Masters in Public Administration - MPA / Community participation and awareness in disaster risk management is widely recognized as a cornerstone for disaster risk reduction and effective response and recovery strategies. This goes parallel with the world paradigm shift form relief and response to prevention and mitigation. There is gradually increase of fire and floods in informal settlements and Khayelitsha TR- Section in particular. “From 1995-2005 more than 8554 informal dwelling fire incidents occurred in Cape Town alone, affecting 40 558 households and around 160 000 peoples" (DiMP, 2008). And in 2007 alone floods affected 8,000 households and 38 residents in the Cape Town informal settlement of Khayelitsha; Bongani TR-Section and Phillippi; Phola park (Bouchard et al, 2007). This study analyzed community participation and awareness mechanisms in disaster risk management, its implementation, practice and effectiveness, following the promulgation of the Disaster Management Act No 57 of 2002, taking Khayelitsha TR- Section as a case study. In order to achieve the stated objectives, the researcher employed a combination of both qualitative and quantitative research paradigms. In qualitative context semi-structured interviews were conducted with the key informants disaster management officials and Khayelitsha TR-Section ward structure officials. Quantitative method, 100 structured questionnaires were distributed to Khayelitsha TR-Section residents. Using Khayelitsha TR- Section as a case study the thesis argues that despite the enabling policy and resource allocation for community participation and awareness its implementation proved to be a failure. Most of the mechanisms directed by the act are not implemented and those implemented its practice is not effective to achieve its stated objectives of risk reduction and effective response and recovery to disaster incidents. The study reviewed literature and theories of community participation and awareness in disaster risk management. It reviewed and outlined a policy framework and institutional arrangement for community participation and awareness in disaster risk management in accordance with the Disaster Management Act (No 57 of 2002). It further determined the level of community participation and awareness mechanism implementation. Records the level of community awareness and understanding, it determines the effectiveness of community participation and awareness mechanisms and finally based on the empirical results, literature reviews and theories, the study provides a number of recommendations to enhance and improved of community participation and awareness to disaster risk management officials and policy makers.

Diese Arbeit beschäftigt sich mit der Entwicklung eines empirischen Modells zur Simulation von TokenRing-Netzwerken auf Basis eines MonteCarlo-Ansatzes. Desweiteren werden die Ergebnisse aus verschiedenen Beispielsimulationsläufen dargelegt und diskutiert. Hierbei werden vor allem die Auswirkungen der einzelnen Protokolle und Protokollebenen auf die Systemleistung und -auslastung betrachtet.

Background Medically managed tricuspid regurgitation (TR) has detrimental outcomes. Transcatheter tricuspid valve interventions (TTVIs) represent an alternative to surgery in high-risk patients; however, only early experiences exist. Aim The aim of this study was to analyze the clinical and echocardiographic outcomes of TTVI. Methods MEDLINE, ISI Web of Science, and SCOPUS databases were searched for studies published up to June 2021. Studies reporting data on outcome post-TTVIs were included. This study was designed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) requirements. The primary endpoint was all-cause mortality at 30-day and 1-year post-TTVI. Results Out of 2,718 studies, 27 were included. Notably, 30-day and 1-year all-cause mortalities were 5% (95% confidence interval [CI]: 4–8%, p < 0.001) and 25% (95% CI: 12–45%, p = 0.016). Procedural success was associated with a 58% risk reduction in 1-year mortality vs. lack thereof (odds ratio 0.42, 95% CI: 0.27–0.66, p < 0.001). TTVI is associated with a significant reduction in TR severity (TR EROA, mean difference [MD] 0.31 cm2; 95% CI: 0.23–0.39 cm2, p < 0.001; regurgitant volume, MD 23.54 ml; 95% CI: 17.4–29.68 ml, p = 0.03) and increase in forward stroke volume (FSV, MD 3.98 ml; 95% CI: 0.11–7.86 ml, p = 0.04). Conclusion TTVI significantly reduces TR severity and increases FSV and is associated with improved survival at 1 year compared with patients without procedural success. Long-term outcomes compared with medical therapy await the results of ongoing pivotal trials; nonetheless, TTVIs appear to be a promising alternative to surgery for TR.

