Melbourne School of Health Sciences Collected Works - Theses
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ItemModelling residential aged care in Australia: entry and exit( 2017)Ageing of the Australian population affects the residential aged care system, yet the structure and dynamics of the system remain uncertain. A comprehensive model of residential care based on the individual perspective of residential aged care events is missing. Thus, older Australians, government and care providers have only a limited model of aged care actions. This study uses big administrative unit record data on aged care assessments (ACAP), aged care appraisals (ACFI) and unit record survey data (SDAC) to identify factors associated with aged care events in older persons’ trajectories towards and through residential care. To achieve this goal and broaden understanding of Australian residential care, this study uses the following steps: (1) modelling of the probability of entry to and exit from residential care, with a multi-state model of transitions between levels of care needs; (2) modelling the applications for aged care and approvals for entry to residential care; (3) derivation of transition and mortality assumptions for individual care needs that can be used in a projection model; (4) estimation of life expectancy in residential care based on needs for assistance; and (5) assessing the quality of Australian data on aged care for statistical modelling and projections of residential care demand. The results show that health factors, above all needs for assistance, determine the speed and direction of a person’s progression towards institutional care. Probabilities of aged care events, transition rates and life expectancy estimates, derived in this study, provide a comprehensive picture of Australian residential aged care. These findings are expected to have important implications for residential aged care policies in Australia in terms of having better understanding and more accurate predictive power for the future of aged care.
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ItemPerceptual suppression mechanisms in healthy ageing( 2017)Healthy ageing alters contextual spatial interactions such as centre surround contrast suppression and spatial suppression of motion discrimination. However, the exact neural mechanisms that underlie age related changes to contextual spatial interactions are still elusive. The body of work reported in this thesis explored the perceptual mechanisms behind altered contextual spatial interactions in younger and older adults using psychophysical and neuroimaging methods. Experiment 1 investigated the strength of foveal centre surround contrast suppression under intraocular and interocular viewing for two stimulus durations (40 ms and 200 ms) in younger and older adults. Foveal intraocular center surround contrast suppression decreased with longer stimulus duration whereas interocular surround suppression did not, suggesting contributions from separate mechanisms to these forms of suppression. In addition, intraocular center surround contrast suppression was increased in older adults compared to younger adults; however, interocular suppression was similar in both groups. Experiment 2 studied the effect of orientation of the surround grating in relation to the orientation of the centre grating (surround orientation effect) on centre surround contrast suppression under intraocular and interocular viewing in younger and older adults. Interocular and intraocular centre surround contrast suppression showed different surround orientation effect, and older adults demonstrated unaltered levels of surround orientation effect compared to younger adults under both intraocular and interocular viewing. Experiment 3 measured Gamma Aminobutyric Acid (GABA, the principal inhibitory neurotransmitter of the adult brain) levels in visual cortex of younger and older adults using magnetic resonance spectroscopy. Visual cortical GABA levels were increased in older adults compared to younger adults. In addition, visual cortical Glx (combined estimate of glutamate - the principal excitatory neurotransmitter, and glutamine) levels were reduced in older adults compared to younger adults. Neither GABA levels nor Glx levels in visual cortex correlated with foveal centre surround contrast suppression. The final experiment of this thesis (Experiment 4) investigated the relationship between visual cortical GABA levels and performance on two visual tasks that are hypothesised to be mediated, at least in part, by GABAergic inhibition: spatial suppression of motion discrimination and binocular rivalry. Both younger and adults participated in this experiment as well. Increased visual cortical GABA levels were associated with prolonged binocular rivalry percept durations and reduced spatial suppression of motion discrimination. The experimental frameworks used in the thesis were based on our modern understanding of cortical circuits that are implicated in mediating centre surround contrast suppression, and a neuroimaging technique that could potentially link physiology with behaviour. The novel findings reported in thesis answered some of the important questions related to perceptual surround suppression in younger and older adults. The current findings suggested that healthy ageing differentially affects distinct forms of suppression arising at various levels of the visual pathway, and challenged prior assumptions regarding age related changes to GABA levels within the visual cortex and its association with centre surround contrast suppression and spatial suppression of motion discrimination.
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ItemThe role of Dlk1 in haematopoiesis, leukaemia and angiogenesis( 2017)Delta-Like Homologue 1 (DLK1), also known as Preadipocyte Factor 1 (PREF-1), is a non-canonical EGF-like NOTCH ligand. It is maternally imprinted at the Dlk1-Dio3 imprinted locus, and has been shown to regulate embryonic growth, lipid metabolism and skeletal development. However, the precise role of Dlk1 in haematopoiesis, leukaemia and angiogenesis, processes in which it has been previously implicated, is unknown. We generated Dlk1 knockout and conditional knockout mice and used a constitutive overexpression system via retroviral transduction to specifically study Dlk1 in these contexts. Dlk1 knockout mice showed distinctive phenotype of increased perinatal mortality and growth retardation. In foetal livers, significant expression of Dlk1 was detected in the haematopoietic cells, with higher level of expression in the haematopoietic stem cells compared to lineage positive mature cells, with overall expression decreasing with embryonic age. Dlk1 knockout mice were not significantly different from wild type mice in the mature haematopoietic lineages, but serial competitive transplant assays demonstrated Dlk1 knockout bone marrow cells were inferior to controls in reconstituting lethally irradiated recipient mice in short term haematopoietic reconstitution assays, suggesting that Dlk1 knockout led to a defect in adult short term haematopoietic stem cells. Despite frequent overexpression of DLK1 found in many human acute myeloid leukaemias, constitutive overexpression of Dlk1 did not lead to increase in acute leukaemia or death in reconstituted mice. However, Dlk1-overexpressing haematopoietic cells demonstrated competitive repopulation advantage compared to MIG-transduced controls. Using a retinal model of angiogenesis, Dlk1 was found to be expressed by the pericytes rather than endothelium of newly developing blood vessels in postnatal murine pups, in contrast to the published data. Conditional knockout of Dlk1 in endothelial cells using the endothelial specific Tie2 Cre transgene did not lead to significant abnormality in postnatal retina, confirming that Dlk1 did not have a functional role in the retinal endothelium. These new findings add to our current knowledge of stem cell biology and leukaemia, and the role of Dlk1 in angiogenesis.
