O Tronco encefálico é uma estrutura singular do sistema nervoso central, pois nele passam tratos sensoriais ascendentes da medula espinal, tratos sensoriais da cabeça e do pescoço, os tratos descendentes motores originados no prosencéfalo, as vias ligadas a centros de movimento dos olhos, contemos núcleos dos nervos cranianos, e também está envolvido na regulação do nível de consciência através de projeções ao prosencéfalo oriundas da formação reticular. Tudo isto compactado em um espaço muito exíguo o que faz deste um local particularmente sensível às alterações patológicas, mesmo que pequenas, que acabam cursando com uma riqueza de sinais neurológicos devido a presença muito próxima das estruturas já citadas. Compreender a anatomia interna do tronco encefálico é essencial para o diagnóstico neurológico e a prática da medicina clínica. Por tudo que foi exposto, o tronco encefálico é um terreno fértil para o estudo através do diagnóstico por imagem, principalmente quando realizado por novas tecnologias, como exames em aparelho de ressonância magnética de alto campo (3 teslas). No entanto, pouco se sabe sobre as correlações existentes entre a microscopia e as imagens de ressonância magnética do tronco encefálico. Sendo assim, o objetivo deste estudo foi analisar e correlacionar as diversas estruturas encontradas no tronco encefálico, visualizadas em peças microscópicas de encéfalos humanos post mortem, com as imagens de ressonância magnética dos mesmos, antes da dissecção, mapeandoas e discernindo-as, contribuindo assim para diagnósticos mais precisos e topográficos das patologias que acometem o tronco encefálico, justificando o presente estudo. O estudo foi de caráter observacional exploratório e descritivo, adotando as seguintes técnicas para coleta da informações: os encéfalos humanos (n=3) foram submersos em recipiente contendo água e então lacrados de forma que o ar ambiente não entrasse no recipiente. As imagens de RM foram adquiridas em sequência gradiente echo (FFE) 2D em equipamento de campo 3T (PHILIPS ACHIEVA), com bobina de 8 canais de encéfalo. Foi utilizado TE=9,0 ms, TR=1000 ms e o ângulo de flip 90°; número de médias igual 10 e BW por pixel igual a 72 Hz/pixel. O Fator EPI utilizado foi igual a um e a resolução espacial de 0,219x0,219x2,0 mm3 com FOV de 210x210x90mm3. O tempo total de aquisição foi de 3 horas e 01 minuto e 96 segundos. Imagens histológicas utilizadas no presente estudo são do banco de dados do departamento de patologia da UNICAMP e foram comparadas às imagens obtidas na ressonância magnética. Demonstramos que foi possível a identificação das estruturas visíveis, histologicamente, nas imagens obtidas, com definição e resolução suficiente para a geração de um atlas de imagens de ressonância magnética de cortes do tronco encefálico / The Brainstem is a unique structure of the central nervous system, because in it pass ascending sensory tracts of the spinal cord, sensory tracts of head and neck, descending tracts originated in the forebrain, the pathways linked to eye movement centers, contains nuclei of cranial nerves, and is also involved in regulating the level of consciousness through projections to the forebrain that arise from the reticular formation. All these estructures are packed into a very small space which makes the brainstem a particularly sensitive place to pathological changes, that bring up a large amount of neurological signs due to very close packing of the aforementioned structures.Understanding the internal anatomy of the brainstem is essential for the neurological diagnosis and the clinical medicine practice. Thus, the brainstem is fertile ground for the study through diagnostic imaging, especially when performed by new technologies such as high-field (3 tesla) MRI machines. However, little is known about the correlation between the microscopy and magnetic resonance imaging of the brainstem. The aim of this study was to analyze and correlate the various structures found in the brainstem, viewed in microscopic slides of human brains post mortem, with the magnetic resonance imaging thereof, prior to dissection, mapping them and defining them, thus contributing to more accurate diagnoses and surveying of pathologies that affect the brainstem. Human brains (n = 3) were submerged in a container containing water, and then sealed so that the ambient air does not enter the container. MRI images were acquired in gradient echo sequence (FFE) 2D 3T field equipment (PHILIPS ACHIEVA) with coil 8- channel brain. It was used TE = 9.0 ms, TR = 1000 ms and flip angle 90°; number of averages equal to 10 and BW per pixel equal to 72 Hz/pixel. Factor PPE used was equal to one and the spatial resolution of FOV with 0,219x0,219x2,0 mm3 210x210x90mm3. The total acquisition time was 3 hours, 01 minute and 96 seconds. Histological images used in this study are from the pathology department of State University of Campinas (UNICAMP) database and compared to images obtained in MRI. We demonstrated that it was possible to identify histologically visible structures in images acquired with sufficient resolution and definition to generate an magnetic resonance imaging atlas of the brainstem sections

