The goal of this thesis was to evaluate the cost-effectiveness of implantable Doppler technology (IDT) used to monitor free tissue transfer (FTT) procedures in the treatment of cancer of the upper aerodigestive tract (UADT). First, a systematic review of the literature on the effectiveness of traditional and IDT monitoring techniques was performed. Second, a utility survey using a time trade-off technique was created and administered. The results from this survey were used to establish utility values for health states common in patients undergoing FTT procedures. Third, a cost study using the microcosting data available through the Ottawa Hospital was performed. Finally, a decision analytic model was created and an economic evaluation from the payer perspective was completed. A probabilistic sensitivity analysis (PSA) and a value of information analysis (VOI) were performed. The thesis found that the currently available evidence supports IDT as a cost-effective intervention. Further research should be directed towards determining the effectiveness of both traditional and IDT monitoring.

The objective of this research was to better understand how impact angle influences headform dynamic response and brain tissue deformation. A bare headform was impacted using a pneumatic linear impactor at 5.5 m/s. The impacts were directed on the front and side location at angles of 0, 5, 10 and 15° rightward rotations as well as -5, -10 and -15° (leftward) rotations at the side to examine the characteristics of the head and neckform on the results. Peak resultant linear and rotational accelerations from the headform as well as peak maximum principal strain (MPS) and von Mises stress (VMS) estimated from a brain finite element model were used to measure the effect of impact angle. Significant results were dependent upon the impact angle and location as well as the dependent variable used for comparison (p <0.05). Impact angle produced significant differences in rotational acceleration and MPS at both the front and side; however angle only had an effect on VMS and linear acceleration at the front and side locations, respectively. These findings show that the effect of impact angle is asymmetrical and is specific to the dependent variable. This study suggests that varying impact angle alone may not be as influential on headform dynamic response and brain tissue deformation and that the severity of an impact may be more of a function of how both location and angle create high risk conditions.

Every year, several thousand individuals suffer spinal cord injury (SCI) in North America, while 1.5 million suffer traumatic brain injury in the U.S.A. alone. Primary mechanical trauma to the CNS is followed by a complex pathology, including vascular dysregulation, ischemia, edema and traumatic hemorrhage. Secondary damage is to a large extent caused by oxidative stress and inflammatory processes, resulting in necrosis and apoptosis of neural cells. If secondary tissue injury could be limited by interference with any of the pathomechanisms involved, preservation of structure and function would increase the potential for functional recovery. Experiments performed in other laboratories have shown that the polyphenolic flavonoid quercetin acts as an anti-oxidant and anti-inflammatory, reduces edema formation and apoptotic cell death. Quercetin is also an excellent iron chelator. This action profile suggested a high therapeutic potential for acute CNS trauma. Therefore, I used models of both spinal cord injury and head trauma in adult male rats to test the hypothesis that administration of quercetin is beneficial for the therapy of acute traumatic CNS injury. While the primary focus of my work was on therapy of acute traumatic spinal cord injury, quercetin was also evaluated in the settings of chronic SCI and acute head trauma. I found that, in a rat model of mid-thoracic spinal cord compression injury, 1) administration of quercetin, starting 1 hr after injury and continued every 12 hr, improved recovery of motor function in the hind limbs in more than half of the injured animals to a degree that allowed previously paraplegic animals to step or walk. The minimum quercetin dose that was efficacious was 5 µmol/kg. The minimum treatment duration for optimal outcome was determined to be 3 days. In control animals, some spontaneous recovery of motor function did occur, but never to an extent that allowed animals to step or walk. Quercetin administration was associated with more efficient iron clearance from the site of injury, decreased inflammatory response as reflected in decrease of myeloperoxidase activity and decreased apoptosis of neural cells at the site of injury. 2) Quercetin administered in the same injury model as late as 2 weeks after injury, given in a higher dose than that used for treatment in the acute phase, still resulted in significant recovery of motor function in 40% of the injured animals, although at a lower level of performance, when compared to early onset of treatment. 3) Quercetin administered after moderate fluid percussion brain injury resulted in decreased oxidative stress, as reflected in higher tissue glutathione levels at the site of injury. In animals receiving quercetin, the amplitude of compound action potentials was significantly better maintained at 24 hr and 72 hr after injury than in saline-treated control animals. My experiments have shown that the flavonoid quercetin is neuroprotective in a rat model of brain trauma and in a rat model of spinal cord injury. My data show that administration of quercetin after CNS trauma promotes iron clearance, decreases oxidative stress and inflammation. Quercetin also decreases apoptotic cell death following neurotrauma. These results suggest that quercetin may be a valuable adjunct in the therapy of acute CNS trauma. There is a possibility that administration of quercetin may be beneficial even in certain settings of chronic CNS trauma. These conclusions are based solely on the results from animal experiments. However, the fact that few adverse reactions have been noted to date in either animal experiments or human trials targeting other diseases is encouraging for the progression to human clinical trials for patients with spinal cord injury.

