Abstract Personality disorders (PDs) are relatively common mental disorders associating with other psychiatric disorders and disability. The aim of the study was to determine the occurrence of PDs in a general population subsample and psychiatric hospital patients, the associations of PDs with childhood family structure, the co-occurrence of PD with common psychiatric disorders, and the associations between PDs and temperament. The study is part of the Northern Finland 1966 Birth Cohort Project (NFBC 1966), consisting of cohort members living in Oulu (N = 1,609) on 1st January 1997 (the Oulu Study). The study consisted of a two-stage psychiatric field survey with questionnaires and a structured clinical interview and analysis of the patient records in public outpatient care. Information concerning psychiatric illness of all cohort members (N = 12,058) was gathered from the Finnish Hospital Discharge register (FHDR). The best-estimate procedure was used for the assessment of psychiatric morbidity including PDs. Childhood family structure and other sociodemographic variables were drawn from questionnaires of the field study conducted during earlier follow-up studies. In this study PDs were classified into three clusters: Cluster A (paranoid, schizoid and schizotypal PD), Cluster B (antisocial, borderline, histrionic, and narcissistic PD), and Cluster C (avoidant, dependent, obsessive-compulsive, and passive-aggressive PD). The most common PDs in the Oulu Study sample were Cluster C PDs, whereas Cluster B PDs were most common in the hospital-treated sample. PDs were highly associated with mood, anxiety and substance use disorders. Single-parent family type in childhood was associated with PDs, especially Cluster B PDs in adulthood. PD clusters were associated with different profiles of temperament, but the temperament dimensions could not distinguish different PDs very well. These results indicated that it is important to recognize PDs and their comorbid psychiatric disorders. This will have implications in both general outpatient care and psychiatry. These results indicate the importance of recognition of childhood risk factors for PDs for the prevention of severe PDs. The results suggest a need for more studies about the aetiology and development of PDs. / Tiivistelmä Persoonallisuushäiriöt ovat yleisiä mielenterveyden ongelmia, joihin liittyy usein psykiatrista oheissairastavuutta ja toimintakyvyn laskua. Tämän tutkimuksen tarkoituksena oli arvioida persoonallisuushäiriöiden yleisyyttä nuorilla aikuisilla. tehtävänä oli arvoida yhteyksiä lapsuuden perherakenteeseen ja yleisimpiin psykiatrisiin häiriöihin sekä arvioida persoonallisuushäiriöiden yhteyksiä temperamenttitekijöihin. Tutkimus on osa Pohjois-Suomen vuoden 1966 syntymäkohortin psykiatrista osaprojektia, Oulu Studyä. Tutkimusaineiston muodostivat Oulu Studyn otokseen kuuluvat kaikki 1. tammikuuta 1997 Oulussa asuneet kohortin jäsenet (N = 1 609) sekä sairaalahoidossa olleiden persoonallisuushäiriö- diagnoosin saaneiden osalta koko alkuperäisen syntymäkohortin (N =  12 058) jäsenet. Tutkimus koostui kaksivaiheisesta psykiatrisesta kenttätutkimuksesta, jossa tietoja tutkittavilta kerättiin sekä kyselylomakkeiden ja haastattelututkimuksen avulla. Lisäksi tutkittavilta kerättiin tiedot heidän elinaikanaan toteutuneesta julkisten psykiatristen sairaala- ja avohoitopalvelujen käytöstä sairauskertomustietojen perusteella. Niin kutsutun best-estimated -menetelmän avulla arvioitiin tutkittavien psykiatrista sairastavuutta mukaan lukien persoonallisuushäiriöt. Tutkittavien lapsuuden perherakennetta ja sosiodemografisia tekijöitä arvioitiin aiempien seurantatutkimusten tietojen avulla. Tutkimuksessa persoonallisuushäiriöt luokiteltiin DSM-III-R-diagnoosiluokituksen mukaisesti kolmeen eri pääryhmään ja niiden mukaisiin alaryhmiin: Ryhmä A (epävakaa, eristäytyvä ja psykoosipiirteinen persoonallisuus), ryhmä B (epäsosiaalinen, epävakaa, huomionhakuinen ja narsistinen persoonallisuus) ja ryhmä C (estynyt, riippuvainen, pakko-oireinen ja passiivis-aggressiivinen persoonallisuus). Oulu Studyn väestöotoksessa yleisimpiä näistä olivat ns. C-ryhmän persoonallisuushäiriöt, kun taas sairaalahoidetuilla henkilöillä B-ryhmän persoonallisuushäiriöt olivat yleisimpiä. Persoonallisuushäiriöiden todettiin liittyvän yleisesti masennus- ja ahdistuneisuushäiriöihin sekä päihteiden käyttöön. Vanhemman yksinhuoltajuuden todettiin liittyvän persoonallisuushäiriöihin, etenkin B-ryhmän persoonallisuushäiriöihin. Persoonallisuushäiriöryhmät erosivat toisistaan temperamenttiprofiilien perusteella. Eri persoonallisuushäiriöistä kärsivillä tutkittavilla ei todettu tyypillisiä temperamenttiprofiileja. Johtopäätöksenä voidaan todeta, että persoonallisuushäiriöiden ja niihin yleisesti liittyvän psykiatrisen oheissairastavuuden tunnistaminen on tärkeää. Havainnot korostavat perusterveydenhuollon ja erikoissairaanhoidon yhteistyön merkitystä persoonallisuushäiriöistä ja psykiatrisista häiriöistä kärsivien henkilöiden tutkimuksessa ja hoidossa. Persoonallisuushäiriöille altistavien lapsuuden tekijöiden tunnistaminen on tärkeää vaikeiden persoonallisuushäiriöiden ehkäisemiseksi. Persoonallisuushäiriöiden etiologian ja kehittymisen selvittämiseksi tarvitaan uusia tutkimuksia.

Reproduction de : Thèse de doctorat : Parasitologie : Lille 2 : 2008. / Résumé en français et en anglais. Titre provenant de l'écran-titre. Bibliogr. f. 178-195.

Au cours de leur développement, les cellules du système hématopoïétique sont très exposées aux dommages à l’ADN qui peuvent avoir une origine exogène ou endogène. Les organismes vivants ont développé de nombreux mécanismes de réparation pour y faire face, et leur dysfonctionnement est responsable de maladies rares mais sévères chez l’Homme. Un des deux mécanismes de réparation des cassures double-brin (CDB) de l’ADN joue un rôle prépondérant dans le développement du système immunitaire (SI) des mammifères. Il s’agit de la voie de réparation des extrémités non-homologues (NHEJ) qui est absolument essentiel au bon déroulement de la recombinaison V(D)J dans les progéniteurs lymphocytaires de la moelle osseuse et du thymus. En effet, la formation de CDB de l’ADN est une étape clé de ce remaniement. De même, bien que dans une moindre mesure, le NHEJ intervient pour réparer les cassures induites par AID lors de la commutation de classe des immunoglobulines (Ig- CSR). Notre équipe a précédemment identifié un nouveau facteur du NHEJ, Cernunnos (ou XLF), responsable chez l’Homme de déficit immunitaire combiné sévère (DCIS) associé à une sensibilité aux rayonnements ionisants (RI) et à une microcéphalie. Afin de mieux comprendre le rôle de Cernunnos dans le système hématopoïétique et dans le développement des lymphocytes en particulier, nous avons créé un modèle murin invalidé pour ce gène. De façon surprenante, le développement lymphocytaire se fait quasi normalement dans ces souris, le seul défaut observé est une diminution du nombre de lymphocytes. Cependant, l’analyse fine du répertoire des cellules T a permis de mettre en évidence un biais dans l’utilisation des segments variables V et J de la chaîne α du récepteur (TCRα). Ce serait là la signature d’un défaut de survie des thymocytes, passant par une activation chronique de la voie de l’apoptose dépendante de p53 en réponse à l’accumulation de dommages de l’ADN. Certaines sous- populations de lymphocytes T, comme les iNKTs et les MAITs, seraient ainsi affectées. Par ailleurs, notre équipe poursuit la caractérisation génétique et fonctionnelle de pathologies chez des patients dont le tableau clinique laisse penser qu’il existe un déficit immunitaire ou hématologique primaire associé à un défaut de réparation de l’ADN. Nous nous sommes intéressés à un patient dont le tableau clinique combinant déficit hématopoïétique et instabilité génomique suggère une origine génétique forte. Grâce aux techniques de séquençage haut- débit et à l’étude de ségrégation au sein de la famille nous avons pu isoler plusieurs mutations dont une nous a interpellé plus particulièrement / Throughout their development, hematopoietic cells are exposed to many DNA damages of either exogenous or endogenous origin. Living organisms evolved a variety of DNA repair mechanisms in order to face those threats, and their impairment leads to rare but severe diseases in human. Of the two mechanisms involved in the repair of DNA double-strand break (DSB) repair, one plays a major role in mammal’s Immune System (IS). The non-homologous end joining (NHEJ) pathway is essential for the correct proceeding of V(D)J recombination in lymphocyte progenitors from bone marrow and thymus. Indeed, the formation of DNA DSB is a key step of the rearrangement. In similar fashion, though to a lesser degree, NHEJ is involved in repair of AID induced breaks during immunoglobulin class switch recombination (Ig-CSR). Our team previously identified a new NHEJ factor, Cernunnos (or XLF), as being responsible for a human syndrome of severe combined immunodeficiency (SCID) associated with ionizing radiation (IR) sensitivity (RS-SCID) and microcephaly. To better understand Cernunnos role in the hematopoietic system and particularly in lymphocyte development, we engineered a knock-out (KO) mouse model for this gene. Surprisingly, lymphocyte development is almost normal in these mice, the only defect observed being a decrease of lymphocyte number. However, a refined analysis of T cell repertoire allowed us to uncover a bias in the use of V and J segments from the receptor’s α chain (TCRα). This is the signature of a survival defect in thymocytes, caused by chronic activation of the p53 dependent apoptosis pathway in response to DNA damage. Some discrete T cell populations, such as iNKTs and MAITS, would be affected. In the meantime, our team pursues the uncovering of genetic diseases and their functional description in patients showing signs of immune or hematopoietic deficiency combined to impaired DNA repair. We focused on a patient harboring clinical signs of genomic instability and hematopoietic defects with strong evidence for genetic cause. Thanks to high-throughput DNA sequencing technology and whole genome association study (WGAS), we identified several mutations, one of them striking us as pertinent

Film has since its inception been a potent storytelling tool, and the concept of illnesses and death havebeen a critical element in the stories mankind has told through cinema since the beginning. While theearly years of film saw few titles which directly named or featured diseases such as cancer, the 1980’sand 1990’s saw a vast increase in illness narratives being produced. By the beginning of the newmillennium, a new subgenre of film was beginning to emerge, specifically targeted at youngaudiences: Sick-Flicks.The purpose of this thesis is to examine the Sick-Flick subgenre, and scrutinize the films which the author has identified according to how they handle a variety of factors. These include the portrayal ofmale and female sufferers in accordance with the feminist theoretical observation of masculinity beingrepresented as active, while femininity is typically passive in nature. Beyond this, the essay alsoattempts to add to Susan Sontag’s essay Illness as Metaphor, exploring how the portrayal of illnessmay have shifted since the essay’s publication in 1978. Finally, this thesis also concerns itself with thereoccurring narrative trend of featuring talented adolescents as terminally ill sufferers and how thismay tie into neoliberalism and belief in the meritocracy.This thesis concludes that while there has been a shift in the metaphorical portrayal of diseases,especially as it pertains to cancer, which Susan Sontag concludes unsuitable for romanticization,overall, many of the criticisms and potentially problematic commonalities which both Sick-Flicks andtheir literary counterpart Sick-Lit have featured through the years remain. There is a remaining focuson heteronormative and racially homogenous victims, and innate talents and intelligence are present,arguably in order to make the eventual loss of the ill characters more tangibly tragic. The authorconcludes that while it is debatable whether or not filmmakers should feel any responsibility to portrayillnesses accurately, they should at least likely strive to reflect the current reality as far as survivalrates are concerned.

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Although the etiology and pathogenesis of inflammatory bowel disease (IBD) is not fully understood, it is generally accepted that the inflammation results from aberrant immune responses to antigens of gut microbiota in genetically susceptible individuals (Sartor et al., 2006). Alteration in intestinal microbiota has been found in IBD patients with increased abundance of certain bacteria and decreased abundance of others. Due to the complexity of the disease, multifaceted interactions between genetic factors, host immune response, gut microbiota and environment factors need to be taken into account. In this thesis, the pathogenesis of IBD was first reviewed in respect with the four factors mentioned above. Then we concentrated on the interaction between IBD-associated bacteria and mucosal immune system. We investigated the ability of mucosal-associated bacteria (MAB) from IBD patients to induce spontaneous colitis in germ-free (GF) mice and the impact of those bacteria on the development of dextran sulfate sodium (DSS)-colitis. Together with the analysis of the composition of gut microbiota of MAB colonized mice, we demonstrated the potential deleterious microbes were able to increase the susceptibility to DSS-colitis once they found a suitable niche. We revealed the mechanism of an E.coli strain...