Biomedical Physiology and Kinesiology - Theses, Dissertations, and other Required Graduate Degree Essays

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Effects of physiological, pharmacological, and toxic factors on cell transport

Date created: 
2014-04-22
Abstract: 

Endocytic transport is a fundamental cell function involved in nutrient assimilation, signal transduction, growth, and other cellular activities. Disruption of this transport has been associated with aging and some chronic diseases. There is growing interest in possible regulation of the endocytic machinery by physiological factors, and in pathological processes. In this project, I analyzed effects of (a) pro-oxidative factors such as ROS and amyloidogenic polypeptide aggregates, (b) physiological factors such as EGF and steroid hormones, and (c) select pharmacological or phytochemical compounds, on different endocytic pathways within a cell, and among different cell types. The results provide evidence that pro-oxidants can inhibit endocytic transport in different cell types; and the pathways can exhibit differences in sensitivity to a pro-oxidant. Select physiological and pharmacological factors can also stimulate or inhibit some of these transport pathways in different cell types. Further screening and testing of pharmacological modulators may identify possible therapeutic compounds.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Amandio Vieira
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Computational models of chronic diseases: understanding and leveraging complexity

Peer reviewed: 
No, item is not peer reviewed.
Date created: 
2014-04-14
Abstract: 

People struggle to implement interventions that create a significant and sustainable weight loss. This suggests that we need to move beyond viewing obesity as a mere matter of diet and exercise. Instead, we need to accept that the system giving rise to obesity is complex and re-think the ways in which we have approached weight management. This thesis is concerned with the development of microsimulation models that address three features of this complexity at the level of individual food and physical activity behaviours: heterogeneity of individuals and environments, many interactions and loops found between drivers and nonlinearity of the relationships between behaviours. These models were used to explore the dynamics of behaviours, and to support `what-if' scenarios in which we can assess the virtual consequences of possible interventions. In particular, we found that social influences can be as important as environmental influences in changing individuals' weight. However, simulations suggested that intervening in social influences has a larger impact on changing weights by promoting healthy eating than either tax-based or zoning interventions. Our models demonstrated that the structure of communities can be a confounder, as strongly-linked communities reduce the effectiveness of interventions based on social influences. We also highlighted the potential of models to generate social theories. Taking binge drinking as a case study, we generated a set of hypotheses that explains the behaviour of half of the binge drinkers and 4 out of 5 non-binge drinkers. This thesis also made several technical advances. First, we presented an innovative computational framework that supports modelers in expressing how social influences are mediated by the specificities of each individual's context. This is a major improvement over previous microsimulation models that were limited to viewing obesity as contagious. The framework was demonstrated for insurgencies and obesity. Second, we designed and evaluated novel techniques to address heterogeneity when performing a randomized controlled trial for behaviour change. Software was created for both. Finally, we created a system to support practitioners in navigating the maze of factors relevant to their patients, and we used health games to empower patients into the management of their own well-being.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Diane Finegood
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) Ph.D.

Automatic pacing: on the use of external timing cues to regulate speed during human walking and running

Author: 
Date created: 
2013-12-16
Abstract: 

Out of all parameters used to describe gait, overground speed is one of the most important. The importance of gait speed is highlighted when used as a measure of performance during exercise, or as a measure of function when walking ability is compromised. Because the ability to control gait speed is imperative to reach optimal results in both exercise and gait rehabilitation, a system that helps people to control their overground speed more accurately might be beneficial. Developing an overground speed control system was the main goal of this thesis. To gain insight in the performance enhancing effects that can be expected from such a system, my colleagues and I first determined the ability of recreational runners to accurately control their own speed. We then used a simulation approach to estimate the effect of pacing inaccuracy on optimal running performance. Our simulation results suggested that the existing pacing error (2.3±4.6%) would decrease optimal performance by approximately 5% for an average recreational runner. These results indicate that the performance of recreational runners could be improved by minutes for typical race distances, simply by helping them achieve and maintain their optimal speed. To determine the viability of controlling overground speed by prescribing step frequency, we quantified the dynamic response in walking and running speed following controlled perturbations in prescribed metronome frequency. We found that perturbations in metronome frequency triggered rapid and predictable changes in speed, suggesting that overground speed is indeed controllable by prescribing step frequency. However, due to the variability present in the speed response, both within and between individuals, accurately controlling overground speed using an open-loop speed control system is not possible. To improve speed control performance we developed and built a closed-loop speed control system, which made the metronome frequency directly dependent on the instantaneous speed error. We tested the performance of this system in both walking and running, and found that the speed control accuracy of a closed-loop system was significantly better compared to self-paced running and an open-loop speed control system. Finally, we translated the speed control system into a training tool available to the general public.

Document type: 
Thesis
File(s): 
Senior supervisor: 
J. Maxwell Donelan
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Dissertation) Ph.D.

