Motivation - Brain-derived neurotrophic factor (BDNF) is a protein complex, synthesised and secreted mainly by the central nervous system and is involved in neuronal maintenance. Research suggests that BDNF is implicated in various neurological and psychiatric diseases, while recent evidence suggests a role for the neurotrophin on the periphery as well. Indeed, the specific functional role of BDNF and its action mechanism in the cardiovascular system, especially in that of Africans, is yet to be determined. The cardiovascular health profile of black South Africans is a major concern as research has shown that this group suffers from an array of cardiovascular risk factors that may result in organ damage. Sub-clinical atherosclerosis or structural endothelial dysfunction contributes to ever-increasing morbidity and mortality in the world. However, no studies regarding the associations between BDNF and structural vascular disease have been undertaken relating to black African participants. Objectives - The objective of this study was to determine whether BDNF is associated with changes in ambulatory blood pressure (BP) and whether a relationship between BDNF and structural endothelial dysfunction exists in black African male and female participants, determined by cross sectional wall area (CSWA) and albumin:creatinine ratio (ACR). Methodology - The study included 172 black African teachers (82 males and 90 females) who were employed by the Kenneth Kaunda Education district of the North-West Province, South Africa. Ambulatory blood pressure recordings were obtained with the use of a Meditech CE120 CardioTens ® apparatus. Blood pressure readings were measured at 30 min intervals during the day and 60 min intervals during the night. Anthropometric measurements were performed in triplicate by registered level II anthropometrists according to standardised procedures. A high-resolution ultrasound scan with carotid intima-media thickness (CIMT) images from at least two optimal angles of the left and right common carotid artery were obtained using a SonoSite Micromaxx ultrasound system. The lumen diameter between the near and far wall of the lumen-intima interface and the averages of both the left and right common carotid arteries were calculated. Subsequently, the carotid cross-sectional wall area (CSWA) was calculated. Participants, who fasted overnight, provided eight-hour blood and urine samples to determine serum BDNF and metabolic markers, for example, hyperglycaemia (HbA1c) and gamma glutamyl transferase (GGT). Urinary albumin and creatinine levels were determined by means of a turbidimetric method with the use of a Unicel DXC 800 analyser from Beckman and Coulter (Germany) and expressed as a ratio between albumin and creatinine (ACR). BDNF median split x Gender interaction effects for structural ED justified stratification of BDNF into low and high (≤ / > 1.37 ng/ml) gender groups. Results and Conclusion - On average, male participants were overweight (BMI 25-30kg/m2) and abused more alcohol.21 African men revealed a vulnerable cardiometabolic profile with values exceeding cut–points (European Society of Hypertension). These men demonstrated increased acute and chronic glucose (HbA1c) levels indicating a pre-diabetic state; as well as a disturbed lipid profile with lower HdL and increased triglycerides. Overall BDNF levels were lower than reference ranges (6.97 – 42.6 ng/ml). The men revealed mean lower BDNF levels, ambulatory BP values exceeding guideline cut-points (ambulatory SBP > 130mmHg; DBP > 80mmHg) as well as a hypertensive state compared to their female counterparts. Pertaining to structural endothelial dysfunction, the mean ACR value in men exceeded normal laboratory values (< 3.5mg/mmol). The African women displayed an obese state with low grade inflammation (CRP, 12.27 ± 11.67mg/l). A single two-way ANCOVA interaction on main effects (BDNF median split x Gender) demonstrated significant interaction for CIMTf [F (1,164); 3.99, p=0.05] and cholesterol [F (1,164); 4.12, p=0.05]. Therefore, a median split approach was followed which stratified gender groups into lower (≤ 1.37 ng/ml) and higher BDNF levels (>1.37 ng/ml). The low BDNF men revealed higher cholesterol than the high BDNF group, independent of BMI and age. Only the low BDNF women indicated significantly higher values for structural vascular markers (p< 0.05) than the high BDNF female group. In conclusion, we accept our hypothesis, as hypertrophic remodelling of the carotid artery was associated with lower BDNF levels. This may imply attenuated or possibly down-regulated BDNF levels acting as a compensatory mechanism for the mean higher BP levels. In women, metabolic risk and hypertrophic remodelling were evident within higher circulating levels of BDNF, underpinning different underlying mechanisms for impaired neurotrophin health in men and women. Novel findings of BDNF revealed the impact of central neural regulation on the circulatory system, which may contribute to cardiometabolic risk in Africans. / MSc (Physiology), North-West University, Potchefstroom Campus, 2014

