30 research outputs found
Pratiques de l'espace dans les établissements d'enseignement secondaire: Collège d'enseignement secondaire Villeneuve (Grenoble) : entretiens avec sept élèves et une enseignante (tome 1). Collège Malraux à Molliens (tome 2). Collège d'enseignement secondaire "les Aurelles", Mollien la Neuve (tome 3)
Tome 2 : Description architecturale et spatiale du collège Malraux, installé sur les anciens bâtiments du collège construit en 1885. Elle est précédée d'une description analogue de la ville de Molliens des origines à nos jours.Tome 3 : En prenant l'exemple du collège d'enseignement secondaire "Les Aurelles" (Mollien-la-Neuve), la question ici posée n'est pas de savoir si, dans un cadre donné -un collège- un individu sait dessiner ou parler d'espace. Il s'agit simplement de discerner par excès ou par défaut, ce dont parle l'individu par rapport à un cadre donné -un collège-, ce qu'il dessine, lorsqu'on lui demande d'évoquer espaces et pratiques d'espaces, c'est à dire, de ses multiples gestes et mouvements de corps quotidiens, de ce que ses yeux voient, lesquels sa mémoire conserve
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Recherches ● Une revue de littérature sur le rôle et la place des contrats dans l’organisation verticale des filières agricoles examine à quels objectifs économiques ils répondent. ● La coordination entre les acteurs, agriculteurs ou entreprises de transformation, peut-elle améliorer la qualité des produits en développant une réputation collective aux produits agricoles ? Faits et chiffres ● Les éleveurs de porcs se sont organisés sous forme d’Organisation de producteurs depuis le début des années 1960 afin de mieux structurer et valoriser leur offre, laissant une place dominante aux marchés spot. ● Dans la filière avicole, les contrats sont historiquement plus développés. La qualité des modes de coordination est prépondérante pour la compétitivité de la filière. ● Dans la filière laitière, le développement plus récent de la contractualisation est mis en perspective avec les enjeux posés par la suppression des quotas. Note de lecture ● Les enjeux du développement régional et territorial en zones rurale
CFTR mutation combinations producing frequent complex alleles with different clinical and functional outcomes
International audienceGenotype-phenotype correlations in cystic fibrosis (CF) may be difficult to establish because of phenotype variability, which is associated with certain CF transmembrane conductance regulator (CFTR) gene mutations and the existence of complex alleles. To elucidate the clinical significance of complex alleles involving p.Gly149Arg, p.Asp443Tyr, p.Gly576Ala, and p.Arg668Cys, we performed a collaborative genotype-phenotype correlation study, collected epidemiological data, and investigated structure-function relationships for single and natural complex mutants, p.[Gly576Ala;Arg668Cys], p.[Gly149Arg;Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala;Arg668Cys]. Among 153 patients carrying at least one of these mutations, only three had classical CF and all carried p.Gly149Arg in the triple mutant. Sixty-four had isolated infertility and seven were healthy individuals with a severe mutation in trans, but none had p.Gly149Arg. Functional studies performed on all single and natural complex mutants showed that (1) p.Gly149Arg results in a severe misprocessing defect; (2) p.Asp443Tyr moderately alters CFTR maturation; and (3) p.Gly576Ala, a known splicing mutant, and p.Arg668Cys mildly alter CFTR chloride conductance. Overall, the results consistently show the contribution of p.Gly149Arg to the CF phenotype, and suggest that p.[Arg668Cys], p.[Gly576Ala;Arg668Cys], and p.[Asp443Tyr;Gly576Ala;Arg668Cys] are associated with CFTR-related disorders. The present study emphasizes the importance of comprehensive genotype-phenotype and functional studies in elucidating the impact of mutations on clinical phenotype
Déclaration des erreurs médicamenteuses dans les recherches portant sur le médicament : place du pharmacien des essais cliniques ?
