Objetivos: Avaliar a concordância da percepção da qualidade de vida (QV) entre mulheres com câncer de mama e seus parceiros, e investigar os fatores demográficos e clínicos que interferem na QV destas mulheres. Método: Realizou-se um estudo transversal em mulheres com câncer de mama nos estágios I, II, III, na faixa etária de 18 a 65 anos, com parceiro há pelo menos um ano, coabitando e em condições de compreender os instrumentos, que são autopreenchíveis. As participantes foram selecionadas no Ambulatório do Serviço de Mastologia do Hospital de Clínicas de Porto Alegre. Foram incluídas 73 mulheres e seus respectivos parceiros. O tamanho da amostra foi calculado para comparação entre dois grupos, com nível de significância de 0,05 e poder de 80%. A QV das mulheres foi avaliada através do questionário do World Health Organization Quality of Life, versão Bref (WHOQOL-Bref); a percepção dos parceiros sobre a QV delas, foi medida através do WHOQOL-bref adaptado à terceira pessoa, os sintomas depressivos das pacientes foram avaliados através do Beck Depression Inventory (BDI) e as características demográficas e clínicas, através da ficha demográfica. Análise estatística: Foi utilizado o Programa SPSS, versão 12.0. o teste T de Student para as variáveis independentes, a correlação de Pearson e o modelo de regressão linear múltipla hierárquica. Resultados: A média de idade das mulheres com câncer de mama foi de 47,8 (7,8) anos e o tempo de doença de 3,08(3,2) anos. As variáveis do estudo foram agrupadas em blocos temporalmente relacionadas e realizada regressão linear múltipla hierárquica: bloco 1 (idade e grau de instrução), bloco 2 (estadiamento, tempo de doença, mastectomia e quimioterapia) e bloco 3 (BDI). O ponto de corte do BDI é 10, sendo consideradas deprimidas as mulheres com escore acima. Não houve diferença entre as percepções dos pares em todos os domínios. Entretanto, quando as mulheres estavam deprimidas, os parceiros pontuaram mais alto do que elas os domínios psicológicos e de relações sociais. Conclusões: Os parceiros das mulheres com câncer de mama percebem de forma acurada a QV delas, porém, quando elas estão deprimidas, a percepção difere nos domínios psicológico e de relações sociais. O parceiro pode ser útil como um substituto confiável quando a paciente não puder responder por si. A pior QV esteve associada à presença de mastectomia nos domínios físico e psicológico, e os sintomas depressivos em todos os domínios do WHOQOLBref. A avaliação da QV tem utilidade potencial na prática clínica e parece fundamental que os profissionais da saúde estejam alertas aos sintomas de depressão de suas pacientes, inclusive muitos anos após o diagnóstico de câncer. / Objectives: To assess the concurrence in perception of quality of life (QOL) between women with breast cancer and their mates and to invetigate the demografhic and clinical factors interfering in the QOL of these women. Method: A cross-sectional study in women with breast cancer of stages I, II and III, age bracket 18 to 65, with the same mate for at least a year, living together and capable of understanding the self-reporting instruments. Participants were selected at the outpatient breast cancer unit of Hospital de Clínicas de Porto Alegre and comprised 73 women and their respective mates. Sample size was calculated for comparison between two groups, with 0.5 level of significance and 80% power. QOL of these women was evaluated using the World Health Organization Quality of Life Questionnaire, version Bref (WHOQOL-Bref); mate’s perception of their QOL was measured by WHOQOL-Bref adapted to a third person; the depressive symptoms of the patients having been assessed by the Beck Depression Inventory (BDI) and the demographic and clinical characteristics by the demographic record. Statistical analysis: Instruments used were the 12.0, SPSS program, Student’s T test for the independent variables, the Pearson correlation and multiple hierarchic linear regression model. Results: The mean age of women with breast cancer was 47.8 (7.8) years and time of disease 3.08 (3.2) years. Study variables were grouped in time related blocks and muliple hierarchic linear regression carried out: block 1 (age and level of education), block 2 (staging, time of disease, mastectomy and chemotherapy) and block 3 (BDI). BDI’s cutting point is 10, women with a higher score being considered depressed.There was no difference in the partner’s perception in all domains. However, when the women were depressed the mates got higher points in the psychological and social relationship domains. The partner can be usefull as a reliable surrogate whenever the patient is unable to give her own answers. The worst QOL was associated to the presence of mastectomy in the physical and psychological domains, and the depressive symptoms in all domains of the WHOQOL-Bref. The assessment of QOL has a potential use in clinical practice and it seems fundamental that all health professionals be allert to depression symptoms of their patients, even many years after cancer diagnosis.

