The human ankle joint is hypothesized to be a primary controller of support, propulsion and steering during locomotion. A series of experiments were initiated to understand ankle plantarflexor muscle kinematics and kinetics in normal and pathological gait, and to define the specific locomotor demands of community ambulation. Additional experiments were then conducted to quantify the effects of walking speed on plantar pressures and centre of mass motion, to illuminate the role of the ankle in acceleration and deceleration during walking, and to examine how humans alter their kinematics and kinetics to turn. The results of these experiments provide support for the hypothesis that the ankle joint is important in a wide range of locomotor movements beyond walking straight ahead at constant speed. The ankle appears instrumental in adapting to different walking speeds, altering both the pressures on specific regions the plantar surface and the motion of the centre of mass across a range of speeds. The ankle also has subtle kinetic changes that appear to modulate acceleration and deceleration during single limb stance. For turning, the ankle plays a role during slowing into the turn and accelerating after the turn, but mediolateral shears appear to alter the trajectory of the body to negotiate a corner and the external hip rotators appear to rotate the trunk toward the new direction of travel. This work extends our understanding of the ankle in functionally relevant gait activities beyond simple straight-ahead walking at constant speed. The published papers included in this supporting statement have been cited by 180 different subsequent peerreviewed publications, suggesting that this work has had some impact on the field.

Doctorat en sciences psychologiques / info:eu-repo/semantics/nonPublished

As the business evolves, organisations are faced with challenges as today’s customers have changed, and demand a value for the products and services purchased. Customer satisfaction is a key factor to business excellence. The health sector and its service providers are faced with such demands, having to ensure customer satisfaction with limited resources. The aim of the study was to investigate a business model that could be implemented within the public sector to render pathology services. Particular reference was given to the National Health Laboratory Service as a provider of choice for rendering medical laboratory services within public health institutions and related departments. The data has been collected using a self constructed questionnaire which has been distributed to the NHLS centers within the Nelson Mandela Metropolitan Municipality. 45 percent of the employees, in the region took part in the survey. The study tested the perceptions of the respondents with respect to the business model, specifically the determinants of a business model and its effects. The results of the empirical study revealed that a relationship exists between the business model, its determinants and customer satisfaction. Correlation analysis was done between the business model, customer relation management, continuous improvement, talent management, business process reengineering and customer satisfaction. Conclusions and recommendations have been drawn from the study. The NHLS needs to change its approach to business, invest in people education, training and development, improve its communication strategies with customers and realign its processes in order to maintain business excellence and provide a better service within the public sector

A delayed, differential, classical conditioning paradigm was used to investigate defense and reward conditioning of autonomic responses in psychopaths. The CSs were tones and the UCSs were shock and pictures of nudes. The Ss were drawn from the inmate population of a maximum security penitentiary and were classified as primary psychopaths (P), secondary psychopaths (S), and nonpsychopaths (NP), according to criteria proposed by Cleckley and Karpman. The three dependent variables of chief interest, the GSR, HR, and finger vasoconstriction, were recorded simultaneously on an Offner Type R Dynograph. Differential conditioning was expressed as the amplitude of response to a reinforced CS minus the amplitude of response to the unreinforced CS. The primary hypothesis of the study was that Group P would show less defense conditioning of electrodermal, cardiac, and vasomotor responses than would Group NP. The secondary hypothesis predicted no significant differences between Groups P and NP in amount of reward conditioning on any of the autonomic measures investigated. The results showed that of the three physiological systems studied only the electrodermal differentiated between Groups P and NP with Group P; (1) showing significantly less defense conditioning; (2) giving smaller conditioned ORs, and smaller UCRs to shock; and (3) having a significantly lower level of basal skin conductance midway through the experiment. There was no significant difference between the two groups in reward conditioning although the tendency was for Group P to give ORs and ARs of smaller amplitude than those given by Group NP. No significant difference was found between groups in shock detection threshold or shock tolerance level - hence these variables were ruled out as significant contributors to the difference in defense conditioning. It was also shown that a difference in basal conductance between Groups P and NP was not significantly related to the observed difference in conditioning. Under both defense and reward stimulus conditions all groups showed evidence of conditioned HR deceleration, and an increase in the amplitude of vasomotor responses. There was no significant difference between Groups P and NP on any index of either cardiac or vasomotor activity. The GSR findings pertaining to defense conditioning were interpreted as providing additional evidence that primary psychopaths are deficient in the acquisition of conditioned fear responses. The reward conditioning results indicate that there is still no evidence that primary psychopaths differ from nonpsychopaths in the conditioning of reward responses. The difference between the amount of electrodermal and cardiovascular conditioning shown by Group P was related to structural and functional differences between the physiological systems investigated. The results of this study seem to permit the following tentative conclusions: (1) The GSR may be a more appropriate autonomic correlate of the psychopath's emotional reactivity than is either HR or finger vasoconstriction. (2) The primary psychopath's autonomic conditioning deficit may be restricted to the GSR. (3) In comparison with nonpsychopaths primary psychopaths are deficient in the acquisition of classically conditioned fear responses expressed as electrodermal measures. (4) There is no evidence that primary psychopaths and non-psychopaths differ significantly in the acquisition of classically conditioned reward responses. (5) Relative to nonpsychopaths primary psychopaths appear to be electrodermally hyporeactive. / Arts, Faculty of / Psychology, Department of / Graduate

