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Orientadores: Edi Lúcia Sartorato, Arthur Menino Castilho / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-20T16:24:36Z (GMT). No. of bitstreams: 1 Ramos_PriscilaZonzini_M.pdf: 3611007 bytes, checksum: 2be9b03e75155e4bfaecc2357fec2c70 (MD5) Previous issue date: 2012 / Resumo: A surdez é considerada a doença sensorial mais prevalente em humanos, causada por uma variedade de fatores ambientais e genéticos. No Brasil, não há dados oficiais referentes à prevalência e à etiologia das deficiências auditivas, mas sabe-se que os fatores ambientais ainda superam os de origem genética. No diagnóstico etiológico da surdez, a realização concomitante de exames laboratoriais, de imagem e genéticos, embora amplie a chance diagnóstica, onera o Sistema de Saúde, devido ao alto custo. Deste modo, o objetivo do presente estudo foi avaliar a eficácia dos exames de imagem e genéticos e seu impacto em Saúde Pública, bem como estabelecer um protocolo diagnóstico, visando maior eficiência e redução de custos na determinação da etiologia das perdas auditivas. Foi realizada a análise de 100 indivíduos com perda auditiva neurossensorial, atendidos no Ambulatório de Otorrinolaringologia do Hospital das Clínicas da UNICAMP, no período de 2002 a 2010, e que foram submetidos ao implante coclear. Uma investigação detalhada foi realizada nos pacientes, incluindo exames de imagem, genéticos e laboratoriais (em casos específicos). Após a realização dos exames específicos, o número de casos com a etiologia não esclarecida foi reduzido de 72 para 42, representando redução de 42%. Alterações radiológicas foram identificadas em 29 pacientes, enquanto alterações moleculares foram encontradas em 31 indivíduos, incluindo a c.35delG, p.V27I, p.M34T, p.V37I, p.E47X, p.L90P, p.V95M, p.K168R, p.W172X no gene GJB2, a del(GJB6-D13S1830) no gene GJB6 e a m.1555A>G no gene mitocondrial MTRNR1. Os exames de imagem e genéticos contribuíram, respectivamente, para o diagnóstico etiológico de 20% e 19% dos casos analisados. A etiologia não foi esclarecida em 42% dos pacientes, em 25% foi de origem ambiental, 19% genética, e em 14% dos casos decorrente de malformações ou outros problemas na orelha interna. Pôde-se concluir que tanto os exames de imagem quanto os genéticos foram importantes para a identificação da etiologia das perdas auditivas, no entanto, os testes moleculares contribuíram principalmente para o diagnóstico dos pacientes com surdez congênita, enquanto os exames radiológicos tiveram maior contribuição para os casos com perda progressiva ou abrupta. A alta prevalência de mutações no gene GJB2 foi confirmada, especialmente da mutação c.35delG, nos casos de perda auditiva neurossensorial severa a profunda bilateral. A pesquisa molecular teve importante contribuição no diagnóstico etiológico da surdez, além de possibilitar o aconselhamento genético e sugerir melhor prognóstico para o implante coclear, como observado em estudos prévios. O TaqMan® OpenArray® Genotyping é uma técnica promissora para o diagnóstico molecular da perda auditiva, pois permite a análise de diversas mutações em vários pacientes de uma só vez, o que implica em um diagnóstico mais rápido a um custo mais baixo. O protocolo sequencial permite a otimização do diagnóstico etiológico e redução dos custos, ao contrário da realização concomitante de exames de imagem, laboratoriais e genéticos. Por fim, mesmo com uma investigação detalhada, a etiologia desconhecida continuou prevalecendo, o que aponta para a necessidade de estudos moleculares mais aprofundados, para que a real causa possa ser esclarecida / Abstract: Deafness is considered the most prevalent sensory disorder in humans, caused by a variety of environmental and genetics factors. In Brazil, there are no official data regarding the prevalence and etiology of hearing impairment, but it is known that environmental factors are among the major causes. Although a simultaneous testing approach, including clinical exams, audiological, laboratorial, imaging and genetic expands the etiological diagnosis, overloads the healthcare system due to high costs. Thus, the goal of the present study is to evaluate the effectiveness of imaging and genetics tests and their impact on public health, aiming to increase efficiency