The research reported in this thesis investigated staff-student collaboration in advanced undergraduate mathematics course design and delivery at a research-intensive UK university. Staff and students collaborated to redesign and deliver two courses: Vector Spaces and Complex Variables. The collaboration in the design of the two courses involved students who had completed the courses and then who worked as interns together with a small team of academic staff. The collaboration in the delivery of the two courses involved the implementation of a Peer Assisted Learning (PAL) scheme in which third-year students facilitated the learning of second-year students in optional scheduled sessions. The study employed a mixed-methods research strategy involving an ethnographic approach to the study of the course design process and PAL sessions followed by an observational study (a quasi-experimental design) to investigate the impact of PAL attendance on the achievement of PAL participants. This thesis reports findings from a three-phase research design. Phase one explored the nature of the collaborations in course design and its impact on staff teaching practices and on the student collaborators. Phase two investigated the characteristics of the PAL sessions for the advanced undergraduate mathematics courses and the roles played in those sessions. Phase two also explored the impact of PAL in qualitative terms on both PAL participants and PAL leaders. Phase three investigated the impact of PAL in quantitative terms on the achievement of students who participated as PAL participants. The study found that staff-student collaboration in course design and delivery led to emergent Communities of Practice in which staff and students engaged in mathematics practice which led to identity transformation of student collaborators, a deeper understanding of the mathematics on which the students worked and some change in staff teaching and course design practice. The also showed that staff-student collaboration in the delivery of course units via PAL resulted in a learning community in which PAL participants and PAL leaders engaged in mathematics practice which led to increased student achievement and enhanced affective outcomes for both PAL participants and PAL leaders.

Made available in DSpace on 2014-06-11T19:33:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-07-16Bitstream added on 2014-06-13T19:04:43Z : No. of bitstreams: 1 batista_ee_dr_prud.pdf: 5013494 bytes, checksum: abce5592206940965608c8110a4fba22 (MD5) / PROPG / Este trabalho visa compreender as condições de vida e de trabalho de um grupo de sitiantes, pequenos proprietários de terra ou parceiros, que ainda se mantém na terra tendo como produto principal o café. Esses cafeicultores ocupam parte de uma das últimas áreas em que a cafeicultura ainda existe no município de Londrina: os bairros rurais da Laranja Azeda e da Limeira, no distrito de Lerroville. A permanência na terra só foi possível devido ao fato da lavoura cafeeira propiciar trabalho e renda para as famílias dos sitiantes durante mais de três décadas. No entanto, a partir do final da década de 1990, devido à implantação do modelo de políticas neoliberais na economia do país, o Estado brasileiro, que até então sempre havia estabelecido as regras para o funcionamento do complexo agroindustrial do café saiu de cena, deixando a cargo do mercado a regulamentação dos preços do produto. A partir desse momento uma forte crise se abateu sobre a cafeicultura brasileira, sendo os produtores os mais prejudicados. Para tentar superar a crise... / This work aims to understand the work and life conditions of a group of ranchers, small land owners or partners, which still remain on the farm having as main product the coffee. These growers occupy part of one of the last areas in which coffee still exists in Londrina: the rural neighbourhoods of Laranja Azeda and Limeira and the District of Lerroville. The permanence on the land was only possible due to the fact that the coffee plantations have provided jobs and income for the families of the ranchers for more than three decades. However, since the late 1990s, due to the implementation of the model of neoliberal policies in the economy of the country, the Brazilian state, which so far had always set the rules for the functioning of the agroindustrial complex of coffee, left the pitcure, leaving the market in charge of the regulation of the prices of the products. From this moment... (Complete abstract click electronic access below)

