La diffusion du séquençage haut débit (ou NGS pour Next Generation Sequencing) représente un tel changement d’échelle par rapport aux méthodes classiques de séquençage que les indications et l’organisation du diagnostic moléculaire s’en trouvent profondément modifiées. Le NGS permet à la fois de raccourcir le temps d’analyse et de rendu de résultat et d'élargir considérablement le nombre de gènes testés. Il promet donc d’augmenter la proportion de diagnostics posés et de faciliter l'identification de nouveaux variants et de nouveaux gènes impliqués en pathologie. Cependant dans tous les cas, il génère une quantité de données importante, données qui doivent être analysées et interprétées à l’aide d’outils bioinformatiques spécifiques.Dans la première partie de ce travail, les stratégies existantes ainsi que les difficultés et les enjeux du séquençage haut débit pour le diagnostic moléculaire des maladies génétiques sont discutés. Dans la deuxième partie, la mise en place et la validation technique de cette approche diagnostique sont décrites au sein du laboratoire de Génétique Moléculaire de la Timone à Marseille et illustrées par trois exemples concrets de diagnostics moléculaires posés grâce à la technique de séquençage à haut débit. Dans le domaine spécifique des maladies rares, ces nouvelles technologies sont porteuses d’un réel espoir pour les patients atteints de maladie génétique, permettant d'améliorer globalement leur prise en charge et d'accélérer les progrès dans le domaine de la recherche. / The diffusion of Next Generation Sequencing (NGS) technologies induces an important change that modifies molecular diagnostics indications and prompts laboratories to re-think their diagnostic strategies, up-to-now based on Sanger sequencing routine. Several high throughput approaches are available from the sequencing of a gene panel, to a whole exome, or even a whole genome. In all cases, a tremendous amount of data are generated, that have to be filtered, interpreted and analyzed by the use of powerful bioinformatics tools.In part 1, existing strategies and the difficulties and challenges of high-throughput sequencing for molecular diagnosis in genetic diseases are discussed. In part 2, the set up and the technical validation of this diagnostic approach in the Molecular Genetics’ Laboratory of the Timone Hospital in Marseille is presented and illustrated by 3 examples of complex diagnostics solved thanks to NGS. NGS promises to shorten significantly the time of analysis and results reporting, and to expand the number of tested genes. It also promises to increase the proportion of positive diagnoses. Finally, the NGS can identify new variants and new genes involved in human pathology, thus will globally improve patient clinical care.

Summaries in Afrikaans and English / Die begin van die nuwe millennium word gekenmerk deur radikale vooruitgang op tegnologiese gebied, paradigmatiese verskuiwings in natuur- en geesteswetenskappe, toenemende onsekerheid oor wat die ware aard van die mens is en hoe die een mens die ander verantwoordbaar kan help met die oplossing van probleme en herstel van menswaardigheid deur middel van opvoedkundige sielkundige ondersteuning. Navorsing is ondemeem om 'n beeld te verkry van wat 'n verantwoordbare opvoedkundige sielkundige praktyk met besondere verwysing na pedoterapie, kan wees. 'n Literatuurstudie is gedoen aangaande grondeise van 'n verantwoordbare opvoedkundige sielkundige praktyk in historieskomtemporere konteks. 'n Verdere literatuurstudie is gedoen aangaande 'n verantwoordelike en verantwoordbare pedoterapeutiese praktyk in opvoedings- en medemenslikheidsperspektief. 'n Teoretiese fundering van pedoterapie is gedoen, waarin daar, onder andere, klem geplaas is op 'n ontleding van die begrip en idee pedoterapie, pedoterapeutiese verhoudinge, diagnostisering, vorme van pedoterapie en die aard enrol van 'n mensbeeld in die opvoedkundige sielkundige praktyk. 'n Soektog na kategoriee waarmee 'n verantwoordbare Sielkundige Opvoedkundige wetenskap en opvoedkundige sielkundige praktyk beskryf kan word, is ondemeem. Daarna is kriteria vir die evaluering van pedoterapeutiese arbeid geformuleer. Die oorsprong vir en die waarde van 'n universele etiese kode vir terapeute is teen die agtergrond van 'n mensbeeld bespreek. Aan die hand van 'n empiriese ondersoek is daar bepaal wat die stand van opvoedkundige sielkundige teorie en praktyk teenswoordig sou wees. Hierdie empiriese ondersoek is met idiografiese onderhoude uitgevoer, waama idiogramme saamgestel is. Met die empiriese ondersoek is daar gepoog om 'n beeld te verkry van hoe vertroud hedendaagse praktisyns met teoretiese grondslae en die waarde van 'n ontologiese mensbeeld, die waarde van evalueringskriteria en die stand van die Sielkundige Opvoedkunde se toepassingsmoontlikhede vir die pedoterapeutiese praktyk is of nie is nie. Deelnemende opvoedkundige sielkundige praktisyns se praktyksbenadering in etiese en praktiese konteks is verkry asook bulle oordele van, onder meer, heersende voorskrifte en voorstelle ter bevordering van die opvoedkundige sielkundige praktyk. 