Ex vivo investigation of novel wound healing therapies and development of a 3-D human skin equivalent wound model

It has previously been found that complexes comprised of vitronectin and growth factors (VN:GF) enhance keratinocyte protein synthesis and migration. More specifically, these complexes have been shown to significantly enhance the migration of dermal keratinocytes derived from human skin. In view of this, it was thought that these complexes may hold potential as a novel therapy for healing chronic wounds. However, there was no evidence indicating that the VN:GF complexes would retain their effect on keratinocytes in the presence of chronic wound fluid. The studies in this thesis demonstrate for the first time that the VN:GF complexes not only stimulate proliferation and migration of keratinocytes, but also these effects are maintained in the presence of chronic wound fluid in a 2-dimensional (2-D) cell culture model. Whilst the 2-D culture system provided insights into how the cells might respond to the VN:GF complexes, this investigative approach is not ideal as skin is a 3-dimensional (3-D) tissue. In view of this, a 3-D human skin equivalent (HSE) model, which reflects more closely the in vivo environment, was used to test the VN:GF complexes on epidermopoiesis. These studies revealed that the VN:GF complexes enable keratinocytes to migrate, proliferate and differentiate on a de-epidermalised dermis (DED), ultimately forming a fully stratified epidermis. In addition, fibroblasts were seeded on DED and shown to migrate into the DED in the presence of the VN:GF complexes and hyaluronic acid, another important biological factor in the wound healing cascade. This HSE model was then further developed to enable studies examining the potential of the VN:GF complexes in epidermal wound healing. Specifically, a reproducible partial-thickness HSE wound model was created in fully-defined media and monitored as it healed. In this situation, the VN:GF complexes were shown to significantly enhance keratinocyte migration and proliferation, as well as differentiation. This model was also subsequently utilized to assess the wound healing potential of a synthetic fibrin-like gel that had previously been demonstrated to bind growth factors. Of note, keratinocyte re-epitheliasation was shown to be markedly improved in the presence of this 3-D matrix, highlighting its future potential for use as a delivery vehicle for the VN:GF complexes. Furthermore, this synthetic fibrin-like gel was injected into a 4 mm diameter full-thickness wound created in the HSE, both keratinocytes and fibroblasts were shown to migrate into this gel, as revealed by immunofluorescence. Interestingly, keratinocyte migration into this matrix was found to be dependent upon the presence of the fibroblasts. Taken together, these data indicate that reproducible wounds, as created in the HSEs, provide a relevant ex vivo tool to assess potential wound healing therapies. Moreover, the models will decrease our reliance on animals for scientific experimentation. Additionally, it is clear that these models will significantly assist in the development of novel treatments, such as the VN:GF complexes and the synthetic fibrin-like gel described herein, ultimately facilitating their clinical trial in the treatment of chronic wounds.

The Financial Benefit For Insurers : Mediate in Personal Injuries Disputes

Resolving insurance disputes can focus only on quantum. Where insurers adopt integrative solutions they can enjoy cost savings and higher customer satisfaction. An integratively managed process can expand the negotiation options. The potential inherent in plaintiff’s emotions to resolve matters on an emotional basis, rather than an economic one, is explored. Using research, the author demonstrates how mediations are more likely to obtain integrative outcomes than unmediated conferences. Using a combination of governmental reports, published studies and academic publications, the paper demonstrates how mediation is more likely to foster an environment where the parties communicate and cooperate. Research is employed to demonstrate where mediators can reduce hostilities, in circumstances where negotiating parties alone would likely fail. Generally the paper constructs an argument to support the proposition that mediation can offer insurers an effective mechanism to reduce costs and increase customer satisfaction. INTRODUCTION Mediation can offer insurers an effective mechanism to reduce costs and increase customer satisfaction. This paper will first demonstrate the differences between distributive and integrative outcomes. It is argued insurer’s interest can be far better served through obtaining an integrative solution. The paper explains how the mediator can assist both parties to obtain an integrative outcome. Simultaneously the paper explores the extreme difficulties conference participants face in obtaining an integrative outcome without a mediator in an adversarial climate. The mediator’s ability to assist in the facilitation of integrative information exchange, defuse hostilities and reality check expectations is discussed. The mediator’s ability to facilitate in this area is compared to the inability of conference participants to achieve similar results. This paper concludes, the potential financial benefit offered by integrative solutions, combined with the ability of mediation to deliver such outcomes where unmediated conferences cannot deliver, leads to the recommendation that insurers opt for a mediation to best serve their commercial interests.

Early detection : a strategy to reduce risk and severity?

Despite changes in surgical techniques, radiotherapy targeting and the apparent earlier detection of cancers, secondary lymphoedema is still a significant problem for about 20–30% of those who receive treatment for cancer, although the incidence and prevalence does seem to be falling. The figures above generally relate to detection of an enlarged limb or other area, but it seems that about 60% of all patients also suffer other problems with how the limb feels, what can or cannot be done with it and a range of social or psychological issues. Often these ‘subjective’ changes occur before the objective ones, such as a change in arm volume or circumference. For most of those treated for cancer lymphoedema does not develop immediately, and, while about 60–70% develop it in the first few years, some do not develop lymphoedema for up to 15 or 20 years. Those who will develop clinically manifest lymphoedema in the future are, for some time, in a latent or hidden phase of lymphoedema. There also seems to be some risk factors which are indicators for a higher likelihood of lymphoedema post treatment, including oedema at the surgical site, arm dominance, age, skin conditions, and body mass index (BMI).

Contemporary behavioural influences in an organisational setting and implications for intervention development

Professional drivers and safety Within the industrialised world, work-related crashes are the most common cause of work-related death, injury and reduced productivity (Charbotel et al., 2001; Toscano and Windau, 1994). Likewise in Australia, road crashes are the most common cause of work-related fatalities, injuries and absence from work (Haworth et al., 2000), with the average time lost being greater than any other workplace claim (Stewart-Bogle, 1999). There are obvious costs related to work crashes such as vehicle and property repair costs. There are also many hidden expenses including third party costs, workers compensation, medical costs, rehabilitation, customer-related costs, increased insurance premiums, administrative costs, legal fees and loss of productivity (Collingwood, 1997; Haworth et al, 2000).

Motorcycle rider protective apparel wearing : observational study results from the Brisbane and Canberra regions

The continued growth in popularity of motorcycling is an area of concern within the road safety domain due to the vulnerability of motorcyclists sustaining injury in the event of a crash. Currently in Australia only motorcycle helmets are mandatory for motorcyclists or pillions to wear and there is no legislative standard for other protective apparel. This paper reports the results obtained from a series of motorcyclists’ apparel observational studies undertaken in the Brisbane and Canberra regions. The sites selected for the research were designed to enable the observation of both recreational and commuter riders. The results highlight both similarities and differences in the type of protective apparel worn by motorcyclists and pillions observed across the two regions. Encouragingly, across all the sites the majority of riders were wearing protective apparel on their upper body. However, a lower proportion of riders were observed wearing protective apparel on their lower body, particularly at the commuter sites in Brisbane. Similarly, the wearing of full face helmets was very high, except at the commuter sites in Brisbane. The generally lower use of protective apparel among commuter riders in Brisbane would appear to reflect both situational factors, such as climate, and the higher proportion of scooters observed at the sites. The implications of these results are discussed and recommendations are made for future research to identify factors that influence the wearing of protective motorcycle apparel.

Tip-over injuries in children under 5 years of age in Queensland 1999-2008

Furniture and appliance related injuries in children under 5 years of age accounts for an estimated 180 emergency presentations annually in Queensland. Injuries occur when children push or pull items over, climb and fall off furniture, or climb and tip the item over. Children under 2 years of age tend to injure themselves by pulling items over onto themselves Children over 2 years of age are more likely to be injured after climbing the item and either falling off or tipping the item over onto themselves. Tip over injuries (where the item falls over and injures the child) in children under 5 years of age account for an estimated 115 emergency presentations annually in Queensland. The item most commonly associated with a tip over injury is a television (with or without the cabinet) Prevention requires better design and selection of furniture with inherent stability coupled with mechanisms to install or fix less stable items

Pram and stroller related injury in Queensland children under 5 years of age

An estimated 200 Queensland children under 5 years of age are injured every year in incidents involving prams or strollers. The majority of injuries are due to falls from or falls with the pram or stroller Nineteen children were identified as having been caught in the pram or stroller mechanism (13 sustained finger injuries). Stairs and escalators were a factor in nearly 10 percent of pram or stroller fall injuries, with children being tipped out of the pram or stroller, or rolling down the stairs in the device. Roll away injuries accounted for eight percent of all pram or stroller fall injuries (some also involving stairs) Roll away injuries could be prevented by a default brake system similar to airport trolleys. Pram or stroller failure was identified in 2% of injuries

