Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

Multiple types of child maltreatment and adolescent mental health in Viet Nam

Objective To examine the prevalence of multiple types of maltreatment (MTM), potentially confounding factors and associations with depression, anxiety and self-esteem among adolescents in Viet Nam. Methods In 2006 we conducted a cross-sectional survey of 2591 students (aged 12–18 years; 52.1% female) from randomly-selected classes in eight secondary schools in urban (Hanoi) and rural (Hai Duong) areas of northern Viet Nam (response rate, 94.7%). Sequential multiple regression analyses were performed to estimate the relative influence of individual, family and social characteristics and of eight types of maltreatment, including physical, emotional and sexual abuse and physical or emotional neglect, on adolescent mental health. Findings Females reported more neglect and emotional abuse, whereas males reported more physical abuse, but no statistically significant difference was found between genders in the prevalence of sexual abuse. Adolescents were classified as having nil (32.6%), one (25.9%), two (20.7%), three (14.5%) or all four (6.3%) maltreatment types. Linear bivariate associations between MTM and depression, anxiety and low self-esteem were observed. After controlling for demographic and family factors, MTM showed significant independent effects. The proportions of the variance explained by the models ranged from 21% to 28%. Conclusion The combined influence of adverse individual and family background factors and of child maltreatment upon mental health in adolescents in Viet Nam is consistent with research in non-Asian countries. Emotional abuse was strongly associated with each health indicator. In Asian communities where child abuse is often construed as severe physical violence, it is important to emphasize the equally pernicious effects of emotional maltreatment.

Children with special health care needs : social and learning competence in the early years

The number of children with special health care needs surviving infancy and attending school has been increasing. Due to their health status, these children may be at risk of low social-emotional and learning competencies (e.g., Lightfoot, Mukherjee, & Sloper, 2000; Zehnder, Landolt, Prchal, & Vollrath, 2006). Early social problems have been linked to low levels of academic achievement (Ladd, 2005), inappropriate behaviours at school (Shiu, 2001) and strained teacher-child relationships (Blumberg, Carle, O‘Connor, Moore, & Lippmann, 2008). Early learning difficulties have been associated with mental health problems (Maughan, Rowe, Loeber, & Stouthamer-Loeber, 2003), increased behaviour issues (Arnold, 1997), delinquency (Loeber & Dishion, 1983) and later academic failure (Epstein, 2008). Considering the importance of these areas, the limited research on special health care needs in social-emotional and learning domains is a factor driving this research. The purpose of the current research is to investigate social-emotional and learning competence in the early years for Australian children who have special health care needs. The data which informed this thesis was from Growing up in Australia: The Longitudinal Study of Australian Children. This is a national, longitudinal study being conducted by the Commonwealth Department of Families, Housing, Community Services and Indigenous Affairs. The study has a national representative sample, with data collection occurring biennially, in 2004 (Wave 1), 2006 (Wave 2) and 2008 (Wave 3). Growing up in Australia uses a cross-sequential research design involving two cohorts, an Infant Cohort (0-1 at recruitment) and a Kindergarten Cohort (4-5 at recruitment). This study uses the Kindergarten Cohort, for which there were 4,983 children at recruitment. Three studies were conducted to address the objectives of this thesis. Study 1 used Wave 1 data to identify and describe Australian children with special health care needs. Children who identified as having special health care needs through the special health care needs screener were selected. From this, descriptive analyses were run. The results indicate that boys, children with low birth weight and children from families with low levels of maternal education are likely to be in the population of children with special health care needs. Further, these children are likely to be using prescription medications, have poor general health and are likely to have specific condition diagnoses. Study 2 used Wave 1 data to examine differences between children with special health care needs and their peers in social-emotional competence and learning competence prior to school. Children identified by the special health care needs screener were chosen for the case group (n = 650). A matched case control group of peers (n = 650), matched on sex, cultural and linguistic diversity, family socioeconomic position and age, were the comparison group. Social-emotional competence was measured through Social/Emotional Domain scores taken from the Growing up in Australia Outcome Index, with learning competence measured through Learning Domain scores. Results suggest statistically significant differences in scores between the two groups. Children with special health care needs have lower levels of social-emotional and learning competence prior to school compared to their peers. Study 3 used Wave 1 and Wave 2 data to examine the relationship between special health care needs at Wave 1 and social-emotional competence and learning competence at Wave 2, as children started school. The sample for this study consisted of children in the Kindergarten Cohort who had teacher data at Wave 2. Results from multiple regression models indicate that special health care needs prior to school (Wave 1) significantly predicts social-emotional competence and learning competence in the early years of school (Wave 2). These results indicate that having special health care needs prior to school is a risk factor for the social-emotional and learning domains in the early years of school. The results from these studies give valuable insight into Australian children with special health care needs and their social-emotional and learning competence in the early years. The Australia population of children with special health care needs were primarily male children, from families with low maternal education, were likely to be of poor health and taking prescription medications. It was found that children with special health care needs were likely to have lower social-emotional competence and learning competence prior to school compared to their peers. Results indicate that special health care needs prior to school were predictive of lower social-emotional and learning competencies in the early years of school. More research is required into this unique population and their competencies over time. However, the current research provides valuable insight into an under researched 'at risk' population.

