A proposed model membrane and test method for microneedle insertion studies

A commercial polymeric film (Parafilm M (R), a blend of a hydrocarbon wax and a polyolefin) was evaluated as a model membrane for microneedle (MN) insertion studies. Polymeric MN arrays were inserted into Parafilm M (R) (PF) and also into excised neonatal porcine skin. Parafilm M (R) was folded before the insertions to closely approximate thickness of the excised skin. Insertion depths were evaluated using optical coherence tomography (OCT) using either a force applied by a Texture Analyser or by a group of human volunteers. The obtained insertion depths were, in general, slightly lower, especially for higher forces, for PF than for skin. However, this difference was not a large, being less than the 10% of the needle length. Therefore, all these data indicate that this model membrane could be a good alternative to biological tissue for MN insertion studies. As an alternative method to OCT, light microscopy was used to evaluate the insertion depths of MN in the model membrane. This provided a rapid, simple method to compare different MN formulations. The use of Parafilm M (R), in conjunction with a standardised force/time profile applied by a Texture Analyser, could provide the basis for a rapid MN quality control test suitable for in-process use. It could also be used as a comparative test of insertion efficiency between candidate MN formulations. 

Membrane fission is promoted by insertion of amphipathic helices and is restricted by crescent BAR domains

Shallow hydrophobic insertions and crescent-shaped BAR scaffolds promote membrane curvature. Here, we investigate membrane fission by shallow hydrophobic insertions quantitatively and mechanistically. We provide evidence that membrane insertion of the ENTH domain of epsin leads to liposome vesiculation, and that epsin is required for clathrin-coated vesicle budding in cells. We also show that BAR-domain scaffolds from endophilin, amphiphysin, GRAF, and β2-centaurin limit membrane fission driven by hydrophobic insertions. A quantitative assay for vesiculation reveals an antagonistic relationship between amphipathic helices and scaffolds of N-BAR domains in fission. The extent of vesiculation by these proteins and vesicle size depend on the number and length of amphipathic helices per BAR domain, in accord with theoretical considerations. This fission mechanism gives a new framework for understanding membrane scission in the absence of mechanoenzymes such as dynamin and suggests how Arf and Sar proteins work in vesicle scission.

L'insertion professionnelle de l'infirmière experte comme enseignante novice en soins infirmiers au collégial : l'apport du mentorat

Les infirmières et les infirmiers qui s'engagent comme enseignantes et enseignants en soins infirmiers passent du statut d'infirmière et d'infirmier expert à celui d'enseignante et d'enseignant novice sans vraiment être préparés. Le manque de connaissances en pédagogie, l'absence de modèles de référence et la lourdeur de la tâche contribuent à leur incertitude quant au désir de persévérer dans le domaine de l'enseignement. Cette situation s'avère critique puisqu'en ce moment on prévoit une pénurie d'infirmières et d'infirmiers et une pénurie de professeurs pour les former. Comment leur venir en aide à travers un horaire déjà chargé? Un programme de mentorat serait-il la solution? Notre recherche a visé à dégager les points de vue des enseignantes et des enseignants expérimentés en soins infirmiers, susceptibles d'être mentors, sur les défis à relever dans la pratique du mentorat auprès d'enseignantes et d'enseignants novices ainsi que les points de vue des novices sur le sujet.

Dimensions examinées par des novices en enseignement en adaptation scolaire en insertion professionnelle devant un problème éthique à l'école

