La schizophrénie précoce (SP), trouble rare (~0,01%) du neurodéveloppement est décrite sous deux formes : la schizophrénie très précoce, avant 13 ans et celle de l’adolescence entre 13 et 18 ans. Le diagnostic complexe à poser et les méconnaissances de la SP font supposer qu’elle est sous diagnostiquée et que les propositions thérapeutiques et de prise en charge sont encore peu spécifiques. Nous avons mené une première étude épidémiologique de prévalence pour : (1) évaluer le taux de sujets répondant au diagnostic de SP dans un échantillon de 302 enfants issus des structures médico-sociales et sanitaires en région PACA ; (2) caractériser sur le plan clinique et neurocognitif les enfants avec SP ; (3) évaluer le taux d’enfants répondant à la fois aux diagnostics de SP et de Troubles du Spectre Autistique (TSA). Puis, une deuxième étude, du sous-groupe d’enfants ayant une comorbidité SP et TSA, a exploré la psychopathologie, la personnalité et les capacités cognitives des membres du 1er degré des familles de ces enfants. Les résultats sont : un taux de 8,9% de patients avec SP, dont 59,3% de garçons âgés de 12,4 ans en moyenne (ET=3,2), avec un Quotient Intellectuel moyen de 72,5 (ET=21,4), des hallucinations (82,8%), des symptômes négatifs (70%), une comorbidité avec un TSA (41.2%) et des traitements neuroleptiques (51,5%). L’étude des familles a montré que les mères ont plus de troubles de la personnalité, de traits autistiques, de pathologies psychiatriques et un QI moyen plus faible. La constitution et le phénotypage de cette cohorte a permis dans les suites de ce travail, de lancer une étude génétique familiale avec séquençage d’exome des parents et des enfants avec SP. / Early Onset Schizophrenia (EOS), a rare neurodevelopmental disorder (≈0.01%) is categorized into two types: Very Early Onset Schizophrenia, before age 13 and Adolescent Schizophrenia between ages 13 and 18. This diagnosis is a difficult one to make and considering the lack of knowledge on EOS, we can presume that it is in fact under-diagnosed and that our treatment and management options are still not very specific. We conducted a first epidemiological prevalence study consisted in evaluating: (1) the rate of subjects with EOS diagnostic criteria among 302 children who receive care in psychosocial and sanitary care facilities in the PACA region; (2) the clinical and neurocognitive characteristics of those children with EOS; (3) the rate of children with both EOS and ASD criteria within the same sample. In a second study, focusing on a subgroup of children with comorbid EOS and ASD, we analyzed first-degree relatives from a psychopathological, personality and cognitive viewpoint. The results are: a high rate of patients (8.9%) with an EOS diagnosis, a male gender majority (59.3%), an average age of 12.4 (SD=3.2), an average intelligence quotient of 72.5 (SD=21.4), a rate of 82.8% of subjects with hallucinations, 70% with EOS negative symptoms, 41.2% with comorbid autism, and 51.5% with antipsychotic medications. The study of family members shows that mothers have a higher rate of personality disorders, autistic traits and psychiatric disorders, as well as a lower average IQ. The creation and the characterization of a phenotype of this cohort have led to a family-genetic analysis based on exome sequencing in the parents and children with EOS following this study.

OBJECTIVES: The aim of our study was to assess clinical presentation of early-onset schizophrenia spectrum disoders (EO-SSD), the time to first improvement and efficacy associated with selected atypical (AAPs) and typical (TAPs) antipsychotics, as well as two main side effects - weight gain and treatment-emergent extrapyramidal symptoms (EPSs) during the treatment in patients with EO-SSD. METHODS: This was a systematic chart review of all patients receiving routine clinical care in our department, with selected AAPs (risperidone, olanzapine, ziprasidone, quetiapine and clozapine) and TAPs (haloperidol, perphenazine and sulpiride), for schizophrenic psychoses, between 1997 and 2007. During this period, our review identified 173 patients (85 males, 88 females; mean age 15.8±1.6 years); their treatment included 297 treatment trials. Data on premorbid adjustment, prodromal symptoms and psychopathology at admission, as well as comorbidity were evaluated based on the patients' medical records. The time to first improvement could be estimated in 258 treatment trials; of these, 195 (76%) comprised AAPs and 63 (24%) TAPs. The time to first improvement was assessed in agreement with the methodology established for retrospective studies as the number of treatment days prior to the first record of improvement...

Die klinische Erfahrung zeigt, dass sich depressive Episoden sehr schnell innerhalb weniger Stunden bis Tage oder sehr langsam innerhalb mehrerer Wochen bis Monate entwickeln können. Hauptziel dieser Arbeit war es, die zeitliche Entwicklung depressiver Episoden bei Patienten mit einer unipolaren oder bipolaren affektiven Störung zu untersuchen. Mithilfe des dafür entwickelten und im Rahmen dieser Studie weiter modifizierten strukturierten Patienteninterview ODI (Onset of Depression Inventory) wurde die Geschwindigkeit des Depressionsbeginns bei 223 konsekutiven Patienten erfasst, von denen 129 in die Auswertung eingeschlossen werden konnten. Es zeigte sich, dass sich depressive Episoden bei Patienten mit bipolarer affektiver Störung signifikant schneller manifestieren als bei Patienten mit unipolarer affektiver Störung. Somit kann die Geschwindigkeit des Depressionsbeginns, gemessen mit dem ODI, als Differenzierungsmerkmal zwischen unipolarer und bipolarer affektiver Störung gewertet werden und im klinischen Alltag helfen, zwischen den beiden Störungsbildern zu unterscheiden.

Background: Human Leucocyte Antigens (HLA) represent the genetic loci most strongly linked to Multiple Sclerosis (MS). Apart from HLA-DR and HLA–DQ, HLA-DP alleles have been previously studied regarding their role in MS pathogenesis, but to a much lesser extent. Our objective was to investigate the risk/resistance influence of HLA-DPB1 alleles in Hellenic patients with early- and adult-onset MS (EOMS/AOMS), and possible associations with the HLA-DRB1*15:01 risk allele. Methods: One hundred MS-patients (28 EOMS, 72 AOMS) fulfilling the McDonald-2010 criteria were enrolled. HLA genotyping was performed with standard low-resolution Sequence-Specific Oligonucleotide techniques. Demographics, clinical and laboratory data were statistically processed using well-defined parametric and nonparametric methods and the SPSSv22.0 software. Results: No significant HLA-DPB1 differences were found between EOMS and AOMS patients for 23 distinct HLA-DPB1 and 12 HLA-DRB1 alleles. The HLA-DPB1*03 allele frequency was found to be significantly increased, and the HLA-DPB1*02 allele frequency significantly decreased, in AOMS patients compared to controls. The HLA-DPB1*04 allele was to be found significantly decreased in AOMS and EOMS patients compared to controls. Conclusions: Our study supports the previously reported risk susceptibility role of the HLA-DPB1*03 allele in AOMS among Caucasians. Additionally, we report for the first time a protective role of the HLA-DPB1*04 allele among Hellenic patients with both EOMS and AOMS.

C1QTNF5 is a 25kDa short chain collagen of unknown function which is mutated in late-onset retinal macular degeneration (L-ORMD). L-ORMD is an autosomal dominant disease characterised by sub-retinal pigment epithelial deposits leading to photoreceptor death and visual loss and shows several similarities to age-related macular degeneration (AMD). A Tyr402His polymorphism in complement factor H (CFH), a regulatory protein in the innate immune system, has been associated with increased risk of AMD. C1QTNF5 and CFH are both expressed and secreted by the retinal pigment epithelium (RPE) which supports photoreceptors and is responsible for phagocytosis of shed rod photoreceptor outer segments (ROS). The properties of the normal C1QTNF5 and disease-associated Ser163Arg mutation were examined in detail, including protein characterisation, cellular processing and function. Recombinant wild type and mutant C1QTNF5 were produced and their multimerisation and solubility functions compared. Both proteins were found to be soluble and to form similar multimeric species which were resistant to reducing conditions, as seen in other short chain collagens. Due to the similarities between LORMD and AMD, a proposed interaction between C1QTNF5 and CFH was investigated. CFH is composed of 20 short consensus repeats (SCR) and interactions were confirmed between C1QTNF5 and both CFH and SCR modules 7-8 and 19-20. CFH showed a greater affinity for mutant C1QTNF5 compared with wild type on the basis of surface plasmon resonance assays. Stably transfected RPE-derived cell lines were created which expressed either wild type or mutant C1QTNF5. Both proteins were found to be secreted and showed similar cellular processing with no evidence of aggregation or retention of the mutant protein within the endoplasmic reticulum. In order to investigate C1QTNF5 function, phagocytosis of ROS by the stably transfected cell lines was carried out. Cells expressing wild type C1QTNF5 showed greater ROS phagocytosis compared with mutant C1QTNF5-expressing or untransfected cells. Addition of anti-C1QTNF5 antibody increased ROS phagocytosis further. In summary, it is proposed that wild type and mutant C1QTNF5 are secreted by the RPE where they interact with CFH. C1QTNF5 is also shown to have a role in ROS phagocytosis, with mutation in C1QTNF5 affecting phagocytosis efficiency, which may contribute to sub-RPE deposit formation. The results suggest that CFH may also be involved in this process, suggesting a common pathogenic pathway between L-ORMD and AMD.

<p>The focus of this research is the experiences of patients with regard to social and health services factors that contribute to delays in seeking treatment for tuberculosis. The goal of this&nbsp / research study was to do an explorative study in order to establish the experiences of patients with regard to social and health services factors that contribute to delays in seeking treatment for Tuberculosis. The objectives to meet the goal were an exploration and description of patients&rsquo / experiences with regards to social and health service factors contributing to delays in seeking&nbsp / treatment for Tuberculosis. Another goal was to make recommendations on social and health service factors that contribute to patients&rsquo / delays in seeking treatment based on the findings. The research study had been of a qualitative nature exploring patients&rsquo / experiences of social and health services factors that contribute to delays in seeking treatment for Tuberculosis. Qualitative&nbsp / research was used in this study using semi-structured interviews with an interview guide. Data analysis was done according to the eight steps as recorded in Tesch in Creswell (1994: 155). The&nbsp / findings of this research were or include social factors contributing to patients&rsquo / delays in seeking treatment for TB. There were four categories related to social factors namely socio-economic,&nbsp / substance abuse, psycho-social and interpersonal relations factors. The findings also indicated that there were health service factors contributing to patients&rsquo / delay in seeking treatment for TB.&nbsp / These include quality of health care services, attitudes of medical staff and other medical conditions treatment. It was concluded that social and health services, as mentioned indeed contribute to patients&rsquo / delays in seeking treatment for Tuberculosis. Recommendations for practice included better case detection, treatment and health education. In order to address the various social&nbsp / factors as described above it is necessary to treat TB holistically and include a social worker as part of the multidisciplinary team.</p>

According to research applying a social constructionist perspective, the sense of self is not lost in people with Alzheimer’s disease (AD). It is, however, greatly influenced by the symptoms and by how they are treated by other people. Without support, it is difficult to preserve a positive sense of self, when living with progressing cognitive impairments. The stigma associated with cognitive impairment also threatens their sense of self. Harré’s social constructionist theories of self and positioning have been used to study how people with AD express their sense of self. As there is a need to expand the previous research by involving additional participants and research contexts, the aim of the present thesis was to describe, in accordance with Harré’s theories of self and positioning, how people with AD expressed their sense of self in personal interviews and in support groups with other people with AD. The research consists of four substudies (I–IV), and has a qualitative, descriptive, and theory-testing approach. Thirteen people with mild and moderate AD were included, 11 of whom had the early onset form of the disease. Two support groups were formed, led by facilitators who supported the communication and the participants’ expressions of self. Each group met 10 times during an eight-month period. Topics were not predetermined, and introduced by both facilitators and participants. Semistructured interviews were conducted before the groups started and after they ended. The interviews and support group conversations were audio-recoded and analysed with qualitative content analysis, guided by Harré’s theories. In substudy I, the initial interviews were deductively analysed. The findings showed that Self 1 (the sense of being a singular, embodied person) was expressed by the participants without difficulties. Self 2 (the perception of one’s personal attributes and life history) was expressed as feeling mainly the same person. While some abilities had been lost, other had been developed. Self 3 (the socially constructed self) was described as mostly supported, but sometimes threatened in interactions with other people (I). In substudy II, support group conversations were analysed abductively with respect to expressions of Self 2. It was found that participants expressed Self 2 in terms of agency and communion, and a lack of agency and communion (II).In substudy III, a secondary analysis of the data from substudy II was performed inductively with the aim of describing how Self 3 was constructed in the interaction of the support group. Five first-order positions, generating lively interaction, were described: the project manager, the storyteller, the moral agent, the person burdened with AD, and the coping person (III). In substudy IV, all the collected data were reanalysed inductively, focusing on how participants expressed the experience of being research participants. Three themes were constructed: contributing to an important cause, gaining from participating, and experiencing risks and drawbacks (IV). In conclusion, it was found that participants constructed positive social selves through the support from each other, the facilitator, and researchers in the support group (III), and as research participants (IV). Agency and communion were central to Self 2, and decreased with the progression of AD (II). In spite of change, participants perceived themselves as basically the same people, with a potential to learn and develop as persons (I).

