Neural precursor cells (NPCs) are excellent candidates for use in therapeutic applications which aim to replace lost or damaged cells in an injured central nervous system (CNS); however, to effectively harness their potential, the factors that regulate NPC behaviour and fate must be well understood. Herein, we examine the effects of Cyclosporin A on NPC proliferation kinetics, survival, and fate using in vitro assays at the population level and at the single cell level. Cyclosporin A acts directly on NPCs to enhance cell survival, without altering NPC proliferation kinetics or differentiation profiles, resulting in greater numbers and size of NPC colonies. Additionally, Cyclosporin A decreases cell-cell adhesions. Analogous with our in vitro results, administration of Cyclosporin A to uninjured adult animals increases NPC numbers. Thus, Cyclosporin A can effectively increase the NPC pool making it a promising molecule for developing clinically relevant strategies for CNS repair.

Neural precursor cells (NPCs) are excellent candidates for use in therapeutic applications which aim to replace lost or damaged cells in an injured central nervous system (CNS); however, to effectively harness their potential, the factors that regulate NPC behaviour and fate must be well understood. Herein, we examine the effects of Cyclosporin A on NPC proliferation kinetics, survival, and fate using in vitro assays at the population level and at the single cell level. Cyclosporin A acts directly on NPCs to enhance cell survival, without altering NPC proliferation kinetics or differentiation profiles, resulting in greater numbers and size of NPC colonies. Additionally, Cyclosporin A decreases cell-cell adhesions. Analogous with our in vitro results, administration of Cyclosporin A to uninjured adult animals increases NPC numbers. Thus, Cyclosporin A can effectively increase the NPC pool making it a promising molecule for developing clinically relevant strategies for CNS repair.

This thesis examined post-stroke gait asymmetry: a prevalent issue and one that has a number of associated negative consequences (e.g. challenged balance control, gait inefficiencies, increased risk of musculoskeletal injury to the non-paretic limb and decreased overall activity levels). This thesis is comprised of three studies that focused on 1) how gait symmetry should be measured, 2) how gait asymmetry may change in the long term post-stroke and 3) whether gait asymmetry is responsive to a rehabilitation intervention. A comparison of the most common expressions of spatiotemporal gait symmetry revealed that the simple symmetry ratio calculation was most appropriate on the basis of ease of interpretation and clinical usefulness. Swing time, stance time and step length were found to be the most useful gait parameters to assess for symmetry. Although related, swing time, stance time and step length ratios exhibit variation in the discrimination of post-stroke individuals, in their inter-relationships and in their relationship velocity. When when used together, swing time, stance time and step length asymmetry ratios may provide a complementary picture of the gait pattern and the quality of gait control. It was also demonstrated that swing time and stance time asymmetry were worse in later stages post-stroke when assessed cross-sectionally. In contrast, gait velocity did not exhibit this pattern. These results indicate that the control of gait (symmetry) may decline over time post-stroke, independent from the capacity for gait which remains constant (velocity). This dissociation in characteristics supports the concept that these two variables (symmetry and velocity) may represent separate features of post-stroke gait. Finally, individuals with sub-acute stroke are capable of altering the temporal symmetry of their gait in response to visual biofeedback. Individuals with sub-acute stroke differ in terms of the strategy they employ in response to biofeedback and the observed improvements in gait symmetry were not always achieved in the desired manner: increased use of the paretic lower extremity. This thesis presents new information regarding the asymmetrical nature of post-stroke gait. Future work may extend these findings to develop a comprehensive approach to gait measurement as well as gait interventions that encourage increased paretic limb use instead of compensatory behaviour.

This research investigated aspects of the morphosyntactic language development of 115 3-, 4-, and 5-year-old monolingual Spanish-speaking preschool children who resided in Cali, Colombia. Two general language measures were collected from the children: a standardized receptive vocabulary measure (Test de Vocabulario en Imágenes, TVIP), and a parental report of speech and language problems. In addition, morphosyntactic measures of language development were obtained using both a story retelling and an elicitation task. Developmental language measures such as number of T-units (NU-TU), mean length of T-units (MLTU), subordination index (SUB-I), and grammatical errors per T-unit (GRE-TU) were derived from the narratives. Percentages of correct use of direct and indirect object pronouns, reflexive pronouns, definite articles, indefinite articles, plurals and adjectives were obtained from an elicitation task that was specifically designed for this study. Counts of use of these grammatical structures were also calculated from the narratives. There were no statistically significant differences between the three age groups on standard scores for the TVIP or scores for the parent questionnaires, indicating that the three age groups were comparable. For the developmental language measures there was an increasing developmental pattern for NU-TU, MLTU and SUB-I, but no changes were found for GRE-TU. Statistically significant changes for the productive use of the grammatical structures of interest to this study were almost always seen between 3 and 4 years of age. Adult use of these grammatical structures was always statistically significantly more correct than child productions. This investigation provides novel normative data for NU-TU, MLTU, SUB-I and GRE-TU for preschool children. This investigation also offers original data on the productive use of object pronouns, articles, adjectives and plurals across the preschool years. The language battery used in this investigation proved to be sensitive to developmental changes between 3 and 4-5 year olds and has the potential to be used as an eventual diagnostic tool for the identification of children with language disorders. Speech-language pathologists who work with Spanish-speaking children will be able to use this normative information to conduct more objective language assessments.