Les novices en enseignement, particulièrement celles et ceux qui oeuvrent en adaptation scolaire, doivent composer avec de nombreux rôles dès leur entrée en milieu professionnel. Cette réalité multiplie les occasions de rencontrer des problèmes d'ordre éthique à l'école, soit des problèmes pour lesquels il n'existe pas de réponses ou de balises claires, qui exigent une prise de décisions et un choix d'actions qui doivent tenir compte de plusieurs éléments dont il faudra déterminer l'importance et, par conséquent, qui génèrent des conflits de valeurs. Être capable de résoudre un problème éthique implique au départ de développer la capacité à reconnaître les dimensions présentes à l'intérieur du problème. Nous avons dégagé quatre dimensions généralement présentes dans l'analyse d'un problème éthique: les personnes impliquées, les valeurs en jeu, les principes de conduite professionnelle appropriée et le cadre professionnel.Les personnes impliquées, puisque les professionnelles et professionnels sont amenés à anticiper les conséquences de leurs actions sur le bien-être des personnes concernées.Les valeurs en jeu, soit les structures internes sur lesquelles chaque individu se réfère spontanément, que ce soit des valeurs acquises durant l'enfance, dans l'expérience personnelle ou dans l'expérience professionnelle.Les principes de conduite professionnelle appropriée qui sont adoptés à titre de références par les membres de la communauté enseignante. Finalement, le cadre professionnel, car l'enseignante et l'enseignant s'inscrivent dans un cadre qui repose sur des lois et des normes des milieux. L'objectif de cette recherche a été de mettre en évidence les dimensions examinées par des enseignantes et des enseignants en adaptation scolaire en insertion professionnelle lorsqu'ils sont devant un problème éthique à l'école. La méthodologie utilisée était de nature qualitative et la cueillette de données a été effectuée par le moyen d'entrevues individuelles semi-dirigées.Les résultats obtenus à la suite de deux phases de collecte nous ont permis de mettre en évidence, entre autres, que certaines dimensions étaient examinées par les participantes de manière plus approfondie que d'autres devant des problèmes éthiques et dégager le sens accordé à chacune des dimensions par les participantes. Nous avons aussi analysé certaines préoccupations relatives à l'insertion professionnelle ayant émergé durant les entrevues.

Development of new methodologies for C-H insertion

Tese de doutoramento, Farmácia (Química Farmacêutica e Terapêutica), Universidade de Lisboa, Faculdade de Farmácia, 2014

Insertion dans les soins après une première hospitalisation dans un secteur pour psychose [Linkage to care after first hospitalisation for psychosis]

BACKGROUND: First hospitalisation for a psychotic episode causes intense distress to patients and families, but offers an opportunity to make a diagnosis and start treatment. However, linkage to outpatient psychiatric care remains a notoriously difficult step for young psychotic patients, who frequently interrupt treatment after hospitalisation. Persistence of symptoms, and untreated psychosis may therefore remain a problem despite hospitalisation and proper diagnosis. With persisting psychotic symptoms, numerous complications may arise: breakdown in relationships, loss of family and social support, loss of employment or study interruption, denial of disease, depression, suicide, substance abuse and violence. Understanding mechanisms that might promote linkage to outpatient psychiatric care is therefore a critical issue, especially in early intervention in psychotic disorders. OBJECTIVE: To study which factors hinder or promote linkage of young psychotic patients to outpatient psychiatric care after a first hospitalisation, in the absence of a vertically integrated program for early psychosis. Method. File audit study of all patients aged 18 to 30 who were admitted for the first time to the psychiatric University Hospital of Lausanne in the year 2000. For statistical analysis, chi2 tests were used for categorical variables and t-test for dimensional variables; p<0.05 was considered as statistically significant. RESULTS: 230 patients aged 18 to 30 were admitted to the Lausanne University psychiatric hospital for the first time during the year 2000, 52 of them with a diagnosis of psychosis (23%). Patients with psychosis were mostly male (83%) when compared with non-psychosis patients (49%). Furthermore, they had (1) 10 days longer mean duration of stay (24 vs 14 days), (2) a higher rate of compulsory admissions (53% vs 22%) and (3) were more often hospitalised by a psychiatrist rather than by a general practitioner (83% vs 53%). Other socio-demographic and clinical features at admission were similar in the two groups. Among the 52 psychotic patients, 10 did not stay in the catchment area for subsequent treatment. Among the 42 psychotic patients who remained in the catchment area after discharge, 20 (48%) did not attend the scheduled or rescheduled outpatient appointment. None of the socio demographic characteristics were associated with attendance to outpatient appointments. On the other hand, voluntary admission and suicidal ideation before admission were significantly related to attending the initial appointment. Moreover, some elements of treatment seemed to be associated with higher likelihood to attend outpatient treatment: (1) provision of information to the patient regarding diagnosis, (2) discussion about the treatment plan between in- and outpatient staff, (3) involvement of outpatient team during hospitalisation, and (4) elaboration of concrete strategies to face basic needs, organise daily activities or education and reach for help in case of need. CONCLUSION: As in other studies, half of the patients admitted for a first psychotic episode failed to link to outpatient psychiatric care. Our study suggests that treatment rather than patient's characteristics play a critical role in this phenomenon. Development of a partnership and involvement of patients in the decision process, provision of good information regarding the illness, clear definition of the treatment plan, development of concrete strategies to cope with the illness and its potential complications, and involvement of the outpatient treating team already during hospitalisation, all came out as critical strategies to facilitate adherence to outpatient care. While the current rate of disengagement after admission is highly concerning, our finding are encouraging since they constitute strategies that can easily be implemented. An open approach to psychosis, the development of partnership with patients and a better coordination between inpatient and outpatient teams should therefore be among the targets of early intervention programs. These observations might help setting up priorities when conceptualising new programs and facilitate the implementation of services that facilitate engagement of patients in treatment during the critical initial phase of psychotic disorders.

