Associations of Galectin-3 Levels With Measures of Vascular Disease in Patients With Rheumatoid Arthritis

OBJECTIVES: Galectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA). METHODS: RA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic SUV, and MFR. RESULTS: A total of 124 RA patients (mean age 57; 82 % women, 45 % Hispanic; median RA duration 6.8 years; 75 % seropositive; median CDAI 16; 33 % on prednisone; 89 % on DMARDs; median CAC score 0; median aorta SUV 2.59; mean MFR 2.86; median galectin-3 level 8.54 ng/mL) were analyzed. In univariable analysis, higher galectin-3 levels were associated with higher aortic SUV (p = 0.007) but CAC score and MFR were not. In multivariable analysis, higher galectin-3 level remained significantly associated with higher aortic SUV (ß Coefficient=0.1786, p value=0.002). CONCLUSION: In our cohort of RA patients without clinical CVD, higher serum galectin-3 levels were independently associated with higher levels of aortic inflammation, but not CAC score or MFR. This suggests that galectin-3 may be a biomarker for an inflammatory and potentially reversible stage, but not a later (calcified) stage, of atherosclerosis in patients with RA

Language and educational policies in favour of Francophonie, a comparative analysis in Ghana and in Vietnam : a regional approach, West Africa and South-East Asia

A la croisée des champs d’étude que sont les sciences du langage, l’analyse du discours et la recherche-action, cette thèse propose une approche comparée des politiques linguistiques et éducatives de deux aires géographiques - l’une en Afrique de l’Ouest, l’autre en Asie du Sud-Est. Il s’agit de proposer une étude sur l’influence des facteurs géographiques, linguistiques, économiques et culturels sur les politiques mises en place dans deux États en particulier avec une présentation de deux systèmes éducatifs sensibles pour la Francophonie, à savoir le Ghana et le Vietnam (ayant respectivement dans l’Organisation Internationale de la Francophonie, les statuts d’État associé et d’État membre). Nous procéderons à cette occasion à une étude des langues en présence sur ces deux territoires ainsi que du statut de la langue française et des représentations qui lui sont associées. A partir de l’étude d’un corpus de textes officiels, et d’entretiens semi-directifs auprès de décideurs, de responsables éducatifs locaux mais également d’opérateurs de la Francophonie (OIF, AUF, RFI, TV5), nous proposerons une approche diachronique de 2000 à nos jours. Nous examinerons en outre l’état actuel de la F/francophonie et envisagerons son avenir dans ces deux pays pour proposer enfin, dans une approche prospective, un certain nombre d’orientations concernant le développement de la langue française et de son enseignement dans ces deux aires. Enfin, cette recherche s’inscrit résolument dans le champ de la recherche-intervention ainsi que dans une démarche professionnelle avec la création d’un outil d’aide à la décision destiné aux futurs décideurs dans le domaine de la Francophonie en France, au Ghana et au Vietnam.Situated at the intersection of the fields of study which are language sciences, discourse analysis and research-action, this work presents a comparative approach of the linguistic and educational policies of two geographical areas – the first one in West Africa and the second one in South-East Asia. The purpose is to conduct a study on the influence of geographical, linguistic, economic and cultural factors on the policies put into place in those two states with a presentation, in particular, of the two sensitive educational systems for Francophonie, that is Ghana and Vietnam (the two states having respectively the status of associate member and member state within the Organisation of Francophonie). A study on the languages present on the two territories, the status of French language and the representations associated to French language, will therefore be conducted.From the study of a corpus of official texts as well as semi-directive interviews with local persons in charge of education, policy makers but also operators of Francophonie : International Organisation of Francophonie (OIF), Higher Education Agency for Francophonie (AUF), French International Radio (RFI), TV5, we will present a diachronic approach from the year 2000 to today. Moreover, we will examine the present situation of Francophonie et will consider its future in those two countries. Finally, in a prospective approach, we will state a number of recommendations concerning the development of French language and its teaching in those two areas.Lastly, this research falls within a professional approach with the creation of a decision making tool aimed at present and future policy makers in the field of Francophonie in France, Ghana and Vietnam

Politiques linguistiques éducatives en faveur de la F/francophonie, étude comparative au Ghana et au Vietnam : approches régionales, Afrique de l'Ouest et Asie du Sud-Est

