Enhancing the Visualization of the Peripheral Retina with Wide Field-of-View Optical Coherence Tomography

The goal of my Ph.D. thesis is to enhance the visualization of the peripheral retina using wide-field optical coherence tomography (OCT) in a clinical setting.

OCT has gain widespread adoption in clinical ophthalmology due to its ability to visualize the diseases of the macula and central retina in three-dimensions, however, clinical OCT has a limited field-of-view of 300. There has been increasing interest to obtain high-resolution images outside of this narrow field-of-view, because three-dimensional imaging of the peripheral retina may prove to be important in the early detection of neurodegenerative diseases, such as Alzheimer's and dementia, and the monitoring of known ocular diseases, such as diabetic retinopathy, retinal vein occlusions, and choroid masses.

Before attempting to build a wide-field OCT system, we need to better understand the peripheral optics of the human eye. Shack-Hartmann wavefront sensors are commonly used tools for measuring the optical imperfections of the eye, but their acquisition speed is limited by their underlying camera hardware. The first aim of my thesis research is to create a fast method of ocular wavefront sensing such that we can measure the wavefront aberrations at numerous points across a wide visual field. In order to address aim one, we will develop a sparse Zernike reconstruction technique (SPARZER) that will enable Shack-Hartmann wavefront sensors to use as little as 1/10th of the data that would normally be required for an accurate wavefront reading. If less data needs to be acquired, then we can increase the speed at which wavefronts can be recorded.

For my second aim, we will create a sophisticated optical model that reproduces the measured aberrations of the human eye. If we know how the average eye's optics distort light, then we can engineer ophthalmic imaging systems that preemptively cancel inherent ocular aberrations. This invention will help the retinal imaging community to design systems that are capable of acquiring high resolution images across a wide visual field. The proposed model eye is also of interest to the field of vision science as it aids in the study of how anatomy affects visual performance in the peripheral retina.

Using the optical model from aim two, we will design and reduce to practice a clinical OCT system that is capable of imaging a large (800) field-of-view with enhanced visualization of the peripheral retina. A key aspect of this third and final aim is to make the imaging system compatible with standard clinical practices. To this end, we will incorporate sensorless adaptive optics in order to correct the inter- and intra- patient variability in ophthalmic aberrations. Sensorless adaptive optics will improve both the brightness (signal) and clarity (resolution) of features in the peripheral retina without affecting the size of the imaging system.

The proposed work should not only be a noteworthy contribution to the ophthalmic and engineering communities, but it should strengthen our existing collaborations with the Duke Eye Center by advancing their capability to diagnose pathologies of the peripheral retinal.

Temporal Regulation of LMP1 and Apoptosis Resistance After Primary EBV Infection

Epstein-Barr virus (EBV) is a ubiquitous human pathogen that establishes a lifelong latent infection in over ninety percent of all adult humans worldwide. While typically benign, EBV has been causally associated with a number of human malignancies in the settings of immune suppression, genetic, and/or environmental factors. While a highly successful pathogen based on prevalence, the ability of the virus to immortalize human B cells (a stage of infection thought to be critical for the establishment of latency) is quite poor. We hypothesize that the interactions between the virus and the human host early after infection are ultimately important for the outcome of viral latency establishment. To answer this question we broadly profiled primary human B cells at both early and late times after EBV infection to assay both host mRNA expression and the host-driven response to apoptotic stimuli. We found that EBV infection induces host gene expression signatures early after infection that are functionally distinct from the gene expression program late after infection. These studies also led to the novel discovery that viral gene expression is controlled differently early after infection, including the delayed expression of a viral protein that is critical for the establishment of latency. Furthermore, we have also shown that EBV can use a single viral protein to alter and repress host apoptotic sensitivity in the face of an anti-viral apoptotic response.

