<p>The purpose of this work was to improve the diagnosis of intracranial hemorrhage with MRI, using, among others, T2*-w GE sequences. Various sequences were tested in rabbits at two magnetic field strengths. Then, the most effective technique was applied to stroke patients. </p><p>Experimental studies: The MR detectability of small experimental haematomas in the brain and of blood in the cerebrospinal fluid (CSF) spaces of 30 rabbits was evaluated. MRI examinations were performed at determined intervals. The last MR images were compared to formalin fixed brain sections and, in 16 rabbits, also to the histological findings. T2*-weighted GE sequences revealed all the intraparenchymal haematomas at 1.5 T, appearing strongly hypointense. Their signal patterns remained unchanged during the follow-up. Blood in the CSF spaces was best detected at 1.5T with T2*-weighted GE sequences during the first 2 days. FLAIR and SE sequences were rather insensitive.</p><p>Clinical studies: MR examinations were performed at 1.5T, including T1- and T2-w SE, FLAIR and T2*-w GE sequences. In the first clinical study, 66 intraparenchymal hematomas (IPH) of different sizes and ages were examined. T2*-w GE sequence was the most sensitive. On all the sequences, we found a big variety of signal patterns, without a clear relationship to the age of the hematomas. </p><p>In a second clinical study, MR examinations were performed to 83 patients with acute stroke: 43 presented acute IPH and 40 were used as controls. Old microhemorrhages (OMHs) were found in 60% of the patients with IPH, and in 15% of the controls. </p><p>Conclusion: T2*-weighted GE sequences are capable of revealing very small intraparenchymal hemorrhages at any stage, and blood in CSF spaces during at least the first 2 days. The age of IPHs cannot reliably be estimated with MRI. We have found a correlation between the presence of OMHs and acute intraparenchymal hematomas.</p>

The purpose of this work was to improve the diagnosis of intracranial hemorrhage with MRI, using, among others, T2*-w GE sequences. Various sequences were tested in rabbits at two magnetic field strengths. Then, the most effective technique was applied to stroke patients. Experimental studies: The MR detectability of small experimental haematomas in the brain and of blood in the cerebrospinal fluid (CSF) spaces of 30 rabbits was evaluated. MRI examinations were performed at determined intervals. The last MR images were compared to formalin fixed brain sections and, in 16 rabbits, also to the histological findings. T2*-weighted GE sequences revealed all the intraparenchymal haematomas at 1.5 T, appearing strongly hypointense. Their signal patterns remained unchanged during the follow-up. Blood in the CSF spaces was best detected at 1.5T with T2*-weighted GE sequences during the first 2 days. FLAIR and SE sequences were rather insensitive. Clinical studies: MR examinations were performed at 1.5T, including T1- and T2-w SE, FLAIR and T2*-w GE sequences. In the first clinical study, 66 intraparenchymal hematomas (IPH) of different sizes and ages were examined. T2*-w GE sequence was the most sensitive. On all the sequences, we found a big variety of signal patterns, without a clear relationship to the age of the hematomas. In a second clinical study, MR examinations were performed to 83 patients with acute stroke: 43 presented acute IPH and 40 were used as controls. Old microhemorrhages (OMHs) were found in 60% of the patients with IPH, and in 15% of the controls. Conclusion: T2*-weighted GE sequences are capable of revealing very small intraparenchymal hemorrhages at any stage, and blood in CSF spaces during at least the first 2 days. The age of IPHs cannot reliably be estimated with MRI. We have found a correlation between the presence of OMHs and acute intraparenchymal hematomas.

This thesis compares two novels each by Nigerian writer Ben Okri and Moroccan writer Tahar Ben Jelloun. By examining apparently transformative moments in the lives of each protagonist, Azaro and Zahra, its principal aim is to show how liminality characterises their identities, and is a source of personal and potentially political liberation, mirrored in the narrative techniques. The Introduction demonstrates the centrality of identity to these novels and the domain of postcolonial studies and defines the key concepts in relevant literary, theoretical and political contexts: identity, hybridity, liminality, magical realism and the postcolonial/postmodern debate. Chapter I establishes Azaro and Zahra as liminal beings from birth, whose childhood rituals are incomplete and who continually subvert parental and social expectation. This examination of liminality may be extended by reading the characters as emblems of their respective nations-in-waiting. Chapter II focuses on the tension between biology and culture within Zahra's gendered identity and demonstrates empowerment in her choice to remain liminal in a 'potential space'. Azaro's shifting sexual awareness is examined as a manifestation of his liminality. The allegorical reading of Zahra's life is continued, and a connection made between sexual and political corruption in the English texts. Chapter III centres on the fluidity of Azaro's boundaries and perception. Like Zahra's, his liminality is chosen, as he decides to live in a potential space between human and spirit. Zahra, too, has a special relationship with the spirit world; she and Azaro are shown to have revelatory visions of political significance. The Conclusion brings together the analysis of Azaro's and Zahra's identities before extending the liminal states of the protagonists to those of reader and artist. It concludes that these texts offer new opportunities for the understanding of postcolonial texts and moving beyond the duality of the postcolonial/postmodern debate.

