Improved Accuracy in Optical Motion Capture Measurements Leads to Increased Sensitivity to Kinematic Changes

Clinical optical motion capture allows us to obtain kinematic and kinetic outcome measures that aid clinicians in diagnosing and treating different pathologies affecting healthy gait. The long term aim for gait centres is for subject-specific analyses that can predict, prevent, or reverse the effects of pathologies through gait retraining. To track the body, anatomical segment coordinate systems are commonly created by applying markers to the surface of the skin over specific, bony anatomy that is manually palpated. The location and placement of these markers is subjective and precision errors of up to 25mm have been reported [1]. Additionally, the selection of which anatomical landmarks to use in segment models can result in large angular differences; for example angular differences in the trunk can range up to 53o for the same motion depending on marker placement [2]. These errors can result in erroneous kinematic outcomes that either diminish or increase the apparent effects of a treatment or pathology compared to healthy data. Our goal was to improve the accuracy and precision of optical motion capture outcome measures. This thesis describes two separate studies. In the first study we aimed to establish an approach that would allow us to independently quantify the error among trunk models. Using this approach we determined if there was a best model to accurately track trunk motion. In the second study we designed a device to improve precision for test, re-test protocols that would also reduce the set-up time for motion capture experiments. Our method to compare a kinematically derived centre of mass velocity to one that was derived kinetically was successful in quantifying error among trunk models. Our findings indicate that models that use lateral shoulder markers as well as limit the translational degrees of freedom of the trunk through shared pelvic markers result in the least amount of error for the tasks we studied. We also successfully reduced intra- and inter-operator anatomical marker placement errors using a marker alignment device. The improved accuracy and precision resulting from the methods established in this thesis may lead to increased sensitivity to changes in kinematics, and ultimately result in more consistent treatment outcomes.

The Psychometric Properties of the Developmental Reading Assessment

ABSTRACT The purpose of this study was to examine the technical adequacy of the Developmental Reading Assessment (Beaver & Carter, 2004). Internal consistency analysis, factor analysis, and linear regression analyses were used to test whether the DRA is a statistically reliable measuring of reading comprehension for Grades 7 and 8 students. Correlational analyses, decision consistency analyses, and a focus group of experienced Intermediate (Grades 7 and 8) teachers examined whether there is evidence that the results from the DRA provide valid interpretations regarding students’ reading skills and comprehension. Results indicated that, as currently scored, internal consistency is low and skewness of distribution is high. Factor analyses did not replicate those cited by the DRA developers to prove construct validity. Two-way contingency analyses determined that decision consistency did not vary greatly between the DRA, EQAO, scores and report card marks. Views expressed during the focus group echoed many of the challenges to validity found in the statistical analysis. The teachers found that the DRA was somewhat useful, as there were limited alternative reading assessments available for the classroom, but did not endorse it strongly. The study found little evidence that the DRA provides valid interpretations regarding Intermediate students’ reading skills. Indicated changes to the structure and administration procedures of the DRA may ameliorate some of these issues.

IMPACT OF RNA VIRUSES ON THE REGULATION OF IL-23 IN MOUSE AND HUMAN MODELS OF INFECTION.

Interluekin-23 (IL-23) is a pro-inflammatory cytokine critical to the regulation of innate and adaptive immune responses. The main role for this cytokine is in the proliferation and differentiation of the IL-17 producing CD4 T helper cell, Th17. Virus infection deregulates IL-23 expression and function, but little is known about the mechanism behind this phenomena. Here, I demonstrate a reduction of Toll like receptor (TLR) ligand-induced IL-23 expression in lymphocytic choriomeningitis virus (LCMV)-infected bone marrow-derived dendritic cells (BMDCs), indicating that a function of these cells is disrupted during virus infection. I propose a mechanism of TLR ligand-induced IL-23 expression inhibition upon LCMV infection via the deactivation of p38, AP-1, and NF-κB. Further analysis revealed a direct relationship between LCMV infection with the IL-10 and SOCS3 expression. To understand IL-23 function, I characterized IL-23-induced JAK/STAT signalling pathway and IL-23 receptor expression on human CD4 T cells. My results demonstrate that IL-23 induces activation of p-JAK2, p-Tyk2, p-STAT1, p-STAT3, and p-STAT4 in CD4 T cells. For the first time I show that IL-23 alone induces the expression of its own receptor components, IL-12Rβ1 and IL-23Rα, in CD4 T cells. Blocking JAK2, STAT1, and STAT3 activation with specific inhibitors detrimentally effected expression of IL-23 receptor demonstrating that activation of JAK/STAT signalling is important for IL-23 receptor expression. I also addressed the effect of viral infection on IL-23 function and receptor expression in CD4 T cells using cells isolated from HIV positive individuals. These studies were based on earlier reports that the expression of IL-23 and the IL-23 receptor are impaired during HIV infection. I demonstrate that the phosphorylation of JAK2, STAT1, and STAT3 induced by IL-23, as well as IL-23 receptor expression are deregulated in CD4 T cells isolated from HIV positive individuals. This study has furthered the understanding of how the expression and function of IL-23 is regulated during viral infections.