - 1755-098X .- 1755-0998. ; 13:4, s. 760-762
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Journal article (peer-reviewed)abstract
- This article documents the addition of 142 microsatellite marker loci to the Molecular Ecology Resources database. Loci were developed for the following species: Agriophyllum squarrosum, Amazilia cyanocephala, Batillaria attramentaria, Fungal strain CTeY1 (Ascomycota), Gadopsis marmoratus, Juniperus phoenicea subsp. turbinata, Liriomyza sativae, Lupinus polyphyllus, Metschnikowia reukaufii, Puccinia striiformis and Xylocopa grisescens. These loci were cross-tested on the following species: Amazilia beryllina, Amazilia candida, Amazilia rutila, Amazilia tzacatl, Amazilia violiceps, Amazilia yucatanensis, Campylopterus curvipennis, Cynanthus sordidus, Hylocharis leucotis, Juniperus brevifolia, Juniperus cedrus, Juniperus osteosperma, Juniperus oxycedrus, Juniperus thurifera, Liriomyza bryoniae, Liriomyza chinensis, Liriomyza huidobrensis and Liriomyza trifolii.
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| 29. |
- Brito, H. O., et al.
(author)
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Female Sex Hormones Influence the Febrile Response Induced by Lipopolysaccharide, Cytokines and Prostaglandins but not by Interleukin-1 beta in Rats
- 2016
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In: Journal of neuroendocrinology (Print). - : Wiley-Blackwell. - 0953-8194 .- 1365-2826. ; 28:10
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Journal article (peer-reviewed)abstract
- There are differences in the immune response, and particularly fever, between males and females. In the present study, we investigated how the febrile responses induced by lipopolysaccharide (LPS) and different endogenous pyrogens were affected by female gonadal hormones. The febrile response to i.p. injection of LPS (50g/kg) was 40% lower in female rats compared to male or ovariectomised (OVX) female rats. Accordingly, oestrogen replacement in OVX animals reduced LPS-induced fever. Treatment with the prostaglandin synthesis inhibitor indomethacin (2mg/kg, i.p. 30min before) reduced the febrile response induced by LPS in both OVX (88%) and sham-operated (71%) rats. In line with the enhanced fever in OVX rats, there was increased expression of cyclooxygenase-2 (COX-2) in the hypothalamus and elevated levels of prostaglandin E-2 (PGE(2)). In addition, OVX rats were hyper-responsive to PGE(2) injected i.c.v. By contrast to the enhanced fever in response to LPS and PGE(2), the febrile response induced by i.c.v. injection of interleukin (IL)-1 was unaffected by ovariectomy, whereas the responses induced by tumour necrosis factor (TNF)- and macrophage inflammatory protein (MIP)-1 were completely abrogated. These results suggest that the mediators involved in the febrile response in females are similar to males, although the reduction of female hormones may decrease the responsiveness of some mediators such as TNF- and MIP-1. Compensatory mechanisms may be activated in females after ovariectomy such as an augmented synthesis of COX-2 and PGE(2).
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| 30. |
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| 31. |
- Retamozo, S., et al.
(author)
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Influence of the age at diagnosis in the disease expression of primary Sjogren's syndrome : Analysis of 12,753 patients from the Sjogren Big Data Consortium
- 2021
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In: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 39:6, s. S166-S174
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Journal article (peer-reviewed)abstract
- Objective. To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjogren's syndrome (pSS).Methods. By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression.Results. There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R-2 0.87) and the frequency of abnormal oral tests (adjusted R-2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase).Conclusion. The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.
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| 32. |
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| 33. |
- Soubiran, C., et al.
(author)
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Gaia FGK benchmark stars : Fundamental Teff and log g of the third version
- 2024
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 682
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Journal article (peer-reviewed)abstract
- Context. Large spectroscopic surveys devoted to the study of the Milky Way, including Gaia, use automated pipelines to determine the atmospheric parameters of millions of stars. The Gaia FGK benchmark stars are reference stars with T-eff and log g derived through fundamental relations, independently of spectroscopy, to be used as anchors for the parameter scale. The first and second versions of the sample have been extensively used for that purpose, and more generally to help constrain stellar models. Aims. We provide the third version of the Gaia FGK benchmark stars, an extended set intended to improve the calibration of spectroscopic surveys, and their interconnection. Methods. We have compiled about 200 candidates that have precise measurements of angular diameters and parallaxes. We determined their bolometric fluxes by fitting their spectral energy distribution. Masses were determined using two sets of stellar evolution models. In a companion paper, we describe the determination of metallicities and detailed abundances. Results. We provide a new set of 192 Gaia FGK benchmark stars with their fundamental T-eff and log g, and with uncertainties lower than 2% for most stars. Compared to the previous versions, the homogeneity and accuracy of the fundamental parameters are significantly improved thanks to the high quality of the Gaia photometric and astrometric data.