and reduce costs of the etiological diagnosis of hearing loss. It was conducted an analysis of 100 patients with sensorineural hearing loss, from Department of Otorhinolaryngology of the State University of Campinas (UNICAMP), submitted to cochlear implantation between 2002 and 2010. A detailed investigation was performed in patients, including imaging and genetics analysis. After specific tests, the number of individuals with unknown cause was reduced from 72 to 42 (42% of reduction). Radiologic abnormalities were identified in 29 of the patients, while molecular alterations were found in 31 individuals, including c.35delG, p.V27I, p.M34T, p.V37I, p.E47X, p.L90P, p.V95M, p.K168R, p.W172X in the GJB2 gene, del(GJB6-D13S1830) in the GJB6 gene and m.1555A>G in the MTRNR1 mitochondrial gene. Genetic and imaging results contributed to the etiological diagnosis of 19% and 20% of the cases, respectively. The etiology remained unknown in 42% of the patients, was due to environmental factors in 25%, genetics in 19% and inner ear malformations or other defects in 14% of the cases. It was concluded that both imaging and genetic analysis were important to identify the etiology of hearing loss, however, molecular tests contributed mainly for diagnosis of patients with congenital deafness, while radiologic exams had greater contribution for diagnosis of cases with progressive or sudden hearing loss. The high prevalence of mutations in the GJB2 gene was confirmed, especially the c.35delG mutation, in cases of sensorineural severe to profound bilateral hearing loss. The molecular research had an important contribution to the etiology of deafness, besides providing genetic counseling and a better prognosis for cochlear implantation, as suggested by previous studies. The TaqMan® OpenArray® Genotyping is a promising technique for molecular diagnostic of hearing loss, because it allows the analisys of many mutations in several patients at once, which implies in a faster diagnosis at a lower cost. The sequential protocol enables an optimization of the etiological diagnosis and cost reduction, as opposed to simultaneously holding imaging, laboratory and genetic tests. Finally, even with a careful investigation, the unknown etiology prevailed as main cause which points to the need of carrying out detailed genetic studies in those cases with idiopathic hearing loss in order to elucidate the diagnosis / Mestrado / Genetica Animal e Evolução / Mestre em Genética e Biologia Molecular

Le transport multicast est une solution efficace pour envoyer le même contenu à plusieurs récepteurs en même temps. Ce mode est principalement utilisé pour fournir des flux multimédia en temps réel. Cependant, le multicast classique de l’IEEE 802.11 n'utilise aucun mécanisme d’acquittement. Ainsi, l’échec de réception implique la perte définitive du paquet. Cela limite la fiabilité du transport multicast et impact la qualité des applications vidéo. Pour résoudre ce problème, 802.11v et 802.11aa sont définis récemment. Le premier amendement propose Direct Multicast Service (DMS). D'autre part, le 802.11aa introduit GroupCast with Retries (GCR). GCR définit deux nouvelles politiques de retransmission : Block Ack (BACK) et Unsolicited Retry (UR).Dans cette thèse, nous évaluons et comparons les performances de 802.11v/aa. Nos résultats montrent que tous les nouveaux protocoles multicast génèrent un overhead de transmission important. En outre, DMS a une scalabilité très limitée, et GCR-BACK n'est pas approprié pour des grands groupes multicast. D’autre part, nous montrons que DMS et GCR-BACK génèrent des latences de transmission importantes lorsque le nombre de récepteurs augmente. Par ailleurs, nous étudions les facteurs de pertes dans les réseaux sans fil. Nous montrons que l'indisponibilité du récepteur peut être la cause principale des pertes importantes et de leur nature en rafales. En particulier, nos résultats montrent que la surcharge du processeur peut provoquer un taux de perte de 100%, et que le pourcentage de livraison peut être limité à 35% lorsque la carte 802.11 est en mode d’économie d'énergie.Pour éviter les collisions et améliorer la fiabilité du transport multicast, nous définissons le mécanisme Busy Symbol (BS). Nos résultats montrent que BS évite les collisions et assure un taux de succès de transmission très important. Afin d'améliorer davantage la fiabilité du trafic multicast, nous définissons un nouveau protocole multicast, appelé Block Negative Acknowledgement (BNAK). Ce protocole opère comme suit. L’AP envoi un bloc de paquets suivi par un Block NAK Request (BNR). Le BNR permet aux membres de détecter les données manquantes et d’envoyer une demande de retransmission, c.