Technological enhancements to optometric clinical tests

A sizeable amount of the testing in eye care, requires either the identification of targets such as letters to assess functional vision, or the subjective evaluation of imagery by an examiner. Computers can render a variety of different targets on their monitors and can be used to store and analyse ophthalmic images. However, existing computing hardware tends to be large, screen resolutions are often too low, and objective assessments of ophthalmic images unreliable. Recent advances in mobile computing hardware and computer-vision systems can be used to enhance clinical testing in optometry. High resolution touch screens embedded in mobile devices, can render targets at a wide variety of distances and can be used to record and respond to patient responses, automating testing methods. This has opened up new opportunities in computerised near vision testing. Equally, new image processing techniques can be used to increase the validity and reliability of objective computer vision systems. Three novel apps for assessing reading speed, contrast sensitivity and amplitude of accommodation were created by the author to demonstrate the potential of mobile computing to enhance clinical measurement. The reading speed app could present sentences effectively, control illumination and automate the testing procedure for reading speed assessment. Meanwhile the contrast sensitivity app made use of a bit stealing technique and swept frequency target, to rapidly assess a patient’s full contrast sensitivity function at both near and far distances. Finally, customised electronic hardware was created and interfaced to an app on a smartphone device to allow free space amplitude of accommodation measurement. A new geometrical model of the tear film and a ray tracing simulation of a Placido disc topographer were produced to provide insights on the effect of tear film breakdown on ophthalmic images. Furthermore, a new computer vision system, that used a novel eye-lash segmentation technique, was created to demonstrate the potential of computer vision systems for the clinical assessment of tear stability. Studies undertaken by the author to assess the validity and repeatability of the novel apps, found that their repeatability was comparable to, or better, than existing clinical methods for reading speed and contrast sensitivity assessment. Furthermore, the apps offered reduced examination times in comparison to their paper based equivalents. The reading speed and amplitude of accommodation apps correlated highly with existing methods of assessment supporting their validity. Their still remains questions over the validity of using a swept frequency sine-wave target to assess patient’s contrast sensitivity functions as no clinical test provides the range of spatial frequencies and contrasts, nor equivalent assessment at distance and near. A validation study of the new computer vision system found that the authors tear metric correlated better with existing subjective measures of tear film stability than those of a competing computer-vision system. However, repeatability was poor in comparison to the subjective measures due to eye lash interference. The new mobile apps, computer vision system, and studies outlined in this thesis provide further insight into the potential of applying mobile and image processing technology to enhance clinical testing by eye care professionals.

Drug repurposing screen identifies Foxo1-dependent angiopoietin-2 regulation in sepsis

Objective: The recent withdrawal of a targeted sepsis therapy has diminished pharmaceutical enthusiasm for developing novel drugs for the treatment of sepsis. Angiopoietin-2 is an endothelial-derived protein that potentiates vascular inflammation and leakage and may be involved in sepsis pathogenesis. We screened approved compounds for putative inhibitors of angiopoietin-2 production and investigated underlying molecular mechanisms. Design: Laboratory and animal research plus prospective placebo-controlled randomized controlled trial (NCT00529139) and retrospective analysis (NCT00676897). Setting: Research laboratories of Hannover Medical School and Harvard Medical School. Patients: Septic patients/C57Bl/6 mice and human endothelial cells. Interventions: Food and Drug Administration-approved library screening. Measurements and Main Results: In a cell-based screen of more than 650 Food and Drug Administration-approved compounds, we identified multiple members of the 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitor drug class (referred to as statins) that suppressed angiopoietin-2. Simvastatin inhibited 3-hydroxy-3-methyl-glutaryl-CoA reductase, which in turn activated PI3K-kinase. Downstream of this signaling, PI3K-dependent phosphorylation of the transcription factor Foxo1 at key amino acids inhibited its ability to shuttle to the nucleus and bind cis-elements in the angiopoietin-2 promoter. In septic mice, transient inhibition of angiopoietin-2 expression by liposomal siRNA in vivo improved absolute survival by 50%. Simvastatin had a similar effect, but the combination of angiopoietin-2 siRNA and simvastatin showed no additive benefit. To verify the link between statins and angiopoietin-2 in humans, we performed a pilot matched case-control study and a small randomized placebo-controlled trial demonstrating beneficial effects on angiopoietin-2. Conclusions: 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors may operate through a novel Foxo1-angiopoietin-2 mechanism to suppress de novo production of angiopoietin-2 and thereby ameliorate manifestations of sepsis. Given angiopoietin-2's dual role as a biomarker and candidate disease mediator, early serum angiopoietin-2 measurement may serve as a stratification tool for future trials of drugs targeting vascular leakage.

