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1.	Aad, G, et al. (author) 2015 swepub:Mat__t
2.	Bonaca, MP, et al. (author) Long-term use of ticagrelor in patients with prior myocardial infarction 2015 In: The New England journal of medicine. - 1533-4406. ; 372:19, s. 1791-1800 Journal article (peer-reviewed)
3.	Bousquet, J, et al. (author) Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19 2021 In: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 76:3, s. 735-750 Journal article (peer-reviewed)
4.	Bousquet, J, et al. (author) Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies 2020 In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58- Journal article (peer-reviewed)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.
5.	Aaron, F. D., et al. (author) Multi-leptons with high transverse momentum at HERA 2009 In: Journal of High Energy Physics. - : Springer Science and Business Media LLC. - 1029-8479. ; :10 Journal article (peer-reviewed)abstract Events with at least two high transverse momentum leptons (electrons or muons) are studied using the H1 and ZEUS detectors at HERA with an integrated luminosity of 0.94 fb(-1). The observed numbers of events are in general agreement with the Standard Model predictions. Seven di- and tri-lepton events are observed in e(+)p collision data with a scalar sum of the lepton transverse momenta above 100 GeV while 1.94 +/- 0.17 events are expected. Such events are not observed in e(-)p collisions for which 1.19 +/- 0.12 are predicted. Total visible and differential di-electron and di-muon photoproduction cross sections are extracted in a restricted phase space dominated by photon-photon collisions.
6.	Aaron, F. D., et al. (author) Combined inclusive diffractive cross sections measured with forward proton spectrometers in deep inelastic ep scattering at HERA 2012 In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 72:10 Journal article (peer-reviewed)abstract A combination of the inclusive diffractive cross section measurements made by the H1 and ZEUS Collaborations at HERA is presented. The analysis uses samples of diffractive deep inelastic ep scattering data at a centre-of-mass energy root s = 318 GeV where leading protons are detected by dedicated spectrometers. Correlations of systematic uncertainties are taken into account, resulting in an improved precision of the cross section measurement which reaches 6 % for the most precise points. The combined data cover the range 2.5 < Q(2) < 200 GeV2 in photon virtuality, 0.00035 < x(P) < 0.09 in proton fractional momentum loss, 0.09 < vertical bar t vertical bar < 0.55 GeV2 in squared four-momentum transfer at the proton vertex and 0.0018 < beta < 0.816 in beta = x/x(P), where x is the Bjorken scaling variable.
7.	Aaron, F. D., et al. (author) Combined measurement and QCD analysis of the inclusive e(+/-)p scattering cross sections at HERA 2010 In: Journal of High Energy Physics. - 1029-8479. ; :1 Journal article (peer-reviewed)abstract A combination is presented of the inclusive deep inelastic cross sections measured by the H1 and ZEUS Collaborations in neutral and charged current unpolarised e(+/-)p scattering at HERA during the period 1994-2000. The data span six orders of magnitude in negative four-momentum-transfer squared, Q(2), and in Bjorken x. The combination method used takes the correlations of systematic uncertainties into account, resulting in an improved accuracy. The combined data are the sole input in a NLO QCD analysis which determines a new set of parton distributions, HERAPDF1.0, with small experimental uncertainties. This set includes an estimate of the model and parametrisation uncertainties of the fit result.
8.	Aaron, F. D., et al. (author) Events with an isolated lepton and missing transverse momentum and measurement of W production at HERA 2010 In: Journal of High Energy Physics. - 1029-8479. ; 2010:3, s. 1-19 Journal article (peer-reviewed)abstract A search for events containing an isolated electron or muon and missing trans verse momentum produced in e(+/-)p collisions is performed with the H1 and ZEUS detectors at HERA. The data were taken in the period 1994-2007 and correspond to an integrated luminosity of 0.98 fb(-1). The observed event yields are in good overall agreement with the Standard Model prediction, which is dominated by single W production. In the e(+)p data, at large hadronic transverse momentum P-T(X) > 25GeV, a total of 23 events are observed compared to a prediction of 14.0 +/- 1.9. The total single W boson production cross section is measured as 1.06 +/- 0.16 (stat.) +/- 0.07 (sys.) pb, in agreement with an Standard Model (SM) expectation of 1.26 +/- 0.19 pb.
9.	Abdellaoui, G., et al. (author) Meteor studies in the framework of the JEM-EUSO program 2017 In: Planetary and Space Science. - : Elsevier. - 0032-0633 .- 1873-5088. ; 143, s. 245-255 Journal article (peer-reviewed)abstract We summarize the state of the art of a program of UV observations from space of meteor phenomena, a secondary objective of the JEM-EUSO international collaboration. Our preliminary analysis indicates that JEM-EUSO, taking advantage of its large FOV and good sensitivity, should be able to detect meteors down to absolute magnitude close to 7. This means that JEM-EUSO should be able to record a statistically significant flux of meteors, including both sporadic ones, and events produced by different meteor streams. Being unaffected by adverse weather conditions, JEM-EUSO can also be a very important facility for the detection of bright meteors and fireballs, as these events can be detected even in conditions of very high sky background. In the case of bright events, moreover, exhibiting some persistence of the meteor train, preliminary simulations show that it should be possible to exploit the motion of the ISS itself and derive at least a rough 3D reconstruction of the meteor trajectory. Moreover, the observing strategy developed to detect meteors may also be applied to the detection of nuclearites, exotic particles whose existence has been suggested by some theoretical investigations. Nuclearites are expected to move at higher velocities than meteoroids, and to exhibit a wider range of possible trajectories, including particles moving upward after crossing the Earth. Some pilot studies, including the approved Mini-EUSO mission, a precursor of JEM-EUSO, are currently operational or in preparation. We are doing simulations to assess the performance of Mini-EUSO for meteor studies, while a few meteor events have been already detected using the ground-based facility EUSO-TA.