Bactrocera dorsalis Preference for and performance on two mango varieties at three stages of ripeness

Most tropical fruit flies only lay into mature fruit, but a small number can also oviposit into unripe fruit. Little is known about the link between adult oviposition preference and offspring performance in such situations. In this study we examine the influence of different ripening stages of two mango Mangifera indica L. (Anacardiaceae) varieties on the preference and performance of the Oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), a fly known to be able to develop in unripe fruit. Work was carried out as a series of laboratory-based choice and no-choice oviposition experiments and larval growth trials. In oviposition choice trials, female B. dorsalis demonstrated a preference for ripe fruit of mango variety Namdorkmai over variety Oakrong, but generally the dependent variable most influencing oviposition results was fruit ripening stage. Ripe and fully-ripe mangoes were most preferred for oviposition by B. dorsalis. In contrast, unripe mango was infrequently used by ovipositing females, particularly in choice trials. Consistent with the results of oviposition preference, ripe and fully-ripe mangoes were also best for offspring survival, with a higher percentage of larval survival to pupation and shorter development times in comparison to unripe mango. Changes in Total Soluble Solids, TSS, and skin toughness correlate with changing host use across the ripening stages. Regardless of the mango variety or ripeness stage, B. dorsalis had difficulty penetrating the pericarp of our experimental fruit. Larval survival was also often poor. We discuss the possibility that there may be differences in the ability of laboratory and wild flies to penetrate fruit for oviposition, or that in the field flies more regularly utilize natural fruit wounds as oviposition sites.

Mathematical modelling of muscle recruitment and function in the lumbar spine

Low back pain is an increasing problem in industrialised countries and although it is a major socio-economic problem in terms of medical costs and lost productivity, relatively little is known about the processes underlying the development of the condition. This is in part due to the complex interactions between bone, muscle, nerves and other soft tissues of the spine, and the fact that direct observation and/or measurement of the human spine is not possible using non-invasive techniques. Biomechanical models have been used extensively to estimate the forces and moments experienced by the spine. These models provide a means of estimating the internal parameters which can not be measured directly. However, application of most of the models currently available is restricted to tasks resembling those for which the model was designed due to the simplified representation of the anatomy. The aim of this research was to develop a biomechanical model to investigate the changes in forces and moments which are induced by muscle injury. In order to accurately simulate muscle injuries a detailed quasi-static three dimensional model representing the anatomy of the lumbar spine was developed. This model includes the nine major force generating muscles of the region (erector spinae, comprising the longissimus thoracis and iliocostalis lumborum; multifidus; quadratus lumborum; latissimus dorsi; transverse abdominis; internal oblique and external oblique), as well as the thoracolumbar fascia through which the transverse abdominis and parts of the internal oblique and latissimus dorsi muscles attach to the spine. The muscles included in the model have been represented using 170 muscle fascicles each having their own force generating characteristics and lines of action. Particular attention has been paid to ensuring the muscle lines of action are anatomically realistic, particularly for muscles which have broad attachments (e.g. internal and external obliques), muscles which attach to the spine via the thoracolumbar fascia (e.g. transverse abdominis), and muscles whose paths are altered by bony constraints such as the rib cage (e.g. iliocostalis lumborum pars thoracis and parts of the longissimus thoracis pars thoracis). In this endeavour, a separate sub-model which accounts for the shape of the torso by modelling it as a series of ellipses has been developed to model the lines of action of the oblique muscles. Likewise, a separate sub-model of the thoracolumbar fascia has also been developed which accounts for the middle and posterior layers of the fascia, and ensures that the line of action of the posterior layer is related to the size and shape of the erector spinae muscle. Published muscle activation data are used to enable the model to predict the maximum forces and moments that may be generated by the muscles. These predictions are validated against published experimental studies reporting maximum isometric moments for a variety of exertions. The model performs well for fiexion, extension and lateral bend exertions, but underpredicts the axial twist moments that may be developed. This discrepancy is most likely the result of differences between the experimental methodology and the modelled task. The application of the model is illustrated using examples of muscle injuries created by surgical procedures. The three examples used represent a posterior surgical approach to the spine, an anterior approach to the spine and uni-lateral total hip replacement surgery. Although the three examples simulate different muscle injuries, all demonstrate the production of significant asymmetrical moments and/or reduced joint compression following surgical intervention. This result has implications for patient rehabilitation and the potential for further injury to the spine. The development and application of the model has highlighted a number of areas where current knowledge is deficient. These include muscle activation levels for tasks in postures other than upright standing, changes in spinal kinematics following surgical procedures such as spinal fusion or fixation, and a general lack of understanding of how the body adjusts to muscle injuries with respect to muscle activation patterns and levels, rate of recovery from temporary injuries and compensatory actions by other muscles. Thus the comprehensive and innovative anatomical model which has been developed not only provides a tool to predict the forces and moments experienced by the intervertebral joints of the spine, but also highlights areas where further clinical research is required.