The need for a better understanding of journey to work behavior has never before been so important. Many transportation corridors are functioning at unacceptable levels of service and many at times to their capacity. This phenomenon is more pronounced during peak period when majority of the population is making their work trip. This research builds on the recent developments in structural equations modeling technique for identifying the socio-demographic influences on the commute behavior of the population in Florida. Towards this purpose a series of five structural equations models are estimated using aggregate level data from Census 2000. Each of these models has a set of journey to work characteristics that are observed for their behavior against prevalent sociodemographic characteristics. The journey to work characteristics identified are exhaustively studied for various relationships to the socio-demographic characteristics. The model estimation led to the identification of relations between various journey to work characteristics and the socio-demographic characteristics at the Census Tract level. Some of the results obtained supported other studies performed earlier. It is hoped that the findings of this research would broaden the horizon in understanding journey to work behavior of the population of Florida.

Victorian scholars of fiction have hitherto largely overlooked that fiction was an important site for Victorian authors and readers to engage in open discussion of religious issues in the Victorian period, often known, even to itself, as the "Age of 'Faith and Doubt.'" Along with sermons and religious tracts, which often directly addressed popular audiences, fiction became one of the most popular arenas for debating theology and religious practices. My project aims to revive interest in the religious novel genre by defining the genre, positioning it within its cultural context, and looking at how it engages in active and reciprocal conversations with other genres, fictional and nonfictional. This new approach reveals how the religious novel, long derided or ignored by critics, often leads the way with narrative innovations. Most interestingly, the religious novel, whose alternative name is tellingly the "theological romance," embraces and adopts one of the most popular plot lines of the Victorian novel tradition, namely the marriage/courtship plot, and develops it into the post-marriage plot, a plot that focuses on and examines marital life. The marriage plot serves, for many of these novels, in place of detailed theological arguments as a way of producing and embodying conversion. The religious novel actually anticipates changes in the nineteenth- century novel by expanding the plot beyond courtship and marriage.

O Tronco encefálico é uma estrutura singular do sistema nervoso central, pois nele passam tratos sensoriais ascendentes da medula espinal, tratos sensoriais da cabeça e do pescoço, os tratos descendentes motores originados no prosencéfalo, as vias ligadas a centros de movimento dos olhos, contemos núcleos dos nervos cranianos, e também está envolvido na regulação do nível de consciência através de projeções ao prosencéfalo oriundas da formação reticular. Tudo isto compactado em um espaço muito exíguo o que faz deste um local particularmente sensível às alterações patológicas, mesmo que pequenas, que acabam cursando com uma riqueza de sinais neurológicos devido a presença muito próxima das estruturas já citadas. Compreender a anatomia interna do tronco encefálico é essencial para o diagnóstico neurológico e a prática da medicina clínica. Por tudo que foi exposto, o tronco encefálico é um terreno fértil para o estudo através do diagnóstico por imagem, principalmente quando realizado por novas tecnologias, como exames em aparelho de ressonância magnética de alto campo (3 teslas). No entanto, pouco se sabe sobre as correlações existentes entre a microscopia e as imagens de ressonância magnética do tronco encefálico. Sendo assim, o objetivo deste estudo foi analisar e correlacionar as diversas estruturas encontradas no tronco encefálico, visualizadas em peças microscópicas de encéfalos humanos post mortem, com as imagens de ressonância magnética dos mesmos, antes da dissecção, mapeandoas e discernindo-as, contribuindo assim para diagnósticos mais precisos e topográficos das patologias que acometem o tronco encefálico, justificando o presente estudo. O estudo foi de caráter observacional exploratório e descritivo, adotando as seguintes técnicas para coleta da informações: os encéfalos humanos (n=3) foram submersos em recipiente contendo água e então lacrados de forma que o ar ambiente não entrasse no recipiente. As imagens de RM foram adquiridas em sequência gradiente echo (FFE) 2D em equipamento de campo 3T (PHILIPS ACHIEVA), com bobina de 8 canais de encéfalo. Foi utilizado TE=9,0 ms, TR=1000 ms e o ângulo de flip 90°; número de médias igual 10 