10.	Abdellaoui, G., et al. (author) First observations of speed of light tracks by a fluorescence detector looking down on the atmosphere 2018 In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 13 Journal article (peer-reviewed)abstract EUSO-Balloon is a pathfinder mission for the Extreme Universe Space Observatory onboard the Japanese Experiment Module (JEM-EUSO). It was launched on the moonless night of the 25(th) of August 2014 from Timmins, Canada. The flight ended successfully after maintaining the target altitude of 38 km for five hours. One part of the mission was a 2.5 hour underflight using a helicopter equipped with three UV light sources (LED, xenon flasher and laser) to perform an inflight calibration and examine the detectors capability to measure tracks moving at the speed of light. We describe the helicopter laser system and details of the underflight as well as how the laser tracks were recorded and found in the data. These are the first recorded laser tracks measured from a fluorescence detector looking down on the atmosphere. Finally, we present a first reconstruction of the direction of the laser tracks relative to the detector.
11.	Abramowicz, H., et al. (author) Combination and QCD analysis of charm production cross section measurements in deep-inelastic ep scattering at HERA 2013 In: European Physical Journal C. Particles and Fields. - : Springer Science and Business Media LLC. - 1434-6044. ; 73:2 Journal article (peer-reviewed)abstract Measurements of open charm production cross sections in deep-inelastic ep scattering at HERA from the H1 and ZEUS Collaborations are combined. Reduced cross sections sigma(c (c) over bar)(red) for charm production are obtained in the kinematic range of photon virtuality 2.5 <= Q(2) <= 2000 GeV2 and Bjorken scaling variable 3 . 10(-5) <= x <= 5 . 10(-2). The combination method accounts for the correlations of the systematic uncertainties among the different data sets. The combined charm data together with the combined inclusive deep-inelastic scattering cross sections from HERA are used as input for a detailed NLO QCD analysis to study the influence of different heavy flavour schemes on the parton distribution functions. The optimal values of the charm mass as a parameter in these different schemes are obtained. The implications on the NLO predictions for W-+/- and Z production cross sections at the LHC are investigated. Using the fixed flavour number scheme, the running mass of the charm quark is determined.
12.	Gilmore, G., et al. (author) The Gaia-ESO Public Spectroscopic Survey : Motivation, implementation, GIRAFFE data processing, analysis, and final data products star 2022 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 666 Journal article (peer-reviewed)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.
13.	Malago, M, et al. (author) Outcomes of elective liver surgery worldwide: a global, prospective, multicenter, cross-sectional study 2023 In: International journal of surgery (London, England). - 1743-9159. ; 109:12, s. 3954-3966 Journal article (peer-reviewed)
14.	Randich, S., et al. (author) The Gaia-ESO Public Spectroscopic Survey : Implementation, data products, open cluster survey, science, and legacy 2022 In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 666 Journal article (peer-reviewed)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.
15.	O'Dushlaine, C, et al. (author) Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways 2015 In: Nature neuroscience. - : Springer Science and Business Media LLC. - 1546-1726 .- 1097-6256. ; 18:2, s. 199-209 Journal article (peer-reviewed)
16.	Lee, SH, et al. (author) Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs 2013 In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:9, s. 984- Journal article (peer-reviewed)
17.	Stroth, U., et al. (author) Progress from ASDEX Upgrade experiments in preparing the physics basis of ITER operation and DEMO scenario development 2022 In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 62:4 Journal article (peer-reviewed)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.
18.	Altavilla, R., et al. (author) Anticoagulation After Stroke in Patients With Atrial Fibrillation: To Bridge or Not With Low-Molecular-Weight Heparin? 2019 In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 50:8, s. 2093-2100 Journal article (peer-reviewed)abstract Background and Purpose- Bridging therapy with low-molecular-weight heparin reportedly leads to a worse outcome for acute cardioembolic stroke patients because of a higher incidence of intracerebral bleeding. However, this practice is common in clinical settings. This observational study aimed to compare (1) the clinical profiles of patients receiving and not receiving bridging therapy, (2) overall group outcomes, and (3) outcomes according to the type of anticoagulant prescribed. Methods- We analyzed data of patients from the prospective RAF and RAF-NOACs studies. The primary outcome was defined as the composite of ischemic stroke, transient ischemic attack, systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding observed at 90 days after the acute stroke. Results- Of 1810 patients who initiated oral anticoagulant therapy, 371 (20%) underwent bridging therapy with full-dose low-molecular-weight heparin. Older age and the presence of leukoaraiosis were inversely correlated with the use of bridging therapy. Forty-two bridged patients (11.3%) reached the combined outcome versus 72 (5.0%) of the nonbridged patients (P=0.0001). At multivariable analysis, bridging therapy was associated with the composite end point (odds ratio, 2.3; 95% CI, 1.4-3.7; P<0.0001), as well as ischemic (odds ratio, 2.2; 95% CI, 1.3-3.9; P=0.005) and hemorrhagic (odds ratio, 2.4; 95% CI, 1.2-4.9; P=0.01) end points separately. Conclusions- Our findings suggest that patients receiving low-molecular-weight heparin have a higher risk of early ischemic recurrence and hemorrhagic transformation compared with nonbridged patients.
