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Dominantly inherited GAA repeat expansions in FGF14 are a common cause of spinocerebellar ataxia (GAA-FGF14 ataxia; spinocerebellar ataxia 27B). Molecular confirmation of FGF14 GAA repeat expansions has thus far mostly relied on long-read sequencing, a technology that is not yet widely available in clinical laboratories. We developed and validated a strategy to detect FGF14 GAA repeat expansions using long-range PCR, bidirectional repeat-primed PCRs, and Sanger sequencing. We compared this strategy to targeted nanopore sequencing in a cohort of 22 French Canadian patients and next validated it in a cohort of 53 French index patients with unsolved ataxia. Method comparison showed that capillary electrophoresis of long-range PCR amplification products significantly underestimated expansion sizes compared to nanopore sequencing (slope, 0.87 [95% CI, 0.81 to 0.93]; intercept, 14.58 [95% CI, - 2.48 to 31.12]) and gel electrophoresis (slope, 0.84 [95% CI, 0.78 to 0.97]; intercept, 21.34 [95% CI, - 27.66 to 40.22]). The latter techniques yielded similar size estimates. Following calibration with internal controls, expansion size estimates were similar between capillary electrophoresis and nanopore sequencing (slope: 0.98 [95% CI, 0.92 to 1.04]; intercept: 10.62 [95% CI, - 7.49 to 27.71]), and gel electrophoresis (slope: 0.94 [95% CI, 0.88 to 1.09]; intercept: 18.81 [95% CI, - 41.93 to 39.15]). Diagnosis was accurately confirmed for all 22 French Canadian patients using this strategy. We also identified 9 French patients (9/53; 17%) and 2 of their relatives who carried an FGF14 (GAA)≥250 expansion. This novel strategy reliably detected and sized FGF14 GAA expansions, and compared favorably to long-read sequencing.

Introduction: there is a lot of indications for the use of the electrocardiogram (ECG) in general medicine but it seems little practised. The objectives of this study were to evaluate the population performing the ECG, its prevalence, the follow-up of the recommendations, there interpretation and to study for those not performing ECG the brakes and their axes of improvement.Method: This was a descriptive, cross-sectional epidemiological study. It concerned general practitioners settled in Picardy. 620 doctors randomly selected were assessed by questionnaire.Results: 136 answered or 22% of respondents. The ECG was practiced by 38% of the population and in 18% of the cases more than once a week. The reasons for achievement in acute were rhythm disorder, chest pain, discomfort and finally ionic disorder. The non-acute reasons for achievement were the ECG for the certificate of non-contra-indication to sports practice, the follow-up of a chronic pathology, the reference ECG and the introduction of a treatment. Practitioners were confident of their interpretation in 65% of cases (p

Le poly(acide méthacrylique) (PMAA) est un polyélectrolyte relativement peu étudié qui présente cependant des caractéristiques physico-chimiques variées et très intéressantes. La présence d'un groupement méthyle en alpha du groupement acide carboxylique lui confère un comportement très différent de son homologue beaucoup plus étudié : le poly(acide acrylique). En solvant aqueux et à faible taux d'ionisation, la synergie entre les interactions hydrophobes provenant des groupements méthyle et les liaisons hydrogène intramoléculaires entre les groupements acides carboxyliques sont à l'origine de la conformation très compacte adoptée par la chaîne polymère. Néanmoins, au-delà d'un taux d'ionisation critique, la chaîne de PMAA adopte une conformation très étendue semblable à celle adoptée par un polyélectrolyte classique à taux de charges élevé. L'objectif principal de ce travail est de relier les propriétés rhéologiques à la structure de solutions semi-diluées de PMAA.Le comportement rhéologique des solutions de PMAA a été étudié en fonction du régime de concentration et du taux d'ionisation. Les solutions semi-diluées suffisamment concentrées de PMAA présentent un comportement antithixotrope lorsque les macromolécules sont dans leur état globulaire. Le cisaillement entraîne la formation de liaisons intermoléculaires à l'origine de la formation d'un gel physique. Cette évolution a été reliée à une valeur de contrainte critique de cisaillement indépendante de la concentration pour laquelle le gel se forme. Ce phénomène présente des caractéristiques analogues à celles observées pour des suspensions colloïdales nanométriques.En solution aqueuse, les chaînes de PMAA non ionisées