Quantification of the accuracy of MRI generated 3D models of long bones compared to CT generated 3D models

Orthopaedic fracture fixation implants are increasingly being designed using accurate 3D models of long bones based on computer tomography (CT). Unlike CT, magnetic resonance imaging (MRI) does not involve ionising radiation and is therefore a desirable alternative to CT. This study aims to quantify the accuracy of MRI-based 3D models compared to CT-based 3D models of long bones. The femora of five intact cadaver ovine limbs were scanned using a 1.5T MRI and a CT scanner. Image segmentation of CT and MRI data was performed using a multi-threshold segmentation method. Reference models were generated by digitising the bone surfaces free of soft tissue with a mechanical contact scanner. The MRI- and CT-derived models were validated against the reference models. The results demonstrated that the CT-based models contained an average error of 0.15mm while the MRI-based models contained an average error of 0.23mm. Statistical validation shows that there are no significant differences between 3D models based on CT and MRI data. These results indicate that the geometric accuracy of MRI based 3D models was comparable to that of CT-based models and therefore MRI is a potential alternative to CT for generation of 3D models with high geometric accuracy.

Small animal bone healing models : standards, tips, and pitfalls results of a consensus meeting

Small animal fracture models have gained increasing interest in fracture healing studies. To achieve standardized and defined study conditions, various variables must be carefully controlled when designing fracture healing experiments in mice or rats. The strain, age and sex of the animals may influence the process of fracture healing. Furthermore, the choice of the fracture fixation technique depends on the questions addressed, whereby intra- and extramedullary implants as well as open and closed surgical approaches may be considered. During the last few years, a variety of different, highly sophisticated implants for fracture fixation in small animals have been developed. Rigid fixation with locking plates or external fixators results in predominantly intramembranous healing in both mice and rats. Locking plates, external fixators, intramedullary screws, the locking nail and the pin-clip device allow different degrees of stability resulting in various amounts of endochondral and intramembranous healing. The use of common pins that do not provide rotational and axial stability during fracture stabilization should be discouraged in the future. Analyses should include at least biomechanical and histological evaluations, even if the focus of the study is directed towards the elucidation of molecular mechanisms of fracture healing using the largely available spectrum of antibodies and gene-targeted animals to study molecular mechanisms of fracture healing. This review discusses distinct requirements for the experimental setups as well as the advantages and pitfalls of the different fixation techniques in rats and mice.

Occupational Therapy and Clinical Research in Mental Health Rehabilitation

Practitioners working in Australian mental health services are faced with the challenge of providing appropriate evidence-based interventions that lead to measurable improvement and good outcomes. Current government policy is committed to the development of strategic mental health research. One focus has been on under-researched practice areas, which include the development of psychosocial rehabilitation systems and models that facilitate recovery. To meet this challenge, an Australian rehabilitation service formed a collaborative partnership with a university. The purposes of the collaboration were to implement new forms of service delivery based on consumer need and evidence and to design research projects to evaluate components of the rehabilitation programme. This article examines the process of developing the collaboration and provides examples of how research projects have been used to inform practice and improve the effectiveness of service delivery. Challenges to the sustainability of this kind of collaboration are considered.

An architecture for enhanced assurance in e-health systems

Notwithstanding the obvious potential advantages of information and communications technology (ICT) in the enhanced provision of healthcare services, there are some concerns associated with integration of and access to electronic health records. A security violation in health records, such as an unauthorised disclosure or unauthorised alteration of an individual's health information, can significantly undermine both healthcare providers' and consumers' confidence and trust in e-health systems. A crisis in confidence in any national level e-health system could seriously degrade the realisation of the system's potential benefits. In response to the privacy and security requirements for the protection of health information, this research project investigated national and international e-health development activities to identify the necessary requirements for the creation of a trusted health information system architecture consistent with legislative and regulatory requirements and relevant health informatics standards. The research examined the appropriateness and sustainability of the current approaches for the protection of health information. It then proposed an architecture to facilitate the viable and sustainable enforcement of privacy and security in health information systems under the project title "Open and Trusted Health Information Systems (OTHIS)". OTHIS addresses necessary security controls to protect sensitive health information when such data is at rest, during processing and in transit with three separate and achievable security function-based concepts and modules: a) Health Informatics Application Security (HIAS); b) Health Informatics Access Control (HIAC); and c) Health Informatics Network Security (HINS). The outcome of this research is a roadmap for a viable and sustainable architecture for providing robust protection and security of health information including elucidations of three achievable security control subsystem requirements within the proposed architecture. The successful completion of two proof-of-concept prototypes demonstrated the comprehensibility, feasibility and practicality of the HIAC and HIAS models for the development and assessment of trusted health systems. Meanwhile, the OTHIS architecture has provided guidance for technical and security design appropriate to the development and implementation of trusted health information systems whilst simultaneously offering guidance for ongoing research projects. The socio-economic implications of this research can be summarised in the fact that this research embraces the need for low cost security strategies against economic realities by using open-source technologies for overall test implementation. This allows the proposed architecture to be publicly accessible, providing a platform for interoperability to meet real-world application security demands. On the whole, the OTHIS architecture sets a high level of security standard for the establishment and maintenance of both current and future health information systems. This thereby increases healthcare providers‘ and consumers‘ trust in the adoption of electronic health records to realise the associated benefits.

