<p>Tuberkulos (tbc) är en luftburen droppsmitta orsakad av mykobakterium tuberkulosis. Tbc är den sjukdom som efter AIDS orsakar flest dödsfall, trots att botande behandling finns. Behandlingen är krävande för den tbc-smittade att genomgå och bygger på en kombination av en rad antibiotika som måste intas under minst sex månader. Ett avvikande i behandlingen kan resultera i att mykobakterium tuberkulosis blir resistent mot de ordinerade antibiotika. Följsamhet av långtidsbehandlingar som tbc-behandling graderas till 50 %. Syftet med litteraturstudien var att ur ett globalt perspektiv beskriva hur sjuksköterskan kan påverka följsamhet vid tbc-behandling i syfte att minska resistensutvecklingen av mykobakterium tuberkulosis. Studien genomfördes som en litteraturstudie där 12 vetenskapliga artiklar granskades och analyserades. Resultatet visar tydligt att specifika faktorer påverkar följsamhet och därigenom resistensutvecklingen. Faktorerna innefattar patientundervisning, behandlingsstrategier, omgivningens påverkan och stöd.  Undervisningen resulterar i att patienten får ökad förståelse för behandlingen. För att minska stigmatiseringen och det lidande den innebär för den tbc-smittade är även omgivningen i behov av ökad kunskap och information om tbc. Ett flertal studier visar att DOTS-strategin är betydelsefull för ökad följsamhet vid antituberkulos behandling. Litteraturstudien medför ett förslag om att sjuksköterskeprogrammet ska öka fokuseringen på följsamhet vid läkemedelsanvändning. Sjuksköterskan är i behov av att redan under grundutbildningen få kunskap om ansvarsfull antibiotikahantering som leder till en följsamhetsomtanke.</p> / <p>Tuberculosis (TB) is an airborne droplet infection caused by mycobacterium tuberculosis. TB is the disease after AIDS that is most deadly, even though curative treatment exists. The treatment is demanding for the TB-infected to undergo and consists of a combination of a number of antibiotics that must be administered for at least six months. A dissenting in anti-tuberculosis treatment might result in mycobacterium tuberculosis strains that are resistant to antibiotics. As adherence to long-term treatment is graded at a low percentage (50 %) the aim of the literature study was from a global perspective to develop a working-strategy for nurses that promote compliance in TB-treatment in order to reduce resistance development of mycobacterium tuberculosis. The study was conducted as a literature study where 12 research articles were reviewed and analyzed. The results describe specific factors that are essential to compliance. These factors comprise patient education, treatment strategies, social influences and support. As knowledge gives the patient a better understanding for the treatment it provokes compliance. The social environment of the TB-infected patient demands increased knowledge in order to reduce stigma. Several studies show that the DOTS strategy is important for increasing compliance in anti-tuberculosis treatment. The literature study results in a proposal for the nursing program to focus more on compliance in taking medication. The nursing program’s attendants need to gain knowledge about prudent antibiotic treatment that leads to a compliance concern.</p>

Les propriétés structurales et de luminescence de couches minces de TiO2 et Y2O3 dopées terres rares (thulium, terbium et ytterbium) ont été étudiées en vue de les intégrer dans une cellule photovoltaïque comme couche de conversion spectrale du proche UV vers l'infrarouge afin d'en améliorer l'efficacité. Ces couches minces ont été synthétisées par dépôt chimique en phase vapeur à pression atmosphérique à l'aide de précurseurs organo-métalliques et assisté par aérosol (aerosol assisted MOCVD). Les couches minces sont partiellement cristallisées dès la synthèse (400°C pour le TiO2 en phase anatase, 540°C pour Y2O3 en phase cubique). Après traitement thermique la cristallisation est largement améliorée et la luminescence des ions dopant terres rares est obtenue dans les deux matrices oxydes. Le thulium émet dans une large bande située vers 800 nm et l'ytterbium vers 980 nm. Le terbium quand à lui émet dans une gamme située principalement dans le visible. Les spectres d'excitation ont montré que l'absorption des photons se fait via la matrice. En matrice TiO2 une efficacité de transfert d'énergie du Tm3+ vers l'Yb3+ de l'ordre de 20 % a été déterminée pour des teneurs de 0,8 % des deux dopants, ce qui correspond à la limite d'auto-extinction. Le rendement global mesuré est faible, nous avons montré que les causes probables de cette faible valeur sont le manque d'absorption des couches minces pour obtenir l'excitation de l'ion sensibilisateur ainsi que des processus de luminescence et de down conversion pas assez efficaces.