Nicotinamide cofactor-dependent oxidoreductases have become a valuable tool for the synthesis of high value chiral compounds. The feasibility of biocatalytic processes involving these enzymes stands and falls with the efficiency of the regeneration of cofactors. In this study, we describe a novel NADPH regeneration method based on the natural thioredoxin electron delivery system. Thioredoxin 1 (Trx1) and thioredoxin reductase (TR) from Thermus thermophilus were characterized for the dithiol-dependent reduction of NADP+, revealing good catalytic activities and a particularly remarkable thermostability. The TR/Trx1 system was then coupled with two representative NADPH-dependent oxidoreductases, alcohol dehydrogenase and cyclohexanone monooxygenase. Reaction conditions for both systems were optimized for reaction yield and selectivity. The results demonstrate the feasibility of the TR/Trx1-system for its application as NADPH regeneration system.

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No description available.

This study examines the stressful responses of faculty/staff and students after experiencing the April 16, 2007 school shootings at Virginia Tech. Understanding people's responses to trauma not only assists in more knowledge about what is stressful after a traumatic event but also may facilitate the finessing of tools and strategies for resilience and recovery in the aftermath of trauma. After investigating stressful responses to the April 16, 2007 shootings at Virginia Tech, and in particular those with probable PTSD (posttraumatic stress disorder), I found it was not always necessary to meet the "stressor" A criterion of PTSD. This is crucial because the "stressor" criterion A of PTSD is required to receive the diagnosis of PTSD. Although I found subtle stress differences for women compared to men, and faculty/staff compared to students, none of the differences were statistically significant. This research additionally contributes to the literature by detailing a profile of stressors for both faculty/staff and students in the aftermath of the worst college campus shooting in U.S. history to date. Findings suggest future research should examine the "stressor" criterion A of PTSD as well as the full spectrum of stressful responses both in the "immediate" and "delayed" aftermath of trauma(s). / Ph. D. / This study looks at responses of stress for faculty/staff and students after being exposed to the April 16, 2007 school shootings at Virginia Tech. Understanding responses to trauma not only provides more knowledge about what is stressful after a traumatic event, it may help us to learn and better fine-tune ways for recovery in the aftermath of trauma. After investigating these stressful responses to the April 16, 2007 shootings at Virginia Tech, and in particular those likely to go on to develop PTSD (posttraumatic stress disorder), I found that it was not always necessary to meet the “stressor” criterion A of PTSD. This is important because the “stressor” criterion A of PTSD is required to receive the PTSD diagnosis. Although I found some interesting differences in stressors for women compared to men, and faculty/staff compared to students, none of the differences were significant statistically. This work also contributes to research by detailing a profile of stressors for both faculty/staff and students in the aftermath of the worst college campus shooting in U.S. history to date. Findings suggest the need to continue to examine criterion A of PTSD as well as the full range of stressful responses both during, and in the aftermath of, trauma(s).