An integrative case study of positive youth development in a recreational community sport program

Participation in organized activities is associated with many markers of positive youth development (PYD) such as improved self-esteem, social competence, and academic achievement (Mahoney et al., 2009). Sport is an extra-curricular activity that is particularly popular among youth, as nearly three quarters of Canadian children and adolescents are engaged in organized sport or physical activity (CFLRI, 2012). Much of the research in this area has examined sport programs which are explicitly structured to promote life skills or PYD outcomes; however, the sustainability of such programs has recently been called into question (Turnnidge, Hancock, & Côté, 2014). The purpose of this program of research was to conduct an in-depth case study of a successful, sustainable community youth basketball league. Study 1 was a qualitative descriptive exploration of coaches’ perceptions of the basketball league. This study provided a general overview of the structure and perceived benefits of the league, from the perspective of current coaches. Coaches highlighted the unique emphasis that the league places on fun and positive immediate sport experiences. Study 2 expanded on selected themes from Study 1, namely, the salience of the league’s culture and tendency for former players to return to the league as volunteers. This study used an ethnographic approach wherein the first author volunteered as an assistant coach on a basketball team over the course of a six-month season. This approach enabled him to gain considerable first hand insight into the organizational culture of the basketball league. The third and final study adopted a quantitative approach using both systematic observation and questionnaires to investigate the relationship between PYD outcomes and observed athlete behaviour during basketball games. A cluster analysis revealed the presence of two distinct groups of athletes characterized by relatively high and low perceptions of PYD outcomes, which were also associated with varying behavioural characteristics during competition. The results of these three studies provide a detailed blueprint of a successful youth sport program that has been sustained over 60 years. While not without limitations, many characteristics of the league should prove useful in structuring youth sport programs in other contexts.

The Rotational Evolution and Magnetospheric Emission of the Magnetic Early B-type Stars

How do the magnetic fields of massive stars evolve over time? Are their gyrochronological ages consistent with ages inferred from evolutionary tracks? Why do most stars predicted to host Centrifugal Magnetospheres (CMs) display no H$\alpha$ emission? Does plasma escape from CMs via centrifugal breakout events, or by a steady-state leakage mechanism? This thesis investigates these questions via a population study with a sample of 51 magnetic early B-type stars. The longitudinal magnetic field \bz~was measured from Least Squares Deconvolution profiles extracted from high-resolution spectropolarimetric data. New rotational periods $P_{\rm rot}$ were determined for 15 stars from \bz, leaving only 3 stars for which $P_{\rm rot}$ is unknown. Projected rotational velocities \vsini~were measured from multiple spectral lines. Effective temperatures and surface gravities were measured via ionization balances and line profile fitting of H Balmer lines. Fundamental physical parameters, \bz, \vsini, and $P_{\rm rot}$ were then used to determine radii, masses, ages, dipole oblique rotator model, stellar wind, magnetospheric, and spindown parameters using a Monte Carlo approach that self-consistently calculates all parameters while accounting for all available constraints on stellar properties. Dipole magnetic field strengths $B_{\rm d}$ follow a log-normal distribution similar to that of Ap stars, and decline over time in a fashion consistent with the expected conservation of fossil magnetic flux. $P_{\rm rot}$ increases with fractional main sequence age, mass, and $B_{\rm d}$, as expected from magnetospheric braking. However, comparison of evolutionary track ages to maximum spindown ages $t_{\rm S,max}$ shows that initial rotation fractions may be far below critical for stars with $M_*>10 M_\odot$. Computing $t_{\rm S,max}$ with different mass-loss prescriptions indicates that the mass-loss rates of B-type stars are likely much lower than expected from extrapolation from O-type stars. Stars with H$\alpha$ in emission and absorption occupy distinct regions in the updated rotation-magnetic confinement diagram: H$\alpha$-bright stars are found to be younger, more rapidly rotating, and more strongly magnetized than the general population. Emission strength is sensitive both to the volume of the CM and to the mass-loss rate, favouring leakage over centrifugal breakout.