présentent une température critique inférieure de solubilité (LCST) située autour 67 $^{circ}$C. Une étude de ce phénomène par RMN a permis de sonder la mobilité des molécules d'eau au cours de la transition et de mettre en évidence un phénomène de déshydratation des macromolécules. Des mesures de diffusion de neutrons aux petits angles en température ont également montré la formation d'interfaces entre domaines riches et pauvres en polymère. L'emploi de ces différentes approches expérimentales a permis d'identifier un mécanisme de transition de phase très semblable à celui du poly(N-isopropylacrylamide) (PNIPAM). La température de point de trouble coïncide également avec une température de gel pour laquelle un gel viscoélastique se forme.La compréhension du comportement rhéologique et en température du PMAA est une étude nécessaire préalablement à l'élaboration de nanocomposites à base de PMAA et de nanoparticules de silice. Les nanocomposites sont préparés en solution et la fonctionnalisation des particules de silice permet d'augmenter les interactions polymère/silice. Le choix des groupements fonctionnels greffés à la surface des particules de silice a permis de rendre ces interactions variables par le pH de la solution. Une perspective à ce travail sera de corréler les propriétés structurales du nanocomposite à ses propriétés rhéologiques au cours du séchage Poly(methacrylic acid) (PMAA) is a polyelectrolyte which has been rather scarcely investigated in the literature, despite its various and very interesting physical properties. The behavior of PMAA solutions is drastically different from the one displayed by the extensively studied poly(acrylic acid), due to the methyl group located in the alpha position of the carboxylic acid function. At low ionization degrees in aqueous solvent, synergetic effects resulting from both hydrophobic interactions (methyl groups) and intramolecular hydrogen bonds between acidic groups are responsible for the hypercoiled conformation of the PMAA chains. Nevertheless, above a critical ionization degree, the PMAA macromolecule behaves as an extended chain similar to a usual highly charged polyelectrolyte. The main purpose of this work is to correlate the rheological properties to the structure of the chains for semi-dilute solutions of PMAA.In the semi-dilute regime, above a critical concentration, PMAA solutions display a sharp increase in their viscosity over time under shear. This phenomenon known as antithixotropy occurs only when the macromolecules adopt a hypercoiled conformation. The influence of both concentration and ionization degree on the rheological behavior of PMAA solutions was studied. Shear induces the formation of intermolecular bonds which are responsible for the formation of a physical gel. We have demonstrated that the critical shear stress at which the gel is formed does not depend on the concentration. Interestingly, the results obtained remind some features observed in the case of the shear thickening of charged colloids.Neutral PMAA chains in water also display a Lower Critical Solution Temperature (LCST) around 67 $^{circ}$C. The reorientational dynamics of water molecules above the LCST was studied by means of NMR experiments, which evidenced the dehydration of the polymer coils during phase separation. The formation of interfaces between polymer-rich and polymer-poor domains was investigated by small-angle neutron scattering experiments. A possible mechanism describing the transition at the molecular level was derived from the results obtained throughout the use of complementary experimental approaches. This mechanism is very similar to the one proposed for the LCST transition of poly(N-isopropylacrylamide) (PNIPAM). The cloud point temperature of PMAA solutions is the same as the gel temperature at which a viscoelastic gel is formed.The understanding of the behavior of PMAA solutions under shear as well as under temperature is an essential prerequisite to the design of PMAA/silica nanocomposites. These nanocomposites were are prepared in the solution state. The interactions between PMAA chains and silica were clearly increased by the functionalization of the silica particles. Such interactions between PMAA and filler particles were found to be related to the pH of the solutions, due to the nature of the chemical groups at the surface of the functionalized silica. A possible perspective to this work would be the correlation between the structural features of the nanocomposites and their rheological properties during the drying process