'n Aantal aanbevelings is gemaak op grond van die bevindinge vanuit die totale studie. 'n Aanloop tot die daarstelling van 'n etiese kode vir opvoedkundige sielkundiges is gemaak. / The beginning of the new millennium is characterized by radical technological progress, paradigm shifts in natural and human sciences, increasing uncertainty about the real nature of the human being and how one person can assist another in an accountable way with solving problems in order to restore human dignity through educational psychological assistance. Research is carried out to determine what an accountable educational psychological practice, with special reference to pedotherapy, should entail. A literature study regarding basic requirements of an accountable educational psychological practice in historical and contemporary perspective is included. A further literature study is executed concerning an accountable pedotherapeutic practice. A theoretical grounding of pedotherapy is included in the literature study and specific attention is given to an analysis of the concepts and ideas of pedotherapy. pedotherapeutic relationships, the diagnostic approach and forms of pedotherapy. The nature and role of a view of human kind in educational psychological practice is also discussed. Categories describing an accountable science of Psychology of Education and its practice are presented. Subsequent criteria for the evaluation of pedotherapeutic endeavour are formulated. Origins for and the value of a universal code of ethics for pedotherapists are discussed against the background of a view of human kind. By means of an empirical investigation it is determined what the current status of Psychology of Education in theory and practice is. This investigation is conducted by means of idiographic interviews and afterwards idiogrammes are compiled to determine to what extent practitioners are conversant with theoretical foundations and an ontological view of human kind, the value of evaluation criteria and the possibilities presented by the insights of Psychology of Education and how practitioners approach their practice in ethical stance. Also the views of practitioners on current prescriptions and their suggestions for improving educational psychological practice are obtained. A number of recommendations is presented in the light of findings from the entire study. A trial run for the formulation of an ethical code for educational psychologists is presented. / Psychology of Education / D. Ed. (Sielkundige Opvoedkunde)

No description available.

Summaries in Afrikaans and English / Die begin van die nuwe millennium word gekenmerk deur radikale vooruitgang op tegnologiese gebied, paradigmatiese verskuiwings in natuur- en geesteswetenskappe, toenemende onsekerheid oor wat die ware aard van die mens is en hoe die een mens die ander verantwoordbaar kan help met die oplossing van probleme en herstel van menswaardigheid deur middel van opvoedkundige sielkundige ondersteuning. Navorsing is ondemeem om 'n beeld te verkry van wat 'n verantwoordbare opvoedkundige sielkundige praktyk met besondere verwysing na pedoterapie, kan wees. 'n Literatuurstudie is gedoen aangaande grondeise van 'n verantwoordbare opvoedkundige sielkundige praktyk in historieskomtemporere konteks. 'n Verdere literatuurstudie is gedoen aangaande 'n verantwoordelike en verantwoordbare pedoterapeutiese praktyk in opvoedings- en medemenslikheidsperspektief. 'n Teoretiese fundering van pedoterapie is gedoen, waarin daar, onder andere, klem geplaas is op 'n ontleding van die begrip en idee pedoterapie, pedoterapeutiese verhoudinge, diagnostisering, vorme van pedoterapie en die aard enrol van 'n mensbeeld in die opvoedkundige sielkundige praktyk. 'n Soektog na kategoriee waarmee 'n verantwoordbare Sielkundige Opvoedkundige wetenskap en opvoedkundige sielkundige praktyk beskryf kan word, is ondemeem. Daarna is kriteria vir die evaluering van pedoterapeutiese arbeid geformuleer. Die oorsprong vir en die waarde van 'n universele etiese kode vir terapeute is teen die agtergrond van 'n mensbeeld bespreek. Aan die hand van 'n empiriese ondersoek is daar bepaal wat die stand van opvoedkundige sielkundige teorie en praktyk teenswoordig sou wees. Hierdie empiriese ondersoek is met idiografiese onderhoude uitgevoer, waama idiogramme saamgestel is. Met die empiriese ondersoek is daar gepoog om 'n beeld te verkry van hoe vertroud hedendaagse praktisyns met teoretiese grondslae en die waarde van 'n ontologiese mensbeeld, die waarde van evalueringskriteria en die stand van die Sielkundige Opvoedkunde se toepassingsmoontlikhede vir die pedoterapeutiese praktyk is of nie is nie. Deelnemende opvoedkundige sielkundige praktisyns se praktyksbenadering in etiese en praktiese konteks is verkry asook bulle oordele van, onder meer, heersende voorskrifte en voorstelle ter bevordering van die opvoedkundige sielkundige praktyk. 