Ablation of Steel by Microsecond Pulse Trains

Laser micromachining is an important material processing technique used in industry and medicine to produce parts with high precision. Control of the material removal process is imperative to obtain the desired part with minimal thermal damage to the surrounding material. Longer pulsed lasers, with pulse durations of milli- and microseconds, are used primarily for laser through-cutting and welding. In this work, a two-pulse sequence using microsecond pulse durations is demonstrated to achieve consistent material removal during percussion drilling when the delay between the pulses is properly defined. The light-matter interaction moves from a regime of surface morphology changes to melt and vapour ejection. Inline coherent imaging (ICI), a broadband, spatially-coherent imaging technique, is used to monitor the ablation process. The pulse parameter space is explored and the key regimes are determined. Material removal is observed when the pulse delay is on the order of the pulse duration. ICI is also used to directly observe the ablation process. Melt dynamics are characterized by monitoring surface changes during and after laser processing at several positions in and around the interaction region. Ablation is enhanced when the melt has time to flow back into the hole before the interaction with the second pulse begins. A phenomenological model is developed to understand the relationship between material removal and pulse delay. Based on melt refilling the interaction region, described by logistic growth, and heat loss, described by exponential decay, the model is fit to several datasets. The fit parameters reflect the pulse energies and durations used in the ablation experiments. For pulse durations of 50 us with pulse energies of 7.32 mJ +/- 0.09 mJ, the logisitic growth component of the model reaches half maximum after 8.3 us +/- 1.1 us and the exponential decays with a rate of 64 us +/- 15 us. The phenomenological model offers an interpretation of the material removal process.

The Causes and Effects of Consumer Competence Perceptions

Consumers are constantly making consumption decisions and engaging in marketplace activities that require some level of competence. In other words, consumers possess and require some knowledge, skills, and abilities to engage in the marketplace and obtain what they want. But what causes consumers to infer they are or are not competent? And, what are the consequences of these competence inferences on consumer behaviour? This dissertation examines the role consumption plays in consumers’ inferences of their own competence to enhance our understanding of these issues. By integrating the literature on competence and attributions of blame, this dissertation develops a theory for when and how consumption influences self-perceptions of competence and how these self-perceptions of competence impact future consumer behaviours. Evidence from five studies suggests that consumers infer their own competence from their consumption outcomes, despite who is actually responsible for causing these outcomes. This means consumers potentially see themselves as incompetent for negative outcomes that are entirely firm-caused. This dissertation argues that people infer their own competence from firm-caused outcomes because they conflate their decisions made prior to an outcome with the cause of that outcome. This dissertation also examines how these variations in self-perceptions of competence can influence future consumer behaviours.

Youth sport coaches’ reflections on leadership behaviours during games and practices

Youth sport coaches shape the developmental sporting experience for their athletes (Camiré, Trudel, & Forneris, 2014). Specifically, coaches who form individualized, supportive relationships with their athletes can increase the development of personal and social skills (Fraser-Thomas, Côté, & Deakin, 2005). In light of the value of these relationships, increasing evidence is prompting the application of leadership theories, such as Transformational Leadership (TFL), in youth sport (Vella et al., 2013). The aim of this study was to explore coach perceptions of how and why leadership behaviours are applied in the youth sport context. Eleven coaches (Mage= 42.3, SD= 15.2) were recruited from competitive youth soccer and volleyball clubs (athletes’ Mage= 15.8, SD= 1.9) in Eastern Ontario and participated in a stimulated recall interview. During the interviews, coaches reflected upon their own coaching behaviours and provided insight into the application of leadership behaviours in youth sport. Responses were prompted by relevant video sequences from recorded practice and game sessions. A thematic content analysis revealed that; i) coaches use a variety of leadership behaviours in youth sport, ii) the use of leadership behaviours vary across sport contexts or settings, and iii) contrasting leadership styles (e.g., transactional vs. transformational) are associated with distinctive coach objectives (e.g., promoting confidence vs. establishing respect). These findings have helped identify gaps within coach education, and provide theoretical insight for applying leadership theories, and more specifically TFL, to help improve the sport experiences of young athletes.

β-Arrestin-mediated Regulation of the Human Ether-a-go-go-Related Gene (hERG) Potassium Channel