Made available in DSpace on 2015-05-14T13:16:31Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 2220780 bytes, checksum: f739fa31fb669e34ba74a85d469731fd (MD5) Previous issue date: 2012-03-02 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / Understand how loving relationships are configured has been one of major field of interest in Psychology, mainly under an evolutionary and social perspectives. In this sense, the main goal of this thesis was to know how gender differences, human values and personality traits could explain the choice of the ideal partner. Thus, three empirical studies were accomplished. The study 1 aimed to identify affective and cognitive characteristics between men and women. Participated 208 heterosexual people, 108 men and 100 women, with age ranging between 18 and 52 years (m = 24,3 years; sd = 6,08). They have answered a questionnaire that assessed affective and cognitive characteristics. Related to cognitive aspects, men obtained higher scores than women in the studied constructs. On the other hand, women had higher scores on affective aspects than men, except on cooperation. These results highlights that gender differences might play an important role to understand the way people choose an ideal partner. The study 2 intended to verify differences among gender, human values and personality traits regarding to partner preference. Participated 244 people, mostly women (62,7%), with a mean age of 20,9 years (sd = 4,06). They answered to Attributes of Ideal Partner Scale (AIPS), Basic Values Questionnaire (BVQ), The Big Five Inventory and demographic questions. Beyond the relationship among studied variables, the main result of this study showed that human values mediate the relationship among personality traits and partners attributes. Lastly, aiming to replicate study 2, the study 3 was carried out. On this purpose, was counted with 3.124 people from each of nine Northeast states, divided in 49,3% living in the country and 50,7% living in the city, with a mean age of 23,6 years (sd = 6,72) and mostly women (63,6%). Participants answered the same questionnaire applied on study 2. The relationship among variables was found once again in this study, nevertheless, no significant differences were found among northeast states. A hierarchical regression was accomplished and identified that values are better predictors to partner preference than personality traits and demographic variables. It is reinforced that mediation models among personality traits and partners attributes by values found in the previous study were corroborated in all states and between country and city residents. It is expected that studies like this one might contribute to strengthen the knowledge in the loving relationship field. / Compreender como se configuram os relacionamentos amorosos, tem sido uma das áreas de maior interesse dentro da Psicologia, sobretudo, com ênfase nas perspectivas evolucionista e sociais. Neste sentido, o objetivo principal desta tese foi conhecer em que medida diferenças entre gênero, valores humanos e traços de personalidade poderiam explicar a preferênca do (a) parceiro (a) ideal. Para tanto, foram realizados três estudos empíricos. O estudo 1 teve como objetivo principal conhecer características afetivas e cognitivas entre homens e mulheres. Participaram 208 pessoas, sendo 108 homens e 100 mulheres heterossexuais, com idades variando de 18 a 52 anos (m = 24,3 anos; dp = 6,08). Estes responderam instrumentos que avaliavam características afetivas e cognitivas. Em relação às características cognitivas, os homens pontuaram mais alto do que as mulheres nos construtos investigados. Quanto às características afetivas, as mulheres obtiveram maior média que os homens em relação a todos os construtos, com exceção de cooperação. Tais resultados evidenciam que diferenças entre gênero podem ser importantes para compreender como se configura a preferência do(a) parceiro(a). O estudo 2 objetivou conhecer diferenças entre gênero, valores humanos e traços de personalidade quanto à preferência pelo parceiro(a). Contou-se com 244 participantes, sendo a maioria do sexo feminino (62,7%), com idade média de 20,9 anos (dp = 4,06). Estes responderam a Escala de Atributos do Parceiro Ideal (EAPI), o Questionário dos Valores Básicos (QVB), o Inventário dos Cinco Grandes Fatores de Personalidade (Big Five) e questões demográficas. Foi possível verificar a relação entre os construtos estudados, verificando-se, sobretudo, que os valores medeiam a relação entre traços de personalidade e atributos do parceiro. Finalmente, com o objetivo de replicar o estudo 2, foi realizado o estudo 3 contando com a participação de 3.124 pessoas dos nove estados do Nordeste, sendo 49,3% residentes em cidades do interior e 50,7% das capitais, com idade média de 23,60 anos (dp = 6,72), sendo a maioria do sexo feminino (63,6%). Foram usados os mesmos instrumentos do estudo 2. Quanto aos resultados, também foram verificadas correlações entre os construtos estudados, não observando-se diferenças expressivas entre dados dos diferentes estados nordestinos. Por meio de análises de regressão hierárquica foi possível identificar que os valores são melhores preditores da preferência do(a) parceiro(a) do que os traços de personalidade e variáveis demográficas. Ressalta-se ainda, a confirmação dos modelos de mediação dos valores entre traços de personalidade e atributos do parceiro nos diferentes estados nordestinos e entre capital e interior. Estima-se que estudos dessa natureza possam contribuir na construção do conhecimento na área dos relacionamentos amorosos.