No description available.

<p>MR phase images contain essential information about local magnetic susceptibility sources in the brain, creating a new type of contrast in magnetic resonance imaging (MRI). The goal of this thesis is to demonstrate with a model of the brain how accurately the transformation of phase to susceptibility takes place.</p> <p>A 3D brain model uses the Forward process to calculate magnetic field perturbations caused by susceptibility properties of the tissues in the model. Homodyne High Pass (HP) filter and SHARP algorithm are used to process the simulated phase images. Similarly, MR magnitude data are simulated using tissue properties such as T₁, T₂^* relaxation times and spin density.</p> <p>The halo ring around red nucleus in the real phase data is believed to be an indicator of a capsule around red nucleus. Similar effect is seen in the simulated phase images without including the capsule of red nucleus in the model, this comparison explains that the halo effect may just be entirely or a part of the phase behavior around red nucleus. A negative susceptibility in the internal capsule region, seen in both simulated and real susceptibility maps, is discussed as a possible artifact caused by the processing techniques after comparing the simulated susceptibility maps produced from unprocessed and processed phase data. The brain model is used to determine the optimum echo time of the initial gradient echo sequence in order to produce a high quality susceptibility map with reasonably low error and better time efficiency.</p> / Master of Applied Science (MASc)

Profile monitoring is a relatively new approach in quality control best used where the process data follow a profile (or curve) at each time period. The essential idea for profile monitoring is to model the profile via some parametric, nonparametric, and semiparametric methods and then monitor the fitted profiles or the estimated random effects over time to determine if there have been changes in the profiles. The majority of previous studies in profile monitoring focused on the parametric modeling of either linear or nonlinear profiles, with both fixed and random effects, under the assumption of correct model specification. Our work considers those cases where the parametric model for the family of profiles is unknown or at least uncertain. Consequently, we consider monitoring profiles via two techniques, a nonparametric technique and a semiparametric procedure that combines both parametric and nonparametric profile fits, a procedure we refer to as model robust profile monitoring (MRPM). Also, we incorporate a mixed model approach to both the parametric and nonparametric model fits. For the mixed effects models, the MMRPM method is an extension of the MRPM method which incorporates a mixed model approach to both parametric and nonparametric model fits to account for the correlation within profiles and to deal with the collection of profiles as a random sample from a common population. For each case, we formulated two Hotelling's T 2 statistics, one based on the estimated random effects and one based on the fitted values, and obtained the corresponding control limits. In addition,we used two different formulas for the estimated variancecovariance matrix: one based on the pooled sample variance-covariance matrix estimator and a second one based on the estimated variance-covariance matrix based on successive differences. A Monte Carlo study was performed to compare the integrated mean square errors (IMSE) and the probability of signal of the parametric, nonparametric, and semiparametric approaches. Both correlated and uncorrelated errors structure scenarios were evaluated for varying amounts of model misspecification, number of profiles, number of observations per profile, shift location, and in- and out-of-control situations. The semiparametric (MMRPM) method for uncorrelated and correlated scenarios was competitive and, often, clearly superior with the parametric and nonparametric over all levels of misspecification. For a correctly specified model, the IMSE and the simulated probability of signal for the parametric and theMMRPM methods were identical (or nearly so). For the severe modelmisspecification case, the nonparametric andMMRPM methods were identical (or nearly so). For the mild model misspecification case, the MMRPM method was superior to the parametric and nonparametric methods. Therefore, this simulation supports the claim that the MMRPM method is robust to model misspecification. In addition, the MMRPM method performed better for data sets with correlated error structure. Also, the performances of the nonparametric and MMRPM methods improved as the number of observations per profile increases since more observations over the same range of X generally enables more knots to be used by the penalized spline method, resulting in greater flexibility and improved fits in the nonparametric curves and consequently, the semiparametric curves. The parametric, nonparametric and semiparametric approaches were utilized for fitting the relationship between torque produced by an engine and engine speed in the automotive industry. Then, we used a Hotelling's T 2 statistic based on the estimated random effects to conduct Phase I studies to determine the outlying profiles. The parametric, nonparametric and seminonparametric methods showed that the process was stable. Despite the fact that all three methods reach the same conclusion regarding the –in-control– status of each profile, the nonparametric and MMRPM results provide a better description of the actual behavior of each profile. Thus, the nonparametric and MMRPM methods give the user greater ability to properly interpret the true relationship between engine speed and torque for this type of engine and an increased likelihood of detecting unusual engines in future production. Finally, we conclude that the nonparametric and semiparametric approaches performed better than the parametric approach when the user's model is misspecified. The case study demonstrates that, the proposed nonparametric and semiparametric methods are shown to be more efficient, flexible and robust to model misspecification for Phase I profile monitoring in a practical application. Thus, our methods are robust to the common problem of model misspecification. We also found that both the nonparametric and the semiparametric methods result in charts with good abilities to detect changes in Phase I data, and in charts with easily calculated control limits. The proposed methods provide greater flexibility and efficiency than current parametric methods used in profile monitoring for Phase I that rely on correct model specification, an unrealistic situation in many practical problems in industrial applications. / Ph. D.

[EN] Digital Terrestrial Television (DTT), offers greater robustness against noise and interference, more efficient use of radioelectric spectrum by the possibility of using single frequency networks (SFN) and the possibility of transmitting several television channels for the same radio channel. In addition, it is possible to provide value-added services such as HDTV and 3D. In the transition from analog to digital television, it must be perform a first stage of simulcast, where both analogue and digital signals should coexist. In this stage, a critical point is the low availability of frequencies. Therefore, first it is necessary to perform a frequency planning at regional level between the countries and internally for each country. Due to the high power that DTT transmitters normally radiate, and the locations of the transmitters at high points, frequency planning at regional level should take into account coordination areas and protection distances inside the border of each country. Finally, DTT network planning should be perform for the assigned frequencies. Additionally, the most efficient usage of the radio electric spectrum involved the introduction of the DTT, have allowed the release of certain frequency bands traditionally allocated for broadcasting. The released bands are known as Digital Dividend (DD), and correspond to the 800 MHz band (790-862 MHz) and 700 MHz (698-806 MHz) in Europe, and 700 MHz band in America. These bands have been allocated for the use of fourth generation mobile communications 4G LTE. The inclusion of LTE in the digital dividend bands, represents an additional problem for the deploy of DTT networks. Because both, DTT and LTE networks must coexist in adjacent frequency channels. Therefore, two coexistence cases must be considered. On the one hand, to the deployment of new DTT networks, must be analyzed the potential interference from LTE networks, as well the possible solutions to mitigate the interference. Moreover, for DTT networks already deployed, interference problems must be solved at the lowest possible cost and impact. This thesis deals with frequency planning for DTT networks in South America, where several DTT standards have been adopted. Most countries in the region have adopted the Japanese-Brazilian standard ISDB-Tb. However, Colombia has adopted the European second generation standard DVB-T2, with the particularity that Colombia is the first country in the world in which DVB-T2 must work with 6 MHz channelization, and must coexist with the analog TV standard NTSC. This along with the late release of the DD band in America, presents a much more complex scenario for DTT planning network in the region. First the frequency planning at the regional level for all countries of South America is studied, later the frequency planning at national level for Colombia is addressed. For this purpose, is investigated the coexistence of the European second generation standard (DVB-T2), the Japanese-Brazilian first generation standard (ISDB-Tb), the American analog TV standard NTSC and the mobile communications standard LTE working in digital dividend bands, as well as different technical solutions to mitigate interference on DTT networks. Finally, the recommendations of coexistence between analogue television networks NTSC, digital television networks ISDB-T, DVB-T2 and mobile communications networks 4G LTE are presented. These recommendations constitute a useful handbook for DTT network planning in South America. / [ES] La Televisión Digital Terrestre (TDT) con respecto a la difusión de televisión analógica ofrece, mayor robustez en la señal frente a ruido e interferencias, uso más eficiente del espectro radioeléctrico gracias a la posibilidad de utilizar redes de frecuencia única, en ingles SFNs (Single Frequency Network) y la posibilidad de transmitir varios canales de televisión por un mismo canal radioeléctrico. Además, es posible ofrecer servicios de valor añadido, tales como televisión en alta definición y programación 3D. En el proceso de transición de televisión analógica a digital, se debe llevar a cabo una primera etapa de simulcast, donde tanto señales analógicas como digitales deben convivir. En esta etapa, un punto crítico es la baja disponibilidad de frecuencias. Por tanto, en primer lugar es necesario hacer una planificación de frecuencias a nivel regional entre los países y a nivel interno de cada país. Debido a las altas potencias con que normalmente radian los transmisores de TDT, y las ubicaciones de los transmisores en puntos elevados, la planificación de frecuencias a nivel regional debe tener en cuenta zonas de coordinación y distancias de protección dentro de la frontera de cada país. Finalmente se debe planificar las redes de TDT a las frecuencias asignadas. Adicionalmente, la utilización más eficiente del espectro radioeléctrico que conlleva la introducción de la TDT, ha permitido la liberación de ciertas bandas de frecuencia asignadas tradicionalmente a radiodifusión. Las bandas liberadas son conocidas como Dividendo Digital (DD), y corresponden a la banda de 800 MHz (790-862 MHz) y 700 MHz (698-806 MHz) en Europa, y la banda de 700 MHz en América. Dichas bandas han sido asignadas para la utilización de servicios de comunicaciones móviles de cuarta generación 4G LTE. La inclusión del estándar LTE en las bandas de dividendo digital, representa un problema adicional para el despliegue de las redes de TDT. Debido a que tanto la TDT como las redes LTE deben coexistir en canales adyacentes en frecuencia. Por tanto, dos casos de convivencia deben ser considerados. Por un lado, para el despliegue de nuevas redes de TDT, se deben analizar las posibles interferencias desde las redes LTE, así como las posibles soluciones para mitigar dichas interferencias. Por otra parte para redes de TDT ya desplegadas, los problemas de interferencias deben ser resueltos con el menor impacto y costo posibles. La presente tesis aborda la planificación de frecuencias para las redes de TDT en Sudamérica, donde varios estándares de TDT han sido adoptados. La mayoría de los países de la región han adoptado el estándar Japones-Brasileño ISDB-Tb. Sin embargo, Colombia ha adoptado el estándar europeo de segunda generación DVB-T2, con la particularidad de ser el primer lugar en el mundo en que DVB-T2 debe trabajar con canalización de 6 MHz, y debe convivir con el estándar de televisión analógica NTSC. Esto junto con la tardía liberación del Dividendo Digital (DD) en América, presentan un escenario mucho más complejo para la planificación de las redes de TDT en la región. En primer lugar se estudia la planificación de frecuencias a nivel regional para todos los países de Sudamérica, para posteriormente abordar la planificación a nivel nacional para Colombia. Con tal fin, se investiga la convivencia entre el estándar de TDT europeo de segunda generación (DVB-T2), el estándar Japones-Brasileño de primera generación (ISDB-Tb), el estándar americano de televisión analógica NTSC y el estándar de comunicaciones móviles LTE en las bandas del dividendo digital, así como las diferentes soluciones técnicas para mitigar interferencias sobre las redes de TDT. Finalmente, se presentan las recomendaciones de convivencia entre redes de televisión analógica NTSC, redes de televisión digital ISDB-T, DVB-T2 y redes de comunicaciones móviles 4G LTE, que constituyen un útil manual para la pl / [CA] La Televisió Digital Terrestre (TDT) respecte a la difusió de televisió analògica oferix, major robustesa en el senyal enfront de soroll i interferències, ús més eficient de l'espectre radioelèctric gràcies a la possibilitat d'utilitzar xarxes de freqüència única, en engonals SFNs (Single Frequency Networks) i la possibilitat de transmetre uns quants canals de televisió per un mateix canal radioelèctric. A més, és possible oferir servicis de valor afegit, com ara televisió en alta definició i programació 3D. En el procés de transició de televisió analògica a digital, s'ha de dur a terme una primera etapa de simulcast, on tant senyals analògics com digitals han de conviure. En esta etapa, un punt crític és la baixa disponibilitat de freqüències. Per tant, en primer lloc és necessari fer una planificació de freqüències a nivell regional entre els països i a nivell intern de cada país. A causa de les altes potències amb què normalment radien els transmissors de TDT, i les ubicacions dels transmissors en punts elevats, la planificació de freqüències a nivell regional ha de tindre en compte zones de coordinació i distàncies de protecció dins de la frontera de cada país. Finalment s'ha de planificar la les xarxes de TDT a les freqüències assignades. Addicionalment, la utilització més eficient de l'espectre radioelèctric que comporta la introducció de la TDT, ha permés l'alliberament de certes bandes de freqüència assignades tradicionalment a radiodifusió. Les bandes alliberades són conegudes com a Dividend Digital (DD), i corresponen a la banda de 800 MHz (790-862 MHz) i 700 MHz (698-806 MHz) a Europa, i la banda de 700 MHz a Amèrica. Les dites bandes han sigut assignades per a la utilització de servicis de comunicacions mòbils de quarta generació 4G LTE. La inclusió de l'estàndard LTE en les bandes de dividend digital, representa un problema addicional per al desplegament de les xarxes de TDT. Pel fet que tant la TDT com les xarxes LTE han de coexistir en canals adjacents en freqüència. Per tant, dos casos de convivència han de ser considerats. D'una banda, per al desplegament de noves xarxes de TDT, s'han d'analitzar les possibles interferències des de les xarxes LTE, així com les possibles solucions per a mitigar les dites interferències. D'altra banda per a xarxes de TDT ja desplegades, els problemes d'interferències han de ser resolts amb el menor impacte i cost possibles. La present tesi aborda la planificació de freqüències per a les xarxes de TDT a Sud-amèrica, on diversos estàndards de TDT han sigut adoptats. La majoria dels països de la regió han adoptat l'estàndard Japones-Brasileño ISDB-Tb. Sin embargo, Colòmbia ha adoptat l'estàndard europeu de segona generació DVB-T2, amb la particularitat de ser el primer lloc en el món en què DVB-T2 ha de treballar amb canalització de 6 MHz, i ha de conviure amb l'estàndard de televisió analògica NTSC. Açò junt amb el tardà alliberament del DD a Amèrica, presenten un escenari molt més complex per a la planificació de les xarxes de TDT en la regió. En primer lloc s'estudia la planificació de freqüències a nivell regional per a tots els països de Sud-amèrica, per a posteriorment abordar la planificació a nivell nacional per a Colòmbia. Amb tal fi, s'investiga la convivència entre l'estàndard de TDT europeu de segona generació (DVB-T2), l'estàndard Japones-Brasileño de primera generació (ISDB-T), l'estàndard americà de televisió analògica NTSC i l'estàndard de comunicacions mòbils LTE en les bandes del dividend digital, així com les diferents solucions tècniques per a mitigar interferències sobre les xarxes de TDT. Finalment, es presenten les recomanacions de convivència entre xarxes de televisió analògica NTSC, xarxes de televisió digital ISDB-T, DVB-T2 i xarxes de comunicacions mòbils 4G LTE, que constituïxen un útil manual per a la planificació de les xarxes de / Ribadeneira Ramírez, JA. (2016). Planificación de Frecuencias para Televisión Digital Terrestre (TDT) en Sudamérica [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/63669

[ES] La fabricación de nanopartículas con tamaños por debajo de los 100 nm ha permitido el desarrollo de innovadores nanodispositivos capaces de interactuar de forma directa con sistemas vivos a nivel celular y molecular, convirtiéndose en una parte fundamental dentro del campo de la nanomedicina. Uno de los principales retos a los que se enfrenta la ingeniería de nanopartículas es el desarrollo de nanodispositivos con propiedades físico-químicas bien definidas, ya que de ellas depende el comportamiento y biodistribución de dichos sistemas una vez introducidos en el organismo. No menos importante es el desarrollo de protocolos de síntesis reproducibles y optimizados, indispensables para la fabricación y escalado de nanodispositivos que puedan ser trasladados a futuras aplicaciones biomédicas. El principal objetivo de este proyecto de doctorado es el estudio y fabricación de nanopartículas magnéticas mesoporosas de sílice con estructura "core-shell" para su aplicación como agentes teranósticos en el campo de la nanomedicina. En este estudio se analiza en profundidad la síntesis y caracterización de dichos nanomateriales con el objetivo de producir nanopartículas con unas propiedades físico-químicas bien definidas de forma controlada y reproducible. La obtención de dichas nanopartículas supondría un gran avance de cara al desarrollo de nanodispositivos más complejos y sofisticados. El contenido de la tesis se ha estructurado en distintos capítulos que se detallan brevemente a continuación: ¿El capítulo 1 es una introducción a la nanomedicina, destacando el papel fundamental que tienen las nanopartículas en el desarrollo de nuevas aplicaciones biomédicas. A continuación se presentan las nanopartículas de sílice mesoporosa, mostrando la gran versatilidad de dichos nanomateriales para el desarrollo de dispositivos teranósticos así como sistemas para la liberación controlada de fármacos. Por último, se destaca la importancia de fabricar nanodispositivos con unas propiedades físico-químicas bien definidas como requisito indispensable para la traslación de los resultados experimentales hacia el campo clínico. ¿El capítulo 2 incluye los objetivos principales de la tesis. ¿El capítulo 3 se centra en la síntesis y caracterización de nanopartículas superparamagnéticas de óxido de hierro (USPIONs), siendo estas utilizadas en capítulos posteriores para la síntesis de las nanopartículas mesoporosas tipo "core-shell". Las USPIONs son preparadas a través de un método sencillo de coprecipitación en el que se emplean condiciones de reacción moderadas. Las nanopartículas obtenidas son caracterizadas en profundidad, analizando sus propiedades magnéticas para su aplicación en hipertermia magnética y como agentes de contraste dual en imagen por resonancia magnética (MRI). ¿El capítulo 4 está dedicado a la preparación de nanopartículas magnéticas mesoporosas de sílice con estructura "core-shell". Los conceptos fundamentales relacionados con los mecanismos de formación de este tipo de nanomateriales son ampliamente analizados, así como los parámetros de reacción involucrados en la síntesis. Como punto de partida, se propone un protocolo de síntesis general para la obtención de las nanopartículas tipo "core-shell". A continuación, se analiza en profundidad el efecto que los distintos parámetros de reacción tienen en las propiedades físico-químicas de dichas nanopartículas. Para la fase de optimización se utiliza un modelo semi-empírico como referencia, racionalizando los resultados experimentales observados en base a un posible mecanismo de formación. ¿El capítulo 5 se centra en el análisis y caracterización de la estructura mesoporosa de las nanopartículas tipo "core-shell". Además, se analiza el efecto que los distintos parámetros de reacción tienen sobre la estructura final de las nanopartículas, aportando información adicional sobre su posible mecanismo / [CA] La fabricació de nanopartícules amb grandàries per davall dels 100 nm ha permés el desenvolupament d'innovadors nanodispositius capaços d'interactuar de forma directa amb sistemes vius a nivell cel¿lular i molecular, convertint-se en una part fonamental dins del camp de la nanomedicina. Un dels principals reptes als quals s'enfronta l'enginyeria de nanopartícules és el desenvolupament de nanodispositius amb propietats físic-químiques ben definides, ja que d'elles depén el comportament i biodistribució d'aquests sistemes una vegada introduïts en l'organisme. No menys important és el desenvolupament de protocols de síntesis reproduïbles i optimitzats, indispensables per a la fabricació a gran escala de nanodispositius que puguen ser utilitzats en futures aplicacions biomèdiques. El principal objectiu d'aquest projecte de doctorat és l'estudi i fabricació de nanopartícules magnètiques mesoporoses de sílice amb estructura "core-shell" per a la seua aplicació com a agents teranòstics en el camp de la nanomedicina. En aquest estudi s'analitza en profunditat la síntesi i caracterització d'aquests nanomaterials amb l'objectiu de produir nanopartícules amb unes propietats físic-químiques ben definides de forma controlada i reproduïble. L'obtenció d'aquestes nanopartícules suposaria un gran avanç de cara al desenvolupament de nanodispositius més complexos i sofisticats. El contingut de la tesi s'ha estructurat en diferents capítols que es detallen breument a continuació: ¿El capítol 1 és una introducció a la nanomedicina, destacant el paper fonamental que tenen les nanopartícules en el desenvolupament de noves aplicacions biomèdiques. A continuació es presenten les nanopartícules de sílice mesoporosa, mostrant la gran versatilitat d'aquests nanomaterials per al desenvolupament de dispositius teranòstics així com sistemes per a l'alliberament controlat de fàrmacs. Finalment, es destaca la importància de fabricar nanodispositius amb unes propietats físic-químiques ben definides com a requisit indispensable per a la translació dels resultats experimentals al camp clínic. ¿El capítol 2 inclou els objectius principals de la tesi així com els objectius específics proposats per a cada capítol de la tesi. ¿El capítol 3 està dedicat a la síntesi i caracterització de nanopartícules superparamagnétiques d'òxid de ferro (USPIONs), sent aquestes utilitzades en capítols posteriors per a la síntesi de les nanopartícules mesoporoses tipus "core-shell". Les USPIONs són preparades a través d'un mètode senzill de coprecipitació en el qual s'empren condicions de reacció moderades. Les nanopartícules obtingudes són caracteritzades en profunditat, analitzant les seues propietats magnètiques per a la seua aplicació en hipertèrmia magnètica i com a agents de contrast dual en imatge per ressonància magnètica (MRI). ¿El capítol 4 està dedicat a la preparació de nanopartícules magnètiques mesoporoses de sílice amb estructura "core-shell". Els conceptes fonamentals relacionats amb els mecanismes de formació d'aquest tipus de nanomaterials són àmpliament analitzats, així com els paràmetres de reacció involucrats en la síntesi. Com a punt de partida, es proposa un protocol de síntesi general per a l'obtenció de les nanopartícules tipus "core-shell". A continuació, s'analitza en profunditat l'efecte que els diferents paràmetres de reacció tenen en les propietats físic-químiques d'aquestes nanopartícules. Per a la fase d'optimització s'utilitza un model semi-empíric com a referència, racionalitzant els resultats experimentals observats sobre la base d'un possible mecanisme de formació. ¿El capítol 5 està dedicat a l'anàlisi i caracterització de l'estructura mesoporosa de les nanopartícules tipus "core-shell". A més, s'analitza l'efecte que els diferents paràmetres de reacció tenen sobre l'estructura final de les nanopartícules, aportant informació / [EN] The fabrication of nanoparticles with sizes below 100 nm has opened the door to the development of innovative nanodevices that directly interact with living systems at the cellular and molecular level, becoming an essential part of nanomedicine. One of the main challenges that nanoparticle engineering is currently facing is the design of nanodevices with well-defined physico-chemical properties, which ultimately determine the fate and function of these systems inside the organism. Similarly, the development of reproducible and versatile synthetic protocols is of great importance for manufacture purposes, a fundamental requirement for an efficient translation of this technology into the clinic. The main objective of this PhD thesis is the study and fabrication of core-shell-type magnetic mesoporous silica nanoparticles (M-MSNs) for their application as theranostic nanodevices in the field of nanomedicine. A comprehensive study about the synthesis and characterization of this type of nanomaterials is presented with the aim of obtaining core-shell M-MSNs with well-defined physico-chemical properties in a robust and reproducible way. The fabrication of such particles would provide a versatile and reliable platform for the development of more complex nanodevices with advanced functionalities. The thesis has been structured into several chapters that are briefly summarized as follows: ¿Chapter 1 is an introduction to the topic of nanomedicine, highlighting the importance of nanoparticles in the development of new biomedical applications. Mesoporous silica nanoparticles are then introduced, showing the great versatility that this nanomaterials offer for the development of theranostic nanodevices and smart drug delivery systems. Finally, the development of nanodevices with well-defined physico-chemical properties is identified as a crucial requirement for overcoming biological barriers and facilitate the translation of nanomedicines from the bench to bedside. ¿Chapter 2 presents the aims of this thesis and the specific objectives that are addressed in the following chapters. ¿Chapter 3 is devoted to the synthesis and characterization of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), which are later used as magnetic seeds for the synthesis of core-shell M-MSNs. USPIONs are prepared through a simple coprecipitation method using mild reaction conditions. The obtained nanoparticles are fully characterized and their magnetic properties are analyzed focusing on magnetic hyperthermia and dual MR imaging applications. ¿Chapter 4 is a comprehensive study about the preparation of monodisperse core-shell M-MSNs. The main concepts related to the synthesis and formation mechanisms of this type of nanomaterials are revised, together with the reaction parameters that are expected to have a major contribution on the reaction. As a starting point, a general synthetic protocol for the synthesis of core-shell M-MSNs is presented. Then, specific reaction parameters are investigated in order to understand their effect on the physico-chemical properties of the obtained nanoparticles. The application of a semi-empirical model to the optimization stage is presented in an attempt to provide an adequate reference framework to understand the formation of this complex nanodevices. ¿Chapter 5 presents a detailed analysis about the characterization of mesoporous silica materials and, in particular, the assessment of the mesoporous structure of MSNs with a radial distribution of wormhole-like channels. The effects that specific reaction parameters have on the mesoporous silica structure of core-shell M-MSNs are also analysed, providing additional information about the formation of this type of nanoparticles. ¿Chapter 6 gathers the main conclusions of this thesis. / Sánchez Cabezas, S. (2019). Development of a reproducible and optimized synthetic protocol for the preparation of monodisperse core-shell-type magnetic mesoporous silica nanoparticles [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/129878

