Non-invasive assessment of tear film surface quality

The tear film plays an important role preserving the health of the ocular surface and maintaining the optimal refractive power of the cornea. Moreover dry eye syndrome is one of the most commonly reported eye health problems. This syndrome is caused by abnormalities in the properties of the tear film. Current clinical tools to assess the tear film properties have shown certain limitations. The traditional invasive methods for the assessment of tear film quality, which are used by most clinicians, have been criticized for the lack of reliability and/or repeatability. A range of non-invasive methods of tear assessment have been investigated, but also present limitations. Hence no “gold standard” test is currently available to assess the tear film integrity. Therefore, improving techniques for the assessment of the tear film quality is of clinical significance and the main motivation for the work described in this thesis. In this study the tear film surface quality (TFSQ) changes were investigated by means of high-speed videokeratoscopy (HSV). In this technique, a set of concentric rings formed in an illuminated cone or a bowl is projected on the anterior cornea and their reflection from the ocular surface imaged on a charge-coupled device (CCD). The reflection of the light is produced in the outer most layer of the cornea, the tear film. Hence, when the tear film is smooth the reflected image presents a well structure pattern. In contrast, when the tear film surface presents irregularities, the pattern also becomes irregular due to the light scatter and deviation of the reflected light. The videokeratoscope provides an estimate of the corneal topography associated with each Placido disk image. Topographical estimates, which have been used in the past to quantify tear film changes, may not always be suitable for the evaluation of all the dynamic phases of the tear film. However the Placido disk image itself, which contains the reflected pattern, may be more appropriate to assess the tear film dynamics. A set of novel routines have been purposely developed to quantify the changes of the reflected pattern and to extract a time series estimate of the TFSQ from the video recording. The routine extracts from each frame of the video recording a maximized area of analysis. In this area a metric of the TFSQ is calculated. Initially two metrics based on the Gabor filter and Gaussian gradient-based techniques, were used to quantify the consistency of the pattern’s local orientation as a metric of TFSQ. These metrics have helped to demonstrate the applicability of HSV to assess the tear film, and the influence of contact lens wear on TFSQ. The results suggest that the dynamic-area analysis method of HSV was able to distinguish and quantify the subtle, but systematic degradation of tear film surface quality in the inter-blink interval in contact lens wear. It was also able to clearly show a difference between bare eye and contact lens wearing conditions. Thus, the HSV method appears to be a useful technique for quantitatively investigating the effects of contact lens wear on the TFSQ. Subsequently a larger clinical study was conducted to perform a comparison between HSV and two other non-invasive techniques, lateral shearing interferometry (LSI) and dynamic wavefront sensing (DWS). Of these non-invasive techniques, the HSV appeared to be the most precise method for measuring TFSQ, by virtue of its lower coefficient of variation. While the LSI appears to be the most sensitive method for analyzing the tear build-up time (TBUT). The capability of each of the non-invasive methods to discriminate dry eye from normal subjects was also investigated. The receiver operating characteristic (ROC) curves were calculated to assess the ability of each method to predict dry eye syndrome. The LSI technique gave the best results under both natural blinking conditions and in suppressed blinking conditions, which was closely followed by HSV. The DWS did not perform as well as LSI or HSV. The main limitation of the HSV technique, which was identified during the former clinical study, was the lack of the sensitivity to quantify the build-up/formation phase of the tear film cycle. For that reason an extra metric based on image transformation and block processing was proposed. In this metric, the area of analysis was transformed from Cartesian to Polar coordinates, converting the concentric circles pattern into a quasi-straight lines image in which a block statistics value was extracted. This metric has shown better sensitivity under low pattern disturbance as well as has improved the performance of the ROC curves. Additionally a theoretical study, based on ray-tracing techniques and topographical models of the tear film, was proposed to fully comprehend the HSV measurement and the instrument’s potential limitations. Of special interested was the assessment of the instrument’s sensitivity under subtle topographic changes. The theoretical simulations have helped to provide some understanding on the tear film dynamics, for instance the model extracted for the build-up phase has helped to provide some insight into the dynamics during this initial phase. Finally some aspects of the mathematical modeling of TFSQ time series have been reported in this thesis. Over the years, different functions have been used to model the time series as well as to extract the key clinical parameters (i.e., timing). Unfortunately those techniques to model the tear film time series do not simultaneously consider the underlying physiological mechanism and the parameter extraction methods. A set of guidelines are proposed to meet both criteria. Special attention was given to a commonly used fit, the polynomial function, and considerations to select the appropriate model order to ensure the true derivative of the signal is accurately represented. The work described in this thesis has shown the potential of using high-speed videokeratoscopy to assess tear film surface quality. A set of novel image and signal processing techniques have been proposed to quantify different aspects of the tear film assessment, analysis and modeling. The dynamic-area HSV has shown good performance in a broad range of conditions (i.e., contact lens, normal and dry eye subjects). As a result, this technique could be a useful clinical tool to assess tear film surface quality in the future.

Bond characteristics between CFRP and steel plates in double strap joints

This paper describes a series of double strap shear tests loaded in tension to investigate the bond between CFRP sheets and steel plates. Both normal modulus (240 GPa) and high modulus (640 GPa) CFRPs were used in the test program. Strain gauges were mounted to capture the strain distribution along the CFRP length. Different failure modes were observed for joints with normal modulus CFRP and those with high modulus CFRP. The strain distribution along the CFRP length was found to be similar for the two cases. A shorter effective bond length was obtained for joints with high modulus CFRP whereas larger ultimate load carrying capacity can be achieved for joints with normal modulus CFRP when the bond length is long enough. The Hart-Smith Model was modified to predict the effective bond length and ultimate load carrying capacity of joints between the normal modulus CFRP and steel plates. The Multilayer Distribution Model developed by the authors was modified to predict the load carrying capacity of joints between the high modulus CFRP and steel plates. The predicted values agreed well with experimental ones.

Dynamic axial ligand-site exchange in facially discriminated ruthenium(II) carbonyl and rhodium(III) halide metalloporphyrins

For a series of six-coordinate Ru(II)(CO)L or Rh(III)(X–)L porphyrins which are facially differentiated by having a naphthoquinol- or hydroquinol-containing strap across one face, we show that ligand migration from one face to the other can occur under mild conditions, and that ligand site preference is dependent on the nature of L and X–. For bulky nitrogen-based ligands, the strap can be displaced sideways to accommodate the ligand on the same side as the strap. For the ligand pyrazine, we show 1 H NMR evidence for monodentate and bidentate binding modes on both faces, dependent on ligand concentration and metalloporphyrin structure, and that inter-facial migration is rapid under normal conditions. For monodentate substituted pyridine ligands there is a site dependence on structure, and we show clear evidence of dynamic ligand migration through a series of ligand exchange reactions.

Stochastic chemical kinetics and the quasi-steady-state assumption : application to the stochastic simulation algorithm and chemical master equation

Recently the application of the quasi-steady-state approximation (QSSA) to the stochastic simulation algorithm (SSA) was suggested for the purpose of speeding up stochastic simulations of chemical systems that involve both relatively fast and slow chemical reactions [Rao and Arkin, J. Chem. Phys. 118, 4999 (2003)] and further work has led to the nested and slow-scale SSA. Improved numerical efficiency is obtained by respecting the vastly different time scales characterizing the system and then by advancing only the slow reactions exactly, based on a suitable approximation to the fast reactions. We considerably extend these works by applying the QSSA to numerical methods for the direct solution of the chemical master equation (CME) and, in particular, to the finite state projection algorithm [Munsky and Khammash, J. Chem. Phys. 124, 044104 (2006)], in conjunction with Krylov methods. In addition, we point out some important connections to the literature on the (deterministic) total QSSA (tQSSA) and place the stochastic analogue of the QSSA within the more general framework of aggregation of Markov processes. We demonstrate the new methods on four examples: Michaelis–Menten enzyme kinetics, double phosphorylation, the Goldbeter–Koshland switch, and the mitogen activated protein kinase cascade. Overall, we report dramatic improvements by applying the tQSSA to the CME solver.

Measuring the effectiveness of computer-based scientific visualisations for conceptual development in Australian chemistry classrooms

Visual modes of representation have always been very important in science and science education. Interactive computer-based animations and simulations offer new visual resources for chemistry education. Many studies have shown that students enjoy learning with visualisations but few have explored how learning outcomes compare when teaching with or without visualisations. This study employs a quasi-experimental crossover research design and quantitative methods to measure the educational effectiveness - defined as level of conceptual development on the part of students - of using computer-based scientific visualisations versus teaching without visualisations in teaching chemistry. In addition to finding that teaching with visualisations offered outcomes that were not significantly different from teaching without visualisations, the study also explored differences in outcomes for male and female students, students with different learning styles (visual, aural, kinesthetic) and students of differing levels of academic ability.

The flammability of metallic materials in normal and reduced gravity

Metallic materials exposed to oxygen-enriched atmospheres – as commonly used in the medical, aerospace, aviation and numerous chemical processing industries – represent a significant fire hazard which must be addressed during design, maintenance and operation. Hence, accurate knowledge of metallic materials flammability is required. Reduced gravity (i.e. space-based) operations present additional unique concerns, where the absence of gravity must also be taken into account. The flammability of metallic materials has historically been quantified using three standardised test methods developed by NASA, ASTM and ISO. These tests typically involve the forceful (promoted) ignition of a test sample (typically a 3.2 mm diameter cylindrical rod) in pressurised oxygen. A test sample is defined as flammable when it undergoes burning that is independent of the ignition process utilised. In the standardised tests, this is indicated by the propagation of burning further than a defined amount, or „burn criterion.. The burn criterion in use at the onset of this project was arbitrarily selected, and did not accurately reflect the length a sample must burn in order to be burning independent of the ignition event and, in some cases, required complete consumption of the test sample for a metallic material to be considered flammable. It has been demonstrated that a) a metallic material.s propensity to support burning is altered by any increase in test sample temperature greater than ~250-300 oC and b) promoted ignition causes an increase in temperature of the test sample in the region closest to the igniter, a region referred to as the Heat Affected Zone (HAZ). If a test sample continues to burn past the HAZ (where the HAZ is defined as the region of the test sample above the igniter that undergoes an increase in temperature of greater than or equal to 250 oC by the end of the ignition event), it is burning independent of the igniter, and should be considered flammable. The extent of the HAZ, therefore, can be used to justify the selection of the burn criterion. A two dimensional mathematical model was developed in order to predict the extent of the HAZ created in a standard test sample by a typical igniter. The model was validated against previous theoretical and experimental work performed in collaboration with NASA, and then used to predict the extent of the HAZ for different metallic materials in several configurations. The extent of HAZ predicted varied significantly, ranging from ~2-27 mm depending on the test sample thermal properties and test conditions (i.e. pressure). The magnitude of the HAZ was found to increase with increasing thermal diffusivity, and decreasing pressure (due to slower ignition times). Based upon the findings of this work, a new burn criterion requiring 30 mm of the test sample to be consumed (from the top of the ignition promoter) was recommended and validated. This new burn criterion was subsequently included in the latest revision of the ASTM G124 and NASA 6001B international test standards that are used to evaluate metallic material flammability in oxygen. These revisions also have the added benefit of enabling the conduct of reduced gravity metallic material flammability testing in strict accordance with the ASTM G124 standard, allowing measurement and comparison of the relative flammability (i.e. Lowest Burn Pressure (LBP), Highest No-Burn Pressure (HNBP) and average Regression Rate of the Melting Interface(RRMI)) of metallic materials in normal and reduced gravity, as well as determination of the applicability of normal gravity test results to reduced gravity use environments. This is important, as currently most space-based applications will typically use normal gravity information in order to qualify systems and/or components for reduced gravity use. This is shown here to be non-conservative for metallic materials which are more flammable in reduced gravity. The flammability of two metallic materials, Inconel® 718 and 316 stainless steel (both commonly used to manufacture components for oxygen service in both terrestrial and space-based systems) was evaluated in normal and reduced gravity using the new ASTM G124-10 test standard. This allowed direct comparison of the flammability of the two metallic materials in normal gravity and reduced gravity respectively. The results of this work clearly show, for the first time, that metallic materials are more flammable in reduced gravity than in normal gravity when testing is conducted as described in the ASTM G124-10 test standard. This was shown to be the case in terms of both higher regression rates (i.e. faster consumption of the test sample – fuel), and burning at lower pressures in reduced gravity. Specifically, it was found that the LBP for 3.2 mm diameter Inconel® 718 and 316 stainless steel test samples decreased by 50% from 3.45 MPa (500 psia) in normal gravity to 1.72 MPa (250 psia) in reduced gravity for the Inconel® 718, and 25% from 3.45 MPa (500 psia) in normal gravity to 2.76 MPa (400 psia) in reduced gravity for the 316 stainless steel. The average RRMI increased by factors of 2.2 (27.2 mm/s in 2.24 MPa (325 psia) oxygen in reduced gravity compared to 12.8 mm/s in 4.48 MPa (650 psia) oxygen in normal gravity) for the Inconel® 718 and 1.6 (15.0 mm/s in 2.76 MPa (400 psia) oxygen in reduced gravity compared to 9.5 mm/s in 5.17 MPa (750 psia) oxygen in normal gravity) for the 316 stainless steel. Reasons for the increased flammability of metallic materials in reduced gravity compared to normal gravity are discussed, based upon the observations made during reduced gravity testing and previous work. Finally, the implications (for fire safety and engineering applications) of these results are presented and discussed, in particular, examining methods for mitigating the risk of a fire in reduced gravity.