Although long evading scientific scrutiny, the emotion awe has recently come under sustained analysis by experimental social psychologists. Nevertheless, very little is known about its nature, function, elicitors and effects on human behavior. This thesis offers a data-driven experimental analysis of awe, exploring the theme that the emotion involves a transcendence from mental maps of the self and the world. From this central motif, we explore more narrowly-defined questions, such as whether awe is associated with transcendence from implicit social cognition, the desire to conform, and the need for social inclusion. We also explore whether other techniques that elicit self-transcendence serve to amplify the awe experience. Utilizing a randomized control trial methodology, we found that awe, compared to other positive emotions and neutral states, was causally associated with lower implicit prejudice towards groups based on gender and ethnicity. We also proposed and successfully detected a mechanism for this effect, namely the strengthening of an identification with all humanity. We found mixed support for the idea that awe is associated with a lesser need to conform and be socially included. Finally, in exploring possible elicitors and amplifiers, we detected a positive association between dispositional awe and mindfulness and found that experimentally-elicited mindfulness can activate awe even towards relatively ordinary stimuli. This thesis builds upon and refines the idea of awe as a self-transcending emotion, offering insights on particular aspects of cognition and behavior that are changed by the experience. We have also located some promising new paths of investigation that future researchers may find useful to follow further. In summary, the present work helps extend the exploration of the nature and function of an undeniably profound human experience.

Section A: A review of current research literature relating to the impact of child ASD upon non-affected siblings and the utility of sibling group interventions. The first section summarises and critiques studies relating to the social, emotional and behavioural adjustment of siblings, including consideration of potential mediating factors and discussion of methodological issues. The second section considers evidence for one intervention for this group, ASD-specific sibling support groups. The review suggests that inconsistencies remain within the sibling research literature and that there is a clear need for UK-based outcome research. Section B: Background: Having a brother or sister with an ASD can be challenging for non-affected siblings. These children may experience reduced parental attention, isolation from peers and difficult sibling behaviours. This pilot study aimed to investigate the utility of support groups for siblings of children with ASDs. Methods: A within group, mixed methods design was used with a pre-intervention baseline. Participants were 35 children, aged 7-15 years, with an ASD sibling. All were attending ASD-specific sibling group interventions across the South East of England. Sibling rated self-concept, anxiety and anger and parent-rated emotional difficulties were collected at pre group, post group and follow up. One group also participated in a focus group. Results: Results indicated significant improvements in self concept and significant decreases in anger and anxiety following participation in an ASD-specific sibling group. Anxiety continued to decrease at 3 month follow up. Parent-rated sibling emotional difficulties did not change. All siblings valued the groups. Four main themes were identified from qualitative data: Siblings valued the opportunity to meet similar others, have fun, learn new information about ASD and apply this knowledge to their own situation. Conclusions: The present pilot study extends existing literature on ASD-specific sibling groups. This is one of the first studies to combine qualitative data with standardised outcome measures. Participation in an ASD-specific support group may be associated with more positive self concept and decreased anger and anxiety. Given inherent study limitations, further, controlled research studies are warranted. Section C: A critical appraisal of the study conducted in section B and a reflective account of the process. This includes consideration of research skills learnt, future adaptations, clinical implications and ideas for future research.

Questions have been raised as to whether the patterns of thoughts and behaviours experienced by individuals with autistic spectrum disorders (ASD) can be indicative of comorbid obsessive compulsive disorder (OCD). The current study aimed to compare the experiences of adults with ASD or OCD and healthy controls (HC) in terms of the symptoms experienced and the associated emotions and responses. Associations between autistic traits and OCD severity were explored. A cross-sectional design utilising MANOVA, ANOVA and correlation was employed. Methods: Eighteen participants with ASD, 20 with OCD and 19 healthy controls completed self-report measures and interviews assessing IQ, comorbid diagnoses, OCD symptoms, autistic traits and emotions and responses associated with obsessional thoughts. Participants with ASD scored significantly higher than healthy controls in terms of OCD severity and also number of obsessions and compulsions and associated distress. While the OCD and ASD groups did not differ significantly on OCD severity, the OCD group reported significantly higher levels of sadness, worry, shame, guilt and disapproval triggered by obsessions. The ASD and healthy control groups were largely comparable on these factors. Associations were found between OCD severity and particular domains which are typically impaired in ASD, including social skills, attention switching, communication and imagination. Findings suggest that OCD symptoms may be common and a source of distress in individuals with ASD, thus perhaps warranting psychological intervention. Further research into the exact nature of this distress and how this can be assessed is required.

