Fabry disease

Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones

NIMBY, taxe fonci ere et vote par les pieds

A community of individuals heterogeneous in terms of revenue occupies a territory subdivided into zones characterized by unequal levels of amenities. Starting from the concept of land rent a la Ricardo, we propose a model determining the bid rents in the diff erent zones as well as the distribution of the population among these. We then study the impact of a shock a ffecting negatively the amenities in one zone on the rents of the other zones via a process of "voting with the feet" a la Tiebout. Starting from this analysis, we propose a taxation of land rent that allows for a compensation of the residents whose neighborhood is directly a ffected by the amenity shock by the other members of the community. Such is system may prevent NIMBY attitudes. Moreover, as far as rent is observable, the mechanism has the advantage of having no preference revelation problem.Une communauté e d'individus h ét érog ene en terme de revenus occupe un territoire divis e en zones caract eris ées par des niveaux d'am enit es di fferents. Partant du concept de rente a la Ricardo, nous proposons un mod èle determinant les rentes o ffertes dans les diff erentes zones et la r épartition de la population entre celles-ci. On étudie ensuite l'impact d'un choc a ffectant n egativement les am enit es d'une zone sur les rentes des autres zone via un processus de "vote par les pieds" à la mani ère de Tiebout. Partant de cette analyse, nous proposons un syst eme de taxation de la rente qui permet une compensation fi nanci ere des r esidents directement aff ect es dans leur voisinage par les individus non touch es. Ce syst eme est susceptible d'att enuer les attitudes du type \NIMBY". De plus, dans la mesure o u la rente est observable, le m ecanisme pr esente l'avantage de ne poser aucun probl eme de r ev elation des pr ef erences

REAL-TIME DETECTION OF THE ACTIVITY OF A DOG

International audienceThis paper introduces our preliminary work with assistance dogs. Even when dogs are very well trained some problems may occur in practice, typical examples are dog escaping or running after a cat. Our long term objective is to take advantage of the technology to increase the safety of the dog and its owner. Our first work focuses on the activity classification of the dog. This paper presents preliminary results for recognizing four types of activity: walk, run, lay and sit down. Experiments and results on real data collected with low-cost gyroscopes and accelerometers are presented and discussed

Increasing communication between a man and a dog

International audienceIn this paper, we present the first results we have concerning our ongoing work on a robotic system embedded on a dog to enrich communication. Two problems are addressed here: How to keep control of a dog when the human does not see it? For dog trained to do some specific activities in particular situation, how to detect this activity? We present here results on controlling the dog by an embedded voice and a real-time recognition of some activities of the dog : walk, seat, run, lying

Interdisciplinarité et quiproquos : témoignage à plusieurs voix

Un programme de recherche sur les systèmes de production dans les Andes du Pérou a été l'occasion de prendre conscience de quiproquos qui se manifestent dans les termes et dans la façon de concevoir une recherche. Comme le souligne notre témoignage, ces quiproquos trouvent leur source dans des divisions entre sensibilités individuelles, entre écoles, entre disciplines, entre groupes de disciplines. Pour y mettre fin, quelques précautions doivent être respectées : l'interdisciplinarité ne s'impose pas ; elle se construit et se modifie. (Résumé d'auteur

Médiation et médiatisation en danse contemporaine : quand la profusion opacifie le sens d’un art sans texte

En dépit d’une progression conséquente de la program­mation et du public de la danse contemporaine dans les années 1980 et 1990, la diffusion des spectacles demeure souvent difficile. L’histoire et les techniques de la danse contemporaine restent peu connues, voire méconnues, dans la société et cette lacune grève les possibilités d’action des responsables de lieux de dif­fusion, qui peinent eux-mêmes à suivre l’accélération des rythmes d’innovation artistique. Dans ce contexte, l’article s’appuie à la fois sur l’étude d’un corpus diver­sifié de documents tirés de différents médias et sur une enquête de terrain au sein du monde professionnel pour expliquer l’image confuse de la danse contemporaine parmi le grand public et envisager la façon dont les programmes d’action culturelle menés par les artistes et les lieux de programmation peuvent y remédier. L’analyse comporte une dimension prescriptive sur les conditions d’efficacité de la médiation dans le secteur chorégraphique et sur les moyens de renforcer quantitativement et qualitativement la médiatisation de la danse contemporaine.Despite a consequent increase in the programming and in the numbers of contemporary dance audiences between the 1980s and the 1990s, the distribution of performances often remained difficult. The history and the techniques of contemporary dance remained little known within the entire society and this gap restricted the venue managers’ possibilities of action. They were themselves, indeed, struggling to survive the accelerating pace of artistic innovation. In this context, the article leans both on the study of a diversified corpus of documents taken from various media, and on a field study within the professional world, in order to explain the confused image of contemporary dance among the mass public, and the way in which programmes of cultural actions led by artists and the programmed venues could be remedied. The analysis also includes a perspective dimension on the conditions of effectiveness of mediation in the choreographic sector and the means of reinforcing quantitatively and qualitatively the media exposure of contemporary dance

Exhaustive Screening of the Acid β-Glucosidase Gene, by Fluorescence-Assisted Mismatch Analysis Using Universal Primers: Mutation Profile and Genotype/Phenotype Correlations in Gaucher Disease

SummaryGaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving ∼30% of alleles undetected. Nevertheless, very few exhaustive methods have been developed for extensive gene screening of a large series of patients. Our approach for a complete search of mutations was the association of fluorescent chemical cleavage of mismatches with a universal strand-specific labeling system. The glucocerebrosidase (GBA) gene was scanned by use of a set of six amplicons, comprising 11 exons, all exon/intron boundaries, and the promoter region. By use of this screening strategy, the difficulties due to the existence of a highly homologous pseudogene were easily overcome, and both GD mutant alleles were identified in all 25 patients studied, thus attesting to a sensitivity that approaches 100%. A total of 18 different mutations and a new glucocerebrosidase haplotype were detected. The mutational spectrum included eight novel acid β-glucosidase mutations: IVS2 G(+1)→T, I119T, R170P, N188K, S237P, K303I, L324P, and A446P. These data further indicate the genetic heterogeneity of the lesions causing GD. Established genotype/phenotype correlations generally were confirmed, but notable disparities were disclosed in several cases, thus underlining the limitation in the prognostic value of genotyping. The observed influence of multifactorial control on this monogenic disease is discussed

Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study.

BackgroundThe p.Asn215Ser or p.N215S GLA variant has been associated with late-onset cardiac variant of Fabry disease.MethodsTo expand on the scarce phenotype data, we analyzed natural history data from 125 p.N215S patients (66 females, 59 males) enrolled in the Fabry Registry (NCT00196742) and compared it with data from 401 patients (237 females, 164 males) harboring mutations associated with classic Fabry disease. We evaluated interventricular septum thickness (IVST), left ventricular posterior wall thickness (LVPWT), estimated glomerular filtration rate and severe clinical events.ResultsIn p.N215S males, mildly abnormal mean IVST and LVPWT values were observed in patients aged 25-34 years, and values gradually increased with advancing age. Mean values were similar to those of classic males. In p.N215S females, these abnormalities occurred primarily in patients aged 55-64 years. Severe clinical events in p.N215S patients were mainly cardiac (males 31%, females 8%) while renal and cerebrovascular events were rare. Renal impairment occurred in 17% of p.N215S males (mostly in patients aged 65-74 years), and rarely in females (3%).Conclusionp.N215S is a disease-causing mutation with severe clinical manifestations found primarily in the heart. Cardiac involvement may become as severe as in classic Fabry patients, especially in males