Mathematical modelling of controlled drug release from polymer micro-spheres : incorporating the effects of swelling, diffusion and dissolution via moving boundary problems

Controlled drug delivery is a key topic in modern pharmacotherapy, where controlled drug delivery devices are required to prolong the period of release, maintain a constant release rate, or release the drug with a predetermined release profile. In the pharmaceutical industry, the development process of a controlled drug delivery device may be facilitated enormously by the mathematical modelling of drug release mechanisms, directly decreasing the number of necessary experiments. Such mathematical modelling is difficult because several mechanisms are involved during the drug release process. The main drug release mechanisms of a controlled release device are based on the device’s physiochemical properties, and include diffusion, swelling and erosion. In this thesis, four controlled drug delivery models are investigated. These four models selectively involve the solvent penetration into the polymeric device, the swelling of the polymer, the polymer erosion and the drug diffusion out of the device but all share two common key features. The first is that the solvent penetration into the polymer causes the transition of the polymer from a glassy state into a rubbery state. The interface between the two states of the polymer is modelled as a moving boundary and the speed of this interface is governed by a kinetic law. The second feature is that drug diffusion only happens in the rubbery region of the polymer, with a nonlinear diffusion coefficient which is dependent on the concentration of solvent. These models are analysed by using both formal asymptotics and numerical computation, where front-fixing methods and the method of lines with finite difference approximations are used to solve these models numerically. This numerical scheme is conservative, accurate and easily implemented to the moving boundary problems and is thoroughly explained in Section 3.2. From the small time asymptotic analysis in Sections 5.3.1, 6.3.1 and 7.2.1, these models exhibit the non-Fickian behaviour referred to as Case II diffusion, and an initial constant rate of drug release which is appealing to the pharmaceutical industry because this indicates zeroorder release. The numerical results of the models qualitatively confirms the experimental behaviour identified in the literature. The knowledge obtained from investigating these models can help to develop more complex multi-layered drug delivery devices in order to achieve sophisticated drug release profiles. A multi-layer matrix tablet, which consists of a number of polymer layers designed to provide sustainable and constant drug release or bimodal drug release, is also discussed in this research. The moving boundary problem describing the solvent penetration into the polymer also arises in melting and freezing problems which have been modelled as the classical onephase Stefan problem. The classical one-phase Stefan problem has unrealistic singularities existed in the problem at the complete melting time. Hence we investigate the effect of including the kinetic undercooling to the melting problem and this problem is called the one-phase Stefan problem with kinetic undercooling. Interestingly we discover the unrealistic singularities existed in the classical one-phase Stefan problem at the complete melting time are regularised and also find out the small time behaviour of the one-phase Stefan problem with kinetic undercooling is different to the classical one-phase Stefan problem from the small time asymptotic analysis in Section 3.3. In the case of melting very small particles, it is known that surface tension effects are important. The effect of including the surface tension to the melting problem for nanoparticles (no kinetic undercooling) has been investigated in the past, however the one-phase Stefan problem with surface tension exhibits finite-time blow-up. Therefore we investigate the effect of including both the surface tension and kinetic undercooling to the melting problem for nanoparticles and find out the the solution continues to exist until complete melting. The investigation of including kinetic undercooling and surface tension to the melting problems reveals more insight into the regularisations of unphysical singularities in the classical one-phase Stefan problem. This investigation gives a better understanding of melting a particle, and contributes to the current body of knowledge related to melting and freezing due to heat conduction.

Understanding the operational structure of Southeast Asian drug trafficking groups in Australia

This thesis examined the operational structure of Southeast Asian drug trafficking groups operating on the eastern seaboard of Australia by testing the validity and application of organised crime and drug trafficking typologies using data obtained from 159 drug trafficking cases in three Australian states: New South Wales; Queensland; and Victoria. Key findings indicated that the usefulness of typologies is limited when classifying and analysing organised crime groups. In particular, Southeast Asian drug trafficking groups operated largely in small, informal, family-based hierarchies or groups that were better conceptualised using theoretical perspectives from network and cultural studies. The study recommended that replicating previous empirical research in the field is an effective approach that will contribute towards building a cumulative body of knowledge on organised crime structures.

Developing national level informatics competencies for undergraduate nurses : methodological approaches from Australia and Canada

Health information systems are being implemented in countries by governments and regional health authorities in an effort to modernize healthcare. With these changes, there has emerged a demand by healthcare organizations for nurses graduating from college and university programs to have acquired nursing informatics competencies that would allow them to work in clinical practice settings (e.g. hospitals, clinics, home care etc). In this paper we examine the methods employed by two different countries in developing national level nursing informatics competencies expected of undergraduate nurses prior to graduation (i.e. Australia, Canada). This work contributes to the literature by describing the science and methods of nursing informatics competency development at a national level.

