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.

Development and synthesis of innovative approaches to the surgical assessment of articular cartilage degeneration

This research has established, through ultrasound, near infrared spectroscopy and biomechanics experiments, parameters and parametric relationships that can form the framework for quantifying the integrity of the articular cartilage-on-bone laminate, and objectively distinguish between normal/healthy and abnormal/degenerated joint tissue, with a focus on articular cartilage. This has been achieved by: 1. using traditional experimental methods to produce new parameters for cartilage assessment; 2. using novel methodologies to develop new parameters; and 3. investigating the interrelationships between mechanical, structural and molec- ular properties to identify and select those parameters and methodologies that can be used in a future arthroscopic probe based on points 1 and 2. By combining the molecular, micro- and macro-structural characteristics of the tissue with its mechanical properties, we arrive at a set of critical benchmarking parameters for viable and early-stage non-viable cartilage. The interrelationships between these characteristics, examined using a multivariate analysis based on principal components analysis, multiple linear regression and general linear modeling, could then to deter- mine those parameters and relationships which have the potential to be developed into a future clinical device. Specifically, this research has found that the ultrasound and near infrared techniques can subsume the mechanical parameters and combine to characterise the tissue at the molecular, structural and mechanical levels over the full depth of the cartilage matrix. It is the opinion in this thesis that by enabling the determination of the precise area of in uence of a focal defect or disease in the joint, demarcating the boundaries of articular cartilage with dierent levels of degeneration around a focal defect, better surgical decisions that will advance the processes of joint management and treatment will be achieved. Providing the basis for a surgical tool, this research will contribute to the enhancement and quanti�cation of arthroscopic procedures, extending to post- treatment monitoring and as a research tool, will enable a robust method for evaluating developing (particularly focalised) treatments.

The Biology, Epidemiology, and Management of Rice Tungro Disease in Asia

Many farmers in South and Southeast Asia describe rice tungro disease as a cancer disease because of the severe damage it causes and the difficulty of controlling it (121). As the most important of the 14 rice viral diseases, tungro was first recognized as a leafhopper-transmitted virus disease in 1963 (88). However, tungro, which means “degenerated growth” in a Filipino dialect, has a much longer history. It is almost certain that tungro was responsible for a disease outbreak that occurred in 1859 in Indonesia, which was referred to at the time as mentek (83). In the past, a variety of names has been given to tungro, including accep na pula in the Philippines, penyakit merah in Malaysia, and yelloworange leaf in Thailand (83).

"Surviving" adolescence : apocalyptic and post-apocalyptic transformations in young adult fiction

This study, entitled "Surviving" Adolescence: Apocalyptic and post-apocalyptic transformations in young adult fiction‖, analyses how discourses surrounding the apocalyptic and post-apocalyptic are represented in selected young adult fiction published between 1997 and 2009. The term ―apocalypse‖ is used by current theorists to refer to an uncovering or disclosure (most often a truth), and ―post-apocalypse‖ means to be after a disclosure, after a revelation, or after catastrophe. This study offers a double reading of apocalyptic and post-apocalyptic discourses, and the dialectical tensions that are inherent in, and arise from, these discourses. Drawing on the current scholarship of children‘s and young adult literature this thesis uses post-structural theoretical perspectives to develop a framework and methodology for conducting a close textual analysis of exclusion, ‗un‘differentiation, prophecy, and simulacra of death. The combined theoretical perspectives and methodology offer new contributions to young adult fiction scholarship. This thesis finds that rather than conceiving adolescence as the endurance of a passing phase of a young person‘s life, there is a new trend emerging in young adult fiction that treats adolescence as a space of transformation essential to the survival of the young adult, and his/her community.

Developing a model of care to improve the health and well-being for Indigenous people receiving renal dialysis treatment

