The Gaia mission

Gaia is a cornerstone mission in the science programme of the EuropeanSpace Agency (ESA). The spacecraft construction was approved in 2006, following a study in which the original interferometric concept was changed to a direct-imaging approach. Both the spacecraft and the payload were built by European industry. The involvement of the scientific community focusses on data processing for which the international Gaia Data Processing and Analysis Consortium (DPAC) was selected in 2007. Gaia was launched on 19 December 2013 and arrived at its operating point, the second Lagrange point of the Sun-Earth-Moon system, a few weeks later. The commissioning of the spacecraft and payload was completed on 19 July 2014. The nominal five-year mission started with four weeks of special, ecliptic-pole scanning and subsequently transferred into full-sky scanning mode. We recall the scientific goals of Gaia and give a description of the as-built spacecraft that is currently (mid-2016) being operated to achieve these goals. We pay special attention to the payload module, the performance of which is closely related to the scientific performance of the mission. We provide a summary of the commissioning activities and findings, followed by a description of the routine operational mode. We summarise scientific performance estimates on the basis of in-orbit operations. Several intermediate Gaia data releases are planned and the data can be retrieved from the Gaia Archive, which is available through the Gaia home page. http://www.cosmos.esa.int/gai

[Evaluation of non invasive methods for the diagnosis of atherosclerosis of the graft after orthotopic cardiac transplantation]

International audienceThe frequency and severity of atherosclerosis of the cardiac transplant make it an essential complication of cardiac transplantation. Coronary angiography is the usual diagnostic method but it has severe limitations. In order to evaluate other diagnostic methods coronary angiography and non-invasive techniques: echocardiography, exercise stress ECG, exercise radionuclide ejection fraction, stress Thallium scintigraphy, were performed practically simultaneously in 60 patients after cardiac transplantation. These non-invasive methods were said to be positive in the presence of, respectively, a segmental wall motion abnormality, ischaemic ST segment depression, absence of increased ejection fraction on exercise, reversible or irreversible myocardial hypofixation. Coronary angiography was considered as the reference procedure for distinction between "normal coronary circulation" (no angiographically detectable lesion) and "graft atherosclerosis" (at least one coronary stenosis irrespective of the severity and extension). None of the non-invasive methods had an adequate sensibility when compared with coronary angiography (echocardiography 0.27, exercise stress ECG 0.28, exercise radionuclide ejection fraction 0.64, myocardial scintigraphy 0.62) or negative predictive value (echocardiography 0.56, exercise stress ECG 0.58, exercise radionuclide ejection fraction 0.68, myocardial scintigraphy 0.66). This inadequacy of the non-invasive technique may be explained by the fact that they are more adapted to the diagnosis of myocardial ischaemia than that of coronary studies. In addition, the extent of the coronary lesions may have masked discordance between 2 segments by the global hypovascularisation. The results of this study indicate that the non-invasive methods studied cannot be recommended for diagnosis of atherosclerosis of cardiac transplants

[Evaluation of non invasive methods for the diagnosis of atherosclerosis of the graft after orthotopic cardiac transplantation]

International audienceThe frequency and severity of atherosclerosis of the cardiac transplant make it an essential complication of cardiac transplantation. Coronary angiography is the usual diagnostic method but it has severe limitations. In order to evaluate other diagnostic methods coronary angiography and non-invasive techniques: echocardiography, exercise stress ECG, exercise radionuclide ejection fraction, stress Thallium scintigraphy, were performed practically simultaneously in 60 patients after cardiac transplantation. These non-invasive methods were said to be positive in the presence of, respectively, a segmental wall motion abnormality, ischaemic ST segment depression, absence of increased ejection fraction on exercise, reversible or irreversible myocardial hypofixation. Coronary angiography was considered as the reference procedure for distinction between "normal coronary circulation" (no angiographically detectable lesion) and "graft atherosclerosis" (at least one coronary stenosis irrespective of the severity and extension). None of the non-invasive methods had an adequate sensibility when compared with coronary angiography (echocardiography 0.27, exercise stress ECG 0.28, exercise radionuclide ejection fraction 0.64, myocardial scintigraphy 0.62) or negative predictive value (echocardiography 0.56, exercise stress ECG 0.58, exercise radionuclide ejection fraction 0.68, myocardial scintigraphy 0.66). This inadequacy of the non-invasive technique may be explained by the fact that they are more adapted to the diagnosis of myocardial ischaemia than that of coronary studies. In addition, the extent of the coronary lesions may have masked discordance between 2 segments by the global hypovascularisation. The results of this study indicate that the non-invasive methods studied cannot be recommended for diagnosis of atherosclerosis of cardiac transplants