My goal is to learn the history of Hilton Head Island and logically reason out the way it grew, marking Sea Pine’s design influence over time and place. This paper is meant to be a piece of nature and history writing, which has implications for the study of environmental economics and real-estate design practices, but is not strictly about either. The thrust of this piece is the mapping of developmental philosophies and their reflection in the land. This topic interests me because at its core, it looks at how decisions are made, and the trade offs that influence them. The paper is also about the formation of ideas that explore sustainable forms of human-environment interaction, but which do not give up the high quality of life that modern man has come to expect. Environmental issues will continue to influence social, economic and political thought as we move towards midcentury. Sea Pines champions a blending of man and nature that may be able to provide alternative and more efficient solutions to the problems that our society faces.

La patología de origen traumático, cuarta causa de mortalidad y primera en cuanto a años perdidos, es un relevante problema de salud, que ocasiona además una elevada morbilidad e incapacidad y un alto coste sanitario y social. El conocimiento de su abordaje se ha realizado mediante el análisis de bases de datos de pacientes y encuestas a profesionales. El presente trabajo de investigación va dirigido a conocer si la asistencia al paciente adulto con TCE en las UCI catalanas de referencia para esta patología es comparable en cuanto a epidemiología, abordaje y resultados, a los que muestra la literatura referente a otros países de nuestro entorno. Se planteó un estudio con un objetivo principal doble, por un aparte describir las características demográficas y clínicas de los pacientes y por otro analizar el abordaje terapéutico y la monitorización. Como objetivos secundarios se plantearon conocer la variabilidad de los apartados anteriores según la gravedad del TCE, conocer si la práctica clínica se adhería a las principales recomendaciones de las Guías de Práctica Clínica vigentes y conocer el resultado neurológico final de los pacientes, identificando las posibles variables epidemiológicas estudiadas que pudieran influir en el resultado neurológico y la presencia de de insultos secundarios que se producen. Se realizó un estudio observacional, multicéntrico y prospectivo en las 7 UCIs catalanas de referencia para esta patología. Se recogieron datos demográficos, clínicos, radiológicos, monitorización, terapéuticos, complicaciones y de resultado de los pacientes que ingresaban en una UCI afectos de un TCE, con o sin politraumatismo durante los primeros 15 días de estancia. Se incluyeron pacientes 370 pacientes durante un año.Los principales resultados muestran un predomina el sexo masculino, edad media de 40 años, causa principal el accidente de tráfico. Un 36% de los casos ingresaron directamente en el centro de referencia pero únicamente el 26% en los primeros 60 minutos. El perfil de gravedad del TCE fue un 53% Graves, 27% Moderados y 20% Leves, con una lesión encefálica predominante tipo II de Marshall (39%). La presencia de HSA fue del 49%. Se monitorizó la PIC en el 69% de los TCE grave, la SjO2 en el 27% y el DTC en el 50%. La intensidad de la monitorización y el uso de la terapéutica se incrementa de acuerdo a la mayor gravedad del paciente. Hay una alta adherencia para las recomendaciones de las guías de práctica clínica en lo que hace referencia a la utilización de monitorización sistémica y neurológica, la utilización de barbitúricos, y menor en cuanto a la utilización de corticoides, e hiperventilación. La tasa global de mortalidad en UCI fue del 22%, un 31 % para los graves. Las variables explicativas de "éxitus" fueron el estado de las pupilas, el tipo de lesión radiológica, el sexo y la gravedad del TCE. La presencia de complicaciones prehospitalarias (hipoxia, hipotensión, broncoaspiración, paro cardiorrespiratorio, hipotermia o convulsiones) se constata en el 15% de los pacientes y se asocia de forma acumulativa con un mal resultado.Como conclusión general este trabajo de investigación apoya la hipótesis inicial de que la atención al TCE en las UCI catalanas estudiadas es comparable en cuanto a epidemiología, abordaje y resultados, a los que muestra la literatura referente a otros países de nuestro entorno. Palabras clave:Head injury, traumatic brain injury, neurocritical care. / Trauma disease represents the fourth cause of mortality in frequency and the first one in terms of lifetime waste. It constitutes a significant health problem that provokes a high morbidity and incapacity in addition to striking health and social costs. Since now, its management approach has been done through patient data bases analysis and surveys directed to professionals. This research report attempts to elucidate epidemiologic, management and clinical results' comparability between actual adult BTI clinical practice in Catalan ICU's, which are of reference for this pathology, and practice shown in medical literature in our environment. The study was planned with a double main objective; for one part, to describe demographic and clinical patient characteristics, and for the second part, to analyse patient monitoring and therapeutic management. As secondary objectives we proposed to explore variability by BTI clinical severity, adherence rate to recommendations addressed in Clinical Practice Guidelines in force, and patient neurological outcome, identifying those epidemiologic parameters probably influencing neurological outcome, apart from secondary insults incidence. An observational and prospective study was conducted in 7 reference ICU's in Catalonia. Patient data collected covered demographic, clinical, radiological, monitoring and therapeutic aspects, besides complications and outcome variables for patients that were admitted in the ICU with a BTI diagnosis, with or without multiple trauma, that were followed in their length of stay for a 15-day period. A total of 370 patients were included in the study period of 1 year.Main results show a predominance of males with a mean age of 40, being traffic accident the main cause of BTI. 36% were directly admitted to the reference hospital, but only 26% were admitted in the first hour after the accident. The BTI severity profile was: 53% severe, 27% moderate and 20% mild, being the highest prevalence (39%) type II Marshall encephalic injury. The existence of SH was 49%. ICP was monitored in 69% of severe patients and SjO2 in 27% and TCD in 50%. Monitoring and therapeutic use was shown to increase depending on the higher patient severity. Close adherence to clinical guidelines recommendations was proven for systemic and neurological monitoring and barbiturate use, and was lesser the adherence for hyperventilation and corticoid utilization. ICU mortality rate was 22%, raising 31% for severe patients. Dependent variables for mortality were found to be pupil status, type of radiological finding, sex and BTI severity. Pre-hospital complications (hypoxia, hypotension, bronchial aspiration, cardiac arrest, hypothermia, convulsions) were found in 15% of patients, and are cumulative associated with a worse outcome.As a general conclusion, this research report supports the initial hypothesis that BTI clinical practice reviewed in reference Catalan ICU's, is comparable to practice in other countries of our environment, as is shown from the medical literature published.