This thesis reports the results of a large study to evaluate the kinetics of pencil grasp patterns in terms of speed and legibility of handwriting of children in Grade 4. Current clinical practice as recent as 2008 suggests that teachers identify the dynamic tripod pencil grasp as an optimal pencil grasp for handwriting. Research findings had suggested that three other pencil grasps may be functional for handwriting, though there was still inconclusive evidence upon which to base clinical practice. The purpose of the present study was to: assess the impact of pencil grasp on the speed and legibility of handwriting; to determine the effect of grasp on speed and legibility following a 10-minute copy task intended to induce fatigue; and to describe the axial and grip forces of the four pencil grasps. 120 children were assessed, completing a standardized handwriting assessment before and after a 10-minute copy task. The participants utilized an instrumented pen and wrote on a digitizing tablet, which measured, respectively, the axial and grip forces associated with their grasp patterns. Pencil grasp was not found to impact the speed or legibility of the written product in either short or long duration copy tasks. Fatigue decreased the legibility of the product across all pencil grasps but increased the speed across all pencil grasps equally. Grip and axial forces were only different in grasps with an adducted thumb and mainly during the initial assessment. Collectively, these results suggest that four mature grasps are equally functional for handwriting in children of this age. These findings contradict common clinical impressions that the dynamic tripod pencil grasp is optimal.

Hyperkinetic movement (HKM) can encumber nonverbal communication of preference. Caregiver and clinician interpretation of preference are recognized as a valuable but limited proxy translation. It is known that biomechanical signals can differentiate among movement patterns in various populations. We hypothesize that preference is encoded in HKM; to test this hypothesis we propose a unified approach to detect preference within HKM, fusing observational and quantitative techniques while incorporating caregiver and clinician perspectives. We illustrate this method through two case studies; in the first case preference is detectable by both visual (fair agreement) and accelerometer classification (68.5% accuracy) whereas in the second case preference is only detectable by accelerometer-based classification with 62.9% accuracy. The proposed procedure may enable researchers to effectively explore communicative movement patterns in children with HKM. The findings warrant further investigation into potential communicative patterns in HKM.

Rationale: Many community-dwelling stroke survivors receive care from their family, often daughters. However, we lack in-depth information on the caregiver/care-recipient relationship and its impact on adult daughter caregivers (ADCs). Objective: To systematically review the caregiving literature and qualitatively explore the pre-and post-stroke parent-to-child relationship and its association with ADCs’ well being. Method: A qualitative descriptive methodology used in-depth interviews of 23 ADCs. Analyses generated themes. Findings: Four themes were revealed: 1) The pre-stroke ADC-to-parent relationship is associated with the decision to take on the caregiving role; 2) Changes in the parent-to-child relationship occur as a result of providing care; 3) Changes to an ADC’s relationships with others arises from providing care to a parent and 4) Changes to caregiver lifestyle, outlook and physical and emotional well being arise from caregiving. Conclusion: There is a need for interventions that focus on role strains and issues related to relationship loss.

Hyperkinetic movement (HKM) can encumber nonverbal communication of preference. Caregiver and clinician interpretation of preference are recognized as a valuable but limited proxy translation. It is known that biomechanical signals can differentiate among movement patterns in various populations. We hypothesize that preference is encoded in HKM; to test this hypothesis we propose a unified approach to detect preference within HKM, fusing observational and quantitative techniques while incorporating caregiver and clinician perspectives. We illustrate this method through two case studies; in the first case preference is detectable by both visual (fair agreement) and accelerometer classification (68.5% accuracy) whereas in the second case preference is only detectable by accelerometer-based classification with 62.9% accuracy. The proposed procedure may enable researchers to effectively explore communicative movement patterns in children with HKM. The findings warrant further investigation into potential communicative patterns in HKM.

Rationale: Many community-dwelling stroke survivors receive care from their family, often daughters. However, we lack in-depth information on the caregiver/care-recipient relationship and its impact on adult daughter caregivers (ADCs). Objective: To systematically review the caregiving literature and qualitatively explore the pre-and post-stroke parent-to-child relationship and its association with ADCs’ well being. Method: A qualitative descriptive methodology used in-depth interviews of 23 ADCs. Analyses generated themes. Findings: Four themes were revealed: 1) The pre-stroke ADC-to-parent relationship is associated with the decision to take on the caregiving role; 2) Changes in the parent-to-child relationship occur as a result of providing care; 3) Changes to an ADC’s relationships with others arises from providing care to a parent and 4) Changes to caregiver lifestyle, outlook and physical and emotional well being arise from caregiving. Conclusion: There is a need for interventions that focus on role strains and issues related to relationship loss.

This thesis reports the results of a large study to evaluate the kinetics of pencil grasp patterns in terms of speed and legibility of handwriting of children in Grade 4. Current clinical practice as recent as 2008 suggests that teachers identify the dynamic tripod pencil grasp as an optimal pencil grasp for handwriting. Research findings had suggested that three other pencil grasps may be functional for handwriting, though there was still inconclusive evidence upon which to base clinical practice. The purpose of the present study was to: assess the impact of pencil grasp on the speed and legibility of handwriting; to determine the effect of grasp on speed and legibility following a 10-minute copy task intended to induce fatigue; and to describe the axial and grip forces of the four pencil grasps. 120 children were assessed, completing a standardized handwriting assessment before and after a 10-minute copy task. The participants utilized an instrumented pen and wrote on a digitizing tablet, which measured, respectively, the axial and grip forces associated with their grasp patterns. Pencil grasp was not found to impact the speed or legibility of the written product in either short or long duration copy tasks. Fatigue decreased the legibility of the product across all pencil grasps but increased the speed across all pencil grasps equally. Grip and axial forces were only different in grasps with an adducted thumb and mainly during the initial assessment. Collectively, these results suggest that four mature grasps are equally functional for handwriting in children of this age. These findings contradict common clinical impressions that the dynamic tripod pencil grasp is optimal.