19.	Meyer, H.F., et al. (author) Overview of physics studies on ASDEX Upgrade 2019 In: Nuclear Fusion. - : IOP Publishing. - 1741-4326 .- 0029-5515. ; 59:11 Research review (peer-reviewed)abstract The ASDEX Upgrade (AUG) programme, jointly run with the EUROfusion MST1 task force, continues to significantly enhance the physics base of ITER and DEMO. Here, the full tungsten wall is a key asset for extrapolating to future devices. The high overall heating power, flexible heating mix and comprehensive diagnostic set allows studies ranging from mimicking the scrape-off-layer and divertor conditions of ITER and DEMO at high density to fully non-inductive operation (q 95 = 5.5, ) at low density. Higher installed electron cyclotron resonance heating power 6 MW, new diagnostics and improved analysis techniques have further enhanced the capabilities of AUG. Stable high-density H-modes with MW m-1 with fully detached strike-points have been demonstrated. The ballooning instability close to the separatrix has been identified as a potential cause leading to the H-mode density limit and is also found to play an important role for the access to small edge-localized modes (ELMs). Density limit disruptions have been successfully avoided using a path-oriented approach to disruption handling and progress has been made in understanding the dissipation and avoidance of runaway electron beams. ELM suppression with resonant magnetic perturbations is now routinely achieved reaching transiently . This gives new insight into the field penetration physics, in particular with respect to plasma flows. Modelling agrees well with plasma response measurements and a helically localised ballooning structure observed prior to the ELM is evidence for the changed edge stability due to the magnetic perturbations. The impact of 3D perturbations on heat load patterns and fast-ion losses have been further elaborated. Progress has also been made in understanding the ELM cycle itself. Here, new fast measurements of and E r allow for inter ELM transport analysis confirming that E r is dominated by the diamagnetic term even for fast timescales. New analysis techniques allow detailed comparison of the ELM crash and are in good agreement with nonlinear MHD modelling. The observation of accelerated ions during the ELM crash can be seen as evidence for the reconnection during the ELM. As type-I ELMs (even mitigated) are likely not a viable operational regime in DEMO studies of 'natural' no ELM regimes have been extended. Stable I-modes up to have been characterised using -feedback. Core physics has been advanced by more detailed characterisation of the turbulence with new measurements such as the eddy tilt angle - measured for the first time - or the cross-phase angle of and fluctuations. These new data put strong constraints on gyro-kinetic turbulence modelling. In addition, carefully executed studies in different main species (H, D and He) and with different heating mixes highlight the importance of the collisional energy exchange for interpreting energy confinement. A new regime with a hollow profile now gives access to regimes mimicking aspects of burning plasma conditions and lead to nonlinear interactions of energetic particle modes despite the sub-Alfvénic beam energy. This will help to validate the fast-ion codes for predicting ITER and DEMO.
20.	Paciaroni, M., et al. (author) Hemorrhagic transformation in patients with acute ischemic stroke and atrial fibrillation: Time to initiation of oral anticoagulant therapy and outcomes 2018 In: Journal of the American Heart Association. - 2047-9980. ; 7:22 Journal article (peer-reviewed)abstract Background—In patients with acute ischemic stroke and atrial fibrillation, early anticoagulation prevents ischemic recurrence but with the risk of hemorrhagic transformation (HT). The aims of this study were to evaluate in consecutive patients with acute stroke and atrial fibrillation (1) the incidence of early HT, (2) the time to initiation of anticoagulation in patients with HT, (3) the association of HT with ischemic recurrences, and (4) the association of HT with clinical outcome at 90 days. Methods and Results—HT was diagnosed by a second brain computed tomographic scan performed 24 to 72 hours after stroke onset. The incidence of ischemic recurrences as well as mortality or disability (modified Rankin Scale scores >2) were evaluated at 90 days. Ischemic recurrences were the composite of ischemic stroke, transient ischemic attack, or systemic embolism. Among the 2183 patients included in the study, 241 (11.0%) had HT. Patients with and without HT initiated anticoagulant therapy after a mean 23.3 and 11.6 days, respectively, from index stroke. At 90 days, 4.6% (95% confidence interval, 2.3-8.0) of the patients with HT had ischemic recurrences compared with 4.9% (95% confidence interval, 4.0-6.0) of those without HT; 53.1% of patients with HT were deceased or disabled compared with 35.8% of those without HT. On multivariable analysis, HT was associated with mortality or disability (odds ratio, 1.71; 95% confidence interval, 1.24-2.35). Conclusions—In patients with HT, anticoagulation was initiated about 12 days later than patients without HT. This delay was not associated with increased detection of ischemic recurrence. HT was associated with increased mortality or disability. © 2018 The Authors.
21.	Paciaroni, M., et al. (author) Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes 2020 In: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. Journal article (peer-reviewed)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.
22.	Paciaroni, M., et al. (author) Prediction of Early Recurrent Thromboembolic Event and Major Bleeding in Patients With Acute Stroke and Atrial Fibrillation by a Risk Stratification Schema The ALESSA Score Study 2017 In: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 48:3, s. 726-732 Journal article (peer-reviewed)abstract Background and Purposes-This study was designed to derive and validate a score to predict early ischemic events and major bleedings after an acute ischemic stroke in patients with atrial fibrillation. Methods-The derivation cohort consisted of 854 patients with acute ischemic stroke and atrial fibrillation included in prospective series between January 2012 and March 2014. Older age (hazard ratio 1.06 for each additional year; 95% confidence interval, 1.00-1.11) and severe atrial enlargement (hazard ratio, 2.05; 95% confidence interval, 1.08-2.87) were predictors for ischemic outcome events (stroke, transient ischemic attack, and systemic embolism) at 90 days from acute stroke. Small lesions (1.5 cm) were inversely correlated with both major bleeding (hazard ratio, 0.39; P=0.03) and ischemic outcome events (hazard ratio, 0.55; 95% confidence interval, 0.30-1.00). We assigned to age 80 years 2 points and between 70 and 79 years 1 point; ischemic index lesion >1.5 cm, 1 point; severe atrial enlargement, 1 point (ALESSA score). A logistic regression with the receiver-operating characteristic graph procedure (C statistic) showed an area under the curve of 0.697 (0.632-0.763; P=0.0001) for ischemic outcome events and 0.585 (0.493-0.678; P=0.10) for major bleedings. Results-The validation cohort consisted of 994 patients included in prospective series between April 2014 and June 2016. Logistic regression with the receiver-operating characteristic graph procedure showed an area under the curve of 0.646 (0.529-0.763; P=0.009) for ischemic outcome events and 0.407 (0.275-0.540; P=0.14) for hemorrhagic outcome events. Conclusions-In acute stroke patients with atrial fibrillation, high ALESSA scores were associated with a high risk of ischemic events but not of major bleedings.
23.	Tobias, Deirdre K, et al. (author) Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine 2023 In: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457 Research review (peer-reviewed)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.