Multi-unit, multi-location organization is one of the most salient characteristics of contemporary enterprise. The transformation in the structure of enterprise from the independent, small-scale operation to the complex, multi-unit, multi-location system has been an integral part of wider societal change. Yet the current functioning of these systems and the processes underlying their transformation is not well understood. Particular deficiencies exist in our understanding of the relationship among the technology, organization and location of multi-unit enterprise. A case study of transformation in the British Columbia laboratory system between 1954 and 1984 shows that the spatial and organizational structure of enterprise is not driven by any single variable and, in particular, technology is not the "prime mover" behind structural change. The process of structural change is a synergistic one in which external environmental factors and strategic choice have a more dominant influence on transformation than does technology. Thus organizational and location options are not dictated, rather they are perceived and selected as a purposeful response to environmental conditions. This conclusion is reached from a critical evaluation of literature drawn from organization theory, decision-theory, cybernetics and the geography of enterprise; and from the case study. In particular, it is shown that in the 1950s and early 1960s, strategic decisions were taken that resulted in relative decentralization of laboratory activity, organizationally (down the hospital hierarchy) and geographically (towards the periphery). These decisions were taken in response to the changing political, social and medical environment. But these decisions clearly predate the availability of technologies that might encourage such dispersion, indicating that technology is not a necessary and sufficient condition for structural change. Technology can have an impact on the degree of centralization in multi-unit enterprise. In certain circumstances, the development and deployment of specific technologies coincides with a strategic decision to either centralize or decentralize activity. In such circumstances, equipment embodied technology can make a powerful contribution in transforming the relative centralization or decentralization of the system, but it does not determine the choice between centralized or decentralized. Rather, it amplifies the chosen direction. These findings have policy and research implications for society, for the urban system, for enterprise, in general, and for the future of the clinical laboratory system of B.C., in particular. / Graduate and Postdoctoral Studies / Graduate

Psychopathy is a complex personality disorder denned by a constellation of affective and behavioral characteristics. There is accumulating behavioral evidence suggesting that the condition is associated with impairments in affective, cognitive, and language functions. However, relatively little is known regarding the neural systems underlying these abnormalities. The present thesis is comprised of five experiments designed to elucidate and characterize the abnormal functional architecture underlying these abnormalities in psychopathic criminals. In Experiments 1 and 2, functional magnetic resonance imaging (fMRI) was used to elucidate the neural systems underling abnormal semantic and affective processes in these individuals. In Experiments 3, 4 and 5, event-related potentials (ERPs) were used to characterize the temporal features of cognitive and language functions in psychopaths. The results from Experiment 1 revealed that compared to control participants, psychopaths performed more poorly and failed to showed the appropriate neural differentiation between abstract and concrete stimuli during a lexical decision task. These deficits were located in the right anterior superior temporal gyrus. The results from Experiment 2 indicated that psychopaths, relative to control participants, showed less activation for processing affective stimuli than for neutral stimuli in several neural regions, including the right amygdala/hippocampal formation, left parahippocampal gyrus, ventral striatum, and in the anterior and posterior cingulate. Psychopaths did show greater activation for processing affective than for neutral stimuli in regions located outside the limbic system, including bilateral inferior frontal gyrus. These latter data suggesting that psychopaths used different neural systems than did controls for performing the task. The results from Experiments 3 and 4 indicated that psychopathy is associated with abnormalities in the P3 ERP component elicited by target stimuli during visual and auditory oddball tasks. In addition, the psychopaths' ERPs to visual and auditory target stimuli were characterized by large fronto-central negativities in the 350-600 millisecond time window. These fronto-central ERP negativities are similar to those observed for patients with temporal lobe damage. In Experiment 5, using a standard sentence processing paradigm, no group differences were observed between psychopaths and nonpsychopaths in the amplitude of the N400 potential elicited by terminal words of sentences that were either congruent or incongruent with the previous sentence context. These results indicate that the abnormal fronto-central ERP negativities observed in previous studies of language function in psychopaths are not related to processes involved in the generation of the N400. Taken together, these data suggest that one of the cardinal abnormalities in psychopathy is abnormal semantic processing of conceptually abstract information and affective information and that these abnormalities are related to the function of neural circuits in the anterior temporal lobes and lateral frontal cortex. / Arts, Faculty of / Psychology, Department of / Graduate