National audienceThe investigational drugs circuit has specific risks, and medication errors may occur in clinical trials, possibly associated with adverse reactions. These risks must therefore be managed. In fact, there are few reports of medication errors during clinical trials. In a context of regulatory interpretation difficulties on this subject, we conducted a national survey that highlighted the heterogeneity of the methods used by academic sponsors to collect, code and report medication errors and the need to develop a culture of reporting these errors in clinical trials. This is why the REVISE group (safety officers of French institutional sponsors) has issued recommendations to clarify the sponsor and investigator responsibilities and guide them in the management of medication errors. These new guidelines recommend that any serious or potentially serious medication error or other "special situation" (e.g. overdose, misuse, quality defect) should be notified immediately to the sponsor by the investigator. The clinical research pharmacist place is strategic to detect medication errors and other special situations. The integration of the pharmacist into the reporting system, in collaboration with the investigator, could be discussed with clinical research professionals and health authorities
A recurrent deep-intronic splicing CF mutation emphasizes the importance of mRNA studies in clinical practice
International audienceBACKGROUND:The identification by CFTR mRNA studies of a new deep-intronic splicing mutation, c.870-1113_1110delGAAT, in one patient of our series with mild CF symptoms and in three CF patients of an Italian study, led us to evaluate the mutation frequency and phenotype/genotype correlations.METHODS:266 patients with CF and related disorders and having at least one undetected mutation, were tested at the gDNA level in three French reference laboratories.RESULTS:In total, the mutation was found in 13 unrelated patients (5% of those already carrying a mutation) plus 4 siblings, including one homozygote and 12 heterozygotes having a severe CF mutation. The sweat test was positive in 10/14 documented cases, the diagnosis was delayed after 20 years in 9/15 and pancreatic insufficiency was present in 5/16.CONCLUSION:c.870-1113_1110delGAAT should be considered as CF-causing with phenotype variability and overall delayed diagnosis. Its frequency highlights the potential of mRNA studies
A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies
Human Hereditary Sensory Autonomic Neuropathies (HSANs) are characterized by insensitivity to pain, sometimes combined with self-mutilation. Strikingly, several sporting dog breeds are particularly affected by such neuropathies. Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact. Through a Genome Wide Association Study (GWAS) with 24 affected and 30 unaffected sporting dogs using the Canine HD 170K SNP array (Illumina), we identified a 1.8 Mb homozygous locus on canine chromosome 4 (adj. p-val = 2.5x10-6). Targeted high-throughput sequencing of this locus in 4 affected and 4 unaffected dogs identified 478 variants. Only one variant perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in a long intergenic non-coding RNAs (lincRNA), GDNF-AS. Using human comparative genomic analysis, we observed that the canine variant maps onto an enhancer element. Quantitative RT-PCR of dorsal root ganglia RNAs of affected dogs showed a significant decrease of both GDNF mRNA and GDNF-AS expression levels (respectively 60% and 80%), as compared to unaffected dogs. We thus performed gel shift assays (EMSA) that reveal that the canine variant significantly alters the binding of regulatory elements. Altogether, these results allowed the identification in dogs of GDNF as a relevant candidate for human HSAN and insensitivity to pain, but also shed light on the regulation of GDNF transcription. Finally, such results allow proposing these sporting dog breeds as natural models for clinical trials with a double benefit for human and veterinary medicine.This study was supported by the CNRS (Centre National de la Recherche Scientifique), the Brittany Region (France) (PhD funding for JP), the European Commission (FP7-LUPA, GA-201370), the Rosembloom Family and the Companion animal health fund from the Faculté de Médecine Vétérinaire, Université de Montréal, and the CRB-Anim infrastructure, ANR-11-INBS-0003, funded by the French National Research Agency in the frame of the ‘Investing for the Future’ program.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
A Point Mutation in a lincRNA Upstream of GDNF Is Associated to a Canine Insensitivity to Pain: A Spontaneous Model for Human Sensory Neuropathies
Human Hereditary Sensory Autonomic Neuropathies (HSANs) are characterized by insensitivity to pain, sometimes combined with self-mutilation. Strikingly, several sporting dog breeds are particularly affected by such neuropathies. Clinical signs appear in young puppies and consist of acral analgesia, with or without sudden intense licking, biting and severe self-mutilation of the feet, whereas proprioception, motor abilities and spinal reflexes remain intact. Through a Genome Wide Association Study (GWAS) with 24 affected and 30 unaffected sporting dogs using the Canine HD 170K SNP array (Illumina), we identified a 1.8 Mb homozygous locus on canine chromosome 4 (adj. p-val = 2.5x10-6). Targeted high-throughput sequencing of this locus in 4 affected and 4 unaffected dogs identified 478 variants. Only one variant perfectly segregated with the expected recessive inheritance in 300 sporting dogs of known clinical status, while it was never present in 900 unaffected dogs from 130 other breeds. This variant, located 90 kb upstream of the GDNF gene, a highly relevant neurotrophic factor candidate gene, lies in a long intergenic non-coding RNAs (lincRNA), GDNF-AS. Using human comparative genomic analysis, we observed that the canine variant maps onto an enhancer element. Quantitative RT-PCR of dorsal root ganglia RNAs of affected dogs showed a significant decrease of both GDNF mRNA and GDNF-AS expression levels (respectively 60% and 80%), as compared to unaffected dogs. We thus performed gel shift assays (EMSA) that reveal that the canine variant significantly alters the binding of regulatory elements. Altogether, these results allowed the identification in dogs of GDNF as a relevant candidate for human HSAN and insensitivity to pain, but also shed light on the regulation of GDNF transcription. Finally, such results allow proposing these sporting dog breeds as natural models for clinical trials with a double benefit for human and veterinary medicine.This study was supported by the CNRS (Centre National de la Recherche Scientifique), the Brittany Region (France) (PhD funding for JP), the European Commission (FP7-LUPA, GA-201370), the Rosembloom Family and the Companion animal health fund from the Faculté de Médecine Vétérinaire, Université de Montréal, and the CRB-Anim infrastructure, ANR-11-INBS-0003, funded by the French National Research Agency in the frame of the ‘Investing for the Future’ program.The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Phenotype-genotype correlations of pediatric patients with biallelic mutations in ABCA3 and SFTPB surfactant-related genes
International audienc
Phenotype-genotype correlations of pediatric patients with biallelic mutations in ABCA3 and SFTPB surfactant-related genes
International audienc