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ItemSwallowing difficulties in Friedreich ataxia( 2017)Swallowing is an important biological function reliant on the coordinated interaction between motor and sensory mechanisms. Swallowing dysfunction (dysphagia) is a common sequela of neurodegenerative disease and is associated with significant morbidity and mortality. Dysphagia is associated with malnutrition, dehydration, and aspiration-related pneumonia, and psychological issues such as reduced self-esteem and social isolation. For individuals with movement disorders, dysphagia can be exacerbated by concurrent upper limb impairment, making it difficult to feed independently. Friedreich ataxia (FRDA) is an autosomal recessive condition resulting in a deficiency of frataxin, most commonly due to homozygosity for a GAA trinucleotide repeat expansion in intron 1 of FXN. FRDA manifests in widespread central and peripheral nervous system degeneration, as well as impairment of the cardiac, skeletal, and endocrine systems. Pneumonia (a common implication of dysphagia) is the cause of death in approximately 10% of individuals with FRDA. Whilst dysphagia is a widely accepted feature of FRDA, understanding of the underlying mechanisms and characteristics of dysphagia in FRDA is limited. This project (and resulting thesis) sought to investigate and characterise the swallowing function of individuals with FRDA suspected of having dysphagia, and document the frequency of concomitant aspiration in this cohort. It was also aimed to determine relationship between oropharyngeal dysphagia and clinical markers of FRDA, including age at time of disease onset, disease duration, the GAA repeat size on the smaller (GAA1) and larger (GAA2) FXN allele. Predictors of aspiration in this cohort were also explored. In addition the psychosocial implications of dysphagia were considered using a standardised questionnaire. The study was largely cross-sectional in design, with a smaller group of individuals with FRDA receiving a 12 month follow up to investigate the relationship between dysphagia and disease progression. Results confirm oropharyngeal dysphagia with concomitant aspiration is present in individuals with FRDA and worsens with disease duration and severity. Aspiration in this population can occur at any time during the course of the disease, and therefore swallowing function should be monitored closely. Dysphagia was also shown to significantly affect the quality of life of individuals with FRDA compared to a group of healthy controls. The clinical implications of these findings are discussed along with future directions.
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ItemToward relationship-centred care: patient-physiotherapist interaction in private practice( 2017)Interacting with patients is integral to the practice of physiotherapy. Notably, however, empirically derived knowledge about how physiotherapists interact with their patients is limited, particularly in the private practice setting. In addition, heavily promoted approaches for interacting with patients, such as patient-centred care and the biopsychosocial approach, have been adopted from the medical profession, are not derived from research evidence, and therefore may not adequately reflect how physiotherapists interact with patients in physiotherapy practice. Thus, this qualitative research had two aims: first, to detail how patients and physiotherapists interact in private practice; second, to consider how the research findings related to promoted healthcare interaction approaches. Methodologically, the research incorporated features of both ethnography and grounded theory. Observations of 52 consultations, as well as in-depth interviews with 9 patient and 9 physiotherapist participants, were undertaken. Data comprised field notes and audio-recordings of observations and interviews, and were analyzed iteratively using principles of thematic analysis and grounded theory. The data analysis yielded two central and complementary themes. The theme ‘physiotherapist-led communication’ encapsulates how physiotherapists directed the style and content of communication to achieve clinical goals by providing structure, making decisions, and focussing on biomedical aspects. The second theme, ‘adapting to build rapport’, describes how physiotherapists incorporated adaptive communication such as eye contact, body language, touch, casual conversation, and humour into their interactions with patients. These adaptations were often intuitively enacted, were responsive to individual patient characteristics, and functioned to build rapport. The findings neither clearly correlated to features of patient-centred care nor to the biopsychosocial approach. Rather, the findings portrayed a dynamic integration of clinical and responsive communication that fostered the development of a trusting relationship between patient and physiotherapist. These results extend knowledge of interactions in physiotherapy by providing detailed descriptions of interactional elements that incorporated patient and physiotherapist perspectives. Furthermore, the findings explain how rapport was developed between patient and physiotherapist with trust as an underlying construct. Relationship-centred care and relational notions of trust are discussed as alternative explanations for how patients and physiotherapists interact in private practice. These findings and explanations have the potential to benefit educators, physiotherapists and, by extension, patients, by offering a framework for education and the practice of patient-physiotherapist interactions.