Objetivos: Avaliar a concordância da percepção da qualidade de vida (QV) entre mulheres com câncer de mama e seus parceiros, e investigar os fatores demográficos e clínicos que interferem na QV destas mulheres. Método: Realizou-se um estudo transversal em mulheres com câncer de mama nos estágios I, II, III, na faixa etária de 18 a 65 anos, com parceiro há pelo menos um ano, coabitando e em condições de compreender os instrumentos, que são autopreenchíveis. As participantes foram selecionadas no Ambulatório do Serviço de Mastologia do Hospital de Clínicas de Porto Alegre. Foram incluídas 73 mulheres e seus respectivos parceiros. O tamanho da amostra foi calculado para comparação entre dois grupos, com nível de significância de 0,05 e poder de 80%. A QV das mulheres foi avaliada através do questionário do World Health Organization Quality of Life, versão Bref (WHOQOL-Bref); a percepção dos parceiros sobre a QV delas, foi medida através do WHOQOL-bref adaptado à terceira pessoa, os sintomas depressivos das pacientes foram avaliados através do Beck Depression Inventory (BDI) e as características demográficas e clínicas, através da ficha demográfica. Análise estatística: Foi utilizado o Programa SPSS, versão 12.0. o teste T de Student para as variáveis independentes, a correlação de Pearson e o modelo de regressão linear múltipla hierárquica. Resultados: A média de idade das mulheres com câncer de mama foi de 47,8 (7,8) anos e o tempo de doença de 3,08(3,2) anos. As variáveis do estudo foram agrupadas em blocos temporalmente relacionadas e realizada regressão linear múltipla hierárquica: bloco 1 (idade e grau de instrução), bloco 2 (estadiamento, tempo de doença, mastectomia e quimioterapia) e bloco 3 (BDI). O ponto de corte do BDI é 10, sendo consideradas deprimidas as mulheres com escore acima. Não houve diferença entre as percepções dos pares em todos os domínios. Entretanto, quando as mulheres estavam deprimidas, os parceiros pontuaram mais alto do que elas os domínios psicológicos e de relações sociais. Conclusões: Os parceiros das mulheres com câncer de mama percebem de forma acurada a QV delas, porém, quando elas estão deprimidas, a percepção difere nos domínios psicológico e de relações sociais. O parceiro pode ser útil como um substituto confiável quando a paciente não puder responder por si. A pior QV esteve associada à presença de mastectomia nos domínios físico e psicológico, e os sintomas depressivos em todos os domínios do WHOQOLBref. A avaliação da QV tem utilidade potencial na prática clínica e parece fundamental que os profissionais da saúde estejam alertas aos sintomas de depressão de suas pacientes, inclusive muitos anos após o diagnóstico de câncer. / Objectives: To assess the concurrence in perception of quality of life (QOL) between women with breast cancer and their mates and to invetigate the demografhic and clinical factors interfering in the QOL of these women. Method: A cross-sectional study in women with breast cancer of stages I, II and III, age bracket 18 to 65, with the same mate for at least a year, living together and capable of understanding the self-reporting instruments. Participants were selected at the outpatient breast cancer unit of Hospital de Clínicas de Porto Alegre and comprised 73 women and their respective mates. Sample size was calculated for comparison between two groups, with 0.5 level of significance and 80% power. QOL of these women was evaluated using the World Health Organization Quality of Life Questionnaire, version Bref (WHOQOL-Bref); mate’s perception of their QOL was measured by WHOQOL-Bref adapted to a third person; the depressive symptoms of the patients having been assessed by the Beck Depression Inventory (BDI) and the demographic and clinical characteristics by the demographic record. Statistical analysis: Instruments used were the 12.0, SPSS program, Student’s T test for the independent variables, the Pearson correlation and multiple hierarchic linear regression model. Results: The mean age of women with breast cancer was 47.8 (7.8) years and time of disease 3.08 (3.2) years. Study variables were grouped in time related blocks and muliple hierarchic linear regression carried out: block 1 (age and level of education), block 2 (staging, time of disease, mastectomy and chemotherapy) and block 3 (BDI). BDI’s cutting point is 10, women with a higher score being considered depressed.There was no difference in the partner’s perception in all domains. However, when the women were depressed the mates got higher points in the psychological and social relationship domains. The partner can be usefull as a reliable surrogate whenever the patient is unable to give her own answers. The worst QOL was associated to the presence of mastectomy in the physical and psychological domains, and the depressive symptoms in all domains of the WHOQOL-Bref. The assessment of QOL has a potential use in clinical practice and it seems fundamental that all health professionals be allert to depression symptoms of their patients, even many years after cancer diagnosis.