The purpose of the investigation was to compare mean voice onset time in young and old male subjects, as well as to examine variability of VOT productions with age for prevocalic bilabial, alveolar, and velar voiced and voiceless stop consonants. Forty-five Caucasion.males were divided equally into three.age groups. Ten tokens of six stimulus words were recorded and wide band spectrograms were made. Results of an analysis of variance revealed no significant differences in VOT with age when averages of the phonemes were used for analysis; however, a significant interaction between age and voiced phonemes was found when individual trials of phoneme productions were used for analysis.

Music signal analysis is a research field concerning the extraction of meaningful information from musical audio signals. This thesis analyses the music signals from the note-level to the song-level in a bottom-up manner and situates the research in two Music information retrieval (MIR) problems: audio onset detection (AOD) and music structural segmentation (MSS). Most MIR tools are developed for and evaluated on Western music with specific musical knowledge encoded. This thesis approaches the investigated tasks from a cross-cultural perspective by developing audio features and algorithms applicable for both Western and non-Western genres. Two Chinese Jingju databases are collected to facilitate respectively the AOD and MSS tasks investigated. New features and algorithms for AOD are presented relying on fusion techniques. We show that fusion can significantly improve the performance of the constituent baseline AOD algorithms. A large-scale parameter analysis is carried out to identify the relations between system configurations and the musical properties of different music types. Novel audio features are developed to summarise music timbre, harmony and rhythm for its structural description. The new features serve as effective alternatives to commonly used ones, showing comparable performance on existing datasets, and surpass them on the Jingju dataset. A new segmentation algorithm is presented which effectively captures the structural characteristics of Jingju. By evaluating the presented audio features and different segmentation algorithms incorporating different structural principles for the investigated music types, this thesis also identifies the underlying relations between audio features, segmentation methods and music genres in the scenario of music structural analysis.

The degree of academic achievement following early onset brain injury is poorly understood. Furthermore, it is unclear if academic success can be predicted by age of onset or other lesion variables (e.g., size, laterality). The purpose of the current study was to describe patterns of academic achievement in individuals with childhood-onset focal brain lesions and to determine the role of variables in the plasticity or vulnerability of the developing brain with regard to achievement. Academic achievement data were collected from 58 individuals with childhood-onset focal brain lesions. The participants' reading, spelling, and arithmetic scores, as measured by the Wide Range Achievement Test, were analyzed in relation to several neuroanatomical variables, including lesion laterality, lesion site, and lesion size. The relationship between achievement and gender, age of onset, etiology, age at testing, and time since lesion onset was also identified. As a group, achievement scores did not differ from normative data, and the majority of the sample demonstrated adequate skills in each domain. However, the frequency of deficits was larger than expected when compared to base rates, suggesting vulnerability to early insult. Achievement scores were correlated with intelligence scores, but did not differ based on lesion laterality, lesion site, age of onset, or etiology. Size of lesion was significantly correlated with reading and spelling but not with arithmetic outcomes. Gender differences were identified, with males performing significantly better on the arithmetic measure than females. The age of onset, age at testing, and time since lesion onset were not correlated with achievement scores in any domain. No interactions were found between lesion laterality and gender or lesion site and lesion laterality. An interaction between gender and lesion site was found, but the significance of the finding is unclear. The current findings provide mixed evidence for the plasticity-vulnerability debate, as many individuals were able to achieve adequate academic skills whereas others demonstrated significant impairments. Further research is needed to elucidate factors that may predict achievement outcomes in individuals with childhood-onset focal brain injury.