L'hormone thyroïdienne (T3) contrôle à la fois les processus développementaux et physiologiques. Elle agit via les récepteurs de l'hormone thyroïdienne (TR), membres de la famille des récepteurs hormonaux nucléaires. Ils agissent comme des facteurs de transcription dépendants du ligand. La méthylation de l'ADN en position 5 de la cytosine est une modification épigénétique importante qui affecte la structure de la chromatine et l'expression des gènes. Des études récentes ont établi un rôle important des protéines de la famille TET (Ten-eleven translocation) dans la régulation de la dynamique de la méthylation de l'ADN. Elles convertissent la 5-méthyl-cytosine (5mC) en 5-hydroxyméthylcytosine (5hmC). D’autres études ont démontré que les protéines TET (TET1, TET2 et TET3) possèdent des fonctions de régulation transcriptionnelle dépendantes et indépendantes de leur activité catalytique. Notre étude a identifié TET3 comme une nouvelle protéine interagissant avec TR. Le domaine AF2 de TR ainsi que le domaine catalytique et le domaine CXXC de TET3 sont responsables de cette interaction. Celle-ci permet la stabilisation de TR lié à la chromatine, entraînant une potentialisation de son activité transcriptionnelle. L'effet de modulation de TET3 sur TR présenté ici est indépendant de son activité hydroxylase de TET3. Ainsi, cette étude met en évidence un nouveau mode d'action de TET3 en tant que régulateur non classique de TR, modulant sa stabilité et son accès à la chromatine plutôt que son activité de transcription intrinsèque. Des mutations du gène codant pour TRα provoquent le symptôme RTHα dont la gravité varie en fonction de la mutation. Les différentes capacités d’interaction des mutants TRα, pertinents pour la maladie de RTHα humaine, avec TET3 pourraient expliquer les différences d’effet dominant négatif. La fonction de régulation de TET3 pourrait s’appliquer plus généralement aux facteurs de transcription des récepteurs nucléaires, car différents membres de la superfamille des récepteurs nucléaires présentent la même interaction avec TET3, tels que AR (récepteur des androgènes), ERR (récepteur des œstrogènes) et RAR (récepteur de l'acide rétinoïque). L'interaction entre TET3 et RAR implique le domaine de liaison ADN de RAR. La pertinence fonctionnelle de l'interaction TET3 / RAR a été étudiée plus en détail dans les cellules souches embryonnaire (cellules ES). L’absence combinée des trois TET a entraîné la diminution de 5hmC et la dérégulation des gènes impliqués dans la différenciation des cellules ES. Parmi les gènes dérégulés, nous avons identifié un sous-ensemble de gènes cibles de l’acide rétinoïque, suggérant que les RAR (récepteurs d'acide rétinoïque) et les TET pourraient travailler ensemble pour réguler la différenciation des cellules ES. Une étude supplémentaire a révélé que les protéines TET peuvent jouer un rôle dans la facilitation du recrutement de RAR aux régions promotrices de ses gènes cibles. En outre, nos résultats montrent un rôle potentiel de l'activité hydroxylase des protéines TET dans la modulation de l'activité transcriptionnelle des RAR. En conclusion, notre travail a identifié les protéines TET comme nouveaux régulateurs des récepteurs nucléaires. Les mécanismes exacts impliqués doivent être étudiés plus avant. / Thyroid hormone (T3) controls both developmental and physiological processes. Its nuclear receptors, thyroid hormone receptors (TRs), are members of the nuclear hormone receptor family which act as ligand-dependent transcription factors. DNA methylation at the fifth position of cytosine is an important epigenetic modification that affects chromatin structure and gene expression. Recent studies have established a critical function of the Ten-eleven translocation (TET) family proteins in regulating DNA methylation dynamics by converting 5-methyl-cytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Studies demonstrated that TETs proteins (including TET1, TET2 and TET3) possess catalytic activity dependent and independent transcriptional regulatory functions. Our study identified TET3 as a new TR interacting protein. The AF2 domain of TR and the catalytic domain and CXXC domain of TET3 are responsible for their interaction. This interaction allows the stabilization of chromatin bound TR, resulting in a potentiation of its transcriptional activity. The modulation effect of TET3 on TR presented here is independent of its hydroxylase activity. Thus this study evidences a new mode of action for TET3 as a non-classical regulator of TR, modulating its stability and access to chromatin rather that its intrinsic transcriptional activity. Mutations in TR cause the RTH symptom which severity varies with the particular mutation. The differential ability of different TRα mutants, relevant for the human RTHα disease, to interact with TET3 might explain their differential dominant negative activity. The regulatory function of TET3 might be more general towards the nuclear receptor transcriptional factors since different members of the superfamily present the same interaction with TET3, such as AR (androgen receptor), ERR (Estrogen-related receptor) and RAR (retinoic acid receptor). The interaction between TET3 and RAR involves the DNA binding domain of RAR. The functional relevance of TET3/RAR interaction was further studied in ES cells. Combined deficiency of all three TETs led to depletion of 5hmC and deregulation of genes involved in ES differentiation. Among the deregulated genes, a subset of RA response genes was identified, suggesting that RARs (retinoic acid receptors) and TETs might work together to regulate ES cell differentiation. Further dissection revealed that TET proteins may have a role in facilitating RAR recruitment to the promoter regions of these RAR target genes. Moreover, our results indicated a potential role of the hydroxylase activity of TET proteins in modulating RAR transcriptional activity. Altogether, our work identified TET proteins as new regulators of NR (Nuclear Receptors). The exact mechanisms involved need to be further studied.