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| 34. |
- Sprovieri, F., et al.
(author)
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Atmospheric mercury concentrations observed at ground-based monitoring sites globally distributed in the framework of the GMOS network
- 2016
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In: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 16:18, s. 11915-11935
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Journal article (peer-reviewed)abstract
- Long-term monitoring of data of ambient mercury (Hg) on a global scale to assess its emission, transport, atmospheric chemistry, and deposition processes is vital to understanding the impact of Hg pollution on the environment. The Global Mercury Observation System (GMOS) project was funded by the European Commission (http://www.gmos.eu) and started in November 2010 with the overall goal to develop a coordinated global observing system to monitor Hg on a global scale, including a large network of ground-based monitoring stations, ad hoc periodic oceanographic cruises and measurement flights in the lower and upper troposphere as well as in the lower stratosphere. To date, more than 40 ground-based monitoring sites constitute the global network covering many regions where little to no observational data were available before GMOS. This work presents atmospheric Hg concentrations recorded worldwide in the framework of the GMOS project (2010-2015), analyzing Hg measurement results in terms of temporal trends, seasonality and comparability within the network. Major findings highlighted in this paper include a clear gradient of Hg concentrations between the Northern and Southern hemispheres, confirming that the gradient observed is mostly driven by local and regional sources, which can be anthropogenic, natural or a combination of both.
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| 37. |
- Bohn, T., et al.
(author)
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Mind the gap - deficits in our knowledge of aspects impacting bioavailability of phytochemicals and their metabolites - a position paper focusing on carotenoids and polyphenols
- 2015
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In: Molecular Nutrition and Food Research. - : Wiley. - 1613-4133 .- 1613-4125. ; 59:7, s. 1307-13231-17-1323
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Research review (peer-reviewed)abstract
- Various secondary plant metabolites or phytochemicals, including polyphenols and carotenoids, have been associated with a variety of health benefits, such as reduced incidence of type 2 diabetes, cardiovascular diseases, and several types of cancer, most likely due to their involvement in ameliorating inflammatory and oxidative stress. However, discrepancies exist between their putative effects when comparing observational and intervention studies, especially when using pure compounds. These discrepancies may in part be explained by differences in intake levels and their bioavailability. Prior to exerting their bioactivity, these compounds must be made bioavailable, and considerable differences may arise due to their their matrix release, changes during digestion, uptake, metabolism, and biodistribution, even before considering dose and host related factors. Though many insights have been gained on factors affecting secondary plant metabolite bioavailability, many gaps still exist in our knowledge. In this position paper, we highlight several major gaps in our understanding of phytochemical bioavailability, including effects of food processing, changes during digestion, involvement of cellular transporters in influx/efflux through the gastrointestinal epithelium, changes during colonic fermentation, and their phase I and phase II metabolism following absorption.
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| 39. |
- Brito, Camila C.B., et al.
(author)
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Molecular Cloning and Biochemical Characterization of Iron Superoxide Dismutase from Leishmania braziliensis
- 2018
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In: Molecular Biotechnology. - : Springer Science and Business Media LLC. - 1073-6085 .- 1559-0305. ; 60:8, s. 595-600
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Journal article (peer-reviewed)abstract
- Leishmaniasis is one of the most important neglected tropical diseases, with a broad spectrum of clinical manifestations. Among the clinical manifestations of the disease, cutaneous leishmaniasis, caused by species of Leishmania braziliensis, presents wide distribution in Brazil. In this work, we performed the cloning, expression, and purification of the enzyme superoxide dismutase of Leishmania braziliensis (LbSOD-B2) considered a promising target for the search of new compounds against leishmaniasis. In vitro assays based on pyrogallol oxidation showed that LbSOD-B2 is most active around pH 8 and hydrogen peroxide is a LbSOD-B2 inhibitor at low millimolar range (IC50 = 1 mM).
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| 40. |
- Brito, Fernanda, et al.
(author)
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Subgingival microflora in inflammatory bowel disease patients with untreated periodontitis.
