Modulation of dermal microvascular endithelial cell responses to growth factors and haemostatic factors in the presence of vitronectin

In order to effect permanent closure in burns patients suffering from full thickness wounds, replacing their skin via split thickness autografting, is essential. Dermal substitutes in conjunction with widely meshed split thickness autografts (+/- cultured keratinocytes) reduce scarring at the donor and recipient sites of burns patients by reducing demand for autologous skin (both surface area and thickness), without compromising dermal delivery at the wound face. Tissue engineered products such as Integra consist of a dermal template which is rapidly remodelled to form a neodermis, at which time the temporary silicone outer layer is removed and replaced with autologous split thickness skin. Whilst provision of a thick tissue engineered dermis at full thickness burn sites reduces scarring, it is hampered by delays in vascularisation which results in clinical failure. The ultimate success of any skin graft product is dependent upon a number of basic factors including adherence, haemostasis and in the case of viable tissue grafts, success is ultimately dependent upon restoration of a normal blood supply, and hence this study. Ultimately, the goal of this research is to improve the therapeutic properties of tissue replacements, through impregnation with growth factors aimed at stimulating migration and proliferation of microvascular endothelial cells into the donor tissue post grafting. For the purpose of my masters, the aim was to evaluate the responsiveness of a dermal microvascular endothelial cell line to growth factors and haemostatic factors, in the presence of the glycoprotein vitronectin. Vitronectin formed the backbone for my hypothesis and research due to its association with both epithelial and, more specifically, endothelial migration and proliferation. Early work using a platform technology referred to as VitroGro (Tissue Therapies Ltd), which is comprised of vitronectin bound BP5/IGF-1, aided keratinocyte proliferation. I hypothesised that this result would translate to another epithelium - endothelium. VitroGro had no effect on endothelial proliferation or migration. Vitronectin increases the presence of Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) receptors, enhancing cell responsiveness to their respective ligands. So, although Human Microvascular Endothelial Cell line 1 (HMEC-1) VEGF receptor expression is generally low, it was hypothesised that exposure to vitronectin would up-regulate this receptor. HMEC-1 migration, but not proliferation, was enhanced by vitronectin bound VEGF, as well as vitronectin bound Epidermal Growth Factor (EGF), both of which could be used to stimulate microvascular endothelial cell migration for the purpose of transplantation. In addition to vitronectin's synergy with various growth factors, it has also been shown to play a role in haemostasis. Vitronectin binds thrombin-antithrombin III (TAT) to form a trimeric complex that takes on many of the attributes of vitronectin, such as heparin affinity, which results in its adherence to endothelium via heparan sulfate proteoglycans (HSP), followed by unaltered transcytosis through the endothelium, and ultimately its removal from the circulation. This has been documented as a mechanism designed to remove thrombin from the circulation. Equally, it could be argued that it is a mechanism for delivering vitronectin to the matrix. My results show that matrix-bound vitronectin dramatically alters the effect that conformationally altered antithrombin three (cATIII) has on proliferation of microvascular endothelial cells. cATIII stimulates HMEC-1 proliferation in the presence of matrix-bound vitronectin, as opposed to inhibiting proliferation in its absence. Binding vitronectin to tissues and organs prior to transplant, in the presence of cATIII, will have a profound effect on microvascular infiltration of the graft, by preventing occlusion of existing vessels whilst stimulating migration and proliferation of endothelium within the tissue.

Business Leaders Hall of Fame collection

"Qld Business Leaders Hall of Fame" is a research project that includes interviews with eminent Qlders that produced oral history interviews and digital stories about their life/company's achievements. This model was able to test and evaluate the use of oral history and digital storytelling for learning and community heritage purposes. Interviewees include; Sir John and Valmai Pidgeon, Joseph Saragossi, Robert Bryan, Clem Jones, Jim Kennedy, Sr Angela Mary, Castelmaine Perkins, Burns and Philp, Qantas, Don Argus & Steve Irwin.