The high levels of end-stage renal disease among Indigenous Australians, particularly in remote areas of the country, are a serious public health concern. The magnitude of the problem is reflected in figures from the Australian and New Zealand Transplant and Dialysis Registry that show that Indigenous Australians experience end-stage renal disease at a rate almost 9–10 times higher than other non-Indigenous Australians. A majority of Indigenous Australians have to relocate to receive appropriate renal dialysis treatment. In some Australian states, renal treatment is based on self-care dialysis which allows those Indigenous Australians to be treated back in their community. Evidence clearly shows that reuniting renal patients with community and family improves overall health and well-being for those Indigenous Australians. With the appropriate resources, training, and support, self-care management of renal dialysis treatment is an effective way for Indigenous people with end-stage renal failure to be treated at home. In this context, the study was used to gain insight and further understanding of the impact that end-stage renal disease and renal dialysis treatment has had on the lives of Indigenous community members. The study findings are from 14 individually interviewed people from South East Queensland. Data from the interviews were analysed using a combination of thematic and content analysis. The study methodology was based on qualitative data principles where the Indigenous community members were able to share their experiences and journeys living with end-stage renal disease. Many of the experiences and understanding closely relate to the renal disease pattern and the treatment with other outside influences, such as social, cultural, and environmental influences, all having an equal impact. Each community member’s experience with end-stage renal disease is unique; some manage with family and medical support, while others try to manage independently. From the study, community members who managed their renal dialysis treatment independently were much more aware of their renal health status. The study provides recommendations towards a model of care to improve the health and well-being is based on self-care and self-determination principles.

Quality of life after total laparoscopic hysterectomy versus total abdominal hysterectomy for stage I endometrial cancer (LACE) : a randomised trial

Background: The two-stage Total Laparoscopic Hysterectomy (TLH) versus Total Abdominal Hysterectomy (TAH) for stage I endometrial cancer (LACE) randomised controlled trial was initiated in 2005. The primary objective of stage 1 was to assess whether TLH results in equivalent or improved QoL up to 6 months after surgery compared to TAH. The primary objective of stage 2 was to test the hypothesis that disease-free survival at 4.5 years is equivalent for TLH and TAH. Results addressing the primary objective of stage 1 of the LACE trial are presented here. Methods: The first 361 LACE participants (TAH n= 142, TLH n=190) were enrolled in the QoL substudy at 19 centres across Australia, New Zealand and Hong Kong, and 332 completed the QoL analysis. Randomisation was performed centrally and independently from other study procedures via a computer generated, web-based system (providing concealment of the next assigned treatment) using stratified permuted blocks of 3 and 6, and assigned patients with histologically confirmed stage 1 endometrioid endometrial adenocarcinoma and ECOG performance status <2 to TLH or TAH stratified by histological grade and study centre. No blinding of patients or study personnel was attempted. QoL was measured at baseline, 1 and 4 weeks (early), and 3 and 6 months (late) after surgery using the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire. The primary endpoint was the difference between the groups in QoL change from baseline at early and late time points (a 5% difference was considered clinically significant). Analysis was performed according to the intention-to-treat principle using generalized estimating equations on differences from baseline for the early and late QoL recovery. The LACE trial is registered with clinicaltrials.gov (NCT00096408) and the Australian New Zealand Clinical Trials Registry (CTRN12606000261516). Patients for both stages of the trial have now been recruited and are being followed up for disease-specific outcomes. Findings: The proportion of missing values at the 5%, 10% 15% and 20% differences in the FACT-G scale was 6% (12/190) in the TLH and 14% (20/142) in the TAH group. There were 8/332 conversions (2.4%, 7 of which were from TLH to TAH). In the early phase of recovery, patients undergoing TLH reported significantly greater improvement of QoL from baseline compared to TAH in all subscales except the emotional and social well-being subscales. Improvements in QoL up to 6 months post-surgery continued to favour TLH except for the emotional and social well-being of the FACT and the visual analogue scale of the EuroQoL five dimensions (EuroQoL-VAS). Length of operating time was significantly longer in the TLH group (138±43 mins), than in the TAH group at (109±34 mins; p=0.001). While the proportion of intraoperative adverse events was similar between the treatment groups (TAH 8/142, 5.6%; TLH 14/190, 7.4%; p=0.55), postoperatively, twice as many patients in the TAH group experienced adverse events of CTC grade 3+ than in the TLH group (33/142, 23.2% and 22/190, 11.6%, respectively; p=0.004). Postoperative serious adverse events occurred more frequently in patients who had a TAH (27/142, 19.0%) than a TLH (15/190, 7.9%) (p=0.002). Interpretation: QoL improvements from baseline during early and later phases of recovery, and the adverse event profile significantly favour TLH compared to TAH for patients treated for Stage I endometrial cancer.

Geekdom for Grrrls health : Australian undergraduate experiences developing and promoting women’s health in cyberspace

There is an increasing global reliance on the Internet for retrieving information on health, illness, and recovery (Sillence et al, 2007; Laurent et al, 2009; Adams, 2010). People suffering from a vast array of illnesses, conditions, and complaints, as well as healthy travelers seeking advice about safe practices abroad, and teens seeking information about safe sexual practices are all now more likely to go to the internet for information than they are to rely solely on a general practitioner or physician (Santor et al, 2007; Moreno et al, 2009; Bartlett et al, 2010). Women in particular seek advice and support online for a number of health-related concerns regarding issues such as puberty, conception, pregnancy, postnatal depression, mothering, breast-cancer recovery, and ageing healthily (van Zutphen, 2008; Raymond et al, 2005). In keeping with this increasing socio-technological trend, the Women’s Health Unit at the Queensland University of Technology (Q.U.T), Brisbane, Australia, introduced the research, design, and development of online information resources for issues affecting the health of Australian women as an assessment item for students in the undergraduate Public Health curriculum. Students were required to research a particular health issue affecting Australian women, including pregnancy, pregnancy terminations, postnatal depression, returning to the work force after having a baby, breast cancer recovery, chronic disease prevention, health and safety for sex-workers, and ageing healthily. Students were required to design and develop websites that supported people living with these conditions, or who were in these situations. The websites were designed for communicating effectively with both women seeking information about their health, and their health practitioners. The pedagogical challenge inherent in this exercise was twofold: firstly, to encourage students to develop the skills to design and maintain software for online health forums; and secondly, to challenge public health students to go beyond generating ‘awareness’ and imparting health information to developing a nuanced understanding of the worlds and perspectives of their audiences, who require supportive networks and options that resonate with their restrictions, capabilities, and dispositions. This latter challenge spanned the realms of research, communication, and aesthetic design. This paper firstly, discusses an increasing reliance on the Internet by women seeking health-related information and the potential health risks and benefits of this trend. Secondly, it applies a post-structural analysis of the de-centred and mobile female self, as online social ‘spaces’ and networks supersede geographical ‘places’ and hierarchies, with implications for democracy, equality, power, and ultimately women’s health. Thirdly, it depicts the processes (learning reflections) and products (developed websites) created within this Women’s Health Unit by the students. Finally, we review this development in the undergraduate curriculum in terms of the importance of providing students with skills in research, communication, and technology in order to share and implement improved health care and social marketing for women as both recipients and providers of health care in the Internet Age.

Collaborative research to develop a specialist, post-graduate competency-based education curriculum and continuing professional development structure for health librarians in Australia

Through a grant received from the Australian Library and Information Association (ALIA), members of Health Libraries Australia (HLA) are collaborating with a researcher/educator to conduct a twelve month research project with the goal of developing an educational framework for the Australian health librarianship workforce of the future. The collaboration comprises the principal researcher and a representative group of practitioners from different sectors of the health industry who are affiliated with ALIA in various committees, advisory groups and roles. The research has two main aims: to determine the future skills requirements for the health librarian workforce in Australia; and to develop a structured, modular education framework for specialist post-graduate qualifications together with a structure for ongoing continuing professional development. The paper highlights some of the major trends in the health sector and some of the main environmental influences that may act as drivers for change for health librarianship as a profession, and particularly for educating the future workforce. The research methodology is outlined and the main results are described; the findings are discussed with regard to their implications for the development of a structured, competency-based education framework.

Vulnerability factors for disaster-induced child post-traumatic stress disorder : the case for low family resilience and previous mental illness

Objective: The aim of the present study was to investigate whether parent report of family resilience predicted children’s disaster-induced post-traumatic stress disorder (PTSD) and general emotional symptoms, independent of a broad range of variables including event-related factors, previous child mental illness and social connectedness. ---------- Methods: A total of 568 children (mean age = 10.2 years, SD = 1.3) who attended public primary schools, were screened 3 months after Cyclone Larry devastated the Innisfail region of North Queensland. Measures included parent report on the Family Resilience Measure and Strengths and Difficulties Questionnaire (SDQ)–emotional subscale and child report on the PTSD Reaction Index, measures of event exposure and social connectedness. ---------- Results: Sixty-four students (11.3%) were in the severe–very severe PTSD category and 53 families (28.6%) scored in the poor family resilience range. A lower family resilience score was associated with child emotional problems on the SDQ and longer duration of previous child mental health difficulties, but not disaster-induced child PTSD or child threat perception on either bivariate analysis, or as a main or moderator variable on multivariate analysis (main effect: adjusted odds ratio (ORadj) = 0.57, 95% confidence interval (CI) = 0.13–2.44). Similarly, previous mental illness was not a significant predictor of child PTSD in the multivariate model (ORadj = 0.75, 95%CI = 0.16–3.61). ---------- Conclusion: In this post-disaster sample children with existing mental health problems and those of low-resilience families were not at elevated risk of PTSD. The possibility that the aetiological model of disaster-induced child PTSD may differ from usual child and adolescent conceptualizations is discussed.

