Le sepsis, cause majeure de décès en réanimation, entraîne des altérations immunitaires associées à un risque augmenté de décès et d'infections secondaires. En particulier, les lymphocytes T (LT) de patients présentent des altérations phénotypiques et fonctionnelles caractéristiques d'un état d'épuisement. Pour améliorer leur réponse, l'IL-7 est actuellement proposée comme immunostimulant. Son récepteur existe sous différentes formes: protéines membranaire (CD127) et soluble (sCD127) et différents transcrits. Leur expression n'a été que peu étudiée dans le sepsis. De plus, dans d'autres contextes cliniques, le phénotype CD127lowPD1high est proposé comme marqueur d'épuisement des LT mais n'a jamais été évalué dans le sepsis. L'objectif de ce projet était d'évaluer l'expression du récepteur de l'IL-7 comme biomarqueur dans le sepsis, d'étudier sa régulation chez les patients et la présence du phénotype CD127lowPD-1high en lien avec les altérations des LT. L'objectif était également de mettre au point un modèle ex vivo reproduisant les altérations intrinsèques aux LT de patients. Nous avons confirmé l'intérêt de la concentration plasmatique de sCD127 comme marqueur de mortalité chez les patients de réanimation. Nous avons mis en évidence l'association de l'expression des transcrits IL7R correspondant à des formes solubles avec la mortalité, ainsi que leur régulation intrinsèque dans les LT. Enfin, la proportion augmentée de LT CD127lowPD-1high chez les patients en choc septique en fait également un candidat potentiel comme marqueur spécifique des altérations des LT. Dans un deuxième temps, nous avons développé un modèle d'altérations induites par l'activation à partir de LT purifiés de volontaires sains reproduisant les altérations des LT de patients en choc septique. Ce modèle suggère un rôle de l'activation des LT dans le développement de leurs altérations et pourrait permettre d'étudier de nouveaux aspects de la physiopathologie des LT dans le sepsis / Sepsis is the leading cause of death in intensive care units (ICU). Septic patients develop immune dysfunctions that are associated with an increased risk of death and secondary infections. In particular, patients’ T lymphocytes present phenotypic and functional alterations characteristic of exhaustion. To restore these alterations, IL-7 is currently proposed as an immunostimulant. Its receptor exists in different forms: a membrane (CD127) and a soluble (sCD127) proteins and different transcripts. The IL-7 receptor expression has not been studied in sepsis. Moreover, the CD127lowPD-1high phenotype is proposed as a T cell exhaustion marker in other clinical contexts but has never been explored in sepsis.In this context, the aim of this project was first to evaluate the expression of the IL-7 receptor as a biomarker in sepsis, to study its regulation in patients and the CD127lowPD-1high phenotype in parallel with T cell alterations in septic shock patients. Secondly, the objective was to develop an ex vivo model reproducing phenotypic and functional T cell alterations observed in patients.We confirmed the role of sCD127 plasmatic concentration as a marker of mortality in septic shock and more generally in ICU patients. In addition, we demonstrated the association of the expression of the IL7R transcripts, corresponding to soluble forms with mortality as well as the intrinsic regulation of their expressions in T lymphocytes. Finally, we found an increased proportion of CD127lowPD-1high T cells in septic shock patients. This population could also be evaluate as a potential specific marker of T lymphocyte alterations. Secondly, we developed an ex vivo model of alterations induced by activation of purified T cell from healthy volunteers reproducing alterations observed in patients’ T cells. This model suggests a role of T cell activation in the development of their alterations and could be used to explore new aspects of T cell alterations pathophysiology in sepsis

