Orientador: Norma Sueli Pinheiro Módolo / Resumo: Justificativa: O magnésio potencializa o efeito dos bloqueadores neuromusculares, atenua a resposta hemodinâmica à intubação e reduz o consumo de anestésico no intraoperatório. A inibição da liberação de acetilcolina mediada pelo cálcio nos terminais pré-sinápticos das junções neuromusculares, a redução da sensibilidade pós-sináptica à acetilcolina e os efeitos diretos no potencial de membrana dos miócitos parecem ser responsáveis pela ação relaxante muscular do magnésio. Além da ação do magnésio na placa motora e nos miócitos, esse íon pode interferir na farmacocinética dos bloqueadores neuromusculares por alteração do fluxo sanguíneo provocado pela vasodilatação e consequentemente aumento do aporte de bloqueador neuromuscular na placa motora. O objetivo do presente estudo é avaliar o efeito do magnésio sobre a latência de três doses diferentes do rocurônio. Avaliou-se ainda, a ação sobre a resposta hemodinâmica à intubação traqueal, as condições de intubação traqueal e a relação da variação do índice de perfusão com a latência do rocurônio. Métodos: 180 pacientes foram distribuídos em seis grupos de acordo com a administração ou não de magnésio (60 mg.kg-1) e pela dose de rocurônio (0,3, 0,6 ou 1,2 mg.kg-1) utilizada na indução anestésica. Determinando desse modo os seguintes grupos: ROC0.3, ROC0.6, ROC1.2, ROC0.3MG, ROC0.6MG e ROC1.2MG. A latência do rocurônio foi aferida por meio da aceleromiografia ... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Submitted by CARLOS EDUARDO DAVID DE ALMEIDA null (cedalmeida@terra.com.br) on 2017-03-09T03:15:29Z No. of bitstreams: 1 Carlos Eduardo David de Almeida (Doutorado) após a defesa.pdf: 870499 bytes, checksum: 641d701ba65d5d16a6acd96d7d003702 (MD5) / Approved for entry into archive by LUIZA DE MENEZES ROMANETTO (luizamenezes@reitoria.unesp.br) on 2017-03-14T16:57:13Z (GMT) No. of bitstreams: 1 almeida_ced_dr_bot.pdf: 870499 bytes, checksum: 641d701ba65d5d16a6acd96d7d003702 (MD5) / Made available in DSpace on 2017-03-14T16:57:13Z (GMT). No. of bitstreams: 1 almeida_ced_dr_bot.pdf: 870499 bytes, checksum: 641d701ba65d5d16a6acd96d7d003702 (MD5) Previous issue date: 2017-02-17 / Justificativa: O magnésio potencializa o efeito dos bloqueadores neuromusculares, atenua a resposta hemodinâmica à intubação e reduz o consumo de anestésico no intraoperatório. A inibição da liberação de acetilcolina mediada pelo cálcio nos terminais pré-sinápticos das junções neuromusculares, a redução da sensibilidade pós-sináptica à acetilcolina e os efeitos diretos no potencial de membrana dos miócitos parecem ser responsáveis pela ação relaxante muscular do magnésio. Além da ação do magnésio na placa motora e nos miócitos, esse íon pode interferir na farmacocinética dos bloqueadores neuromusculares por alteração do fluxo sanguíneo provocado pela vasodilatação e consequentemente aumento do aporte de bloqueador neuromuscular na placa motora. O objetivo do presente estudo é avaliar o efeito do magnésio sobre a latência de três doses diferentes do rocurônio. Avaliou-se ainda, a ação sobre a resposta hemodinâmica à intubação traqueal, as condições de intubação traqueal e a relação da variação do índice de perfusão com a latência do rocurônio. Métodos: 180 pacientes foram distribuídos em seis grupos de acordo com a administração ou não de magnésio (60 mg.kg-1) e pela dose de rocurônio (0,3, 0,6 ou 1,2 mg.kg-1) utilizada na indução anestésica. Determinando desse modo os seguintes grupos: ROC0.3, ROC0.6, ROC1.2, ROC0.3MG, ROC0.6MG e ROC1.2MG. A latência do rocurônio foi aferida por meio da aceleromiografia do nervo ulnar (tempo entre o início da injeção do bloqueador neuromuscular até a redução da resposta motora a 5% da resposta inicial). A avaliação hemodinâmica foi feita imediatamente antes do início da infusão da solução estudada e um minuto após a intubação traqueal. As condições de intubação traqueal foram avaliadas pelo anestesiologista por meio das condições de laringoscopia, do posicionamento das cordas vocais e da resposta a inserção do tubo traqueal. Os níveis séricos de magnésio foram avaliados por coleta de 3 mL sangue do paciente antes e após a administração de magnésio. A aferição do índice de perfusão foi realizado com o objetivo de correlacionar a perfusão tecidual periférica com a alteração da latência do rocurônio. Resultados: Todos os pacientes tiveram condições excelentes ou boas de intubação traqueal. O MgSO4 reduziu a latência do rocurônio nas doses de 0,3 (de 88,5 s para 60 s) ou 0,6 mg.kg-1 (de 76 s para 44 s). Não ocorreu potencialização