No description available.

The global aim of this thesis was to assess retinal vascular reactivity in glaucoma patients using a standardised hypercapnic stimulus. There is a suggestion of disturbance in the regulation of retinal and optic nerve head (ONH) hemodynamics in patients with Primary Open Angle Glaucoma (POAG), although much of the work to-date has either been equivocal or speculative. Previous studies have used non-standardised hypercapnic stimuli to assess vascular reactivity. To explain, hypercapnia induces hyperventilation which disturbs arterial oxygen concentration, an effect that varies between individuals resulting in the non-standardised provocation of vascular reactivity. Therefore, a normoxic hypercapnic provocation was developed to avoid additional and potentially uncontrolled vasoconstriction in what is thought to be a vasospastic disease. The development of a safe, sustained and stable normoxic hypercapnic stimulus was essential for the assessment of retinal arteriolar vascular reactivity so that repeated hemodynamic measurements could be obtained. Furthermore, most techniques used to measure vascular reactivity do not comprehensively assess retinal hemodynamics, in terms of the simultaneous measurement of vessel diameter and blood velocity in order to calculate flow. In this respect, this study utilized a technique that quantitatively assesses retinal blood flow and vascular reactivity of the major arterioles in close proximity to the ONH. The stimulus and vascular reactivity quantification technique was validated in healthy controls and then was clinically applied in patients with POAG. Newly diagnosed patients with untreated POAG (uPOAG) were recruited in order to avoid any confounding pharmacological effects and patients with progressive POAG (pPOAG) were also selected since they are thought to likely manifest vascular dysregulation. Finally, the results of the functional vascular reactivity assessment were compared to those of systemic biochemical markers of endothelial function in patients with untreated and progressive POAG and in healthy controls. Overall summary A safe, sustained, stable and repeatable normoxic hypercapnic stimulus was developed, evaluated and validated. In terms of the physiology of retinal vascular regulation, the percent magnitude of vascular reactivity of the arterioles and capillaries was found to be comparable in terms of flow. The new stimulus was successfully applied in POAG and in healthy controls to assess vascular reactivity and was also compared to plasma levels of ET-1 and cGMP. In terms of the patho-physiology of POAG, the study revealed a clear impairment of vascular reactivity in the uPOAG and pPOAG groups. There were reduced levels of plasma ET-1 in the uPOAG and ntPOAG groups. In addition, treatment with Dorzolamide improved vascular reactivity in the ntPOAG group in the absence of any change in the expression of plasma ET-1 or cGMP. Future work will address this apparent contradiction between the outcome of the functional vascular reactivity assessment and the biochemical markers of endothelial function in newly diagnosed POAG patients treated with Dorzolamide. Aims of chapters  Chapter 3: To determine the effect of hypercapnia on retinal capillary blood flow in the macula and ONH using scanning laser Doppler flowmetry (SLDF) in young healthy subjects.  Chapter 4: To describe a new manual methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. The secondary aim was to determine the magnitude of the vascular reactivity response of the retinal arterioles to hypercapnic provocation in young healthy subjects.  Chapter 5: To compare the magnitude of vascular reactivity of the retinal arterioles in terms of percentage change of flow to that of the retinal capillaries using a novel automated standardized methodology to provoke normoxic, or isoxic, hypercapnia.  Chapter 6: To determine the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated POAG (uPOAG), progressive POAG (pPOAG) and controls. The secondary aim was to determine retinal vascular reactivity in newly treated POAG (ntPOAG, i.e. after treatment with 2% Dorzolamide, twice daily for 2 weeks).  Chapter 7: To compare plasma endothelin-1 (ET-1) and cyclic guanosine monophosphate (cGMP) between groups of patients with untreated primary open angle glaucoma (uPOAG), progressive POAG (pPOAG), newly treated POAG (ntPOAG) and controls. The effect of normoxic hypercapnia on plasma ET-1 and cGMP was also assessed. The functional measures of retinal blood flow and vascular reactivity were correlated with systemic biochemical markers of endothelial function. Methods Chapters 3, 4 and 5 were conducted on young healthy control subjects, where as Chapters 6 and 7 were conducted on patients with glaucoma and healthy controls.  Chapter 3: Subjects breathed unrestricted air for 15 minutes (baseline) via a sequential gas delivery circuit and then the fractional (percent) end-tidal concentration of CO2 (FETCO2) was manually raised for 15 minutes by adding a low flow of CO2 to the inspired air. For the last 15 minutes, FETCO2 was returned to baseline values to establish a recovery period. Heidelberg Retina Flowmeter (HRF) images centered on both the ONH and the macula were acquired during each phase.  