Demographics and Baseline Characteristics of Patients with Idiopathic Pulmonary Fibrosis (IPF) in a Real-World Setting: Results of 847 Patients Enrolled in the Radico-ILD Cohort in France

International audienceRationale: Idiopathic pulmonary fibrosis (IPF) is a rare condition and few epidemiological dataare available in France. This specific research project aims to describe characteristics of treatedIPF patients and the impact of antifibrotic treatments in terms of morbidity and mortality in theFrench real-life setting. Methods: The French RaDiCo (Rare Disease Cohort)-ILD (idiopathicInterstitial Lung Diseases) registry is an ongoing observational study initiated in June 2017, witha sub-analysis of IPF patients. This longitudinal long-term cohort includes pediatric and adultpatients with ILD and is supported by the national network of reference and competence centersfor rare pulmonary diseases. IPF was diagnosed using international ATS/ERS 2011 criteria witha diagnosis of IPF or working diagnosis of IPF by multidisciplinary discussion. Here, we presentthe baseline data of IPF patients. Results: Between June 15th 2017 and September 4th 2019,1246 ILD patients were enrolled in the RaDiCo-ILD registry from 18 centers, including 847 withIPF (68%). IPF patients were mostly male (82.7%), with a mean age of 72.5 ± 9 years at inclusionand a mean BMI of 26.8 ± 4.3; 44.6 % of IPF patients included were incident cases, with amedian length between diagnosis and inclusion of 8.9 months (Q1=0.9 and Q3=26.4); 25.3% hada biopsy. The mean FVC at IPF diagnosis was 73.4 ± 25.0 % of predicted value (n=561), and themean DLCO at IPF diagnosis was 39.6 ± 18.2 % predicted value (n=498). Among patients withavailable information on anti-fibrotic treatment, 347 had been treated (at least one dose) withnintedanib, and 312 with pirfenidone; among patients treated with antifibrotics, 113 were treatedwith both treatments sequentially. Conclusions: The RaDiCo-ILD registry provides accurate real-world data on the demographics of patients with IPF in France. It will generate a long-term follow-up and will be an invaluable tool to describe the natural history and progression of patients withIPF in real-life conditions

Etude des mucopolysaccharidoses en France : constitution de la cohorte RaDiCo-MPS