Made available in DSpace on 2016-12-08T17:19:24Z (GMT). No. of bitstreams: 1 Maressa Budal Arins Bruno.pdf: 5840233 bytes, checksum: 01acb21e863b1fac362408711ebd6277 (MD5) Previous issue date: 2015-01-29 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The molding process of green sand generates large amount of exhaustion powders. These powders contain silica, carbon, iron oxide, and clay, that is, in their composition are present the elements predominantly found in raw materials employed on the fabrication of: bricks, tiles, cement and ceramic coatings. However, the exhaustion powder is presented as a powder of very fine particle size and higher level of non-plastic materials that can interfere in the performance processing and use of materials in which they are employed. Initially were characterized clays and exhaustion powders from one casting company through analysis of the chemical composition, mineralogy and grain size distribution. In laboratory was used an experimental design to evaluate the influence of the variables: effect of addition exhaustion powder and temperature on the mechanical properties. Thus, test samples were prepared with the adding 0, 10 and 20% powder exhaustion on the ceramic mass and submitted to firing at 800, 900 and 1000 °C. And then were evaluated the properties: linear shrinkage, water absorption, porosity, density and flexural strength at three points. The exhaustion powder was also evaluated as to its environmental classification and the results attended the requirements of the standard. Were produced at the industrial scale holes eight of ceramic blocks with added 0, 10 and 20% exhaustion powder and the ceramic mass burned at 800ºC temperature. The compressive strength and water absorption properties were evaluated. In the laboratory the best strength results were obtained with the addition of 20% of exhaustion powder and temperature of 900ºC. In industrial scale the best strength results were obtained with 10% of exhaustion powder. Finally, the results showed the feasibility of using this waste for the preparation of ceramic materials. / O processo de moldagem em areia verde gera grande quantidade de pós de exaustão. Estes pós contêm sílica, carbono, óxido de ferro, e argila, ou seja, em sua composição estão presentes os elementos predominantemente encontrados em matérias primas empregadas na fabricação de: tijolos, telhas, cimentos e revestimentos cerâmicos. Entretanto, o pó de exaustão apresenta-se como um pó de granulometria muito fina e elevado teor de materiais não plásticos que podem interferir no desempenho de processamento e de uso dos materiais em que sejam empregados. Inicialmente foram caracterizados as argilas e o pó de exaustão proveniente de uma mesma empresa de fundição através de análises da composição química, mineralógica e distribuição granulométrica. Em laboratório foi utilizado um planejamento experimental para avaliar a influência das variáveis: efeito da adição de pó de exaustão e temperatura sobre as propriedades mecânicas. Desta forma, foram confeccionados corpos de prova com adição de 0, 10 e 20% de pó de exaustão na massa cerâmica e submetidos à queima a 800, 900 e 1000ºC. Em seguida foram avaliadas as propriedades de retração linear, absorção de água, porosidade, densidade e resistência a flexão a 3 pontos. O pó de exaustão foi avaliado também quanto a sua classificação ambiental e os resultados atenderam aos requisitos da norma. Em escala industrial foram produzidos blocos cerâmicos de oito furos com adição de 0, 10 e 20% de pó de exaustão na massa cerâmica e queimados na temperatura de 800ºC. Foram avaliadas as propriedades de resistência a compressão e absorção de água. Em laboratório os melhores resultados de resistência mecânica foram obtidos com adição de 20% de pó de exaustão e temperatura de 900ºC. Em escala industrial os melhores resultados de resistência mecânica foram obtidos com 10% de pó de exaustão. Por fim, os resultados mostraram a viabilidade do uso deste resíduo para a preparação de materiais cerâmicos.