This study undertook to explore the experience of pathological pain of twelve individuals from a psychological perspective, within the context of Spontaneous Healing Intrasystemic Process (SHIP®), using an interpretative phenomenological analysis as method. All of the participants are Caucasian South Africans, of which eleven are women, and one a man. Various aspects of the influence of physical symptoms and psychological influences are expanded upon in the available literature, indicating a greater association of relationship than is generally accepted in the treatment modalities from a medical perspective. The experience of each of these individuals was explored to gain information on the impact of this bidirectional influence in the lives of these persons. Although each experience held a uniqueness to that particular individual, a shared process of meaning evolved in many of the themes derived from the study. The themes derived from the research are discussed, embedded within the relevant literature supporting it. It is seen from the results of this study that the individuals gained a sense of ownership of their own experiences and an empowerment which they carried through into their lives, as a consequence of their experience of pain. The psychotherapy process that they entered into provided the platform from which this empowerment could be engendered. Although many of the findings were corroborated by the literature, each of these people had an experience that was unique to them, derived from every aspect of their lives and all that had influenced it. Several facets that emerged were not found in the literature. From the experiences of the participants in this research project, it appears that the experience of pain may have far greater value in a broader epistemological context than just the physical function generally attributed to it. What becomes clear is that neither the pain nor these experiences should be ignored on this level or taken merely at face value. Controlling or trying to contain pain may sometimes have less value than validating it, exploring it and surrendering to other facets of its contents. Allowing the human system its spontaneous expression of physical manifestations as it would unfold if not inhibited, may produce a surprisingly abundant spectrum of otherwise hidden wealth. / Dissertation (MA (Psychology))--University of Pretoria, 2008. / Psychology / unrestricted

Cognitive impairments are a hallmark of many, if not all, psychiatric disorders. They include deficits in working memory, attention, and cognitive flexibility. The prefrontal cortex (PFC) is essential for these cognitive functions and has been implicated in psychiatric disorders, including schizophrenia. The PFC receives reciprocal inputs from the thalamus, and this thalamo-PFC circuitry supports cognition. In patients with schizophrenia, who have impaired cognitive functioning, thalamo-PFC connectivity is disrupted. This finding is also seen in adolescents at high risk for the disorder, even before diagnosis.While impaired cortical maturation has been postulated as a mechanism in the etiology of schizophrenia, the postnatal development of thalamo-PFC circuitry is still poorly understood. In sensory cortex, activity relayed by the thalamus during a postnatal sensitive period is essential for proper cortical maturation. However, whether thalamic activity also shapes maturation of the PFC is unknown. Here, I will present evidence to support the hypothesis that adolescence represents a sensitive period, during which the PFC is susceptible to transient perturbations in thalamic input activity, resulting in persistent changes in circuitry. In Chapter 1, I present the existing literature on schizophrenia and our current understanding of its etiology. I then review the structure and connectivity of the PFC and its inputs, including the thalamus, in the context of schizophrenia and cognition. Next, I discuss the role of adolescence in the development of these structures and circuits. Finally, I introduce the concept of sensitive periods and outline the hypothesis that a similar process may occur in the context of the adolescent development of thalamo-PFC circuitry. To assess cognitive functioning in mouse models, I developed an operant-based working memory task. In Chapter 2, I describe this newly developed task and demonstrate that behavioral performance in the task is susceptible to PFC lesions. Thus, the task offers a new approach to studying PFC cognitive function. In Chapter 3, I discuss work done to address the hypothesis of adolescence as a sensitive period in the development of thalamo-PFC circuitry. I established an approach whereby I can transiently reduce activity in the thalamus during specific time windows. In this way, I compared the persistent effects of transient thalamic inhibition during adolescence and adulthood. I found that adolescent thalamic inhibition causes long-lasting deficits in cognitive behavioral performance, including the operant-based working memory task described in Chapter 2 and a cognitive flexibility task, decreased PFC cellular excitability, and reduced thalamo-PFC projection density. Meanwhile, adult thalamic inhibition has no persistent consequences on behavior or PFC excitability. Adolescent thalamic inhibition also results in disrupted PFC cellular cross-correlations and task outcome encoding during the cognitive flexibility task. Strikingly, exciting the thalamus in adulthood during the behavioral task rescues PFC cross-correlations, task outcome encoding, and the cognitive deficit. These data support the hypothesis that adolescence is a sensitive period in thalamo-PFC circuit maturation as adolescent thalamic inhibition has long-lasting consequences on PFC circuitry, while adult thalamic inhibition has no persistent effects. Moreover, these results highlight the role of the thalamus as a non-specific facilitator of PFC activity, expanding our understanding of this thalamic function to additional cognitive contexts. By supporting PFC network activity, boosting thalamic activity provides a potential therapeutic strategy for rescuing cognitive deficits in neurodevelopmental disorders. Finally, in Chapter 4, I conclude with a general discussion. I highlight major take-aways from this work as well as next steps in our exploration of these crucial neural circuits. Together, the findings outlined here offer new promise for early diagnosis and treatment options for patients with cognitive impairments and psychiatric disorders.