da dose de 1,2 mg.kg-1 de rocurônio. Os grupos que receberam MgSO4 apresentaram maiores variações do índice de perfusão comparativamente aos controles. Houve correlação entre redução da latência e aumento do índice de perfusão para as doses de 0,3 mg.kg-1 (p < 0,001 R= -0,50) e 0,6 mg.kg-1 (p < 0,001, R= -0,424) de rocurônio. Para a dose de 1,2 mg.kg-1 de rocurônio não existiu essa correlação. Entre os grupos que receberam MgSO4 e controles, não houve diferença estatística nos valores de pressão arterial, havendo um aumento discreto da frequência cardíaca nos pacientes do MgSO4. Conclusões: Neste estudo, o MgSO4 reduziu a latência do rocurônio nas doses de 0,3 e 0,6 mg.kg-1 . Não houve alteração da latência quando utilizado 1,2 mg.kg-1 de rocurônio. O aumento do índice de perfusão provocado pelo MgSO4 pode ter contribuído para a redução da latência. O sulfato de magnésio não alterou as condições de intubação entre os grupos que receberam a mesma dose de rocurônio. O sulfato de magnésio não promoveu alterações estatisticamente significante da pressão arterial, no entanto promoveu uma elevação da frequência cardíaca 1 min após a intubação traqueal. / Background: Magnesium potentiates the effect of neuromuscular blockers (NMBs), attenuates the hemodynamic response to intubation, and reduces intraoperative anesthetic consumption. Inhibition of calcium-mediated acetylcholine release at the presynaptic terminals of the neuromuscular junctions, the reduction of postsynaptic sensitivity to acetylcholine, and the direct effects on myocyte membrane potential appear to be responsible for the muscle relaxant action of magnesium. In addition to the action of magnesium on the motor plate and myocytes, this ion may interfere with the pharmacokinetics of NMB due to changes in the blood flow caused by vasodilation and consequently an increase in the NMB load in the motor plate. The aim of the present study is evaluate the effect of magnesium on the onset time of three different doses of rocuronium. We also evaluated action on the hemodynamic response to tracheal intubation, intubation conditions and the relationship between perfusion index variation and rocuronium onset time. Method: One hundred and eighty patients were randomised into six groups according to rocuronium dose received (0.3, 0.6, or 1.2 mg.kg-1) and the administration of saline or MgSO4 (60 mg. kg-1). The following groups were determined: ROC0.3, ROC0.6, ROC1.2, ROC0.3MG, ROC0.6MG e ROC1.2MG. Rocuronium onset time was measured by ulnar nerve acceleromyography (time between onset of NMB injection and reduction of motor response to 5% of initial response). The hemodynamic parameters were done immediately before the beginning of the infusion of the studied solution and one minute after the tracheal intubation. The conditions of tracheal intubation were evaluated by the anesthesiologist using the conditions of laryngoscopy, positioning of the vocal cords and response to the insertion of the tracheal tube. Serum magnesium levels were assessed by blood collection (3 mL) of the patient before and after administration of magnesium. The correlation between tissue perfusion and rocuronium onset time was determined by measuring variations in the perfusion index. Results: All patients had excellent or good conditions for tracheal intubation. Magnesium sulphate decreased onset time of rocuronium at doses of 0.3 and 0.6 mg.kg-1 (60 and 44 seconds, respectively; p < 0.05). Potentiation was not observed for rocuronium dosis of 1.2 mg.kg-1. Perfusion index variations in the groups that received MgSO4 were greater than in controls. A correlation between reduced onset time and increased perfusion index was observed for rocuronium doses of 0.3 mg.kg-1 (p < 0.001, R = -0.50) and 0.6 mg.kg-1 (p < 0.001, R = -0.424). However, this correlation was not observed for rocuronium doses of 1.2 mg.kg-1. There was no significant difference in blood pressure among the study groups; however, heart rate was increased slightly in patients who received MgSO4. Conclusions: In this study, MgSO4 reduced the rocuronium onset time at doses of 0.3 and 0.6 mg.kg-1, and onset time was not significantly affected for rocuronium dosis of 1.2 mg.kg-1. The increase in perfusion index may have contributed to the reduction in rocuronium onset time. Magnesium sulfate did not alter the intubation conditions between the groups receiving the same dose of rocuronium. Magnesium sulphate did not promote statistically significant changes in blood pressure, however, it promoted an increase in heart rate 1 min after tracheal intubation.