Mucosal associated invariant T (MAIT) cells are a population of innate-like lymphocytes, with an emerging role in tuberculosis (TB). They are characterised by the expression of high levels of CD161 and IL-18Rα, possession of a Vα7.2⁺ T cell receptor (TCR), and restriction by the MHC class I-related protein (MR1). MAIT cells can be activated by MR1 presenting microbe-derived riboflavin metabolites; or, by the cytokines IL-12 and IL-18 in a TCR-independent fashion. How human MAIT cells integrate these signals for their activation in response to Mtb is unclear. Lymphatic TB (LNTB) is a common extra-pulmonary manifestation of TB; however, little is known about the status of MAIT cells in LNTB - or in other granulomatous diseases, such as sarcoidosis. In this study, an in vitro approach was used to probe MAIT cell activation by Mtb, and the roles of IL-12/-18, the TCR, cell-cell contact and the immunological synapse (IS). Following TCR ligation, TNFα expression was rapid and transient, and was enhanced following sustained IL-12/-18 exposure. IFNγ expression occurred following sustained exposure to ng/ml concentrations of IL-12/-18; however, alongside TCR stimulation, pg/ml concentrations were sufficient. Using an artificial bilayer system, CD161 was excluded from the central regions of the MAIT cell IS, whilst the distribution of IL-18Rα remained unaffected. In response to Mtb and BCG, MR1 was necessary for rapid activation and TNFα expression, IL-12/-18 were necessary for robust and sustained IFNy expression, whilst an anti-Mtb effect was indicated in an intracellular infection model. Assessment of patients with TB or sarcoid lymphadenopathy revealed a depletion of MAIT cells in the blood in sarcoidosis, but not LNTB. In both groups, MAIT cells could be detected within a proportion of sampled lymph nodes. Overall, these findings indicate the importance of inflammatory cytokine signals in the induction of high-intensity and sustained MAIT cell effector function, including in response to Mtb. The observation of a numerical deficiency of MAIT cells in sarcoidosis requires further investigation.

Submitted by Fábio Henrique de Azevedo (fhazvdo@yahoo.com.br) on 2018-10-09T11:47:48Z No. of bitstreams: 1 Relatório técnico-científico.pdf: 7773319 bytes, checksum: a4494c93c456073f98183f0e5cc7d4ba (MD5) / Rejected by Lucilene Cordeiro da Silva Messias null (lubiblio@bauru.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: 1 - Inserir no corpo do texto a ata de defesa, pois é um ítem obrigatório Agradecemos a compreensão on 2018-10-09T11:59:07Z (GMT) / Submitted by Fábio Henrique de Azevedo (fhazvdo@yahoo.com.br) on 2018-10-09T12:34:34Z No. of bitstreams: 1 Relatório técnico-científico (com ata de defesa e parecer circunstanciado).pdf: 9097240 bytes, checksum: b71a5582e2b7e262dc5c6bca51828641 (MD5) / Rejected by Lucilene Cordeiro da Silva Messias null (lubiblio@bauru.unesp.br), reason: Solicitamos que realize uma nova submissão seguindo as orientações abaixo: 1 - A ficha catalográfica deve ser inserida logo após a folha de rosto 2 - A ata de defesa deve ser inserida logo após a ficha catalográfica. Agradecemos a compreensão on 2018-10-09T13:28:26Z (GMT) / Submitted by Fábio Henrique de Azevedo (fhazvdo@yahoo.com.br) on 2018-10-09T14:43:08Z No. of bitstreams: 1 Relatório técnico-científico (com ficha após folha e ata após ficha).pdf: 8492090 bytes, checksum: df7b797887e36395132db5ba2202de80 (MD5) / Approved for entry into archive by Lucilene Cordeiro da Silva Messias null (lubiblio@bauru.unesp.br) on 2018-10-09T17:19:37Z (GMT) No. of bitstreams: 1 azevedo_fh_me_bauru.pdf: 8492090 bytes, checksum: df7b797887e36395132db5ba2202de80 (MD5) / Made available in DSpace on 2018-10-09T17:19:37Z (GMT). No. of bitstreams: 1 azevedo_fh_me_bauru.pdf: 8492090 bytes, checksum: df7b797887e36395132db5ba2202de80 (MD5) Previous