Dans le contexte du conflit opposant le principe de libre circulation des marchandises et les droits de propriété intellectuelle, le dilemme auquel ont été confrontées les autorités nationales et communautaires était de savoir si les autorités nationales devaient renforcer la protection des titulaires de propriété intellectuelle (courant conservateur) ou accroître le libre accès aux monopoles (courant libertaire). Sans se prononcer pour l'un des deux courants de manière radicale, le droit communautaire prône une solution en demi-teinte avec la théorie de l'épuisement, clairement ancrée dans le panorama de la propriété intellectuelle. Ultérieurement à la première mise en circulation des produits couverts d'un droit de propriété intellectuelle, sur le territoire communautaire, par le titulaire lui-même ou avec son consentement, ce dernier n'est plus légitimé à invoquer son droit privatif détenu dans un Etat membre afin d'interdire les opérations commerciales ultérieures ainsi que l'importation de produits mis en circulation dans un autre Etat membre pour lequel il bénéficie d'une protection identique. De cette étude, il ressort que si, à l'origine, les instances communautaires ont raisonné davantage en termes d'opposition, le conflit se résout, désormais, en termes de complémentarité, les droits de propriété intellectuelle impliquant des enjeux économiques majeurs dans notre économie de marché. La jurisprudence et les législateurs communautaires et nationaux ont su au gré des casuistiques trouver un juste équilibre entre les intérêts des différents acteurs de l'économie de marché que sont les titulaires de droit, les consommateurs-utilisateurs et les exploitants. / The dilemma in which the national and the European authorities had to face in the context of the conflict between the principle of the free movement of goods and the intellectual property rights was to know if the national authorities had to reinforce their protection of the intellectual property holders (conservative trend) or to increase their monopoly free access (libertarian trend). The European law did not vote for any of the two trends but chose a half-tone solution with the “exhaustion theory”, clearly anchored in the intellectual property panorama. From now on, once a good is put on the market for the first time, covered by a intellectual property right, on European market, by the owner himself or with his agreement, this person can no longer ask for his private right owned in another member state in order to prohibit further commercial actions such as importation of goods put on the market in another European member country that has as a similar protection. In this study emerges the fact that, if at the beginning, the opposition was the reasoning process of the community authorities to solve the conflicts in intellectual property rights, now with the major economic stakes in our market economy the complementarity prevails. Community and national authorities have found the right balance for the interests of all the different characters in the market economy who are the holder of rights, the consumers-users and the industrials.

Bakgrund: Sjuktalen har ökat till följd av psykisk ohälsa världen över. En av de främsta orsakerna till detta har varit den ökade förekomsten av stressrelaterad ohälsa och utmattningssyndrom. En grupp som har varit extra utsatt är personer i inom yrken i hälso- och sjukvården. Idag fokuseras det huvudsakligen på behandling och rehabilitering av utmattningssyndrom i forskning och praxis och det finns begränsad kunskap och initiativ kring primär- och sekundärprevention för utmattningssyndrom. Det är dock viktigt ur både ett individ- och samhällsperspektiv att förebygga utmattningssyndrom då utmattningssyndrom är ett allvarligt tillstånd som kan leda till stort lidande för individen och lång sjukfrånvaro från arbetslivet, vilket även är kostsamt för samhällsekonomin. Syfte: Syftet med detta examensarbete var att undersöka skyddsfaktorer mot utmattningssyndrom hos personer inom yrken i hälso- och sjukvården. Metod: En litteraturöversikt genomfördes och 12 vetenskapliga artiklar uppfyllde inklusion- och exklusionskriterierna och matchade forskningsfrågorna. Dessa lästes igenom. En tematisk analys av studiernas resultat genomfördes och resulterade i ett övergripande tema och fem underteman. Resultat: Resultatet beskriver faktorer som skyddar mot utmattningssyndrom för personer inom yrken i hälso- och sjukvården. Exempel på dessa faktorer var vikten av autentisk och god arbetsmiljö, känsla av egenmakt och kontroll, deltagande i meningsfulla aktiviteter, återhämtning och praktiska tekniker som exempelvis mindfulness, yoga och bildterapi. Att få socialt stöd från närstående, kollegor och exempelvis kuratorer och präster var även en viktig faktor för att skydda mot utmattningssyndrom. Slutsats: Skyddande faktorer för utmattningssyndrom finns på både individ-, organisations- och samhällsnivå och bör beaktas i utvecklingen av förebyggande insatser för utmattningssyndrom.