Validity and reliability of the Spanish version of Caregiver Abuse Screen (CASE)

Detection of elder abuse risk is a critical issue because a lot of cases remain hidden. Screening tools can be used to detect elder abuse. However, few tools have been developed for use with caregivers. The purpose was to develop a translation and adaptation of a Spanish version of the Caregiver Abuse Screen (CASE) and to assess its validity and reliability. The CASE was then used with 211 primary caregivers. Validity and reliability were evaluated, as well as the factorial structure of the instrument. This version showed good psychometric properties. It was found to have strong internal consistency and split-half reliability as well as allowing for a good replication of the original factorial structure. Additionally, several variables related to elder abuse were linked to the CASE such as depression, burden, frequency, and reactions to problem behaviors. The version developed showed sufficient validity and reliability and could be considered as a suitable instrument to assess risks of elder abuse in a Spanish-speaking context.

The lived experience of healing touch with cancer patients

The recent use of complementary therapies by cancer patients has prompted the study of the use of Healing Touch, an energy based therapy, to learn the meaning of the experience. By using Ray's Caring Inquiry, a phenomenologic-hermeneutic process, the lived experience of receiving Healing Touch was elicited from three cancer patients. Through the interactions of the Healing Touch practitioners, the cancer patient participants, and the energy in and around them, specific themes were expressed: body-physical, emotion-feeling, mental-knowing, and spirit-essence. Further abstracting lead to the metathemes sensation and perception. Through a change in consciousness, a oneness/wholeness was experienced. The unity of meaning elicited was the Rhythm of Oneness Through Energy which is the connecting, opening, and cocreating through caring, the wholeness of each to become one through rhythms of energy. ^

Types and amplitudes of touch as reinforcing stimuli in operant conditioning of infant behavior

The reinforcing effects of diverse tactile stimuli were examined in this study. The study had two purposes. First, this study expanded on the Pelaez-Nogueras, Field, Gewirtz, Cigales, Gonzalez, Sanchez and Clasky (1997) finding that stroking increases infants' gaze duration, and smiling and vocalization frequencies more than tickling/poking. Instead of presenting poking and tickling as a single stimulus combination, this study separated poking and tickling in order to measure the effects of each component separately. Further, the effects of poking, tickling/tapping and stroking intensity (i.e., tactile pressure) were compared by having both mild and intense conditions. Second, this study compared the reinforcing efficacy of mother-delivered tactile stimulation to that of infant-originated tactile exploration. Twelve infants from 2- to 5-months of age participated in this study. The experiment was conducted using a repeated measures A-B-A-C-A-D reversal design. The A phases signified baselines and reversals. The B, C, and D phases consisted of alternating treatments (either mild stroking vs. mild poking vs. mild tickling/tapping, intense stroking vs. intense poking vs. intense tickling/tapping, or mother-delivered tactile stimulation vs. infant-originated tactile exploration). Three experimental hypotheses were assessed: (1) infant leg kick rate would be greater when it produced stroking or tickling/tapping (presumptive positive reinforcers), than when it produced poking (a possible punisher), regardless of tactile pressure; (2) infant leg kick rate would be greater when it produced a more intense level of stroking or tickling/tapping and lower when it produced intense poking compared to mild poking; (3) infant leg-kick rate would be greater for mother-delivered tactile stimulation than for infant-originated tactile exploration. Visual inspection and inferential statistical methods were used to analyze the results. The data supported the first two hypotheses. Mixed support emerged for the third hypothesis. This study made several important contributions to the field of psychology. First, this was the first study to quantify the pressure of tactile stimulation, via a pressure meter developed by the researcher. Additionally, the results of this study yielded valuable information about the effects of different modalities of touch. ^

