Introduction Menopause which is defined as a permanent physiological, or natural, cessation of menstrual cycle, plays an important role in the development of ocular surface dryness symptoms and there is an increased prevalence of dry eye in women, especially those aged over 50. Despite the high prevalence of dry eye in post-menopausal women (PMW), very few studies have been undertaken to understand dry eye disease in a group of PMW who are not on Hormone Replacement Therapy (HRT). Studies in the past on PMW have primarily focused on the relationship between HRT and dry eye. Hence, a series of studies were undertaken to understand the clinical aspects of dry eye and their relationship to a variety of tear film components, in a group of PMW with and without symptoms of dry eye. The specific aims of each chapter were as follows: • Chapter 4: To characterize symptoms of dry eye using questionnaires, namely Ocular Surface Disease Index Questionnaire© (OSDI) and the Indiana Dry Eye Questionnaire (DEQ). • Chapter 5: To characterize clinical signs and symptoms in participants who present with and without symptoms of dry eye. • Chapter 6: To compare tear osmolality and ferning patterns in participants with and without dry eye symptoms. • Chapter 7: To investigate the potential relationship between subjective symptoms and clinical signs with tear film lipocalin and lysozyme concentrations in participants with and without dry eye symptoms. • Chapter 8: To optimize a technique for the isolation of total RNA (ribo nucleic acid) and total protein derived from conjunctival epithelial cells collected via conjunctival impression cytology (CIC). • Chapter 9: To quantify the expression of MUC1 (mucin1) and MUC16 (mucin16) mRNA and protein and to investigate the potential relationship between mucin expression and tear film breakup time in a group of participants with and without dry eye symptoms. Methods • Chapter 4: Participants were categorized as being symptomatic or asymptomatic of dry eye based on their response to the OSDI questionnaire. These results were then compared to the DEQ, which has questions related to the frequency of ocular surface symptoms and their diurnal intensity. • Chapter 5: Non invasive tear breakup time (NITBUT) was evaluated using the ALCON Eyemap®. Tear volume was assessed using the Phenol Red Thread (PRT) test and bulbar conjunctival hyperemia was measured using objective (SpectraScan PR650© Spectrophotometer) and subjective (slit lamp) methods. • Chapter 6: Tears were collected via capillary tube. A freezing point depression osmometer was used to measure the osmolality of the tear film. The tear ferning test was performed and evaluated for the quality of ferning, based on the Rolando grading system. • Chapter 7: Tears were collected via capillary tube and an eye wash method. Tear lysozyme and lipocalin concentrations were determined via Western blotting. • Chapter 8: CIC was collected using either Millipore (MP) or Poly Ether Sulfone (PES) membranes. RNA and protein isolation was performed using two different RNA isolation techniques. Two methods of protein isolation from CIC discs were evaluated. RT-PCR of mRNA for MUC1 and western blotting of lipoxygenase type 2 protein (LOX2) was performed to confirm the collection of intact RNA and total protein respectively. • Chapter 9: Tears were collected via capillary tube and an eye wash method. CIC was collected using MP membrane. Expression of MUC1 and MUC16 mRNA was assessed via real time PCR. Expression of both membrane-bound and soluble MUC1 and MUC16 were quantified via Western blotting. Results • Chapter 4: The OSDI total score and sub scores for the Non Dry Eye (NDE) and Dry Eye (DE) groups were significantly different (NDE =7.43 ± 7.71 vs DE = 24.87 ± 13.89; p<0.001). The DEQ scores showed that the DE group exhibited a higher frequency and intensity of symptoms than the NDE group, which worsened as the day progressed (p<0.001). • Chapter 5: The DE group exhibited a significantly shorter NITBUT (5.3 ± 1.7 vs 7.0 ± 