Using economic data to reduce healthcare-acquired infection

In this issue Burns et al. report an estimate of the economic loss to Auckland City Hospital from cases of healthcare-associated bloodstream infection. They show that patients with infection stay longer in hospital and this must impose an opportunity cost because beds are blocked. Harder to measure costs fall on patients, their families and non-acute health services. Patients face some risk of dying from the infection.

Gender and political leadership : moving beyond stereotypes

This short paper suggests that the categories of ‘transformational’ and ‘transactional’ leadership styles ( see Burns 1972) may provide analytical purchase on the question of whether current women leaders have radically different styles and approaches to the earlier second wave feminist generation. The two cases chosen for this paper are the senior women in the Labor and Liberal Parties – Julia Gillard and Julie Bishop. The evidence – explored below – indicates there are strong transactional qualities to both women leaders.

Heat effects of promoters and determination of burn criterion in promoted combustion testing

Promoted ignition testing (NASA) Test 17) [1] is used to determine the relative flammability of metal rods in oxygen-enriched atmospheres. A promotor is used to ignite a metal sample rod, initiating sample burning. If a predetermined length of the sample burns, beyond the promotor, the material is considered flammable at the condition tested. Historically, this burn length has been somewhat arbitrary. Experiments were performed to better understand this test by obtaining insight into the effect a burning promotor has on the preheating of a test sample. Test samples of several metallic materials were prepared and coupled to fast-responding thermocouples along their length. Thermocouple measurements and test video were synchronized to determine temperature increase with respect to time and length along each test sample. A recommended flammability burn length, based on a sample preheat of 500 degrees fahrenheit, was determined based on the preheated zone measured from these tests. This length was determined to be 30 mm (1.18 in.). Validation of this length and its rationale are presented.

Reinforced hydrogels for silicone copolymer delivery for scar remediation

Hypertrophic scars are formed by collagen overproduction in wounded areas and often occur in victims of severe burns. There are several methods for hypertrophic scar remediation and silicone gel therapy is one of the more successful methods. Research by others has shown that the activity of these gels may be due to migration of amphiphilic silicone oligomers from the gel and into the dermis, down-regulating production of collagen by fibroblasts. Normal silicone oil (PDMS) does not produce the same effect on fibroblasts. The main purpose of this project is the introduction of a particular amphiphilic silicone rake copolymer into an appropriate network which can absorb and release the silicone copolymer on the scarred area. Hydrogels are polymeric crosslinked networks which can swell in water or a drug solution, and gradually release the drug when applied to the skin. The application of gel enhances the effectiveness of the therapy, reduces the period of treatment and can be comfortable for patients to use. Polyethylene glycol (PEG) based networks have been applied in this research, because the amphiphilic silicone rake copolymer to be used as a therapy has polyethylene oxide (PEO) as a side chain. These PEO side chains have very similar chemical structure to a PEG gel chain so enhancing both the compatibility and the diffusion of the amphiphilic silicone rake copolymer into and out of the gel. Synthesis of PEG-based networks has been performed by two methods: in situ silsesquioxane formation as crosslink with a sol-gel reaction under different conditions and UV curing. PEG networks have low mechanical properties which is a fundamental limitation of the polymer backbone. For mechanical properties enhancement, composite networks were synthesized using nano-silica with different surface modification. The chemical structure of in situ silsesquioxane in the dry network has been examined by Solid State NMR, Differential Scanning Calorimetry (DSC) and swelling measurements in water. Mechanical properties of dry networks were tested by Dynamic Mechanical Thermal Analysis (DMTA) to determine modulus and interfacial interaction between silica and the network. In this way a family of self-reinforced networks has been produced that have been shown to absorb and deliver the active amphiphilic silicone- PEO rake copolymer.