O uso de estímulos olfativos em estudos de discriminação simples e complexa em ratos tem fornecido dados relevantes à área de controle de estímulos porque esta modalidade de estímulo é mais saliente à espécie do que as comumente utilizadas. O objetivo deste estudo foi investigar o efeito da combinação entre as modalidades de estímulo olfativa e auditiva sobre o responder discriminado em um procedimento de bloqueio de estímulos em ratos. Quatro ratos machos Wistar (Rattus norvegicus) foram treinados em três tarefas de discriminação de acordo com o delineamento de bloqueio de estímulos. Na Fase I discriminação prévia, dois ratos foram treinados usando estímulos auditivos (A+/A-) e outros dois usando estímulos olfativos (B+/B-) como S+/S-. Na Fase II discriminação de estímulo composto, um estímulo composto (A+B+/A-B-) foi usado como S+/S- e na Fase III discriminação pós-composto, os estímulos usados na Fase I foram removidos do composto e o treino continuou com os estímulos restantes. Em seguida, foram treinados em fases adicionais: IV - (mesmo treino da Fase II), V (mesmo treino da Fase III) e Fase VI em duas etapas primeira, treino com A+/A- e B+/B- na mesma sessão sem configuração de estímulo composto e segunda, treino de competição de dicas A+B- e B+A-. Todas as fases foram realizadas a partir de um procedimento Go/No-Go. Respostas em esquema de razão fixa três na condição S+ (A+, A+B+ e B+) foram consequenciadas com acesso à solução de sacarose e resposta na condição S- (A-, A-B- e B-) resultou em timeout de 2s após o final da tentativa. Não foi programada consequência específica para o não responder. Para todas as fases o critério de aquisição foi 90% ou mais de índice discriminativo. Na Fase I os resultados mostraram uma aquisição mais rápida do responder discriminado com estímulos olfativos. Os dados das Fases II e III indicaram que houve ocorrência de bloqueio de estímulos para todos os sujeitos, independente da ordem de treino com as modalidades de estímulos. As Fases IV e V indicaram uma replicação do fenômeno de bloqueio apesar do treino realizado na Fase III. A Fase VI sugeriu que o responder discriminado se diferenciou segundo o tipo de configuração de estímulo e que a repetição de bloqueio foi produzida pela discriminação prévia. Os resultados do estudo indicaram que a modalidade de estímulo foi determinante na aquisição de discriminação, mas não para bloqueio de estímulos, discordando da ideia de que odores não são bloqueados quando usados em estímulo composto em ratos e mostrando também que a saliência dos estímulos olfativos foi modulada pela discriminação prévia com outra modalidade / Use of olfactory stimuli in simple and complex discrimination studies with rats has produced important data to stimuli controls area because this stimulus modality is more salient than others usually used. The objective of this study was to investigate combinations effects between olfactory and auditory stimuli modalities on discriminative responding to stimuli blocking design. Four male Wistar rats (Rattus norvegicus) were trained in three discriminative tasks according to the stimuli blocking design. In Phase I prior discrimination, two rats were trained using auditory stimuli (A+/A-) and two rats using olfactory stimuli (B+/B-) as S+/S-. On Phase II compound stimulus discrimination, a compound stimuli (A+B+/A-B-) were used as S+/S- and in Phase III post-compound stimulus discrimination, the stimuli used on Phase I were remove from the compound. After discriminative training, subjects were trained on additional phases: Phase IV (same training Phase II), Phase V (same training Phase III) and Phase VI with two stages: first - A+/A- and B+/B- training presented in the same session without stimulus compound configuration, second - cue competition training (A+B- and B+A-).Discriminative training was carried under a Go/No-Go procedure. Responses on a fixed-ratio three schedule was reinforced by access to a sucrose solution when S+ (A+, A+B+ and B+) was presented and responding in S- (A-, A-B- and B-) resulted in 2s-timeout after trials ending. No consequence was programmed to non-responding. The acquisition criterion was a 90% or more discriminative index. Phase I data showed a discriminative responding acquisition faster with olfactory stimuli compared to auditory stimuli. Phases II and III data revealed stimuli blocking for all subjects regardless of training order with stimulus modalities. Phases IV and V showed a replication of stimuli blocking despite the training occurred on Phase III. Phase VI indicated that discriminative responding differed by type stimulus configuration presented and that stimulus blocking replication was produced by prior discrimination. Thus, results indicated that stimuli sensory modality was relevant for discriminative responding but not for blocking, disagreeing from the idea that odors are not blocked when it are used in compound stimulus in rat and showing also that olfactory stimulus saliency can be changed by prior discrimination training by other modality

A frequent problem that appears in practical survival data analysis is censoring. A censored observation occurs when the observation of the event time (duration or survival time) may be prevented by the occurrence of an earlier competing event (censoring time). Censoring may be due to different causes. For example, the loss of some subjects under study, the end of the follow-up period, drop out or the termination of the study and the limitation in the sensitivity of a measurement instrument. The literature about censored data focuses on the i.i.d. case. However in many real applications the data are collected sequentially in time or space and so the assumption of independence in such case does not hold. Here we only give some typical examples from the literature involving correlated data which are subject to censoring. In the clinical trials domain it frequently happens that the patients from the same hospital have correlated survival times due to unmeasured variables like the quality of the hospital equipment. Censored correlated data are also a common problem in the domain of environmental and spatial (geographical or ecological) statistics. In fact, due to the process being used in the data sampling procedure, e.g. the analytical equipment, only the measurements which exceed some thresholds, for example the method detection limits or the instrumental detection limits, can be included in the data analysis. Many other examples can also be found in other fields like econometrics and financial statistics. Observations on duration of unemployment e.g., may be right censored and are typically correlated. When the data are not independent and are subject to censoring, estimation and inference become more challenging mathematical problems with a wide area of applications. In this context, we propose here some new and flexible tools based on a nonparametric approach. More precisely, allowing dependence between individuals, our main contribution to this domain concerns the following aspects. First, we are interested in developing more suitable confidence intervals for a general class of functionals of a survival distribution via the empirical likelihood method. Secondly, we study the problem of conditional mean estimation using the local linear technique. Thirdly, we develop and study a new estimator of the conditional quantile function also based on the local linear method. In this dissertation, for each proposed method, asymptotic results like consistency and asymptotic normality are derived and the finite sample performance is evaluated in a simulation study.

A frequent problem that appears in practical survival data analysis is censoring. A censored observation occurs when the observation of the event time (duration or survival time) may be prevented by the occurrence of an earlier competing event (censoring time). Censoring may be due to different causes. For example, the loss of some subjects under study, the end of the follow-up period, drop out or the termination of the study and the limitation in the sensitivity of a measurement instrument. The literature about censored data focuses on the i.i.d. case. However in many real applications the data are collected sequentially in time or space and so the assumption of independence in such case does not hold. Here we only give some typical examples from the literature involving correlated data which are subject to censoring. In the clinical trials domain it frequently happens that the patients from the same hospital have correlated survival times due to unmeasured variables like the quality of the hospital equipment. Censored correlated data are also a common problem in the domain of environmental and spatial (geographical or ecological) statistics. In fact, due to the process being used in the data sampling procedure, e.g. the analytical equipment, only the measurements which exceed some thresholds, for example the method detection limits or the instrumental detection limits, can be included in the data analysis. Many other examples can also be found in other fields like econometrics and financial statistics. Observations on duration of unemployment e.g., may be right censored and are typically correlated. When the data are not independent and are subject to censoring, estimation and inference become more challenging mathematical problems with a wide area of applications. In this context, we propose here some new and flexible tools based on a nonparametric approach. More precisely, allowing dependence between individuals, our main contribution to this domain concerns the following aspects. First, we are interested in developing more suitable confidence intervals for a general class of functionals of a survival distribution via the empirical likelihood method. Secondly, we study the problem of conditional mean estimation using the local linear technique. Thirdly, we develop and study a new estimator of the conditional quantile function also based on the local linear method. In this dissertation, for each proposed method, asymptotic results like consistency and asymptotic normality are derived and the finite sample performance is evaluated in a simulation study.

In recent years, Internet and IP technologies have made inroads into almost every communication market ranging from best-effort services such as email and Web, to soft real-time applications such as VoIP, IPTV, and video. However, providing a transport service over IP that meets the timeliness and availability requirements of soft real-time applications has turned out to be a complex task. Although network solutions such as IntServ, DiffServ, MPLS, and VRRP have been suggested, these solutions many times fail to provide a transport service for soft real-time applications end to end. Additionally, they have so far only been modestly deployed. In light of this, this thesis considers transport protocols for soft real-time applications. Part I of the thesis focuses on the design and analysis of transport protocols for soft real-time multimedia applications with lax deadlines such as image-intensive Web applications. Many of these applications do not need a completely reliable transport service, and to this end Part I studies so-called partially reliable transport protocols, i.e., transport protocols that enable applications to explicitly trade reliability for improved timeliness. Specifically, Part I investigates the feasibility of designing retransmission-based, partially reliable transport protocols that are congestion aware and fair to competing traffic. Two transport protocols are presented in Part I, PRTP and PRTP-ECN, which are both extensions to TCP for partial reliability. Simulations and theoretical analysis suggest that these transport protocols could give a substantial improvement in throughput and jitter as compared to TCP. Additionally, the simulations indicate that PRTP-ECN is TCP friendly and fair against competing congestion-aware traffic such as TCP flows. Part I also presents a taxonomy for retransmission-based, partially reliable transport protocols. Part II of the thesis considers the Stream Control Transmission Protocol (SCTP), which was developed by the IETF to transfer telephony signaling traffic over IP. The main focus of Part II is on evaluating the SCTP failover mechanism. Through extensive experiments, it is suggested that in order to meet the availability requirements of telephony signaling, SCTP has to be configured much more aggressively than is currently recommended by IETF. Furthermore, ways to improve the transport service provided by SCTP, especially with regards to the failover mechanism, are suggested. Part II also studies the effects of Head-of-Line Blocking (HoLB) on SCTP transmission delays. HoLB occurs when packets in one flow block packets in another, independent, flow. The study suggests that the short-term effects of HoLB could be substantial, but that the long-term effects are marginal.

DNA bases can be modified by endogenous agents (e.g. oxidized by products of respiration and photosynthesis or methylated by gene silencing processes) as well as by environmental agents (e.g. oxidized by UV light). In the process of removing modified bases, a 3’-phosphate group is sometimes left in the resulting gap, and has to be removed since it blocks the incorporation of a new nucleotide by DNA polymerase. The aim of this thesis was the characterization of AtZDP, a plant enzyme with a DNA 3’-phosphatase activity. By homologous modeling, the existence of four domains was predicted in AtZDP, three independent zinc-finger and one DNA 3’-phosphatase domains. AtZDP was found to be localized in the nucleus by bimolecular fluorescence complementation. Western blotting analysis showed that the enzyme was ubiquitously expressed in plant tissues. AtZDP was found in a 600,000 molecular-weight protein complex by gel chromatography and glycerol gradient sedimentation centrifugation. The fractions containing AtZDP in the complex displayed 3’-DNA phosphatase activity as shown by desphosphorylation of a DNA oligonucleotide with a 3’-phosphate terminus. Also fractions of the gel chromatography corresponding to lower molecular weight showed 3’-DNA phosphatase activity, but antibodies against AtZDP did not recognize this fraction inferring that in plants, at least another protein with similar activity exists. In mammals, polynucleotide kinase, an enzyme with the same activity phosphatase activity as AtZDP, is involved in single-strand and double-strand repair pathways. To elucidate if AtZDP could be part of similar pathways, different double strand and single-strand oligonucleotides with 3’-phosphate termini were separately incubated with AtZDP. All substrates were dephosphorylated by AtZDP, assuming that this enzyme could potentially be involved in double-strand DNA repair. A double-strand oligonucleotide containing a one-bp gap with a 3’-phosphate terminus was repaired by a leaf protein extract. The activities of a 3’-DNA phosphatase, a flap 5’ to 3’ endonuclease-like, a DNA polymerase and a DNA ligase were observed. The presence of these enzymes revealed that these damages are in plants predominantly repaired by long-patch base excision repair.