issue date: 2018-03-28 / No Brasil a televisão (TV) de sinal aberto, apesar da sua grande abrangência, vem perdendo espaço para a televisão a cabo e para a internet com conteúdo via fluxo de mídia (streaming). Apesar dos atuais aparelhos de TV serem hoje denominados televisores inteligentes (SmartTV) eles são, na realidade, uma combinação de TV com internet, dependendo de conexão à rede de banda larga e aplicativos de redes sociais para oferecer interatividade na programação de TV aberta. Essa necessidade de outro dispositivo (smartphone, tablet etc.) faz com que as pessoas percam o interesse e deixem de assistir à televisão, pois se distraem com a variedade de funções que tais equipamentos possuem (e-mail, sites de notícias, dentre outros). Os fabricantes de televisores estão aprimorando a qualidade de imagens e sons dos atuais aparelhos de TV e vendem a sensação de se estar dentro dos programas veiculados. Porém, falta ainda um último passo nessa percepção que é o da interação entre os dois lados da tela. O objetivo desta pesquisa foi propor uma solução ao telespectador, trazendo de volta a simplicidade de assistir à televisão, mas com a capacidade de interação já oferecida em alguns programas televisivos através do uso do controle remoto. Portanto, nesta pesquisa técnico-científica propôs-se um novo método para a interatividade televisiva, utilizando a interatividade do canal de retorno ao Sistema Brasileiro de Televisão Digital: com o uso de um cartão inteligente de telefones celulares de tecnologia GSM (cartão SIM) e dos sinais de telecomunicação utilizados no país, buscou-se oferecer uma alternativa para solucionar o problema de interatividade do canal de retorno sem o uso da internet e suas mídias sociais. Como resultado prático deste projeto, é relatado neste relatório técnico-científico o Pedido Nacional de Invenção, o Modelo de Utilidade, o Certificado de Adição de Invenção e entrada na fase nacional do PCT do Instituto Nacional da Propriedade Industrial – INPI para o registro de patente do cartão inteligente. / Despite its massive scope, the market share for analogue TV in Brazil has been decreasing; cable TV and streaming are taking over. Although TV sets are presently referred to as "intelligent devices" (Smart TV), in fact they blend TV programming and internet, thus needing connection with broadband network and social network applications in order to offer interactivity for analogue TV programming. The need for additional equipment (such as a smartphone or a tablet computer) induces viewers not to watch television; for they get distracted by the diversity of options such devices present (email, news websites, etc.). TV set manufacturers are currently improving the quality of its image and sound, making one feel they are within the show; however there is one step missing in this perception: the intercommunication between the two sides of the screen. This study proposes solutions to the viewer, retrieving that feeling of simplicity inherent to watching TV but with the existing interaction offered in some programs by means of the remote control. Therefore, this technical and scientific study introduces a new method of TV interactivity, employing the return channel interactivity to the Brazilian Digital Television System with the SIM card (intelligent card for GSMtechnology cell phones) and the telecommunication signals used in Brazil. This feature may promote a problem-solving alternative concerning the return channel interactivity, without the internet and its social media, however. As a practical result, the National Patent Application, the Utility Model, the Certificate of Addition to Invention and the entry in the national phase of the PCT at the National Institute of Industrial Property (INPI) are here reported, so that the patent to the intelligent card can be registered.