OBJECTIVES: To determine the association of epithelial lesions and penile Human Papillomavirus infection among women with Human Papillomavirus induced cervical epithelial lesions and their partners.METHODS: To obtain the answer to the objectives were developed two studies. The first cross- sectional with 82 partners of women with cervical lesions Human Papillomavirus induced, examined by peniscopy, cytology and genotyping. The second study a systematic review with meta-analysis. The authors collected published information in databases about the prevalence of penile epithelial lesions and explored potential associations in partners of women with HPV-induced lesions. For the analysis we used methodological standards STROBE Initiative. Additionally meta-analyzes were conducted involving the selected studies.RESULTS: Observed positive peniscopy in 100% of patients. Koilocytosis in76.8%, and viral DNA positive in 14%, Human Papillomavirus types found were 16, 31 and 33. There was a significant association between the presence of penile injury and the time of contact with the partner p = 0.02. The authors included 29 studies in systematic review with a total of 8033 patients. Studies of case-control showed better methodological quality assessment in STROBE (Strengthening the Reporting of Observational Studies in Epidemiology). All patients were included in the meta-analyzes. There was a positive association between the detection methods for HPV and peniscopy among partners of women with cervical lesions and HPV infection in cross-sectional studies with Relative Risk (RR) of 0.87 and 0.34, and case-control (RR 0.13 and 0.58). The association was negative among cohort studies (RR 2.41 and 1.40).CONCLUSION: Positive peniscopy prevalence was higher than those found in the literature. There was significant association between penile lesion and time for socializing, in detriment of other risk variables A significant positive association in the meta-analysis of cross-sectional studies and case-control seems to demonstrate that there is a positive risk to partner of the woman s cervical lesion also acquires viral infection. The relative risk observed in the search for associations between HPV infection and peniscopy with both, positive and negative results appeared as a protective factor for acquiring HPV induced lesions in man. These tests could represent preventive methods for acquiring viral infection. / OBJETIVOS: Determinar a prevalência e associação de lesões epiteliais penianas e infecção por HPV entre mulheres com lesões epiteliais cervicais induzidas pelo HPV, e seus parceiros. MÉTODOS: Para obtenção da resposta aos objetivos foram elaborados dois estudos. O primeiro do tipo transversal prospectivo em 82 parceiros de mulheres com lesões cervicais HPV induzidas examinados através de peniscopia, citologia e genotipagem. O segundo uma revisão sistemática com metanálise onde os autores coletaram informações publicadas em bases de dados sobre a prevalência das lesões epiteliais penianas e exploraram as potenciais associações com as lesões HPV induzidas das parceiras. Para a análise metodológica utilizou-se os padrões da iniciativa STROBE (Strengthening the Reporting of Observational Studies in Epidemiology). Adicionalmente foram realizadas metanálises envolvendo os estudos selecionados. RESULTADOS: Observou-se peniscopia positiva em 100% dos pacientes, coilocitose em 76,8% , o DNA viral positivo em 14% , os tipos de HPVs encontrados foram 16, 31 e 33. Houve significativa associação entre a presença de lesão peniana e o tempo de convívio com a parceira p=0,02. Os autores incluíram 29 artigos na revisão sistemática, com um total de 8033 pacientes. Os estudos do tipo caso-controle apresentaram melhor qualidade metodológica na avaliação STROBE. Todos os pacientes foram incluídos nas metanálises. Houve associação positiva entre os métodos de detecção para o HPV e a peniscopia entre os parceiros de mulheres com lesão cervical ou infecção por HPV nos estudos transversais com Riscos Relativos (RR) de 0,87 e 0,34 e de caso- controle (RR de 0,13 e 0,58). A associação foi negativa entre os estudos de coorte (RR de 2,41 e 1,40). CONCLUSÃO: A prevalência de peniscopias positivas foi acima do encontrado na literatura. A associação entre a lesão peniana e o tempo de convívio, se mostrou significativo em detrimento de outras variáveis de risco. A associação significativa positiva na metanálise dos estudos transversais parece demonstrar que existe um risco positivo para o parceiro da mulher com lesão cervical também adquirir a infecção. O risco relativo observado nas associações entre a pesquisa para o HPV e peniscopias tanto com resultados positivos quanto negativos, apareceu como fator protetor para a infecção pelo Papilomavírus Humano no homem. Estes exames poderiam representar métodos preventivos para a aquisição da infecção viral.