à.d. un Block NAK Response (BNAK). Un BNAK est transmis en utilisant la procédure classique d’accès au canal afin d'éviter toute collision avec d'autres paquets. En plus, cette demande est acquittée. Sous l'hypothèse que 1) le récepteur est situé dans la zone de couverture du débit de transmission utilisé, 2) les collisions sont évitées et 3) le terminal a la bonne configuration, très peu de demandes de retransmission sont envoyées, et la bande passante est préservée. Nos résultats montrent que BNAK a une très grande scalabilité et génère des délais très limités. En outre, nous définissons un algorithme d'adaptation de débit pour BNAK. Nous montrons que le bon débit de transmission est sélectionné moyennant un overhead très réduit de moins de 1%. En plus, la conception de notre protocole supporte la diffusion scalable de lavvidéo. Cette caractéristique vise à résoudre la problématique de la fluctuation de la bande passante, et à prendre en considération l'hétérogénéité des récepteurs dans un réseau sans fil. / The multicast transport is an efficient solution to deliver the same content to many receivers at the same time. This mode is mainly used to deliver real-time video streams. However, the conventional multicast transmissions of IEEE 802.11 do not use any feedback policy. Therefore missing packets are definitely lost. This limits the reliability of the multicast transport and impacts the quality of the video applications. To resolve this issue, the IEEE 802.11v/aa amendments have been defined recently. The former proposes the Direct Multicast Service (DMS). On the other hand, 802.11aa introduces Groupcast with Retries (GCR) service. GCR defines two retry policies: Block Ack (BACK) and Unsolicited Retry (UR).In this thesis we evaluate and compare the performance of 802.11v/aa. Our simulation results show that all the defined policies incur an important overhead. Besides, DMS has a very limited scalability, and GCR-BACK is not appropriate for large multicast groups. We show that both DMS and GCR-BACK incur important transmission latencies when the number of the multicast receivers increases. Furthermore, we investigate the loss factors in wireless networks. We show that the device unavailability may be the principal cause of the important packet losses and their bursty nature. Particularly, our results show that the CPU overload may incur a loss rate of 100%, and that the delivery ratio may be limited to 35% when the device is in the power save mode.To avoid the collisions and to enhance the reliability of the multicast transmissions, we define the Busy Symbol (BS) mechanism. Our results show that BS prevents all the collisions and ensures a very high delivery ratio for the multicast packets. To further enhance the reliability of this traffic, we define the Block Negative Acknowledgement (BNAK) retry policy. Using our protocol, the AP transmits a block of multicast packets followed by a Block NAK Request (BNR). Upon reception of a BNR, a multicast member generates a Block NAK Response (BNAK) only if it missed some packets. A BNAK is transmitted after channel contention in order to avoid any eventual collision with other feedbacks, and is acknowledged. Under the assumption that 1) the receiver is located within the coverage area of the used data rate, 2) the collisions are avoided and 3) the terminal has the required configuration, few feedbacks are generated and the bandwidth is saved. Our results show that BNAK has a very high scalability and incurs very low delays. Furthermore, we define a rate adaptation scheme for BNAK. We show that the appropriate rate is selected on the expense of a very limited overhead of less than 1%. Besides, the conception of our protocol is defined to support the scalable video streaming. This capability intends to resolve the bandwidth fluctuation issue and to consider the device heterogeneity of the group members.