Identifying work related injuries : comparison of methods for interrogating text fields

Background: Work-related injuries in Australia are estimated to cost around $57.5 billion annually, however there are currently insufficient surveillance data available to support an evidence-based public health response. Emergency departments (ED) in Australia are a potential source of information on work-related injuries though most ED’s do not have an ‘Activity Code’ to identify work-related cases with information about the presenting problem recorded in a short free text field. This study compared methods for interrogating text fields for identifying work-related injuries presenting at emergency departments to inform approaches to surveillance of work-related injury.---------- Methods: Three approaches were used to interrogate an injury description text field to classify cases as work-related: keyword search, index search, and content analytic text mining. Sensitivity and specificity were examined by comparing cases flagged by each approach to cases coded with an Activity code during triage. Methods to improve the sensitivity and/or specificity of each approach were explored by adjusting the classification techniques within each broad approach.---------- Results: The basic keyword search detected 58% of cases (Specificity 0.99), an index search detected 62% of cases (Specificity 0.87), and the content analytic text mining (using adjusted probabilities) approach detected 77% of cases (Specificity 0.95).---------- Conclusions The findings of this study provide strong support for continued development of text searching methods to obtain information from routine emergency department data, to improve the capacity for comprehensive injury surveillance.

Mining patterns and factors contributing to crash severity on road curves

Road curves are an important feature of road infrastructure and many serious crashes occur on road curves. In Queensland, the number of fatalities is twice as many on curves as that on straight roads. Therefore, there is a need to reduce drivers’ exposure to crash risk on road curves. Road crashes in Australia and in the Organisation for Economic Co-operation and Development(OECD) have plateaued in the last five years (2004 to 2008) and the road safety community is desperately seeking innovative interventions to reduce the number of crashes. However, designing an innovative and effective intervention may prove to be difficult as it relies on providing theoretical foundation, coherence, understanding, and structure to both the design and validation of the efficiency of the new intervention. Researchers from multiple disciplines have developed various models to determine the contributing factors for crashes on road curves with a view towards reducing the crash rate. However, most of the existing methods are based on statistical analysis of contributing factors described in government crash reports. In order to further explore the contributing factors related to crashes on road curves, this thesis designs a novel method to analyse and validate these contributing factors. The use of crash claim reports from an insurance company is proposed for analysis using data mining techniques. To the best of our knowledge, this is the first attempt to use data mining techniques to analyse crashes on road curves. Text mining technique is employed as the reports consist of thousands of textual descriptions and hence, text mining is able to identify the contributing factors. Besides identifying the contributing factors, limited studies to date have investigated the relationships between these factors, especially for crashes on road curves. Thus, this study proposed the use of the rough set analysis technique to determine these relationships. The results from this analysis are used to assess the effect of these contributing factors on crash severity. The findings obtained through the use of data mining techniques presented in this thesis, have been found to be consistent with existing identified contributing factors. Furthermore, this thesis has identified new contributing factors towards crashes and the relationships between them. A significant pattern related with crash severity is the time of the day where severe road crashes occur more frequently in the evening or night time. Tree collision is another common pattern where crashes that occur in the morning and involves hitting a tree are likely to have a higher crash severity. Another factor that influences crash severity is the age of the driver. Most age groups face a high crash severity except for drivers between 60 and 100 years old, who have the lowest crash severity. The significant relationship identified between contributing factors consists of the time of the crash, the manufactured year of the vehicle, the age of the driver and hitting a tree. Having identified new contributing factors and relationships, a validation process is carried out using a traffic simulator in order to determine their accuracy. The validation process indicates that the results are accurate. This demonstrates that data mining techniques are a powerful tool in road safety research, and can be usefully applied within the Intelligent Transport System (ITS) domain. The research presented in this thesis provides an insight into the complexity of crashes on road curves. The findings of this research have important implications for both practitioners and academics. For road safety practitioners, the results from this research illustrate practical benefits for the design of interventions for road curves that will potentially help in decreasing related injuries and fatalities. For academics, this research opens up a new research methodology to assess crash severity, related to road crashes on curves.