Stroke is the 2nd leading cause of death in the UK and worldwide. 150,000 people have a stroke each year in the UK (ischaemic stroke being the most common) and a significant proportion of NHS resources go towards the treatment of these individuals (~£2.8 billion). Twin and family history studies have shown that having affected relatives makes you between 30 and 76% more likely to suffer a stroke, suggesting that there is a genetic component to the disease. So far, no genes have been convincingly associated with stroke. Intermediate traits may be useful tools for identifying genetic factors in complex disease. For stroke, two commonly used intermediate traits are carotid intima-media thickness (CIMT) and white matter hyperintensities (WMHs), which both show high heritabilities. These traits have both been studied widely for associations with many candidate gene polymorphisms. In this thesis I systematically reviewed the literature for all genetic association studies of these two traits. Where particular associations have been studied in large numbers I meta-analysed the available data, developing novel methods for meta-analysis of genetic association data. I found there was substantial heterogeneity and small study bias in the literature and most polymorphisms have still been studied in too small numbers to make accurate conclusions. Apolipoprotein E (APOE) ε is the only polymorphism which shows a consistent association with CIMT, even when only the largest studies are analysed (MD 8μm (95% CI 6 to 11) between E4 and E3, and E3 and E2). No polymorphism has shown a convincing association with WMHs and interestingly APOE appears unlikely to be associated with this trait. This is consistent with previous work that shows that APOE is associated with large artery but not small artery stroke. Taking this hypothesis I attempted to investigate the association of APOE comparing patients who have had a large artery stroke with those who have had a small artery stroke in the Edinburgh Stroke Study cohort. However, genotyping of this polymorphism failed and I present investigatory analyses of problems from the genotyping laboratory.

Multiphase flows occurring in pipelines with a serpentine configuration is an important phenomenon, which can be encountered in heat exchangers used in a variety of industrial processes. More specifically, in many industrial units such as a large cracking furnace in a refinery, the tubes are arranged in a serpentine manner and are relatively short. As flow negotiates round the 180o bend at the ends of the tubes, the generated centrifugal force could cause flow maldistribution creating local dry spots, where no steady liquid film is formed on the adjacent straight sections of the pipe. As a result, events including coking, cracking and overheating of heat transfer surfaces may occur and lead to frequent shutdown of the facilities. Consequently, this could increase operating costs and reduce production revenue. Thus, it is desirable to know the effect that the bends exert on the flow in the straight part of the pipe. Apart from this, knowledge of the bend effects on the flows in the pipeline could also be important for the design of other pipelines for gas/liquid transport, e.g. offshore gas and oil pipelines. Quite a large number of studies have been found in the literature. The majority of them were for two-phase flow with small diameter pipes (i.d. ≤ 50 mm). However, studies with large diameter pipes (i.d. ≥ 100 mm), have increasingly been considered in recent years as problems related to large diameter vertical pipes are being encountered more and more often in industrial situations. This thesis studies the effect of 180o bends on the characteristics and development of gas-liquid two-phase flows in large diameter downward and upward pipes. The study particularly focuses on the influence of serpentine configuration on flow structure, cross-sectional void distribution and circumferential liquid film profiles and their development along the downward and upward sections. It was found that both the top and bottom bends have considerable impacts on flow behaviour, although to varying degrees. These impacts were highly dependent on the air and water flow rates. For sufficient flow rates, the bends were observed to create flow maldistribution in the adjacent straight section, due to the effects of centrifugal force. The air moved towards the inner zone of the bend and the water towards the outer zone, while a lesser quantity of water was identified on the other surfaces of the pipe. Investigation of the film thickness development in the downward and upward sections showed that, the liquid film behaviour close to the bends was significantly different from those located further away. This can be attributed to the centrifugal force of the bends. Examination of the power spectral density (PSD) along the downward and upward sections showed that, the shape of PSD located in the adjacent section to the bends, was substantially different from those located further away. Furthermore, several flow regime maps were generated which showed that, in addition to bubbly, intermittent and annular flows, unstable flows existed along the upward section, particularly for low gas and water flow rates. In this study it was found that, the lower bend was periodically blocked by the liquid and then blown through by the accumulated air. The data obtained from this study were compared with different theoretical correlations found in the existing literature. Some discrepancy between the results of the current study and those of previous published materials was noted. Updated correlations were presented which provided well results when they applied for the data obtained from the current study and previous studies.

The gas assisted injection moulding process is an important extension to conventional injection moulding. Gas assist can be applied in a number of ways, but here the penetration of a gas bubble through the polymer melt is of interest. A 3D fi nite element implementation of a pseudo concentration method is employed to simulate the primary penetration of the gas bubble. The wall thickness prediction is an important result since the extent of bubble penetration is sensitive to the remaining melt fraction. A number of methods for experimental measurement are developed to measure characteristics of the gas assisted injection moulding process dynamics and product. Key process variables, on an industrial gas-assist machine, were measured and analysed, leading to an empirical model for wall thickness prediction. Gas delay time and injection velocity are shown to be most influential in controlling residual wall thickness. Simulation results are evaluated against the empirical model. The trends observed, for simulation and experiment, in wall thickness after changes in process variable settings are found to agree qualitatively. The wall thickness prediction is found to be within 10% of the experimentally obtained measurements.