T cells chronically stimulated by their antigen often become dysfunctional and lose effector functions and proliferative capacity. This state of unresponsiveness is referred as T cell exhaustion. In order to investigate this, we developed a laboratory model, which allowed us to stimulate chronically in vivo a monoclonal population of CD4+ T cells. This model is based on the adoptive transfer of TCR transgenic CD4+ T cells specific for the male mHAg into male recipient mice. We found that systemic exposure to the male antigen modified deeply anti-male TcR-transgenic CD4+ T cells, plunging them into a state of functional unresponsiveness. Microarray analysis revealed that, in comparison with naive T cells, transferred T cells displayed a gene expression profile very similar to that of virus-specific exhausted CD8+ T cells. Moreover, like exhausted CD8+ T cells, exhausted CD4+ T cells lost their capacity to secrete IFN-ã as well as to proliferate in response to antigen stimulation, and T cell unresponsiveness was controlled by the engagement of programmed death receptor 1 (PD-1) present at the surface of T cells. <p>MicroRNAs are key molecules in shaping T cell function. In order to explore the possibility that chronic antigenic stimulation could shape the pool of microRNAs in exhausted anti-male CD4+ T cells that would account for specific changes in protein synthesis, we compared by microarray analysis the specific expression of microRNAs in naive CD4+ T cells and exhausted CD4+ T cells. Ninety five of them were found differentially expressed, among which, microRNA-155 (miR-155) displayed one of the highest changes. To identify the importance of miR-155 in T cell exhaustion, we analyzed miR-155-deficient CD4+ T cells after chronic exposure to systemic antigen. We found that, chronically-stimulated miR-155-/- CD4+ T cells were retained in a deeper state of unresponsiveness than miR-155+/+ CD4+ T cells. Furthermore, inhibition of PD-1/PD-L1 interaction did not promote antigen-dependent expansion of miR-155-deficient CD4+ T cells, nor did it stimulate T cell inflammation of several organs, contrary to what was observed in mice that received miR-155-sufficient CD4+ T cells. Thus, our observations demonstrated that miR-155 deficiency played a dominant role over PD-1-mediated inhibition of T cells and that miR-155 was required for restoring function in exhausted CD4+ T cells.<p>Next, we explored the mechanism by which exhausted miR-155-/- CD4+ T cells were kept in a deeper unresponsiveness state than miR-155+/+ counterparts. By comparative microarray analysis of gene expression between exhausted miR-155+/+ CD4+ T cells and miR-155-/- CD4+ T cells, heme oxygenase 1 (HO-1) was identified as a specific target of miR-155. Finally, inhibition of HO-1 activity restored the capacity of exhausted miR-155-/- CD4+ T cells to promote autoimmune inflammation in adoptively-transferred recipients. <p>Taken together, our study identified miR-155-mediated regulation of protein expression as a critical factor for restoring function in exhausted CD4+ T cells. Our results also present regulation of HO-1 expression in T cells as one of the mechanisms by which miR-155 promote T cell-driven inflammation. / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Routing policies are now represented by RPSL and by its evolutionary extension called RPSLng. These languages can be used for describing unique routing policy of each autonomous system. Experience shows that even though there are translation tools from RPSL and RPSLng to configuration formats of commonly used routers, the actual network configuration is rarely generated from RPSL sources and routing policy is then perceived as marginal paperwork, which often does not reflect the real network settings. There will be most likely a need for RPSL format change in order to remedy the discrepancies. To support this I present long-term measurements of inaccuracies in routing policies compared to real paths in the Internet. I also present a list of the most frequent problems, and I offer suggestions, how to reform RPSL to improve situation in the long term. Powered by TCPDF (www.tcpdf.org)

Routing policies are now represented by RPSL and by its evolutionary extension called RPSLng. These languages can be used for describing unique routing policy of each autonomous system. Experience shows that even though there are translation tools from RPSL and RPSLng to configuration formats of commonly used routers, the actual network configuration is rarely generated from RPSL sources and routing policy is then perceived as marginal paperwork, which often does not reflect the real network settings. There will be most likely a need for RPSL format change in order to remedy the discrepancies. To support this I present long-term measurements of inaccuracies in routing policies compared to real paths in the Internet. I also present a list of the most frequent problems, and I offer suggestions, how to reform RPSL to improve situation in the long term. Powered by TCPDF (www.tcpdf.org)