Magister Chirurgiae Dentium (MChD) / Aging is a biological process under the influence of genetic and pathological factors wh ich can be more or less advanced in different individuals with the same, chronological age. Silverman (1961) defined age as a three-dimensional phenomenon wherein there is a constant interaction between chronologie age, physiologic age and psychologic age. Vinton (1964) also points out that there are physiologic, pathologic, psychologic and sociologic changes which are unique to the latter span of life. These changes are not synonomous with illness as long as they fall within the physiologic limits of normality. If these limits are exceeded the changes are pathological in character. Age is a phase of life which brings about changed circumstances and a new pattern of life which must be adapted to and accepted. This may necessitate an invironmental change which causes a loss of friends and social standing and may bring about a feeling of insecurity in some people, suppressing the incentive to live for the future. To counter these emotions it is imper~tive to create a quality of life in which the aged can be productive within the limits of their physical abilities and which will give them the assurance that they are still needed by society. Life expectancy is determined by the circumstances under which people live. The average age of life expectancy during the Roman period and the Middle Ages was 25 to 30 years; today it is 70 years (Sharry 1974). Nature normally maintains an equilibrium between young and old so that each can provide for the other's needs. Modern science and technology however have upset that balance and brought about new developments in medicine ich have succeeded in increasin and reducin infant mortality, causing the ectancy explosion. This has brought about a situatiop where 10 million humans are born and only 3 million die every month; thus the inflow into life far exceeds the outflow and there is consequently a global increase of 80 million people per year. At this rate the world population will double itself by the end of this century (Pistorius 1978). Birth control has been encouraged as a counter measure to this and the result has been a marked drop in the birth rate, especially in the more advanced countries of the world. This changing relationship between the birth and death rates is referred to as the population-shift. In the U.S.A. 4% of the total population was over the age of 65 years at the beginning of this century. In 1975 the figure was 10% and at the present rate of population-shift will be 20% by the end of this century (Winkler 1977). In England and Wales 6% of the total population was over the age of 65 years in 1931, 10% in 1951 and 12% in 1962. In Scotland 7% was over the age of 65 years in 1931, 9% in 1951 and 10% in 1962 (Storer 1965). In Canada 4,8% of the total population was over the age of 65 years in 1921 and 7,8% in 1971. The average life expectancy was 50 years in 1900 and 70 years in 1960 (Sherman 1970). This pattern of change is also evident in the Republic of South Atrica but there is a marked variation in the different ethnic groups (White, Asian, Coloureds and Blacks) making up the South African population.

Mental illness has been a perplexing mystery for centuries, inciting both fear and stigmatization. Yet, the knowledge that the brain gives rise to the mind transformed the field of psychiatry; biological studies of aberrant human behavior has revealed that mental disorders are rooted in physical abnormalities that may be targeted to alleviate symptoms. Even with recent progress, there remains many open questions, one of which is: how exactly are some individuals more susceptible to developing these disorders than others? Excess, or traumatic, stress can lead to the onset of maladaptive disorders such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). But what if it were possible to prevent these diseases from occurring in the first place? What if there was a prophylactic or vaccine-like approach to increase resilience against environmental stressors? Would we be able to target susceptible populations and administer this prophylactic? In this thesis, I present our work demonstrating the potential for prophylactic pharmaceuticals to enhance stress resilience and protect against stress-induced psychopathology. (R,S)-ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has been demonstrated to be a viable candidate drug to administer as a prophylactic against stress-induced psychopathology. It was serendipitously discovered to rapidly (in as little as a half hour) and persistently (up to 2 weeks) alleviate depressive symptoms in patients with MDD. Since its discovery as an effective antidepressant, research has been focused on its mechanism of action with the goal of ultimately developing more efficacious, rapid-acting, long-lasting antidepressant drugs. However, in our lab, we made a truly unexpected discovery in 2016, described in Chapter 2: (R,S)-ketamine prevents the development of psychiatric symptoms when administered before a stressor. We found that prophylactic (R,S)-ketamine is effective against behavioral despair and buffers against learned fear in a time- and dose-specific manner, described in Chapter 3. This was the first indication that a drug can be administered before stress to prevent stress-induced psychopathology, opening a novel field of preventative psychopharmaceuticals. Follow-up studies in our and other labs have consistently replicated this effect using different stressors and mouse strains, in rats, and in both males and females. These data demonstrate that (R,S)-ketamine can effectively enhance resilience pre-clinically. To address how (R,S)-ketamine is inducing long-lasting protection, in Chapter 4, I describe a study that used a metabolomics platform to uncover the long-term effects of (R,S)-ketamine in buffering against learned fear. We found that (R,S)-ketamine alters purine and pyrimidine metabolism in brain and, most notably, the periphery. These data suggest the potential to conduct a simple blood test to screen for biomarkers of prophylactic efficacy in the clinic. However, while these data revealed the end-products of therapeutic efficacy, it was unknown what brain mechanisms may mediate such long-lasting protection against a psychological stressor. In a separate study, the ventral CA3 (vCA3) region of the hippocampus was uncovered to be necessary for (R,S)-ketamine’s prophylactic fear buffering effects, and that targeting this region both mimics and occludes its effects. It was then discovered that 1 week after a single administration of (R,S)-ketamine or FENM, AMPA bursts were attenuated in vCA3. These data reveal vCA3 a central node for prophylactic (R,S)-ketamine efficacy. The biggest limitation of these preliminary studies is that they each only assessed changes at single timepoints rather than mapped out what occurs throughout treatment, during stress, and during recall of a stressor. It remained unknown whether (R,S)-ketamine alters the experience or recollection of a stressor to induce long-lasting protection. The next goal was to use in vivo technologies such as 1-photon Ca2+ imaging in freely-moving mice to develop a more thorough understanding of how exactly (R,S)-ketamine is acting on vCA3 to confer its prophylactic fear buffering effects, which is outlined in Chapter 5. Mice were imaged in the ventral hippocampus throughout a prophylactic (R,S)-ketamine administration paradigm. We found that prophylactic (R,S)-ketamine administration buffered against the experience of the stressor specifically in vCA3 and reduced ventral hippocampal correlated network activity to ultimately buffer against learned fear. These data indicate that (R,S)-ketamine actively buffers against learned fear in the ventral hippocampal at the time of stress. The promise of (R,S)-ketamine is that it is also beneficial as a prophylactic in other settings beyond MDD and PTSD, such as in patients with traumatic brain injury (TBI). In Chapter 6, I describe a study that sought to determine whether (R,S)-ketamine can be useful as a prophylactic for TBI-induced neuropsychiatric effects. Here, TBI mice developed fear generalization, or the inability to distinguish between fear-inducing and neutral stimuli. To understand how TBI alters fear memory traces to promote fear generalization, we used the ArcCreERT2 x enhanced yellow fluorescent protein (eYFP) activity-dependent memory tagging strategy developed by Dr. Christine Ann Denny and found that TBI-induced fear generalization is partially mediated by dentate gyrus (DG) memory trace dysregulation. To reverse this fear generalization phenotype, a single administration of (R,S)-ketamine 1 hour after a TBI prevented the fear generalization phenotype. These data reveal the possibility of administering (R,S)-ketamine or other prophylactics in the clinic as part of post-operative care for TBI patients to prevent long-term fear generalization deficits. Altogether, this thesis demonstrates the potential for pharmacotherapies for stress resilience enhancement and reveals potential targets for prophylactic drug development. We have uncovered the long-term metabolomic changes that occur after a single dose of (R,S)-ketamine, revealed a central node for prophylactic efficacy, mapped the dynamic changes that occur throughout treatment, and applied the prophylactic paradigm to a model of TBI to demonstrate the broad range of applications of this approach. This work paves the way for the novel field of preventative psychiatry and opens new avenues to explore ways to reduce the devastating impact of mental illness on individuals and society.