A proporção de idosos portadores da síndrome da imunodeficiência adquirida (aids) tem aumentado de maneira importante nos últimos anos e, até a presente data, existem poucos estudos que abordam a infecção nessa população especial. As particularidades imunológicas decorrentes do fenômeno da imunossenescência podem acarretar mudanças significativas na evolução da infecção pelo HIV, bem como na resposta ao tratamento. O objetivo maior desta Tese foi avaliar o impacto da idade na recuperação funcional do sistema imune de pacientes com aids acima de 55 anos, quando tratados adequadamente com terapia anti-retroviral, caracterizando a resultante imunológica da idade avançada e da infecção pelo HIV. Para tanto, foram estudados quatro grupos experimentais: indivíduos jovens saudáveis ou com aids, e indivíduos acima de 55 anos saudáveis ou com aids. Todos os pacientes com aids estavam recebendo terapia anti-retroviral, em sucesso terapêutico. No primeiro artigo apresentado, avaliamos resposta linfoproliferativa e produção de citocinas in vitro e resposta humoral in vivo mediante desafio antigênico com toxóide tetânico (TT) em indivíduos previamente vacinados contra o tétano. Os resultados mostraram deficiências imunológicas significativas relacionadas à idade avançada no que diz respeito a produção de IgG anti-TT, resposta linfoproliferativa e produção de IFN-&#61543;. Em contrapartida, a produção de IL-10 foi significativamente maior nos indivíduos acima de 55 anos, infectados ou não pelo HIV. No segundo artigo, foram caracterizadas as subpopulações de células T mediante estímulo policlonal ou específico com antígenos do envelope do HIV (Env). Em culturas não-estimuladas de PBMC do grupo com aids e idade avançada, observamos frequência reduzida de células T naive e de memória central, associada a aumento de células T efetoras. Quando estimuladas policlonalmente, essas culturas apresentaram deficiência na produção de IFN-&#61543; e hiperprodução de IL-10, como na resposta ao TT. Mediante estímulo específico com Env, a citometria de fluxo revelou frequência elevada de células T CD4+FoxP3-CD152+ com forte marcação intracelular para IL-10, indicando predomínio do fenótipo Tr-1, e não das células Treg clássicas. Interessantemente, em ambos os artigos, a replicação viral in vitro foi significativamente menor nos pacientes com aids acima de 55 anos, condizendo com a excelente resposta virológica desses pacientes ao tratamento antirretroviral. A neutralização da IL-10 com anticorpo anti-IL-10 nas culturas ativadas pelos peptídeos Env aumentou de forma significativa a replicação viral no sobrenadante. Tanto na resposta ao TT quanto aos peptídeos Env, o bloqueio da IL-10 aumentou os níveis de citocinas pró-inflamatórias, mas não melhorou a produção de IFN-&#61543; dos pacientes acima de 55 anos com aids. Coletivamente, os achados dessa Tese revelam distúrbios em vários segmentos da resposta imune, particularmente no compartimento Th1, de pacientes acima 55 anos com aids e adequadamente tratados, sugerindo que, para esses pacientes, a reconstituição imune pós-tratamento não ocorre com a mesma eficácia que no jovem. Apesar do aumento da produção de IL-10 provavelmente contribuir, ao menos em parte, para o controle virológico, pode comprometer a resposta tanto ao próprio HIV, quanto a outros desafios antigênicos, a exemplo do toxóide tetânico. Sugere-se, portanto, a necessidade de recomendações específicas de manejo clínico para esse grupo de pacientes / The proportion of aged persons living with the acquired immunodeficiency syndrome (aids) has importantly increased in recent years and, up to the present moment, there are few studies that address the infection in this particular population. The immunological nuances resulting from the immunosenescence phenomenon may promote significant alterations in the clinical course of HIV infection, as well as in treatment response. The major purpose of this Thesis was to evaluate the impact of age on the functional immune recovery in aids patients aged more than 55 years, when adequately treated with anti-retroviral therapy, characterizing the immunological result of advanced age and HIV infection. Thus, four experimental groups were enrolled: healthy or HIV-infected young adults, and healthy or HIV-infected adults over 55 years