A natureza das ligações de hidrogênio e a influência destas interações na estrutura eletrônica de complexos neutros, catiônicos, aniônicos e radicalares foi estudada utilizando-se análises geométricas, energéticas, eletrônicas e topológicas. Inicialmente, verificaram-se alterações na aromaticidade do cátion pirílio após a complexação com uma a três moléculas de água. Tais complexos foram ainda estudados em meio reacional com constante dielétrica igual a da água com o emprego do modelo PCM (Polarizable Continuum Model). Adicionalmente, os efeitos da hidroxilação na estrutura eletrônica dos cátions benzopirílio e flavílio foram considerados. Posteriormente, analisaram-se os efeitos das fortes ligações de hidrogênio na ressonância do grupo carboxila em complexos formados entre o radical hidroperoxil e os ácidos fórmico, acético e trifluoroacético. Como extensão desse trabalho, estudos envolvendo complexos obtidos com e sem restrições na otimização de geometria possibilitaram obter informações a respeito da ressonância dos grupos carboxila e carboxilato quando o fluoreto de hidrogênio interage linear ou perpendicularmente com todos os átomos do ácido fórmico e do ânion formiato. O desenvolvimento das atividades supracitadas compreendeu a análise da função de onda pelos métodos NBO (Natural Bond Orbital), NSA (Natural Steric Analysis), NRT (Natural Resonance Theory) e AIM (Atoms in Molecules). As alterações em parâmetros geométricos e nas cargas atômicas foram consideradas. Uma análise energética foi realizada com o emprego do método de decomposição de energia proposto por Xantheas. As freqüências vibracionais e a intensidade das bandas do estiramento do grupo X-H, doador da ligação de hidrogênio, foram analisadas. As densidades de spin para os complexos radicalares também foram obtidas. A influência das ligações de hidrogênio e o efeito do substituinte na aromaticidade dos cátions foram verificados com o emprego dos métodos e índices NICS (Nucleus Independent Chemical Shifts), HOMA (Harmonic Oscillator Model of Aromaticity), HOSE (Harmonic Oscillator Stabilization Energy) e PDI (para-Delocalization Index). Os cálculos foram efetuados com os modelos B3LYP/6-31+G(d,p), B3LYP/6-311++G(3df,3pd) e UB3LYP/6-311++G(3df,3pd). Ocasionalmente, outras funções de base (EPR-III e cc-pVDZ), assim como o método MP2, foram utilizados para testar a confiabilidade dos resultados obtidos. As interações intermoleculares pouco alteraram a estrutura eletrônica e a aromaticidade do cátion pirílio. Analogamente, a substituição de um átomo de hidrogênio por um grupo hidroxila em diversas posições dos cátions benzopirílio e flavílio também não provocou modificações muito significativas na estrutura eletrônica desses cátions, embora tenha se verificado uma dependência da aromaticidade com a posição da hidroxila. Por outro lado, a distorção geométrica associada às ligações de hidrogênio foram responsáveis pelo incremento ou diminuição da ressonância do grupo carboxila nos ácidos fórmico, acético, trifluoroacético e do grupo carboxilato no ânion formiato. Os efeitos dos grupos doador e sacador de elétrons na estabilização dos complexos radicalares foram evidenciados. Adicionalmente, pode-se atribuir um caráter covalente parcial em algumas ligações de hidrogênio. / The nature of hydrogen bonds and their influence on electronic structure of neutral, cationic, anionic, and radical complexes was studied by using geometric, energetic, electronic, and topological analysis. The changes in aromaticity of the pyrylium cation upon complexation with one up to three water molecules were investigated. The PCM (Polarizable Continuum Model) model was employed to study the pyrylium-water complexes in a water reaction medium. In addition, the effects of hydroxylation on electronic structure of the benzopyrylium and flavilium cations were also considered. In addition, the effects of strong hydrogen bonds on carboxyl group resonance in the complexes formed between the hydroperoxyl radical and formic, acetic, and trifluoroacetic acids were analyzed. In extension of this work, studies including complexes, obtained with and without geometric restrictions, provided information about the resonance of the carboxyl and carboxylate groups when the hydrogen fluoride interacts, linear or perpendicularly, with all atoms of formic acid and formate anion. The analysis of the wavefunction by using NBO (Natural Bond Orbital), NSA (Natural Steric Analysis), NRT (Natural Resonance Theory), and AIM (Atoms in Molecules) methods was necessary to the development of the above mentioned activities. The changes in geometric parameters and atomic charges were also considered. An energetic analysis of complexes was done with the energy decomposition method proposed by Xantheas. The vibrational frequencies and the intensity of the X-H (hydrogen bond donor group) stretching bands were studied. The spin densities for the radical complexes were also obtained. The Nucleus Independent Chemical Shifts (NICS), Harmonic Oscillator Model of Aromaticity (HOMA), HOSE (Harmonic Oscillator Stabilization Energy), and PDI (para-Delocalization Index) aromaticity criteria were employed to verify the hydrogen bond influence and the effect of hydroxylation in the aromaticity of the cations. The calculations were carried out by using B3LYP/6-31+G(d,p), B3LYP/6-311++G(3df,3pd), and UB3LYP/6-311++G(3df,3pd) models. Occasionally, other basis set (EPR-III and cc-pVDZ), as well as the MP2 method, were applied to test the accuracy of the results. The intermolecular interactions lead to small alterations in the electronic structure and aromaticity of pyrylium cation. Similarly, the substitution at different positions of the benzopyrylium and flavilium cations by a hydroxyl group does not cause significant changes in the electronic structure of these cations. However, a dependence of the hydroxyl group position on aromaticity was observed. On the other hand, for formic, acetic, trifluoroacetic acids, as well as for the formate anion, the resonance of the carboxyl and carboxylate groups is affected not only by the geometric distortions but also by the hydrogen bonds. The effects of the electron-donating and electron-withdrawing groups in the stabilization of radical complexes were characterized. Furthermore, a partial covalent character can be attributed to some hydrogen bonds.

Neste trabalho foram estudados computacionalmente os [2.2]ciclofanos ([2.2]paraciclofano (1), anti-[2.2]metaciclofano (2a), sin-[2.2]metaciclofano (2b) e [2.2]metaparaciclofano (3)), que são os [2n]ciclofanos mais simples, contendo dois anéis fenílicos conectados por duas pontes etilênicas. Os ciclofanos têm apresentado inúmeras aplicações importantes, podendo atuar como auxiliares em sínteses assimétricas e como catalisadores que simulam funções enzimáticas, apresentando seletividade em relação aos substratos. Eles são empregados tanto em químicab supramolecular quanto em áreas biomédicas. Estudos que empregam ressonância de spin eletrônico ou que investigam propriedades ópticas não-lineares dos [2.2]ciclofanos indicam que os mesmos apresentam interações transanulares, que ocorrem através de recobrimento direto entre orbitais pertencentes a anéis diferentes, through-space, ou através de recobrimento entre orbitais dos anéis e das pontes, through-bond. As interações transanulares possuem um papel fundamental na química dos ciclofanos, alterando o comportamento reacional destes compostos e as transições espectroscópicas. Apesar dos métodos de preparação de ciclofanos, desde os mais simples aos mais complexos, serem intensamente investigados, estudos computacionais, que busquem compreender as correlações entre tensão e aromaticidade, estrutura eletrônica e o mecanismo de ocorrência das interações transanulares, são raramente encontrados na literatura. Desse modo, o objetivo deste trabalho foi estudar as interações transanulares, bem como correlacionar as diferenças estruturais, a tensão sobre anéis e pontes, cargas atômicas, aromaticidade e os deslocamentos químicos, não apenas para os isômeros dos [2.2]ciclofanos, mas também seus derivados fluorados (perfluoração de um dos anéis dos [2.2]ciclofanos), bem como avaliar os efeitos de diversos substituintes (CN, Cl, C=O, NH2 e NO2) e da protonação na estrutura eletrônica do isômero [2.2]paraciclofano. As otimizações de geometria de 1, realizadas com diferentes métodos e conjuntos de funções de base, mostraram que os modelos MP2/6-31+G(d,p) e B3PW91/6-31+G(d,p) fornecem os melhores resultados em comparação com os dados de raios-x. Buscas conformacionais mostraram que 2a e 2b são confôrmeros com energias diferentes e que 3 possui dois confôrmeros degenerados. As energias relativas e de tensão das pontes, seguiram a mesma ordem, indicando que a tensão sobre as pontes e a repulsão entre as nuvens ? dos anéis aromáticos são determinantes para a estabilidade dos [2.2]ciclofanos. As reações isodésmicas indicaram que os anéis comportam-se como absorvedores de tensão. NICS e HOMA mostraram que apesar das perdas de planaridade dos anéis a aromaticidade é mantida. O método NBO confirmou que todos os [2.2]ciclofanos apresentam interações through-bond, mas apenas 2a e 2b apresentaram interações through-space significantes. A análise AIM mostrou que as interações transanulares observadas são do tipo camada fechada (iônica ou ligação de hidrogênio) e que estabilizam os [2.2]ciclofanos. Para os derivados fluorados as principais alterações geométricas observadas foram para os diedros das pontes. As reações isodésmicas revelaram que as tensões das pontes e as energias relativas são afetadas pela fluoração. Além disso, os anéis dos isômeros fluorados absorvem mais tensão que os anéis dos isômeros não fluorados. NICS e HOMA mostraram que a substituição por flúor aumenta a aromaticidade dos [2.2]ciclofanos. A análise NBO indicou que a perfluoração aumentou o número e a intensidade das interações through-space, mas as mesmas ficaram restritas principalmente aos derivados fluorados de 2a e 2b. A mesma análise evidenciou que há uma conjugação dos pares de elétrons dos átomos de flúor com o sistema ?. Por outro lado, a análise AIM sugeriu que a substituição não aumenta o número de interações through-space, mas confirmou a conjugação dos pares de elétrons dos átomos de flúor. Os demais substituintes empregados afetam os parâmetros geométricos do [2.2]paraciclofano (1) de maneira diferenciada. A análise particionada das reações isodésmicas mostrou que as tensões nos anéis e nas pontes dependem não apenas do substituinte empregado, mas também da posição da substituição. NICS e HOMA indicaram que a aromaticidade no anel não-substituído dos derivados substituídos é maior que em 1. A análise NBO revelou que a substituição e a protonação aumentam a ocorrência de interações transanulares through-space. O método AIM indicou a presença de interações transanulares apenas para o derivado substituído com NH2 e CN e para a espécie protonada. No entanto, tais interações apresentaram características de interações de camada fechada. com pequenas estabilizações. As cargas atômicas e os deslocamentos químicos confirmaram as mudanças na densidade eletrônica, observadas através do método AIM. / In this work, the [2.2]cyclophanes ([2.2]paracyclophane (1), anti-[2.2]metacyclophane (2a), syn-[2.2]metacyclophane (2b) e [2.2]metaparacyclophane (3)), which are the simplest [2n] cyclophanes that contain two phenyl rings connected by two ethanediyl linkages, were studied computationally. Cyclophanes have presented several important applications, such as auxiliary in asymmetric synthesis, catalysts that simulate enzymatic functions, presenting selectivity in relation to the substrates. They are employed either in supramolecular chemistry or in biomedical areas. Studies that apply electron spin resonance or that investigate the non-linear optical properties of [2.2]cyclophanes, indicate that these compounds present transannular interactions, which occur through direct overlap of orbitals lying in different rings, throughspace, or through overlap between orbitals from rings and bridges, through-bond. The transannular interactions have a fundamental role in cyclophane chemistry, changing the reactional behavior of these compounds, and the spectroscopic transitions. Despite the fact that the well known methods of preparation, from the simplest to the most complex cyclophanes, have been studied intensively, computational studies that intent to comprehend the correlations between tension and aromaticity, electronic structure, and the mechanism of the transannular interactions are rarely found in the literature. Therefore, the aim of this work was not only to study the transannular interactions, correlating the structural differences, tension in rings and bridges, atomic charges, aromaticity, and chemical shifts of the [2.2]cyclophanes isomers but also to extent a similar treatment to the fluorinated derivatives. In addition, the effects of substituents such as (CN, Cl, C=O, NH2, and NO2) and the protonation on the electronic structure of [2.2]paracyclophane were also evaluated. The geometry optimizations of 1, carried out by using different methods and basis set, showed that the models MP2/6-31+G(d,p) and B3PW91/6-31+G(d,p) provide the best results in comparison with the x-ray data. Conformational searches showed that 2a and 2b are the conformers that present the same energy and the isomer 3 has two degenerated conformers. The strain energies of the bridges followed the same tendency as the relative energies, indicating that the tension on the bridges and the repulsions between the ? clouds of the aromatic rings are the key factors that determine the [2.2]cyclophane stabilities. The isodesmic reactions indicated that the rings are absorbents of tension. NICS and HOMA showed that the aromaticity of the rings is preserved despite the changes on the planarity. The NBO method confirmed that all [2.2]cyclophanes present through-bond interactions, but only 2a and 2b exhibit noteworthy through-space interactions. The AIM analysis pointed out that the transannular interactions behave as closed shell interactions (ionic or hydrogen bond), stabilizing the [2.2]cyclophanes. The main geometric changes, observed to the fluorinated derivatives, were those related with the dihedral angle of bridges. The isodesmic reactions pointed out that the tensions of bridges and the relative energies are affected by the fluorination. In addition, the fluorinated rings absorb more tension than the non-fluorinated rings. NICS and HOMA showed that the substitution by fluorine increases the aromaticity of the [2.2]cyclophanes. The NBO analysis indicated that the number of through-space interactions increase with the fluorination, but it is restrict to the derivatives of 2a and 2b. In addition, the same analysis pointed out a conjugation of the fluorine lone pairs with the ? system. On the other hand, the AIM analysis suggested that the substitution do not increase the number of through-space interactions, but confirmed the conjugation of the fluorine lone pairs. The other substituents can affect the geometric parameter of 1 noticeably. The partitioned analysis of isodesmic reactions showed that the tensions in bridges and rings not only depend on the substituents employed but also on the position of substitution. NICS and HOMA pointed out that the aromaticity is bigger in the non-substituted rings of [2.2]paracyclophane derivatives than in 1. The NBO analysis showed that the substitution and protonation increase the number of through-space interactions. AIM method indicated the transannular interactions occur only to the derivate substituted by NH2 and CN, and to the protonated specie. However, these interactions presented features of closed shell interactions with small stabilizations. The atomic charges and the chemical shifts confirmed the changes of the electronic density, observed through the AIM method.

Black Cottonwood (Populus trichocarpa) is a fast-growing, economically important tree species. P. trichocarpa was the first tree to have its genome fully sequenced and is considered the model organism for genomic research in trees. Of the macronutrients in plants, Nitrogen (N) is required in the greatest amounts and is generally the limiting nutrient in terrestrial ecosystems. Inorganic N-transport is performed by four families of transporter proteins, AMT1 and AMT2 for ammonium (NH4+) and NRT1 and NRT2 for nitrate (NO3-). I have created phylogenetic reconstructions of each of these transporter families in 22 members of Viridiplantae whose genomes have been fully sequenced. Based on these phylogenies, I have introduced a new classification system for the transporter families that better represents the evolutionary and functional relatedness of the proteins. These phylogenies were supplemented with topology predictions, subcellular localization predictions, and in silico expression profiling in order to suggest functional characterization of the groups. This facilitated candidate gene selection for NH4+ and NO3- uptake transporters from P. trichocarpa. Expression profiling was performed on two of these candidates. Results suggest that PtAMT1-1 may be a high-affinity, root-localized NH4+ transporter. In contrast, PtNRT2-6 is a high-affinity NO3- transporter localized to the dormant bud, but its physiological functions remain largely enigmatic. Flux profiles of NH4+, NO3-, and H+ in the first 1.4 cm of root tips of three-week-old P. trichocarpa seedlings and cuttings were measured using the Microelectrode Ion Flux mEasurement (MIFE) system to demonstrate the activity of AMTs and NRTs under nutrient-abundant and nutrient-deficient conditions. I found mainly N-efflux from roots of cuttings while seedling roots exhibited N-uptake. This is the first report of such a difference. This highlights an unexpected but clear physiological difference between seedling and cutting roots, which are frequently used in experimental setups. / Graduate / 0817 / 0369 / 0715 / neilvonw@gmail.com

Nicotine replacement therapy (NRT) is a pharmacotherapy used commonly to help tobacco smokers quit smoking. All forms of NRT are demonstrably efficacious for this indication, and several forms, including transdermal nicotine (TN) are available over-the-counter in the United States. NRT is less efficacious in women than in men, although the specific reasons for this gender difference are unknown. NRT generally, and TN specifically, is thought to work, at least in part, by suppressing withdrawal symptoms in abstinent smokers. While TN-induced withdrawal suppression has been demonstrated, the degree to which this withdrawal suppression is influenced by smokers' gender is uncertain. The purpose of this acute laboratory study is to determine if TN-induced withdrawal suppression is influenced by smokers' gender.One hundred twenty eight overnight-abstinent smokers completed four, double-blind, randomized, 6.5-hour laboratory sessions in which further cigarette abstinence was required. Sessions differed by TN dose (0, 7, 21, or 42 mg). All sessions were double-blind and randomly ordered. Each session included regular assessment of subjective symptoms of nicotine/tobacco withdrawal, subjective effects of transdermal nicotine dose, psychomotor performance, heart rate and plasma nicotine level. Results from this laboratory study revealed clear nicotine dose-related effects for plasma nicotine and heart rate, symptoms of nicotine intoxication (e.g. Nausea, Lightheaded) and suppression of Urges to smoke and Craving. Many DSM IV nicotine/tobacco withdrawal symptoms did not show dose-related suppression (e.g. Irritability/frustration/anger, Anxious, Difficulty concentrating). Importantly, results from this study indicated that there were very few differences between men and women in nicotine-induced suppression of the nicotine/tobacco withdrawal syndrome. Future research addressing this important issue may benefit from focusing on a potential interaction between gender and other effects of TN (i.e., blunting the effects of a concurrently administered cigarette) and/or on other triggers for relapse (i.e., smoking-related stimuli).

An important goal in modern weather prediction is to improve short-term weather forecasts, especially of severe weather and precipitation. However, the ability to achieve this goal is hindered by the lack of timely and accurate observations of atmospheric water vapour, which is one of the most poorly measured and least understood constituents of the Earth's atmosphere due to its high temporal and spatial variability. This situation is being addressed by the Global Positioning System (GPS) technology. GPS radio signals are slowed and bent by changes in temperature, pressure and water vapour in the atmosphere. Traditionally, the GPS signal propagation delay is considered a nuisance parameter that is an impediment to obtaining precise coordinates using GPS. Recent development in GPS precise positioning and orbit determination has enabled the atmospheric parameters to be determined to a high degree of accuracy on a routine basis, using continuous tracking data from ground-based GPS receivers. The aim of this research is to address several critical scientific challenges in estimating the atmospheric water vapour content in near-real-time (NRT) in Australia. Contributions are made to the field of GPS meteorology in the following five areas: First of all, research efforts were made to develop a technical platform for the ground-based GPS meteorology studies and demonstration of GPS Precipitable Water Vapour (PWV) estimation using observations from Australian Regional GPS Networks (ARGN). Methods of estimation of water vapour from GPS and radiosonde data have been developed and tested. GAMIT-based GPS data processing strategies and compare analysis with radiosonde water vapour solutions from the Australia Upper Air Network (AUAN) were undertaken, providing an effective technical basis for further studies. Secondly, the research has developed techniques to allow estimation of atmospheric water vapour from GPS data and surface meteorological observations collected around the GPS sites. Ideally a dedicated meteorological sensor is installed adjacent to the GPS antenna. However, meteorological sensors are normally not installed at most Australian GPS stations. Installing a new meteorological sensor at each GPS station would involve additional cost at the level of one-third or half of the geodetic GPS receiver cost. We have experimentally developed and demonstrated interpolation methods for making use of hourly collected surface meteorological data from the Australian Automatic Weather Station (AWS) network operated by the Bureau of Meteorology (BOM) to estimate atmospheric water vapour. Thirdly, the research has studied ocean tidal loading and its effects on GPS derived precipitable water vapour estimates. The periodic motion of the Earth's surface due to ocean loading is one of the largest periodic motions. However, very little work has been done to quantify their effects on GPS-derived solutions at the GPS sites in the Australian region surrounded by ocean waters. The research presents the theoretical analysis and experimental results from the ARGN network, focusing on ocean loading and its effects on GPS derived precipitable water vapour estimates. The fourth important effort was the development of techniques for estimating highrate Slant Water Vapour (SWV) values for future operational meteorological applications in Australia, including addressing such issues as slant-path delay recovery from post-fit double-difference residuals, and overcoming site multipath effects. The experimental results have demonstrated the efficiency of the proposed methods. Finally, in order to address the meteorological applications with the existing and anticipated GPS reference stations in the Australian region, and measure the atmospheric water vapour content in near-real-time, the technical issues to implement NRT GPS water vapour estimation were identified and discussed, including the data requirements for meteorological and climate applications, NRT data processing and quality control procedures for GPS orbits. The experimental GPS PWV results from NRT and post data processing are compared and presented.

Gamete donors are actively searched by companies dedicated to assisted reproduction in the Spanish State, and advertising is not only legal but rather common. This thesis provides an overview of the main themes that arise from the analysis of mostly visual materials used to promote ovum donation in public spaces in Barcelona, and critically links them to current debates in intersectional feminist cultural studies of technoscience, bodily theory and visual studies. Conceptual and affective tensions between characterisations of women’s bodies, reproductive function and desires are identified and brought forward in terms that imply tropes of sacralisation, reification of cells/organs/tissues, and fragmentation of the bodily reality. It is argued that egg donation advertisements use an imagery that deeply connects with practices well rooted in Western biomedical traditions when it comes to female bodies, physiology and reproductive function, and that such practices are to be understood against the backdrop of neoliberalism. The analysis supports the idea that the publicity discourse of the assisted reproduction industry in Spain actively engages in a legitimation of the desire of biological parenthood as a right, in ways that value lives conceived in different circumstances and geopolitical contexts in radically different ways, and that can be interpreted as paving the way to prosurrogacy and/or eugenic positions. Future research is encouraged and directed towards exploring issues of agency, particularly in vulnerable groups such as migrant, poor, uneducated or racialised women. Further research is needed in order to build the foundations of a feminist ethical reflection on reproductive technologies and particularly of ovum donation.

Electrophysiological measures such as impedance telemetry and Neural Response Telemetry (NRT™) were developed by Cochlear™ in 1992 as clinical tools allowing the objective setting of stimulus levels for cochlear implant users. Extensive research proved the usefulness of NRT™’s as an aid in the programming process of audible and comfortable stimulus levels for children younger than six years. The Nucleus® Freedom™, launched in 2005, introduced new developments in cochlear implantation. Approval from the FDA for this system was obtained in March 2005 and for the first time included children from age 12 months with profound hearing loss. The Joint Committee on Infant Hearing suggested that children be diagnosed and that treatment commenced by the age of six months. The new features of the Nucleus Freedom™ give clinicians the necessary tools to treat this challenging population. An urgent need exists to ascertain the stability and accuracy of the new features introduced by this system, especially the Auto-NRT™ software, to validate its use within the paediatric population. A longitudinal descriptive design was utilized implementing quantitative research methods to critically describe the behaviour of impedance telemetry and NRT™’s in a group of young cochlear implant users. The quantitative method included the application of the Custom Sound™ software and the Auto-NRT™ feature for this group at implantation, device activation, and then at determined follow-up visits. Nine young children between nine months and five years and eleven months were used as participants during the twelve months of research. Impedance telemetry was described in terms of the mean Common Ground (CG) and Monopolar 1+2 (MP1+2) values calculated from measurement data collected on the basal, medial, and apical electrodes of the electrode array. The electrodes identified for statistical procedures for both measurement types were E3, E6, E8, E11, E13, E16, E19 and E21. Friedman’s ANOVA was used as a statistical measure to determine the level of significance in changes among the measurement modes and conditions. The Wilcoxon signed-rank test was indicated in the presence of significant changes identified by Friedman’s ANOVA to calculate the level of significance in a pair-wise comparison. Results indicate that impedance telemetry remained consistent over the electrode array and over time in both measurement modes. A slight increase in mean values was observed during the first three months, followed by a gradual decrease at the six months interval. These changes were statistically nonsignificant. No specific trends were evident in impedance telemetry over time. NRT™-measurements remained consistent across the electrode array over time. Significant changes were present between the intra-operative to device activation measurement intervals. This trend is also described in studies of adult cochlear implant users. NRT™-measurements were stable during the first year postimplantation within the paediatric population. A comparison between the mean impedance telemetry and NRT™’s disclosed an inverse trend during the first six months post-implantation. Most changes were non-significant, indicating that these measures can be used effectively in the new semi-automated fitting software. The implementation of these measurements can lead to streamlined and accountable service delivery to young cochlear implant users. AFRIKAANS : In 1992 is elektrofisiologiese metings soos impedanstelemetrie en Neurale Respons Telemetrie (NRT™) deur Cochlear™ ontwikkel as kliniese hulpmiddels om objektiewe instelling van stimulasievlakke vir kogleêre gebruikers moontlik te maak. Navorsing het bewys dat NRT™’s ‘n effektiewe hulpmiddel is tydens programmering van hoorbare en gemaklike stimulasievlakke by kinders jonger as ses jaar. Die Nucleus® Freedom™ met nuwe ontwikkelings ten opsigte van kogleêre inplantings is in 2005 bekendgestel. Die FDA het in Maart 2005 hierdie sisteem goedgekeur vir gebruik by kinders selfs so jonk as 12 maande met uitermatige gehoorverlies. Die Joint Committee on Infant Hearing het voorgestel dat diagnose en aanvang van rehabilitasie teen ses maande ouderdom moet plaasvind. Die nuwe funksies van die Nucleus® Freedom™ stel oudioloë in staat om hierdie uitdagende bevolking te hanteer. ‘n Dringende behoefte bestaan om te bepaal of hierdie sagteware, veral Auto-NRT™ wat saam met hierdie sisteem bekendgestel is, oor voldoende akkuraatheid en stabiliteit beskik om in die hantering van die pediatriese bevolking te gebruik. ‘n Longitudinale, beskrywende ontwerp, wat kwantitatiewe metodes implementeer, is aangewend om die beweging van impedanstelemetrie en NRT™’s by ‘n groep jong gebruikers van kogleêre inplantings krities te beskryf. Dit het die gebruik van die Custom Sound™ sagteware en die ingeslote Auto- NRT™ funksie behels. Dit is tydens inplantering, by aktivering van die toestel, en bepaalde opvolgsessies uitgevoer. Nege jong kinders tussen die ouderdomme van nege maande en vyf jaar en 11 maande is tydens die 12 maande navorsingsperiode as proefpersone benut. Die impedansmetings is beskryf in terme van die Common Ground (CG) en Monopolar 1+2 (MP1+2) stimulasiemodaliteite. Data is verkry vanaf geselekteerde elektrodes op die basale, mediale en apikale gedeeltes van die elektrode. Vir statistiese ontledings van impedans en NRT™ is hierdie elektrodes geselekteer: E3, E6, E8, E11, E13 E16, E19 en E21. As statistiese ontledingsmetode, is Friedman se ANOVA toegepas om die vlakke van beduidenheid van beweging tussen die verskillende toetsmodaliteite en -omstandighede te bepaal. Die Wilcoxon signed-rank toets is aangedui in die teenwoordigheid van statisties beduidende veranderinge. Die doel van hierdie toets was om die vlak van beduidenheid paarsgewys te verifieer. Resultate dui op konstante impedansmetings oor die elektrode asook oor tyd in beide toetsmodaliteite. ‘n Geringe, statisties nie-beduidende, verhoging in gemiddelde waardes is waargeneem tydens die eerste drie maande na inplantering, waarna die waardes weer geleidelik afgeneem het tot en met die ses maande opvolginterval. Geen spesifieke neiging kon vir impedanstelemetrie bepaal word nie. NRT™-metings het konstant gebly oor die elektrode en met tyd. Statisties beduidende veranderinge is gemeet tussen die intra-operatiewe en aktiveringsintervalle. Hierdie neiging is ook beskryf in studies van volwasse gebruikers van kogleêre inplantings. NRT™-metings, binne die pediatriese populasie, het dus stabiel gebly oor die 12 maande periode post-inplantering. ‘n Vergelyking tussen die gemiddelde impedans- en NRT™-metings het ‘n inverse neiging geïdentifiseer gedurende die eerste ses maande na inplantering. Veranderinge was oor die algemeen statisties nie-beduidend, wat daarop dui dat hierdie metings effektief gebruik kan word. Die implementering van hierdie metings kan meer doeltreffende dienslewering aan die jong gebruikers van kogleêre inplantings tot gevolg hê. / Dissertation (MCommunication Pathology)--University of Pretoria, 2010. / Speech-Language Pathology and Audiology / unrestricted

<div>Electrical nerve stimulation (ENS) is an emerging therapy for many neurological disorders. Compared with conventional one-way stimulations, closed-loop ENS approaches increase the stimulation efficacy and minimize patient's discomfort by constantly adjusting the stimulation parameters according to the feedback biomarkers from patients. Wireless neurostimulation devices capable of both stimulation and telemetry of recorded physiological signals are welcome for closed-loop ENS systems to improve the quality and reduce the costs of treatments, and real-time digital signal processing (DSP) engines processing and extracting features from recorded signals can reduce the data transmission rate and the resulting power consumption of wireless devices. Electrically-evoked compound action potential (ECAP) is an objective measure of nerve activity and has been used as the feedback biomarker in closed-loop ENS systems including neural response telemetry (NRT) systems and a newly proposed autonomous nerve control (ANC) platform. It's desirable to design a DSP engine for real-time processing of ECAP in closed-loop ENS systems. </div><div><br></div><div>This thesis focuses on developing the DSP architecture for real-time processing of ECAP, including stimulus artifact rejection (SAR), denoising, and extraction of nerve fiber responses as biomedical features, and its VLSI implementation for optimal hardware costs. The first part presents the DSP architecture for real-time SAR and denoising of ECAP in NRT systems. A bidirectional-filtered coherent averaging (BFCA) method is proposed, which enables the configurable linear-phase filter to be realized hardware efficiently for distortion-free filtering of ECAPs and can be easily combined with the alternating-polarity (AP) stimulation method for SAR. Design techniques including folded-IIR filter and division-free averaging are incorporated to reduce the computation cost. The second part presents the fiber-response extraction engine (FREE), a dedicated DSP engine for nerve activation control in the ANC platform. FREE employs the DSP architecture of the BFCA method combined with the AP stimulation, and the architecture of computationally efficient peak detection and classification algorithms for fiber response extraction from ECAP. FREE is mapped onto a custom-made and battery-powered wearable wireless device incorporating a low-power FPGA, a Bluetooth transceiver, a stimulation and recording analog front-end and a power-management unit. In comparison with previous software-based signal processing, FREE not only reduces the data rate of wireless devices but also improves the precision of fiber response classification in noisy environments, which contributes to the construction of high-accuracy nerve activation profile in the ANC platform. An application-specific integrated circuit (ASIC) version of FREE is implemented in 180-nm CMOS technology, with total chip area and core power consumption of 19.98 mm² and 1.95 mW, respectively. </div><div><br></div>