Touch of AIDS : A love story

Touch of AIDS: A Love Story is a memoir covering the ten years since my husband, Steven's HIV positive diagnosis in 1987. The story begins when we find our circumstances redefined and our future challenged by the plague of this century. Steven's inability to withstand the toxic effects of the earliest approved antiviral drugs leads us to turn to alternative therapies. After his conversion to AIDS we return to Western medicine but continue on a quest that takes us from Taoist studies at home in Florida to sacred Navajo ceremonies in Arizona. As Steven finds that healing comes in great part from the journey itself and that he is stronger physically, emotionally and spiritually than he was before his HIV diagnosis, I realize that we can live with fear as long as we don't become its victims. Love and hope empower our lives as we live with AIDS.

3D navigation with six degrees-of-freedom using a multi-touch display

With the introduction of new input devices, such as multi-touch surface displays, the Nintendo WiiMote, the Microsoft Kinect, and the Leap Motion sensor, among others, the field of Human-Computer Interaction (HCI) finds itself at an important crossroads that requires solving new challenges. Given the amount of three-dimensional (3D) data available today, 3D navigation plays an important role in 3D User Interfaces (3DUI). This dissertation deals with multi-touch, 3D navigation, and how users can explore 3D virtual worlds using a multi-touch, non-stereo, desktop display. ^ The contributions of this dissertation include a feature-extraction algorithm for multi-touch displays (FETOUCH), a multi-touch and gyroscope interaction technique (GyroTouch), a theoretical model for multi-touch interaction using high-level Petri Nets (PeNTa), an algorithm to resolve ambiguities in the multi-touch gesture classification process (Yield), a proposed technique for navigational experiments (FaNS), a proposed gesture (Hold-and-Roll), and an experiment prototype for 3D navigation (3DNav). The verification experiment for 3DNav was conducted with 30 human-subjects of both genders. The experiment used the 3DNav prototype to present a pseudo-universe, where each user was required to find five objects using the multi-touch display and five objects using a game controller (GamePad). For the multi-touch display, 3DNav used a commercial library called GestureWorks in conjunction with Yield to resolve the ambiguity posed by the multiplicity of gestures reported by the initial classification. The experiment compared both devices. The task completion time with multi-touch was slightly shorter, but the difference was not statistically significant. The design of experiment also included an equation that determined the level of video game console expertise of the subjects, which was used to break down users into two groups: casual users and experienced users. The study found that experienced gamers performed significantly faster with the GamePad than casual users. When looking at the groups separately, casual gamers performed significantly better using the multi-touch display, compared to the GamePad. Additional results are found in this dissertation.^

On-screen pre-deblurring of digital images using the wavefront aberration function of the human eye to improve computer access for the visually impaired

Traditional Optics has provided ways to compensate some common visual limitations (up to second order visual impairments) through spectacles or contact lenses. Recent developments in wavefront science make it possible to obtain an accurate model of the Point Spread Function (PSF) of the human eye. Through what is known as the "Wavefront Aberration Function" of the human eye, exact knowledge of the optical aberration of the human eye is possible, allowing a mathematical model of the PSF to be obtained. This model could be used to pre-compensate (inverse-filter) the images displayed on computer screens in order to counter the distortion in the user's eye. This project takes advantage of the fact that the wavefront aberration function, commonly expressed as a Zernike polynomial, can be generated from the ophthalmic prescription used to fit spectacles to a person. This allows the pre-compensation, or onscreen deblurring, to be done for various visual impairments, up to second order (commonly known as myopia, hyperopia, or astigmatism). The technique proposed towards that goal and results obtained using a lens, for which the PSF is known, that is introduced into the visual path of subjects without visual impairment will be presented. In addition to substituting the effect of spectacles or contact lenses in correcting the loworder visual limitations of the viewer, the significance of this approach is that it has the potential to address higher-order abnormalities in the eye, currently not correctable by simple means.

Silent screen: book review.

