5 à 10% des cancers du sein sont héréditaires mais parmi ceux-ci seulement la moitié est expliquée par une altération constitutionnelle d’un gène de prédisposition connu tels que les gènes BRCA1 et BRCA2. L’importante hétérogénéité génétique qui caractérise les famillesBRCAx rend difficile la réalisation d’études familiales groupées et ne permet pas l’identification de nouveaux gènes de prédisposition au cancer du sein selon les méthodes classiques de liaison génétique ou d’association. Les techniques de séquençage de nouvelle génération (NGS) à l’échelle de l’exome ou du génome entier, autorisent en revanche l’étude de familles individuelles à la recherche de mutations constitutionnelles privées mais le nombre considérable de variants génétiques identifiés impose leur tri sur des critères de pathogénicité ou de récurrence. Un autre critère de tri peut être représenté par l’identification de régions candidates définies en fonction de réarrangements génomiques tumoraux communs à plusieurs tumeurs au sein d’une même famille. Le génotypage tumoral par puces SNP (pour single nucleotide polymorphism) permet en effet la détection d’haplotypes conservés dans des régions récurrentes de LOH (pour loss of heterozygosity) communes à plusieurs tumeurs familiales et donc l’identification de régions candidates suspectes d’abriter des mutations germinales dans des gènes de prédisposition au cancer. La combinaison de ces deux approches, génotypage tumoral puis NGS, a été appliquée à une série de 17 familles avec agrégation de cancers du sein pour lesquelles au moins deux échantillons tumoraux étaient disponibles. Aucun nouveau gène de prédisposition au cancer du sein n’a été identifié mais une mutation délétère constitutionnelle du gène ATM a ainsi été retrouvée, associée à une perte de l’allèle sauvage dans les 2 tumeurs d’une famille BRCAx. L’analyse de 17 tumeurs du sein supplémentaires provenant de 10 familles avec agrégation de cancers du sein et mutation constitutionnelle du gène ATM identifiée chez le cas index, a révélé que l’allèle sauvage d’ATM était fréquemment perdu dans ces tumeurs (>80% contre 20% attendu en situation sporadique ; p<0.001). Ce résultat plaide fortement en faveur de l’implication d’ATM dans la carcinogénèse de ces cancers du sein tel un gène suppresseur de tumeur et suggère que les mutations constitutionnelles d’ATM sont impliquées dans des formes familiales de cancer du sein. / Hereditary breast cancers (BCs) account for 5-10% of all diagnosed BCs, yet only 50% of such tumors arise in the context of a germline mutation in known tumor suppressor genes such as BRCA1 or BRCA2. The vast genetic heterogeneity which characterizes BRCAx families makes grouped studies impossible to perform. Next generation sequencing (NGS) techniques, however, allow individual families to be studied in order to identify private mutations. Single nucleotide polymorphism (SNP) arrays allow the detection of conserved haplotypes within recurrent regions of loss of heterozygosity, common to several familial tumors, therefore identifying genomic loci likely to harbor a germline mutation in cancer predisposition genes. The combination of both exome sequencing and SNP arrays for a series of 17 familial BC did not allow the identification of a novel BC predisposition gene, but revealed a germline ATM mutation associated with a loss of the wild-type allele in a BRCAx family. The analysis of 17 additional breast tumors from ten BC families in which a germline ATM mutation had been identified revealed a high frequency of wild-type allele loss in these tumors (>80% compared to the 20% expected in sporadic BC; p <0.001). This result argues strongly in favor of the involvement of ATM in the carcinogenesis of these tumors as a tumor suppressor gene and suggests that germline ATM mutations are involved in a subset of familial BC.