Biomechanics of Falls and Hip Fractures in Older Adults

Date created: 
2013-09-05
Abstract: 

Over 90% of hip fractures are due to falls. Yet, only 1-2% of falls result in hip fracture. This suggests that there exist factors that determine injurious and non-injurious falls, but we have limited information on this area. My PhD research addresses this issue through three related studies. My first study examined age-related changes in the dynamic compressive properties (stiffness and damping) of soft tissues over the hip region. My results indicate that the soft tissues of older adults absorb 70% less energy than those of young adults, thereby requiring more energy to be absorbed in the underlying skeletal components, with corresponding increase in fracture risk. My second study determined the effect of hip abductor muscle forces and knee boundary conditions on bone stress at the femoral neck during simulated falls. My results show that physiologically feasible increases in muscle force can reduce peak compressive and tensile stresses by up to 24 and 47%, respectively. These effects are similar to the magnitude of decline in fracture strength associated with osteoporosis. Therefore, muscle contraction at impact may be as important as bone density in determining hip fracture risk during a fall. My third study analyzed the kinematics of real-life falls in older adults, as captured by surveillance cameras, to estimate velocity of the pelvis at impact -- a primary determinant of impact force and fracture risk. Results show that the pelvis impact velocity averages 2.08 m/s, which is 48% below simple free-fall predictions based on fall height ((2gh)^0.5) and 20% below average previously reported for young adults. Results also show that several mechanisms contribute to reducing the pelvis impact velocity, including hand impact and attempts to recover balance by stepping. Collectively, these findings should add important pieces to the puzzle of whether a particular fall will result in hip fracture, and informs future direction for clinical and laboratory-based research on hip fracture prevention.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Stephen Robinovitch
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Dissertation) Ph.D.

Serial ultrasonographic evaluation of diaphragm thickness during mechanical ventilation in ICU patients.

Date created: 
2013-08-29
Abstract: 

While mechanical ventilation (MV) is life-saving in patients with acute respiratory failure, prolonged mechanical ventilation is associated with numerous potential complications. Recent studies have suggested that the ventilator is a likely cause of the decreased diaphragm force generating capacity (dFGC) seen in mechanically ventilated patients. Further, mode of ventilation has been associated with diaphragm atrophy, which has been identified as a key factor influencing dFGC. Animal studies suggest that even as little as 18 hours of mandatory modes of ventilation lead to diaphragm-muscle atrophy and weakness. This study utilizes ultrasound to investigate the rate at which diaphragm thickness changes in response to mode of MV in critically ill patients, and validates the reliability of our sonography techniques. We acquired daily ultrasonographic images of the right diaphragm in the zone of apposition in critically ill patients (n=8) in the ICU of the Royal Columbian hospital. As a control for generalized muscle wasting in the critically ill, we acquired daily ultrasonographic images of the quadriceps from each subject. Patients on all modes of ventilation were included. Inter-operator and inter-observer reliability tests were conducted. A mean increase in diaphragm thickness of 8.41±3.88% was detected over a mean of 5.5±4.28 days in all patients on PS ventilation (n=8), a mean increase of 1.53±1.39% per day. Patients ventilated on AC mode (n=4) showed a mean decline in diaphragm thickness of 21.2±10.8% over 4.5±4.4 days, an average decrease of 4.7±5.7% per day. Mean decline in quadriceps thickness for all participants in this study (n=8) was 14.4±13.6% over a mean period of 7.1±4.7 days, an average decline of 2±2.7% per day. Ultrasound provides a reliable non-invasive method of measuring diaphragm thickness and tracking rates of change in thickness in mechanically ventilated critically ill patients. This may be a useful tool in critical care units to identify patients who may be at risk of weaning difficulties secondary to diaphragms that are weakened as a result of atrophy.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Andy Hoffer
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

A Complex Systems Approach to Perceptions of Obesity in Service Users, Health Care Practitioners and Policy Makers

Date created: 
2013-08-14
Abstract: 

Current research supports the complexity of obesity and the need for collaboration between sectors to create change, yet there is still a pervasive perception that individuals are to blame for their weight. The Applied Research Collaborations for Health Research group, Dalhousie University, Halifax, Nova Scotia conducted key informant interviews to examine the beliefs of service users, health practitioners and policy makers regarding obesity. These data were used to conduct a secondary analysis using qualitative analysis methodology to explore perceptions of obesity within a complex systems framework. Three major themes were common among participant groups. There was a desire for immediate results, a focus on individual blame and a resultant tension for change. Exploring these themes using a complex system lens demonstrated the importance of engaging contradictory groups to work together in a collaborative framework. Aligning paradigms across the treatment spectrum is crucial to working towards solutions that embrace complexity.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Diane Finegood
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Cerebrovascular and respiratory responses to poikilocapnia and eucapnia in resting normothermic and hyperthermic humans

Date created: 
2012-06-07
Abstract: 