Book Review. Kevin Rockett, Irish film censorship: a cultural journey from silent cinema to internet pornography (Dublin, 2004) and Mary Corcoran and Mark O'Brien (eds), Political censorship and the democratic state: the Irish broadcasting ban (Dublin, 2005)

Diversity, difference and nation: indigenous peoples on screen in Mexico

This paper draws on constructivist theories of identity that regard the self as, paradoxically, coming into existence through interaction with the other, to investigate the discursive formation of indigenous people in the forging of Mexican national identity. The aim of the essay is to show how difference has been managed and deployed in the establishment of national Mexican identities from independence until the present. This is done with reference to visual culture and film and illustrated with examples from the ‘Golden Age’ as well as ‘the New Mexican Cinema’.

3D Navigation with Six Degrees-of-Freedom using a Multi-Touch Display

With the introduction of new input devices, such as multi-touch surface displays, the Nintendo WiiMote, the Microsoft Kinect, and the Leap Motion sensor, among others, the field of Human-Computer Interaction (HCI) finds itself at an important crossroads that requires solving new challenges. Given the amount of three-dimensional (3D) data available today, 3D navigation plays an important role in 3D User Interfaces (3DUI). This dissertation deals with multi-touch, 3D navigation, and how users can explore 3D virtual worlds using a multi-touch, non-stereo, desktop display. The contributions of this dissertation include a feature-extraction algorithm for multi-touch displays (FETOUCH), a multi-touch and gyroscope interaction technique (GyroTouch), a theoretical model for multi-touch interaction using high-level Petri Nets (PeNTa), an algorithm to resolve ambiguities in the multi-touch gesture classification process (Yield), a proposed technique for navigational experiments (FaNS), a proposed gesture (Hold-and-Roll), and an experiment prototype for 3D navigation (3DNav). The verification experiment for 3DNav was conducted with 30 human-subjects of both genders. The experiment used the 3DNav prototype to present a pseudo-universe, where each user was required to find five objects using the multi-touch display and five objects using a game controller (GamePad). For the multi-touch display, 3DNav used a commercial library called GestureWorks in conjunction with Yield to resolve the ambiguity posed by the multiplicity of gestures reported by the initial classification. The experiment compared both devices. The task completion time with multi-touch was slightly shorter, but the difference was not statistically significant. The design of experiment also included an equation that determined the level of video game console expertise of the subjects, which was used to break down users into two groups: casual users and experienced users. The study found that experienced gamers performed significantly faster with the GamePad than casual users. When looking at the groups separately, casual gamers performed significantly better using the multi-touch display, compared to the GamePad. Additional results are found in this dissertation.

Examination of body image among Canadian adolescents: Relations with physical activity and screen time

Background: Adolescence is a period of life associated with self-perceptions of negative body image. Physical activity levels are low and screen time levels are also high during this stage. These perceptions and behaviours are associated with poor health outcomes, making research on their determinants important. With adolescent populations, certain groups may be at higher risk of body dissatisfaction than others, and body dissatisfaction may influence individual physical activity and screen time levels. Objectives: The objectives of this thesis were to: 1) describe body image among young Canadians, examining possible health inequalities 2) estimate the strength and significance of associations between body satisfaction, physical activity and screen time, and 3) examine the potential etiological role of biological sex. Methods: Objective 1: The 2013/2014 Health Behaviour in School-aged Children study was employed. Sex-stratified Rao-Scott chi-square analyses were conducted to examine associations between socio-demographic factors and body satisfaction. Objective 2: The 2005/2006 and 2013/2014 cross-sectional and 2006 longitudinal HBSC data sets were used. Sex-stratified modified Poisson regressions were conducted and risk estimates and associated confidence intervals obtained. Results: Objective 1: Among males, being older, of East and Southeast Asian ethnicity, and reporting low SES all were associated with body dissatisfaction. Among females, being older, of Arab and West Asian or African ethnicity, being born in Canada, and reporting low SES were all associated with being body dissatisfied. Objective 2: Cross-sectionally, males who reported ‘too fat’ body dissatisfaction were more likely to be physically inactive. Adolescents of both sexes who reported ‘too fat’ body dissatisfaction were more likely to engage in high levels of screen time. Data from the longitudinal component supported the idea that male ‘too fat’ body dissatisfaction temporally leads to physical inactivity, but showed an inverse relationship between body dissatisfaction and screen time. Conclusions: Objective 1: Future prevention efforts in Canada should target subgroups to effectively help those at greatest risk of body dissatisfaction, and ameliorate potential inequalities at the population level. Objective 2: The presence of these relationships may inform future interventions as part of a multi-factorial etiology, in order to increase physical activity and decrease screen time among youth.

