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.

Road safety issues for older road users : CARRS-Q Monograph 1

[Selection of papers from the Older Road User Safety Symposium, 26 November 2000, Brisbane, Australia.]----- This publication is a selection of papers on older road user safety which were presented at the Older Road User Safety Symposium on Sunday 26 November 2000 at the Sheraton Brisbane Hotel, Queensland, Australia. The Symposium was held on the day before Australia’s annual Road Safety Research, Policing and Education Conference, which provided an opportunity to garner both presenters and participants from the wider road safety community in Australia. Road safety is a large and diverse area of scholarship and practice, and many disciplines are drawn on in the processes of understanding and addressing road safety problems. The safety of older road users is no different. As this selection shows, work on older road user safety can be informed by demography, research on the mental and physical effects of ageing, social research on older people as road users, evaluation of educational and behavioural interventions, road crash analysis, engineering research and practice, and reviews of policy approaches within Australia and elsewhere. It is possible to summarise these into four constellations, which are reflected in the papers selected for this publication: social impacts and responses; physical and cognitive capability; specific road use performance; and environment/ecology. Though three years have passed since the Symposium, the issues raised in these papers remain current.

Sonic loom (Volume 1)

Sonic Loom is a purpose built classroom tool for teachers and students of drama that will enable them to explore the use of music in live performance in theory and practice. It’s intended as a resource for drama classrooms, to encourage communication and exchange about the way music works on us so we can find new ways we can make it work for us. Working to consciously attend to music and how it’s used, particularly in cinema (as a popular way in to styles of western theatre and live performance) will allow students and teachers to use music in more subtle and complex ways an aid to narrative in performance. Sonic Loom encourages active listening, (aided but not encumbered by traditional musicology) so students (and teachers) can develop a ‘critical ear’ in the transformation and adaptation of music for their own artistic purposes, whether it’s soundtracking existing scene work, or acting as a pre-text for scenes which have yet to be created.

Analysis of Object-Specific Authorization Protocol (OSAP) using coloured petri nets - Version 1.0

Analyzing security protocols is an ongoing research in the last years. Different types of tools are developed to make the analysis process more precise, fast and easy. These tools consider security protocols as black boxes that can not easily be composed. It is difficult or impossible to do a low-level analysis or combine different tools with each other using these tools. This research uses Coloured Petri Nets (CPN) to analyze OSAP trusted computing protocol. The OSAP protocol is modeled in different levels and it is analyzed using state space method. The produced model can be combined with other trusted computing protocols in future works.

Diagnosing dry eye with dynamic-area high-speed videokeratoscopy

Dry eye syndrome is one of the most commonly reported eye health conditions. Dynamic-area highspeed videokeratoscopy (DA-HSV) represents a promising alternative to the most invasive clinical methods for the assessment of the tear film surface quality (TFSQ), particularly as Placido-disk videokeratoscopy is both relatively inexpensive and widely used for corneal topography assessment. Hence, improving this technique to diagnose dry eye is of clinical significance and the aim of this work. First, a novel ray-tracing model is proposed that simulates the formation of a Placido image. This model shows the relationship between tear film topography changes and the obtained Placido image and serves as a benchmark for the assessment of indicators of the ring’s regularity. Further, a novel block-feature TFSQ indicator is proposed for detecting dry eye from a series of DA-HSV measurements. The results of the new indicator evaluated on data from a retrospective clinical study, which contains 22 normal and 12 dry eyes, have shown a substantial improvement of the proposed technique to discriminate dry eye from normal tear film subjects. The best discrimination was obtained under suppressed blinking conditions. In conclusion,this work highlights the potential of the DA-HSV as a clinical tool to diagnose dry eye syndrome.

Functional role of cell surface CUB domain-containing protein 1 in tumour cell dissemination

The function of CUB domain-containing protein 1 (CDCP1), a recently described transmembrane protein expressed on the surface of hematopoietic stem cells and normal and malignant cells of different tissue origin, is not well defined. The contribution of CDCP1 to tumor metastasis was analyzed by using HeLa carcinoma cells overexpressing CDCP1 (HeLa-CDCP1) and a high-disseminating variant of prostate carcinoma PC-3 naturally expressing high levels of CDCP1 (PC3-hi/diss). CDCP1 expression rendered HeLa cells more aggressive in experimental metastasis in immunodeficient mice. Metastatic colonization by HeLa-CDCP1 was effectively inhibited with subtractive immunization-generated, CDCP1-specific monoclonal antibody (mAb) 41-2, suggesting that CDCP1 facilitates relatively late stages of the metastatic cascade. In the chick embryo model, time- and dose-dependent inhibition of HeLa-CDCP1 colonization by mAb 41-2 was analyzed quantitatively to determine when and where CDCP1 functions during metastasis. Quantitative PCR and immunohistochemical analyses indicated that CDCP1 facilitated tumor cell survival soon after vascular arrest. Live cell imaging showed that the function-blocking mechanism of mAb 41-2 involved enhancement of tumor cell apoptosis, confirmed by attenuation of mAb 41-2–mediated effects with the caspase inhibitor z-VAD-fmk. Under proapoptotic conditions in vitro, CDCP1 expression conferred HeLa-CDCP1 cells with resistance to doxorubicin-induced apoptosis, whereas ligation of CDCP1 with mAb 41-2 caused additional enhancement of the apoptotic response. The functional role of naturally expressed CDCP1 was shown by mAb 41-2–mediated inhibition of both experimental and spontaneous metastasis of PC3-hi/diss. These findings confirm that CDCP1 functions as an antiapoptotic molecule and indicate that during metastasis CDCP1 facilitates tumor cell survival likely during or soon after extravasation.

Managing wetlands sustainably as ecosystems : The contribution of the law (part 1)

The ways in which a society set standards of behaviour and of conduct for its members vary hugely. For example, accepted practices, recognised customs, spiritually or morally inspired norms, judicially declared rules, executively formulated edicts, formal legislative enactments or constitutionally embedded rights and duties. Whatever form they assume, these standards are the artificial construction of the human mind. Accordingly the law - whatever its form - can do no more and no less than regulate or set standards for human behaviour, human conduct, and human decision-making. The law cannot regulate the environment. It can only regulate human activities that impact directly or indirectly upon the environment. This applies as much to wetlands as components of the environment as it does to any other components of the environment or the environment at large. The capacity of the law to protect the environment and therefore wetlands is thus totally dependent upon the capacity of the law to regulate human behaviour, human conduct and human decision-making. At the same time the law needs to reflect the specific nature, functions and locations of wetlands. A wetland is an ecosystem by itself; it comprises a range of ecosystems within it; and it is part of a wider set of ecosystems. Hence, the significant ecological functions performed by wetlands. Then there are the benefits flowing to humans from wetlands. These may be social, economic, cultural, aesthetic, or a combination of some or of all of these. It is a challenge for a society acting through its legal system to find the appropriate balance between these ecological and these human values. But that is what sustainability requires.The ways in which a society set standards of behaviour and of conduct for its members vary hugely. For example, accepted practices, recognised customs, spiritually or morally inspired norms, judicially declared rules, executively formulated edicts, formal legislative enactments or constitutionally embedded rights and duties. Whatever form they assume, these standards are the artificial construction of the human mind. Accordingly the law - whatever its form - can do no more and no less than regulate or set standards for human behaviour, human conduct, and human decision-making. The law cannot regulate the environment. It can only regulate human activities that impact directly or indirectly upon the environment. This applies as much to wetlands as components of the environment as it does to any other components of the environment or the environment at large. The capacity of the law to protect the environment and therefore wetlands is thus totally dependent upon the capacity of the law to regulate human behaviour, human conduct and human decision-making. At the same time the law needs to reflect the specific nature, functions and locations of wetlands. A wetland is an ecosystem by itself; it comprises a range of ecosystems within it; and it is part of a wider set of ecosystems. Hence, the significant ecological functions performed by wetlands. Then there are the benefits flowing to humans from wetlands. These may be social, economic, cultural, aesthetic, or a combination of some or of all of these. It is a challenge for a society acting through its legal system to find the appropriate balance between these ecological and these human values. But that is what sustainability requires.

Halogen bonding between an isoindoline nitroxide and 1,4-diiodotetrafluorobenzene: new tools and tectons for self-assembling organic spin systems

Halogen bonding has been observed for the first time between an isoindoline nitroxide and an iodoperfluorocarbon (see figure), which cocrystallize to form a discrete 2:1 supramolecular compound in which NO.⋅⋅⋅I halogen bonding is the dominant intermolecular interaction. This illustrates the potential use of halogen bonding and isoindoline nitroxide tectons for the assembly of organic spin systems...