The human ether-a-go-go-related gene (hERG) encodes the voltage-gated K+ channel, hERG (Kv11.1). This channel passes the rapidly-activating delayed rectifier K+ current (IKr), which is important for cardiac repolarization. A reduction in IKr due to loss-of-function mutations or drug interactions causes long QT syndrome (LQTS), which can lead to cardiac arrhythmias and sudden cardiac death. The density of hERG channels in the plasma membrane is a key determinant of normal physiological function, and is balanced by trafficking to and from the cell surface. Many LQTS-associated hERG mutations result in a trafficking deficiency of otherwise functional channels. Thus, elucidating mechanisms of hERG regulation at the plasma membrane is useful for the prevention and treatment of LQTS. We previously demonstrated that M3 muscarinic receptor activation increases mature hERG expression through a Gq protein-dependent protein kinase C (PKC) pathway. In addition to conventional Gq protein-coupling, M3 receptors recruit β-arrestins upon agonist binding. Traditionally known for their role in receptor desensitization and internalization, β-arrestins also act as adaptor proteins to facilitate G protein-independent signaling. In the present work, I investigated the exclusive effect of β-arrestin signaling on hERG expression by utilizing an arrestin-biased M3 designer receptor (M3D-arr) exclusively activated by clozapine-N-oxide (CNO). By expressing M3D-arr in hERG-HEK cells and treating with CNO under various conditions, I found that M3D-arr activation increased mature hERG expression and current. Within this paradigm, M3D-arr recruited β-arrestin to the plasma membrane, and promoted the PI3K-dependent activation of Akt. I further found that the activated Akt acted through phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) and Rab11 to facilitate endosomal recycling of hERG channels to the plasma membrane.

Bipartite Assertion: A New Account of Assertion, Defined in Terms of Responsibility and Explicit Presentation

Assertion is a speech act that stands at the intersection of the philosophy of language and social epistemology. It is a phenomenon that bears on such wide-ranging topics as testimony, truth, meaning, knowledge and trust. It is thus no surprise that analytic philosophers have devoted innumerable pages to assertion, trying to give the norms that govern it, its role in the transmission of knowledge, and most importantly, what assertion is, or how assertion is to be defined. In this thesis I attempt to show that all previous answers to the question “What is assertion?” are flawed. There are four major traditions in the literature: constitutive norm theories of assertion, accounts that treat assertion as the expression of speaker attitudes, accounts that treat assertion as a proposal to add some proposition to the common ground, and accounts that treat assertion as the taking of responsibility for some claim. Each tradition is explored here, the leading theories within the tradition developed, and then placed under scrutiny to demonstrate flaws within the positions surveyed. I follow the work of G.E. Moore and William P. Alston, whilst drawing on the work of Robert Brandom in order to give a new bipartite theory of assertion. I argue that assertion consists in the explicit presentation of a proposition, along with a taking of responsibility for that proposition. Taking Alston's explicit presentation condition and repairing it in order to deal with problems it faces, whilst combining it with Brandom's responsibility condition, provides, I believe, the best account of assertion.

The relationship between changes in cardiovascular function and changes in VO2peak following SIT

Background: It is well known that sprint interval training (SIT), induces significant increases in peak oxygen uptake (VO2peak) at the group level. However, there have been only a few studies that have addressed the variability of VO2peak response following SIT, and precise mechanism(s) that may explain individual magnitude of response are unknown. Purpose: Therefore, the purpose of this thesis was to: 1) examine the inter-individual variability of the VO2peak response following SIT, 2) to inspect the relationship between changes in both central and peripheral measures and changes in VO2peak, and 3) to assess if peripheral or central adaptations play a role in whether an individual is a high or low responder with respect to VO2peak. Subjects: Twenty-two young, recreationally active males (age: 20.4 1.7 years; weight: 78.4 10.2 kg; VO2peak: 3.7 0.62 L/min) Methods: VO2peak (L/min), peak cardiac output (Qpeak [L/min]), and peak deoxygenated hemoglobin (HHbpeak [mM]) were measured before and after 16 sessions of SIT (Tabata Protocol) over four weeks. Peak a-vO2diff was calculated using a derivation of the Fick equation. Results: Due to a systematic error, HHbpeak could not be used to differentiate between individual responses. There was a large range of VO2peak response from pre to post testing (-4.75 to 32.18% change) and there was a significant difference between the Low Response Group (LRG) (n=8) and the High Response Group (HRG) (n=8) [f(1, 14)= 64.27, p<0.001]. Furthermore, there was no correlation between delta () VO2peak and Qpeak (r=-0.18, p=0.46) for all participants, nor was there an interaction effect between the Low and High Response Groups [f(1,11)=0.572, p=0.47]. Lastly, there was a significant correlation between VO2peak and peak a-vO2diff [r=0.692, p<0.001], and a significant interaction effect with peak a-vO2diff [f(1, 14)= 13.27, p<0.004] when comparing the HRG to the LRG. Conclusions: There was inter-individual variability of VO2peak response following 4 weeks of SIT, but central adaptations did not influence this variation. This suggests that peripheral adaptations may be responsible for VO2peak adaptation.