O estudo analisou a sustentabilidade da estratégia DOTS na visão de coordenadores de Programa de Controle Tuberculose (PCT) em sete municípios do interior do estado de São Paulo, prioritários para o controle da Tuberculose (TB). O quadro teórico está sustentado nas dimensões operacional, organizacional e política da gerência e sua articulação no contexto atual das políticas e serviços de saúde. A partir de uma abordagem quantitativa, de estudo epidemiológico descritivo por meio de levantamento de fontes secundárias, foram analisados os indicadores epidemiológicos do PCT: cura, abandono e óbito de casos novos com baciloscopia de escarro positiva, cobertura de Tratamento Supervisionado (DOT/TS) e de detecção de casos. Também optou-se pela abordagem qualitativa, análise de conteúdo-modalidade temática que utilizou como fonte a entrevista semi-estruturada com coordenadores de PCT. A Unidade Temática central foi a sustentabilidade da estratégia DOTS como um desafio para coordenadores de PCT, contendo dois sub-temas: A organização da estratégia DOTS diante da necessidade de captar/otimizar recursos e definir estratégias e A operacionalização das ações de controle da TB: raciocínio estratégico e negociação como ferramentas gerenciais. Os resultados quantitativos mostraram um coeficiente angular positivo para cura, mas a maioria não atingiu a meta de 85%; declínio no percentual de abandono, ainda aquém do esperado. A cobertura de DOT/TS apresentou aumento em todos os municípios, contudo, apenas um atingiu 95%. Nenhum município atingiu a meta de 70% de detecção de casos. Os temas que emergiram neste estudo apontaram nós críticos na captação e manutenção de incentivos financeiros; recursos humanos (RH) insuficientes e despreparados; rotatividade de pessoal; desconhecimento do destino da verba da TB e falta de autonomia para gerenciar os recursos; dificuldades de comunicação e integração com gestores; falta de priorização da doença na agenda política; priorização de agravos com repercussão política e necessidade de parcerias. Sobre a operacionalização do DOTS, o estudo apontou a cooperação de pessoas de fora do serviço como ferramenta gerencial estratégica, quando estimula a coresponsabilização da família e da comunidade como cuidadores ou multiplicadores. A avaliação, pautada em indicadores epidemiológicos, é utilizada prioritariamente para alcançar recursos, ao invés de subsidiar o planejamento. A gerência do PCT parece ser uma gerência burocrática, fundamentada no planejamento normativo. Acredita-se que a efetividade das ações gerenciais para sustentar a estratégia DOTS dependa de atores com conhecimento técnico, habilidades políticas e organizacionais, além de raciocínio estratégico para estimular e envolver todos os atores que lidam com a TB. Habilidades estas que, dificilmente são adquiridas na formação profissional. Conclui-se que os coordenadores trabalham em meio a pressões de cima e de baixo, ocupando dupla posição de transmissão, no plano hierárquico e das relações. Neste sentido, a sustentabilidade da estratégia DOTS representa desafios importantes para estes atores que utilizam poucos instrumentos gerenciais, têm pouca autonomia no processo decisório, lidam com recursos escassos e, muitas vezes, sem preparo para esta função, reforçando a necessidade de investimento na formação e capacitação contínua tanto para estes atores como para aqueles que lidam com a TB / This study analyzed the sustainability of the DOTS (Directly Observed Treatment Strategy). It shows the point of view of the TCP (Tubercolosis Control Program) coordinators of seven priority municipalities in the Sao Paulo State. The theorical framework is based on operational, organizational and political levels of the management and on its articulation in the current context of health policies and services. We carried out an epidemiological-descriptive study, using secondary sources, and through a quantitative approach. The following epidemiological TCP indicators were analyzed: cure, abandonment and death of new cases with positive sputum bacilloscopy, Supervised Treatment (DOTS/ST) and case detection coverage. We also chose to apply a qualitative approach, through a semi-structured interview with TCP Coordinators, and with the application of content analysis in the thematic modality. The main thematic unity is the sustainability of the DOTS strategy as a challenge to the TBP coordinators. It contains two sub-themes: The organization of the DOTS strategy faced with the need for resource captation/optimization and for clearly outlined strategies, and The operationalization of TB control actions: strategic thinking and the negociation as key management skills. Quantititive results show a positive angular coefficient for cure. Nonetheless, the majority did not achieve the 85% goal and the decline in the abandonment rate is still lower than expected. The ST coverage rose in all municipalities. However, only one municipality achieved coverage of 95%. None of the municipalities achieved the goal of 70% case detection rate. The themes analyzed in this study pointed to critical knots in the collection and maintenance of financial incentives; insuficient and unprepared Human Resources (HR); staff turnover; lack of knowledge concerning the destination of the TB funds, as well as lack of