Post-glacial sea-level changes around the Australian margin : a review

It has been known since Rhodes Fairbridge’s first attempt to establish a global pattern of Holocene sea-level change by combining evidence from Western Australia and from sites in the northern hemisphere that the details of sea-level history since the Last Glacial Maximum vary considerably across the globe. The Australian region is relatively stable tectonically and is situated in the ‘far-field’ of former ice sheets. It therefore preserves important records of post-glacial sea levels that are less complicated by neotectonics or glacio-isostatic adjustments. Accordingly, the relative sea-level record of this region is dominantly one of glacio-eustatic (ice equivalent) sea-level changes. The broader Australasian region has provided critical information on the nature of post-glacial sea level, including the termination of the Last Glacial Maximum when sea level was approximately 125 m lower than present around 21,000–19,000 years BP, and insights into meltwater pulse 1A between 14,600 and 14,300 cal. yr BP. Although most parts of the Australian continent reveals a high degree of tectonic stability, research conducted since the 1970s has shown that the timing and elevation of a Holocene highstand varies systematically around its margin. This is attributed primarily to variations in the timing of the response of the ocean basins and shallow continental shelves to the increased ocean volumes following ice-melt, including a process known as ocean siphoning (i.e. glacio-hydro-isostatic adjustment processes). Several seminal studies in the early 1980s produced important data sets from the Australasian region that have provided a solid foundation for more recent palaeo-sea-level research. This review revisits these key studies emphasising their continuing influence on Quaternary research and incorporates relatively recent investigations to interpret the nature of post-glacial sea-level change around Australia. These include a synthesis of research from the Northern Territory, Queensland, New South Wales, South Australia and Western Australia. A focus of these more recent studies has been the re-examination of: (1) the accuracy and reliability of different proxy sea-level indicators; (2) the rate and nature of post-glacial sea-level rise; (3) the evidence for timing, elevation, and duration of mid-Holocene highstands; and, (4) the notion of mid- to late Holocene sea-level oscillations, and their basis. Based on this synthesis of previous research, it is clear that estimates of past sea-surface elevation are a function of eustatic factors as well as morphodynamics of individual sites, the wide variety of proxy sea-level indicators used, their wide geographical range, and their indicative meaning. Some progress has been made in understanding the variability of the accuracy of proxy indicators in relation to their contemporary sea level, the inter-comparison of the variety of dating techniques used and the nuances of calibration of radiocarbon ages to sidereal years. These issues need to be thoroughly understood before proxy sea-level indicators can be incorporated into credible reconstructions of relative sea-level change at individual locations. Many of the issues, which challenged sea-level researchers in the latter part of the twentieth century, remain contentious today. Divergent opinions remain about: (1) exactly when sea level attained present levels following the most recent post-glacial marine transgression (PMT); (2) the elevation that sea-level reached during the Holocene sea-level highstand; (3) whether sea-level fell smoothly from a metre or more above its present level following the PMT; (4) whether sea level remained at these highstand levels for a considerable period before falling to its present position; or (5) whether it underwent a series of moderate oscillations during the Holocene highstand.

An overview of level I evidence for the management of radiation dermatitis literature

Background: Despite the technologic advances, radiation dermatitis is still a prevalent and distressing symptom in patients with cancer undergoing radiotherapy. Systematic reviews (SRs) are regarded as level I evidence providing direction for clinical practice and guidelines. This overview aims to provide a critical appraisal of SRs published on interventions for the prevention/management of radiation dermatitis. Methodology: We searched the following electronic databases: MEDLINE, CINAHL, EMBASE, and the Cochrane Library (up to Feb 2012). We also hand-searched reference lists of potentially eligible articles and a number of key journals in the area. Two authors screened all potential articles and included eligible SRs. Two authors critically appraised and extracted key findings from the included reviews using the “A Measurement Tool to Assess Systematic Reviews” (AMSTAR). Results: Of 1837 potential titles, six SRs were included. A number of interventions have been reported to be potentially beneficial for managing radiation dermatitis. Interventions evaluated in these reviews included skin care advice, steroidal/non-steroidal topical agents, systematic therapies, modes of radiation delivery, and dressings. However, all the included SRs reported that there is insufficient evidence supporting any single effective intervention. The methodological quality of the included studies varied, and methodological shortfalls in these reviews may create biases to the overall results or recommendations for clinical practice. Conclusions and implications: An up-to-date high quality SR in preventing/managing radiation dermatitis is needed to guide practice and direction for future research. Clinicians or guideline developers are recommended to critically evaluate the information of SRs in their decision making.