Velocity-jump models with crowding effects

Velocity jump processes are discrete random walk models that have many applications including the study of biological and ecological collective motion. In particular, velocity jump models are often used to represent a type of persistent motion, known as a “run and tumble”, which is exhibited by some isolated bacteria cells. All previous velocity jump processes are non-interacting, which means that crowding effects and agent-to-agent interactions are neglected. By neglecting these agent-to-agent interactions, traditional velocity jump models are only applicable to very dilute systems. Our work is motivated by the fact that many applications in cell biology, such as wound healing, cancer invasion and development, often involve tissues that are densely packed with cells where cell-to-cell contact and crowding effects can be important. To describe these kinds of high cell density problems using a velocity jump process we introduce three different classes of crowding interactions into a one-dimensional model. Simulation data and averaging arguments lead to a suite of continuum descriptions of the interacting velocity jump processes. We show that the resulting systems of hyperbolic partial differential equations predict the mean behavior of the stochastic simulations very well.

Social and emotional determinants of health

- describe what is meant by socioeconomic differences in health, and the social and emotional determinants of health - understand how health inequalities are affected by the social and economic circumstances that people experience throughout their lives - discuss how factors such as living and working conditions, income, place and education can impact on health - identify actions for public health policy-makers that have the potential to make a difference in improving health outcomes within populations - appreciate the concept of social cohesion and social capital, and their role as potential protective factors in health - understand conceptual models that can assist in analysing these issues.

Preliminary study on bridge health prediction using Dynamic Objective Oriented Bayesian Network (DOOBN)

The availability of bridges is crucial to people’s daily life and national economy. Bridge health prediction plays an important role in bridge management because maintenance optimization is implemented based on prediction results of bridge deterioration. Conventional bridge deterioration models can be categorised into two groups, namely condition states models and structural reliability models. Optimal maintenance strategy should be carried out based on both condition states and structural reliability of a bridge. However, none of existing deterioration models considers both condition states and structural reliability. This study thus proposes a Dynamic Objective Oriented Bayesian Network (DOOBN) based method to overcome the limitations of the existing methods. This methodology has the ability to act upon as a flexible unifying tool, which can integrate a variety of approaches and information for better bridge deterioration prediction. Two demonstrative case studies are conducted to preliminarily justify the feasibility of the methodology

Evaluation of modal analysis techniques using physical models to detect osseointegration of implants in transfemoral amputees

Non-invasive vibration analysis has been used extensively to monitor the progression of dental implant healing and stabilization. It is now being considered as a method to monitor femoral implants in transfemoral amputees. This paper evaluates two modal analysis excitation methods and investigates their capabilities in detecting changes at the interface between the implant and the bone that occur during osseointegration. Excitation of bone-implant physical models with the electromagnetic shaker provided higher coherence values and a greater number of modes over the same frequency range when compared to the impact hammer. Differences were detected in the natural frequencies and fundamental mode shape of the model when the fit of the implant was altered in the bone. The ability to detect changes in the model dynamic properties demonstrates the potential of modal analysis in this application and warrants further investigation.

Models of collective cell motion for cell populations with different aspect ratio : diffusion, proliferation and travelling waves

Continuum, partial differential equation models are often used to describe the collective motion of cell populations, with various types of motility represented by the choice of diffusion coefficient, and cell proliferation captured by the source terms. Previously, the choice of diffusion coefficient has been largely arbitrary, with the decision to choose a particular linear or nonlinear form generally based on calibration arguments rather than making any physical connection with the underlying individual-level properties of the cell motility mechanism. In this work we provide a new link between individual-level models, which account for important cell properties such as varying cell shape and volume exclusion, and population-level partial differential equation models. We work in an exclusion process framework, considering aligned, elongated cells that may occupy more than one lattice site, in order to represent populations of agents with different sizes. Three different idealizations of the individual-level mechanism are proposed, and these are connected to three different partial differential equations, each with a different diffusion coefficient; one linear, one nonlinear and degenerate and one nonlinear and nondegenerate. We test the ability of these three models to predict the population level response of a cell spreading problem for both proliferative and nonproliferative cases. We also explore the potential of our models to predict long time travelling wave invasion rates and extend our results to two dimensional spreading and invasion. Our results show that each model can accurately predict density data for nonproliferative systems, but that only one does so for proliferative systems. Hence great care must be taken to predict density data for with varying cell shape.

Theorising a framework for contemporary health literacies in schools

While schools are mandated to teach health education, there is considerable disjunction between government and community expectations, definitions of health literacy, and what schools are currently teaching. Health literacy in the health sector tends to be dominated by a pathogenic approach, where the health of a person is generally referenced against states of illness. In this paper we argue for a salutogenic approach to health literacies. Further, we utilise mainstream literacy theories and models to propose a robust framework for health literacy in schools that accounts for the complexity of health and well being in contemporary society.