Chapter 4: Subjects breathed air via a sequential gas delivery circuit for 15 minutes and the air flow was then manually decreased so that subjects inspired gases from the rebreathing reservoir until a stable 10-15% increase in FETCO2 concentration was achieved for 20 minutes. Air flow rate was then manually elevated so that subjects breathed primarily from the fresh gas reservoir to return FETCO2 back to baseline for the last 15 minutes. Retinal arteriolar hemodynamics was assessed using the Canon Laser Blood Flowmeter (CLBF) during all three breathing phases.  Chapter 5: Normoxic, or isoxic, hypercapnia was induced using an automated gas flow controller (RespirActTM, Thornhill Research Inc. Toronto, Canada). Subjects breathed air with PETCO2 normalized at 38 mmHg. An increase in PETCO2 of 15% above baseline, whilst maintaining normoxia, was then implemented for 20 minutes and then PETCO2 was returned to baseline conditions for 10 minutes. Retinal and ONH hemodynamic measurements were performed using the CLBF and HRF in random order across sessions.  Chapter 6: Retinal arteriolar vascular reactivity was assessed in patients with uPOAG, pPOAG (defined by the occurrence of optic disc hemorrhage within the past 24 months) and controls during normoxic hypercapnia. Using the automated gas flow controller, patients breathed air for 10 mins and PETCO2 was maintained at 38mmHg. Following this normoxic hypercapnia (a 15% increase in PETCO2 while PETO2 was maintained at resting levels) was induced for 15 mins and then for the last 10 mins PETCO2 was returned to baseline (post-hypercapnia) to establish recovery blood flow values. Retinal arteriolar diameter, blood velocity and blood flow was assessed using the CLBF in both patient groups and controls. A similar paradigm was repeated in the newly treated POAG group (ntPOAG, i.e. after treatment with 2% Dorzolamide, twice daily for 2 weeks).  Chapter 7: Blood samples were collected from the cubital vein of all participants (uPOAG, pPOAG, ntPOAG and controls) during baseline conditions (PETCO2=38mmHg) and then during normoxic hypercapnia (i.e. a 15% increase in PETCO2 relative to the baseline) using the paradigm described for Chapter 6. ET-1 and cGMP was assessed using immunoassay. Results  Chapter 3: The group mean nasal macula capillary blood flow increased from 127.17 a.u. (SD 32.59) at baseline to 151.22 a.u. (SD 36.67) during hypercapnia (p=0.028), while foveal blood flow increased from 92.71 a.u. (SD 28.07) to 107.39 a.u. (SD 34.43) (p=0.042). There was a concomitant and uncontrolled +13% increase in the group mean PETO2 during the hypercapnic provocation of +14% increase in PETCO2.  Chapter 4: Retinal arteriolar diameter, blood velocity and blood flow increased by 3.2% (p=0.0045), 26.4% (p<0.0001) and 34.9% (p<0.0001), respectively during hypercapnia. There was a stable ¬+12% increase in PETCO2 during hypercapnia and a concomitant -6% decrease in PETO2.  Chapter 5: Using an automated gas flow controller the co-efficient of repeatability (COR) was 5% of the average PETCO2 at baseline and during normoxic hypercapnia. The COR for PETO2 was 10% and 7% of the average PETO2 at baseline and during normoxic hypercapnia, respectively. Group mean PETCO2 increased by approximately +14.4% and there was only a +4.3% increase in PETO2 during hypercapnia across both study sessions. Retinal arteriolar hemodynamics increased during hypercapnia (p<0.001). Similarly, there was an increase in the capillary blood flow of the temporal rim of the ONH (p<0.001), nasal macula (p<0.001) and foveal areas (p<0.006) during hypercapnia. A non-significant trend for capillary blood flow to increase in the macula temporal area (+8.2%) was noted. In terms of percentage change of blood flow, retinal capillary vascular reactivity (i.e. all 4 analyzed areas = 22.4%) was similar to the magnitude of arteriolar (= 24.9%) vascular reactivity.  Chapter 6: Retinal arteriolar diameter, blood velocity and flow did not increase during normoxic hypercapnia in uPOAG compared to controls. Diameter and blood velocity did not change in pPOAG during normoxic hypercapnia but there was a significant increase in blood flow (+9.1%, p=0.030). After treatment with 2% Dorzolamide for 2 weeks there was a 3% (p=0.040), 19% (p<0.001) and 26% (p<0.001) increase in diameter, velocity and flow, respectively, in the ntPOAG group. Group mean PETCO2 increased by approximately +15% in all the groups and there was only a +3% increase in PETO2 during hypercapnia.  