24.	Weiner, D. J., et al. (author) Polygenic transmission disequilibrium confirms that common and rare variation act additively to create risk for autism spectrum disorders 2017 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:7 Journal article (peer-reviewed)abstract Autism spectrum disorder (ASD) risk is influenced by common polygenic and de novo variation. We aimed to clarify the influence of polygenic risk for ASD and to identify subgroups of ASD cases, including those with strongly acting de novo variants, in which polygenic risk is relevant. Using a novel approach called the polygenic transmission disequilibrium test and data from 6,454 families with a child with ASD, we show that polygenic risk for ASD, schizophrenia, and greater educational attainment is over-transmitted to children with ASD. These findings hold independent of proband IQ. We find that polygenic variation contributes additively to risk in ASD cases who carry a strongly acting de novo variant. Lastly, we show that elements of polygenic risk are independent and differ in their relationship with phenotype. These results confirm that the genetic influences on ASD are additive and suggest that they create risk through at least partially distinct etiologic pathways.
25.	Anney, R. J. L., et al. (author) Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia 2017 In: Molecular Autism. - : Springer Science and Business Media LLC. - 2040-2392. ; 8 Journal article (peer-reviewed)abstract Background: Over the past decade genome-wide association studies (GWAS) have been applied to aid in the understanding of the biology of traits. The success of this approach is governed by the underlying effect sizes carried by the true risk variants and the corresponding statistical power to observe such effects given the study design and sample size under investigation. Previous ASD GWAS have identified genome-wide significant (GWS) risk loci; however, these studies were of only of low statistical power to identify GWS loci at the lower effect sizes (odds ratio (OR) < 1.15). Methods: We conducted a large-scale coordinated international collaboration to combine independent genotyping data to improve the statistical power and aid in robust discovery of GWS loci. This study uses genome-wide genotyping data from a discovery sample (7387 ASD cases and 8567 controls) followed by meta-analysis of summary statistics from two replication sets (7783 ASD cases and 11359 controls; and 1369 ASD cases and 137308 controls). Results: We observe a GWS locus at 10q24.32 that overlaps several genes including PITX3, which encodes a transcription factor identified as playing a role in neuronal differentiation and CUEDC2 previously reported to be associated with social skills in an independent population cohort. We also observe overlap with regions previously implicated in schizophrenia which was further supported by a strong genetic correlation between these disorders (Rg = 0.23; P= 9 x10(-6)). We further combined these Psychiatric Genomics Consortium (PGC) ASD GWAS data with the recent PGC schizophrenia GWAS to identify additional regions which may be important in a common neurodevelopmental phenotype and identified 12 novel GWS loci. These include loci previously implicated in ASD such as FOXP1 at 3p13, ATP2B2 at 3p25.3, and a 'neurodevelopmental hub' on chromosome 8p11.23. Conclusions: This study is an important step in the ongoing endeavour to identify the loci which underpin the common variant signal in ASD. In addition to novel GWS loci, we have identified a significant genetic correlation with schizophrenia and association of ASD with several neurodevelopmental- related genes such as EXT1, ASTN2, MACROD2, and HDAC4.
26.	Elhai, M, et al. (author) Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study 2019 In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 78:7, s. 979-987 Journal article (peer-reviewed)abstract To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice.MethodsWe performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab.Results254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47–5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55–1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56–3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83–9.62]; p=0.019 as compared with controls vs 3 [0.66–5.35]; p=0.012).ConclusionRituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.
27.	Giustozzi, M., et al. (author) Safety of Anticoagulation in Patients Treated with Urgent Reperfusion for Ischemic Stroke Related to Atrial Fibrillation 2020 In: Stroke. - 0039-2499. ; 51:8, s. 2347-2354 Journal article (peer-reviewed)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.
28.	Sobanski, V, et al. (author) Phenotypes Determined by Cluster Analysis and Their Survival in the Prospective European Scleroderma Trials and Research Cohort of Patients With Systemic Sclerosis 2019 In: Arthritis & rheumatology (Hoboken, N.J.). - : Wiley. - 2326-5205 .- 2326-5191. ; 71:9, s. 1553-1570 Journal article (peer-reviewed)
29.	Solmi, M, et al. (author) 2022 In: Journal of affective disorders. - : Elsevier BV. - 1573-2517 .- 0165-0327. ; 299, s. 367-376 Journal article (peer-reviewed)
30.	Anney, Richard, et al. (author) A genome-wide scan for common alleles affecting risk for autism. 2010 In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082 Journal article (peer-reviewed)abstract Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
31.	Magrini, L., et al. (author) The Gaia -ESO survey: Mixing processes in low-mass stars traced by lithium abundance in cluster and field stars 2021 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651 Journal article (peer-reviewed)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.
32.	Paciaroni, M., et al. (author) Early Recurrence and Major Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation Treated With Non-Vitamin-K Oral Anticoagulants (RAF-NOACs) Study 2017 In: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 6:12 Journal article (peer-reviewed)abstract Background-The optimal timing to administer non-vitamin K oral anticoagulants (NOACs) in patients with acute ischemic stroke and atrial fibrillation is unclear. This prospective observational multicenter study evaluated the rates of early recurrence and major bleeding (within 90 days) and theirtiming in patients with acute ischemic stroke and atrial fibrillation who received NOACs for secondary prevention. Methods and Results-Recurrence was defined as the composite of ischemic stroke, transient ischemic attack, and symptomatic systemic embolism, and major bleeding was defined as symptomatic cerebral and major extracranial bleeding. For the analysis, 1127 patients were eligible: 381 (33.8%) were treated with dabigatran, 366 (32.5%) with rivaroxaban, and 380 (33.7%) with apixaban. Patients who received dabigatran were younger and had lower admission National Institutes of Health Stroke Scale score and less commonly had a CHA(2)DS(2)-VASc score >4 and less reduced renal function. Thirty-two patients (2.8%) had early recurrence, and 27 (2.4%) had major bleeding. The rates of early recurrence and major bleeding were, respectively, 1.8% and 0.5% in patients receiving dabigatran, 1.6% and 2.5% in those receiving rivaroxaban, and 4.0% and 2.9% in those receiving apixaban. Patients who initiated NOACs within 2 days after acute stroke had a composite rate of recurrence and major bleeding of 12.4%; composite rates were 2.1% for those who initiated NOACs between 3 and 14 days and 9.1% for those who initiated > 14 days after acute stroke. Conclusions-In patients with acute ischemic stroke and atrial fibrillation, treatment with NOACs was associated with a combined 5% rate of ischemic embolic recurrence and severe bleeding within 90 days.