Situated at the intersection of the fields of study which are language sciences, discourse analysis and research-action, this work presents a comparative approach of the linguistic and educational policies of two geographical areas – the first one in West Africa and the second one in South-East Asia. The purpose is to conduct a study on the influence of geographical, linguistic, economic and cultural factors on the policies put into place in those two states with a presentation, in particular, of the two sensitive educational systems for Francophonie, that is Ghana and Vietnam (the two states having respectively the status of associate member and member state within the Organisation of Francophonie). A study on the languages present on the two territories, the status of French language and the representations associated to French language, will therefore be conducted.From the study of a corpus of official texts as well as semi-directive interviews with local persons in charge of education, policy makers but also operators of Francophonie : International Organisation of Francophonie (OIF), Higher Education Agency for Francophonie (AUF), French International Radio (RFI), TV5, we will present a diachronic approach from the year 2000 to today. Moreover, we will examine the present situation of Francophonie et will consider its future in those two countries. Finally, in a prospective approach, we will state a number of recommendations concerning the development of French language and its teaching in those two areas.Lastly, this research falls within a professional approach with the creation of a decision making tool aimed at present and future policy makers in the field of Francophonie in France, Ghana and Vietnam.A la croisée des champs d’étude que sont les sciences du langage, l’analyse du discours et la recherche-action, cette thèse propose une approche comparée des politiques linguistiques et éducatives de deux aires géographiques - l’une en Afrique de l’Ouest, l’autre en Asie du Sud-Est. Il s’agit de proposer une étude sur l’influence des facteurs géographiques, linguistiques, économiques et culturels sur les politiques mises en place dans deux États en particulier avec une présentation de deux systèmes éducatifs sensibles pour la Francophonie, à savoir le Ghana et le Vietnam (ayant respectivement dans l’Organisation Internationale de la Francophonie, les statuts d’État associé et d’État membre). Nous procéderons à cette occasion à une étude des langues en présence sur ces deux territoires ainsi que du statut de la langue française et des représentations qui lui sont associées. A partir de l’étude d’un corpus de textes officiels, et d’entretiens semi-directifs auprès de décideurs, de responsables éducatifs locaux mais également d’opérateurs de la Francophonie (OIF, AUF, RFI, TV5), nous proposerons une approche diachronique de 2000 à nos jours. Nous examinerons en outre l’état actuel de la F/francophonie et envisagerons son avenir dans ces deux pays pour proposer enfin, dans une approche prospective, un certain nombre d’orientations concernant le développement de la langue française et de son enseignement dans ces deux aires. Enfin, cette recherche s’inscrit résolument dans le champ de la recherche-intervention ainsi que dans une démarche professionnelle avec la création d’un outil d’aide à la décision destiné aux futurs décideurs dans le domaine de la Francophonie en France, au Ghana et au Vietnam

Politiques linguistiques éducatives en faveur de la F/francophonie, étude comparative au Ghana et au Vietnam : approches régionales, Afrique de l'Ouest et Asie du Sud-Est

Situated at the intersection of the fields of study which are language sciences, discourse analysis and research-action, this work presents a comparative approach of the linguistic and educational policies of two geographical areas – the first one in West Africa and the second one in South-East Asia. The purpose is to conduct a study on the influence of geographical, linguistic, economic and cultural factors on the policies put into place in those two states with a presentation, in particular, of the two sensitive educational systems for Francophonie, that is Ghana and Vietnam (the two states having respectively the status of associate member and member state within the Organisation of Francophonie). A study on the languages present on the two territories, the status of French language and the representations associated to French language, will therefore be conducted.From the study of a corpus of official texts as well as semi-directive interviews with local persons in charge of education, policy makers but also operators of Francophonie : International Organisation of Francophonie (OIF), Higher Education Agency for Francophonie (AUF), French International Radio (RFI), TV5, we will present a diachronic approach from the year 2000 to today. Moreover, we will examine the present situation of Francophonie et will consider its future in those two countries. Finally, in a prospective approach, we will state a number of recommendations concerning the development of French language and its teaching in those two areas.Lastly, this research falls within a professional approach with the creation of a decision making tool aimed at present and future policy makers in the field of Francophonie in France, Ghana and Vietnam.A la croisée des champs d’étude que sont les sciences du langage, l’analyse du discours et la recherche-action, cette thèse propose une approche comparée des politiques linguistiques et éducatives de deux aires géographiques - l’une en Afrique de l’Ouest, l’autre en Asie du Sud-Est. Il s’agit de proposer une étude sur l’influence des facteurs géographiques, linguistiques, économiques et culturels sur les politiques mises en place dans deux États en particulier avec une présentation de deux systèmes éducatifs sensibles pour la Francophonie, à savoir le Ghana et le Vietnam (ayant respectivement dans l’Organisation Internationale de la Francophonie, les statuts d’État associé et d’État membre). Nous procéderons à cette occasion à une étude des langues en présence sur ces deux territoires ainsi que du statut de la langue française et des représentations qui lui sont associées. A partir de l’étude d’un corpus de textes officiels, et d’entretiens semi-directifs auprès de décideurs, de responsables éducatifs locaux mais également d’opérateurs de la Francophonie (OIF, AUF, RFI, TV5), nous proposerons une approche diachronique de 2000 à nos jours. Nous examinerons en outre l’état actuel de la F/francophonie et envisagerons son avenir dans ces deux pays pour proposer enfin, dans une approche prospective, un certain nombre d’orientations concernant le développement de la langue française et de son enseignement dans ces deux aires. Enfin, cette recherche s’inscrit résolument dans le champ de la recherche-intervention ainsi que dans une démarche professionnelle avec la création d’un outil d’aide à la décision destiné aux futurs décideurs dans le domaine de la Francophonie en France, au Ghana et au Vietnam