e BW por pixel igual a 72 Hz/pixel. O Fator EPI utilizado foi igual a um e a resolução espacial de 0,219x0,219x2,0 mm3 com FOV de 210x210x90mm3. O tempo total de aquisição foi de 3 horas e 01 minuto e 96 segundos. Imagens histológicas utilizadas no presente estudo são do banco de dados do departamento de patologia da UNICAMP e foram comparadas às imagens obtidas na ressonância magnética. Demonstramos que foi possível a identificação das estruturas visíveis, histologicamente, nas imagens obtidas, com definição e resolução suficiente para a geração de um atlas de imagens de ressonância magnética de cortes do tronco encefálico / The Brainstem is a unique structure of the central nervous system, because in it pass ascending sensory tracts of the spinal cord, sensory tracts of head and neck, descending tracts originated in the forebrain, the pathways linked to eye movement centers, contains nuclei of cranial nerves, and is also involved in regulating the level of consciousness through projections to the forebrain that arise from the reticular formation. All these estructures are packed into a very small space which makes the brainstem a particularly sensitive place to pathological changes, that bring up a large amount of neurological signs due to very close packing of the aforementioned structures.Understanding the internal anatomy of the brainstem is essential for the neurological diagnosis and the clinical medicine practice. Thus, the brainstem is fertile ground for the study through diagnostic imaging, especially when performed by new technologies such as high-field (3 tesla) MRI machines. However, little is known about the correlation between the microscopy and magnetic resonance imaging of the brainstem. The aim of this study was to analyze and correlate the various structures found in the brainstem, viewed in microscopic slides of human brains post mortem, with the magnetic resonance imaging thereof, prior to dissection, mapping them and defining them, thus contributing to more accurate diagnoses and surveying of pathologies that affect the brainstem. Human brains (n = 3) were submerged in a container containing water, and then sealed so that the ambient air does not enter the container. MRI images were acquired in gradient echo sequence (FFE) 2D 3T field equipment (PHILIPS ACHIEVA) with coil 8- channel brain. It was used TE = 9.0 ms, TR = 1000 ms and flip angle 90°; number of averages equal to 10 and BW per pixel equal to 72 Hz/pixel. Factor PPE used was equal to one and the spatial resolution of FOV with 0,219x0,219x2,0 mm3 210x210x90mm3. The total acquisition time was 3 hours, 01 minute and 96 seconds. Histological images used in this study are from the pathology department of State University of Campinas (UNICAMP) database and compared to images obtained in MRI. We demonstrated that it was possible to identify histologically visible structures in images acquired with sufficient resolution and definition to generate an magnetic resonance imaging atlas of the brainstem sections

In study 1, thirty-eight healthy controls were used for optimization of the method. Fifteen patients with progressive supranuclear palsy and an equal number of age-matched healthy controls underwent diffusion tensor MRI and were then investigated and compared groupwise. It was shown that tractography analyses may preferably be performed regionally, such as along the tracts or in different segments of the tracts. Normalization of white matter tracts can be performed using anatomical landmarks. In study 2, 104 males and 153 females in the age interval 13 to 84 years of age participated as healthy individuals in order to investigate age-related changes with diffusion tensor MRI. It was shown that spatially differences in age-related changes exist between subdivided segments within white matter tracts. The aging processes within the CB and the IFO vary regionally. In study 3, 38 human brains were used for investigation of the white matter tract inferior longitudinal fasciculus (ILF) and its subcomponents. Of these, white matter anatomical dissection was performed in 14 post-mortem normal human brains. The remaining 24 brains were investigated in vivo with diffusion tensor MRI in healthy individuals. It was validated that fibers of the ILF in the occipito-temporal region have a clear, constant and detailed organisation. The anatomical connectivity pattern, and quantitative differences between the ILF subcomponents, confirmed a pivotal role of the ILF. In study 4, 12 patients with iNPH were included in the study and examined with diffusion tensor at three time points. For comparison, 12 healthy controls, matched by gender and age were also included. Controls were examined with MRI only once. It was shown that DTI measures differ significantly between patients with iNPH and healthy controls. DTI measures of the CC, the CST and the SLF, correlated to changes in clinical symptoms after shunt surgery. Deeper knowledge about functions of the brain increases possibilities to take advantages from DTI analyses with tractography.

