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

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Transvascular nerve stimulation electrodes

Author: 
Date created: 
2012-05-30
Abstract: 

Patients in intensive care units (ICU) who require mechanical ventilation (MV) for more than a week have an increased risk of medical complications, such as ventilator acquired pneumonia and nosocomial infections, and are seven-times more likely to die in the ICU. The disused diaphragm muscle atrophies rapidly in ventilated patients, contributing to complications and frequent failure to wean from MV. Current phrenic nerve and diaphragm pacing systems require long, complicated, and risky surgery, unsuitable for those in the ICU. This study documents the prototype development of a simple, minimally invasive, transvascular device for electrically pacing the diaphragm intended to maintain diaphragm viability, reduce mortality, facilitate weaning from MV, shorten duration of ICU stay, and decrease hospitalization costs. Proof-of-concept, safety and stability data from acute and 3-week chronic pig experiments were analyzed. This thesis provides insight into endovascular electrode designs, fabrication, material selection, and configuration and orientation effects on phrenic nerve stimulation.

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

Sensitivity to Visuomotor Prediction Errors During Precision Walking

Date created: 
2015-04-20
Abstract: 

All human movements happen in the face of uncertainty. The objective of this thesis was to determine how the nervous system deals with sensorimotor uncertainty when adapting to visuomotor perturbations during walking. We asked subjects to walk and step on a target while wearing prism goggles that shifted the perception of the target’s location. We manipulated uncertainty by varying the strength and perturbation direction of the prism lenses on a trial-by-trial basis in three conditions: no, low and high noise. We measured lateral end-point errors of foot placement from the target in a visuomotor adaptation paradigm with baseline, adaptation and post-adaptation phases. Results showed increases in error variability, slower adaptation rates, and smaller errors in the first adaptation trial when increasing uncertainty. These results suggest that the nervous system relies on a predictive mechanism, which is sensitive to errors, and weights prior experiences to adapt walking.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Daniel Marigold
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

The association of perceived and objective built environment features with physical activity, adiposity and blood glucose

Author: 
Date created: 
2014-12-19
Abstract: 

Physical inactivity, obesity and diabetes are major public health problems and risk factors for cardiovascular disease, a number one cause of death globally. There is growing evidence to link built environment (BE) with physical inactivity, obesity and diabetes. However, published studies mostly focused on the macro-environment; perceived or objective BE measures; and self-reported rather than objectively assessed adiposity. There is also a lack of investigation of metabolic risk factors and lack of consideration for distinct demographic and socio-economic groups. Therefore, the objectives of this study were to explore the associations of both perceived and objective BE measures with distinct domains of physical activity (PA), objectively measured adiposity and fasting blood glucose (FBG); and to investigate the differences in environmental perceptions and the agreement between perceived and objective BE features based on gender, income level and ethnicity. Adults (n=356) between the ages of 35 and 70 years, from high- (median household income >$75,000) and low-income (<$55,000) areas in Vancouver were assessed for socio-demographics, PA (reported), adiposity (measured; body mass index, waist circumference, waist-to-hip ratio, and percentage of body fat), FBG, and environmental perceptions (Neighborhood Environment Walkability Scale). Neighbourhoods, a 500-meter buffer around a participant’s home, were directly assessed using the Irvine Minnesota Inventory (122 BE features). The study results indicate that more objective than perceived BE features were associated with PA; and associations were strongest for transportation PA followed with overall walking. Greatest effects were observed for features related to safety from traffic and presence of sidewalks. Associations of BE features with adiposity and FBG were limited. Additionally, environmental perceptions and the agreement between perceived and objective BE measures differed across gender, ethnicity, and income. The results suggest that improving pedestrian infrastructure and increasing safety from traffic may help residents engage more in transport PA and overall walking. Observed differences in BE perceptions may be used to direct the development of public health interventions aimed at increasing awareness about facilities in the neighbourhood whereby special consideration should be given to ethnic minorities and residents from low-income neighbourhoods.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Scott A. Lear
Department: 
Science:
Thesis type: 
(Dissertation) Ph.D.

Video Analysis of the Circumstances of Falls in Long-term Care

Author: 
Date created: 
2015-03-24
Abstract: 