autonomy to manage resources; difficulties in the communication and in the integration with other managers; failure in making the disease a priority on the political agenda; priorization of aggravations with political repercussion and the need for partnerships. Concerning the DOTS operationalization, the study pointed to the cooperation of people outside the job as an important strategic management tool. It encourages family and community to take co-responsibility as caretakers and multipliers. The evaluation, which is based on epidemiological indicators, is especially used to achieve resources, instead of subsidizing the planning process. TCP management seems to be exceedingly bureaucratic and based on normative planning. We believe that the effectiveness of management actions to support the DOTS strategy needs characters with technical knowledge, political and organizational skills and strategic thinking. These skilss are important in order to encourage and get involved all those who deal with TB. These skills are hardly achieved in the professional training. We conclude that the coordinators work under pressure from the top and from the bottom of the hierarchy, and occupy a double transmission position: in the hierarchic level and in the relationship level. Thus, the sustainability of the DOTS strategy represents an important challenge for these characters, who use few management tools, have little authonomy in the decisionmaking process, have to work with scarce resources and are usually unprepared for the position they occupy. These findings highlight the need for more investments in continuing education and capacitation not only for coordinators but also for all those who have to deal with TB

Made available in DSpace on 2015-04-22T22:00:47Z (GMT). No. of bitstreams: 1 jose.pdf: 2255469 bytes, checksum: cebe37770c4719e5ebf2b60e4ae0d2a6 (MD5) Previous issue date: 2013-06-07 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Currently, the majority of multicarrier transmission systems are based on the Fourier transform, which is used as frequency multiplexing technique. The main advantages of this approach include multipath immunity and low computational complexity, due to the use of a family of fast algorithms, known as Fast Fourier Transform (FFT). However, when used to provide a robust transmission, this technique presents some disadvantages, like the need for a cyclic prefix, which demands part of the useful datarate. In this work, a study for verifying the possibility of replacing the FFT, by the wavelet transform, was carried out, which has the potential to raise some advantages, such as the removal of the cyclic prefix and a simpler synchronization procedure. A computational model for the transmission layer of the Integrated Services Digital Broadcasting Terrestrial, Brazilian version (ISDB-Tb) was created, aiming to provide a direct comparison between two versions: the traditional one, which is based on FFT, and a new proposal, which is based on wavelets. Such an evaluation was performed through the relation between error bit rate and signal-to-noise ratio, in additive white gaussian noise, Rayleigh and Rician fading and also in frequency-selective Rayleigh fading channels. Similar comparisons were also performed for the ETSI TS 101 475 (HIPERLAN-2) and Digital Video Broadcasting Terrestrial (DVB-T) systems. The simulation results show that the wavelet-based systems present a similar performance, when compared with the FFT-based ones, for the chosen channel models, and without employing a cyclic prefix, which allows a more efficiente spectrum use. / Atualmente, uma grande parte dos sistemas de transmissão multiportadoras é baseada na transformada de Fourier, como técnica de multiplexação em frequência. Dentre as suas principais vantagens, encontram-se a imunidade a multipercursos e a baixa complexidade computacional, através de algoritmos rápidos conhecidos como Fast Fourier Transform (FFT). Esta técnica, entretanto, para proporcionar uma transmissão robusta, apresenta a desvantagem de exigir prefixo cíclico, o que resulta no consumo de uma fatia do espectro útil. Neste trabalho, um estudo para se verificar a viabilidade de substituição da FFT pela transformada wavelet foi realizado, o que promete trazer algumas vantagens, tais como a não exigência de prefixo cíclico e uma sincronização mais simples. Um modelo computacional para a camada de transmissão do Integrated Services Digital Broadcasting - Terrestrial, Brazilian version (ISDB-Tb) foi criado, com o objetivo de proporcionar uma comparação entre duas versões: a atual, baseada em FFT, e uma nova proposta, baseada em wavelets. Tal avaliação foi realizada em termos das curvas de taxa de erro de bit versus relação sinal ruído, em canais com adição de ruído gaussiano branco, com desvanecimento plano de Rayleigh e Rice e também com desvanecimento seletivo em frequência de Rayleigh. Comparações similares também foram realizadas para os sistemas ETSI TS 101 475 (HIPERLAN-2) e Digital Video Broadcasting Terrestrial (DVB-T). Os resultados obtidos mostram que os sistemas baseados em wavelets apresentam desempenhos similares aos dos baseados em FFT, para os modelos de canal simulados, com a vantagem adicional de não utilizarem prefixo cíclico, o que promove um uso mais eficiente do espectro.