- 2013
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In: European Journal of Gastroenterology and Hepathology. - 0954-691X .- 1473-5687. ; 25:2, s. 239-245
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To analyze the subgingival microflora composition of inflammatory bowel disease (IBD) patients with untreated chronic periodontitis and compare them with systemically healthy controls also having untreated chronic periodontitis.METHOD: Thirty IBD patients [15 with Crohn's disease (CD) and 15 with ulcerative colitis (UC)] and 15 control individuals participated in the study. All patients had been diagnosed with untreated chronic periodontitis. From every patient, subgingival plaque was collected from four gingivitis and four periodontitis sites with paper points. Samples from the same category (gingivitis or periodontitis) in each patient were pooled together and stored at -70 °C until analysis using a checkerboard DNA-DNA hybridization technique for 74 bacterial species.RESULTS: Multiple-comparison analysis showed that the groups differed in bacterial counts for Bacteroides ureolyticus, Campylobacter gracilis, Parvimonas micra, Prevotella melaninogenica, Peptostreptococcus anaerobius, Staphylococcus aureus, Streptococcus anginosus, Streptococcus intermedius, Streptococcus mitis, Streptococcus mutans, and Treponema denticola (P<0.001). CD patients had significantly higher levels of these bacteria than UC patients either in gingivitis or in periodontitis sites (P<0.05). CD patients harbored higher levels of P. melaninogenica, S. aureus, S. anginosus, and S. mutans compared with controls both at gingivitis and at periodontitis sites (P<0.05). UC patients harbored higher levels of S. aureus (P=0.01) and P. anaerobius (P=0.05) than controls only in gingivitis sites.CONCLUSION: Our study showed that even with similar clinical periodontal parameters, IBD patients harbor higher levels of bacteria that are related to opportunistic infections in inflamed subgingival sites that might be harmful for the crucial microbe-host interaction.
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- Brito-Zeron, P., et al.
(author)
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Exposure to air pollution as an environmental determinant of how Sjögren's disease is expressed at diagnosis
- 2023
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In: Clinical and Experimental Rheumatology. - : Clinical and Experimental Rheumatology. - 0392-856X .- 1593-098X. ; 41:12, s. 2448-2457
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Journal article (peer-reviewed)abstract
- ObjectiveTo analyse how the potential exposure to air pollutants can influence the key components at the time of diagnosis of Sjogren's phenotype (epidemiological profile, sicca symptoms, and systemic disease). MethodsFor the present study, the following variables were selected for harmonisation and refinement: age, sex, country, fulfilment of 2002/2016 criteria items, dry eyes, dry mouth, and overall ESSDAI score. Air pollution indexes per country were defined according to the OECD (1990-2021), including emission data of nitrogen and sulphur oxides (NO/SO), particulate matter (PM2.5 and 1.0), carbon monoxide (CO) and volatile organic compounds (VOC) calculated per unit of GDP, Kg per 1000 USD.ResultsThe results of the chi-square tests of independence for each air pollutant with the frequency of dry eyes at diagnosis showed that, except for one, all variables exhibited p-values <0.0001. The most pronounced disparities emerged in the dry eye prevalence among individuals inhabiting countries with the highest NO/SO exposure, a surge of 4.61 percentage points compared to other countries, followed by CO (3.59 points), non-methane (3.32 points), PM2.5 (3.30 points), and PM1.0 (1.60 points) exposures. Concerning dry mouth, individuals residing in countries with worse NO/SO exposures exhibited a heightened frequency of dry mouth by 2.05 percentage points (p<0.0001), followed by non-methane exposure (1.21 percentage points increase, p=0.007). Individuals inhabiting countries with the worst NO/SO, CO, and PM2.5 pollution levels had a higher mean global ESSDAI score than those in lower-risk nations (all p-values <0.0001). When systemic disease was stratified according to DAS into low, moderate, and high systemic activity levels, a heightened proportion of individuals manifesting moderate/severe systemic activity was observed in countries with worse exposures to NO/SO, CO, and PM2.5 pollutant levels. ConclusionFor the first time, we suggest that pollution levels could influence how SjD appears at diagnosis in a large international cohort of patients. The most notable relationships were found between symptoms (dryness and general body symptoms) and NO/SO, CO, and PM2.5 levels.
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| 47. |
- Brito-Zeron, P., et al.
(author)
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How immunological profile drives clinical phenotype of primary Sjögren's syndrome at diagnosis : analysis of 10,500 patients (Sjögren Big Data Project)
- 2018
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In: Clinical and Experimental Rheumatology. - : CLINICAL & EXPER RHEUMATOLOGY. - 0392-856X .- 1593-098X. ; 36:3, s. S102-S112
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Journal article (peer-reviewed)abstract
- Objective: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjogren's syndrome (SjS).Methods: The Big Data Sjogren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.Results: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti-La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglobulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for ctyoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESSDAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).Conclusion: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.
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