Habitants tout comme la distribution du pays. L’enfant qui occupe une place importante dans la société vietnamienne est bien entendu associé à ce changement. Les enfants sont par exemple nombreux dans les nouveaux supermarchés vietnamiens,ou dans les centres commerciaux nouvellement crées. Notre recherche est née de cette interrogation : Les enfants peuvent-ils être des alliés pour la grande distribution qui se développe au Vietnam ?La revue de littérature nous amène à étudier l’enfant consommateur avec les spécificités par rapport à l’adulte. De plus, comme l’enfant consommateur est dépendant de ses parents qui décident l’achat familial dans la plupart des cas, nous étudions l’enfant dans l’achat familial avec le rôle des parents dans le processus de socialisation du consommateur de l’enfant.Cette revue de littérature a été ensuite combinée avec une enquête qualitative de 20 entretiens avec les parents et 20 entretiens avec les enfants élèves scolaires à Hanoi pour la vérification sur la coïncidence entre les concepts et les pratiquesde consommation dans le contexte occidental et ceux dans le contexte du Vietnam. De plus, cette enquête a pour but de générer les items susceptibles d’enrichir les échelles occidentales. Le résultat de cette enquête nous a amené à présenterdeux modèles distinctifs, l’un lié aux parents, l’autre lié aux enfants au Vietnam.Après les prétests avec les démarches positivistes, nous arrivons à vérifier la fiabilité des variables de nos modèles tout en respectant le paradigme de Churchill (1977). Ensuite, nous avons pu lancer notre enquête finale dans les 3 écoles primaires de Hanoï.1181 enfants élèves des classes en 4e et en 5e, ainsi que 921 parents de ces élèves ont participé à répondre à nosquestionnaires. Le résultat de cette enquête nous donne des conclusions sur l’existence de la participation de l’enfant à l’achat familial au Vietnam, la préférence de l’enfant à l’achat dans les types de commerce moderne. Cette participation est liée à la communication au sein de la famille dont ce qui compte, c’est la fréquence de communication plus que sa nature (l’orientation)de cette communication. De plus, les familles vietnamiennes n’ont pas toutes les mêmes objectifs éducatifs tandis que les pratiques sont assez semblables selon les familles, mais les attentes varient, et la classe sociale semble jouer un rôle. / The current Vietnam saw a significant change in its economic system. This system influences the lifestyle of the inhabitants as the retailing of the country. The child as an important place in Vietnamese society is of course associated with this change. Children are for example in many new Vietnamese supermarkets, or in newly created shopping centers. Our research grew out of this question: Can children be allies for retailing that develops in Vietnam?The literature review leads us to study consumer-child with specifics compared to adults. Furthermore, as consumer-child is dependent on his parents who choose to family purchase in most cases, we study the child in the family purchase withparenting in consumer socialization of children’s process.This literature review was then combined with a qualitative survey of 20 interviews with parents and 20 interviews with children in primary schools in Hanoi for checking the coincidence between the concepts and practices of consumption in the Western context and those in the context of Vietnam. In addition, this survey aims to produce items that can enrich Western scales. Theresult of this investigation has led us to present two distinct models, one related to the parents, the other related to children in Vietnam.After pretesting with positivist approaches, we can verify the reliability of the variables in our models while respecting the paradigm of Churchill (1977). Then we were able to launch our final survey in three primary schools in Hanoi.1181 children's in 4th and 5th grades and 921 parents of these children participated in answering our questionnaire. The result of this survey give us conclusions on the existence of the child's participation in family purchase in Vietnam, the preference of the child to purchase in modern commerce. This participation is related to communication within the family that what matters isthe communication frequency than its nature (guidance) of that communication. In addition, Vietnamese families do not all have the same educational objectives while practices are quite similar among families, but expectations vary, and social class seems to play a role.

Dentre todos os tipos de câncer, excluindo-se o câncer de pele do tipo não melanoma, o de mama é o mais frequente em mulheres, sendo a segunda maior causa de morte por neoplasias nesse segmento da população. Em determinadas famílias, a incidência de câncer é superior à esperada para a população em geral, devido principalmente ao compartilhamento de fatores ambientais e/ou mutações genéticas responsáveis por facilitar ou dirigir a oncogênese. Os indivíduos que apresentam câncer de mama e histórico familial dessa patologia são descritos dentro do grupo câncer de mama familial (CMF), responsável por aproximadamente 5 a 10% do total de casos de câncer de mama. Atualmente, pacientes com CMF são frequentemente testados para mutações nos genes BRCA1 e BRCA2. Entretanto, estima-se que as variantes patogênicas presentes nos dois genes são responsáveis por somente 20% dos casos de CMF em que a etiologia genética é conhecida. Com relação aos testes genéticos para predisposição hereditária ao câncer de mama, torna-se relevante, portanto, a reavaliação da constituição dos painéis multigênicos frente ao estado do conhecimento científico atual, contemplando-se as mais recentes atualizações acerca dos genes e variantes genéticas associadas ao CMF. Neste trabalho, realizamos uma revisão bibliográfica que identificou 45 genes com associação estatística ao CMF, dentre eles 16 são frequentemente avaliados em painéis multigênicos brasileiros e internacionais. Em análise in silico, avaliamos as funções celulares e interações entre os produtos gênicos associados à patologia. Nossos resultados sugerem a adição de oito genes à composição de painéis multigênicos realizados no Brasil, EUA e Europa para avaliação da predisposição hereditária ao câncer de mama. Essa análise crítica pode auxiliar o aprimoramento de estratégias de prevenção, triagem, manejo clínico e determinação do risco de ocorrência e recorrência, com impactos sobre o aconselhamento genético (AG) oferecido aos pacientes afetados pelo câncer familial e seus familiares. Complementarmente, avaliamos as variantes gênicas presentes em pacientes com câncer de mama que realizaram o painel multigênico para predisposição hereditária ao câncer no Centro de Pesquisa sobre o Genoma Humano e Células-Tronco (CEGH-CEL). As frequências de mutações da coorte do CEGH-CEL são semelhantes às obtidas em estudos internacionais, possibilitando a utilização de painéis multigênicos com composições similares em populações de diversas localidades / Of all types of cancer, except for non-melanoma skin cancer, breast cancer is the most common among women, and it\'s the second leading cause of death by neoplasia in this segment of the population. In some families, the incidence rates of cancer are higher than expected for the general population because of the environmental factors and/or genetic mutations responsible for facilitating or driving oncogenesis. The individuals who have breast cancer and a family history of this pathology fall into the group of familial breast cancer (FBC), which is responsible for approximately 5-10% of all breast cancer cases. Currently, patients with FBC are frequently tested for mutations in the BRCA1 and BRCA2 genes. It is estimated, however, that the pathogenic variants of these genes account for only 20% of all FBC cases in which the genetic etiology is known. In relationship to the genetic tests for inherited predisposition for breast cancer, therefore it is relevant to reassess the multi-gene panel composition, considering the state of scientific knowledge today, including the most recent research on the genes and its variants associated with FBC. In this paper we did a literature review, which identified 45 genes statistically associated with FBC, out of which 16 are frequently assessed in multi-gene panels in Brazil and abroad. Through in silico analysis we were able to evaluate cell functions and interactions with gene products associated with cancer. Our results suggest the addition of eight genes to the multi-gene panel composition carried out in Brazil, in the USA and in Europe to assess hereditary predisposition to breast cancer. This critical analysis can assist in the development of preventive actions, triage, clinical management and in determining the risk of occurrence and recurrence, which impacts on the genetic counseling (GC) offered to the patients of familial cancer and their relatives. Additionally, we evaluated the genetic variants in patients diagnosed with breast cancer who have undergone multi-gene panel testing for hereditary predisposition to cancer at the Centro de Pesquisa sobre o Genoma Humano e Células-Tronco (CEGH-CEL). These cohort\'s mutation frequencies are similar to the results in international studies, which could enable the use of multi-gene panels with similar compositions in populations from various locations

No description available.

Background: Primary aldosteronism (PAL) has emerged as the commonest specifically treatable and potentially curable form of secondary hypertension. With its propensity towards cardiovascular complications above that expected from hypertension alone, PAL is a potentially highly detrimental state which should be detected as early as possible in the course of the disease and treated appropriately. The detection of earlier, milder, normokalaemic forms of PAL using the aldosterone/renin ratio (ARR) as a screening test has significantly enlarged the clinical spectrum of PAL and facilitated identification of a new familial variety (familial hyperaldosteronism type II, FH-II). Unlike familial hyperaldosteronism type I (FH-I), FH-II is not glucocorticoid remediable and is not caused by the CYP11B1/CYP11B2 “hybrid” gene mutation. The genetic defects underlying FH-II have not yet been elucidated and hence, detection of FH-II still involves complicated and time-consuming biochemical screening by ARR testing and confirmation by carefully performed suppression testing such as fludrocortisone suppression testing. Diagnosing PAL by currently available biochemical methods is tedious. Finding a simple and reliable genetic test for FH-II which could be applied to all members of a family with known FH-II and also to apparently sporadic PAL would simplify patient management. A genome-wide search has already demonstrated linkage of FH-II to chromosome 7p22, consistent with this locus harbouring the causative gene/s for FH-II. Three candidate genes [retinoblastoma-associated Kruppel-associated box gene (RBaK, involved in tumorigenesis and cell cycle control), postmeiotic segregation increased 2 (PMS2, involved in DNA mismatch repair and tumour predisposition) and guanine nucleotide-binding protein alpha-12 (GNA12, a transforming oncogene)] within this linked locus have been examined in an attempt to find the causative mutations for FH-II, but no clear causative mutations have so far been found. PAL continues to be a challenging yet rewarding disease to manage. Although much has been learnt about PAL, there are still many areas which have not been explored. PAL considered due to bilateral autonomous production of aldosterone is usually treated medically because unilateral adrenalectomy has been considered ineffective. Since medical treatment may cause adverse effects or fail to control hypertension, defining the role of unilateral adrenalectomy in bilateral PAL is an important clinical issue, but quality outcome data are lacking. The candidate therefore peformed a retrospective study of the efficacy of unilateral adrenalectomy in patients with bilateral PAL. In patients with unilateral PAL, unilateral laparoscopic adrenalectomy has been shown to correct hypokalaemia and lead to cure or improvement in hypertension control. While most studies have focused on clinical and biochemical outcomes, to the candidate’s knowledge, there are no data on the effects of adrenalectomy on quality of life (QOL). Assessing the QOL in patients with unilateral PAL before and after unilateral laparoscopic adrenalectomy (which cured hypokalaemia in all and hypertension in the majority) provided an insight into the degree to which the disease process and/or its treatment affects the life of an individual with PAL. Aims: The overall aims of this thesis were to further explore the genetic basis of FH-II, to examine the role of adrenalectomy in patients with bilateral PAL and the effects of unilateral adrenalectomy on QOL in unilateral PAL as a first step in dissecting out the effects of medical and surgical treatment on QOL in the more common bilateral PAL. In order to address the overall aims, the specific aims of the thesis were (1) to narrow the linked region at 7p22 by phenotyping and genotyping additional FH-II families from Italy, using more closely spaced microsatellite markers at 7p22, and then assess the combined multipoint logarithm of odds (LOD) score for these Italian as well as two Australian and one South American families; (2) to sequence candidate genes in the narrowed linked region for FH-II associated mutations; (3) to assess the role of unilateral adrenalectomy in bilateral PAL and identify predictive parameters; and (4) to assess the quality of life following unilateral adrenalectomy in patients with unilateral PAL. Methods and Results: Two Italian families with FH-II were genotyped using seven closely spaced microsatellite markers at 7p22. All known affected individuals from each of the two Italian families were found to share identical haplotypes for the seven markers, consistent with linkage of the disease locus with the 7p22 region. The multipoint LOD score of the now five known families with FH-II which demonstrate linkage at 7p22, calculated using MERLIN linkage analysis was highly significant at 5.22. Three candidate genes in this linked region were then examined for mutations causing FH-II; the replication protein A 3 (RPA3), zinc finger protein 12 (ZNF12) and glucocorticoid induced transcripts 1 (GLCCI1) genes were selected as they are involved in cell cycle control, and adrenal hyperplasia and adenomas are common in FH-II. Using the method of polymerase chain reaction-sequencing, coding regions, splice sites, proximal promoter, 5’ and 3’ untranslated regions (UTR) were sequenced in affected and unaffected subjects from the 7p22-linked FH-II families. Identified single nucleotide polymorphisms (SNPs) were genotyped to assess significance. For RPA3, four different SNPs were initially found to segregate with the affectation status, that is, they were present in the two affected and not the two unaffected subjects from the largest Australian family (family 1, eight affecteds) with FH-II. However, only two SNPs (rs2024374 G/C and rs17169194 T/G) were further genotyped as that they were in functionally important positions of the gene (that is, in regulatory regions within the promoter and 5’ UTR) and because of the relatively low allele frequency reported in the literature for these two SNPs in controls. Further genotyping of these SNPs was carried out in another six affecteds and four unaffecteds from the same family and a complete segregation of these two SNPs with affectation status was seen in family 1. The G/C mutation rs2024374 in the RPA3 promoter results in the loss of three transcription factor binding sites and creation of one new site. The factors for which the binding sites in the RPA3 promoter and 5’UTR were altered by these two SNPs were involved in regulation of cell differentiation, proliferation and apoptosis. Hence, it is possible that altered activity of the RPA3 promoter and 5’UTR in family 1 could result in predisposition to adrenal hyperplasia or neoplasia, altered ARR and/or hypertension. Genotyping of these SNPs was then carried out in another two pedigrees (families 2 and 3) that showed linkage to 7p22, and in 75 normotensive, non-PAL control subjects. However, neither of these two SNPs segregated with the affectation status in family 2 and 3, and they were present in 30% and 20% of controls, respectively. For ZNF12 and GLCCI1, no evidence of causative mutations was found in the coding regions, splice sites, proximal promoter region and proximal 5’ and 3’ UTR. Between 1984 and 2004, 51 of 684 patients diagnosed with bilateral PAL underwent unilateral adrenalectomy. Forty patients fulfilled the inclusion criteria and were followed for at least 12 (median 56.4) months. Hypertension was cured in 15% and improved in 20%, usually within one year of unilateral adrenalectomy. The proportion with controlled hypertension was significantly (p<0.001) higher after adrenalectomy (65%) than before (25%). Mean systolic (p<0.001) and diastolic (p<0.001) blood pressure, left ventricular mass index (p<0.05) and aldosterone/renin ratio (p<0.001) fell. Serum creatinine independently predicted hypertension cure. From 2007 through 2008, QOL was evaluated prospectively using the internationally validated SF-36 questionnaire before and 3 and 6 months post-operatively in 22 patients [14 males, 8 females; mean age 50.0 ± 2.0 (range 27-69) years] with unilateral PAL who underwent adrenalectomy within the Endocrine Hypertension Centre, Greenslopes and Princess Alexandra Hospitals. Pre-operatively, the SF36 score for each QOL domain was lower for PAL patients than reported for the Australian general population, significantly so for physical functioning (p<0.05), role physical (p<0.001), vitality (p<0.001) and general health (p<0.05). Compared with pre-adrenalectomy, there were significant increments in mean scores at 3 months for physical functioning (p<0.05), role physical (p<0.05), general health (p<0.001), role emotional (p<0.05), social functioning (p<0.05), mental health (p<0.001) and vitality (p<0.001); and at 6 months for physical functioning (p<0.05), role physical (p<0.05), general health (p<0.05), role emotional (p<0.05), mental health (p<0.05) and vitality (p<0.001). Mean SBP and DBP improved significantly (p<0.001), with 86% of these patients cured (BP≤140/90, no drugs) and the remaining 14 % improved. Mean plasma potassium (p<0.001) and renin concentration rose (p<0.01), whereas mean upright plasma aldosterone (p<0.001), aldosterone/renin ratio (p<0.001) and number of antihypertensive agents fell (p<0.001). Conclusion: In the Italian families with FH-II available for study, work by the candidate included in this thesis confirmed linkage of FH-II to chromosome 7p22. The combined multipoint LOD score of 5.22 for the five families showing linkage at 7p22 was highly significant. Linkage to 7p22 in Italian families with FH-II extends the previous positive findings to a third geographical area, bringing greater certainty regarding the importance of this locus in identifying causative mutations. Although no clear causative mutations were found in the three 7p22 candidate genes examined, it is conceivable that the rs2024374 G/C and/or rs17169194 T/G SNPs in RPA3 could act in conjunction with another 7p22 mutation in family 1, resulting in the FH-II phenotype. Examination of the outcome of unilateral adrenalectomy in patients with bilateral PAL suggests that this surgical approach can be beneficial in certain carefully selected patients and should not be automatically excluded as a treatment option. Unilateral adrenalectomy in patients with unilateral PAL has positive impacts not only on clinical and biochemical parameters but also on QOL. The findings of this thesis provide new insights into the genetic basis and therapeutic options and treatment outcomes of PAL and further highlight its importance as a common, genetically based, specifically treatable and potentially curable cause of hypertension and cardiovascular disease. It also points the way to potentially very useful studies in future by exploring longer term effects of unilateral laparoscopic adrenalectomy as treatment for PAL on QOL, to compare unilateral adrenalectomy in those with unilateral versus bilateral PAL, and to compare surgery with specific medical treatment.

Si certaines formes de violence sont aujourd'hui l'objet de toutes les attentions, d'autres comme la violence conjugale, restent tues, considérées trop souvent comme un problème privé. La violence masculine constitue une véritable atteinte aux droits fondamentaux: droit à la liberté et à la sécurité notamment. La violence conjugale, quelle que soit sa forme, présente des constantes. Ainsi ce type de violence existe dans les sociétés orientales et occidentales mais le contexte diffère. Si les violences conjugales dans les sociétés orientales notamment celle libanaise reflètent le patriarcat, la reproduction sociale et l’héritage familial et que les lois et les codes civiles favorisent le statut de l’homme, celles qui existent dans les sociétés occidentales sont reliées aux affects psychologiques, aux dissociations familiales et aux problèmes familiaux. Dans tous les pays du Moyen-Orient, comme au Liban, les femmes ne bénéficient pas pleinement de leur citoyenneté civile. Elles sont notamment spoliées de droits, privilèges et garanties de sécurité auxquelles elles devraient avoir accès. Des lois inéquitables, des constitutions discriminatoires et des préjugés culturels, qui ne les reconnaissent pas comme des citoyennes égales, entravent leur participation à la vie politique et limitent leur sécurité en matière économique, de mobilité et de protection sociale. A la différence du contexte occidental, comme en France et au Canada, où l’individu est l’unité de base de l’Etat, c’est la famille qui forme la base des Etats arabes.On tente donc de confirmer que la violence conjugale comme toutes sortes de violence, elle s’échappe à toutes nominations sociales, elle existe dans toutes les sociétés et les régions même les plus favorisées d’entre elles et elle est présente chez toutes les catégories sociales.Une approche interculturelle de ce phénomène s’avère donc nécessaire, des facteurs comme religion et migration demeurent être parfois déclenchant ou légitimant d’un tel type de violence. L’analyse psycho-sociale de plusieurs études de cas de violences conjugales ne peut que dévoiler le latent, le caché des hommes violents et des femmes violentées. / If some forms of silence are today the center of attention, other forms such as conjugal violence remain unrevealed and are often considered as private problems. Men violence is affecting fundamental rights in particular the right of liberty and security. Conjugal violence, whatever its forms are, presents some constants. This type of violence is found in oriental and occidental societies but the context differs. If conjugal violence in oriental societies particularly in Lebanon reflects the patriarchy and the social reproduction and the family inheritance, it also shows that the law and the civil codes are in favor of men. The conjugal violence existing in the occidental societies are related to psychological affects and family separations and family problems. In all Middle – Eastern countries like Lebanon, women do not benefit completely from their civil citizenship. They are despoiled of rights, and privileges and security guarantee that they should have access to. Inequitable laws, discriminatory constitutions and cultural prejudice that doesn’t take the woman as an equal citizen, hinder their participation in politics and limit to the women’s economic security going from mobility to social welfare. Unlike the occidental context where the individual unites the base of the country like in France and Canada, family constitutes the base of Arab countries.They tend to confirm that conjugal violence like any form of violence escapes from any social nominations. This violence exists in all societies and even in the most favored regions. And it also exists in all social categories.A cross-cultural approach of this phenomenon is necessary. Factors such as religion or migration launch or justify such type of violence. Psychosocial analysis of several studies made about conjugal violence unveil the latent and the hidden secrets of violent men and abused women.

Ce mémoire par article s'intitule Caractéristiques familiales associées aux trois profils du trouble déficitaire de l'attention/hyperactivité chez les enfants âgés de 6 à 9 ans . Celui-ci fait suite aux nombreuses études s'étant intéressées à la catégorisation du trouble déficitaire de l'attention/hyperactivité (TDA/H; American Psychiatric Association, 1994) qui entraîne la subdivision du trouble en trois profils distincts : inattention prédominante (TDA/H-I), hyperactivité-impulsivité prédominante (TDA/H-H) et mixte (TDA/H-M). Plusieurs différences sur le plan individuel ont été identifiées jusqu'ici entre les enfants des trois profils, mais les différences sur le plan des caractéristiques familiales restent encore à éclaircir. L'objectif de cette étude est de vérifier si les familles d'enfants ayant un TDA/H se distinguent en fonction du profil diagnostique de leur enfant. Les participants sont 110 familles d'enfants d'âge primaire présentant un TDA/H (TDA/H-I : n = 31, TDA/H-H : n = 11, TDA/H-M : n = 68). Les résultats démontrent que les familles d'enfants ayant un TDA/H se différencient uniquement au niveau du stress parental en fonction du profil de leur enfant lorsqu'un contrôle statistique est exercé pour la présence du trouble oppositionnel. Ainsi, peu de différences sont observées entre les trois profils sur la base de leurs caractéristiques familiales.

La présente étude visait à identifier parmi un ensemble de caractéristiques familiales (telles que le ratio de cohésion et de flexibilité, la qualité de la communication, l'expression des émotions négatives et positives, la satisfaction concernant le fonctionnement familial et la qualité de la relation des parents à l'égard des jeunes) celles qui sont les plus fortement associées à l'anorexie boulimique. Pour atteindre cet objectif, nous avons effectué une étude descriptive et comparative transversale. Notre échantillon est composé de 38 familles d'adolescentes anorexiques, dont 29 adolescentes présentant une anorexie restrictive et neuf présentant une anorexie boulimique. Selon les résultats obtenus, le fonctionnement des familles des adolescentes anorexiques boulimiques ne semble pas différencier de façon significative de celui des familles des adolescentes anorexiques restrictives sur presque toutes les variables considérées (ratio de cohésion et de flexibilité familiale, qualité de la communication, satisfaction concernant le fonctionnement familial, niveau d'expression des émotions positives et niveau de l'appréciation de la relation des parents à l'égard des adolescentes).La seule différence observée entre ces deux sous-groupes indique que les adolescentes anorexiques boulimiques obtiennent un score significativement plus élevé à la sous-échelle expression des émotions négatives dans la famille comparativement aux adolescentes anorexiques restrictives.

L'objectif de ce mémoire est de vérifier quelles caractéristiques familiales fonctionnelles jouent un rôle médiateur dans la relation entre le SSE et les troubles de comportement intériorisés et extériorisés. Pour ce faire, des régressions linéaires multiples ont été effectuées selon la procédure de MacKinnon à l'aide des données d'un échantillon de 480 enfants de 6 à 11 ans. Les résultats obtenus sous-tendent que la relation entre le SSE et les troubles de comportement n'est pas directe, mais transmise indirectement par les pratiques positives et le fonctionnement familial en ce qui concerne le lien entre le SSE et les troubles intériorisés alors que le lien entre le SSE et les troubles extériorisés est transmis indirectement par le manque de supervision et le fonctionnement familial. Les résultats sont similaires pour les 2 catégories de troubles, militant en faveur de l'utilisation de mêmes programmes pour prévenir les troubles intériorisés et extériorisés.

Knee osteoarthritis (OA) is the commonest form of lower limb OA with a lifetime risk of over 40%. It is a disease characterised by symptoms such as pain and loss of function. In addition there are typical structural features on both radiographs and MRI. Knee OA represents a spectrum of disease, ranging from early preclinical cartilage change to established full thickness disease. Anteromedial knee OA is a particular phenotype of knee OA where disease is confined to the medial compartment. Whilst end stage arthritis is treated reliably with joint arthroplasty, those with early stage disease are treated with a variety of non- surgical interventions with varying success. This thesis is concerned with understanding the disease of patients that have early radiographic changes but symptoms not controlled by conservative measures. Up to 150 of these patients a year present to the Nuffield Orthopaedic Centre, Oxford. They have been described as being in the “Treatment Gap”. A series of validation studies were performed to determine the optimal method for diagnosing cartilage defects within the knee. The three commonest diagnostic methods were examined for their validity. Arthroscopic assessments of cartilage lesions demonstrated a moderate level of intra and inter observer reliability. In contrast, radiographs and MRI demonstrated high levels of reliability. When using MRI as a criterion standard, both radiographs and arthroscopic assessment were found to have poor accuracy. Based on the work in this thesis a formal definition of the cartilage changes exhibited in early knee OA was proposed. A cross sectional cohort of 100 patients with the symptoms and radiological features of early knee OA were identified. Their pain and function profile was compared to two comparison groups of patients at the end stage of knee OA (defined by the need for partial or total arthroplasty). In up to 78% of individual cases those with early OA had pain and function profiles as bad as those with end stage disease. The cross sectional symptoms of early knee OA demonstrate a marked discordance with their mild radiographic changes. The same cohort was extended to 125 patients. They were followed over one year with monthly PROM assessments to determine how symptoms change over time. 43% of patients experience a clinical improvement over 12 months, 31% experience a clinical deterioration and 26% remain unchanged. The range in OKS variation over 12 months was on average 12 points, with clinically relevant variation occurring on 45% of monthly measurements. Patients with early knee OA can expect to experience considerable variation in their symptoms over 12 months and this must be considered when planning interventions. A number of patients with early knee OA were noticed to demonstrate medial meniscal extrusion. Using data from the Osteo Arthritis Initiative (OAI) a nested case control study was designed to determine how the presence of meniscal extrusion in an otherwise normal knee affects the risk of developing knee OA over the next 48 months. This demonstrated an Odds Ratio of 3.5, suggesting that meniscal extrusion is a considerable risk factor for the development of OA. The presence of a knee injury or operative intervention to the index meniscus was shown to increase this risk. Many phenotypes of OA are known to demonstrate familial aggregation. In an attempt to determine where the earliest structural changes occur in medial compartment knee OA, a cohort of patients selected only for their family history of the disease were developed. This cohort was compared to spouse controls for the presence of knee OA, as well as meniscal extrusion and long leg alignment. In addition, a functional analysis of their cartilage was performed. This cohort was not shown to be at increased risk of disease compared to controls. Discussion of the possible reasons for this finding is presented. Early knee osteoarthritis is a considerable clinical problem. This thesis has aided the understanding of the condition by firstly defining the radiological description of these patients. Secondly, their cross sectional and longitudinal symptom profile have been described for the first time. In addition, the presence of an extruded meniscus has been demonstrated as a substantial risk factor for the disease. Finally, family history has not been demonstrated as a risk factor for the disease within the limits of the study described here. Future work has been proposed.