Magister Administrationis - MAdmin / The call centre industry has been one of the fastest growing industries in South Africa. Call centres have for most companies become a basic business requirement for servicing customers. Zapf, Isic, Bechtoldt and Blau (2003: 311) argue that there are high levels of stress amongst employees in call centres, which they believe to be the result of both the work tasks and the interactions with customers. The aim of this study was to establish whether call centre work design and structure contributed to role stress amongst client service representatives (CSRs). It was also the aim of this study to establish whether role stress affected the CSRs' levels of job satisfaction and their intentions to quit from their jobs. / South Africa

Magister Commercii (Industrial Psychology) - MCom(IPS) / The social work profession is strongly client based with workers being involved in complex social situations (Lloyd, King & Chenoweth, 2002). Social workers judgement and decision making are influenced by their emotions and the emotional context of the situation. Thus emotional intelligence is a core skill for every social worker. Morrison (2007) purported that in order to be a good practitioner one had to be able to comprehend and mange one‟s emotions and be completely aware of the power of these emotions. Social work thus requires emotional involvement and it is therefore not uncommon for social workers to be emotionally drained and frustrated, which inevitably can lead to burnout (Lukelelo, 2004). According to Howe (2008), on a daily basis social workers face the complex world of human behaviour within the social context. Within this world relationships are broken, emotions run high and personal needs may not be met. However, Kinman and Grant (2010) postulated if social workers possessed the correct emotional and social competencies it would assist them in coping with the stressors of the profession and could reduce psychological distress and enhance well-being.

Magister Commercii - MCom / In recent years, there has been a proliferation in research on work-family conflict which has become more prevalent in recent years due to the economic climate in which increasingly large numbers of women are entering or returning to the labour market. Finding equilibrium in work and family arenas has also become more important to South African employees. Traditional gender roles have evolved and the role of females as homemakers is no longer the norm. However, an alternative set of social standards have not yet been established as a substitute to new patterns of work and family life. As a result, it is important to focus on concerns relating to female experiences in the workplace to try and overcome the effects of work-family conflict on females.Job stress and role stress have increased dramatically in work and family life, as more women attempt to balance responsibilities at home whilst simultaneously trying to overcome challenges faced with at the office. Typically role ambiguity, role overload and role interference arises and ultimately produces two forms of conflict: time-based conflict and strain-based conflict. Self-efficacy and implementing coping strategies are means to overcome this.The objective of this study was to explore and add to existing research done on work-family conflict amongst females in the workplace. More specifically the study is to determine whether relationships exist between the variables: job stress, role stress, role overload, inter-role conflict, spousal support, coping behaviours; job, family and life satisfaction, emotional exhaustion; the nature of the relationships and the causal impacts between these variables.Two hundred questionnaires were administered and 150 were returned to women employed in a service oriented organisation in the Western Cape.The statistical package for social sciences (SPSS) was utilized to analyze and present data in this research with frequency tables and graphical illustrations to provide information on key demographic variables in this study. The results reveal that there are statistically significant relationships amongst work overload and work-family conflict (WFC). There was also a significant relationship between parental overload and WFC. Moreover, the strongest relationship emerged between WFC and family-to-work conflict (FWC). Females experiencing WFC showed a tendency to rely on problem-focused coping strategies. In addition, there was an inverse relationship between job satisfaction and WFC. There was a significant difference in WFC based on age, tenure, number of children, income and tenure. There was no significant difference in WFC on the basis of marital status. There were statistically significant differences in FWC based on some of the biographical characteristics of the respondents. There was a significant difference in FWC based on age, tenure, income and occupation.Approximately 35% of the variance in WFC can be explained by age, education, income, work overload, parental overload and spousal support. These variables account for 33.53% of the variance in WFC, and suggest that other unexplored variables could explain the variance in WFC levels experienced by respondents. Approximately 38% of the variance in role stressors can be attributed to age, education, income, work overload, parental overload and spousal support in relation to FWC. The results which emanated from the current study assist in furthering an understanding of WFC and FWC. Individual and organisational implications are discussed and recommendations are made to further enhance this study with additional research into this area being warranted.