Trauma and Injury Severity Score (TRISS) coefficients 2009 revision

Background: Currently used Trauma and Injury Severity Score (TRISS) coefficients, which measure probability of survival (Ps), were derived from the Major Trauma Outcome Study (MTOS) in 1995 and are now unlikely to be optimal. This study aims to estimate new TRISS coefficients using a contemporary database of injured patients presenting to emergency departments in the United States; and to compare these against the MTOS coefficients.---------- Methods: Data were obtained from the National Trauma Data Bank (NTDB) and the NTDB National Sample Project (NSP). TRISS coefficients were estimated using logistic regression. Separate coefficients were derived from complete case and multistage multiple imputation analyses for each NTDB and NSP dataset. Associated Ps over Injury Severity Score values were graphed and compared by age (adult ≥ 15 years; pediatric < 15 years) and injury mechanism (blunt; penetrating) groups. Area under the Receiver Operating Characteristic curves was used to assess coefficients’ predictive performance.---------- Results: Overall 1,072,033 NTDB and 1,278,563 weighted NSP injury events were included, compared with 23,177 used in the original MTOS analyses. Large differences were seen between results from complete case and imputed analyses. For blunt mechanism and adult penetrating mechanism injuries, there were similarities between coefficients estimated on imputed samples, and marked divergences between associated Ps estimated and those from the MTOS. However, negligible differences existed between area under the receiver operating characteristic curves estimates because the overwhelming majority of patients had minor trauma and survived. For pediatric penetrating mechanism injuries, variability in coefficients was large and Ps estimates unreliable.---------- Conclusions: Imputed NTDB coefficients are recommended as the TRISS coefficients 2009 revision for blunt mechanism and adult penetrating mechanism injuries. Coefficients for pediatric penetrating mechanism injuries could not be reliably estimated.

Reparations for Indigenous People: International and Comparative Perspectives

Published in concomitance with the adoption of the United Nations Declaration on the Rights of Indigenous Peoples, this volume brings together a group of renowned legal experts and activists from different parts of the world who, from international and comparative perspectives, investigate the right of indigenous peoples to reparation for breaches of their individual and collective rights. The first part of the book is devoted to general aspects of this important matter, providing a comprehensive assessment of the relevant international legal framework and including overviews of the topic of reparations for human rights violations, the status of indigenous peoples in international law, and the vision of reparations as conceived by the communities concerned. The second part embraces a comprehensive investigation of the relevant practice at the international, regional, and national level, examining the best practices of reparations according to the ideologies and expectations of indigenous peoples and offering a comparative perspective on the ways in which the right of these peoples to redress for the injuries suffered is realized worldwide. The global picture painted by these contributions provides a view of the status of relevant international law that is synthesized in the two final chapters of the book, which include a concrete example of how a judicial claim for reparation is to be structured and prescribes the best practices and strategies to be adopted in order to maximize the opportunities for indigenous peoples to obtain effective redress. As a whole, this volume offers a comprehensive vision of its subject matter in international and comparative law, with a practical approach aimed at supporting legal academics, administrators, and practitioners in improving the avenues and modalities of reparations for indigenous peoples

Parental beliefs about supervising children when crossing roads and cycling

Pedestrian and cyclist injuries are significant public health issues together accounting for 11-30% of road deaths in highly motorised countries. Children are particularly at risk. In Australia in 2009 children 0-16 years comprised 11.4% of pedestrian deaths and 6.4% of cyclist deaths. Parental attitudes and level of supervision are important to children’s road safety. Results from a telephone survey with parents of children 5-9 years (N=147) are reported. Questions addressed beliefs about preventability of injury, appropriate ages for children to cross the road or cycle independently, and the frequency of holding 5-9 year old children’s hands while crossing the road. Results suggest that parents believe most injuries are preventable and that they personally can act to improve their own safety in the home, on the road, at work, as well as in or on the water. Most parents (68%) indicated children should be 10 years or older before crossing the road or cycling independently. Parents were more likely to report holding younger children’s hands (5-6 years) when crossing the road and less likely to do so for 7-9 year olds. There was a small effect of child gender, with parents more likely to hold boy’s hand than a girl’s.