33.	Pinto, Dalila, et al. (author) Functional impact of global rare copy number variation in autism spectrum disorders. 2010 In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372 Journal article (peer-reviewed)abstract The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
34.	Smiljanic, R., et al. (author) The Gaia-ESO Survey: The analysis of high-resolution UVES spectra of FGK-type stars 2014 In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 570 Journal article (peer-reviewed)abstract Context. The ongoing Gaia-ESO Public Spectroscopic Survey is using FLAMES at the VLT to obtain high-quality medium-resolution Giraffe spectra for about 10(5) stars and high-resolution UVES spectra for about 5000 stars. With UVES, the Survey has already observed 1447 FGK-type stars. Aims. These UVES spectra are analyzed in parallel by several state-of-the-art methodologies. Our aim is to present how these analyses were implemented, to discuss their results, and to describe how a final recommended parameter scale is defined. We also discuss the precision (method-to-method dispersion) and accuracy (biases with respect to the reference values) of the final parameters. These results are part of the Gaia-ESO second internal release and will be part of its first public release of advanced data products. Methods. The final parameter scale is tied to the scale defined by the Gaia benchmark stars, a set of stars with fundamental atmospheric parameters. In addition, a set of open and globular clusters is used to evaluate the physical soundness of the results. Each of the implemented methodologies is judged against the benchmark stars to define weights in three different regions of the parameter space. The final recommended results are the weighted medians of those from the individual methods. Results. The recommended results successfully reproduce the atmospheric parameters of the benchmark stars and the expected T-eff-log g relation of the calibrating clusters. Atmospheric parameters and abundances have been determined for 1301 FGK-type stars observed with UVES. The median of the method-to-method dispersion of the atmospheric parameters is 55K for T-eff, 0.13dex for log g and 0.07 dex for [Fe/H]. Systematic biases are estimated to be between 50-100 K for T-eff, 0.10-0.25 dex for log g and 0.05-0.10 dex for [Fe/H]. Abundances for 24 elements were derived: C, N, O, Na, Mg, Al, Si, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Y, Zr, Mo, Ba, Nd, and Eu. The typical method-to-method dispersion of the abundances varies between 0.10 and 0.20 dex. Conclusions. The Gaia-ESO sample of high-resolution spectra of FGK-type stars will be among the largest of its kind analyzed in a homogeneous way. The extensive list of elemental abundances derived in these stars will enable significant advances in the areas of stellar evolution and Milky Way formation and evolution.
35.	Acciarresi, M., et al. (author) Prestroke CHA(2)DS(2)-VASc Score and Severity of Acute Stroke in Patients with Atrial Fibrillation: Findings from RAF Study 2017 In: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057. ; 26:6, s. 1363-1368 Journal article (peer-reviewed)abstract Background and Purpose: The aim of this study was to investigate for a possible association between both prestroke CHA(2)DS(2)-VASc score and the severity of stroke at presentation, as well as disability and mortality at 90 days, in patients with acute stroke and atrial fibrillation (AF). Methods: This prospective study enrolled consecutive patients with acute ischemic stroke, AF, and assessment of prestroke CHA2DS2-VASc score. Severity of stroke was assessed on admission using the National Institutes of Health Stroke Scale (NIHSS) score (severe stroke: NIHSS >= 10). Disability and mortality at 90 days were assessed by the modified Rankin Scale (mRS < 3 or >= 3). Multiple logistic regression was used to correlate prestroke CHA(2)DS(2)-VASc and severity of stroke, as well as disability and mortality at 90 days. Results: Of the 1020 patients included in the analysis, 606 patients had an admission NIHSS score lower and 414 patients higher than 10. At 90 days, 510 patients had mRS >= 3. A linear correlation was found between the prestroke CHA(2)DS(2)-VASc score and severity of stroke (P = .001). On multivariate analysis, CHA(2)DS(2)-VASc score correlated with severity of stroke (P = .041) and adverse functional outcome (mRS = 3) (P = .001). A logistic regression with the receiver operating characteristic graph procedure (C-statistics) evidenced an area under the curve of .60 (P = .0001) for severe stroke. Furthermore, a correlation was found between prestroke CHA(2)DS(2)-VASc score and lesion size. Conclusions: In patients with AF, in addition to the risk of stroke, a high CHA(2)DS(2)-VASc score was independently associated with both stroke severity at onset and disability and mortality at 90 days.
