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.

Real-time performance modelling of a sustained attention to response task

Vigilance declines when exposed to highly predictable and uneventful tasks. Monotonous tasks provide little cognitive and motor stimulation and contribute to human errors. This paper aims to model and detect vigilance decline in real time through participant’s reaction times during a monotonous task. A lab-based experiment adapting the Sustained Attention to Response Task (SART) is conducted to quantify the effect of monotony on overall performance. Then relevant parameters are used to build a model detecting hypovigilance throughout the experiment. The accuracy of different mathematical models are compared to detect in real-time – minute by minute - the lapses in vigilance during the task. We show that monotonous tasks can lead to an average decline in performance of 45%. Furthermore, vigilance modelling enables to detect vigilance decline through reaction times with an accuracy of 72% and a 29% false alarm rate. Bayesian models are identified as a better model to detect lapses in vigilance as compared to Neural Networks and Generalised Linear Mixed Models. This modelling could be used as a framework to detect vigilance decline of any human performing monotonous tasks.

Marginalising the mainstream : a signed performance of The Miracle Worker places deaf issues centre-stage

William Gibson’s The Miracle Worker was staged at the Brisbane Powerhouse June 2009 by Crossbow Productions. In this adaption, people with hearing impairment were privileged through the use of shadow-signing, unscripted signing and the appropriation of signing as a theatrical language in itself. 250 people living with hearing impairment attended the production, 70 had never attended a theatrical event before. During the post-performance discussions hearing audience members expressed feelings of displacement through experiencing the culture of the deaf society and not grasping some of the ideas. This paper argues that this inversion enhanced meaning making for all and illustrates a way forward to encourage the signing of more theatrical events.

The naked audience : audience performance at a recent staging of Gibson’s "the Miracle Worker"

Contemporary mainstream theatre audiences observe etiquette strictures that regulate behaviour. As Baz Kershaw argues, “the idea of the passive audience for performance has been associated usually with mainstream theatre.” This paper explores a mainstream event where the extant contract of audience silence was replaced with a raw, emotional audience response that continued into the post-performance discussion. William Gibson’s The Miracle Worker was performed by Crossbow Productions at the Brisbane Powerhouse to an audience made up of mainstream theatre patrons and people living with hearing and visual impairment. Various elements such as shadow signing and tactile tours worked metatheatrically and self-referentially to heighten audience awareness. During the performances the verbal and non-verbal responses of the audience were so pervasive that the audience became not only co-creators of the performance text but performers of a rich audience text that had a dramatic impact on the theatrical experience for audience and actors alike. During the post-performance discussion the audience performers spilled onto the stage interacting with the actors, extending the pleasure of the experience. This paper discusses how in privileging the audience as co-creators and performers, the chasm between stage and audience was bridged. The audiences’ performance changed, enriched and created new meanings for each performance.

Comparison of U.S., Canadian, and Australian participants' performance on the Algase Wandering Scale-Version 2 (AWS-V2)

Background Wandering represents a major problem in the management of patients with Alzheimer’s disease (AD). In this study we examined the utility of the Algase Wandering Scale (AWS), a newly developed psychometric instrument that asks caregivers to assess the likelihood of wandering behavior. Methods The AWS was administered to the caregivers of 40 AD patients and total and subscale scores were examined in relation to measures of mental and functional status, depressive symptoms and medication usage. Results AWS scores were comparable, though slightly lower, than those normative values previously published. Higher scores were associated with more severe dementia. The Negative Outcome subscale showed a significant increase in reported falls or injuries in association with anti-depressant use. Conclusions These data provide some construct validation for the AWS as a potentially useful scale to assess wandering behaviors in AD.

Performance study of two different compensating devices in a custom power park

Simulation study of a custom power park (CPP) is presented. It is assumed that the park contains unbalanced and nonlinear loads in addition to a sensitive load. Two different types of compensators are used separately to protect the sensitive load against unbalance and distortion caused by the other loads. It has been shown that a shunt compensator can regulate the voltage of the CPP bus, whereas the series compensator can only regulate the sensitive load terminal voltage. Additional issues such as the load transfer through a static transfer switch, detection of sag/fault etc. are also discussed. The concepts are validated through PSCAD/EMTDC simulation studies on a sample distribution system.

Performance evaluation of an adaptive travel time prediction model

This paper presents a travel time prediction model and evaluates its performance and transferability. Advanced Travelers Information Systems (ATIS) are gaining more and more importance, increasing the need for accurate, timely and useful information to the travelers. Travel time information quantifies the traffic condition in an easy to understand way for the users. The proposed travel time prediction model is based on an efficient use of nearest neighbor search. The model is calibrated for optimal performance using Genetic Algorithms. Results indicate better performance by using the proposed model than the presently used naïve model.