2.7 secs; p=0.0012). Tear volume was significantly lower for the DE group (19.3 ± 5.1mm vs. 16.3 ± 5.6mm; p=0.031). Bulbar hyperemia was significantly higher in the DE group for both objective (u’ = 0.285 ± 0.006 vs. 0.282 ± 0.006; p=0.005) and subjective techniques (48.4 ± 10.0 vs 40.6 ± 10.4; p=0.0011). • Chapter 6: Osmolality values in DE individuals were significantly higher than the NDE (328.1 ± 20.8 vs. 315.1 ± 11.3 mOsm/kg; p = 0.02). There was a significant difference between the DE and NDE participants for the ferning patterns (p = 0.019). No significant correlation between tear osmolality and tear ferning was noted (DE: r = 0.12; p > 0.05, NDE: r = -0.17; p > 0.05). • Chapter 7: No difference in tear lysozyme or lipocalin concentration was found between DE and NDE groups, irrespective of tear collection method. Method of collection significantly influenced absolute concentrations (p<0.008). • Chapter 8: There was no significant difference between the two procedures used to isolate RNA and protein from CIC membranes (p>0.05). Total RNA yield was greater with the MP membrane. The mean yield of protein extracted from MP membrane using the two protein isolation techniques also did not show a significant difference. • Chapter 9: No difference was found in the expression of either MUC1 or MUC16 protein or mRNA expression between symptomatic DE and NDE (p>0.05). Weak correlations were found between the NITBUT values compared with either soluble or membrane bound MUC1 and MUC16 expression. Conclusions • Chapter 4: Questionnaires are useful tools to symptomatically divide participants into dry eyed and non dry eyed candidates. However, the questionnaire used to categorise patients can impact on the outcome variables determined. • Chapter 5: Post-menopausal women with dry eye symptoms demonstrate shorter NITBUT, lower tear volume and increased bulbar conjunctival hyperemia than those who have no symptoms. • Chapter 6: Tear osmolality in DE is higher than in NDE. There is a tendency towards less ferning in persons over 50 years of age, regardless of their symptoms. • Chapter 7: Comparison of clinical data with lipocalin and lysozyme concentrations failed to reveal statistically significant correlations. The concentration of either protein was not associated with tear stability or secretion. • Chapter 8: The total RNA yield was greater with the MP membrane. RNeasy Mini (RN) (Qiagen) method is recommended due to enhanced speed as well as on-column isolation and DNase digestion capabilities. CIC with MP membranes followed by immediate freezing and then extraction and processing facilitates the collection of total protein from human conjunctival cells. • Chapter 9: No difference was found in the expression of either MUC1 or MUC16 protein or mRNA expression between symptomatic PMW and asymptomatic controls.

Sjogren’s syndrome (SS) is a systemic autoimmune disease that presents to eye care practitioners with the hallmark symptom of “dry eye.” Stratifying dry eye patients as Sjogren’s positive or negative is a critical differential diagnosis, as SS patients have numerous systemic complications and a forty times greater risk of developing lymphoma. As such, management of this relatively common dry eye sub-population requires specialized care. Since a firm diagnosis requires testing that is both invasive and expensive, patients should be protected from these tests if they are not warranted. In this thesis, studies were therefore undertaken to determine if SS dry eye could be differentiated from other forms of dry eye using two methods: 1) standard clinical tests used in a multi-disciplinary Sjogren’s syndrome clinic and 2) subsequent biological evaluation of collected tear samples and cells from the ocular surface. The former would allow eye care practitioners to conduct appropriate tests and pose suitable questions to ifferentiate these subgroups, and the latter might serve in the future as a relatively non-invasive quantitative means of differentiating such groups through biomarkers.

Introduction: Tear film osmolality is a product of the varying concentrations of dissolved solutes (proteins, lipids and mucins) in the tear fluid. Research suggests that a hyperosmotic tear film is a trait common to all forms of dry eye, and it may be the driving force causing the discomfort, ocular surface damage and inflammation found in both evaporative and tear deficient forms of dry eye disease. Tear film osmolality has been proposed to be the “gold standard” diagnostic test for the evaluation of dry eye disease, as a distinct separation between tear film osmolalities in normal and dry-eyed (aqueous deficient or evaporative) populations has become evident. Historically, tear film osmolality could only be measured in a laboratory setting and required a highly skilled technician to use the instrumentation. The recent development of easy-to-use, small volume osmometers has made it possible for tear film osmolality to be measured clinically. As these instruments are quite new, there has been very little research completed with them. Therefore, a series of studies was conducted to investigate the utility of one of these new osmometers – the Advanced Instruments Model 3100 Nanolitre Osmometer. The specific aims of each chapter were: - Chapter 3: To determine if the Advanced Instruments Model 3100 Nanolitre Osmometer was capable of quantitatively measuring tear film osmolality in a normal population, using 0.5μL tear samples. - Chapter 4: Previous studies have shown the Advanced Instruments Model 3100 Nanolitre Osmometer not significantly different from another commercially available osmometer (Wescor Vapor Pressure Osmometer) for the measurement of human tears. This chapter examined the repeatability of the new instrument over multiple measurements on the same sample and over multiple days. - Chapter 5: To determine if tear film osmolality values varied significantly over the course of a normal working day in a population that was primarily free from symptoms of dry eye. - Chapter 6: To investigate the relationships between tear film osmolality and other commonly used clinical tests for dry eye disease. The clinical tests examined included various questionnaires designed to assess patient symptoms (Single Item Dry Eye Questionnaire (SIDEQ), the Ocular Surface Disease Index (OSDI), and the McMonnies Dry Eye Questionnaire (MMDEQ) and a linear analogue comfort scale (LACS)), a non-invasive tear break-up time test (NIBUT), and examination of ocular surface redness and tear ferning (TF). Secondarily to determine if the other clinical tests demonstrated significant diurnal variations over the course of a normal working day. - Chapter 7: To measure tear film osmolality in a population with mild to moderate symptoms of dry eye disease, and to compare this value with the osmolality of a population of age-matched controls without the disease. Secondarily, to investigate the relationship between tear film osmolality and patient comfort in a population with mild to moderate symptoms of dry eye disease. Methods: - Chapter 3: Tears were collected from 40 volunteer participants with a capillary tube. Some participants were non-contact lens wearers (Non-CL), while others wore either soft or rigid contact lenses (CL). Tear film osmolality was measured with the Advanced Instruments Model 3100 Nanolitre Osmometer. - Chapter 4: Tears were collected from 10 volunteer participants using two different collection techniques. Collections were repeated on three separate days (6 study visits total); three osmolality measurements per collection were taken using the Advanced Instruments Model 3100 Nanolitre osmometer. - Chapter 5: Tears were collected from 40 volunteer participants in two separate studies (n=80 in total). Tears were collected with a capillary tube three times a day (morning, mid-day and afternoon), on two separate days (6 study visits total). Tear film osmolality was measured with the Advanced Instruments Model 3100 Nanolitre Osmometer. - Chapter 6: Clinical tests were administered and tear samples were collected using a capillary tube from 40 volunteer participants. Measurements were taken three times a day (morning, mid-day and afternoon), on two separate days (6 study visits total). Tear film osmolality was measured with the Advanced Instruments Model 3100 Nanolitre Osmometer. - Chapter 7: Participants were classified as either having dry eye disease (DE) or not having dry eye disease (NDE) based on a clinical examination that included a case