Chapter 7: Plasma ET-1 levels were significantly different across groups at baseline (one way ANOVA; p=0.0012) and this was repeated during normoxic hypercapnia (one way ANOVA; p=0.0014). ET-1 levels were lower in uPOAG compared to pPOAG and controls at baseline and during normoxic hypercapnia (Tukey’s honestly significant difference test). Similarly, ntPOAG group also showed lower ET-1 levels compared to the pPOAG and controls at baseline and during normoxic hypercapnia (Tukey’s honestly significant difference test). The cGMP at baseline and during normoxic hypercapnia across all groups was not different. In the control group, the change in ET-1 during normoxic hypercapnia was negatively correlated with change in retinal arteriolar blood flow (r = -0.52, p=0.04), that is, as the change in ET-1 reduced, the change in blood flow increased. A weak correlation was noted between change in cGMP during normoxic hypercapnia and the change in arteriolar blood flow (r = +0.45, p=0.08). Conclusions  Chapter 3: Hypercapnia resulted in a quantifiable capillary vascular reactivity response in 2 of the 3 assessed retinal locations (i.e., nasal macula and fovea). There was no vascular reactivity response of the ONH. It is critical to minimise the concomitant change in PETO2 during hypercapnia in order to obtain robust vascular reactivity responses.  Chapter 4: A technique to comprehensively assess vascular reactivity during stable and sustained hypercapnia was described. Retinal arteriolar diameter, blood velocity and blood flow increased in response to hypercapnia. The vascular reactivity results of this study served as a reference for future studies using the hypercapnic provocation and CLBF. Also, the concomitant change in PETO2 using the partial rebreathing technique was reduced compared to the manual addition of CO2 technique described in Chapter 3 but was still greater than optimal.  Chapter 5: A new automated gas flow controller was used to induce standardised normoxic, or isoxic, hypercapnia. The magnitude of vascular reactivity in both retinal arterioles and capillaries in response to the new hypercapnic stimulus was robust compared to the previous stimuli. There was a clear ONH vascular reactivity response in this study, unlike the result attained in Chapter 3. Although theoretically it is predictable that the percent magnitude of vascular reactivity of the arterioles and capillaries should be similar, this is the first study to show that they are indeed comparable. The magnitude of hypercapnia was repeatable and the concomitant change in PETO2 was minimal and physiologically insignificant.  Chapter 6: The normal response of the retinal arterioles and capillaries to normoxic hypercapnia is impaired in both uPOAG and pPOAG compared to controls. Short term treatment with 2% topical Dorzolamide for two weeks improved retinal vascular reactivity in ntPOAG. However, it is still unclear whether this improvement is a direct effect of Dorzolamide or as a secondary effect of the decrease in intraocular pressure (IOP).  Chapter 7: We found a reduction in the plasma ET-1 at baseline and during normoxic hypercapnia in the uPOAG and in the ntPOAG groups. This is the first study to show a lower plasma ET-1 level in uPOAG. The fact that this finding was repeated after 2 weeks treatment with Dorzolamide in the ntPOAG group further validates these results. It also suggests that Dorzolamide treatment does not impact ET-1 and cGMP measures, although it clearly results in an improvement of vascular reactivity. Correlation results suggest that as the change in ET-1 reduced during normoxic hypercapnia, the change in blood flow increased in the controls.

Undesirable work factors, such as awkward upper body postures and repetitive arm motion, in the workplace can lead to upper extremity pain. Research suggests that these work-related factors, and subsequent rotator cuff fatigue, may cause the subacromial space (the space between the inferior acromion surface and superior humerus) of the shoulder to decrease. Reducing this space can create impingement of the interposed tissues, which causes shoulder pain. The aim of this study was to examine superior humeral head excursion and changes in the width of the subacromial space (acromio-humeral interval) after fatiguing the rotator cuff musculature. Four anterior-posterior radiographs of the glenohumeral joint at arm abduction angles of 0˚, 45˚, 90˚ and 135˚ were taken before and after a fatiguing task. The fatiguing task was a simulated job task requiring shoulder flexion/abduction and internal/external rotation, with the intention of exhausting the entire rotator cuff. The position of the humeral head with respect to the glenoid cavity was significantly affected both by arm angle and fatigue state; the mean humeral superior excursion following fatigue was 0.63±1.76mm. In the pre-fatigued state, increasing arm angle was related to superior translation until 90˚, after which the humeral head moved inferiorly to a more central position. In the post-fatigued state, the inability of the rotator cuff to centralize the humeral head led to increasing translations with higher elevations. Although the magnitude of translation in this study was smaller than seen in patients with rotator cuff tears, continuous overhead work demonstrably created rotator cuff fatigue, which apparently inhibited the ability of the shoulder musculature to resist upward translation of the humerus. Therefore, jobs that require overhead and repetitive work arguably put the worker at greater risk for superior translation of the humerus and subsequent related tissue damage.