Socioeconomic position, gender, health behaviours and biomarkers of cardiovascular disease and diabetes

Socio-economic gradients in cardiovascular disease (CVD) and diabetes have been found throughout the developed world and there is some evidence to suggest that these gradients may be steeper for women. Research on social gradients in biological risk factors for CVD and diabetes has received less attention and we do not know the extent to which gradients in biomarkers vary for men and women. We examined the associations between two indicators of socio-economic position (education and household income) and biomarkers of diabetes and cardiovascular disease (CVD) for men and women in a national, population-based study of 11,247 Australian adults. Multi-level linear regression was used to assess associations between education and income and glucose tolerance, dyslipidaemia, blood pressure (BP) and waist circumference before and after adjustment for behaviours (diet, smoking, physical activity, TV viewing time, and alcohol use). Measures of glucose tolerance included fasting plasma glucose and insulin and the results of a glucose tolerance test (2 h glucose) with higher levels of each indicating poorer glucose tolerance. Triglycerides and High Density Lipoprotein (HDL) Cholesterol were used as measures of dyslipidaemia with higher levels of the former and lower levels of the later being associated with CVD risk. Lower education and low income were associated with higher levels of fasting insulin, triglycerides and waist circumference in women. Women with low education had higher systolic and diastolic BP and low income women had higher 2 h glucose and lower HDL cholesterol. With only one exception (low income and systolic BP), all of these estimates were reduced by more than 20% when behavioural risk factors were included. Men with lower education had higher fasting plasma glucose, 2 h glucose, waist circumference and systolic BP and, with the exception of waist circumference, all of these estimates were reduced when health behaviours were included in the models. While low income was associated with higher levels of 2-h glucose and triglycerides it was also associated with better biomarker profiles including lower insulin, waist circumference and diastolic BP. We conclude that low socio-economic position is more consistently associated with a worse profile of biomarkers for CVD and diabetes for women.

Theatre audience contribution : facilitating a new text through the post-performance discussion

Theatre Audience Contribution introduces a new approach to theatre audience research: audience contribution through the post-performance discussion. This volume considers the physical and vocal behaviour of audience members as an integral part of the theatrical event that changes, adds to and informs the theatrical experience. Post-performance discussions, although rising in popularity, are yet an under-explored and under-utilised avenue for audience contribution. Beginning with an overview of reception theory and the historical role of theatre audiences, the author introduces a new method for the facilitation of post-performance discussions that encourages audience contribution and privileges the audience voice. Two case studies explore post-performance discussions that inform the theatrical event and discover a new role for the contemporary audience: audience critic. This accessible volume has significant implications for theatre theorists, practitioners and audiences alike.

Adherence to fish oil intervention in patients with chronic kidney disease

Objective: With growing recognition of the role of inflammation in the development of chronic and acute disease, fish oil is increasingly used as a therapeutic agent, but the nature of the intervention may pose barriers to adherence in clinical populations. Our objective was to investigate the feasibility of using a fish oil supplement in hemodialysis patients. ---------- Design: This was a nonrandomized intervention study.---------- Setting: Eligible patients were recruited at the Hemodialysis Unit of Wesley Hospital, Brisbane, Queensland, Australia. Patients The sample included 28 maintenance hemodialysis patients out of 43 eligible patients in the unit. Exclusion criteria included patients regularly taking a fish oil supplement at baseline, receiving hemodialysis for less than 3 months, or being unable to give informed consent.---------- Intervention: Eicosapentaenoic acid (EPA) was administered at 2000 mg/day (4 capsules) for 12 weeks. Adherence was measured at baseline and weekly throughout the study according to changes in plasma EPA, and was further measured subjectively by self-report.---------- Results: Twenty patients (74%) adhered to the prescription based on changes in plasma EPA, whereas an additional two patients self-reported good adherence. There was a positive relationship between fish oil intake and change in plasma EPA. Most patients did not report problems with taking the fish oil. Using the baseline data, it was not possible to characterize adherent patients.---------- Conclusions: Despite potential barriers, including the need to take a large number of prescribed medications already, 74% of hemodialysis patients adhered to the intervention. This study demonstrated the feasibility of using fish oil in a clinical population.