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This thesis investigates the mechanisms underlying the formation, maintenance, and sharing of reference in tasks in which language and vision interact. Previous research in psycholinguistics and visual cognition has provided insights into the formation of reference in cross-modal tasks. The conclusions reached are largely independent, with the focus on mechanisms pertaining to either linguistic or visual processing. In this thesis, we present a series of eye-tracking experiments that aim to unify these distinct strands of research by identifying and quantifying factors that underlie the cross-modal interaction between scene understanding and sentence processing. Our results show that both low-level (imagebased) and high-level (object-based) visual information interacts actively with linguistic information during situated language processing tasks. In particular, during language understanding (Chapter 3), image-based information, i.e., saliency, is used to predict the upcoming arguments of the sentence, when the linguistic material alone is not sufficient to make such predictions. During language production (Chapter 4), visual attention has the active role of sourcing referential information for sentence encoding. We show that two important factors influencing this process are the visual density of the scene, i.e., clutter, and the animacy of the objects described. Both factors influence the type of linguistic encoding observed and the associated visual responses. We uncover a close relationship between linguistic descriptions and visual responses, triggered by the cross-modal interaction of scene and object properties, which implies a general mechanism of cross-modal referential coordination. Further investigation (Chapter 5) shows that visual attention and sentence processing are closely coordinated during sentence production: similar sentences are associated with similar scan patterns. This finding holds across different scenes, which suggests that coordination goes beyond the well-known scene-based effects guiding visual attention, again supporting the existence of a general mechanism for the cross-modal coordination of referential information. The extent to which cross-modal mechanisms are activated depends on the nature of the task performed. We compare the three tasks of visual search, object naming, and scene description (Chapter 6) and explore how the modulation of cross-modal reference is reflected in the visual responses of participants. Our results show that the cross-modal coordination required in naming and description triggers longer visual processing and higher scan pattern similarity than in search. This difference is due to the coordination required to integrate and organize visual and linguistic referential processing. Overall, this thesis unifies explanations of distinct cognitive processes (visual and linguistic) based on the principle of cross-modal referentiality, and provides a new framework for unraveling the mechanisms that allow scene understanding and sentence processing to share and integrate information during cross-modal processing.

Little is understood about the origins of atypical scanpath formation in schizophrenia.  This thesis presents a series of novel investigations which aimed to characterise the viewing abnormality and its correlate in schizophrenia and to investigate a range of putative causal mechanisms. Individuals with schizophrenia and non-clinical comparison participants completed smooth pursuit and ocular fixation tasks, mood assessment scales and free-viewing of novel visual stimuli.  Patients also completed detailed clinical and neurophysical assessment. Results replicated findings of a ‘restricted’ style of visual scanning schizophrenia, characterised by reduced fixation and saccade frequency, increased fixation durations and reduced scanpath length.  Patients also demonstrated increases in medial saccade amplitude, duration and peak velocity relative to non-clinical viewers.  Viewing abnormalities were only minimally associated with clinical and demographic variables, occurred irrespective of the nature of the stimulus and conveyed high sensitivity and specificity in distinguishing cases from controls. Two studies manipulated attention to the viewing task in non-clinical viewers and patients respectively and suggested atypical scanning is not entirely attributable to diminished task engagement.   Restricted scanning was associated with both heightened anxiety and increased interference by irrelevant visual features during fixation.  A possible causal role of anxiety on distractibility and thus scanpath formation is tentatively proposed.  Restricted scanpaths were associated with dimensions of neurocognitive functioning including working memory, short term verbal memory and verbal fluency.  These patterns are argued to be consistent with a role of dysfunction of the dorsolateral prefrontal cortex in atypical scanpath formation.  Finally, scanpath dysfunction was found to occur independently of impairments in smooth pursuit performance, suggesting the independence of neuroanatomical bases for these deficits.