International audienceIntroduction : Les mucopolysaccharidoses (MPS) sont des maladies de surcharge lysosomale : il s’agit de maladies génétiques rares (1/ 25 000 à 30 000 naissances). Ces maladies ont une évolution chronique, progressive et multisystémique avec des symptômes pouvant débuter dès la petite enfance, voire avant la naissance. L’espérance de vie des patients atteints est raccourcie [1]. La cohorte RaDiCo-MPS porte sur les différents types de MPS : MPS-I, MPS-II, MPS-III, MPS-IV, MPS-VI, MPS-VII, MPS-IX et DMS. Elle est soutenue par la plateforme RaDiCo qui est un programme national du Plan d’investissement d’Avenir, développé à l’INSERM U933, financé par l’ANR et dédié à la construction et à l’analyse de cohortes longitudinales de patients atteints de maladies rares. Depuis 2015, en partenariat avec les centres de compétences, de références et les filières de santé maladies rares, RaDiCo construit, enrichit et analyse des collections de données en vie réelle [2]. L’objectif de RaDiCo-MPS est de constituer une base de données prospectives et rétrospectives s’inscrivant dans la recherche de l’amélioration de la prise en charge et de l'organisation des soins. Le développement de traitements spécifiques pour certains types de MPS a permis d’améliorer les perspectives d’évolution des patients [3]. En partenariat avec la cohorte, un projet de recherche spécifique portant sur l’effet de l’enzymothérapie chez les patients atteints de MPS-II est en cours. Méthode : La population d’étude concerne tout patient (adulte ou enfant) avec un diagnostic confirmé de MPS ou de maladie d’Austin (DMS) ayant un consentement éclairé signé. Les données sont collectées de manière anonymisée sur la plateforme Inserm RaDiCo, RGPD compatible, via REDcap, application web sécurisée avec une interface intuitive et un contrôle qualité du circuit des données [4]. La période de recrutement est prévue pour durer 2 ans et le suivi 5 ans. Les résultats présentés proviennent d’une extraction de la base de données du 27 janvier 2021.Résultats : Au total, 254 patients MPS ont été recrutés depuis décembre 2017 par 14 centres français dont 55% des patients par 3 centres (Trousseau-APHP, Necker-APHP et La Timone-APHM) (Fig. 1). Les trois-quarts des patients étaient de type MPS-I, MPS-II ou MPS-III et aucun patient MPS-IX n’avait été inclus (Fig. 2 et Fig. 3). A l’inclusion, 76% des patients étaient vivants et 24% concernaient des dossiers rétrospectifs de patients décédés (Fig. 4). Parmi les 69 patients atteints de MPS-II, un seul patient était de sexe féminin (1%) (Tab. 1). L’ensemble des moyennes et des médianes de l’âge au diagnostic était inférieur à 10 ans, indiquant que, globalement, il s’agit plus souvent de maladies débutant dans l’enfance (Fig. 5). Pour les patients rétrospectifs, l’âge moyen de décès était compris entre 8,8 5,8 ans (MPS-I) et 24,2 3,8 ans (DMS) (Fig. 6). La moitié des patients (52%, n=132) avait reçu au moins une fois pendant l’étude un traitement spécifique de correction de déficits enzymatiques (58% MPS-I, 77% MPS-II, 7% MPS-III, 83% MPS-IV et 27% MPS-VI) (Tab.2).Discussion / Conclusion : Le suivi des patients n’étant pas achevé, les résultats présentés sont préliminaires. RaDiCo-MPS est une opportunité unique d’acquérir une meilleure connaissance des différents types de MPS, de leur histoire naturelle aux effets des traitements spécifiques ou non, ainsi que de la qualité de vie

Prediction of the age at onset in spinocerebellar ataxia type 1, 2, 3 and 6.

BACKGROUND: The most common spinocerebellar ataxias (SCA)--SCA1, SCA2, SCA3, and SCA6--are caused by (CAG)n repeat expansion. While the number of repeats of the coding (CAG)n expansions is correlated with the age at onset, there are no appropriate models that include both affected and preclinical carriers allowing for the prediction of age at onset. METHODS: We combined data from two major European cohorts of SCA1, SCA2, SCA3, and SCA6 mutation carriers: 1187 affected individuals from the EUROSCA registry and 123 preclinical individuals from the RISCA cohort. For each SCA genotype, a regression model was fitted using a log-normal distribution for age at onset with the repeat length of the alleles as covariates. From these models, we calculated expected age at onset from birth and conditionally that this age is greater than the current age. RESULTS: For SCA2 and SCA3 genotypes, the expanded allele was a significant predictor of age at onset (-0.105±0.005 and -0.056±0.003) while for SCA1 and SCA6 genotypes both the size of the expanded and normal alleles were significant (expanded: -0.049±0.002 and -0.090±0.009, respectively; normal: +0.013±0.005 and -0.029±0.010, respectively). According to the model, we indicated the median values (90% critical region) and the expectancy (SD) of the predicted age at onset for each SCA genotype according to the CAG repeat size and current age. CONCLUSIONS: These estimations can be valuable in clinical and research. However, results need to be confirmed in other independent cohorts and in future longitudinal studies. CLINICALTRIALSGOV, NUMBER: NCT01037777 and NCT00136630 for the French patients.peerReviewe