Head tracking is an important way to interact with virtual objects in virtual world. The viewercan move or rotate his head to observe the 3D scene in dierent view. Normally head tracking isused in a cave or just on a at screen.Dome theater has a half sphere screen with multiple projectors together for showing the wholescene onto the big screen. The dome screen could give the viewer a very strong immersion feelingwhen head tracking inside dome theater and that is why we want to implement head tracking indome theater. The half sphere dome screen is so big that multiple projectors should be used forshooting the whole scene onto the big screen. Hence a cluster system is used for manipulating allthe projectors working smoothly. The display system of dome theater has no place for the headtracking part.This thesis tries to introduce a method to do head tracking in dome theater. The mainproblem is how to add head tracking in the display system in dome theater. Frame buer object(FBO) is used as the solution for this problem. The viewer's viewing frustum is created in framebuer object in order to render the 3D scene depending on the viewer's head position. The FBOtexture will then be attached onto a 3D sphere which simulates the dome sphere in virtual world.Since the viewing frustum is always created depending on the viewer's head position, the FBOtextures on the 3D sphere always can represent the 3D scene rendered depending on the viewer'shead position. Using the projectors to shoot the 3D scenes which is the 3D sphere attached by theFBO textures onto the dome screen. That is the main part of how to implement head tracking indome theater.This thesis forcus on rendering the 3D scene onto the dome screen depending on the viewer'shead position. The tracking device controlling part is out of this thesis's scope. VR Juggler (VRJ) is used as the framework in this project. Viewer's position setting and cluster setting are allsetted in the conguration file.

The global aim of this thesis was to assess retinal vascular reactivity in glaucoma patients using a standardised hypercapnic stimulus. There is a suggestion of disturbance in the regulation of retinal and optic nerve head (ONH) hemodynamics in patients with Primary Open Angle Glaucoma (POAG), although much of the work to-date has either been equivocal or speculative. Previous studies have used non-standardised hypercapnic stimuli to assess vascular reactivity. To explain, hypercapnia induces hyperventilation which disturbs arterial oxygen concentration, an effect that varies between individuals resulting in the non-standardised provocation of vascular reactivity. Therefore, a normoxic hypercapnic provocation was developed to avoid additional and potentially uncontrolled vasoconstriction in what is thought to be a vasospastic disease. The development of a safe, sustained and stable normoxic hypercapnic stimulus was essential for the assessment of retinal arteriolar vascular reactivity so that repeated hemodynamic measurements could be obtained. Furthermore, most techniques used to measure vascular reactivity do not comprehensively assess retinal hemodynamics, in terms of the simultaneous measurement of vessel diameter and blood velocity in order to calculate flow. In this respect, this study utilized a technique that quantitatively assesses retinal blood flow and vascular reactivity of the major arterioles in close proximity to the ONH. The stimulus and vascular reactivity quantification technique was validated in healthy controls and then was clinically applied in patients with POAG. Newly diagnosed patients with untreated POAG (uPOAG) were recruited in order to avoid any confounding pharmacological effects and patients with progressive POAG (pPOAG) were also selected since they are thought to likely manifest vascular dysregulation. Finally, the results of the functional vascular reactivity assessment were compared to those of systemic biochemical markers of endothelial function in patients with untreated and progressive POAG and in healthy controls. Overall summary A safe, sustained, stable and repeatable normoxic hypercapnic stimulus was developed, evaluated and validated. In terms of the physiology of retinal vascular regulation, the percent magnitude of vascular reactivity of the arterioles and capillaries was found to be comparable in terms of flow. The new stimulus was successfully applied in POAG and in healthy controls to assess vascular reactivity and was also compared to plasma levels of ET-1 and cGMP. In terms of the patho-physiology of POAG, the study revealed a clear impairment of vascular reactivity in the uPOAG and pPOAG groups. There were reduced levels of plasma ET-1 in the uPOAG and ntPOAG groups. In addition, treatment with Dorzolamide improved vascular reactivity in the ntPOAG group in the absence of any change in the expression of plasma ET-1 or cGMP. Future work will address this apparent contradiction between the outcome of the functional vascular reactivity assessment and the biochemical markers of endothelial function in newly diagnosed POAG patients treated with Dorzolamide. Aims of chapters  Chapter 3: To determine the effect of hypercapnia on retinal capillary blood flow in the macula and ONH using scanning laser Doppler flowmetry (SLDF) in young healthy subjects.  