The Mechanistic Empirical Pavement Design Guide (MEPDG) developed by the National Cooperative Highway Research Program (NCHRP) project 1-37A, is a very powerful tool for the design and analysis of pavements. The designer utilizes an iterative process to select design parameters and predict performance, if the performance is not acceptable they must change design parameters until an acceptable design is achieved. The design process has more than 100 input parameters across many areas, including, climatic conditions, material properties for each layer of the pavement, and information about the truck traffic anticipated. Many of these parameters are known to have insignificant influence on the predicted performance During the development of this procedure, input parameter sensitivity analysis varied a single input parameter while holding other parameters constant, which does not allow for the interaction between specific variables across the entire parameter space. A portion of this research identified a methodology of global sensitivity analysis of the procedure using random sampling techniques across the entire input parameter space. This analysis was used to select the most influential input parameters which could be used in a streamlined design process. This streamlined method has been developed using Multiple Adaptive Regression Splines (MARS) to develop predictive models derived from a series of actual pavement design solutions from the design software provided by NCHRP. Two different model structures have been developed, one being a series of models which predict pavement distress (rutting, fatigue cracking, faulting and IRI), the second being a forward solution to predict a pavement thickness given a desired level of distress. These thickness prediction models could be developed for any subset of MEPDG solutions desired, such as typical designs within a given state or climatic zone. These solutions could then be modeled with the MARS process to produce am “Efficient Design Solution” of pavement thickness and performance predictions. The procedure developed has the potential to significantly improve the efficiency of pavement designers by allowing them to look at many different design scenarios prior to selecting a design for final analysis.

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Image-guided surgeries employ advanced imaging and computing technologies to assist the surgeon when direct visualization is inadequate or unavailable. As modern surgeries continue to move toward minimally invasive procedures, tracked ultrasound (US), an emerging technology that uniquely combines US imaging and position tracking, has been increasingly used for intraoperative guidance in surgical interventions. The intrinsic accuracy of a tracked US system is primarily determined by a unique procedure called ``probe calibration", where a spatial registration between the coordinate systems of the transducer (provided by a tracking device affixed to the probe) and the US image plane must be established prior to imaging. Inaccurate system calibration causes misalignments between the US image and the surgical end-effectors, which may directly contribute to treatment failure. The probe calibration quality is further reduced by the "elevation beamwidth" or "slice thickness", a unique feature of the ultrasound beam pattern that gives rise to localization errors and imaging uncertainties. In this thesis, we aim to provide an automated, pure-computation-based, intraoperative calibration solution that also incorporates the slice thickness to improve the calibration accuracy, precision and reliability. The following contributions have been made during the course of this research. First, we have designed and developed an automated, freehand US calibration system with instant feedback on its calibration accuracy. The system was able to consistently achieve submillimeter accuracy with real-time performance. Furthermore, we have developed a novel beamwidth-weighted calibration framework (USB-FW) that incorporates US slice thickness to improve the estimation of calibration parameters. The new framework provides an effective means of quality control for calibration results. Extensive phantom validation demonstrated that USB-FW introduces statistically significant reduction (p = 0.001) in the calibration errors and produces calibration outcomes that are less variable than a conventional, non-beamwidth-weighted calibration. Finally, we were the first to introduce an automated, intraoperative Transrectal Ultrasound (TRUS) calibration technology for needle guidance in prostate brachytherapy. Our tests with multiple commercial TRUS scanners and brachytherapy stepper systems demonstrated that the proposed method is practical in use and can achieve high calibration accuracy, precision and robustness. / Thesis (Ph.D, Computing) -- Queen's University, 2012-10-22 16:18:55.439

Tree-ring based climate reconstructions have been critical for understanding past variability and recent trends in climate worldwide, but they are scarce in Australia. This is particularly the case for temperature: only one tree-ring width based temperature reconstruction – based on Huon Pine trees from Mt Read, Tasmania – exists for Australia. Here, we investigate whether additional tree- ring parameters derived from Athrotaxis cupressoides trees growing in the same region have potential to provide robust proxy records of past temperature variability. We measured wood properties, including tree-ring width (TRW), mean density, mean cell wall thickness (CWT), and tracheid radial diameter (TRD) of annual growth rings in Athrotaxis cupressoides, a long-lived, high-elevation conifer in central Tasmania, Australia. Mean density and CWT were strongly and negatively correlated with summer temperatures. In contrast, the summer temperature signal in TRW was weakly positive. The strongest climate signal in any of the tree-ring parameters was maximum temperature in January (mid-summer; JanTmax) and we chose this as the target climate variable for reconstruction. The model that explained most of the variance in JanTmax was based on TRW and mean density as predictors. TRW and mean density provided complementary proxies with mean density showing greater high-frequency (inter-annual to multi-year) variability and TRW showing more low-frequency (decadal to centennial-scale) variability. The final reconstruction model is robust, explaining 55% of the variance in JanTmax, and was used to reconstruct JanTmax for the last five centuries (1530–2010 C.E.). The reconstruction suggests that the most recent 60 years have been warmer than average in the context of the last ca. 500 years. This unusually warm period is likely linked to a coincident increase in the intensity of the subtropical ridge and dominance of the positive phase of the Southern Annular Mode in summer, which weaken the influence of the band of prevailing westerly winds and storms on Tasmanian climate. Our findings indicate that wood properties, such as mean density, are likely to provide significant contributions toward the development of robust climate reconstructions in the Southern Hemisphere and thus toward an improved understanding of past climate in Australasia.