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.

The aftermath of the Lehman Brothers collapse in Hong Kong : the saga, regulatory deficiencies and government responses

The paper examines the fallout of the Lehman Brothers collapse in Hong Kong. As an international financial hub in Asia, Hong Kong was profoundly affected by the collapse of this company. As a result, it impacted negatively on the public’s confidence in the Hong Kong’s banking sector. Furthermore, this event has exposed a number of regulatory deficiencies in Hong Kong. In response to this financial crisis, the Hong Kong government had made an unprecedented move to negotiate with local banks to refund the investors. In addition, the government has also sought public consultation on proposal to enhance the regulation of the sale of financial products. This paper argues that there needs to be amendments to the prevailing laws and the inclusions of legal rules to back up those proposed measures so that the disclosed information from the financial institution will not mislead the investors or misrepresent the products offered.

Legal responses to climate change

The challenges of climate change pose problems requiring new and innovative legal responses by legal practitioners, government officials and corporate officers. This book addresses a broad range of topic areas where climate change has impact and systematically analyses the key legal responses to climate change, both at the international level and within Australia at federal, State and local levels. In particular, it critically examines: •the rights, duties and market mechanisms established under the international climate change regime •the effect of climate change policies on the implementation of environmental and planning laws •new regimes for the implementation of renewable energy and energy efficiency initiatives •legal frameworks for the implementation of biological and geological sequestration projects (including forest projects and carbon rights); and •legal principles for the design of an effective carbon trading scheme for Australia It also considers the role of the common law including: •the likely response of the law of torts to emerging forms of climate change harm; and •potential liabilities for professionals who must take climate change into account in their decision-making and advice

Responses to 2008 Apology : Digital story collection

On 13 February 2008 Prime Minister Kevin Rudd made an apology to Australia’s Indigenous People on behalf of the Parliament of Australia. The State Library of Queensland, with assistance from Queensland University of Technology and Queensland’s Aboriginal and Torres Strait Islander communities, captured responses to this historic event in a collection of digital stories. Stories were created with: Tiga Bayles; Jeremy Robertson; Natalie Alberts; Sam Wagan Watson Jr; Nadine McDonald-Dowd; Anna Bligh; and Quentin Bryce.

Defending the patch : a labour geography analysis of unions’ construction of and responses to the problem of declining union membership amongst youth

If the trade union movement is to remain an influential force in the industrial, economic and socio/political arenas of industrialised nations it is vital that its recruitment of young members improve dramatically. Australian union membership levels have declined markedly over the last three decades and youth union membership levels have decreased more than any age group. Currently around 10% of young workers aged between 16-24 years are members of unions in Australia compared to 26% of workers aged 45-58 (Oliver, 2008). This decline has occurred throughout the union movement, in all states and in almost all industries and occupations. This research, which consists of interviews with union organisers and union officials, draws on perspectives from the labour geography literature to explore how union personnel located in various places, spaces and scales construct the issue of declining youth union membership. It explores the scale of connections within the labour movement and the extent to which these connections are leveraged to address the problem of youth union membership decline. To offer the reader a sense of context and perspective, the thesis firstly outlines the historical development of the union movement. It also reviews the literature on youth membership decline. Labour geography offers a rich and apposite analytical tool for investigation of this area. The notion of ‘scale’ as a dynamic, interactive, constructed and reconstructed entity (Ellem, 2006) is an appropriate lens for viewing youth-union membership issues. In this non-linear view, scale is a relational element which interplays with space, place and the environment (Howett, in Marston, 2000) rather than being ‘sequential’ and hierarchical. Importantly, the thesis investigates the notion of unions as ‘spaces of dependence’ (Cox, 1998a, p.2), organisations whose space is centred upon realising essential interests. It also considers the quality of unions’ interactions with others – their ‘spaces of engagement‘(Cox, 1998a, p.2), and the impact that this has upon their ability to recruit youth. The findings reveal that most respondents across the spectrum of the union movement attribute the decline in youth membership levels to factors external to the movement itself, such as changes to industrial relations legislation and the impact of globalisation on employment markets. However, participants also attribute responsibility for declining membership levels to the union movement itself, citing factors such as a lack of resourcing and a need to change unions’ perceived identity and methods of operation. The research further determined that networks of connections across the union movement are tenuous and, to date, are not being fully utilised to assist unions to overcome the youth recruitment dilemma. The study concludes that potential connections between unions are hampered by poor resourcing, workload issues and some deeply entrenched attitudes related to unions ‘defending (and maintaining) their patch’.

The critical meets the cultural : International students’ responses to critical, dialogic postgraduate education in a Western university

What happens when international students encounter critical, dialogic approaches to postgraduate education in a Western university? This chapter works with the narrative accounts of two students from Asian countries about their varied experiences of and responses to critically-oriented, interactive, English-medium study in a Master of Education course in Australia. Beginning from researcher standpoint, it tables the students’ stories of cultural, academic, linguistic and personal border crossings, and their ‘readings’ of course demands prioritising critical analysis, dialogic exchange and problem-solving. Their responses raise ongoing, unresolved epistemological and experiential issues about the cross-cultural and transnational relevance and value of Western/Eurocentric ‘critical’ education.

Integrating Responses to Homelessness: The Contribution of Participatory Action Research

In recent years Participatory Action Research (PAR) and other collaborative inquiry processes have been used in a wide variety of program and service contexts. Early childhood services, Indigenous services, youth drug and alcohol services, and education and vocational training support services have all been sites where PAR has been utilized. Action research is important as it helps improve policy and ensures that best practice and experience can be shared.

Below the ‘tip of the iceberg’: extra-legal responses to workplace sexual harassment

Despite longstanding and explicit legal frameworks for preventing and responding to sexual harassment, only a small proportion of those sexually harassed use legal avenues of redress to seek justice. In contrast to legal cases which constitute the ‘tip of the iceberg’, this study examines extra-legal strategies — the less visible but more frequent, ‘everyday’, formal and informal organizational practices. We report on a national prevalence survey conducted by the Australian Human Rights Commission which examined how ‘targets’ use formal organizational grievance mechanisms, and/or other informal methods to redress, resist or avoid workplace sexual harassment. The findings revealed that the majority of targets do not formally report it because of fear of retribution or that nothing will be done, but they sometimes use apparently proactive or assertive alternative strategies, such as seeking informal assistance and ‘dealing with the problem themselves’. These responses occur in the context of extra-legal facets of organizational life which affect the extent to which sexual harassment and other unfavorable and discriminatory acts are tolerated.

Design of experiments for bivariate binary responses modelled by Copula functions

Optimal design for generalized linear models has primarily focused on univariate data. Often experiments are performed that have multiple dependent responses described by regression type models, and it is of interest and of value to design the experiment for all these responses. This requires a multivariate distribution underlying a pre-chosen model for the data. Here, we consider the design of experiments for bivariate binary data which are dependent. We explore Copula functions which provide a rich and flexible class of structures to derive joint distributions for bivariate binary data. We present methods for deriving optimal experimental designs for dependent bivariate binary data using Copulas, and demonstrate that, by including the dependence between responses in the design process, more efficient parameter estimates are obtained than by the usual practice of simply designing for a single variable only. Further, we investigate the robustness of designs with respect to initial parameter estimates and Copula function, and also show the performance of compound criteria within this bivariate binary setting.