Next generation data centres are expected to support both advance resource reservation and on-demand access, but the system performance for such a computing environment has not been well-investigated. A reservation request is characterized by a start time, duration, and resource requirement. Discrete event simulation is used to study the performance characteristics of reservation systems. The basic strategy is to accept a request if resources are available and reject the request otherwise. The performance metrics considered are resource utilization and blocking probability. Results showing the impact of input parameters on these performance metrics are presented. It is found that the resource utilization is quite low. Two strategies that can be used to improve the performance for advance reservation are evaluated. The first strategy allows the start time to be delayed up to some maximum value, while the second allows the possibility of non-uniform resource allocation over the duration of the reservation. Simulation results showing the performance improvements of these two strategies are presented. Resources not used by advance reservation are used to support on-demand access. The performance metrics of interest is the mean response time. Simulation results showing the impact of resource availability and its variation over time on the mean response time are presented. These results provide valuable insights into the performance of systems with time-varying processing capacity. They can also be used to develop guidelines for the non-uniform resource allocation strategy for advance reservation in case the reserved resources are used for interactive access.

A modality device can today capture high resolution volumetric data sets and as the data resolutions increase so does the challenges of processing volumetric data through a visualization pipeline. Standard volume rendering pipelines often use a graphic processing unit (GPU) to accelerate rendering performance by taking beneficial use of the parallel architecture on such devices. Unfortunately, graphics cards have limited amounts of video memory (VRAM), causing a bottleneck in a standard pipeline. Multi-resolution techniques can be used to efficiently modify the rendering pipeline, allowing a sub-domain within the volume to be represented at different resolutions. The active resolution distribution is temporarily stored on the VRAM for rendering and the inactive parts are stored on secondary memory layers such as the system RAM or on disk. The active resolution set can be optimized to produce high quality renders while minimizing the amount of storage required. This is done by using a dynamic compression scheme which optimize the visual quality by evaluating user-input data. The optimized resolution of each sub-domain is then, on demand, streamed to the VRAM from secondary memory layers. Rendering a multi-resolution data set requires some extra care between boundaries of sub-domains. To avoid artifacts, an intrablock interpolation (II) sampling scheme capable of creating smooth transitions between sub-domains at arbitrary resolutions can be used. The result is a highly optimized rendering pipeline complemented with a preprocessing pipeline together capable of rendering large volumetric data sets in real-time.

Next generation data centres are expected to support both advance resource reservation and on-demand access, but the system performance for such a computing environment has not been well-investigated. A reservation request is characterized by a start time, duration, and resource requirement. Discrete event simulation is used to study the performance characteristics of reservation systems. The basic strategy is to accept a request if resources are available and reject the request otherwise. The performance metrics considered are resource utilization and blocking probability. Results showing the impact of input parameters on these performance metrics are presented. It is found that the resource utilization is quite low. Two strategies that can be used to improve the performance for advance reservation are evaluated. The first strategy allows the start time to be delayed up to some maximum value, while the second allows the possibility of non-uniform resource allocation over the duration of the reservation. Simulation results showing the performance improvements of these two strategies are presented. Resources not used by advance reservation are used to support on-demand access. The performance metrics of interest is the mean response time. Simulation results showing the impact of resource availability and its variation over time on the mean response time are presented. These results provide valuable insights into the performance of systems with time-varying processing capacity. They can also be used to develop guidelines for the non-uniform resource allocation strategy for advance reservation in case the reserved resources are used for interactive access.