Submitted by Geyciane Santos (geyciane_thamires@hotmail.com) on 2015-11-23T21:08:30Z No. of bitstreams: 1 Dissertação - Cláudio Henrique Albuquerque Rodrigues.pdf: 3025271 bytes, checksum: 33bddf32584a136783577f65549474ff (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-11-27T20:36:37Z (GMT) No. of bitstreams: 1 Dissertação - Cláudio Henrique Albuquerque Rodrigues.pdf: 3025271 bytes, checksum: 33bddf32584a136783577f65549474ff (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2015-11-27T20:43:17Z (GMT) No. of bitstreams: 1 Dissertação - Cláudio Henrique Albuquerque Rodrigues.pdf: 3025271 bytes, checksum: 33bddf32584a136783577f65549474ff (MD5) / Made available in DSpace on 2015-11-27T20:43:17Z (GMT). No. of bitstreams: 1 Dissertação - Cláudio Henrique Albuquerque Rodrigues.pdf: 3025271 bytes, checksum: 33bddf32584a136783577f65549474ff (MD5) Previous issue date: 2015-09-11 / Não informada / The Second Screen is a technology created to offer the viewer the ability to interact with the content through mobile devices using applications created for this purpose. It is a platform that is already being used in cable television and satellite television, on some channels available in this type of business, pay TV. It is also used in available content through Bluray media and movie theaters. Among the new applications and services of the companies in the field of electronic games, there are applications that allow players to transform smartphones and tablets on a second screen to enhance the overall experience of a player compared to controls and challenges of a game. The purpose of this work is to create an interactive application prototype for Brazilian System of Digital Television - SBTVD in the ISDB-TB standard (Integrated Services Digital Broadcasting Terrestrial Brazil), that provides the second screen technology in mobile viewers. For this, it will be carried out changes in the signal generated by content providers to inclusion of the second screen option and creating the necessary conditions for detection, synchronization and use of this technology by the end user at his residence. To check the operation of the proposal, it was set up a test environment with the necessary components to simulate the complete system. / A segunda tela, ou em inglês, second screen é uma tecnologia criada para oferecer ao telespectador a possibilidade de interagir com o conteúdo por meio de dispositivos móveis, utilizando aplicativos criados para este fim. Trata-se de uma plataforma que já está sendo utilizada na TV a cabo e na TV via satélite, em alguns canais disponibilizados nesta modalidade de negócio, TV por assinatura. É utilizada também em conteúdos disponibilizados através de mídia BluRay e nas salas de cinema. Entre as novas aplicações e serviços das empresas do ramo de jogos eletrônicos, já existem aplicações que permitem aos jogadores transformarem smartphones e tablets em uma segunda tela para melhorar a experiência geral de um jogador em relação aos controles e desafios de um jogo. A proposta deste trabalho é criar um protótipo de aplicação interativa para o Sistema Brasileiro de Televisão Digital - SBTVD no padrão ISDB-TB (Integrated Services Digital Broadcasting Terrestrial Brazil), que permita disponibilizar a tecnologia de segunda tela em dispositivos móveis aos telespectadores. Para isto, serão realizadas alterações no sinal gerado pelos provedores de conteúdo para inclusão da opção de segunda tela e a criação das condições necessárias para detecção, sincronização e utilização desta tecnologia pelo usuário final em sua residência. Para verificar o funcionamento da proposta, foi criado um ambiente de testes com os componentes necessários para simular o sistema completo.