Program-level support for protecting an application from untrustworthy components

Many software applications extend their functionality by dynamically loading executable components into their allocated address space. Such components, exemplified by browser plugins and other software add-ons, not only enable reusability, but also promote programming simplicity, as they reside in the same address space as their host application, supporting easy sharing of complex data structures and pointers. However, such components are also often of unknown provenance and quality and may be riddled with accidental bugs or, in some cases, deliberately malicious code. Statistics show that such component failures account for a high percentage of software crashes and vulnerabilities. Enabling isolation of such fine-grained components is therefore necessary to increase the stability, security and resilience of computer programs. This thesis addresses this issue by showing how host applications can create isolation domains for individual components, while preserving the benefits of a single address space, via a new architecture for software isolation called LibVM. Towards this end, we define a specification which outlines the functional requirements for LibVM, identify the conditions under which these functional requirements can be met, define an abstract Application Programming Interface (API) that encompasses the general problem of isolating shared libraries, thus separating policy from mechanism, and prove its practicality with two concrete implementations based on hardware virtualization and system call interpositioning, respectively. The results demonstrate that hardware isolation minimises the difficulties encountered with software based approaches, while also reducing the size of the trusted computing base, thus increasing confidence in the solution’s correctness. This thesis concludes that, not only is it feasible to create such isolation domains for individual components, but that it should also be a fundamental operating system supported abstraction, which would lead to more stable and secure applications.

The role for police in addressing alcohol-related harm inside and outside licensed premises

Alcohol consumption is enmeshed with Australian culture (Palk, 2008) and the use and misuse of alcohol contributes to considerable health and social harms (Barbor et al., 2010; English et al., 1995; Gutjahr, Gmel, & Rehm, 2001; Palk, 2008; Steenkamp, Harrison, & Allsop, 2002). Despite shifts in the way that alcohol is consumed and how it is used, it has been reported that one-third of all alcohol consumed is done so within licensed premises (Lang, Stockwell, Rydon, & Gamble, 1992). Consequently, licensed premises are over-represented as settings in which alcohol-related harms occur. These harms, particularly those related to violence, are associated with particular licensed premises operating in the night-time economy (Briscoe & Donnelly, 2001b; Chikritzhs, Stockwell, & Masters, 1997; Homel, Tomsen, & Thommeny, 1991; Stockwell, 1997). Police have a role in not only responding to the manifestation of harms, such as crime, injuries, assaults, domestic violence, stealing and sexual offences, but they also have a role in preventing problems, and thereby reducing alcohol and other drug-related harms (Doherty & Roche, 2003). Given the extent of alcohol consumption within licensed premises and the nature and extent of the harms, as well as the lack of opportunity to influence outcomes in other settings (e.g. the home), licensed premises offer police and other stakeholders a significant opportunity to influence positively the reduction of alcoholrelated harm. This research focuses specifically on the police role in policing licensed premises. Primarily, this research aims to investigate the factors which are relevant to why and how police officers respond to alcohol-related incidents inside and outside licensed premises. It examines the attitudes and beliefs of police and assesses their knowledge, capacity and ability to effectively police licensed premises. The research methodology uses three distinct surveys. Each contributes to understanding the motivations and practice of police officers in this important area of harm reduction. Study One involved a survey of police officers within a police district (Brisbane Central District) in Queensland, Australia and used a comprehensive questionnaire involving both quantitative and qualitative techniques. A key research outcome of Study One was the finding that officers had low levels of knowledge of the strategies that are effective in addressing alcohol-related harm both inside and outside licensed premises. Paradoxically, these officers also reported extensive recent experience in dealing with alcohol issues in these locations. In addition, these officers reported that alcohol was a significant contextual factor in the majority of matters to which they responded. Officers surveyed reported that alcohol increased the difficulty of responding to situations and that licensed premises (e.g. nightclubs, licensed clubs and hotels) were the most difficult contexts to police. Those surveyed were asked to self-assess their knowledge of the Liquor Act (Qld), which is the primary legislative authority in Queensland for regulating licensed premises. Surprisingly, well over half of the officers (65%) reported ‘no’ to ‘fair’ knowledge of the Act, despite officers believing that their skill level to police such premises was in the ‘good to very good range’. In an important finding, officers reported greater skill level to police outside licensed premises than inside such premises, indicating that officers felt less capable, from a skill perspective, to operate within the confines of a licensed premise than in the environment immediately outside such premises. Another key finding was that officers reported greater levels of training in responding to situations outside and around licensed premises than to situations inside licensed premises. Officers were also asked to identify the frequency with which they employed specified regulatory enforcement and community-based strategies. Irrespective of the type of response, ‘taking no action’ or passive policing interventions were not favoured by officers. The findings identified that officers favoured taking a range of strategies (sending home, releasing into the custody of friends, etc.) in preference to arrest. In another key finding, officers generally reported their support for operational stakeholder partnership approaches to policing licensed premises. This was evidenced by the high number of officers (over 90%) reporting that there should be shared responsibility for enforcing the provisions of the Liquor Act. