Publication Search Results

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  • (2008) Rahimpour, Mohammad; Lovell, Nigel; Celler, Branko; McCormick, John
    Journal Article
    Goal: To identify any major factors that could affect patients` perceptions of a Home Telecare Management System (HTMS) and use the findings to contribute to development of a theoretical framework for patient acceptance of HTMS. Materials and methods: Ten Focus Group Interviews (FGIs) were conducted with patients suffering from congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), or both, from seven different ethnic groups in Sydney. Six key discussion points were used to conduct the FGIs. The participants were shown a video demonstrating the HTMS and its operation, followed by the demonstration of an HTMS prototype. The participants, who had no prior experience with the HTMS, were then asked questions to access their perceptions in potentially real situations. The discussions were audio-taped and content analysis performed. Results: Four major themes and 16 sub-themes were identified.

  • (2008) Williams, Charles
    Carbon nanotube (CNT) polymer composites have attracted much attention since the extraordinary electrical and mechanical properties of CNTs were realised. However research into biomedical applications of CNT/polymer composites has received little attention. The aim of this thesis was to fabricate an electrically conductive, biocompatible polymer based on a poly(ether)urethane (PEU) with multiwalled carbon nanotubes (MWNTs) as the conductive filler. Paramount to achieving this was to obtain good dispersion and integration of MWNTs within the host polymer matrix. A number of different strategies were investigated including high energy mixing of MWNTs in PEU and covalent functionalisation of MWNTs with long chain hydrocarbons, poly(tetramethylene oxide) (PTMO) and poly(acrylic acid) (pAA) for enhanced miscibility with PEU. The impact of these strategies was assessed by testing the tensile properties, electrical conductivity as well as cytotoxicity of resulting MWNT/PEU composites. It was found that high energy mixing in the presence of MWNTs caused severe degradation of PEU, resulting in significant cytotoxicity and reductions in composite tensile strength. Covalent functionalisation of MWNTs was achieved by utilising defect group chemistry to attach a range of molecules. PTMO covalently attached to MWNTs was found to cause significant nanotube aggregation in PEU composites. Long chain hydrocarbons covalently attached to MWNTs exhibited enhanced dispersability in PEU with increasing molecular weight, attributed to disrupting intertube Van der Waals forces and providing favourable hydrophobic interactions with PEU. Additionally these composites exhibited increased conductivity and decreased cytotoxicity with increasing hydrocarbon length. However increasing long chain hydrocarbon molecular weight also caused significant reductions in MWNT conductivity. MWNTs surface modified with carboxylic acid groups exhibited favourable hydrophilic interactions with PEU but did not retain tensile properties at nanotube loadings where electrical conductivity was significant. Successful polymerisation of acrylic acid monomer initiated from MWNTs using a reversible addition-fragmentation chain transfer polymerisation was demonstrated. Resulting pAA-MWNTs exhibited enhanced dispersability in water but not in PEU composites, resulting in severe degradation in composite tensile properties. PAA-MWNTs also exhibited decreased conductivity with increasing pAA molecular weight. Incorporating MWNTs in PEU composites has been demonstrated to impart multi-functionality to existing biomaterials for potential uses in a range of biomedical applications.

  • (2008) Bedja, Djahida
    Background: The molecular and cellular mechanisms corresponding to the compensatory and maladaptive hypertrophy and remodeling of the left ventricle with chronic doxorubicin (DOX) treatment are currently unclear. Non-invasive methods of determining these changes are still deficient. To investigate these changes, 8 groups of rats in 4 different studies including a control saline group of the same age, gender and strain were evaluated for cardiac morphology and function including: (1) DOX dose response using a cumulative dose of 7.5mg/kg, and 15mg/kg in 8-10 week old female Sprague-Dawley (SD) rats, (2) strain differences were investigated in response to a cumulative dose of 15mg/kg in 8-10 week old female Fisher (F344) rats compared to the SD rats treated with same dose, (3) the role of gender and aging were studied in response to DOX at a cumulative dose of 3mg/kg in male and female neonates, and (4) combined losartan and a cumulative dose of 15mg/kg of DOX in 8-10 week old female SD rats compared to controls of saline and 15mg/kg treated SD rats. Method: Onset of cardiac toxicity was assessed by echocardiography and the rat model of heart failure was developed when the fractional shortening declined ≤ 40%. The mean arterial pressure and single-photon-emission computer tomography scanning and Tc-99m-HYNIC-Annexin V were performed at week 10 to analyze blood pressure and quantify apoptosis, respectively. All rats were euthanized at week 10 except for the neonates and two of the 7.5mg/kg-treated SD rats that were left alive for study of long -term cardiac side effects. The heart and kidney tissues were harvested for protein isolation and histopathological studies. Blood samples were collected for hematological and lipid profile analysis in all the rats. Results: A dose- and time-dependent increase in LVmass coincided with a parallel increase in MAP, kidney damage, expression of myocardial erbB2, heat shock protein 90 Akt, mTOR, GSK-3β, TGF-β, pSMAD2, and cardiomyocyte apoptosis in SD rats treated with 7.5mg/kg and 15mg/kg of DOX at week 10. The 7.5 kg/kg treatment showed adaptive hypertrophy whereas the 15mg/kg treatment group showed maladaptive hypertrophy. However decompensation was apparent by week 14 in other rats treated with 7.5mg/kg. LVmass, FS, MAP, kidney damage, red blood cells and blood lipid levels were not significantly altered in the F344 rats compared to the 15 mg/kg-treated SD rats. Losartan supplementation reduced the left ventricular hypertrophy, improved myocardial contractility, and reduced TGF-β expression compared to the DOX-treated SD rats. The 3mg/kg of DOX in neonates induced cardiac toxicity and deaths in about 60% of males 50 weeks after treatment; the females instead developed mammary tumors. Conclusion: The results of this study suggest that age, gender, and strain differences are risks factors for doxorubicin-induced harmful reno-cardiovascular toxicity. The inhibition of TGF-β expression by losartan can be used in prevention of chronic doxorubicin-induced cardiac toxicity without interfering with its anti-tumor activities.

  • (2008) Ma, Jin
    Perlecan is an important basement membrane heparan sulfate (HS) proteoglycan that is essential for various cell signaling events involved in tissue development. Heparanase is a lysosomal enzyme involved in the turnover of HS. This project aimed to assist in researching the structure of HS on perlecan and how this structure changes with tissue development. This will be achieved by generating monoclonal antibodies that have an altered affinity for perlecan after heparanase treatment. Recombinant perlecan domain I was characterized by ELISA and western blotting and used as the antigen for two fusions. The first fusion was focused on the production of IgM the common subtype of anti-glycosaminoglycans antibodies. However, no clones were produced, which may have been due to the lack of feeder layers. In order to address this problem, the fibroblast cell line MRC-5 was used as a feeder layer in the second fusion. From this fusion, we obtained 216 positive cultures, which were screened against full length perlecan from endothelial cells. Of these, 26 cultures were tested against heparanase treated perlecan, and then 2 cultures were chosen for subcloning based on the different immunoreactivity between enzyme treated and nontreated perlecan. From the 2 chosen cultures, 13 sub clones were derived and 10 of them were adapted into a serum free culture environment. The 10 monoclonal antibodies displayed strong immunoreactivity with full length perlecan in ELISA and Western Blotting. When they were used as primary antibodies in Immunocytochemistry, they were able to recognize the native perlecan deposited by human chondrocytes. When the cells were incubated with heparanase, antibody 5D7-2E4 and 13E9-3G5 showed an increase in immunoreactivity while antibody 13E9-3B3 gave a decrease. These three antibodies will be the potential tools used in the future to study perlecan turnover in different cells and tissue. The remaining seven antibodies will also be very useful in the research of perlecan as they have been shown to bind to the protein core. In the future, it will be worth subcloning some of the frozen stored stocks of uncloned hybridomas, where there are potential opportunities to select antibodies, which will react with the carbohydrate chains on perlecan.

  • (2008) Hallum, Luke Edward
    Electrical stimulation of the retina affected by photoreceptor loss (e.g., cases of retinitis pigmentosa) elicits the perception of luminous spots (so-called phosphenes) in the visual field. This phenomenon, attributed to the relatively high survival rates of neurons comprising the retina's inner layer, serves as the cornerstone of efforts to provide a microelectronic retinal prosthesis -- a device analogous to the cochlear implant. This thesis concerns phosphenes -- their elicitation and modulation, and, in turn, image analysis for use in a prosthesis. This thesis begins with a comparative review of visual modelling of electrical epiretinal stimulation and analogous acoustic modelling of electrical cochlear stimulation. The latter models involve coloured noise played to normal listeners so as to investigate speech processing and electrode design for use in cochlear implants. Subsequently, four experiments (three psychophysical and one numerical), and two statistical analyses, are presented. Intrinsic signal optical imaging in cerebral cortex is canvassed appendically. The first experiment describes a visual tracking task administered to 20 normal observers afforded simulated prosthetic vision. Fixation, saccade, and smooth pursuit, and the effect of practice, were assessed. Further, an image analysis scheme is demonstrated that, compared to existing approaches, assisted fixation and pursuit (but not saccade) accuracy (35.8% and 6.8%, respectively), and required less phosphene array scanning. Subsequently, (numerical) information-theoretic reasoning is provided for the scheme's superiority. This reasoning was then employed to further optimise the scheme (resulting in a filter comprising overlapping Gaussian kernels), and may be readily extended to arbitrary arrangements of many phosphenes. A face recognition study, wherein stimuli comprised either size- or intensity-modulated phosphenes, is then presented. The study involved unpracticed observers (n=85), and showed no 'size' --versus--'intensity' effect. Overall, a 400-phosphene (100-phosphene) image afforded subjects 89.0% (64.0%) correct recognition (two-interval forced-choice paradigm) when five seconds' scanning was allowed. Performance fell (64.5%) when the 400-phosphene image was stabilised on the retina and presented briefly. Scanning was similar in 400- and 100-phosphene tasks. The final chapter presents the statistical effects of sampling and rendering jitter on the phosphene image. These results may generalise to low-resolution imaging systems involving loosely packed pixels.

  • (2008) Dommel, Norbert Brian
    Restoring vision to the blind has been an objective of several research teams for a number of years. It is known that spots of light -- phosphenes -- can be elicited by way of electrical stimulation of surviving retinal neurons. Beyond this, however, our understanding of prosthetic vision remains rudimentary. To advance the realisation of a clinically viable prosthesis for the blind, a versatile integrated circuit neurostimulator was designed, manufactured, and verified. The neurostimulator provides electrical stimuli to surviving neurons in the visual pathway, affording blind patients some form of patterned vision; besides other benefits (independence), this limited vision would let patients distinguish between day and night (resetting their circadian rhythm). This thesis presents the development of the neurostimulator, an interdisciplinary work bridging engineering and medicine. Features of the neurostimulator include: high-voltage CMOS transistors in key circuits, to prevent voltage compliance issues due to an unknown or changing combined tissue and electrode/tissue interface impedance; simultaneous stimulation using current sources and sinks, with return electrodes configured to provide maximum charge containment at each stimulation site; stimuli delivered to a two dimensional mosaic of hexagonally packed electrodes, multiplexing current sources and sinks to allow each electrode in the whole mosaic to become a stimulation site; electrode shorting to remove excess charge accumulated during each stimulation phase. Detailed electrical testing and characterisation verified that the neurostimulator performed as specified, and comparable to, or better than, other vision prostheses neurostimulators. In addition, results from several animal experiments verified that the neurostimulator can elicit electrically evoked visual responses. The features of the neurostimulator enable research into how simultaneous electrical stimulation affects the visual neural pathways; those research results could impact other neural prosthetics research and devices.

  • (2008) Ly, Mai Thanh
    Problem investigated: Chronic wounds are not only a major burden to the patient arising from general pain and discomfort but also generate economic costs to both these individuals and the health care system. Various electrical stimulation regimes have been employed to study the effects of electrical stimulation on wound healing both in vivo and in vitro. In was hypothesised that electrical stimulation using various waveforms can modulate cell function, particularly cell migration. The aim of this thesis was to study the effects of electrical stimulation on cellular migration, in particular endothelial cells and fibroblasts, key cell types involved in wound healing. The impact of collagen matrix on cell migration was also assessed. Methods: Cells were seeded on either glass or collagen I substrate and stimulated with various electrical regimes via platinum electrodes connected to a constant current source. Cell migration was accessed by manual tracking of cell nuclei over a period of 3 hours from digital time-lapse images acquired during stimulation. Data from cell tracking were analysed for directional migration, migration rates and mean square displacement. Results: No directional cell migration for both endothelial cells and fibroblasts were observed when stimulated with either alternating or biphasic currents. However, surface substrate had impacted on cell motility with opposite effects being observed for the two cell types. Endothelial cells tended to migrate at a faster rate on collagen I substrate than on glass, compared with fibroblasts, which displayed a slower rate of migration on collagen I substrate. Significant changes in mean square displacement of biphasic current stimulated cells on collagen I substrate compared to unstimulated cells were also observed. Conclusion: This thesis has illustrated cell migration can be modulated by electrical stimulation, in particular asymmetric biphasic current. It has also been demonstrated surface substrate can impact cell migration.

  • (2008) Pelletier, Matthew Henry
    Nucleus replacement has recently come into favor as a possible treatment for Degenerative Disc Disease. Replacing degenerative nucleus tissue with a synthetic material that mimics healthy nucleus tissue may restore normal function and biomechanics to the disc and delay or obviate the need for more invasive procedures such as total disc replacement and fusion. This thesis evaluated a novel protein polymer hydrogel composed of silk and elastin as a nucleus replacement material. There are three experimental components; one in vivo and two in vitro portions. In the first experimental portion, a large animal model was developed to evaluate the biocompatibility of the material as well as the effect on surrounding boney and soft tissues. Three discs were evaluated in each animal; sham, discectomy and discectomy treated with hydrogel. Discs were evaluated at 4, 26 and 52 weeks. The hydrogel group showed a quiet cellular response, as well as decreased boney remodeling and fewer degenerative changes when compared to the discectomy group. The second experimental portion evaluated the biomechanics of 9 cadaveric motion segments loaded in axial rotation, lateral bending, flexion/extension (FE) and compression. Specimens were tested sequentially in the intact state, following annulotomy, discectomy and after hydrogel treatment. Range of Motion (ROM) in FE was shown to increase from the intact state (8.50+/-1.44˚) to the discectomy state (9.86+/-1.77˚) and decrease following hydrogel treatment (8.66+/-0.76˚) to be similar to the intact ROM. The third experimental portion investigates the effect of three commonly applied testing conditions on the mechanical properties of spinal segments. 27 motion segments were tested at 18˚C wrapped with Phosphate Buffered Saline (PBS), at 37˚C in a PBS bath, and at 37˚C and 100% humidity. Specimens were tested hourly for 6 hours. The heated conditions were shown to have lower stiffness and increased range of motion when compared 18 ˚C tests. Repeated testing with time increased neutral zone and ROM for all modes of bending. As tests are repeated over time, tissue properties change and may mask the ability of a nucleus replacement to restore biomechanics.

  • (2008) Vizesi, Frank
    The repair of articular cartilage defects is a topic that has received significant focus from both basic science and clinical perspectives. The current gold standard treatment for significantly damaged or degenerated articular cartilage in the knee is a total joint replacement, although there are several drawbacks including reduced range of motion and increased instability. Whilst the total knee replacement will continue to be a valuable treatment, there is a need to find alternatives and part of the solution is having an appropriate animal model to effectively evaluate said alternative treatments. The first part of this dissertation describes the characterization of an ovine osteochondral defect model which ultimately could be used to validate the efficacy of a variety of osteochondral implants. The effect of this femoral defect on the tibial surface, including the meniscus, was also studied and a metallic resurfacing device (HemiCAP) evaluated for its efficacy in protecting the knee from further degenerative changes. Additionally, pressure footprint and contact stresses were measured with flexible pressure sensors at flexion angles and loads determined from the sheep gait cycle. This study found that the HemiCAP device increased peak pressure when compared to all other conditions tested, especially at a point corresponding to heel strike. Since loading is known to modulate bone remodelling, micro computed tomography was used to measure changes in the subchondral and cancellous bone on the tibia opposing the surgical site. Biologically, there were no significant differences detected in the knees treated with the HemiCAP device when compared with those that had untreated osteochondral defects, which suggests that the HemiCAP device is not effective in protecting against tibial degeneration, but at least it does no more harm than not treating the defect in the first place.

  • (2008) Chan, Leroy Lai-Yu
    An aging population is one common challenge faced by many developed countries including Australia. The Australian government has realised that the existing healthcare system must be improved to provide better support longer-term for the healthcare needs of this population. This research examines one such opportunity by suggesting a reform on how the care needs of residents living in Australian residential aged care facilities (RACF) are assessed. A recent study has shown that the current assessment system, known as the Residential Classification Scale (RCS), is subjected to high administrative procedural overhead costs and significant deviations in assessment results. This thesis documents a technical feasibility study of a novel method aimed to solve issues related to the time demands and subjectivity of the RCS through the design and implementation of a Wireless Sensor Network (WSN). This WSN is engineered to unobtrusively collect data from wireless sensor nodes either embedded in the RACF environment or attached to the resident's body. The collected data can be potentially used to provide automatic and accurate care level assessments for the resident. The methodology of preparing and conducting the experiments to prove the hypotheses is justified and described, including the experimental instruments and procedures involved. The results show that this WSN surpasses similar research systems in terms of its application scale, the number and types of sensor nodes involved and the complexity of its hardware and firmware architectures. The major contributions of this thesis are: • The WSN developed satisfies certain technical requirements to be declared fit for use in a mock Australian RACF. • The WSN provides high sensor detection accuracies (between 88% and 100%), superior location tracking capability (94.75%) and activities of daily living inference capability over similar studies. Opportunities for further improvements of this WSN include: • Fine tuning the detection accuracy of Passive Infra-red (PIR) motion sensors. • Minimising the down time of the sensor nodes due to firmware memory leak. • An extra location tracking mechanism to improve location accuracy determination.