history, phenol red thread test and biomicroscopy (white light and sodium fluorescein assessment). Tear samples were then collected from all participants using a capillary tube and tear film osmolality was measured with the Advanced Instruments Model 3100 Nanolitre Osmometer. Participants also completed the SIDEQ, the OSDI, and the MMDEQ. Results: - Chapter 3: The mean tear film osmolality of the population was 298.7±11.4mOsm/Kg. CL wear (soft or rigid) did not appear to have a significant effect on tear film osmolality (CL: 298.5±11.2mOsm/Kg vs. Non-CL: 298.9±11.5mOsm/Kg), although this study was not designed to specifically look at the effects of contact lens wear on tear film osmolality. - Chapter 4: There was reasonably good concordance between measurements of tear film osmolality taken with the Advanced Instruments Model 3100 Nanolitre Osmometer (intraclass correlations range from 0.6497 (F= 0.0582) to 0.9550 (F = 0.5893)). Repeatability appeared to be affected by significant changes in ambient humidity (>10% per day). Concordance was similar with both sampling techniques. - Chapter 5: In the first study, no significant diurnal change in tear film osmolality was found (p>0.05), although a significant difference in measurements taken on Day 1 compared to Day 2 was found (p=0.040). When the first and last 10 participants enrolled were compared, the difference between days was present in the first 10 participants, but not in the last 10; it is likely that the investigator underwent a learning process during the period of the study, and that reflex tearing occurred more often in the early portion of the study compared with the latter portion. In the second study, no significant diurnal change in tear film osmolality was found (p>0.05) and no significant difference in measurements taken on Day 1 compared to Day 2 was found (p>0.05). When tear film osmolality was compared with the number of hours participants were awake, no significant correlation was found (r = 0.07044). - Chapter 6: Significant correlations were not found between tear film osmolality and SIDEQ (r = 0.1347), OSDI (r = 0.0331), MMDEQ (r = 0.2727), LACS (r = -0.1622), NIBUT (r = -0.2280), subjectively graded redness (r=-0.2280), or objectively measured redness (r = 0.1233). A weakly significant correlation was found between TF and tear film osmolality (r = 0.3978). None of the clinical measures (LACS, NIBUT, subjective or objective redness or TF) varied significantly over the course of the day. - Chapter 7: Tear film osmolality was higher in both the right (DE = 311.1±12.4mOsm/Kg, NDE = 306.2±11.2mOsm/Kg) and left eyes (DE = 313.2±11.9mOsm/Kg, NDE = 304.0±7.5mOsm/Kg) of participants, but the difference was only statistically significant in the left eye. Tear film osmolality did not correlate significantly with DE patient symptoms using any of the questionnaires (SIDEQ, OSDI, MMDEQ). Conclusions: - Chapter 3: The Advanced Instruments Model 3100 Nanolitre Osmometer appeared to be capable of measuring tear film osmolality in a normal population. Our population mean was slightly lower than what is reported to be normal (305mOsm/Kg), but it still fell within the range of values reported as normal (297 – 318mOsm/Kg). - Chapter 4: The Advanced Instruments Model 3100 Nanolitre Osmometer demonstrated reasonably good repeatability for the measurement of human tear samples. Unfortunately, the instrumentation appeared to be affected by dramatic weather changes. Maintaining the instrument in a humidity controlled environment may resolve this problem. - Chapter 5: Tear film osmolality did not appear to vary significantly over a normal working day. Inducing reflex tearing, perhaps with an unskilled investigator collecting the tears, can be a significant source of error (as demonstrated in the first study). - Chapter 6: Tear film osmolality did not correlate well with other clinical instruments designed to assess either patient symptoms or signs of dry eye disease in a normal population. Tear film osmolality and tear ferning did demonstrate a weakly significant positive correlation. None of the clinical measures assessed demonstrated a significant diurnal variation over the course of a normal working day. - Chapter 7: Tear film osmolality appeared to be higher in participants with mild to moderate symptoms of dry eye when compared with age matched, asymptomatic controls. Tear film osmolality did not correlate well with patient symptoms in a population of mild to moderate severe dry eyed individuals.

The present study used eye-tracking to investigate whether a model’s gaze direction influences the way observers look at the entire body of the model and how this interacts with the observer and the model’s gender. Participants viewed individual male and female computer agents during both a free-viewing task and a rating task to evaluate the attractiveness of each character. The results indicated that both male and female participants primarily gazed at the models’ faces. Participants also spent more time scanning the face when rating the attractiveness of each model. Observers tended to scan faces with a direct gaze longer than faces with an averted gaze for both the free-viewing and attractiveness rating tasks. Lastly, participants evaluated models with a direct gaze as more attractive than models with an averted gaze. As these results occurred for pictures of computer agents, and not actual people, this suggests that direct gaze, and faces in general, are powerful for engaging attention. In summary, both task requirements and gaze direction modified face viewing preference.

The present four studies are the first to examine the effect of presentation time on accurate facial expression discrimination while concurrently using eye movement monitoring to ensure fixation to specific features during the brief presentation of the entire face. Recent studies using backward masking and evaluating accuracy performance with signal detection methods (A’) have identified a happy-face advantage however differences between other facial expressions of emotion have not been reported. In each study, a specific exposure time before mask (150, 100, 50, or 16.67 ms) and eight different fixation locations were used during the presentation of neutral, disgusted, fearful, happy, and surprised expressions. An effect of emotion was found across all presentation times such that the greatest performance was seen for happiness, followed by neutral, disgust, surprise, and with the lowest performances seen for fear. Fixation to facial features specific to an emotion did not improve performance and did not account for the differences in accuracy performance between emotions. Rather, results suggest that accuracy performance depends on the integration of facial features, and that this varies across emotions and with presentation time.

<p>Although most models of reading development present orthographic knowledge as a more advanced and later developing form of knowledge than phonological knowledge, this dissertation presents a model of the development of orthographic knowledge in which generalized orthographic knowledge, the knowledge of symbol patterns within and across words, develops early, at the same time as phonological knowledge and before lexicalized representations of a whole word. However, because phonological and generalized orthographic knowledge are not fully integrated, phonological knowledge masks orthographic knowledge in typical measures of literacy. </p><p>In study 1 pre-readers' knowledge of the elements that make up words was tested using eye-tracking as a measure of implicit knowledge. We find that pre-reading children as young as 3 have implicit orthographic knowledge regarding the elements that make up words. This supports the prediction that generalized orthographic knowledge develops before lexicalized knowledge. </p><p>In study 2, children's creative spellings were used to gauge children's implicit knowledge of letter patterns in a naturalistic setting. We find that kindergarteners in particular tend to rely on phonology over orthography when the two are in conflict. This supports the hypothesis that phonological knowledge can mask orthographic knowledge.</p><p>In study 3, children were asked to decode non-words and their implicit knowledge of letter patterns was measured using eye tracking. I found that early readers show some implicit knowledge when decoding, This supports the hypothesis that generalized orthographic knowledge can be measured in literacy tasks under certain testing conditions. </p><p>In study 4, children's phonological and orthographic knowledge was tested directly by asking children to sound out and select the best word. Results show that sensitivity to orthographic violations is decreased when phonology is introduced. This is a direct test of the hypothesis that phonological knowledge can mask orthographic knowledge, and findings support this hypothesis. </p><p>These results suggest that pre-readers show generalized orthographic knowledge before lexicalized knowledge and concurrently with phonological knowledge. Furthermore, this generalized orthographic knowledge initially presents itself implicitly, and in many early literacy tasks the orthographic domain is dominated by phonological concerns. Essentially, orthographic and phonological knowledge develop at the same time; however, until children learn to integrate the two dimensions of written language, they rely on one source over the other.</p> / Dissertation

With smaller electronic devices and higher transmission speeds, a digital circuit will cause potential electromagnetic interference (EMI) and signal integrity (SI) problems. Nowadays, the flexible printed circuit board (FPC) is widely used in electronic systems, especially in the video circuit. In this thesis, we used transmission line model to explain effect of the structure of the flexible printed circuit board transmission lines. Eye-diagram is a fast and convenient tool to analyze the quality of the high speed transmission, and we can use the equivalent model to substitute for the electromagnetic (EM) model to simulate the performance. We used differential circuit and the reflection gain to increase the height and width parameters of Eye-diagram, and make the quality of signal transmission higher. For video driver circuit, since the terminal resistance is different depending on whether the IC is on or off, the standard probe cannot measure mixed-mode S-parameter directly due to the connectors. Thus, we provided a de-embedding method to remove the effects of high speed interconnect line on the test board. Finally, we use a simple structure to verify the method, and it can be used to measure mixed-mode S-parameter on the standard of Mobile Industry Processor Interface (MIPI) for D-PHY, v0.90.00.