L’écriture créative : imaginaire et investissement du sujet. Questions à François Migeot

Quels sont les différents moyens d’entrer dans une écriture créative ? Quels sont les moyens de déclencher l’imaginaire ? Peut-être convient-il d’abord de savoir à quel public on s’adresse, et d’établir une différence entre un public francophone qui croit maîtriser sa langue maternelle, et un public d’étudiants étrangers qui sont en cours d’apprentissage du français. Je parlerai ici surtout des seconds, car c’est avant tout avec eux que j’ai travaillé. Pour le premier public, je ne suggérerai..

Prospective changes in diastolic function in patients with rheumatoid arthritis.

BACKGROUND: Diastolic dysfunction (DD) is more prevalent in patients with rheumatoid arthritis (RA) compared to the general population. However, its evolution over time and its significant clinical predictors remain uncharacterized. We report on baseline and prospective changes in diastolic function and its associated RA and cardiovascular (CV) predictors. METHODS: In this study, 158 RA patients without clinical CV disease (CVD) were enrolled and followed up at 4 to 6 years, undergoing baseline and follow-up echocardiography to assess for DD, as well as extensive characterization of RA disease activity and CV risk factors. Novel measures of myocardial inflammation and perfusion were obtained at baseline only. Using baseline and follow-up composite DD (E/e\u27, Left Atrial Volume Index (LAVI) or peak tricuspid regurgitation (TR) velocity; ≥ 1 in top 25%) as the outcome, multivariable regression models were constructed to identify predictors of DD. RESULTS: DD was prevalent in RA patients without clinical heart failure (HF) (40.7% at baseline) and significantly progressed on follow-up (to 57.9%). Baseline composite DD was associated with baseline RA disease activity (Clinical Disease Activity Index; CDAI) (OR 1.39; 95% CI 1.02-1.90; p=0.034). Several individual diastolic parameters (baseline E/e\u27 and LAVI) were associated with troponin-I and brain natriuretic peptide (BNP). Baseline and follow-up composite DD, however, were not associated with myocardial inflammation, myocardial microvascular dysfunction, or subclinical atherosclerosis. CONCLUSIONS: DD is prevalent in RA patients without clinical HF and increases to \u3e50% over time. Higher RA disease activity at baseline predicted baseline composite DD. Future longitudinal studies should explore whether adverse changes in diastolic function lead to clinical HF and are attenuated by disease-modifying antirheumatic drugs (DMARDs)

Parcours dans le texte littéraire

Les études rassemblées ici, autour des travaux de François Migeot, portent sur les processus de création du texte, sur les méthodes relatives à son analyse, sur les enjeux de sa traduction et enfin sur ceux de sa transposition didactique. Interrogeant aussi la notion de « création », elles mettent en avant sa transversalité, montrant qu’elle est à l’œuvre autant chez le poète et l’écrivain que chez l’apprenant. De sorte que la langue, telle qu’elle est envisagée ici, peut largement informer la recherche relative à l’apprentissage d’une langue étrangère ainsi que stimuler la réflexion méthodologique concernant la didactique des langues-cultures

Avoiding misdiagnosis : expert consensus recommendations for the suspicion and diagnosis of transthyretin amyloidosis for the general practitioner