Bibliography: p. 54-62 / 91 p. : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library.

<p>Denna uppsats behandlar ämnet Försvarsmaktens Fysiska Standard. Uppsatsens syfte är att skapa ett underlag för att förbättra eller bibehålla möjligheterna för officerarna vid Artilleriregementet A9 att genomföra Försvarsmaktens Fysiska Standard (FM FysS). Detta för att uppfylla de krav som ställs avseende fysisk prestationsförmåga på en officer i Försvarsmakten. Den frågeställning som använts är <em>Hur uppfattar officerarna på A9 att de genomför FM FysS?</em></p><p>Den metod som använts är en enkätundersökning som genomförts bland officerarna på A9.</p><p>Resultatet från enkätundersökningen visar att det finns både positiva delar som bör bibehållas och förbättringspunkter för genomförandet av FM FysS. De huvuddrag som konstateras är att fördelningen mellan delarna kondition, styrka och rörlighet i träningen är god och skall bibehållas på regementet. Officerarna på A9 sätter i hög grad upp träningsmål för sin träning på arbetstid vilket är positivt. Förbättring bör ske inom uppföljning och utvärdering, samt genomförande av tester på tilläggskraven.</p>

Denna uppsats behandlar ämnet Försvarsmaktens Fysiska Standard. Uppsatsens syfte är att skapa ett underlag för att förbättra eller bibehålla möjligheterna för officerarna vid Artilleriregementet A9 att genomföra Försvarsmaktens Fysiska Standard (FM FysS). Detta för att uppfylla de krav som ställs avseende fysisk prestationsförmåga på en officer i Försvarsmakten. Den frågeställning som använts är Hur uppfattar officerarna på A9 att de genomför FM FysS? Den metod som använts är en enkätundersökning som genomförts bland officerarna på A9. Resultatet från enkätundersökningen visar att det finns både positiva delar som bör bibehållas och förbättringspunkter för genomförandet av FM FysS. De huvuddrag som konstateras är att fördelningen mellan delarna kondition, styrka och rörlighet i träningen är god och skall bibehållas på regementet. Officerarna på A9 sätter i hög grad upp träningsmål för sin träning på arbetstid vilket är positivt. Förbättring bör ske inom uppföljning och utvärdering, samt genomförande av tester på tilläggskraven.

La méthylation de l’ADN est une modification majeure du génome des eucaryotes permettant de moduler l’expression génique et contrôler le développement des mammifères. La protéine Mecp2 (Methyl CpG binding protein 2), dont le gène est situé sur le chromosome X, appartient à la famille des protéines de liaison à l’ADN méthylé. Sur la base de sa structure et de ses interactions Mecp2 a été décrit comme un répresseur de l’expression des gènes. A l’heure actuelle, son implication en tant qu’activateur de la transcription et organisateur de la structure chromatinienne lui confère un rôle plus global dans la régulation de l’épigénome. Des mutations de MECP2 conduisent à des troubles neurologiques dont le principal est le syndrome de Rett (RTT). Cette pathologie dominante liée à l’X affecte principalement les jeunes filles (incidence: 1/15000 naissances). Même si les causes précises du phénotype RTT ne sont pas connues, le profil d’expression de Mecp2 est en lien avec la synaptogenèse, la maturation et la maintenance des réseaux neuronaux. A mon arrivée en thèse l’équipe qui m’a accueilli venait d’identifier des déficits neuronaux, affectant notamment les groupes catécholaminergiques bulbaires et périphériques, à l’origine de troubles respiratoires chez un modèle murin de cette pathologie. Mon travail de thèse a permis de caractériser l’évolution postnatale des déficits moteurs et physiologiques affectant la souris Mecp2-déficiente. L’étude de structures catécholaminergiques d’intérêt telles que la Substantia Nigra et le Locus Coeruleus a révélé que les neurones dopaminergiques et noradrénergiques centraux ont un métabolisme affecté. Le nombre de neurones immunomarqués apparait significativement réduit dans ces groupes ce qui résulterait d’une perte progressive du phénotype « catécholaminergique », en l’absence de mort cellulaire. Nos données suggèrent que ces atteintes constituent un corrélat neuropathologique aux troubles comportementaux observés chez les souris Mecp2-déficientes. Ainsi certains troubles moteurs ont pu être améliorés, à l’aide d’un agent pharmacologique pro-dopaminergique, la L-Dopa. En relation avec les déficits en Bdnf (Brain-derived neurotrophic factor) décrits chez les patientes et les souris Mecp2-déficientes, nous avons identifié qu’une modification du dosage de Mecp2 induit une dérégulation de gènes (Htt, Hap1) codant des protéines impliquées dans le transport intracellulaire des vésicules de Bdnf. Nos travaux nous permettent de postuler que chez la souris Mecp2-déficiente, une altération de la dynamique de transport des vésicules chargées en Bdnf pourrait exacerber le déficit d’expression de cette neurotrophine. Notre traitement des souris Mecp2-déficientes par la cystéamine, une molécule capable d’agir sur les contenus, la libération et la sécrétion du Bdnf permet d’augmenter la survie des animaux et de réduire leurs troubles moteurs. Nos résultats montrent que les déficiences en Mecp2 entrainent des déficits de transport axonal du Bdnf qui s’ajoutent aux déficits de production du Bdnf. Par ailleurs, avec l’utilisation d’agents pharmacologiques agissant sur ce transport, nous offrons de nouvelles perspectives thérapeutiques. / DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. The protein Mecp2 (Methyl CpG binding protein 2), encoded by a gene located on the X chromosome, belongs to the ‘Methyl Binding domain’ protein family. Based on its structure and its interactions Mecp2 has historically been described as a repressor of expression for many genes. Currently, its involvement as an activator of transcription and its role in chromatin architecture suggests that it could be a global regulator of the epigenome. Mutations in MECP2 lead to neurological disorders, among which Rett syndrome (RTT). This dominant X-linked pathology mainly affects girls (incidence: 1/15000 live births). Although the precise causes of the RTT phenotype are unknown, the pattern of Mecp2 expression is related to synaptogenesis, maturation and neuromaintenance. Before my integration in the ‘Human Neurogenetics’ team, this group identified neural deficits, affecting brainstem and peripheral catecholaminergic cell groups, causing respiratory disturbances in a mouse model of this disease. My thesis work enabled the characterization of the postnatal physiological and motor deficits affecting the Mecp2-deficient mice. The study of catecholaminergic structures of interest such as the substantia nigra pars compacta and the locus coeruleus has revealed that the central noradrenergic and dopaminergic neurons are affected in their metabolism. The number of immunolabelled neurons of these groups appears significantly reduced and would result in a gradual loss of the mature ‘catecholaminergic’ phenotype, in the absence of cell death. Our data suggest that these defects are a neuropathological correlate for behavioral disorders observed in Mecp2-deficient mice. Some motor deficits have been improved, with L-Dopa, a pro-dopaminergic drug. In relation with Bdnf (Brain-derived neurotrophic factor) reduction described in patients and Mecp2-deficient mice, we identified that a change in the dosage of Mecp2 deregulates genes (Htt, Hap1) encoding proteins involved in the intracellular transport of Bdnf. Our work allows to postulate that in the Mecp2-deficient neurons, an altered dynamics of Bdnf vesicles transport could exacerbate the deficit of expression of this neurotrophin. Our treatment of Mecp2-deficient mice with cysteamine, a molecule able to increase Bdnf contents and enhancing its release and secretion, increased the survival of the animals and reduced their motor defects. Our results show that the Mecp2-deficiencies lead to alteration in the axonal transport of Bdnf in addition to deficits in Bdnf production. In addition, by the use of pharmacological agents that affect this transport, we offer new therapeutic perspectives.

Introdução: Os stents farmacológicos (SF) de primeira geração surgiram com o intuito de reduzir as taxas de reestenose intra-stent e de revascularização da lesão-alvo, sendo mais eficazes quando comparados aos stents não-farmacológicos (SNF), porém com aumento de risco de trombose do stent (TS) muito tardia. A cobertura tecidual incompleta e a má aposição tardia das hastes dos stents podem estar vinculadas à TS. O SF de segunda geração BioMatrix®, que utiliza um polímero bioabsorvível, surgiu na expectativa de redução da TS. Devido à alta acurácia e reprodutibilidade e à análise precisa da cobertura tecidual e da aposição das hastes dos stents, a tomografia de coerência óptica (TCO) vem se tornando um método útil na análise desses aspectos. O objetivo desse estudo foi avaliar a cobertura tecidual e a aposição das hastes do SF BioMatrix® após longo período do implante. Métodos: Vinte pacientes submetidos ao implante do SF BioMatrix® (n = 15) ou do SNF S-Stent® (n = 5) foram acompanhados por um período mínimo de cinco anos e avaliados por meio da angiografia coronária quantitativa (ACQ), da ultrassonografia intracoronária (USIC) e da TCO. Para a análise estatística, foram utilizados os programas SPSS® versão 16.0 e SAS versão 9.2. O valor de p < 0,05 era considerado estatisticamente significante. As variáveis categóricas foram expressas em números absolutos e porcentuais e comparadas pelo teste exato de Fisher. As variáveis contínuas foram expressas em média e desvio padrão e/ou mediana e intervalo interquartílico e foram comparadas pelo teste não paramétrico de Mann-Whitney. Resultados: A ACQ demonstrou diferença, porém não significativa na perda tardia da luz entre o SF BioMatrix® e o S-Stent® [0,40 (0,21; 0,77) mm vs 0,68 (0,66; 0,82) mm, p = 0,205]. Os pacientes tratados com o SF BioMatrix® apresentaram porcentual de obstrução do stent significativamente menor quando comparados àqueles que receberam o S-Stent® [5,6 (4,4; 9,7)% vs 28,6 (24,7; 29,0)%, p =0,001]. A análise da TCO demonstrou 126 (8,7%) hastes não cobertas nos stents BioMatrix® e 23 (4,0%) nos S-Stents® (p = 0,297), estando a maioria delas bem apostas (117/126 e 21/23, respectivamente, p = 0,292). Apenas nove (0,6%) hastes nos SF e duas (0,4%) hastes nos SNF estavam simultaneamente sem cobertura tecidual e mal apostas (p = 0,924). No grupo BioMatrix®, apenas 1 (11,1%) paciente teve todas as hastes cobertas. Já no grupo S-Stent, 66,7% dos pacientes (2/3) apresentaram cobertura completa das hastes (p = 0,127). Conclusões: A avaliação tardia do SF BioMatrix® pela TCO mostrou cobertura tecidual e aposição em quase a totalidade de suas hastes, de maneira similar àquela encontrada nos SNF S-Stents®. / Introduction: First generation drug-eluting stents (DES) have emerged as a strategy to prevent in-stent restenosis and the need of target-vessel revascularization when compared to bare metal stents (BMS); but at the expense of a higher risk of very late stent thrombosis (ST). Uncovered and malapposed struts may be associated with both late and very late ST. It has been postulated that the second generation DES, the biolimus-eluting stent BioMatrixTM with biodegradable polymer, may reduce the incidence of ST. Given its high accuracy and reproducibility with precise analysis of the complete strut apposition and strut coverage, the optic coherence tomography (OCT) has been extensively used for stent analysis. The aim of this study was to assess the struts coverage and apposition of DES BioMatrixTM in a long-term follow up. Methods: Twenty patients undergoing a BioMatrixTM (n = 15) or BMS S-StentTM (n = 5) implantation were followed up for a period of at least five years and evaluated by means of OCT, quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). All statistical analyses were performed using SPSSTM (v.16.0) and SAS (v.9.2) software. Statistical significance was considered at p values < 0.05. Categorical variables were expressed as counts and percentages, and continuous variables as mean SD and/or median and interquartile range. For per-patient level comparison, the difference between two stent types was evaluated by nonparametric Mann-Whitney U test while categorical variables were evaluated by the Fisher exact test. Results: QCA analysis showed no differences in the occurrence of intrastent late loss between the groups [0.40 (0.21; 0.77) mm vs 0.68 (0.66; 0.82) mm, p = 0.205 for BioMatrixTM and S-StentsTM, respectively]. The vessel, stent and lumen volumes assessed by IVUS after the procedure and 5 years later were similar between the two groups. Patients treated with BioMatrixTM had significantly less stent obstruction percentage when compared to those treated with S-StentTM [5.6 (4.4; 9.7)% vs 28.6 (24.7; 29.0)%, p = 0.001]. OCT analysis demonstrated 126 (8.7%) uncovered struts in the BioMatrixTM group compared to 23 (4.0%) in the S-StentsTM group (p = 0.297), being the majority of them well apposed (117/126 and 21/23, respectively, p = 0.292). Only 9 (0.6%) struts in the DES and 2 (0.4%) struts in the BMS groups were imultaneously uncovered and malapposed (p = 0.924). Among the BioMatrixTM patients, 55.6% (5/9) had more than 95% of covered struts and in only 1 (11.1%) patient all struts were covered. On the other hand, among the S-StentTM patients, 66.7% (2/3) had complete covered struts (p = 0.127). Conclusion: Long term assessment of DES BioMatrixTM by OCT showed tissue coverage and apposition in almost all struts, similary to those found in the BMS S-StentsTM.

Introdução: Os stents farmacológicos (SF) de primeira geração surgiram com o intuito de reduzir as taxas de reestenose intra-stent e de revascularização da lesão-alvo, sendo mais eficazes quando comparados aos stents não-farmacológicos (SNF), porém com aumento de risco de trombose do stent (TS) muito tardia. A cobertura tecidual incompleta e a má aposição tardia das hastes dos stents podem estar vinculadas à TS. O SF de segunda geração BioMatrix®, que utiliza um polímero bioabsorvível, surgiu na expectativa de redução da TS. Devido à alta acurácia e reprodutibilidade e à análise precisa da cobertura tecidual e da aposição das hastes dos stents, a tomografia de coerência óptica (TCO) vem se tornando um método útil na análise desses aspectos. O objetivo desse estudo foi avaliar a cobertura tecidual e a aposição das hastes do SF BioMatrix® após longo período do implante. Métodos: Vinte pacientes submetidos ao implante do SF BioMatrix® (n = 15) ou do SNF S-Stent® (n = 5) foram acompanhados por um período mínimo de cinco anos e avaliados por meio da angiografia coronária quantitativa (ACQ), da ultrassonografia intracoronária (USIC) e da TCO. Para a análise estatística, foram utilizados os programas SPSS® versão 16.0 e SAS versão 9.2. O valor de p < 0,05 era considerado estatisticamente significante. As variáveis categóricas foram expressas em números absolutos e porcentuais e comparadas pelo teste exato de Fisher. As variáveis contínuas foram expressas em média e desvio padrão e/ou mediana e intervalo interquartílico e foram comparadas pelo teste não paramétrico de Mann-Whitney. Resultados: A ACQ demonstrou diferença, porém não significativa na perda tardia da luz entre o SF BioMatrix® e o S-Stent® [0,40 (0,21; 0,77) mm vs 0,68 (0,66; 0,82) mm, p = 0,205]. Os pacientes tratados com o SF BioMatrix® apresentaram porcentual de obstrução do stent significativamente menor quando comparados àqueles que receberam o S-Stent® [5,6 (4,4; 9,7)% vs 28,6 (24,7; 29,0)%, p =0,001]. A análise da TCO demonstrou 126 (8,7%) hastes não cobertas nos stents BioMatrix® e 23 (4,0%) nos S-Stents® (p = 0,297), estando a maioria delas bem apostas (117/126 e 21/23, respectivamente, p = 0,292). Apenas nove (0,6%) hastes nos SF e duas (0,4%) hastes nos SNF estavam simultaneamente sem cobertura tecidual e mal apostas (p = 0,924). No grupo BioMatrix®, apenas 1 (11,1%) paciente teve todas as hastes cobertas. Já no grupo S-Stent, 66,7% dos pacientes (2/3) apresentaram cobertura completa das hastes (p = 0,127). Conclusões: A avaliação tardia do SF BioMatrix® pela TCO mostrou cobertura tecidual e aposição em quase a totalidade de suas hastes, de maneira similar àquela encontrada nos SNF S-Stents®. / Introduction: First generation drug-eluting stents (DES) have emerged as a strategy