Kinome-wide CRISPR-Cas9 screen to identify kinases involved in Taxol resistance in breast cancer

Breast cancer is the most frequently diagnosed cancer in women, accounting for over 25% of cancer diagnoses and 13% of cancer-related deaths in Canadian women. There are many types of therapies for treatment or management of breast cancer, with chemotherapy being one of the most widely used. Taxol (paclitaxel) is one of the most extensively used chemotherapeutic agents for treating cancers of the breast and numerous other sites. Taxol stabilizes microtubules during mitosis, causing the cell cycle to arrest until eventually the cell undergoes apoptosis. Although Taxol has had significant benefits in many patients, response rates range from only 25-69%, and over half of Taxol-treated patients eventually acquire resistance to the drug. Drug resistance remains one of the greatest barriers to effective cancer treatment, yet little has been discerned regarding resistance to Taxol, despite its widespread clinical use. Kinases are known to be heavily involved in cancer development and progression, and several kinases have been linked to resistance of Taxol and other chemotherapeutic agents. However, a systematic screen for kinases regulating Taxol resistance is lacking. Thus, in this study, a set of kinome-wide screens was conducted to interrogate the involvement of kinases in the Taxol response. Positive-selection and negative-selection CRISPR-Cas9 screens were conducted, whereby a pooled library of 5070 sgRNAs targeted 507 kinase-encoding genes in MCF-7 breast cancer cells that were Taxol-sensitive (WT) or Taxol-resistant (TxR) which were then treated with Taxol. Next generation sequencing (NGS) was performed on cells that survived Taxol treatment, allowing identification and quantitation of sgRNAs. STK38, Blk, FASTK and Nek3 stand out as potentially critical kinases for Taxol-induced apoptosis to occur. Furthermore, kinases CDKL1 and FRK may have a role in Taxol resistance. Further validation of these candidate kinases will provide novel pre-clinical data about potential predictive biomarkers or therapeutic targets for breast cancer patients in the future.

Occupied childhoods: discourses and politics of childhood and their place in Palestinian and Pan-­Arab screen content for children

This thesis explores changing discourses of childhood and the ways in which power relations intersect with socio-cultural norms to shape screen-based media for Palestinian children. Situated within the interdisciplinary study of childhood, the research is an institutional and textual analysis that includes discursive and micro-level analysis of the socio-political circumstances within which children consume media in present-day Palestine. The thesis takes a social constructionist view, arguing that ‘childhood’ is not a fixed universal concept and that discourses of childhood are produced at specific historical moments as an effect of power. The study has a three-part research agenda. The first section uses secondary literature to explore theories and philosophies relating to definitions of childhood in Arab societies. The second employs participant observation and semi-structured interviews to understand the history and politics of children’s media in the West Bank. The final part of the research activity focuses on the impact that definitions of childhood and the politics of children’s media have on broadcasting outcomes through an analysis of (a) discourses on children’s media that circulate in Palestinian society, and (b) local and pan-Arab cultural texts consumed by Palestinian children. The analysis demonstrates that complex ideological and political factors are at play, which has led to the marginalisation, politicisation and internationalisation of local production for children. Due to the lack of alternatives, local producers often rely on international funding, and are hence forced to negotiate competing definitions of childhood, which while fitting with an international agenda of normalising the Israeli occupation, conflict culturally and politically with local conceptions of childhood and hopes for the Palestinian nation. While the Palestinian community appreciates the positive potential of local production, discourses and strategies around children’s media show that Palestinian children are constructed as vulnerable, incomplete and in constant need of guidance. Pan-Arab content presents a slightly less didactic approach and in certain cases presents childhood as a dynamic space of empowerment. However, by constructing children as ‘consumercitizens’, it alienates Arab (and Palestinian) children from disadvantaged backgrounds,as the preferred audience is middle-class children living in oil-rich countries of the Gulf.