36.	Anney, Richard, et al. (author) Individual common variants exert weak effects on the risk for autism spectrum disorders. 2012 In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92 Journal article (peer-reviewed)abstract While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
37.	Bousquet, J., et al. (author) Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA 2017 In: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104 Journal article (peer-reviewed)abstract The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
38.	Bouvier, J., et al. (author) The Gaia-ESO Survey: A lithium-rotation connection at 5 Myr? 2016 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 590 Journal article (peer-reviewed)abstract Context. The evolution of lithium abundance in cool dwarfs provides a unique probe of nonstandard processes in stellar evolution. Aims. We investigate the lithium content of young low-mass stars in the 5 Myr old, star forming region NGC 2264 and its relationship with rotation. Methods. We combine lithium equivalent width measurements (EW(Li)) from the Gaia-ESO Survey with the determination of rotational periods from the CSI 2264 survey. We only consider bona fide nonaccreting cluster members to minimize the uncertainties on EW(Li). Results. We report the existence of a relationship between lithium content and rotation in NGC 2264 at an age of 5 Myr. The Li-rotation connection is seen over a restricted temperature range (Teff = 3800-4400 K), where fast rotators are Li-rich compared to slow rotators. This correlation is similar to, albeit of lower amplitude than, the Li-rotation connection previously reported for K dwarfs in the 125 Myr old Pleiades cluster. We investigate whether the nonstandard pre-main-sequence models developed so far to explain the Pleiades results, which are based on episodic accretion, pre-main-sequence, core-envelope decoupling, and/or radius inflation due to enhanced magnetic activity, can account for early development of the Li-rotation connection. While radius inflation appears to be the most promising possibility, each of these models has issues. We therefore also discuss external causes that might operate during the first few Myr of pre-main-sequence evolution, such as planet engulfment and/or steady disk accretion, as possible candidates for the common origin for Li excess and fast rotation in young low-mass pre-main-sequence stars. Conclusions. The emergence of a connection between lithium content and rotation rate at such an early age as 5 Myr suggests a complex link between accretion processes, early angular momentum evolution, and possibly planet formation, which likely impacts early stellar evolution and has yet to be fully deciphered.
39.	Casey, A. R., et al. (author) The Gaia-ESO Survey : Revisiting the Li-rich giant problem 2016 In: Monthly Notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 461:3, s. 3336-3352 Journal article (peer-reviewed)abstract The discovery of lithium-rich giants contradicts expectations from canonical stellar evolution. Here we report on the serendipitous discovery of 20 Li-rich giants observed during the Gaia-ESO Survey, which includes the first nine Li-rich giant stars known towards the CoRoT fields. Most of our Li-rich giants have near-solar metallicities and stellar parameters consistent with being before the luminosity bump. This is difficult to reconcile with deep mixing models proposed to explain lithium enrichment, because these models can only operate at later evolutionary stages: at or past the luminosity bump. In an effort to shed light on the Li-rich phenomenon, we highlight recent evidence of the tidal destruction of close-in hot Jupiters at the sub-giant phase.We note that when coupled with models of planet accretion, the observed destruction of hot Jupiters actually predicts the existence of Li-rich giant stars, and suggests that Li-rich stars should be found early on the giant branch and occur more frequently with increasing metallicity. A comprehensive review of all known Li-rich giant stars reveals that this scenario is consistent with the data. However, more evolved or metal-poor stars are less likely to host close-in giant planets, implying that their Li-rich origin requires an alternative explanation, likely related to mixing scenarios rather than external phenomena.
40.	Lanzafame, A. C., et al. (author) Gaia-ESO Survey: Analysis of pre-main sequence stellar spectra 2015 In: Astronomy & Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576 Journal article (peer-reviewed)abstract Context. The Gaia-ESO Public Spectroscopic Survey is obtaining high-quality spectroscopy of some 100 000 Milky Way stars using the FLAMES spectrograph at the VLT, down to V = 19 mag, systematically covering all the main components of the Milky Way and providing the first homogeneous overview of the distributions of kinematics and chemical element abundances in the Galaxy. Observations of young open clusters, in particular, are giving new insights into their initial structure, kinematics, and their subsequent evolution. Aims. This paper describes the analysis of UVES and GIRAFFE spectra acquired in the fields of young clusters whose population includes pre-main sequence (PMS) stars. The analysis is applied to all stars in such fields, regardless of any prior information on membership, and provides fundamental stellar atmospheric parameters, elemental abundances, and PMS-specific parameters such as veiling, accretion, and chromospheric activity. Methods. When feasible,different methods were used to derive raw parameters (e. g. line equivalent widths) fundamental atmospheric parameters and derived parameters (e. g. abundances). To derive some of these parameters, we used methods that have been extensively used in the past and new ones developed in the context of the Gaia-ESO survey enterprise. The internal precision of these quantities was estimated by inter-comparing the results obtained by these different methods, while the accuracy was estimated by comparison with independent external data, such as effective temperature and surface gravity derived from angular diameter measurements, on a sample of benchmarks stars. A validation procedure based on these comparisons was applied to discard spurious or doubtful results and produce recommended parameters. Specific strategies were implemented to resolve problems of fast rotation, accretion signatures, chromospheric activity, and veiling. Results. The analysis carried out on spectra acquired in young cluster fields during the first 18 months of observations, up to June 2013, is presented in preparation of the first release of advanced data products. These include targets in the fields of the rho Oph, Cha I, NGC2264, gamma Vel, and NGC 2547 clusters. Stellar parameters obtained with the higher resolution and larger wavelength coverage from UVES are reproduced with comparable accuracy and precision using the smaller wavelength range and lower resolution of the GIRAFFE setup adopted for young stars, which allows us to provide stellar parameters with confidence for the much larger GIRAFFE sample. Precisions are estimated to be approximate to 120 K rms in T-eff, approximate to 0.3 dex rms in log g, and approximate to 0.15 dex rms in [Fe/H] for the UVES and GIRAFFE setups.
41.	Magrini, L., et al. (author) The Gaia-ESO Survey : the origin and evolution of s-process elements 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617 Journal article (peer-reviewed)abstract Context. Several works have found an increase of the abundances of the s-process neutron-capture elements in the youngest Galactic stellar populations. These trends provide important constraints on stellar and Galactic evolution and they need to be confirmed with large and statistically significant samples of stars spanning wide age and distance intervals. Aims. We aim to trace the abundance patterns and the time evolution of five s-process elements - two belonging to the first peak, Y and Zr, and three belonging to the second peak, Ba, La, and Ce - using the Gaia-ESO DRS results for open clusters and disc stars. Methods. From the UVES spectra of cluster member stars, we determined the average composition of clusters with ages >0.1 Gyr. We derived statistical ages and distances of field stars, and we separated them into thin and thick disc populations. We studied the time-evolution and dependence on metallicity of abundance ratios using open clusters and field stars whose parameters and abundances were derived in a homogeneous way. Results. Using our large and homogeneous sample of open clusters, thin and thick disc stars, spanning an age range larger than 10 Gyr, we confirm an increase towards young ages of s-process abundances in the solar neighbourhood. These trends are well defined for open clusters and stars located nearby the solar position and they may be explained by a late enrichment due to significant contribution to the production of these elements from long-living low-mass stars. At the same time, we find a strong dependence of the s-process abundance ratios on the Galactocentric distance and on the metallicity of the clusters and field stars. Conclusions. Our results, derived from the largest and most homogeneous sample of s-process abundances in the literature, confirm the growth with decreasing stellar ages of the s-process abundances in both field and open cluster stars. At the same time, taking advantage of the abundances of open clusters located in a wide Galactocentric range, these results offer a new perspective on the dependence of the s-process evolution on the metallicity and star formation history, pointing to different behaviours at various Galactocentric distances.
42.	Randich, S., et al. (author) The Gaia-ESO Survey : open clusters in Gaia-DR1 A way forward to stellar age calibration 2018 In: Astronomy and Astrophysics. - : EDP SCIENCES S A. - 0004-6361 .- 1432-0746. ; 612 Journal article (peer-reviewed)abstract Context. Determination and calibration of the ages of stars, which heavily rely on stellar evolutionary models, are very challenging, while representing a crucial aspect in many astrophysical areas. Aims. We describe the methodologies that, taking advantage of Gaia-DR1 and the Gaia-ESO Survey data, enable the comparison of observed open star cluster sequences with stellar evolutionary models. The final, long-term goal is the exploitation of open clusters as age calibrators.Methods. We perform a homogeneous analysis of eight open clusters using the Gaia-DR1 TGAS catalogue for bright members and information from the Gaia-ESO Survey for fainter stars. Cluster membership probabilities for the Gaia-ESO Survey targets are derived based on several spectroscopic tracers. The Gaia-ESO Survey also provides the cluster chemical composition. We obtain cluster parallaxes using two methods. The first one relies on the astrometric selection of a sample of bona fide members, while the other one fits the parallax distribution of a larger sample of TGAS sources. Ages and reddening values are recovered through a Bayesian analysis using the 2MASS magnitudes and three sets of standard models. Lithium depletion boundary (LDB) ages are also determined using literature observations and the same models employed for the Bayesian analysis.Results. For all but one cluster, parallaxes derived by us agree with those presented in Gaia Collaboration (2017, A&A, 601, A19), while a discrepancy is found for NGC 2516; we provide evidence supporting our own determination. Inferred cluster ages are robust against models and are generally consistent with literature values.Conclusions. The systematic parallax errors inherent in the Gaia DR1 data presently limit the precision of our results. Nevertheless, we have been able to place these eight clusters onto the same age scale for the first time, with good agreement between isochronal and LDB ages where there is overlap. Our approach appears promising and demonstrates the potential of combining Gaia and ground-based spectroscopic datasets.
43.	Smiljanic, R., et al. (author) The Gaia-ESO Survey : properties of newly discovered Li-rich giants 2018 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617 Journal article (peer-reviewed)abstract Aims. We report 20 new lithium-rich giants discovered within the Gaia-ESO Survey, including the first Li-rich giant with an evolutionary stage confirmed by CoRoT (Convection, Rotation and planetary Transits) data. We present a detailed overview of the properties of these 20 stars. Methods. Atmospheric parameters and abundances were derived in model atmosphere analyses using medium-resolution GIRAFFE or high-resolution UVES (Ultraviolet and Visual Echelle Spectrograph) spectra. These results are part of the fifth internal data release of the Gaia-ESO Survey. The Li abundances were corrected for non-local thermodynamical equilibrium effects. Other stellar properties were investigated for additional peculiarities (the core of strong lines for signs of magnetic activity, infrared magnitudes, rotational velocities, chemical abundances, and Galactic velocities). We used Gaia DR2 parallaxes to estimate distances and luminosities. Results. The giants have A(Li) > 2.2 dex. The majority of them (14 of 20 stars) are in the CoRoT fields. Four giants are located in the field of three open clusters, but are not members. Two giants were observed in fields towards the Galactic bulge, but likely lie in the inner disc. One of the bulge field giants is super Li-rich with A(Li) = 4.0 dex. Conclusions. We identified one giant with infrared excess at 22 mu m. Two other giants, with large v sin i, might be Li-rich because of planet engulfment. Another giant is found to be barium enhanced and thus could have accreted material from a former asymptotic giant branch companion. Otherwise, in addition to the Li enrichment, the evolutionary stages are the only other connection between these new Li-rich giants. The CoRoT data confirm that one Li-rich giant is at the core-He burning stage. The other giants are concentrated in close proximity to the red giant branch luminosity bump, the core-He burning stages, or the early-asymptotic giant branch. This is very clear from the Gaia-based luminosities of the Li-rich giants. This is also seen when the CoRoT Li-rich giants are compared to a larger sample of 2252 giants observed in the CoRoT fields by the Gaia-ESO Survey, which are distributed throughout the red giant branch in the T-eff-log g diagram. These observations show that the evolutionary stage is a major factor for the Li enrichment in giants. Other processes, such as planet accretion, contribute at a smaller scale.