Made available in DSpace on 2014-07-29T15:30:37Z (GMT). No. of bitstreams: 1 Dissertacao_sueli.pdf: 1117407 bytes, checksum: d50c0b1dad4e594bc8cd5d3880aadcab (MD5) Previous issue date: 2010-03-11 / Multidrug-resistant tuberculosis is a challenge worldwide. Rapid diagnosis by molecular techniques can provide a more aggressive and appropriate initial therapy. This study aimed to analyze the molecular basis of resistance to isoniazid (INH) and rifampin (R) of Mycobacterium tuberculosis strains isolated from cases of human tuberculosis in Goiás and to genetically determine the causes of the observed resistances. Of the 4.607 cultures for mycobacteria processed in the period of September of 2005 and December of 2007, 24 isolates from 16 patients resistant to at least H and/or R were analyzed. We compared the results obtained by phenotypic tests with mutations in key genes responsible for the development of resistance to these drugs, the rpoB gene for isolates resistant to R and katG gene for strains resistant to H. Seventy one percent of the isolates were resistant to H, and the mutations involved with resistance observed in the katG gene were in codon 315 (41%). The most frequent mutations observed in the rpoB gene of the R resistant isolates (71%) were in codons 456 (76.5%) and 451 (17.6%). Our findings are similar to those reported in the literature. We conclude that the percentage of agreement between genotypic and phenotypic tests was 41% for H and 94% for R considering the number of isolates and 40% and 91%, respectively considering the number of patients. / A tuberculose multidroga resistente representa um desafio em escala mundial. O diagnóstico rápido através de técnicas moleculares é capaz de proporcionar uma terapêutica inicial mais agressiva e adequada. Este trabalho teve como objetivo analisar as bases moleculares da resistência à isoniazida (H) e rifampicina (R) de cepas de Mycobacterium tuberculosis isoladas de casos de tuberculose em Goiás e determinar geneticamente as causas destas resistências. Do total de 4.607 culturas para micobactérias realizadas no período de setembro 2005 a dezembro de 2007, foram analisados 24 isolados de 16 pacientes resistentes a H e/ou R. Os resultados obtidos dos testes fenotípicos de sensibilidade aos antimicrobianos foram comparados às mutações observadas nos principais genes responsáveis pelo desenvolvimento de resistência a estas drogas, gene rpoB para isolados resistentes à R e gene katG para os isolados resistentes à H. Dentre os 24 isolados, 71% eram fenotípicamente resistentes a H e as únicas mutações envolvidas com resistência foram observadas no códon 315 (41%). Dos isolados resistentes a R (71%), foram observadas mutações nos códons 456 (76,5%), 451 (17,6%) e 447 (5,9%). Nossos achados estão em concordância com as principais mutações observadas nos isolados resistentes a R e/ou H descritos na literatura. O percentual de concordância entre os testes fenotípicos e genotípicos foi de 41% para H e 94% para R considerando o número de isolados e de 40% e 91% respectivamente considerando-se o número de pacientes.

WCDMA is an interference limited multiple access technique .It is widely used in the 3rd generation mobile networks like UMTS. When a new call arrives in the system to get admission, it checks whether the call is admitted or not based on some parameters like signal to interference ratio (SIR), transmission power of the Node B and the air interface load .If the call is accepted this will increase some interference to the ongoing calls. This new interference would degrade the ongoing calls and this will also add some extra load which may also lead to the exceeding capacity. So that the system has to decide this admission policy in a systematic way that all the users should maintain their communication with guaranteed quality of service. This decision making algorithm belongs to the radio resource management functionalities of the Radio Network Controller (RNC) in a WCDMA based UMTS network. This thesis paper focuses on the mathematical representation of the call admission control in an interference based environment. There is also a comparative study with different methods.

Tuberculosis (TB) is a potentially fatal contagious disease that can affect almost any part of the body but is mainly an infection of the lungs. It is caused by micro-organisms of the Mycobacterium tuberculosis complex. It is the second greatest killer worldwide due to a single infectious agent, after the Human Immunodeficiency Virus (HIV). Without treatment, fatality is 50% in immune competent persons. TB remains the leading cause of death among HIV positive persons, causing one fifth of the deaths. The World Health Organization estimates that one third of the world population is infected by this micro-organism but only 5 to 10% develop TB disease. Nevertheless, this enormous reservoir leads to around 1.4 millions deaths annually. Standard curative treatment lasts at least 6 months and includes 4 different drugs. Toxicity of the drugs leading to (severe) adverse events and the long duration of the daily administration challenges patient’s compliance. Subinhibitory concentration of the drugs (due to poor adherence) can induce resistance of the mycobacteria to the provided drugs. Unlike most bacteria where resistance is acquired by plasmids, drug resistance of mycobacteria is obtained by genomic mutations. “Multi drug-resistant tuberculosis (MDR-TB)” is strictly defined as TB resistant to specifically isoniazid and rifampicin, the two main first line drugs. “Extensively drug resistance (XDR)” is defined as MDR-TB with additional resistance to any of the fluoroquinolones (such as ofloxacin or moxifloxacin) and to at least one of three injectable second-line drugs (amikacin, capreomycin or kanamycin). The increase of MDR-TB represents an enormous challenge to Public Health globally. This research examined different aspects of tuberculosis resistance performed in the Belgian National Reference Center, a clinical laboratory setting. <p><p>First of all, a profound analysis of the MDR-TB situation in Belgium was conducted. It is the first retrospective population-based survey of MDR-TB in Belgium, covering a 15-year period (1994-2008). It comprises 174 patients representing more than 80% of the culture positive MDR-TB patients reported to the Belgian register, thus this study is considered of national relevance. It includes bacteriological and molecular data on the isolates as well as clinical aspects of the patients and treatment results. Considering only the patient’s first MDR-TB isolate, an increase over time was observed in the number of isolates resistant to a second-line drug as well as the total number of drugs each isolate was resistant to. XDR-TB was detected since 2002 and panresistant TB (resistant to every available antituberculosis drug) since 2009. Overall, a successful treatment outcome was obtained for 67.8% of the MDR-TB cases. Drug susceptibility testing (DST) of Mycobacterium tuberculosis to first line drugs (isoniazid, rifampicin, ethambutol and pyrazinamide) in liquid culture medium has a turn around time of at least two weeks, after identification of the positive culture (obtained after 2 to 4 weeks) from the patient’s clinical isolate. In order to provide the clinician with valuable information about the isolated mycobacteria leading to patient adapted therapy before bacteriological DST results are available, resistance is predicted by detection of mutations in certain genes of the mycobacteria. It is common practice for rifampicin (rpoB gene) and isoniazid (katG gene and/or inhA promoter region). In this MDR-TB collection, rifampicin resistant related mutations were found in 97.1% (168/173) of the clinical isolates and isoniazid resistant related mutations in 94.1% (160/170). The pncA, embB and gyrA genes have been sequenced to identify possible mutations because of their possible involvement with resistance to pyrazinamide, ethambutol and the fluoroquinolones respectively. However, little is known about the resistance prediction value of the mutations in these genes.<p>The study is also the first study on the molecular epidemiology of MDR-TB in the country. DNA fingerprinting showed a large diversity of strains (67% of the patients were infected by a strain with a unique pattern) and further epidemiological examination revealed limited local transmission of MDR-TB in Belgium.<p><p>The second part investigated the pncA gene and its association with pyrazinamide resistance in MDR-TB isolates from Belgium and in vitro cultured spontaneous mutants. The genetic analysis showed that 98.3% (59/60) of the Belgian clinical MDR pyrazinamide resistant (PZAR) isolates present a mutation in the pncA gene. We found 1.7% (1/60) of the PZAR MDR-isolates encoding wild type pncA and flank. A total (PZAR and PZAS) of 41 different amino acid changes, 3 protein truncations and 5 frameshifts were observed including eight novel mutations: 8Asp>Ala, 13Phe>Leu, 64Tyr>Ser, 107Glu>stop, 143Ala>Pro, 172Leu>Arg and frameshifts starting in codon 55 and 82. Analysis of all observed mutations (i.e. in clinical isolates as well as spontaneous mutants) revealed that they are not always associated with drug resistance and that they are not scattered randomly throughout the gene, but occur rather at preferential sites such as in codons with amino acids associated with either iron or substrate binding and catalytic active sites. The frequency of in vitro mutagenesis to pyrazinamide at pH 6.0 was determined and found to be relatively high at 10-5 CFU/ml.<p><p>Finally, the in vitro activity of tobramycin and clarithromycin (with unclear efficacy against M. tuberculosis) was evaluated on 25 M. tuberculosis clinical isolates with various resistance profiles. The effect of the drugs administered together was examined for possible synergistic effect. The median minimum inhibitory concentration (MIC) of 8 µg/ml obtained for both drugs in this study is rather high but are beyond the concentrations obtained in lung tissues. This suggests that both drugs should be investigated further as potential adjuncts to the treatment of resistant TB when other alternatives have failed; in particularly through new drug delivery systems such as the Dry Power Inhaler which allows local drug deposition with high drug concentrations in the lungs but low toxicity due to limited systemic absorption. In addition, for 36% of the tested isolates a decrease of the MIC of clarithromycin by a single or twofold dilution was observed in the presence of a subinhibitory concentration of tobramycin and no antagonistic effect was seen for the remaining isolates.<p><p>This research illustrates different (laboratory) aspects in the fight against drug resistant TB, all using the Belgian TB collection: characterisation of the Belgian MDR-TB situation on bacteriological, molecular and epidemiological level; profound analysis of genomic mutations and their possible association with drug resistance; and investigation of synergistic activity of drugs with low efficacy against M. tuberculosis.<p> / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished