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2.
  • Bousquet, J, et al. (författare)
  • Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
  • 2020
  • Ingår i: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
  • Tidskriftsartikel (refereegranskat)abstract
    • There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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4.
  • Stroth, U., et al. (författare)
  • Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development
  • 2022
  • Ingår i: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4
  • Tidskriftsartikel (refereegranskat)abstract
    • An overview of recent results obtained at the tokamak ASDEX Upgrade (AUG) is given. A work flow for predictive profile modelling of AUG discharges was established which is able to reproduce experimental H-mode plasma profiles based on engineering parameters only. In the plasma center, theoretical predictions on plasma current redistribution by a dynamo effect were confirmed experimentally. For core transport, the stabilizing effect of fast ion distributions on turbulent transport is shown to be important to explain the core isotope effect and improves the description of hollow low-Z impurity profiles. The L-H power threshold of hydrogen plasmas is not affected by small helium admixtures and it increases continuously from the deuterium to the hydrogen level when the hydrogen concentration is raised from 0 to 100%. One focus of recent campaigns was the search for a fusion relevant integrated plasma scenario without large edge localised modes (ELMs). Results from six different ELM-free confinement regimes are compared with respect to reactor relevance: ELM suppression by magnetic perturbation coils could be attributed to toroidally asymmetric turbulent fluctuations in the vicinity of the separatrix. Stable improved confinement mode plasma phases with a detached inner divertor were obtained using a feedback control of the plasma β. The enhanced D α H-mode regime was extended to higher heating power by feedback controlled radiative cooling with argon. The quasi-coherent exhaust regime was developed into an integrated scenario at high heating power and energy confinement, with a detached divertor and without large ELMs. Small ELMs close to the separatrix lead to peeling-ballooning stability and quasi continuous power exhaust. Helium beam density fluctuation measurements confirm that transport close to the separatrix is important to achieve the different ELM-free regimes. Based on separatrix plasma parameters and interchange-drift-Alfvén turbulence, an analytic model was derived that reproduces the experimentally found important operational boundaries of the density limit and between L- and H-mode confinement. Feedback control for the X-point radiator (XPR) position was established as an important element for divertor detachment control. Stable and detached ELM-free phases with H-mode confinement quality were obtained when the XPR was moved 10 cm above the X-point. Investigations of the plasma in the future flexible snow-flake divertor of AUG by means of first SOLPS-ITER simulations with drifts activated predict beneficial detachment properties and the activation of an additional strike point by the drifts.
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5.
  • Solmi, M, et al. (författare)
  • 2022
  • Ingår i: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376
  • Tidskriftsartikel (refereegranskat)
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6.
  • Gilmore, G., et al. (författare)
  • The Gaia-ESO Public Spectroscopic Survey : Motivation, implementation, GIRAFFE data processing, analysis, and final data products star
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The Gaia-ESO Public Spectroscopic Survey is an ambitious project designed to obtain astrophysical parameters and elemental abundances for 100 000 stars, including large representative samples of the stellar populations in the Galaxy, and a well-defined sample of 60 (plus 20 archive) open clusters. We provide internally consistent results calibrated on benchmark stars and star clusters, extending across a very wide range of abundances and ages. This provides a legacy data set of intrinsic value, and equally a large wide-ranging dataset that is of value for the homogenisation of other and future stellar surveys and Gaia's astrophysical parameters. Aims. This article provides an overview of the survey methodology, the scientific aims, and the implementation, including a description of the data processing for the GIRAFFE spectra. A companion paper introduces the survey results. Methods. Gaia-ESO aspires to quantify both random and systematic contributions to measurement uncertainties. Thus, all available spectroscopic analysis techniques are utilised, each spectrum being analysed by up to several different analysis pipelines, with considerable effort being made to homogenise and calibrate the resulting parameters. We describe here the sequence of activities up to delivery of processed data products to the ESO Science Archive Facility for open use. Results. The Gaia-ESO Survey obtained 202 000 spectra of 115 000 stars using 340 allocated VLT nights between December 2011 and January 2018 from GIRAFFE and UVES. Conclusions. The full consistently reduced final data set of spectra was released through the ESO Science Archive Facility in late 2020, with the full astrophysical parameters sets following in 2022. A companion article reviews the survey implementation, scientific highlights, the open cluster survey, and data products.
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7.
  • Randich, S., et al. (författare)
  • The Gaia-ESO Public Spectroscopic Survey : Implementation, data products, open cluster survey, science, and legacy
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 666
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. In the last 15 years different ground-based spectroscopic surveys have been started (and completed) with the general aim of delivering stellar parameters and elemental abundances for large samples of Galactic stars, complementing Gaia astrometry. Among those surveys, the Gaia-ESO Public Spectroscopic Survey, the only one performed on a 8m class telescope, was designed to target 100 000 stars using FLAMES on the ESO VLT (both Giraffe and UVES spectrographs), covering all the Milky Way populations, with a special focus on open star clusters. Aims. This article provides an overview of the survey implementation (observations, data quality, analysis and its success, data products, and releases), of the open cluster survey, of the science results and potential, and of the survey legacy. A companion article reviews the overall survey motivation, strategy, Giraffe pipeline data reduction, organisation, and workflow. Methods. We made use of the information recorded and archived in the observing blocks; during the observing runs; in a number of relevant documents; in the spectra and master catalogue of spectra; in the parameters delivered by the analysis nodes and the working groups; in the final catalogue; and in the science papers. Based on these sources, we critically analyse and discuss the output and products of the Survey, including science highlights. We also determined the average metallicities of the open clusters observed as science targets and of a sample of clusters whose spectra were retrieved from the ESO archive. Results. The Gaia-ESO Survey has determined homogeneous good-quality radial velocities and stellar parameters for a large fraction of its more than 110 000 unique target stars. Elemental abundances were derived for up to 31 elements for targets observed with UVES. Lithium abundances are delivered for about 1/3 of the sample. The analysis and homogenisation strategies have proven to be successful; several science topics have been addressed by the Gaia-ESO consortium and the community, with many highlight results achieved. Conclusions. The final catalogue will be released through the ESO archive in the first half of 2022, including the complete set of advanced data products. In addition to these results, the Gaia-ESO Survey will leave a very important legacy, for several aspects and for many years to come.
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8.
  • Giustozzi, M., et al. (författare)
  • Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation
  • 2020
  • Ingår i: Stroke. - 0039-2499. ; 51:8, s. 2347-2354
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Purpose: The optimal timing for starting oral anticoagulant after an ischemic stroke related to atrial fibrillation remains a challenge, mainly in patients treated with systemic thrombolysis or mechanical thrombectomy. We aimed at assessing the incidence of early recurrence and major bleeding in patients with acute ischemic stroke and atrial fibrillation treated with thrombolytic therapy and/or thrombectomy, who then received oral anticoagulants for secondary prevention. Methods: We combined the dataset of the RAF and the RAF-NOACs (Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants) studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and atrial fibrillation treated with either vitamin K antagonists or nonvitamin K oral anticoagulants. Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Treated-patients were propensity matched to untreated-patients in a 1:1 ratio after stratification by baseline clinical features. Results: A total of 2159 patients were included, 564 (26%) patients received acute reperfusion therapies. After the index event, 505 (90%) patients treated with acute reperfusion therapies and 1287 of 1595 (81%) patients untreated started oral anticoagulation. Timing of starting oral anticoagulant was similar in reperfusion-treated and untreated patients (median 7.5 versus 7.0 days, respectively). At 90 days, the primary study outcome occurred in 37 (7%) patients treated with reperfusion and in 146 (9%) untreated patients (odds ratio, 0.74 [95% CI, 0.50-1.07]). After propensity score matching, risk of primary outcome was comparable between the 2 groups (odds ratio, 1.06 [95% CI, 0.53-2.02]). Conclusions: Acute reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with atrial fibrillation-related acute ischemic stroke, who started on oral anticoagulant. © 2020 Georg Thieme Verlag. All rights reserved.
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9.
  • Panico, B., et al. (författare)
  • Cosmic Rays Investigation by the PAMELA experiment
  • 2020
  • Ingår i: Journal of Physics. - : IOP Publishing.
  • Konferensbidrag (refereegranskat)abstract
    • PAMELA (Payload for Antimatter Matter Exploration and Light-nuclei Astrophysics) is a satellite-borne experiment. It was launched on June 15th 2006 from the Baikonur space centre on board the Russian Resurs-DK1 satellite. For about 10 years PAMELA took data, giving a fundamental contribution to the cosmic ray physics. It made high-precision measurements of the charged component of the cosmic radiation challenging the standard model of the mechanisms of production, acceleration and propagation of cosmic rays in the galaxy and in the heliosphere. PAMELA gave results on different topics on a very wide range of energy. Moreover, the long PAMELA life gives the possibility to study the variation of the proton, electron and positron spectra during the last solar minimum. The time dependence of the cosmic-ray proton and helium nuclei from the solar minimum through the following period of solar maximum activity is currently being studied. Low energy particle spectra were accurately measured also for various solar events that occurred during the PAMELA mission. In this paper a review of main PAMELA results will be reported.
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10.
  • Panico, B., et al. (författare)
  • Time dependence of the proton and helium flux measured by PAMELA
  • 2020
  • Ingår i: Journal of Physics. - : IOP Publishing.
  • Konferensbidrag (refereegranskat)abstract
    • The energy spectra of galactic cosmic rays carry fundamental information regarding their origin and propagation, but, near Earth, cosmic rays are significantly affected by the solar magnetic field which changes over time. The time dependence of proton and electron spectra were measured from July 2006 to December 2009 by PAMELA experiment, that is a ballooon-borne experiment collecting data since 15 June 2006. These studies allowed to obtain a more complete description of the cosmic radiation, providing fundamental information about the transport and modulation of cosmic rays inside the heliosphere. The study of the time dependence of the cosmic-ray protons and helium nuclei from the unusual 23rd solar minimum through the following period of solar maximum activity is presented.
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11.
  • Paciaroni, M., et al. (författare)
  • Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes
  • 2020
  • Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881.
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. Materials and Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
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12.
  • Perez-Nadales, Elena, et al. (författare)
  • Predictors of mortality in solid organ transplant recipients with bloodstream infections due to carbapenemase-producing Enterobacterales : The impact of cytomegalovirus disease and lymphopenia
  • 2020
  • Ingår i: American Journal of Transplantation. - : WILEY. - 1600-6135 .- 1600-6143. ; 20:6, s. 1629-1641
  • Tidskriftsartikel (refereegranskat)abstract
    • Treatment of carbapenemase-producing Enterobacterales bloodstream infections in solid organ transplant recipients is challenging. The objective of this study was to develop a specific score to predict mortality in solid organ transplant recipients with carbapenemase-producing Enterobacterales bloodstream infections. A multinational, retrospective (2004-2016) cohort study (INCREMENT-SOT, ClinicalTrials.gov NCT02852902) was performed. The main outcome variable was 30-day all-cause mortality. The INCREMENT-SOT-CPE score was developed using logistic regression. The global cohort included 216 patients. The final logistic regression model included the following variables: INCREMENT-CPE mortality score >= 8 (8 points), no source control (3 points), inappropriate empirical therapy (2 points), cytomegalovirus disease (7 points), lymphopenia (4 points), and the interaction between INCREMENT-CPE score >= 8 and CMV disease (minus 7 points). This score showed an area under the receiver operating characteristic curve of 0.82 (95% confidence interval [CI] 0.76-0.88) and classified patients into 3 strata: 0-7 (low mortality), 8-11 (high mortality), and 12-17 (very-high mortality). We performed a stratified analysis of the effect of monotherapy vs combination therapy among 165 patients who received appropriate therapy. Monotherapy was associated with higher mortality only in the very-high (adjusted hazard ratio [HR] 2.82, 95% CI 1.13-7.06, P = .03) and high (HR 9.93, 95% CI 2.08-47.40, P = .004) mortality risk strata. A score-based algorithm is provided for therapy guidance.
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13.
  • Magrini, L., et al. (författare)
  • The Gaia -ESO survey: Mixing processes in low-mass stars traced by lithium abundance in cluster and field stars
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims. We aim to constrain the mixing processes in low-mass stars by investigating the behaviour of the Li surface abundance after the main sequence. We take advantage of the data from the sixth internal data release of Gaia-ESO, IDR6, and from the Gaia Early Data Release 3, EDR3s. Methods. We selected a sample of main-sequence, sub-giant, and giant stars in which the Li abundance is measured by the Gaia-ESO survey. These stars belong to 57 open clusters with ages from 130 Myr to about 7 Gyr and to Milky Way fields, covering a range in [Fe/H] between -1.0and +0.5 dex, with few stars between -1.0 and -2.5dex. We studied the behaviour of the Li abundances as a function of stellar parameters. We inferred the masses of giant stars in clusters from the main-sequence turn-off masses, and for field stars through comparison with stellar evolution models using a maximum likelihood technique. We compared the observed Li behaviour in field giant stars and in giant stars belonging to individual clusters with the predictions of a set of classical models and of models with mixing induced by rotation and thermohaline instability. Results. The comparison with stellar evolution models confirms that classical models cannot reproduce the observed lithium abundances in the metallicity and mass regimes covered by the data. The models that include the effects of both rotation-induced mixing and thermohaline instability account for the Li abundance trends observed in our sample in all metallicity and mass ranges. The differences between the results of the classical models and of the rotation models largely differ (up to 2 dex), making lithium the best element with which to constrain stellar mixing processes in low-mass stars. We discuss the nature of a sample of Li-rich stars. Conclusions. We demonstrate that the evolution of the surface abundance of Li in giant stars is a powerful tool for constraining theoretical stellar evolution models, allowing us to distinguish the effect of different mixing processes. For stars with well-determined masses, we find a better agreement of observed surface abundances and models with rotation-induced and thermohaline mixing. Rotation effects dominate during the main sequence and the first phases of the post-main-sequence evolution, and the thermohaline induced mixing after the bump in the luminosity function.
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14.
  • Franciosini, E., et al. (författare)
  • The Gaia-ESO Survey : Lithium measurements and new curves of growth
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 668
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The Gaia-ESO Survey (GES) is a large public spectroscopic survey that was carried out using the multi-object FLAMES spectrograph at the Very Large Telescope. The survey provides accurate radial velocities, stellar parameters, and elemental abundances for ~115 000 stars in all Milky Way components.Aims. In this paper, we describe the method adopted in the final data release to derive lithium equivalent widths (EWs) and abundances.Methods. Lithium EWs were measured using two different approaches for FGK and M-type stars, to account for the intrinsic differences in the spectra. For FGK stars, we fitted the lithium line using Gaussian components, while direct integration over a predefined interval was adopted for M-type stars. Care was taken to ensure continuity between the two regimes. Abundances were derived using a new set of homogeneous curves of growth that were derived specifically for GES, and which were measured on a synthetic spectral grid consistently with the way the EWs were measured. The derived abundances were validated by comparison with those measured by other analysis groups using different methods.Results. Lithium EWs were measured for ~40 000 stars, and abundances could be derived for ~38 000 of them. The vast majority of the measures (80%) have been obtained for stars in open cluster fields. The remaining objects are stars in globular clusters, or field stars in the Milky Way disc, bulge, and halo.Conclusions. The GES dataset of homogeneous lithium abundances described here will be valuable for our understanding of several processes, from stellar evolution and internal mixing in stars at different evolutionary stages to Galactic evolution.
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15.
  • Casali, G., et al. (författare)
  • The Gaia-ESO survey : the non-universality of the age-chemical-clocks-metallicity relations in the Galactic disc
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 639
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. In the era of large spectroscopic surveys, massive databases of high-quality spectra coupled with the products of the Gaia satellite provide tools to outline a new picture of our Galaxy. In this framework, an important piece of information is provided by our ability to infer stellar ages, and consequently to sketch a Galactic timeline.Aims. We aim to provide empirical relations between stellar ages and abundance ratios for a sample of stars with very similar stellar parameters to those of the Sun, namely the so-called solar-like stars. We investigate the dependence on metallicity, and we apply our relations to independent samples, that is, the Gaia-ESO samples of open clusters and of field stars.Methods. We analyse high-resolution and high-signal-to-noise-ratio HARPS spectra of a sample of solar-like stars to obtain precise determinations of their atmospheric parameters and abundances for 25 elements and/or ions belonging to the main nucleosynthesis channels through differential spectral analysis, and of their ages through isochrone fitting.Results. We investigate the relations between stellar ages and several abundance ratios. For the abundance ratios with a steeper dependence on age, we perform multivariate linear regressions, in which we include the dependence on metallicity, [Fe/H]. We apply our best relations to a sample of open clusters located from the inner to the outer regions of the Galactic disc. Using our relations, we are able to recover the literature ages only for clusters located at R-GC > 7 kpc. The values that we obtain for the ages of the inner-disc clusters are much greater than the literature ones. In these clusters, the content of neutron capture elements, such as Y and Zr, is indeed lower than expected from chemical evolution models, and consequently their [Y/Mg] and [Y/Al] are lower than in clusters of the same age located in the solar neighbourhood. With our chemical evolution model and a set of empirical yields, we suggest that a strong dependence on the star formation history and metallicity-dependent stellar yields of s-process elements can substantially modify the slope of the [s/alpha]-[Fe/H]-age relation in different regions of the Galaxy.Conclusions. Our results point towards a non-universal relation [s/alpha]-[Fe/H]-age, indicating the existence of relations with different slopes and intercepts at different Galactocentric distances or for different star formation histories. Therefore, relations between ages and abundance ratios obtained from samples of stars located in a limited region of the Galaxy cannot be translated into general relations valid for the whole disc. A better understanding of the s-process at high metallicity is necessary to fully understand the origin of these variations.
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16.
  • Worley, C. C., et al. (författare)
  • The Gaia-ESO Survey : Spectroscopic-asteroseismic analysis of K2 stars in Gaia-ESO The K2 Galactic Caps Project
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. The extensive stellar spectroscopic datasets that are available for studies in Galactic Archeaology thanks to, for example, the Gaia-ESO Survey, now benefit from having a significant number of targets that overlap with asteroseismology projects such as Kepler, K2, and CoRoT. Combining the measurements from spectroscopy and asteroseismology allows us to attain greater accuracy with regard to the stellar parameters needed to characterise the stellar populations of the Milky Way.Aims. The aim of this Gaia-ESO Survey special project is to produce a catalogue of self-consistent stellar parameters by combining measurements from high-resolution spectroscopy and precision asteroseismology.Methods. We carried out an iterative analysis of 90 K2@Gaia-ESO red giants. The spectroscopic values of Teff were used as input in the seismic analysis to obtain log g values. The seismic estimates of log g were then used to re-determine the spectroscopic values of Teff and [Fe/H]. Only one iteration was required to obtain parameters that are in good agreement for both methods and, thus, to obtain the final stellar parameters. A detailed analysis of outliers was carried out to ensure a robust determination of the parameters. The results were then combined with Gaia DR2 data to compare the seismic log g with a parallax-based log g and to investigate instances of variations in the velocity and possible binaries within the dataset.Results. This analysis produced a high-quality catalogue of stellar parameters for 90 red giant stars from K2@Gaia-ESO that were determined through iterations between spectroscopy and asteroseismology. We compared the seismic gravities with those based on Gaia parallaxes to find an offset which is similar to other studies that have used asteroseismology. Our catalogue also includes spectroscopic chemical abundances and radial velocities, as well as indicators for possible binary detections.
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17.
  • Gutierrez Albarran, M. L., et al. (författare)
  • The Gaia-ESO Survey : Calibrating the lithium-age relation with open clusters and associations I. Cluster age range and initial membership selections
  • 2020
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 643
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Previous studies of open clusters have shown that lithium depletion is not only strongly age dependent but also shows a complex pattern with other parameters that is not yet understood. For pre- and main-sequence late-type stars, these parameters include metallicity, mixing mechanisms, convection structure, rotation, and magnetic activity.Aims: We perform a thorough membership analysis for a large number of stars observed within the Gaia-ESO survey (GES) in the field of 20 open clusters, ranging in age from young clusters and associations, to intermediate-age and old open clusters.Methods: Based on the parameters derived from the GES spectroscopic observations, we obtained lists of candidate members for each of the clusters in the sample by deriving radial velocity distributions and studying the position of the kinematic selections in the EW(Li)-versus-T-eff plane to obtain lithium members. We used gravity indicators to discard field contaminants and studied [Fe/H] metallicity to further confirm the membership of the candidates. We also made use of studies using recent data from the Gaia DR1 and DR2 releases to assess our member selections.Results: We identified likely member candidates for the sample of 20 clusters observed in GES (iDR4) with UVES and GIRAFFE, and conducted a comparative study that allowed us to characterize the properties of these members as well as identify field contaminant stars, both lithium-rich giants and non-giant outliers.Conclusions: This work is the first step towards the calibration of the lithium-age relation and its dependence on other GES parameters. During this project we aim to use this relation to infer the ages of GES field stars, and identify their potential membership to young associations and stellar kinematic groups of different ages.
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18.
  • Tobias, Deirdre K, et al. (författare)
  • Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
  • 2023
  • Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
  • Forskningsöversikt (refereegranskat)abstract
    • Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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19.
  • Baratella, M., et al. (författare)
  • The Gaia-ESO Survey: A new approach to chemically characterising young open cluster : II. Abundances of the neutron-capture elements Cu, Sr, Y, Zr, Ba, La, and Ce
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. Young open clusters (ages of less than 200 Myr) have been observed to exhibit several peculiarities in their chemical compositions. These anomalies include a slightly sub-solar iron content, super-solar abundances of some atomic species (e.g. ionised chromium), and atypical enhancements of [Ba/Fe], with values up to ~0.7 dex. Regarding the behaviour of the other s-process elements like yttrium, zirconium, lanthanum, and cerium, there is general disagreement in the literature: some authors claim that they follow the same trend as barium, while others find solar abundances at all ages. Aims. In this work we expand upon our previous analysis of a sample of five young open clusters (IC 2391, IC 2602, IC 4665, NGC 2516, and NGC 2547) and one star-forming region (NGC 2264), with the aim of determining abundances of different neutron-capture elements, mainly Cu I, Sr I, Sr II, Y II, Zr II, Ba II, La II, and Ce II. For NGC 2264 and NGC 2547 we present the measurements of these elements for the first time. Methods. We analysed high-resolution, high signal-to-noise spectra of 23 solar-type stars observed within the Gaia-ESO survey. After a careful selection, we derived abundances of isolated and clean lines via spectral synthesis computations and in a strictly differential way with respect to the Sun. Results. We find that our clusters have solar [Cu/Fe] within the uncertainties, while we confirm that [Ba/Fe] is super-solar, with values ranging from +0.22 to +0.64 dex. Our analysis also points to a mild enhancement of Y, with [Y/Fe] ratios covering values between 0 and +0.3 dex. For the other s-process elements we find that [X/Fe] ratios are solar at all ages. Conclusions. It is not possible to reconcile the anomalous behaviour of Ba and Y at young ages with standard stellar yields and Galactic chemical evolution model predictions. We explore different possible scenarios related to the behaviour of spectral lines, from the dependence on the different ionisation stages and the sensitivity to the presence of magnetic fields (through the Landé factor) to the first ionisation potential effect. We also investigate the possibility that they may arise from alterations of the structure of the stellar photosphere due to the increased levels of stellar activity that affect the spectral line formation, and consequently the derived abundances. These effects seem to be stronger in stars at ages of less than ∼ 100 Myr. However, we are still unable to explain these enhancements, and the Ba puzzle remains unsolved. With the present study we suggest that other elements, for example Sr, Zr, La, and Ce, might be more reliable tracer of the s-process at young ages, and we strongly encourage further critical observations.
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20.
  • Cescutti, G., et al. (författare)
  • MINCE I. Presentation of the project and of the first year sample
  • 2022
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 668
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. In recent years, Galactic archaeology has become a particularly vibrant field of astronomy, with its main focus set on the oldest stars of our Galaxy. In most cases, these stars have been identified as the most metal-poor. However, the struggle to find these ancient fossils has produced an important bias in the observations - in particular, the intermediate metal-poor stars (-2.5 < [Fe/H] < -1.5) have been frequently overlooked. The missing information has consequences for the precise study of the chemical enrichment of our Galaxy, in particular for what concerns neutron capture elements and it will be only partially covered by future multi object spectroscopic surveys such as WEAVE and 4MOST.Aims. Measuring at Intermediate Metallicity Neutron Capture Elements (MINCE) is gathering the first high-quality spectra (high signal-to-noise ratio, S/N, and high resolution) for several hundreds of bright and metal-poor stars, mainly located in our Galactic halo.Methods. We compiled our selection mainly on the basis of Gaia data and determined the stellar atmospheres of our sample and the chemical abundances of each star.Results. In this paper, we present the first sample of 59 spectra of 46 stars. We measured the radial velocities and computed the Galactic orbits for all stars. We found that 8 stars belong to the thin disc, 15 to disrupted satellites, and the remaining cannot be associated to the mentioned structures, and we call them halo stars. For 33 of these stars, we provide abundances for the elements up to zinc. We also show the chemical evolution results for eleven chemical elements, based on recent models.Conclusions. Our observational strategy of using multiple telescopes and spectrographs to acquire high S/N and high-resolution spectra for intermediate-metallicity stars has proven to be very efficient, since the present sample was acquired over only about one year of observations. Finally, our target selection strategy, after an initial adjustment, proved satisfactory for our purposes.
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21.
  • Heiter, Ulrike, et al. (författare)
  • Atomic data for the Gaia-ESO Survey
  • 2021
  • Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
  • Tidskriftsartikel (refereegranskat)abstract
    • Context. We describe the atomic and molecular data that were used for the abundance analyses of FGK-type stars carried out within the Gaia-ESO Public Spectroscopic Survey in the years 2012 to 2019. The Gaia-ESO Survey is one among several current and future stellar spectroscopic surveys producing abundances for Milky-Way stars on an industrial scale.Aims. We present an unprecedented effort to create a homogeneous common line list, which was used by several abundance analysis groups using different radiative transfer codes to calculate synthetic spectra and equivalent widths. The atomic data are accompanied by quality indicators and detailed references to the sources. The atomic and molecular data are made publicly available at the CDS.Methods. In general, experimental transition probabilities were preferred but theoretical values were also used. Astrophysical gf-values were avoided due to the model-dependence of such a procedure. For elements whose lines are significantly affected by a hyperfine structure or isotopic splitting, a concerted effort has been made to collate the necessary data for the individual line components. Synthetic stellar spectra calculated for the Sun and Arcturus were used to assess the blending properties of the lines. We also performed adetailed investigation of available data for line broadening due to collisions with neutral hydrogen atoms.Results. Among a subset of over 1300 lines of 35 elements in the wavelength ranges from 475 to 685 nm and from 850 to 895 nm, we identified about 200 lines of 24 species which have accurate gf-values and are free of blends in the spectra of the Sun and Arcturus. For the broadening due to collisions with neutral hydrogen, we recommend data based on Anstee-Barklem-O'Mara theory, where possible. We recommend avoiding lines of neutral species for which these are not available. Theoretical broadening data by R.L. Kurucz should be used for ScII, TiII, and YII lines; additionally, for ionised rare-earth species, the Unsold approximation with an enhancement factor of 1.5 for the line width can be used.Conclusions. The line list has proven to be a useful tool for abundance determinations based on the spectra obtained within the Gaia-ESO Survey, as well as other spectroscopic projects. Accuracies below 0.2 dex are regularly achieved, where part of the uncertainties are due to differences in the employed analysis methods. Desirable improvements in atomic data were identified for a number of species, most importantly AlI, SI, and CrII, but also NaI, SiI, CaII, and NiI.
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22.
  • Revelli, A., et al. (författare)
  • Quasimolecular electronic structure of the spin-liquid candidate Ba3 InIr2 O9
  • 2022
  • Ingår i: Physical Review B. - : American Physical Society. - 2469-9950 .- 2469-9969. ; 106:15
  • Tidskriftsartikel (refereegranskat)abstract
    • The mixed-valent iridate Ba3InIr2O9 has been discussed as a promising candidate for quantum spin-liquid behavior. The compound exhibits Ir4.5+ ions in face-sharing IrO6 octahedra forming Ir2O9 dimers with three t2g holes per dimer. Our results establish Ba3InIr2O9 as a cluster Mott insulator. Strong intradimer hopping delocalizes the three t2g holes in quasimolecular dimer states while interdimer charge fluctuations are suppressed by Coulomb repulsion. The magnetism of Ba3InIr2O9 emerges from spin-orbit entangled quasimolecular moments with yet unexplored interactions, opening up a new route to unconventional magnetic properties of 5d compounds. Using single-crystal x-ray diffraction we find the monoclinic space group C2/c already at room temperature. Dielectric spectroscopy shows insulating behavior. Resonant inelastic x-ray scattering reveals a rich excitation spectrum below 1.5 eV with a sinusoidal dynamical structure factor that unambiguously demonstrates the quasimolecular character of the electronic states. Below 0.3 eV, we observe a series of excitations. According to exact diagonalization calculations, such low-energy excitations reflect the proximity of Ba3InIr2O9 to a hopping-induced phase transition based on the condensation of a quasimolecular spin-orbit exciton. The dimer ground state roughly hosts two holes in a bonding j=1/2 orbital and the third hole in a bonding j=3/2 orbital. 
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23.