old. All the HIV-infected patients had diagnosis of aids and were under anti-retroviral treatment with therapeutic success. In the first presented article, we evaluated the lymphoproliferative response and cytokine production in vitro and humoral response in vivo, after antigenic challenge with tetanus toxoid (TT) in previously immunized individuals against tetanus. The results revealed significant age-related immunological impairments concerning anti-TT IgG production, lymphoproliferative response and production of IFN-&#61543;. On the other hand, the production of IL-10 significantly higher in individuals aged more the 55 years, HIV-infected or not. In the second article, T cell subsets were characterized after polyclonal activation or specific stimulus with antigens derived from the HIV envelope (Env). In fresh unstimulated PBMC cultures obtained from the aged aids patients, there was a reduced frequency of naïve and central memory T cells, associated with increased frequency of effector T cells. When polyclonally stimulated, these cultures showed deficient production of IFN-&#61543; and hyperproduction of IL-10, like in response to TT. In Env-stimulated cultures, flow cytometry revealed high frequency of T CD4+FoxP3-CD152+ T cells with strong intracellular staining for IL-10, indicating a dominant Tr-1 phenotype, and not the classical Treg cells. Interestingly, in both articles, the viral replication in vitro was significantly lower aids patients over 55 years old, which is in consonance with their excellent virological response to anti-retroviral treatment. IL-10 neutralization with anti-IL-10 antibody in Env-activated cultures enhanced the viral replication in culture supernantants. Both in TT and in Env-peptides-stimulated cultures, the IL-10 blockade enhanced the levels of pro-inflammatory cytokines, but it did not improve IFN-&#61543; production from aged aids patients. Altogether, the results reported in this Thesis reveal disturbances in several segments of the immune response, particularly in the Th1 compartment, of anti-retroviral-treated aids patients older than 55 years, suggesting that, for these patients, immune reconstitution after treatment does not occur with the same efficacy as in young patients. And although the enhanced IL-10 production probably contributes, at least in part, to the virological control, it can compromise the immune response both to HIV and to other antigenic challenges, such as tetanus toxoid. It is suggested, therefore, the need for specific recommendations regarding the clinical management of these patients

Made available in DSpace on 2014-12-17T15:38:41Z (GMT). No. of bitstreams: 1 FabioHVCS.pdf: 377178 bytes, checksum: 09ec26bbc3b2869ee17c8b8c3044e7a5 (MD5) Previous issue date: 2008-07-14 / The object of this study was to identify the possibility of predicting the involvement in traffic infractions from the results of the psychological tests carried out by psychologists specialized in the process of driver licensing in the state of Rio Grande do Norte (RN). The proposal consisted in identifying the penalty points recorded in national driving licenses (CNH) and identifying the corresponding tests and scores obtained, verifying if the average scores in the tests of drivers with and without an infraction record were significantly different and if there is any relation between the test scores and the frequency of the infractions. The results of the psychological instruments were collected in two moments the first being in the act of acquisition of the CNH and the second being during license renewal at the only certified clinic and at the DETRAN-RN. A population of 839 drivers of 14 municipalities were identified. 127 protocols of psychological tests were identified in the records of the DETRAN-RN (2002) and 76 at the clinic (2007), pointing out failures in the process of safekeeping of the psychological material, as well as in its retrieval from the record files. The sample was thus reduced to 68 drivers, all male, with age range between 18 and 41 years old, mean of 21,72 years old (DP = 5,24). 