Human cerebrovascular responses in the middle cerebral artery (MCA), posterior cerebral artery (PCA), and basilar artery (BA) were assessed in two studies. In the first study, an index of cerebrovascular conductance (ICVC) in the MCA was decreased (P<0.05) in poikilocapnic, hyperthermic humans, while ICVC was maintained in the PCA and BA. Eucapnia during hyperthermia returned ICVC in the MCA, PCA, and BA to resting ICVC values. In the second study the effects of volitional hyperventilation on cerebral blood velocity (CBV) and ICVC responses in normothermic humans were assessed in the same three cerebral vessels. Results indicated that, unlike in hyperthermia, responses were uniform with CBV and ICVC decreases (P<0.05) in normothermic poikilocapnia in all three cerebral vessels with no differences (P>0.05) from normothermic resting values when PETCO2 was restored to eucapnic partial pressures. In conclusion, evidence suggests there are regional differences of cerebrovascular responses in hyperthermic, but not normothermic humans.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Matthew White
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Association of Clinical and Molecular Features of Previously Treated Tumour Sites with Risk for Second Oral Malignancy

Author: 
Date created: 
2013-08-16
Abstract: 

Second oral malignancy (SOM) is a common occurrence for patients with oral cancers, contributing to low 5-year survival rates for this disease (~60%). Oral mucosal changes at previously treated cancer sites are common and can be defined clinically by white-light examination and toluidine blue staining, and molecularly by loss of heterozygosity (LOH) analysis. To determine the role of such changes in predicting SOM, this study analyzed data collected from 194 oral squamous cell carcinoma patients in follow-up after treatment of which 31 (16%) developed SOM. Two features were shown to be associated with elevated risk of SOM: the clinical presence of an oral premalignant lesion (OPL) (P <0.001), and LOH at 9p21 (P = 0.045). The results support the need for biopsy of OPLs observed during follow-up, especially when persistent, and suggest that LOH analysis of such biopsies might differentiate those at-risk for SOM, allowing for early intervention.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Miriam Rosin
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

The interaction between cardiovascular and posture controls and the effects of ageing

Author: 
Date created: 
2010-11-12
Abstract: 

Fainting during quiet standing is a serious problem in syncopal youth and prominent in elderly individuals. This thesis examined the possible interaction of the cardiovascular and posture control systems during quiet stance and the effect of ageing. We hypothesized that there exists a bidirectional interaction between blood pressure (BP) and posture changes through the activation of skeletal muscle pump via the calf muscles. In study one, the analysis methods for non-stationary signals were explored and the wavelet transform coherence method was validated for its applicability. In study two, cardiovascular variables, stabilogram data and posture muscle electromyography (EMG) data were compared to each other. The EMG and BP signals showed discrete regions of high coherence during quiet stance. In a third study, the effect of ageing on the relationship between these two systems was investigated. Age was found to have a statistically significant affect on the relationship between these two systems

Document type: 
Thesis
File(s): 
Senior supervisor: 
Dr. Andrew P. Blaber
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Thesis) M.Sc.

Cardiovascular disease risk after spinal cord injury: The role of autonomic dysfunction

Date created: 
2013-08-07
Abstract: 

Cardiovascular disease (CVD) is the leading cause for mortality and morbidity after spinal cord injury (SCI) with an earlier onset and more rapid progression compared to the general population. Lifestyle changes after injury have been suggested to be the main contributor to CVD risk, but I proposed that the issue is more complicated. Although less well-known, autonomic function is affected by SCI, in addition to motor and sensory dysfunction. Cardiovascular autonomic dysfunction is a particular concern in individuals with high lesions (above T5) due to the possible disruption of descending spinal sympathetic pathways to the heart and main vascular resistance bed. In this thesis, I propose that cardiovascular autonomic impairment plays a role in the elevated CVD risk. The thesis starts with an evaluation of the prevalence and progression of cardiovascular dysfunction after SCI. Then, the contribution of autonomic dysfunction on CVD risk is investigated. In addition, markers for obesity-related CVD risk specific to individuals with SCI and ECG markers for cardiac arrhythmias in relation to autonomic impairments are explored. Prevalence of cardiovascular dysfunction was found not to improve over time after injury and it was highest in those with lesions above T5. The second study showed that autonomic dysfunction contributes to overall CVD risk and specifically to glucose intolerance, either directly or through an interaction with physical activity levels. The data showed that waist circumference is the best marker for obesity considering ability to detect adiposity and CVD risk, and practicality of use. A specific cut-off for waist circumference was found to be lower compared to the general recommendations. The final study showed increased values for the ECG markers Tpeak-Tend variability, P-wave variability and QTVI, only in those with impairments to descending cardiac sympathetic pathways. The ECG characteristics may be indicative of susceptibility to cardiac arrhythmia related to autonomic dysfunction. Implications of these findings are that management of cardiovascular autonomic dysfunction should remain a priority into the chronic phase of injury, not merely due the direct impact on quality of life, but also due to its contribution to the elevated cardiovascular disease risk after SCI.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Victoria Claydon
Department: 
Science: Department of Biomedical Physiology and Kinesiology
Thesis type: 
(Dissertation) Ph.D.