'n Aantal aanbevelings is gemaak op grond van die bevindinge vanuit die totale studie. 'n Aanloop tot die daarstelling van 'n etiese kode vir opvoedkundige sielkundiges is gemaak. / The beginning of the new millennium is characterized by radical technological progress, paradigm shifts in natural and human sciences, increasing uncertainty about the real nature of the human being and how one person can assist another in an accountable way with solving problems in order to restore human dignity through educational psychological assistance. Research is carried out to determine what an accountable educational psychological practice, with special reference to pedotherapy, should entail. A literature study regarding basic requirements of an accountable educational psychological practice in historical and contemporary perspective is included. A further literature study is executed concerning an accountable pedotherapeutic practice. A theoretical grounding of pedotherapy is included in the literature study and specific attention is given to an analysis of the concepts and ideas of pedotherapy. pedotherapeutic relationships, the diagnostic approach and forms of pedotherapy. The nature and role of a view of human kind in educational psychological practice is also discussed. Categories describing an accountable science of Psychology of Education and its practice are presented. Subsequent criteria for the evaluation of pedotherapeutic endeavour are formulated. Origins for and the value of a universal code of ethics for pedotherapists are discussed against the background of a view of human kind. By means of an empirical investigation it is determined what the current status of Psychology of Education in theory and practice is. This investigation is conducted by means of idiographic interviews and afterwards idiogrammes are compiled to determine to what extent practitioners are conversant with theoretical foundations and an ontological view of human kind, the value of evaluation criteria and the possibilities presented by the insights of Psychology of Education and how practitioners approach their practice in ethical stance. Also the views of practitioners on current prescriptions and their suggestions for improving educational psychological practice are obtained. A number of recommendations is presented in the light of findings from the entire study. A trial run for the formulation of an ethical code for educational psychologists is presented. / Psychology of Education / D. Ed. (Sielkundige Opvoedkunde)

Present highly competitive environment has significantly contributed to the state in which success of entrepreneurial subjects is conditioned among others by their ability to identify and eliminate gaps in their performance as fast as possible. It is inevitably connected with the necessity to know the firm itself, which is one of the unexceptionable condition of reaching and maintaining competitiveness. The dissertation thesis reacts to above shown fact and to generally perceived want of suitable methodology of organizational self-assessment aimed at improvement for small and middle enterprises. The issue of organizational self-assessment is analyzed and assessed complexly in this dissertation thesis. Also less known connections and relationships as to the issue of organizational self-assessment are given here, which provides a desirable comprehensive view. In the dissertation thesis there are also specified relevant definitions relating to the subject of the dissertation thesis. The definitions are specified in mutual relationships, which increases their value in light of their contribution both to theory and to practice. In relation to the analysis of the present state in the sphere of organizational self-assessment, the dissertation thesis introduces the most spread and best known models used for organizational self-assessment. A very important part of the analytical part is created by the determination of basic approaches to organizational self-assessment with closer specification of diagnostically oriented self-assessment. A pivotal part of the dissertation thesis is represented by my own draft of the methodology of organizational self-assessment aimed at formation and maintenance of competitiveness. This methodology is based on diagnostically oriented organizational self-assessment and is intended above all for small and middle manufacturing enterprises that are certified according to the ISO 9001/2000 standard. Submitted methodology was verified with positive result in a middle manufacturing enterprise. The methodology itself is based on a frame model and on an algorithm that should facilitate the implementation and regular realization of the organizational self-assessment.