to prevent in-stent restenosis and the need of target-vessel revascularization when compared to bare metal stents (BMS); but at the expense of a higher risk of very late stent thrombosis (ST). Uncovered and malapposed struts may be associated with both late and very late ST. It has been postulated that the second generation DES, the biolimus-eluting stent BioMatrixTM with biodegradable polymer, may reduce the incidence of ST. Given its high accuracy and reproducibility with precise analysis of the complete strut apposition and strut coverage, the optic coherence tomography (OCT) has been extensively used for stent analysis. The aim of this study was to assess the struts coverage and apposition of DES BioMatrixTM in a long-term follow up. Methods: Twenty patients undergoing a BioMatrixTM (n = 15) or BMS S-StentTM (n = 5) implantation were followed up for a period of at least five years and evaluated by means of OCT, quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). All statistical analyses were performed using SPSSTM (v.16.0) and SAS (v.9.2) software. Statistical significance was considered at p values < 0.05. Categorical variables were expressed as counts and percentages, and continuous variables as mean SD and/or median and interquartile range. For per-patient level comparison, the difference between two stent types was evaluated by nonparametric Mann-Whitney U test while categorical variables were evaluated by the Fisher exact test. Results: QCA analysis showed no differences in the occurrence of intrastent late loss between the groups [0.40 (0.21; 0.77) mm vs 0.68 (0.66; 0.82) mm, p = 0.205 for BioMatrixTM and S-StentsTM, respectively]. The vessel, stent and lumen volumes assessed by IVUS after the procedure and 5 years later were similar between the two groups. Patients treated with BioMatrixTM had significantly less stent obstruction percentage when compared to those treated with S-StentTM [5.6 (4.4; 9.7)% vs 28.6 (24.7; 29.0)%, p = 0.001]. OCT analysis demonstrated 126 (8.7%) uncovered struts in the BioMatrixTM group compared to 23 (4.0%) in the S-StentsTM group (p = 0.297), being the majority of them well apposed (117/126 and 21/23, respectively, p = 0.292). Only 9 (0.6%) struts in the DES and 2 (0.4%) struts in the BMS groups were imultaneously uncovered and malapposed (p = 0.924). Among the BioMatrixTM patients, 55.6% (5/9) had more than 95% of covered struts and in only 1 (11.1%) patient all struts were covered. On the other hand, among the S-StentTM patients, 66.7% (2/3) had complete covered struts (p = 0.127). Conclusion: Long term assessment of DES BioMatrixTM by OCT showed tissue coverage and apposition in almost all struts, similary to those found in the BMS S-StentsTM.

Individuals with high functioning Autism Spectrum Disorder (ASD) stand an increased risk of experiencing mental health problems during adolescence. The present study aimed to develop a better understanding of interpersonal relationships in the lives of adolescents with high functioning ASD. Eight adolescents with a diagnosis of Asperger’s syndrome or ASD without an identified intellectual disability engaged in a structured interview based on a personal construct psychology exercise exploring constructs about interpersonal relationships. Interviews were transcribed and subjected to a thematic analysis. Four themes were identified: 1) Relationships as a source of support, 2) Perceptions of similarity and difference, 3) Valued qualities in self and others and 4) The development of and maintenance of relationships. Whilst this exploratory study highlighted some commonality in terms of perceptions of family support and friendships as protective and desirable, the participant group differed in their ability to establish and maintain peer relationships. However, peers were seen by participants as being very important in the development of social skills - a finding which has implications for the delivery of social skills training and other supportive interventions. The personal construct exercise provided an accessible and useful platform for the exploration of the social worlds of adolescents with ASD.