Review of the under the limit drink driving rehabilitation program

The combination of alcohol and driving is a major health and economic burden to most communities in industrialised countries. The total cost of crashes for Australia in 1996 was estimated at approximately 15 billion dollars and the costs for fatal crashes were about 3 billion dollars (BTE, 2000). According to the Bureau of Infrastructure, Transport and Regional Development and Local Government (2009; BITRDLG) the overall cost of road fatality crashes for 2006 $3.87 billion, with a single fatal crash costing an estimated $2.67 million. A major contributing factor to crashes involving serious injury is alcohol intoxication while driving. It is a well documented fact that consumption of liquor impairs judgment of speed, distance and increases involvement in higher risk behaviours (Waller, Hansen, Stutts, & Popkin, 1986a; Waller et al., 1986b). Waller et al. (1986a; b) asserts that liquor impairs psychomotor function and therefore renders the driver impaired in a crisis situation. This impairment includes; vision (degraded), information processing (slowed), steering, and performing two tasks at once in congested traffic (Moskowitz & Burns, 1990). As BAC levels increase the risk of crashing and fatality increase exponentially (Department of Transport and Main Roads, 2009; DTMR). According to Compton et al. (2002) as cited in the Department of Transport and Main Roads (2009), crash risk based on probability, is five times higher when the BAC is 0.10 compared to a BAC of 0.00. The type of injury patterns sustained also tends to be more severe when liquor is involved, especially with injuries to the brain (Waller et al., 1986b). Single and Rohl (1997) reported that 30% of all fatal crashes in Australia where alcohol involvement was known were associated with Breadth Analysis Content (BAC) above the legal limit of 0.05gms/100ml. Alcohol related crashes therefore contributes to a third of the total cost of fatal crashes (i.e. $1 billion annually) and crashes where alcohol is involved are more likely to result in death or serious injury (ARRB Transport Research, 1999). It is a major concern that a drug capable of impairment such as is the most available and popular drug in Australia (Australian Institute of Health and Welfare, 2007; AIHW). According to the AIHW (2007) 89.9% of the approximately 25,000 Australians over the age of 14 surveyed had consumed at some point in time, and 82.9% had consumed liquor in the previous year. This study found that 12.1% of individuals admitted to driving a motor vehicle whilst intoxicated. In general males consumed more liquor in all age groups. In Queensland there were 21503 road crashes in 2001, involving 324 fatalities and the largest contributing factor was alcohol and or drugs (Road Traffic Report, 2001). 23438 road crashes in 2004, involving 289 fatalities and the largest contributing factor was alcohol and or drugs (DTMR, 2009). Although a number of measures such as random breath testing have been effective in reducing the road toll (Watson, Fraine & Mitchell, 1995) the recidivist drink driver remains a serious problem. These findings were later supported with research by Leal, King, and Lewis (2006). This Queensland study found that of the 24661 drink drivers intercepted in 2004, 3679 (14.9%) were recidivists with multiple drink driving convictions in the previous three years covered (Leal et al., 2006). The legal definition of the term “recidivist” is consistent with the Transport Operations (Road Use Management) Act (1995) and is assigned to individuals who have been charged with multiple drink driving offences in the previous five years. In Australia relatively little attention has been given to prevention programs that target high-risk repeat drink drivers. However, over the last ten years a rehabilitation program specifically designed to reduce recidivism among repeat drink drivers has been operating in Queensland. The program, formally known as the “Under the Limit” drink driving rehabilitation program (UTL) was designed and implemented by the research team at the Centre for Accident Research and Road Safety in Queensland with funding from the Federal Office of Road Safety and the Institute of Criminology (see Sheehan, Schonfeld & Davey, 1995). By 2009 over 8500 drink-drivering offenders had been referred to the program (Australian Institute of Crime, 2009).

Closing the gap between policy and 'Law' : Indigenous homelands and a working future

The Northern Territory Government's Working Future: Outstations/Homelands (2009) policy statement gives effect to the Council of Australian Government's Closing the Gap policy on Indigenous housing and remote service delivery. These policies mark a radical shift in public policy that winds back the outstations and homelands movement that began in the 1970's. This paper examines Indigenous homelands policy and considers whether these policies are consistent with the Indigenous human rights and in particular the United Nations Declaration on the Rights of Indigenous Peoples (2007), which Australia endorsed in 2009. The author argues that the current homelands policy breaches a number of Indigenous human rights and promotes assimiliation by forcing Indigenous Australians to relocate to access basic services such as health, housing and education. As a consequence these policies are counter-intuitive to the overall Closing the Gap goals of improving Indigenous health outcomes because they fail to take into account the importance of country and culture to Indigenous wellbeing. She concludes that Australian governments need to formulate a homelands policy that is consistent with Indigenous human rights and in particular the right of self determination, enjoyment of culture and protection against forced assimilation.

Challenging the assumptions of positivism : an analysis of the concept of society in Sampi on behalf of the Bardi and Jawi people v Western Australia [2010] and Bodney v Bennell [2008]

The requirement to prove a society united by a body of law and customs to establish native title rights has been identified as a major hurdle to achieving native title recognition. The recent appeal decision of the Federal Court in Sampi on behalf of the Bardi and Jawi People v Western Australia [2010] opens the potential for a new judicial interpretation of society based on the internal view of native title claimants. The decision draws on defining features of legal positivism to inform the court’s findings as to the existence of a single Bardi Jawi society of ‘one people’ living under ‘one law’. The case of Bodney v Bennell [2008] is analysed through comparitive study of how the application of the received positivist framework may limit native title recognition. This paper argues that the framing of Indigenous law by reference to Western legal norms is problematic due to the assumptions of legal positivism and that an internal view based on Indigenous worldviews, which see law as intrinsically linked to the spiritual and ancestral connection to country, is more appropriate to determine proof in native title claims.

Safeguarding rural Australia: addressing masculinity and violence in rural settings : unintentional violent harm including injuries in an Australian rural context : analysis of secondary data analysis

This report is an update of an earlier one produced in January 2010 (see Carrington et al. 2010) which remains as an ePrint through the project’s home page. This report focuses on our examination of extant data which have been sourced with respect to unintentional serious and violent harm, including injuries, to males living in regional and remote Australia . and which were available in public data bases at production. Such harm typically might be caused by, for example, transport accidents, occupational exposures and hazards, burns and so on. Thus unintentional violent harm can cause physical trauma the consequences of which can lead to chronic conditions including psychological harm or substance abuse.

Queensland Business Women Stories

These projects build on the research of Klaebe and Burgess into digital story-telling, specifically variable workshop scenarios, co-creative media, participatory public history, and the development of co-creative production processes for cultural institutions. The projects represented a partnership between QUT and the State Library of Queensland. The Five Senses project focused on the distributed digital storytelling workshop model and the development of audiences for digital storytelling. The team worked with regional artists whose work had been selected for inclusion in the Five Senses exhibition at the State Library of Queensland to produce stories about their work; these works were then integrated into the physical exhibition space. The Queensland Businesswomen project produced four digital stories profiling the lives of leading Queensland businesswomen. The digital story telling workshop model was disbanded and research teams worked individually with participants to create the digital stories. Academic research and oral history interviews were conducted initially to foreground these productions. This pilot led to a larger project, Business Leaders Hall of Fame, which now has a dedicated viewing room in the SLQ sponsored by an annual silver service dinner event. With the Responses to the Apology project, which stimulated similar projects in Mt Isa and Cairns, the research team worked with Indigenous facilitators, and the participants created their digital stories with assistance from these facilitators and the QUT research team using a mix of workshop and individual meetings. The research component of the work relates to the further development of co-creative production processes for cultural institutions, involving a wide range of institutional and individual partners, while authentically representing the intensely personal perspectives of each of the primary participants. The Queensland Business Leaders Hall of Fame was a research project that included interviews with eminent Queenslanders that produced oral history interviews and digital stories about the achievements of both Queensland personalities and businesses. This model was able to test and evaluate the use of oral history and digital storytelling for learning and community heritage purposes. Interviewees include; Sir John and Valmai Pidgeon, Joseph Saragossi, Robert Bryan, Clem Jones, Jim Kennedy, Sr Angela Mary, Castelmaine Perkins, Burns and Philp, Qantas, Don Argus & Steve Irwin All digital stories, oral history interviews and transcripts were accessioned into the library collection – an international first for digital stories. Two publications in refereed journals have resulted, and the digital stories are stored in the SLQ permanent collection for the benefit of national and international scholars and the general public.