Falls cause more than 95% of hip fractures and 65% of head injuries in older adults. A major barrier to prevention is lack of objective evidence of the circumstances of falls, especially in the high-risk long-term care (LTC) setting. My PhD research addresses this issue through the analysis of falls captured on video in two LTC facilities. My first study involved the development and validation of a 24-item video analysis questionnaire that probes key biomechanical aspects of fall initiation, descent, and impact from video footage. My results demonstrated good inter-rater and intra-rater reliability in 17 of the 24 questions (agreement≥80%, kappa≥0.6). My second study compared the circumstances of falls described in incident reports to information from video analysis (n=309, with 863 falls). I found poor agreement on the cause of imbalance and activity at time of fall (agreement=45%, kappa≤0.25), and moderate agreement on the use of mobility aids (agreement=79.5%, kappa=0.59). My third study examined how risk of head impact during falls was associated with biomechanical factors (from video analysis) and physiological factors (from Minimum Data Set) (n=160, with 520 falls). I found that 33% of falls involved head impact. Odds for head impact were increased more than 2-fold for female, impaired vision, and intact cognition. These trends were explained in part by women and individuals with relatively intact cognition who tend to fall during walking and fall forward (both increased the odds for head impact). Odds for head impact were not reduced by hand impact. Body rotation during descent from forward to sideways or backward decreased the odds of head impact nearly 3-fold. My fourth study used the same data set to examine how risk of hip impact during falls was influenced by biomechanical and physiological factors. I found falling forward was just as likely as falling sideways to cause hip impact. There was no association between physiological factors and odds for hip impact. Collectively, my findings should help guide the development of improved fall and injury prevention strategies, by providing new evidence on the circumstances of falls in LTC, and the risk factors for impact to the head and hip.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Stephen N. Robinovitch
Department: 
Science:
Thesis type: 
(Dissertation) Ph.D.

Drosophila adducin interacts with synaptic modelling proteins: Draper and Discs-large

Author: 
Date created: 
2015-03-30
Abstract: 

Manipulation of the postsynaptic hu-li tai-shao (hts) transcript can affect synaptic development and plasticity. Hts is an actin-spectrin binding protein that is situated close to the synaptic cell membrane where it can co-localize with many synaptic modelling proteins. Two proteins, Draper (Drpr) and Discs large (Dlg), were found to be regulated by Hts at the postsynaptic membrane of Drosophila 3rd instar larval NMJ. Interestingly, both interacting partners are known to be involved in synaptic remodeling, where Drpr is involved in synaptic pruning and Dlg is involved in the regulation of synaptic cell-cell adhesion. In this study I focused on the characterization of interactions between Hts and Drpr while looking into the possibility that Dlg serves as a mediator between these interactions. I found genetic interaction between hts and drpr, and saw a potential triple-protein-complex between Hts, Dlg and Drpr, which may work together to manipulate synaptic development.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Charles Krieger
Nicholas Harden
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Effects of Elevated Core Temperature and Normoxic 30% Nitrous Oxide on Control of Human Breathing during Short Duration, High Intensity Exercise

Author: 
Date created: 
2014-09-17
Abstract: 

It is unresolved how pulmonary ventilation (VE) is influenced by normoxic 30% nitrous oxide (N2O) breathing and hyperthermia during supramaximal intensity exercise. It was hypothesized that normoxic N2O will suppress and hyperthermia will increase exercise ventilation, timing and ventilatory drive during supramaximal intensity exercise. Seven college-aged males volunteered for 4 separate 30 s Wingate cycle ergometer tests. The studies included a 2 x 2 design with factors of Thermal State (normothermia or hyperthermia) and Gas Type (Air or normoxic 30% N2O). A significant interaction (F=8.4, p=0.03) between these 2 factors for VE was explained by a VE from 85 ± 27 L/min (p=0.06) during normothermia with N2O to a VE of 104 ± 23 L/min in hyperthermia with N2O. There were no main effects or interactions for Thermal State and Gas Type for timing components and ventilatory drive. In conclusion, an interaction of Thermal State and Gas Type on VE was explained by its suppression during normothermia relative to its rate in hyperthermia, both during normoxic N2O breathing during supramaximal intensity exercise.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Matthew White
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Sugar-sweetened beverages and their relationship to obesity in South Asian children

Date created: 
2014-09-04
Abstract: 

The prevalence of obesity among South Asian (SA) children is increasing in comparison to their ethnic counterparts. This is of great concern given that SA adults have a greater predisposition to cardiovascular disease and type II diabetes. This increase in obesity may be further exacerbated by the adoption of ‘Westernized’ lifestyle behaviours such as dietary changes. Over the past fifty years, consumption of sugar sweetened beverages (SSBs) has dramatically increased to high levels which have led SSBs to become highly scrutinized as a major contributor to the rise in childhood obesity. Evidence suggests the consumption of SSBs is associated with a rise in body mass index (BMI) in young children and adolescents. It is unknown whether this effect is exacerbated in specific populations at high risk of obesity, such as SA children. For this investigation a total of 363 SA children enrolled in grades 2 and 3 were randomly recruited from communities in Vancouver, British Columbia and Hamilton, Ontario. Children were evaluated using the RICH LEGACY Questionnaire that included a comprehensive assessment of the child’s lifestyle and physical measures. Independent multiple linear regression models adjusted for age and sex displayed an association between consumption of SSBs with z-BMI (p=0.02) but not with waist circumference (WC) (p=0.35) and waist to height ratio (W:Ht) (p=0.86). Diet beverages were not associated to z-BMI, WC or W:Ht (p=0.43, 0.46, 0.43, respectively). This new evidence is key in shaping future public health policies and interventions aimed at reducing the prevalence of childhood obesity.