Chapter 4: To describe a new manual methodology that permits the comprehensive assessment of retinal arteriolar vascular reactivity in response to a sustained and stable hypercapnic stimulus. The secondary aim was to determine the magnitude of the vascular reactivity response of the retinal arterioles to hypercapnic provocation in young healthy subjects.  Chapter 5: To compare the magnitude of vascular reactivity of the retinal arterioles in terms of percentage change of flow to that of the retinal capillaries using a novel automated standardized methodology to provoke normoxic, or isoxic, hypercapnia.  Chapter 6: To determine the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated POAG (uPOAG), progressive POAG (pPOAG) and controls. The secondary aim was to determine retinal vascular reactivity in newly treated POAG (ntPOAG, i.e. after treatment with 2% Dorzolamide, twice daily for 2 weeks).  Chapter 7: To compare plasma endothelin-1 (ET-1) and cyclic guanosine monophosphate (cGMP) between groups of patients with untreated primary open angle glaucoma (uPOAG), progressive POAG (pPOAG), newly treated POAG (ntPOAG) and controls. The effect of normoxic hypercapnia on plasma ET-1 and cGMP was also assessed. The functional measures of retinal blood flow and vascular reactivity were correlated with systemic biochemical markers of endothelial function. Methods Chapters 3, 4 and 5 were conducted on young healthy control subjects, where as Chapters 6 and 7 were conducted on patients with glaucoma and healthy controls.  Chapter 3: Subjects breathed unrestricted air for 15 minutes (baseline) via a sequential gas delivery circuit and then the fractional (percent) end-tidal concentration of CO2 (FETCO2) was manually raised for 15 minutes by adding a low flow of CO2 to the inspired air. For the last 15 minutes, FETCO2 was returned to baseline values to establish a recovery period. Heidelberg Retina Flowmeter (HRF) images centered on both the ONH and the macula were acquired during each phase.  Chapter 4: Subjects breathed air via a sequential gas delivery circuit for 15 minutes and the air flow was then manually decreased so that subjects inspired gases from the rebreathing reservoir until a stable 10-15% increase in FETCO2 concentration was achieved for 20 minutes. Air flow rate was then manually elevated so that subjects breathed primarily from the fresh gas reservoir to return FETCO2 back to baseline for the last 15 minutes. Retinal arteriolar hemodynamics was assessed using the Canon Laser Blood Flowmeter (CLBF) during all three breathing phases.  Chapter 5: Normoxic, or isoxic, hypercapnia was induced using an automated gas flow controller (RespirActTM, Thornhill Research Inc. Toronto, Canada). Subjects breathed air with PETCO2 normalized at 38 mmHg. An increase in PETCO2 of 15% above baseline, whilst maintaining normoxia, was then implemented for 20 minutes and then PETCO2 was returned to baseline conditions for 10 minutes. Retinal and ONH hemodynamic measurements were performed using the CLBF and HRF in random order across sessions.  Chapter 6: Retinal arteriolar vascular reactivity was assessed in patients with uPOAG, pPOAG (defined by the occurrence of optic disc hemorrhage within the past 24 months) and controls during normoxic hypercapnia. Using the automated gas flow controller, patients breathed air for 10 mins and PETCO2 was maintained at 38mmHg. Following this normoxic hypercapnia (a 15% increase in PETCO2 while PETO2 was maintained at resting levels) was induced for 15 mins and then for the last 10 mins PETCO2 was returned to baseline (post-hypercapnia) to establish recovery blood flow values. Retinal arteriolar diameter, blood velocity and blood flow was assessed using the CLBF in both patient groups and controls. A similar paradigm was repeated in the newly treated POAG group (ntPOAG, i.e. after treatment with 2% Dorzolamide, twice daily for 2 weeks).  Chapter 7: Blood samples were collected from the cubital vein of all participants (uPOAG, pPOAG, ntPOAG and controls) during baseline conditions (PETCO2=38mmHg) and then during normoxic hypercapnia (i.e. a 15% increase in PETCO2 relative to the baseline) using the paradigm described for Chapter 6. ET-1 and cGMP was assessed using immunoassay. Results  Chapter 3: The group mean nasal macula capillary blood flow increased from 127.17 a.u. (SD 32.59) at baseline to 151.22 a.u. (SD 36.67) during hypercapnia (p=0.028), while foveal blood flow increased from 92.71 a.u. (SD 28.07) to 107.39 a.u. (SD 34.43) (p=0.042). There was a concomitant and uncontrolled +13% increase in the group mean PETO2 during the hypercapnic provocation of +14% increase in PETCO2.  Chapter 4: Retinal arteriolar diameter, blood velocity and blood flow increased by 3.2% (p=0.0045), 26.4% (p<0.0001) and 34.9% (p<0.0001), respectively during hypercapnia. There was a stable ¬+12% increase in PETCO2 during hypercapnia and a concomitant -6% decrease in PETO2.  