The capability of hand-eye coordination is one of the dexterous skills owned by human beings. In order to reproduce the skillfully operational technique and demonstrate basic hand-eye coordination technique, a robotic wrist system with stereo visual feedback strategy from the viewpoint of table tennis is presented in this thesis. Based on the concept of aerodynamics and collision mechanics, the exerted forces acting on the ball are analyzed. Three stages, including the ball flying in the air, inelastic collision between a racket and the ball, and hitting strategy of humans, will be investigated. At the same time, three-dimensional information for the scene is established using images acquired by dual cameras with a calibration process. Therefore, the flying status of the ball and its position in the space can be calculated. The robotic wrist located underneath will then be controlled to hit the ball to allow it bouncing upwards. The mechanical wrist is operated by three servo motors to simulate actual movement of human wrist. The objective is to successively hit the ball with the racket to achieve intelligent hand-eye coordination control on ball bouncing.

The research involves the creation of an interactive installation showcasing the dynamic nature of human visual observation of a still photograph. Using an eye tracker as an input device, the data collected is used to create a photographic collage in stereoscopic 3D. The installation is artistically inspired by selected photographic works of artists David Hockney, Maurizio Galimberti, Joyce Neimanas and Cubist painters especially Picasso. One of the key factors in their work that is adapted in this research, is the representation of the way eyes search points of interest demonstrated in what they painted/photographed. The installation will demonstrate an expressive representation of the viewers' experience of looking at a photograph. This will be achieved by applying certain manipulations of the photograph based on the input obtained from the viewer using an eye tracker. The eye tracker collects information about the location and number of instances of where the viewer is when observing a photograph. This is fed into software that processes the data and determines the location and the size of the area of the photograph and amount of the manipulation to be applied to that area. These two constitute the artistic rules that are used to create the end product the photo collage. The individual pieces of the collage will be arranged in a virtual 3D model by the artist and will be projected in stereoscopic 3D. The development of this installation progressed through multiple case studies and optimization based on ease of use, cost and availability of resources. This process is intended to be a framework for artists working in interactive visual media.

In film and still photography, depth of field control is often employed to control viewer interest in an image. This technique is also used in computer animation, but, in a medium where artists have near infinite control, must we rely on replicating photorealism? This research is a viable, non-photorealistic solution to the problem of directing viewer interest. Vision is directed by reducing superfluous visual information from parts of the image, which do not directly affect the depictive meaning of that image. This concept is applied to images and animations rendered from three-dimensional, computergenerated scenes, where detail is defined as visual information pertaining to the surface properties of a given object. A system is developed to demonstrate this concept. The system uses distance from a user-defined origin as the main mechanism to modulate detail. This solution is implemented within a modeling and shading environment to serve as a non-photorealistic, functional alternative for depth of field. This approach is conceptually based on a model of human vision, specifically, the relationship between foveal and peripheral vision, and is artistically driven by various works in the disciplines of painting and illustration, that through the careful manipulation of detail, control interest and understanding within the image. The resulting images and animations produced by this system provide viable evidence that detail modulation can be used to control effectively viewer interest in an image eliminating the need to use photographic techniques like depth of field.