54 drivers were identified without a record of infraction, and 14 with a record. The latter committed 29 infractions. The penalty points recorded in their CNH ranged from 0 to 35 and the typical value of points (median) was zero. In the group with a record of infractions the number of points ranged between 3 and 35, mean of 10,79 (DP = 7,73). Differences were observed in the composition of the battery of tests in the two moments with the same subjects. The use of different tests to assess the same construct of the subject, first and second moment of assessment, did not allow for some analyzes with more efficient statistical proof. It was pointed out that five tests were not carried out and 118 were not corrected/analyzed. Significant differences between the groups were not identified with the psychological instruments used. In another attempt to establish differences between the means, the application of the independent t-Test evidenced a significant difference in the scores of the instruments of concentrated attention in 2002 (t = 2,21, gl = 25, p = 0.037) and of diffuse attention in 2002 (t = 2,37, gl = 24, p = 0.026). The results also did not evidence significant correlation between the scores of the tests and the penalty points of the infractions. Based on this study, it cannot be concluded with precision that the high or low scores are good criteria to determine that a driver will commit more or less traffic infractions, nor that the drivers with higher scores in the tests commit less infractions and vice-versa. Furthermore, the problems to find the instruments and the most basic data require a stronger monitoring on the part of the certified clinic and of the DETRAN-RN. / O objetivo deste estudo foi identificar a possibilidade de prever o envolvimento em infra??es de tr?nsito a partir dos resultados dos testes psicol?gicos aplicados por psic?logos peritos no processo de habilita??o de condutores no Rio Grande do Norte (RN). A proposta consistiu em identificar os pontos na carteira nacional de habilita??o (CNH) e identificar os testes e os escores obtidos, verificando se os escores m?dios dos testes dos motoristas com e sem registro de infra??o s?o significativamente distintos e se existem rela??es entre os escores dos testes e a freq??ncia de infra??es. Os resultados dos instrumentos psicol?gicos foram coletados em dois momentos - sendo o primeiro no ato da aquisi??o da CNH e o segundo na renova??o - na ?nica cl?nica credenciada e no DETRAN-RN. Identificou-se uma popula??o de 839 condutores de 14 munic?pios. Encontraram-se nos arquivos do DETRAN-RN 127 protocolos de testes psicol?gicos aplicados (2002) e 76 na cl?nica (2007), evidenciando falhas no processo de guarda do material psicol?gico, bem como de sua recupera??o nos arquivos. A amostra ficou reduzida a 68 motoristas, todos do sexo masculino, com idade de 18 a 41 anos, m?dia de 21,72 anos (DP = 5,24). Identificaram-se 54 motoristas sem registros de infra??o e 14 com registro. Estes ?ltimos cometeram 29 infra??es. A pontua??o na CNH variou de 0 a 35 e o valor t?pico de pontos (mediana) foi zero. No grupo com registro de infra??o a pontua??o variou de 3 a 35, m?dia de 10,79 (DP = 7,73). Observaram-se diferen?as na composi??o das baterias de testes nos dois momentos nos mesmos sujeitos. O uso de testes diferentes para avaliar um mesmo construto do sujeito, primeiro e segundo momento de avalia??o, impossibilitou algumas an?lises com provas estat?sticas mais eficientes. Evidenciou-se que cinco testes n?o foram aplicados e 118 n?o foram corrigidos/analisados. N?o foram identificadas diferen?as significativas entre os grupos nos instrumentos psicol?gicos aplicados. Em outra tentativa para estabelecer diferen?as entre as m?dias, a aplica??o do Teste t independente evidenciou uma diferen?a significativa nos escores nos instrumentos de aten??o concentrada em 2002 (t = 2,21, gl = 25, p = 0.037) e da aten??o difusa em 2002 (t = 2,37, gl = 24, p = 0.026). Os resultados tamb?m n?o evidenciaram correla??es significativas entre os escores dos testes e as pontua??es das infra??es. Com base neste estudo, n?o se pode concluir com precis?o que os altos ou baixos escores s?o bons crit?rios para definir que um motorista cometer? mais ou menos infra??o de tr?nsito, nem que os motoristas com maiores escores nos testes cometem menos infra??o e vice-versa. Al?m disso, os problemas para se encontrar os instrumentos e os dados mais b?sicos requer um acompanhamento mais aprofundado por parte da cl?nica credenciada e do DETRAN-RN.