Diffusion tensor imaging (DTI) is a specialist MRI modality that can identify microstructural changes or abnormalities in the brain. It can also be used to show fibre tract pathways. Both of these features were used in this thesis. Firstly, standard imaging analysis techniques were used to study the effects of mild, repetitive closed head injury on a group of professional boxers. Such data is extremely rare, so the findings of regions of brain abnormalities in the boxers are important, adding to the body of knowledge about more severe traumatic brain injury. The author developed a novel multivariate analysis technique which was used on the same data. This new technique proved to be more sensitive than the standard univariate methods commonly used. An important part of diagnosing and monitoring brain damage involves the use of biomarkers. A novel investigation of whether diffusion parameters obtained from DTI data could serve as bio-markers of cognitive impairment in Parkinson's disease was conducted. This also involved developing a multivariate approach, which displayed increased sensitivity compared with any of the component parameters used singly, and suggested these diffusion measures could be robust bio-markers of cognitive impairment. Fibre tract connectivity between regions of the brain is also a potentially valuable measure for diagnosis and monitoring brain integrity. The feasibility of this was investigated in a multi-modal MRI study. Functional MRI (fMRI) identifies regions of activation associated with a particular task. DTI can then find the pathway of the fibre bundles connecting these regions. The feasibility of using regional connectivity to interrogate brain integrity was investigated using a single healthy volunteer. Fibre pathways between regions activated and deactivated by a working memory paradigm were determined. Though the results are only preliminary, they suggest that this line of research should be continued.

It is relatively straightforward to establish equilibrium inmagnetically confined plasmas, but the plasma is frequentlysucceptible to a variety of instabilities that are driven bythe free energy in the magnetic field or in the pressuregradient. These unstable modes exhibit effects that affect theparticle, momentum and heat confinement properties of theconfiguration. Studies of the dynamics of several of the mostimportant modes are the subject of this thesis. The studies arecarried out on plasmas in the reversed field pinch (RFP)configuration. One phenomenon commonly observed in RFPs is mode walllocking. The localized nature of these phase- and wall lockedstructures results in localized power loads on the wall whichare detrimental for confinement. A detailed study of the walllocked mode phenomenon is performed based on magneticmeasurements from three RFP devices. The two possiblemechanisms for wall locking are investigated. Locking as aresult of tearing modes interacting with a static field errorand locking due to the presence of a non-ideal boundary. Thecharacteristics of the wall locked mode are qualitativelysimilar in a device with a conducting shell system (TPE-RX)compared to a device with a resistive shell (Extrap T2). Atheoretical model is used for evaluating the threshold valuesfor wall locking due to eddy currents in the vacuum vessel inthese devices. A good correlation with experiment is observedfor the conducting shell device. The possibility of succesfully sustaining discharges in aresistive shell RFP is introduced in the recently rebuiltdevice Extrap T2R. Fast spontaneous mode rotation is observed,resulting in low magnetic fluctuations, low loop voltage andimproved confinement. Wall locking is rarely observed. The lowtearingmode amplitudes allow for the theoretically predictedinternal nonresonant on-axis resistive wall modes to beobserved. These modes have not previously been distinguisheddue to the formation of wall locked modes. The internal andexternal nonresonant resistive wall modes grow on the timescale of the shell penetration time. These growth rates dependon the RFP equilibrium. The internal nonresonant resistive wallmodes dominate in Extrap T2R, especially for shallow reverseddischarges. The external nonresonant modes grow solely in deepreversal discharges. <b>Keywords</b>Nuclear fusion, reversed field pinch, resistiveinstabilities, wall locked modes, tearing modes, resistiveshell modes, field errors, EXTRAP-T2, EXTRAP-T2R, TPE-RX