[ES] Las lesiones del sistema nervioso que implican la interrupción de haces axonales son devastadoras para el individuo. La regeneración autónoma de los tractos axonales dañados o degenerados es poco frecuente, ya que intervienen una gran cantidad de factores que limitan esta recuperación. Hoy en día, la medicina convencional no cuenta con tratamientos efectivos y exitosos para estas lesiones, y el tratamiento de los síntomas suele ser la mejor solución. Para revertirlo y lograr la reconexión funcional de las neuronas, la ingeniería de tejidos actualmente opta por el uso de soportes tridimensionales biocompatibles, células y moléculas bioactivas. Específicamente, una de las estrategias propuestas han sido los conductos nerviosos guiados, no solo para lesiones de nervios periféricos sino también para tractos del sistema nervioso central. En esta Tesis Doctoral, se propone la combinación de un conducto tubular hueco de ácido hialurónico (HA) relleno con fibras de ácido poli-L-lactida (PLA) en su lumen, y con células de Schwann (SC) pre-cultivadas como células de soporte de la extension axonal para superar los obstáculos que limitan la regeneración de axones in vivo. Se ha demostrado que el conducto de HA y las fibras de PLA mantienen la proliferación de las SC, las cuales forman una estructura cilíndica denominada 'vaina de SC' en la pared interna del lumen del conducto y a su vez crecen de forma direccional en las fibras de PLA. El conjunto unidireccional paralelo formado por las fibras PLA y las SC recapitula las características direccionales de los tractos axonales en el sistema nervioso. Al sembrar un explante de ganglio de la raíz dorsal (DRG) en uno de los extremos del conducto, se ha conseguido el crecimiento de los axones del DRG y se ha estudiado las características de las SC, los axones crecidos y su asociación, comprobando que el biohíbrido es capaz de soportar el crecimiento axonal. Además, se propone un concepto multimodular para superar las limitaciones típicas de la regeneración axonal a larga distancia, con la combinación de haces de fibras de PLA en el lumen de varios conductos o módulos de HA individuales más cortos que se posicionan uno detrás del otro, diseñando conductos nerviosos guiados con la longitud deseada, junto con SC pre-cultivadas. El conducto multimodular demostró ser eficaz para promover el crecimiento dirigido de axones. Además, se ha desarrollado un constructo compuesto por la estructura formada por las fibras de PLA y las SC, denominado 'cordón neural', tras eliminar el conducto de HA, lo que abre la puerta a la generación de una estructura neural in vitro para su trasplante. / [CA] Les lesions de el sistema nerviós que impliquen la interrupció de feixos axonals són devastadores per a l'individu. La regeneració autònoma dels tractes axonals danyats o degenerats és poc freqüent, ja que intervenen una gran quantitat de factors que limiten aquesta recuperació. Avui dia, la medicina convencional no compta amb tractaments efectius i reeixits per aquestes lesions, i el tractament dels símptomes sol ser la millor solució. Per revertir i aconseguir la reconnexió funcional de les neurones, l'enginyeria de teixits actualment opta per l'ús de suports tridimensionals biocompatibles, cèl·lules i molècules bioactives. Específicament, una de les estratègies proposades han estat els conductes nerviosos guiats, no només per lesions de nervis perifèrics sinó també per tractes de sistema nerviós central. En aquesta tesi doctoral, es proposa la combinació d'un conducte tubular buit d'àcid hialurònic (HA) farcit amb fibres d'àcid poli-L-lactida (PLA) en el seu lumen, i amb cèl·lules de Schwann (SC) pre-cultivades com a cèl·lules de suport de l'extension axonal per superar els obstacles que limiten la regeneració d'axons in vivo. S'ha demostrat que el conducte d'HA i les fibres de PLA mantenen la proliferació de les SC, les quals formen una estructura cilíndica anomenada 'beina de SC' a la paret interna de l'lumen de l'conducte i al seu torn creixen de manera direccional en les fibres de PLA. El conjunt unidireccional paral·lel format per les fibres PLA i les SC recapitula les característiques direccionals dels tractes axonals en el sistema nerviós. A l'sembrar un explantament de gangli de l'arrel dorsal (DRG) en un dels extrems de l'conducte, s'ha seguit el creixement dels axons de l'DRG i s'ha estudiat les característiques de les SC, els axons crescuts i la seva associació, comprovant que el biohíbrido és capaç de suportar el creixement axonal. A més, es proposa un concepte multimodular per superar les limitacions típiques de la regeneració axonal a llarga distància, amb la combinació de feixos de fibres de PLA en el lumen de diversos conductes o mòduls de HA individuals més curts que es posicionen un darrere l'l'altre, dissenyant conductes nerviosos guiats amb la longitud desitjada, juntament amb SC pre-cultivades. El conducte multimodular va demostrar ser eficaç per promoure el creixement dirigit d'axons. A més, s'ha desenvolupat un constructe format per l'estructura formada per les fibres de PLA i les SC, denominat 'cordó neural', després d'eliminar el conducte d'HA, el que obre la porta a la generació d'una estructura neural in vitro per al seu trasplantament. / [EN] Injuries to the nervous system that involve the disruption of axonal bundles are devastating to the individual. Autonomous regeneration of damaged or degenerated axonal tracts is infrequent since a large number of factors are involved limiting this recovery. Nowadays, conventional medicine does not have effective and successful treatments for these injuries, and the treatment of symptoms is often the best solution. In order to reverse it and achieve the functional reconnection of neurons, tissue engineering currently opts for the use of biocompatible three-dimensional supports, cells, and bioactive molecules. Specifically, one of the proposed strategies has been nerve guidance conduits, not only for peripheral nerve injuries but also for tracts of the central nervous system. In this Doctoral Thesis, we propose the combination of hyaluronic acid (HA) single-channel tubular conduit filled with poly-L-lactide acid (PLA) fibres in its lumen, with pre-cultured Schwann cells (SC) as cells supportive of axon extension to overcome the obstacles limiting axon regeneration in vivo. We have proved that HA conduit and PLA fibres sustain the proliferation of SC, which form a cylindrical structure named 'SC sheath' on the inner wall of the lumen of the conduit and in turn grow directionally in the PLA fibres. The parallel unidirectional ensemble formed by PLA fibres and SC recapitulates the directional features of axonal pathways in the nervous system. Planting a dorsal root ganglion (DRG) explant on one of the conduit's ends, we have followed axon outgrowth from the DRG and studied the features of SC, the grown axons and their association, checking that the biohybrid is capable of supporting axonal growth. Furthermore, we propose a multimodular concept to overcome the typical limitations of long-distance axonal regeneration, with the combination of PLA fibres bundle in the lumen of several shorter individual HA conduits or modules which positioned themselves one behind the other, designing nerve guided conduits with the desired length, together with pre-cultured SC. The multimodular conduit proved effective in promoting directed axon growth. Moreover, we developed a construct consisting of the structure formed by the PLA fibres and the SC, named 'neural cord', after eliminating the HA conduit, that opens the door to the generation of a neural structure in vitro for transplantation. / La presente tesis doctoral se ha realizado con la financiación del Ministerio de Economía y Competitividad a través de los proyectos MAT2015-66666-C3-1-R, DPI2015-72863-EXP, y AEI RTI2018-095872-B-C21-C22/ERDF. Agradezco también la beca FPU15/04975 al Ministerio de Educación Cultura y Deportes. / Rodríguez Doblado, L. (2021). Biohybrids for Neural Tracts Regeneration [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/165196 / TESIS

No description available.