Chapter 5: Using an automated gas flow controller the co-efficient of repeatability (COR) was 5% of the average PETCO2 at baseline and during normoxic hypercapnia. The COR for PETO2 was 10% and 7% of the average PETO2 at baseline and during normoxic hypercapnia, respectively. Group mean PETCO2 increased by approximately +14.4% and there was only a +4.3% increase in PETO2 during hypercapnia across both study sessions. Retinal arteriolar hemodynamics increased during hypercapnia (p<0.001). Similarly, there was an increase in the capillary blood flow of the temporal rim of the ONH (p<0.001), nasal macula (p<0.001) and foveal areas (p<0.006) during hypercapnia. A non-significant trend for capillary blood flow to increase in the macula temporal area (+8.2%) was noted. In terms of percentage change of blood flow, retinal capillary vascular reactivity (i.e. all 4 analyzed areas = 22.4%) was similar to the magnitude of arteriolar (= 24.9%) vascular reactivity.  Chapter 6: Retinal arteriolar diameter, blood velocity and flow did not increase during normoxic hypercapnia in uPOAG compared to controls. Diameter and blood velocity did not change in pPOAG during normoxic hypercapnia but there was a significant increase in blood flow (+9.1%, p=0.030). After treatment with 2% Dorzolamide for 2 weeks there was a 3% (p=0.040), 19% (p<0.001) and 26% (p<0.001) increase in diameter, velocity and flow, respectively, in the ntPOAG group. Group mean PETCO2 increased by approximately +15% in all the groups and there was only a +3% increase in PETO2 during hypercapnia.  Chapter 7: Plasma ET-1 levels were significantly different across groups at baseline (one way ANOVA; p=0.0012) and this was repeated during normoxic hypercapnia (one way ANOVA; p=0.0014). ET-1 levels were lower in uPOAG compared to pPOAG and controls at baseline and during normoxic hypercapnia (Tukey’s honestly significant difference test). Similarly, ntPOAG group also showed lower ET-1 levels compared to the pPOAG and controls at baseline and during normoxic hypercapnia (Tukey’s honestly significant difference test). The cGMP at baseline and during normoxic hypercapnia across all groups was not different. In the control group, the change in ET-1 during normoxic hypercapnia was negatively correlated with change in retinal arteriolar blood flow (r = -0.52, p=0.04), that is, as the change in ET-1 reduced, the change in blood flow increased. A weak correlation was noted between change in cGMP during normoxic hypercapnia and the change in arteriolar blood flow (r = +0.45, p=0.08). Conclusions  Chapter 3: Hypercapnia resulted in a quantifiable capillary vascular reactivity response in 2 of the 3 assessed retinal locations (i.e., nasal macula and fovea). There was no vascular reactivity response of the ONH. It is critical to minimise the concomitant change in PETO2 during hypercapnia in order to obtain robust vascular reactivity responses.  Chapter 4: A technique to comprehensively assess vascular reactivity during stable and sustained hypercapnia was described. Retinal arteriolar diameter, blood velocity and blood flow increased in response to hypercapnia. The vascular reactivity results of this study served as a reference for future studies using the hypercapnic provocation and CLBF. Also, the concomitant change in PETO2 using the partial rebreathing technique was reduced compared to the manual addition of CO2 technique described in Chapter 3 but was still greater than optimal.  Chapter 5: A new automated gas flow controller was used to induce standardised normoxic, or isoxic, hypercapnia. The magnitude of vascular reactivity in both retinal arterioles and capillaries in response to the new hypercapnic stimulus was robust compared to the previous stimuli. There was a clear ONH vascular reactivity response in this study, unlike the result attained in Chapter 3. Although theoretically it is predictable that the percent magnitude of vascular reactivity of the arterioles and capillaries should be similar, this is the first study to show that they are indeed comparable. The magnitude of hypercapnia was repeatable and the concomitant change in PETO2 was minimal and physiologically insignificant.  Chapter 6: The normal response of the retinal arterioles and capillaries to normoxic hypercapnia is impaired in both uPOAG and pPOAG compared to controls. Short term treatment with 2% topical Dorzolamide for two weeks improved retinal vascular reactivity in ntPOAG. However, it is still unclear whether this improvement is a direct effect of Dorzolamide or as a secondary effect of the decrease in intraocular pressure (IOP).  Chapter 7: We found a reduction in the plasma ET-1 at baseline and during normoxic hypercapnia in the uPOAG and in the ntPOAG groups. This is the first study to show a lower plasma ET-1 level in uPOAG. The fact that this finding was repeated after 2 weeks treatment with Dorzolamide in the ntPOAG group further validates these results. It also suggests that Dorzolamide treatment does not impact ET-1 and cGMP measures, although it clearly results in an improvement of vascular reactivity. Correlation results suggest that as the change in ET-1 reduced during normoxic hypercapnia, the change in blood flow increased in the controls.