Using data of first time fund in venture capital in United States from 1995 to 2015, I explore characteristics of the funds in relation to the fund performances. Three groups of characteristics that examined are fund characteristics, manager characteristics and limited partners’ characteristics. The paper also incorporates the time effects to show if market cycles have influences in these relationships. Some of the critical findings include that fund sizes have essentially zero impact on the fund return. In manager characteristics, it is very helpful to have a lead manager with MBA or equivalent degree. For limited partners, it is useful to have school endowments as limited partners which could influence the funds’ return positively. Both general partners and limited partners could learn from this paper and be more mindful of certain factor when investing in first time fund.

La promulgation de la loi de la sécurité financière (LSF) en 2003 a modifié l’architecture institutionnelle et la pratique d’audit en France. Au travers l’adjonction de nouvelles règles imposées par cette loi aux spécificités persistantes depuis 1966 comme le co-commissariat aux comptes et la durée du mandat de six ans, le marché d’audit se montre unique. Cette recherche examine l’impact de cette fusion réglementaire sur la qualité et le coût de l’audit en France. En se basant sur un échantillon composé par 888 observations du SBF 250 sur la période 2005-2010, nous avons révélé l’apport de la rotation des équipes signataires dans la restriction de la discrétion managériale. Outre son avantage dans la promotion de la qualité de l’audit, ce dispositif favorise la négociation à la baisse des honoraires d’audit. Nous avons aussi souligné l’évolution sous forme parabolique de la composante discrétionnaire sur la durée de mandat. En effet, la qualité de l’audit est inférieure pendant la première et la dernière phase de l’engagement. Ce postulat renvoie au renforcement de la compétence dans le temps et l’érosion de l’esprit critique à la fin du mandat. Le décalage, issu de la fusion réglementaire, favorise le maintien du niveau de la qualité élevé sur le marché français. L’association des deux équipes avec des durées auditeur-audité différentes est une contrainte à la discrétion managériale. Toutefois, ce décalage ne doit pas être excessif pour limiter la domination du plus ancien. Cet inconvénient du régime du co-commissariat aux comptes s’est trouvé limité sur le marché français. Nos résultats confirment son efficacité, essentiellement dans le cas d’un collège composé par deux Big 4. / In 2003, the promulgation of the financial security act (LSF) has changed the institutional architecture and audit practice in France. Through the addition of new rules imposed by this act to the persistent specificities since 1966 as the joint audit and tenure of six years, the audit market shows unique. This research examines the impact of this regulatory merger on the quality and the cost of the audit in France. Based on a sample composed by 888 observations of the SBF 250 over the 2005-2010, we found the contribution of rotation audit partners in restricting managerial discretion. Besides its advantage in promoting audit quality, this device supports the negotiation of lower audit fees. We also emphasized the evolution in the parabolic form of the discretionary accruals over tenure. Indeed, the audit quality is lower during the first and last phase of the engagement. This assumption refers to strengthening the skills over time and erosion of critical appraisal at the end of audit tenure. The shift from regulatory fusion helps to maintain the level of high quality on the French market. The combination of the two teams with different listener-audited tenures is a constraint to managerial discretion. However, this shift should not be excessive to limit the oldest’ domination. This drawback of the system of joint audits is limited in the French market. Our results confirm its effectiveness, mainly in the case of two Big 4.