Document type: 
Thesis
File(s): 
Senior supervisor: 
Scott Lear
Department: 
Science:
Thesis type: 
(Thesis) M.Sc.

Molecular Dynamics Based Predictions of the Structural and Functional Effects of Disease Causing Cardiac Troponin C Mutations

Date created: 
2014-05-29
Abstract: 

Human cardiac troponin C (HcTnC), the regulatory calcium-binding component of the troponin complex, is responsible for the regulation of cardiac muscle contraction in response to varying cytosolic calcium levels. Mutations that are shown to increase the cTnC Ca2+ affinity are hypothesized to induce hypertrophic cardiomyopathies (HCM). Several mutations in HcTnC have been selected that are associated with HCM. These mutations include A8V, L29Q, C84Y, E134D, and D145E. The structural effects of these mutations have been modeled through equilibrium molecular dynamics and their functional and structural impacts have been assessed. In each mutant that was analyzed, the equilibrated structures have shown notable deviations from wild-type in the regions known to be cardiac troponin I (cTnI) interaction sites. There were differences in the conformation dynamics of site II and cTnC/cTnI interaction sites. We anticipate these correlations may contribute to Ca2+ affinity either directly or indirectly through cTnI association.

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

Scaling of sensorimotor control in terrestrial mammals

Date created: 
2013-12-17
Abstract: 

Terrestrial mammals span a wide range of sizes, with the largest elephant being several million times more massive than the smallest shrew. This huge size range results in small and large animals experiencing very different physical challenges, yet all animals must effectively interact with their environment to survive. In order to sense and respond to stimuli with similar speed and precision, small and large animals may need to control their movement in different ways. To begin to understand whether and how small and large animals coordinate their movement with similar effectiveness despite their different physical challenges, I investigated how size influences the physiological mechanisms underlying sensorimotor control. My general hypothesis was that the sensorimotor systems of larger animals have longer delays and lower precision than those of smaller animals. To investigate the scaling of delays, I combined my own electrophysiology measurements with data from the literature to determine how total response time and its component delays changed with animal mass. To investigate the scaling of precision, I combined my own histology measurements with data from the literature to determine how nerve fiber number and size distribution changed with animal mass. As part of this, I developed a supervised image analysis method to measure nerve fiber characteristics in scanning electron microscope images. I found that larger animals have longer absolute delays and more nerve fibers than smaller animals. However, changes to movement times with animal size almost entirely compensate for increases in absolute delays, resulting in similar relative delays for all sizes of animals. Nerve fiber number increases more slowly than animal mass, area, and muscle force, suggesting that larger animals have relatively fewer sensors and motor units than smaller animals. Nerve fiber size distribution becomes more bimodal as animal size increases, ameliorating the potential tradeoff between speed and precision in peripheral nerves. While small and large animals seem to be able to sense and respond to stimuli within the same relative time, large animals may face challenges in situations requiring short absolute delays and high precision, and may need to rely more heavily on predictive methods of control.

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

In vivo Measurements of Biophysical Properties of a Heart and Aorta in a Mouse Model of Marfan Syndrome

Author: 
Date created: 
2014-05-28
Abstract: 

In Marfan Syndrome (MFS) patients cardiovascular complications are the most life-threatening manifestations and death is often sudden due to aortic dissection and rupture. Echocardiography is critical in the diagnosis and follow-up of MFS patients to detect and evaluate their cardiovascular phenotype. High frequency echocardiography was used to investigate the structural and functional properties on 6- and 12-mo WT and MFS [Fbn1 (C1039G/+)] mice (n = 8). The data show that Pulse Wave Velocity (PWV) was significantly increased in 6-mo MFS vs. WT (366.6 ± 19.9 vs. 205.2 ± 18.1 cm/s; p < 0.001) and 12-mo MFS vs. WT (459.5 ± 42.3 vs. 205.3 ± 30.3 m/s; p = 0.001) and the PWV increased directly in proportion to age in MFS mice but not in WT mice. LV mass (3.06 ± 0.16 vs. 2.46 ± 0.09 μm/g; p = 0.007) was significantly increased in 6-mo MFS mice compared with WT. We also found a significantly enlarged aortic root, decreased E/A ratio, prolonged isovolumic relaxation time and increased myocardial performance index in MFS mice compared with WT for both age groups. This study shows significant aortic dilation and central aortic stiffness in the MFS mice which are associated with LV hypertrophy, systolic and diastolic dysfunction. Moreover, the symptoms progressed with increasing age from six months to twelve months.

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