Ingeniero Civil Industrial / El presente Trabajo de Título tiene como objetivo principal conocer el impacto que significa la incorporación de una nueva fuente de información a la metodología de identificación de Website Keyobjects. Esta nueva fuente de información será la medida de la actividad bioeléctrica cerebral frente a los estímulos presentados en una página web. Específicamente, se busca diseñar e implementar un módulo con algoritmos de Data Mining para clasificar los objetos relevantes presentes en un sitio web según variables de actividad cerebral. El trabajo se enmarca en el proyecto Fondef Plataforma informática basada en web-intelligence y herramientas de análisis de exploración visual para la mejora de la estructura y contenido de sitios web (AKORI: Advanced Kernel for Ocular Research and Web Intelligence) . Este proyecto está siendo llevado a cabo en conjunto por el Laboratorio de Neurosistemas y el Departamento de Ingeniería Industrial de la Universidad de Chile. La hipótesis que se valida en este trabajo es: "Es posible realizar una clasificación de los objetos relevantes de un sitio web según variables que caractericen la actividad bioelétrica cerebral". Para la validación de esta hipótesis se realiza un experimento en que 20 usuarios navegan libremente por un sitio web de estudio, mientras que un dispositivo de Eye Tracking guarda el posicionamiento de los ojos en la pantalla y los cambios en el tamaño de las pupilas y un electroencefalograma graba los potenciales eléctricos en la corteza cerebral en tiempo real. El análisis de los datos obtenidos se realiza mediante el proceso KDD, en un principio se realiza para la dilatación pupilar con el fin de obtener una línea base de estudio. Luego se aplica a los datos del EEG para realizar una comparación a lo obtenido de las señales oculares. Para ambos tipos de data se seleccionan 19 sujetos, cuyos datos son preprocesados y limpiados, luego transformados según distintas características a los que se les aplican diversos algoritmos de clasificación. Con esto se determina como resultado una lista de objetos relevantes dentro del sitio de estudio. Los resultados obtenidos indican que utilizando variables obtenidas de las señales eléctricas producidas en la corteza cerebral es posible clasificar Website Keyobjects con un 90\% de precisión, mediante el algoritmo K-Means. Esta clasificación es en base a la línea base obtenida, donde de un total de 20 objetos, 18 fueron clasificados correctamente, y fue la mejor que se obtuvo dentro de todas las combinaciones de variables y clusterizaciones realizadas. Finalmente se concluye que el trabajo fue exitoso y se proponen diversos trabajos futuros que aportan al proyecto AKORI y la metodología. Además se entrega una reflexión final correspondiente al uso de metodologías, algoritmos y conocimientos similares en otras áreas de estudio que generen valor para la sociedad.

Ingeniero Civil Industrial / El proyecto AKORI está pensado como una plataforma informática basada en técnicas de Web Intelligence, y análisis de la exploración visual para mejorar la estructura y los contenidos de un sitio web. En su etapa de investigación, se han incorporado estudios relacionados con la dilatación pupilar, el posicionamiento ocular y análisis de la actividad cerebral de los usuarios web. Una de las líneas de investigación indagó en la relación entre la dilatación pupilar y la toma de decisión de los usuarios de sitios web. Para profundizar en este estudio, se pretende realizar una investigación exploratoria, relacionando la toma de decisión con un nuevo marcador fisiológico. El objetivo general es determinar si existe una relación entre el potencial eléctrico producido por la actividad cerebral y la toma de decisión de un usuario en un sitio web. La hipótesis de investigación se plantea de la siguiente manera: El potencial bioeléctrico producido por la actividad cerebral puede predecir la toma de decisión de un usuario web . La metodología de esta investigación considera cuatro etapas: Análisis del estado del arte en el área de la neurociencia y técnicas de Data Mining; Diseño e implementación de experimentos; Análisis y procesamiento de los datos para validar la hipótesis de investigación y la construcción del clasificador; y finalmente comparar los resultados de la metodología obtenidas anteriormente. Para obtener los datos, se utilizaron herramientas de Eye-Tracking y EEG, en experimentos que simulan una situación discriminatoria dentro de un sitio web, mostrando imágenes de valencia neutra y donde el usuario debía escoger una de ellas. Para poder realizar extrapolación, se experimentó con 20 sujetos, de los cuales 18 finalizaron con la totalidad de los registros. Para analizar los datos, se separaron las observaciones que coinciden con el objeto elegido y las que no. Aquellas que tenía más de 600ms. de duración, fueron promediadas y graficadas. Al graficar cada una de las curvas, no se observan diferencias significativas. Sin embargo, se observa un patrón de comportamiento común, que consiste en la disminución de la actividad cerebral en los primeros 100ms. y un alza abrupta en la actividad durante los siguientes 200ms. Dado que no hay diferencias significativas, se realizaron dos tipos de caracterizaciones descripción estadística y transformada de Wavelet, que finalmente no permitieron validar la hipótesis de este trabajo. Si bien, la hipótesis de investigación no fue validada con los parámetros descritos, se reconoce que existen variables fisiológicas que constituyen una fuente de información que puede ser aplicadas en diversos ámbitos, ya sea en web-intelligence, web-mining, u otra disciplina ajena a la medicina pura.

Participants executed right-handed reach-to-grasp movements toward horizontally translating targets. Visual feedback of the target when reaching, as well as the presence of additional cues placed close (Experiment 1) or far (Experiment 2) above and below the target’s path was manipulated. Additional cue presence appeared to impair participants’ ability to extrapolate the disappeared target’s motion, and caused grasps for occluded targets to be less accurate. Final gaze and grasp positions were more accurate when reaching for leftward moving targets, suggesting individuals use different grasp strategies when reaching for targets travelling away from the reaching hand. Comparison of average fixations at reach onset and at the time of the grasp suggested that participants accurately extrapolated the occluded target’s motion prior to reach onset, but not after, resulting in inaccurate grasps. New information is provided about the eye-hand strategies used when reaching for moving targets in unpredictable visual conditions. / October 2016

Purpose: To describe the clinical presentation, ocular complications and clinical implications of acute HZO in HIV positive patients. Method: Prospective descriptive clinical case series of 54 individuals aged 18 – 50 years with confirmed HIV infection and acute presentation of HZO. Results: A female preponderance (1.7:1) and mean age of 36.6 years (range 18 – 49 years) was recorded. The majority of patients were referred from CHC and only 28% of referred patients received appropriate antiviral treatment at the referral site. Mean duration of rash at presentation was 4.7 days (range 1 – 12 days) with 31% of patients presenting within 3 days of rash eruption. Patients attended a mean of 2.7 clinical visits. Equal proportions had known and unknown HIV serostatus at presentation. Mean CD4+ was 276 cells/mm3 (range 44 - 859 cells/mm3). 67% of patients had a CD4+ count < 350 cells/mm3. Periocular discomfort was the most common presenting symptom (70%); decreased VA (2%) was an uncommon presenting symptom. Multidermatomal involvement was uncommon (7%). At presentation normal VA was seen in 69% of patients and 94% had no global visual impairment. Corneal complications (89%) and intraocular inflammation (46%) were the most common ocular complications. Ocular complications at presentation and multiple complications were the rule (70% and 61%). Hutchinson sign was found to be of little clinical value. Visual outcome was fair, 22% of patients having residual visual impairment. Post-herpetic neuralgia was common (74%). Conclusion: HZO is a common HIV marker condition with ocular complications. It may have an application as an indication for the initiation of ARV treatment.

A research report submitted to the Faculty of Science, University of the Witwatersrand, in partial fulfillment of the requirements for the degree of Master of Science (Environmental Sciences) Johannesburg, South Africa 7 February 2013 / In 2004 Molemane Eye Nature Reserve was stocked with 46 disease-free buffalo with the intention of generating sustainable revenues for the Reserve. However, the buffalo’s poor population growth rate and poor body condition during the dry seasons led to management reducing the buffalo population to 21 animals in 2010. The buffalo’s poor performance has drawn the attention to the potential nutritional limitations of the forage available during the dry season and to the importance of key resource areas. I examined the nutritional content of the buffalo forage using faecal analyses as proxy for nitrogen (N) and phosphorus (P), expecting a nutritional stress towards the latter part of the dry season. Data from the GPS/GSM collar on one of the buffalo cows was used to determine the dry season vegetation type selection and to identify key resource areas. A comparison of veld conditions was also done on the lowland vegetation types on Molemane Eye Nature Reserve and an adjacent property (Eye Area), which was earmarked for incorporation, to determine whether veld restoration work was required prior incorporation. It was established that the extended period of poor forage quality during the 2010 dry season was an important limiting factor for the buffalo as the forage quality dropped below the buffalo minimum nutritional requirements (Nf < 1.52 %, Pf < 2 %). A faecal sampling during early 2011 indicated that the nutritional stress period may last as long as 5 months (April to August). The buffalo did not select the vegetation types in proportional to their availability and narrowed their selection as the dry season progressed, preferring those containing woody elements. Of the 8 vegetation types indentified as key resource areas for buffalo during the dry season, the Eye Area holds 4 and contributes less than 5% to the key resource area already available on Molemane Eye Nature Reserve. The overall veld condition of the two areas was similar and no veld restoration work was deemed necessary. Although the incorporation of the Eye Area will shorten the distance between water and forage areas and have some nutritional benefits for buffalo in the dry season, mineral supplementation will be necessary for these valuable animals to become more productive and contribute to the economic objectives of Molemane Eye Nature Reserve.