Background Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of ATTR amyloidosis is often a challenge, in large part because of its heterogeneous presentation. Although ATTR amyloidosis was previously considered untreatable, disease-modifying therapies for the treatment of this disease have recently become available. This article aims to raise awareness of the initial symptoms of ATTR amyloidosis among general practitioners to facilitate identification of a patient with suspicious signs and symptoms. Methods These consensus recommendations for the suspicion and diagnosis of ATTR amyloidosis were developed through a series of development and review cycles by an international working group comprising key amyloidosis specialists. This working group met to discuss the barriers to early and accurate diagnosis of ATTR amyloidosis and develop a consensus recommendation through a thorough search of the literature performed using PubMed Central. Results The cardiac and peripheral nervous systems are most frequently involved in ATTR amyloidosis; however, many patients often also experience gastrointestinal and other systemic manifestations. Given the multisystemic nature of symptoms, ATTR amyloidosis is often misdiagnosed as a more common disorder, leading to significant delays in the initiation of treatment. Although histologic evaluation has been the gold standard to confirm ATTR amyloidosis, a range of tools are available that can facilitate early and accurate diagnosis. Of importance, genetic testing should be considered early in the evaluation of a patient with unexplained peripheral neuropathy. Conclusions A diagnostic algorithm based on initial red flag symptoms and manifestations of cardiac or neurologic involvement will facilitate identification by the general practitioner of a patient with clinically suspicious symptoms, enabling subsequent referral of the patient to a multidisciplinary specialized medical center

N-Terminomic Changes in Neurons During Excitotoxicity Reveal Proteolytic Events Associated With Synaptic Dysfunctions and Potential Targets for Neuroprotection.

Excitotoxicity, a neuronal death process in neurological disorders such as stroke, is initiated by the overstimulation of ionotropic glutamate receptors. Although dysregulation of proteolytic signaling networks is critical for excitotoxicity, the identity of affected proteins and mechanisms by which they induce neuronal cell death remain unclear. To address this, we used quantitative N-terminomics to identify proteins modified by proteolysis in neurons undergoing excitotoxic cell death. We found that most proteolytically processed proteins in excitotoxic neurons are likely substrates of calpains, including key synaptic regulatory proteins such as CRMP2, doublecortin-like kinase I, Src tyrosine kinase and calmodulin-dependent protein kinase IIβ (CaMKIIβ). Critically, calpain-catalyzed proteolytic processing of these proteins generates stable truncated fragments with altered activities that potentially contribute to neuronal death by perturbing synaptic organization and function. Blocking calpain-mediated proteolysis of one of these proteins, Src, protected against neuronal loss in a rat model of neurotoxicity. Extrapolation of our N-terminomic results led to the discovery that CaMKIIα, an isoform of CaMKIIβ, undergoes differential processing in mouse brains under physiological conditions and during ischemic stroke. In summary, by identifying the neuronal proteins undergoing proteolysis during excitotoxicity, our findings offer new insights into excitotoxic neuronal death mechanisms and reveal potential neuroprotective targets for neurological disorders

HSP110 T17 simplifies and improves the microsatellite instability testing in patients with colorectal cancer

IF 5.65International audienceBackground Every colorectal cancer (CRC) patient should be tested for microsatellite instability (MSI, a marker for defective DNA mismatch repair) as a first screen for Lynch syndrome (LS). In this study, we investigated whether it may be possible to improve the detection of MSI in CRC. We examined whether the HT17 DNA repeat (critical for correct splicing of the chaperone HSP110) might constitute a superior marker for diagnosis of the MSI phenotype in patients with CRC compared with the standard panel of markers (pentaplex).Methods The HT17 polymorphism was analysed in germline DNA from 1037 multi-ethnic individuals. We assessed its sensitivity and specificity for detecting MSI in a multicentre, population-based cohort of 685 patients with CRC and an additional series of 70 patients with CRC considered to be at-risk of LS. All cases were screened earlier for MSI using pentaplex markers. Cases showing discordant HT17/pentaplex results were further examined for the expression of mismatch repair proteins.Results HT17 status was analysed independently and blinded to previous results from pentaplex genotyping. HT17 showed no germline allelic variation outside a very narrow range. Compared with the pentaplex panel, HT17 showed better sensitivity (0.984 (95% CI 0.968 to 0.995) vs 0.951 (95% CI 0.925 to 0.972)) and similar specificity (0.997 (95% CI 0.989 to 1.000) for both) for the detection of MSI. Furthermore, HT17 alone correctly classified samples judged to be uncertain with the pentaplex panel and showed excellent ability to detect MSI in patients with LS.Conclusions HT17 simplifies and improves the current standard molecular methods for detecting MSI in CRC