Chronic kidney disease (CKD) is a major public health concern, characterized by an irreversible reduction in renal function. Currently, creatinine-based GFR estimation is predominantly used clinically to characterize CKD. However, this method is known to be an insensitive test for early losses of kidney function. Since patient prognosis relies heavily on slowing further decline of kidney function, uncovering novel biomarkers for kidney function, in conjunction with eGFR, will help improve patient outcome. Epigenetic-based biomarkers have been identified in numerous cancers, as DNA methylation changes alter cellular function. Thus, the objective of this study is to determine novel DNA methylation patterns reflecting altered kidney function. Five healthy participants that have undergone a nephrectomy have donated urine samples before and after their surgery, and global DNA methylation changes were analyzed through the 450K HumanMethylation microarray. Site- and region-level analyses were conducted to determine significant differentially methylated probes post-nephrectomy. The differential associations observed post-nephrectomy are statistically significant in both the site-level and regional analyses. Nineteen significant candidate probes have been systematically selected for validation, based on involvement in kidney function and consistent direction of methylation. Pyrosequencing assays have also been successfully designed and tested with control DNA, however replication of the microarray findings in participant DNA was unsuccessful. The inability to validate these candidate probes may be attributed to many influencing factors, and with this in mind, uncovering novel methylation patterns is still a promising biomarker for evaluating kidney function. / Thesis / Master of Science (MSc)

Knee osteoarthritis (OA) is a debilitating and costly chronic health condition affecting approximately 10% of Canadians. Total Knee Arthroplasty (TKA) is an effective procedure restoring quality of life and providing pain relief for patients with knee OA. The benefits of TKA are well established for patients with knee OA, but determining those who would most benefit is a challenging task. Physical functioning in patients with knee OA has been shown to be a key factor for appropriateness for TKA. The Lower Extremity Functional Scale (LEFS) and the Oxford Knee Score (OKS) are two patient-reported outcome measures (PROMs) measuring physical function that can be utilized to assist health care professionals in determining the need for TKA among this population. The LEFS is a regional PROM consisting of 20 questions asking about activities relating to lower extremity functioning. Questions are scored on a 5-point descriptive scale from 0 (extreme difficulty or unable to perform the activity) to 4 (no difficulty) with a total score of 80. Higher scores represent higher functioning. The OKS is a site-specific PROM that asks questions about pain and function and consists of 12 items ranked on a 5-point descriptive scale. Scores range from 1 to 5 (total score of 60) for each item with lower scores representing higher function. The purpose of this thesis was to determine the diagnostic accuracy for the LEFS and the OKS for determining appropriateness for TKA in people with primary knee OA. The hypothesis for the current study was that the LEFS would have higher diagnostic accuracy for appropriateness for TKA compared to the OKS. A cross-sectional retrospective study of patients with knee OA attending a Regional Joint Assessment Program (RJAP) from January to September 2013 was conducted. Classification of appropriateness for TKA was determined by the attending orthopedic surgeon’s decision at the end of the assessment. Diagnostic accuracy for the OKS and the LEFS were determined using the area under the curve (AUC) of the receiver operator characteristic (ROC) curve. Cut-off scores were calculated for both outcome measures. Four hundred and twenty one patients eligible for the study (41.8% males; 66.9 years old) completed the OKS and the LEFS. The diagnostic accuracy for the OKS and the LEFS was determined using the AUC of the ROC curve for each patient-reported measure using Stata ® version 12.1. The cut-off scores were determined as the point on the ROC curve yielding the best sensitivity and specificity for the two outcome measures. The results showed the LEFS did not have higher diagnostic accuracy (LEFS AUC = 0.686 (95% CI = 0.636 – 0.736); OKS AUC = 0.674 (95% CI = 0.623- 0.724)) for determining appropriateness for TKA in patients with primary knee OA in isolation. The best cut-off score for those deemed appropriate for TKA among patients with knee OA was 26 out of 80 LEFS points and 42 points out of 60 OKS points. The results of this thesis agree with previous research reporting that decision-making regarding the need for TKA in patients with knee OA is multi-factorial. Our data confirm that this decision cannot be based on patient-reported physical function alone. Factors other than or in addition to patient-reported lower limb physical functioning should be considered when determining which patients with knee OA would most benefit from TKA. Further research evaluating these factors is warranted to improve triage services for patients with knee OA most likely to benefit from TKA. / Thesis / Master of Science Rehabilitation Science (MSc)

We present the dielectric function of a bcc-In2O3 thin film in the wide spectral range from nearinfrared to vacuum-ultraviolet and for temperatures 10 K–300K, determined by spectroscopic ellipsometry. From the temperature dependence of electronic transition energies, we derive electron-phonon coupling properties and found hints that the direct parabolic band-band transitions involve In-d states. Further we discuss possible excitonic contributions to the dielectric function.

Loudness growth evaluation is important to comprehend the theoretical implication of loudness in both normal hearing and hearing impaired people, as well as applied applications in hearing-aid design. However, current psychoacoustic procedures are subjective, time consuming and require the constant attention of participants. The primary aim of the present study is to investigate the feasibility of objectively assessing the loudness growth function by using the Auditory Brainstem Response (ABR). Previous studies applied either non-frequency specific click stimuli or tone burst stimuli to evoke auditory brainstem responses. Although the advantage of a chirp stimulus in producing a more reliable response has been well documented in many studies, no one has previously used this stimulus to evaluate loudness growth functions. One octave-band chirp stimuli with center frequencies of 1000 Hz and 4000 Hz were chosen to evoke ABRs at 7 different stimulus intensities from 20 dB nHL to 80 dB nHL with 10 dB steps. In the psychoacoustic procedure, subjects were asked to rate the perceived loudness of each presented stimulus. The recorded ABR trials were averaged by a modified version of weighted averaging based on Bayesian inference. This method of averaging decreases the effects of non-stationary noise sources by calculating a number of locally-stationary noise sources based on a series of F-tests. The peak-to-trough amplitude of the most salient peak of the ABR at each intensity constituted the physiological loudness estimate. Linear and power functions relating the psychoacoustical results and the ABR measurements were compared. The obtained results were in good agreement with equal-loudness contours and estimated loudness from the loudness model for time-varying sounds of Glasberg, & Moore (2002). We concluded that loudness growth can be estimated with ABRs to frequency-specific chirp stimuli. / Thesis / Master of Science (MSc)

A common alternative to full resolution of the near-wall region in computational fluid dynamics (CFD) simulations is the use of wall functions that decrease the mesh requirements in this region. This study presents two alternatives to current wall functions. The first method is based on numerically approximating a turbulent velocity profile using a one-dimensional subgrid contained within walljacent control cells. The second method is an analytical approach similar to previous wall function methods, but this method is valid both inside and outside of the fluid boundary layer. Use of both methods allows approximation of boundary layers of varying height relative to the first layer sizing. Use of these methods allows wall adjacent primary grid sizes to vary from low-Re model sizing of y+ ≈ 1 to grid sizes of y+ ~ 1000 or more without significant loss in accuracy, and with computational costs similar to currently used wall functions.

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