Thesis (M. Pharm.)--University of the Witwatersrand, Faculty of Health Sciences, 2013. / Ocular diseases of the anterior segment are ubiquitous, especially among elderly patients. The development of novel drug delivery systems on the journey for improved treatment is therefore imperative. Aside from anatomical and physiological barriers of the eye, the actual dosage form plays a crucial role. Although liquid eye drops are the first-choice dosage form, the shortcomings do not go unnoticed. In an attempt to circumvent these drawbacks, a novel instantly soluble eye drop device was developed. The system aimed to provide an easier administration form, comfort for the patient and improve drug bioavailability to anterior chamber. This was a steer toward attaining patient-convenience and compliance which are critically challenging factors. Preformulatory studies allowed for the screening and selection of candidate components and key processing conditions. Hydrophilic polymers and excipients were selected for attainment of small, rapid disintegrating yet robust matrices via lyophilization of solutions. Design of experiments generated formulations by means of a Face centred central composite design (FCCCD) that underwent thorough physicochemical and mechanical assessment. Overall, robust rapidly disintegrating solid eye drops were produced. Fastest disintegration time was noted to be 0.200s. Drug content ranged from 79-96%. An improved permeation of formulations compared to a pure drug dispersion was seen. Mathematical modeling was conducted for better insight into the behavior of the device on the eye surface. Statistical analysis through constraint optimization yielded a single optimal formulation. Thermal and molecular transition analysis showed congruent findings with no incompatibility between components. Combinatory surface morphology and porositometric studies confirmed the presence of interconnecting pores across the matrix surface. Drug release kinetic evaluation predicted that best model fit was first-order release. Ocular irritancy studies by means of the HET-CAM test indicated that both drug-loaded and drug-free eye drops had an irritation score of 0 with the inference of good tolerability. Ex vivo permeation across excised rabbit cornea showed an improved steady state drug flux (0.00052mg.cm-2.min-1) and permeability co-efficient (1.7x10-4cm.min-1) for the optimized device compared to pure drug and a marketed eye drop preparation. In vivo analysis was conducted on the rabbit model with insertion of the device into the ocular cul-de-sac. Subsequently, ultra performance liquid chromatography (UPLC) analysis of the aspirated aqueous humour for model drug timolol maleate detection was conducted. The device demonstrated improved drug levels (Cmax = 3ug/mL) in comparison to commercial eye drops (Cmax = 1.97ug/mL) and was well tolerated. Level A point-to-point IVIVC plots indicated a R2 value of 0.84. This served to imply that the in vitro dissolution data can be compared to and may serve as a surrogate to that of in vivo pK data. Histopathological assessment on the enucleated eye ball confirmed the lack of noxious effects of the device on ocular tissue. From this study, the solid eye drop device was concluded to be safe as a drug delivery system for the anterior eye. Looking toward innovative trends and modifications, a bi-layered solid eye drop system with enhanced permeability capabilities employing low molecular weight chitosan was further fabricated for preliminary investigation.

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world for people over 60 years of age. The most severe pathological event of AMD is choroidal neovascularization (CNV), the process of new vessel formation emerging from the choroid. The new vessels extend into the normally avascular photoreceptor cell layer, where they leak fluid and cause photoreceptor cell death. CNV is thought to be initiated by hypoxia and chronic inflammation, which occur due to abnormal, age-related changes within the retinal pigmented epithelium (RPE). These events cause increased expression of the angiogenic protein vascular endothelial growth factor (VEGF) via hypoxiainducible factor-1 (HIF-1), a transcription factor that is vital in regulation of cellular responses to hypoxic and inflammatory conditions. Increased VEGF signaling stimulates proliferation and migration of vascular endothelial cells and facilitates the neovascular process. To target the early pathological events that lead to CNV, we have engineered a novel gene therapy vector that uses HIF-1 regulation to stimulate production of an angiostatic protein, endostatin from the RPE. The purpose of this study was to characterize the activity of our hypoxiaregulated, RPE-specific promoter in vitro, and investigate the effects of regulated endostatin expression, driven by our regulated promoter, on CNV in a mousemodel. We found the regulated promoter construct has robust activity in vitro only in RPE cells, and is conditionally responsive in hypoxic conditions. / In the laserinduced CNV model, CNV area was 80% smaller (P<0.0001) in eyes treated with the hypoxia-regulated, RPE-specific endostatin vector than in untreated eyes. CNV area was equally reduced in eyes treated with an unregulated endostatin vector (CMV-endostatin). However, less endostatin protein was detected in eyes treated with the regulated vector. Since it is unknown whether broad and constitutive endostatin expression will have damaging effects within the retina, it may be safer to limit its expression to pathological conditions. We have demonstrated that local, hypoxia-regulated expression of endostatin can effectively inhibit CNV, and thus, offers the further possibility of a prophylactic treatment for neovascular AMD. / by George Wesley Tyler Smith. / Thesis (Ph.D.)--Florida Atlantic University, 2010. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2010. Mode of access: World Wide Web.