Le polynucléaire neutrophile (PMN), cellule clé de l’immunité innée, est la première cellule à être recrutée sur le site inflammatoire. Après avoir détruit l’agent pathogène, il entre en apoptose puis est éliminé par les macrophages pour éviter le déversement de son contenu lytique, dangereux pour l’environnement. La régulation de la balance survie/apoptose du neutrophile est donc une étape cruciale de la résolution de l’inflammation. Notre laboratoire a mis en évidence la présence du Proliferating Cell Nuclear Antigen (PCNA) dans le neutrophile mature. PCNA est exprimé dans le noyau des cellules proliférantes, où il est impliqué dans la réplication/réparation de l’ADN et dans le contrôle du cycle cellulaire. PCNA est une protéine trimérique conservée au cours de l’évolution dépourvue d’activité enzymatique. En effet, PCNA constitue une “plateforme” qui interagit avec différents partenaires protéiques et orchestre leurs fonctions. De plus, pour assurer sa fonction, PCNA doit être obligatoirement sous forme trimérique. Dans le neutrophile mature, il a été démontré que PCNA avait une localisation exclusivement cytosolique et qu’il contrôlait spécifiquement la survie du neutrophile. La translocation de PCNA du noyau au cytosol a lieu pendant la différenciation granulocytaire. Elle est dépendante d'une séquence d'export nucléaire (NES) accessible et fonctionnelle que lorsque PCNA est monomérique. Le but de ma thèse a été d’étudier la plateforme de PCNA dans le cytosol du neutrophile afin d'identifier les protéines associées à PCNA afin de comprendre sa fonction dans les neutrophiles. Nous avons montré la présence de la forme monomérique et de la forme trimérique de PCNA dans le cytosol du neutrophile mature. Nous avons démontré une activité anti-apoptotique de la forme monomérique dans des cellules PLB985 différenciées en neutrophiles. De plus, nous avons identifié des peptides exposés sur la surface monomérique de PCNA qui sont utilisé comme des compétiteurs pour déplacer les interactions entre PCNA et ses partenaires dans le cytosol des neutrophiles. Ces peptides modulent la survie des neutrophiles. Grâce à des analyses de Spectrométrie de Masse, nous avons identifié des nouveaux partenaires de PCNA dans le cytosol du neutrophile impliqués dans plusieurs voies métaboliques. Cela suggère que PCNA régule la survie du neutrophile en interagissant avec différents protéines cytosoliques. Parmi les partenaires identifiés, nous avons trouvé les sous-unités cytosoliques de la NADPH oxydase, enzyme responsable de la production de formes réactives de l’oxygène, à la base de l’activité microbicide du neutrophile. Nous avons montré en particulier l’interaction entre p47phox et PCNA. Nous avons enfin étudié l’implication fonctionnelle de l’interaction de PCNA avec la NADPH oxydase dans des cellules PLB985 et également dans des neutrophiles humains. L’ensemble des résultats suggère que PCNA cytoplasmique maintient le neutrophile dans un état de repos, et aide l’assemblage de la NADPH oxydase lors de son activation. Le réseau protéique associé à PCNA régule l’activité et la survie du neutrophile en modulant différentes voies de signalisation. / Polymorphonuclear neutrophils (PMN), key cells of innate immunity are the first cell recruited to the inflammatory site. After destroying the pathogen, neutrophils undergo apoptosis and are cleared by macrophages to prevent the spillage of their lytic content that is dangerous for the environment. The regulation of the survival/apoptosis balance of neutrophil is a crucial step in the inflammation resolution. Our laboratory has shown the presence of Proliferating Cell Nuclear Antigen (PCNA) in mature neutrophils. PCNA is expressed in the nucleus of proliferating cells, where it is involved in DNA replication/repair and in cell cycle control. PCNA is a trimeric protein conserved during evolution and deprived of enzymatic activity. Indeed, PCNA is a “platform” that