44.	Spina, L., et al. (author) The Gaia-ESO Survey : the present-day radial metallicity distribution of the Galactic disc probed by pre-main-sequence clusters 2017 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 601 Journal article (peer-reviewed)abstract Context. The radial metallicity distribution in the Galactic thin disc represents a crucial constraint for modelling disc formation and evolution. Open star clusters allow us to derive both the radial metallicity distribution and its evolution over time. Aims. In this paper we perform the first investigation of the present-day radial metallicity distribution based on [Fe/H] determinations in late type members of pre-main-sequence clusters. Because of their youth, these clusters are therefore essential for tracing the current interstellar medium metallicity. Methods. We used the products of the Gaia-ESO Survey analysis of 12 young regions (age < 100 Myr), covering Galactocentric distances from 6.67 to 8.70 kpc. For the first time, we derived the metal content of star forming regions farther than 500 pc from the Sun. Median metallicities were determined through samples of reliable cluster members. For ten clusters the membership analysis is discussed in the present paper, while for other two clusters (i.e. Chamaeleon I and Gamma Velorum) we adopted the members identified in our previous works. Results. All the pre-main-sequence clusters considered in this paper have close-to-solar or slightly sub-solar metallicities. The radial metallicity distribution traced by these clusters is almost flat, with the innermost star forming regions having [Fe/H] values that are 0.10-0.15 dex lower than the majority of the older clusters located at similar Galactocentric radii. Conclusions. This homogeneous study of the present-day radial metallicity distribution in the Galactic thin disc favours models that predict a flattening of the radial gradient over time. On the other hand, the decrease of the average [Fe/H] at young ages is not easily explained by the models. Our results reveal a complex interplay of several processes (e.g. star formation activity, initial mass function, supernova yields, gas flows) that controlled the recent evolution of the Milky Way.
45.	Szatmari, Peter, et al. (author) Mapping autism risk loci using genetic linkage and chromosomal rearrangements. 2007 In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 39:3, s. 319-328 Journal article (peer-reviewed)abstract Autism spectrum disorders (ASDs) are common, heritable neurodevelopmental conditions. The genetic architecture of ASDs is complex, requiring large samples to overcome heterogeneity. Here we broaden coverage and sample size relative to other studies of ASDs by using Affymetrix 10K SNP arrays and 1,168 families with at least two affected individuals, performing the largest linkage scan to date while also analyzing copy number variation in these families. Linkage and copy number variation analyses implicate chromosome 11p12-p13 and neurexins, respectively, among other candidate loci. Neurexins team with previously implicated neuroligins for glutamatergic synaptogenesis, highlighting glutamate-related genes as promising candidates for contributing to ASDs.
46.	Adriani, O., et al. (author) A statistical procedure for the identification of positrons in the PAMELA experiment 2010 In: Astroparticle physics. - : Elsevier BV. - 0927-6505 .- 1873-2852. ; 34:1, s. 1-11 Journal article (peer-reviewed)abstract The PAMELA satellite experiment has measured the cosmic-ray positron fraction between 1.5 GeV and 100 GeV. The need to reliably discriminate between the positron signal and proton background has required the development of an ad hoc analysis procedure. In this paper, a method for positron identification is described and its stability and capability to yield a correct background estimate is shown. The analysis includes new experimental data, the application of three different fitting techniques for the background sample and an estimate of systematic uncertainties due to possible inaccuracies in the background selection. The new experimental results confirm both solar modulation effects on cosmic-rays with low rigidities and an anomalous positron abundance above 10 GeV. (c) 2010 Elsevier B.V. All rights reserved.
47.	Baratella, M., et al. (author) 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 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 653 Journal article (peer-reviewed)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.
48.	Casey, Jillian P, et al. (author) A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. 2012 In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579 Journal article (peer-reviewed)abstract Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
49.	De Simone, N., et al. (author) Latitudinal and radial gradients of galactic cosmic ray protons in the inner heliosphere - PAMELA and Ulysses observations 2011 In: Astrophysics and Space Sciences Transactions (ASTRA). - : Copernicus GmbH. - 1810-6528 .- 1810-6536. ; 7:3, s. 425-434 Journal article (peer-reviewed)abstract Ulysses, launched on 6 October 1990, was placed in an elliptical, high inclined (80.2°) orbit around the Sun, and was switched off in June 2009. It has been the only spacecraft exploring high-latitude regions of the inner heliosphere. The Kiel Electron Telescope (KET) aboard Ulysses measures electrons from 3 MeV to a few GeV and protons and helium in the energy range from 6 MeV/nucleon to above 2 GeV/nucleon. The PAMELA (Payload for Antimatter Matter Exploration and Light-nuclei Astrophysics) space borne experiment was launched on 15 June 2006 and is continuously collecting data since then. The apparatus measures electrons, positrons, protons, anti-protons and heavier nuclei from about 100 MeV to several hundreds of GeV. Thus the combination of Ulysses and PAMELA measurements is ideally suited to determine the spatial gradients during the extended minimum of solar cycle 23. For protons in the rigidity interval 1.6-1.8 GV we find a radial gradient of 2.7%/AU and a latitudinal gradient of -0.024%/degree. Although the latitudinal gradient is as expected negative, its value is much smaller than predicted by current particle propagation models. This result is of relevance for the study of propagation parameters in the inner heliosphere.
50.	Duffau, S., et al. (author) The Gaia-ESO Survey : Galactic evolution of sulphur and zinc 2017 In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 604 Journal article (peer-reviewed)abstract Context. Due to their volatile nature, when sulphur and zinc are observed in external galaxies, their determined abundances represent the gas-phase abundances in the interstellar medium. This implies that they can be used as tracers of the chemical enrichment of matter in the Universe at high redshift. Comparable observations in stars are more difficult and, until recently, plagued by small number statistics. Aims. We wish to exploit the Gaia-ESO Survey (GES) data to study the behaviour of sulphur and zinc abundances of a large number of Galactic stars, in a homogeneous way. Methods. By using the UVES spectra of the GES sample, we are able to assemble a sample of 1301 Galactic stars, including stars in open and globular clusters in which both sulphur and zinc were measured. Results. We confirm the results from the literature that sulphur behaves as an α-element. We find a large scatter in [Zn/Fe] ratios among giant stars around solar metallicity. The lower ratios are observed in giant stars at Galactocentric distances less than 7.5 kpc. No such effect is observed among dwarf stars, since they do not extend to that radius. Conclusions. Given the sample selection, giants and dwarfs are observed at different Galactic locations, and it is plausible, and compatible with simple calculations, that Zn-poor giants trace a younger population more polluted by SN Ia yields. It is necessary to extend observations in order to observe both giants and dwarfs at the same Galactic location. Further theoretical work on the evolution of zinc is also necessary.

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