  • Gialluisi, A, et al. (författare)
  • Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia
  • 2021
  • Ingår i: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 26:7, s. 3004-3017
  • Tidskriftsartikel (refereegranskat)abstract
    • Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p  < 2.8 × 10−6) enrichment of associations at the gene level, forLOC388780(20p13; uncharacterized gene), and forVEPH1(3q25), a gene implicated in brain development. We estimated an SNP-based heritability of 20–25% for DD, and observed significant associations of dyslexia risk with PGSs for attention deficit hyperactivity disorder (atpT = 0.05 in the training GWAS: OR = 1.23[1.16; 1.30] per standard deviation increase;p  = 8 × 10−13), bipolar disorder (1.53[1.44; 1.63];p = 1 × 10−43), schizophrenia (1.36[1.28; 1.45];p = 4 × 10−22), psychiatric cross-disorder susceptibility (1.23[1.16; 1.30];p = 3 × 10−12), cortical thickness of the transverse temporal gyrus (0.90[0.86; 0.96];p = 5 × 10−4), educational attainment (0.86[0.82; 0.91];p = 2 × 10−7), and intelligence (0.72[0.68; 0.76];p = 9 × 10−29). This study suggests an important contribution of common genetic variants to dyslexia risk, and novel genomic overlaps with psychiatric conditions like bipolar disorder, schizophrenia, and cross-disorder susceptibility. Moreover, it revealed the presence of shared genetic foundations with a neural correlate previously implicated in dyslexia by neuroimaging evidence.
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24.
  • Bosmans, Laura A., et al. (författare)
  • Myeloid CD40 deficiency reduces atherosclerosis by impairing macrophages’ transition into a pro-inflammatory state
  • 2023
  • Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:5, s. 1146-1160
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims CD40 and its ligand, CD40L, play a critical role in driving atherosclerotic plaque development. Disrupted CD40-signalling reduces experimental atherosclerosis and induces a favourable stable plaque phenotype. We recently showed that small molecule-based inhibition of CD40-tumour necrosis factor receptor associated factor-6 interactions attenuates atherosclerosis in hyperlipidaemic mice via macrophage-driven mechanisms. The present study aims to detail the function of myeloid CD40 in atherosclerosis using myeloid-specific CD40-deficient mice. Method and Cd40flox/flox and LysM-cre Cd40flox/flox mice on an Apoe−/− background were generated (CD40wt and CD40mac−/− , respect-Results ively). Atherosclerotic lesion size, as well as plaque macrophage content, was reduced in CD40mac−/− compared to CD40wt mice, and their plaques displayed a reduction in necrotic core size. Transcriptomics analysis of the CD40mac−/− atherosclerotic aorta revealed downregulated pathways of immune pathways and inflammatory responses. Loss of CD40 in macrophages changed the representation of aortic macrophage subsets. Mass cytometry analysis revealed a higher content of a subset of alternative or resident-like CD206+CD209b− macrophages in the atherosclerotic aorta of CD40mac−/− compared to CD40wt mice. RNA-sequencing of bone marrow-derived macrophages of CD40mac−/− mice demonstrated upregulation of genes associated with alternatively activated macrophages (including Folr2, Thbs1, Sdc1, and Tns1). Conclusions We here show that absence of CD40 signalling in myeloid cells reduces atherosclerosis and limits systemic inflammation by preventing a shift in macrophage polarization towards pro-inflammatory states. Our study confirms the merit of macrophage-targeted inhibition of CD40 as a valuable therapeutic strategy to combat atherosclerosis.
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25.
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26.
  • Al-Abbadi, Mousa A., et al. (författare)
  • A Proposal for the Performance, Classification, and Reporting of Lymph Node Fine-Needle Aspiration Cytopathology : The Sydney System
  • 2020
  • Ingår i: Acta Cytologica. - : S. Karger AG. - 0001-5547 .- 1938-2650. ; 64:4, s. 306-322
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The evaluation of lymph nodes (LN) by fine-needle aspiration cytology (FNAC) is routinely used in many institutions but it is not uniformly accepted mainly because of the lack of guidelines and a cytopathological diagnostic classification. A committee of cytopathologists has developed a system of performance, classification, and reporting for LN-FNAC. METHODS: The committee members prepared a document that has circulated among them five times; the final text has been approved by all the participants. It is based on a review of the international literature and on the expertise of the members. The system integrates clinical and imaging data with cytopathological features and ancillary techniques. The project has received the endorsement and patronage of the International Academy of Cytology and the European Federation of the Cytology Societies. RESULTS: Clinical, imaging, and serological data of lymphadenopathies, indications for LN-FNAC, technical procedures, and ancillary techniques are evaluated with specific recommendations. The reporting system includes two diagnostic levels. The first should provide basic diagnostic information and includes five categories: inadequate/insufficient, benign, atypical lymphoid cells of undetermined/uncertain significance, suspicious, and malignant. For each category, specific recommendations are provided. The second diagnostic level, when achievable, should produce the identification of specific benign or malignant entities and additional information by utilizing ancillary testing. CONCLUSION: The authors believe that the introduction of this system for performing and reporting LN-FNAC may improve the quality of the procedure, the report, and the communication between cytopathologists and the clinicians. This system may lead to a greater acceptance and utilization of LN-FNAC and to a better interdisciplinary understanding of the results of this procedure.
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27.
  • Dib, Lea, et al. (författare)
  • Lipid-associated macrophages transition to an inflammatory state in human atherosclerosis, increasing the risk of cerebrovascular complications
  • 2023
  • Ingår i: Nature Cardiovascular Research. - 2731-0590. ; 2:7, s. 656-672
  • Tidskriftsartikel (refereegranskat)abstract
    • The immune system is integral to cardiovascular health and disease. Targeting inflammation ameliorates adverse cardiovascular outcomes. Atherosclerosis, a major underlying cause of cardiovascular disease, is conceptualized as lipid-driven inflammation in which macrophages play a nonredundant role. However, evidence emerging so far from single-cell atlases suggests a dichotomy between lipid-associated and inflammatory macrophage states. Here, we present an inclusive reference atlas of human intraplaque immune cell communities. Combining single-cell RNA sequencing (scRNA-seq) of human surgical carotid endarterectomies in a discovery cohort with bulk RNA-seq and immunohistochemistry in a validation cohort (the Carotid Plaque Imaging Project), we reveal the existence of PLIN2hi/TREM1hi macrophages as a Toll-like receptor (TLR)-dependent inflammatory lipid-associated macrophage state linked to cerebrovascular events. Our study shifts the current paradigm of lipid-driven inflammation by providing biological evidence for a pathogenic macrophage transition to an inflammatory lipid-associated phenotype and for its targeting as a new treatment strategy for cardiovascular disease.
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28.
  • Doust, C, et al. (författare)
  • Discovery of 42 genome-wide significant loci associated with dyslexia
  • 2022
  • Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:11, s. 1621-
  • Tidskriftsartikel (refereegranskat)abstract
    • Reading and writing are crucial life skills but roughly one in ten children are affected by dyslexia, which can persist into adulthood. Family studies of dyslexia suggest heritability up to 70%, yet few convincing genetic markers have been found. Here we performed a genome-wide association study of 51,800 adults self-reporting a dyslexia diagnosis and 1,087,070 controls and identified 42 independent genome-wide significant loci: 15 in genes linked to cognitive ability/educational attainment, and 27 new and potentially more specific to dyslexia. We validated 23 loci (13 new) in independent cohorts of Chinese and European ancestry. Genetic etiology of dyslexia was similar between sexes, and genetic covariance with many traits was found, including ambidexterity, but not neuroanatomical measures of language-related circuitry. Dyslexia polygenic scores explained up to 6% of variance in reading traits, and might in future contribute to earlier identification and remediation of dyslexia.
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29.
  • Forteza, Maria J., et al. (författare)
  • Pyruvate dehydrogenase kinase regulates vascular inflammation in atherosclerosis and increases cardiovascular risk
  • 2023
  • Ingår i: Cardiovascular Research. - : Oxford University Press (OUP). - 0008-6363 .- 1755-3245. ; 119:7, s. 1524-1536
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent studies have revealed a close connection between cellular metabolism and the chronic inflammatory process of atherosclerosis. While the link between systemic metabolism and atherosclerosis is well established, the implications of altered metabolism in the artery wall are less understood. Pyruvate dehydrogenase kinase (PDK)-dependent inhibition of pyruvate dehydrogenase (PDH) has been identified as a major metabolic step regulating inflammation. Whether the PDK/PDH axis plays a role in vascular inflammation and atherosclerotic cardiovascular disease remains unclear. Methods and results Gene profiling of human atherosclerotic plaques revealed a strong correlation between PDK1 and PDK4 transcript levels and the expression of pro-inflammatory and destabilizing genes. Remarkably, the PDK1 and PDK4 expression correlated with a more vulnerable plaque phenotype, and PDK1 expression was found to predict future major adverse cardiovascular events. Using the small-molecule PDK inhibitor dichloroacetate (DCA) that restores arterial PDH activity, we demonstrated that the PDK/PDH axis is a major immunometabolic pathway, regulating immune cell polarization, plaque development, and fibrous cap formation in Apoe−/− mice. Surprisingly, we discovered that DCA regulates succinate release and mitigates its GPR91-dependent signals promoting NLRP3 inflammasome activation and IL-1β secretion by macrophages in the plaque. Conclusions We have demonstrated for the first time that the PDK/PDH axis is associated with vascular inflammation in humans and particularly that the PDK1 isozyme is associated with more severe disease and could predict secondary cardiovascular events. Moreover, we demonstrate that targeting the PDK/PDH axis with DCA skews the immune system, inhibits vascular inflammation and atherogenesis, and promotes plaque stability features in Apoe−/− mice. These results point toward a promising treatment to combat atherosclerosis.
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30.
  • Shami, Annelie, et al. (författare)
  • Glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) drives atherosclerosis in mice and is associated with an unstable plaque phenotype and cerebrovascular events in humans
  • 2020
  • Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 41:31, s. 2938-2948
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS: GITR-a co-stimulatory immune checkpoint protein-is known for both its activating and regulating effects on T-cells. As atherosclerosis bears features of chronic inflammation and autoimmunity, we investigated the relevance of GITR in cardiovascular disease (CVD). METHODS AND RESULTS: GITR expression was elevated in carotid endarterectomy specimens obtained from patients with cerebrovascular events (n = 100) compared to asymptomatic patients (n = 93) and correlated with parameters of plaque vulnerability, including plaque macrophage, lipid and glycophorin A content, and levels of interleukin (IL)-6, IL-12, and C-C-chemokine ligand 2. Soluble GITR levels were elevated in plasma from subjects with CVD compared to healthy controls. Plaque area in 28-week-old Gitr-/-Apoe-/- mice was reduced, and plaques had a favourable phenotype with less macrophages, a smaller necrotic core and a thicker fibrous cap. GITR deficiency did not affect the lymphoid population. RNA sequencing of Gitr-/-Apoe-/- and Apoe-/- monocytes and macrophages revealed altered pathways of cell migration, activation, and mitochondrial function. Indeed, Gitr-/-Apoe-/- monocytes displayed decreased integrin levels, reduced recruitment to endothelium, and produced less reactive oxygen species. Likewise, GITR-deficient macrophages produced less cytokines and had a reduced migratory capacity. CONCLUSION: Our data reveal a novel role for the immune checkpoint GITR in driving myeloid cell recruitment and activation in atherosclerosis, thereby inducing plaque growth and vulnerability. In humans, elevated GITR expression in carotid plaques is associated with a vulnerable plaque phenotype and adverse cerebrovascular events. GITR has the potential to become a novel therapeutic target in atherosclerosis as it reduces myeloid cell recruitment to the arterial wall and impedes atherosclerosis progression.
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31.