Axon guidance receptors such as deleted in colorectal cancer (DCC) contribute to the normal formation of neural circuits, and their mutations can be associated with neural defects. In humans, heterozygous mutations in have been linked to congenital mirror movements, which are involuntary movements on one side of the body that mirror voluntary movements of the opposite side. In mice, obvious hopping phenotypes have been reported for bi-allelic mutations, while heterozygous mutants have not been closely examined. We hypothesized that a detailed characterization of heterozygous mice may reveal impaired corticospinal and spinal functions. Anterograde tracing of the motor cortex revealed a normally projecting corticospinal tract, intracortical microstimulation (ICMS) evoked normal contralateral motor responses, and behavioral tests showed normal skilled forelimb coordination. Gait analyses also showed a normal locomotor pattern and rhythm in adult mice during treadmill locomotion, except for a decreased occurrence of out-of-phase walk and an increased duty cycle of the stance phase at slow walking speed. Neonatal isolated spinal cords had normal left-right and flexor-extensor coupling, along with normal locomotor pattern and rhythm, except for an increase in the flexor-related motoneuronal output. Although mice do not exhibit any obvious bilateral impairments like those in humans, they exhibit subtle motor deficits during neonatal and adult locomotion.

Centuries of devastating, recurrent outbreaks made the plague the archetypical disease of late medieval and early modern societies. Yet explanations of where it came from changed significantly over time. This dissertation examines how portrayals of the plague’s origins and place in society evolved separately in England and France, from the fourteenth to the eighteenth centuries. It relies in particular on plague tracts, a long-lasting literary genre that offered standardized therapeutic and curative advice. Medical historians have studied these sources to trace the development of medical thinking and practice over time. This dissertation focuses instead on the tracts’ changing discourses about the nature of the plague that are unique to time and to place. The study elaborates a new analytical method to investigate the materiality and contents of these historical documents: it involves close reading and a codicological/bibliographical comparison of approximately 180 tracts in manuscript and printed form, set into their appropriate historical contexts. Tract producers influenced how the plague was understood locally. England’s centralised print industry fostered the idea that London was the de facto site and source of the disease; France’s diffused industry, by contrast, encouraged the discussion and tracking of outbreaks in multiple cities. Understanding of the plague’s origins also evolved: belief in malevolent celestial events gave way, in turn, to blaming unhealthy local landscapes, then the living conditions of the poor, and finally the Ottoman Empire. By the mid-seventeenth century, tract writers pointed to the Ottoman Empire as the historical and geographical source of the disease. Especially during the tumultuous sixteenth century, religious discord, dynastic factionalism, and incapable rulers also appeared in the tracts as causes and effects of the plague. Plague tracts are direct expressions and reflections of the short- and medium-term historical waves in which they appeared. It is possible to trace through them shifts in political, cultural, and intellectual worldviews. The spread of humanism in particular influenced how tract writers discussed the plague’s origins and influence in society. This study thus demonstrates that understanding disease is a cultural construct specific to time and place. Observing the unique aspects of plague tracts enhances our ability to understand the place of disease in past human societies.

This thesis examines how, and the extent to which, the Chittagong Hill Tracts (CHT) Accord of Bangladesh contributed to transform conflicting relations of the parties, and communities living in the CHT. This case study research has combined two methods: (i) key informant interviews and (ii) consultation of wider secondary literature, reports of accord signing parties, international organizations, NGOs and other stakeholders, newspaper articles, working papers etc. We have developed a process-oriented analytical framework through reviewing eight widely studied peace agreements and their following conflict transformation processes. This theme-based distinctive framework has guided us to conduct a comprehensive analyse of the CHT case. We argue that the 1997 CHT Accord, developed as a part of an internal strategic conflict management and negotiation process, and stipulated for limited territorial power-sharing and localized proportional power-sharing of communities, to a considerable extent helped to transform parties’ conflicting relations, and the conflict itself, despite the Accord’s limited nature and partial implementation. The post-accord immediate implementation of some key provisions helped to build confidence of the parties and engaged them in decision-making process. This restrained them not to return to violence, although an incremental accord implementation process helped to address some complexities but created contradictions and dubious relations between them over some issues. The accord considerably contributed to improve socio-economic conditions of CHT people. Nevertheless, it shifted the dynamics of original conflict towards an intra-ethnic dimension, whereas the inter-community relations remained highly polarized due to inadequate attention paid by relevant stakeholders to bridge their gaps for peace. / Commonwealth Scholarship Commission