interacts with different partner proteins and orchestrates their functions. Furthermore, PCNA must be in trimeric form to play its role. In mature neutrophils, PCNA has an exclusively cytosolic localization where it specifically controls their survival. The PCNA translocation from nucleus to the cytosol happened during the granulocytic differentiation. This nuclear-to-cytosol relocalisation is dependent on a nuclear export sequence (NES), which is accessible and functional when PCNA is monomeric. The aim of my thesis was to study the PCNA platform in the neutrophil cytosol to identify the proteins associated with PCNA in order to understand its function in neutrophils. We have shown the expression of monomeric and trimeric forms of PCNA in the cytosol of mature neutrophils. We have demonstrated the anti-apoptotic activity of the monomeric form in PLB985 cells differentiated in neutrophils. Moreover, we have identified the surface-exposed peptides from the monomeric PCNA which are used as competitors of interactions between PCNA and its partner in the cytosol of neutrophils. These peptides modulate neutrophils survival. Thanks to the analysis of Mass Spectrometry, we have identified new partners of PCNA in the neutrophil cytosol involved in several metabolic pathways. This suggests that PCNA regulates neutrophil survival by interacting with different cytosolic proteins. Among the identified partners, we have found the cytosolic subunits of the NADPH oxidase, the enzyme responsible of the reactive oxygen species production, at the base of the neutrophil microbicidal activity. We have shown especially the interaction between p47phox and PCNA. Finally, we have investigated the functional implication of the interaction of PCNA with the NADPH oxidase in PLB985 cells and also in human neutrophils. Taken altogether, results suggest that the cytosolic PCNA maintains the resting state of neutrophils, and it helps the assembly of the NADPH oxidase when activated. The protein network associated with PCNA regulates the activity and the survival of neutrophil by modulating several pathways.

Oral human papillomavirus (HPV) infection and its association with head and neck cancers (HNCs) have been established by many studies. The characteristics of HPV-associated HNCs are distinguishable from those of non HPV-associated HNCs. HPV-associated HNCs are related to sexual behaviour, particularly the lifetime number of oral sex partners. The oral and oropharyngeal HPV epidemiology in South African men has not yet been researched. The objective of this study was to determine the oral and oropharyngeal HPV strain prevalence and associated factors in a selected male population in Pretoria, South Africa. Male factory workers were recruited on a voluntary basis to be part of this study. Oral rinse and gargle samples were tested for 37 HPV types using the HPV linear array genotyping kit (Roche Molecular System). A questionnaire was utilised to obtain information regarding age, medical conditions, substance and alcohol use and sexual behaviour. HIV testing was optional. The HPV prevalence was 5.6% among the men (n=125) aged 17-64 years. High risk HPV (hrHPV) types 16 and 68 were found in two men. Amongst the majority of the participants oral sex seemed to be an uncommon practice however, those participants with hrHPV did practice oral sex. A statistically significant association between HPV infection and an increased number of sexual partners (p=0.027) was seen but not between substance use, HIVstatus or clinical mucosal pathology. Considering the oral and oropharyngeal HPV prevalence found in this study compared to those reported in other countries. It is therefore proposed that a larger nationwide study be conducted to give a more representative view of the burden of oral and oropharyngeal HPV infection in South Africa. / Dissertation (MSc)--University of Pretoria, 2014. / lk2014 / Community Dentistry / MSc / Unrestricted