  • Solmi, Marco, et al. (författare)
  • Balancing risks and benefits of cannabis use: umbrella review of meta-analyses of randomised controlled trials and observational studies
  • 2023
  • Ingår i: BMJ. British Medical Journal. - : BMJ PUBLISHING GROUP. - 0959-8146 .- 0959-535X. ; 382
  • Forskningsöversikt (refereegranskat)abstract
    • OBJECTIVE To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs). DESIGN Umbrella review. DATA SOURCES PubMed, PsychInfo, Embase, up to 9 February 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted. RESULTS 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse event, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses); in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive). CONCLUSIONS Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine, but not without adverse events.
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32.
  • Solmi, Marco, et al. (författare)
  • Physical and mental health impact of COVID-19 on children, adolescents, and their families :
  • 2022
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 367-376
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The COVID-19 pandemic has altered daily routines and family functioning, led to closing schools, and dramatically limited social interactions worldwide. Measuring its impact on mental health of vulnerable children and adolescents is crucial. Methods: The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT - www. coh-fit.com) is an on-line anonymous survey, available in 30 languages, involving >230 investigators from 49 countries supported by national/international professional associations. COH-FIT has thee waves (until the pandemic is declared over by the WHO, and 6-18 months plus 24-36 months after its end). In addition to adults, COH-FIT also includes adolescents (age 14-17 years), and children (age 6-13 years), recruited via nonprobability/snowball and representative sampling and assessed via self-rating and parental rating. Nonmodifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to promote health and prevent mental and physical illness in children and adolescents will be generated by COH-FIT. Co primary outcomes are changes in well-being (WHO-5) and a composite psychopathology P-Score. Multiple behavioral, family, coping strategy and service utilization factors are also assessed, including functioning and quality of life. Results: Up to June 2021, over 13,000 children and adolescents from 59 countries have participated in the COHFIT project, with representative samples from eleven countries. Limitations: Cross-sectional and anonymous design. Conclusions: Evidence generated by COH-FIT will provide an international estimate of the COVID-19 effect on childrens, adolescents and families, mental and physical health, well-being, functioning and quality of life, informing the formulation of present and future evidence-based interventions and policies to minimize adverse effects of the present and future pandemics on youth.
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33.
  • Solmi, Marco, et al. (författare)
  • The collaborative outcomes study on health and functioning during infection times in adults (COH-FIT-Adults) : Design and methods of an international online survey targeting physical and mental health effects of the COVID-19 pandemic
  • 2022
  • Ingår i: Journal of Affective Disorders. - : Elsevier. - 0165-0327 .- 1573-2517. ; 299, s. 393-407
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: . High-quality comprehensive data on short-/long-term physical/mental health effects of the COVID-19 pandemic are needed. Methods: . The Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) is an international, multi-language (n=30) project involving >230 investigators from 49 countries/territories/regions, endorsed by national/international professional associations. COH-FIT is a multi-wave, on-line anonymous, cross-sectional survey [wave 1: 04/2020 until the end of the pandemic, 12 months waves 2/3 starting 6/24 months threreafter] for adults, adolescents (14-17), and children (6-13), utilizing non-probability/snowball and representative sampling. COH-FIT aims to identify non-modifiable/modifiable risk factors/treatment targets to inform prevention/intervention programs to improve social/health outcomes in the general population/vulnerable subgrous during/after COVID-19. In adults, co-primary outcomes are change from pre-COVID-19 to intra-COVID-19 in well-being (WHO-5) and a composite psychopathology P-Score. Key secondary outcomes are a P-extended score, global mental and physical health. Secondary outcomes include health-service utilization/ functioning, treatment adherence, functioning, symptoms/behaviors/emotions, substance use, violence, among others. Results: . Starting 04/26/2020, up to 14/07/2021 >151,000 people from 155 countries/territories/regions and six continents have participated. Representative samples of >= 1,000 adults have been collected in 15 countries. Overall, 43.0% had prior physical disorders, 16.3% had prior mental disorders, 26.5% were health care workers, 8.2% were aged >= 65 years, 19.3% were exposed to someone infected with COVID-19, 76.1% had been in quarantine, and 2.1% had been COVID 19-positive. Limitations: . Cross-sectional survey, preponderance of non-representative participants. Conclusions: . Results from COH-FIT will comprehensively quantify the impact of COVID-19, seeking to identify high-risk groups in need for acute and long-term intervention, and inform evidence-based health policies/strategies during this/future pandemics.
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34.
  • Solmi, Marco, et al. (författare)
  • Validation of the Collaborative Outcomes study on Health and Functioning during Infection Times (COH-FIT) questionnaire for adults
  • 2023
  • Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 249-261
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the in-ternal validity of the co-primary outcome, a composite psychopathology "P-score". Methods: The COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r >= 0.5 with validated companion question-naires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed. Results: From >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (omega = 0.95). Factor structure was consistent across age and sex. Conclusions: COH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.
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35.
  • Zeppa, Pio, et al. (författare)
  • Announcement : The International System for Reporting Lymph Node Cytopathology
  • 2020
  • Ingår i: Acta Cytologica. - : S. Karger AG. - 0001-5547 .- 1938-2650. ; 64:4, s. 299-305
  • Forskningsöversikt (refereegranskat)abstract
    • Fine needle aspiration biopsy cytopathology (FNAC) of lymph nodes is a very common, inexpensive, and rapid diagnostic procedure and can lead to the accurate and timely diagnosis of one of the wide range of pathological processes that involve lymph nodes. These diagnoses include specific reactive processes, specific infections such as tuberculosis, metastatic carcinomas and melanomas, and some lymphomas. The FNAC effectively triages the lymph node material, but the initial diagnosis often requires ancillary testing as a second diagnostic step to make a specific diagnosis, such as the particular infectious agent, the type of lymphoma or Hodgkin lymphoma, or the specific type of metastatic malignancy. An international group of cytopathologists have begun the process of developing a system for the standardized reporting of lymph node FNAC. The group is addressing the pre-analytical issues related to the FNAC, including the role of clinical information and the use of ultrasound, and developing a structure of reporting categories based on the cytopathological findings linked to management recommendations. The basis of the system is the integration of the FNAC with the clinical setting, imaging, and ancillary tests that utilize the FNAC material, to produce a final report that will enhance patient care.
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