Yielding Behaviour of Electron Beam Lithography and Focused Ion Beam Made Nanocrystalline Micro/Nanopillars

Electron beam lithography (EBL) and focused ion beam (FIB) methods were developed in house to fabricate nanocrystalline nickel micro/nanopillars so to compare the effect of fabrication on plastic yielding. EBL was used to fabricate 3 μm and 5 μm thick poly-methyl methacrylate patterned substrates in which nickel pillars were grown by electroplating with height to diameter aspect ratios from 2:1 to 5:1. FIB milling was used to reduce larger grown pillars to sizes similar to EBL grown pillars. X-ray diffraction, electron back-scatter diffraction, scanning electron microscopy, and FIB imaging were used to characterize the nickel pillars. The measured grain size of the pillars was 91±23 nm, with strong <110> and weaker <111> and <110> crystallographic texture in the growth. Load-controlled compression tests were conducted using a MicroMaterials nano-indenter equipped with a 10 μm flat punch at constant rates from 0.0015 to 0.03 mN/s on EBL grown pillars, and 0.0015 and 0.015 mN/s on FIB-milled pillars. The measured Young’s modulus ranged from 55 to 350 GPa for all pillars, agreeing with values in the literature. EBL grown pillars exhibited stochastic strain-bursts at slow loading rates, attributed to local micro yield events, followed by work hardening. Sharp yield points were also observed and attributed to the gold seed layer de-bonding between the nickel pillar and substrate due to the shear stress associated with end effects that arise from the substrate constraint. The onset of yield ranged from 108 to 1800 MPa, which is greater than bulk nickel, but within values given in the literature. FIB-milled pillars demonstrated stochastic yield behaviour at all loading rates tested, yielding between 320 and 625 MPa. Deformation was apparent at FIB-milled pillar tops, where the smallest cross-sectional area was measured, but still exhibited superior yield strength to bulk nickel. The gallium damage at the outer surface of the pillars likely aids in dislocation nucleation and plasticity, leading to lower yield strengths than for the EBL pillars. Thermal drift, substrate effects, and noise due to vibrations within the indenter system contributed to variance and inconsistency in the data.

Spectrally isometric elementary operators

We present criteria for unital elementary operators (of small length) on unital semisimple Banach algebras to be spectral isometries. The surjective ones among them turn out to be algebra automorphisms.

Jigsaw Java: Intelligent, Automated Marking

The popularity of Computing degrees in the UK has been increasing significantly over the past number of years. In Northern Ireland, from 2007 to 2015, there has been a 40% increase in acceptances to Computer Science degrees with England seeing a 60% increase over the same period (UCAS, 2016). However, this is tainted as Computer Science degrees also continue to maintain the highest dropout rates.
In Queen’s University Belfast we currently have a Level 1 intake of over 400 students across a number of computing pathways. Our drive as staff is to empower and motivate the students to fully engage with the course content. All students take a Java programming module the aim of which is to provide an understanding of the basic principles of object-oriented design. In order to assess these skills, we have developed Jigsaw Java as an innovative assessment tool offering intelligent, semi-supervised automated marking of code.
Jigsaw Java allows students to answer programming questions using a drag-and-drop interface to place code fragments into position. Their answer is compared to the sample solution and if it matches, marks are allocated accordingly. However, if a match is not found then the corresponding code is executed using sample data to determine if its logic is acceptable. If it is, the solution is flagged to be checked by staff and if satisfactory is saved as an alternative solution. This means that appropriate marks can be allocated and should another student have submitted the same placement of code fragments this does not need to be executed or checked again. Rather the system now knows how to assess it.
Jigsaw Java is also able to consider partial marks dependent on code placement and will “learn” over time. Given the number of students, Jigsaw Java will improve the consistency and timeliness of marking.