Proteomic and Metabolomic Analyses of Mitochondrial Complex I-deficient Mouse Model Generated by Spontaneous B2 Short Interspersed Nuclear Element (SINE) Insertion into NADH Dehydrogenase (Ubiquinone) Fe-S Protein 4 (Ndufs4) Gene.

Eukaryotic cells generate energy in the form of ATP, through a network of mitochondrial complexes and electron carriers known as the oxidative phosphorylation system. In mammals, mitochondrial complex I (CI) is the largest component of this system, comprising 45 different subunits encoded by mitochondrial and nuclear DNA. Humans diagnosed with mutations in the gene NDUFS4, encoding a nuclear DNA-encoded subunit of CI (NADH dehydrogenase ubiquinone Fe-S protein 4), typically suffer from Leigh syndrome, a neurodegenerative disease with onset in infancy or early childhood. Mitochondria from NDUFS4 patients usually lack detectable NDUFS4 protein and show a CI stability/assembly defect. Here, we describe a recessive mouse phenotype caused by the insertion of a transposable element into Ndufs4, identified by a novel combined linkage and expression analysis. Designated Ndufs4(fky), the mutation leads to aberrant transcript splicing and absence of NDUFS4 protein in all tissues tested of homozygous mice. Physical and behavioral symptoms displayed by Ndufs4(fky/fky) mice include temporary fur loss, growth retardation, unsteady gait, and abnormal body posture when suspended by the tail. Analysis of CI in Ndufs4(fky/fky) mice using blue native PAGE revealed the presence of a faster migrating crippled complex. This crippled CI was shown to lack subunits of the "N assembly module", which contains the NADH binding site, but contained two assembly factors not present in intact CI. Metabolomic analysis of the blood by tandem mass spectrometry showed increased hydroxyacylcarnitine species, implying that the CI defect leads to an imbalanced NADH/NAD(+) ratio that inhibits mitochondrial fatty acid β-oxidation.

Deux approches de l'influence du discours économique sur les phénomènes sociaux

The influence of theoretical discourse on the corresponding field of investigation is an important feature of social science : social scientists shape the world by describing it. This phenomenon has been studied in several ways. Economic sociology has recently focused on the fact that the economy is embedded in the economics through which it is scrutinized. Great names of economic theory have focused on the effects of economists' discourse on agents' behaviours. This article aims to bring out the distinction between these two kinds of contributions which deal with the same object. Finally, it explains the analytical distinction by a difference in the initial problematic. Following trends in the French school of the economics of convention, the social influence of theoretical discourse is analyzed on the strategic side (in connection with economics) and on the interpretative side (in connection with sociology).

Challenge of transition in the socio-professional insertion of youngsters with neurodisabilities

Patients with neurodisabilities require early management, continuing into adulthood. Thus, transition services were implemented in hospitals. To have a better support when they enter into adult life, it is useful to know the problems that they could face. The aim of this study is to evaluate their activities and to assess their insertion problems in the professional world. It is based on medical records of patients, aged 16 to 25 years, followed in the transition clinic of young adults in the Neurorehabilitation services of a tertiary centre. From 387 patients of the paediatric consultation, there are 267 patients (69%), included 224 with neurodevelopmental diseases and 43 with neuromuscular diseases. Nearly half of them (46.8%) were in a protected environment, 37.08% studied and 3.4% worked. Paradoxically, only 29.2% reported work problems. These results highlight the need to increase the integration of young adults with neuromotor disorders in the labor market.

Le Réformiste : revue politique, économique et administrative : paraissant tous les vendredis / dir. Jean S. Barès

1907 (A11,N149)- (A12,N151).

Le Réformiste : revue politique, économique et administrative : paraissant tous les vendredis / dir. Jean S. Barès

1909 (A14,N157)- (A14,N168).

Le Réformiste : revue politique, économique et administrative : paraissant tous les vendredis / dir. Jean S. Barès

1906 (A10,N141)- (A10,N148).

Le Réformiste : revue politique, économique et administrative : paraissant tous les vendredis / dir. Jean S. Barès

1908 (A13,N153)- (A13,N156).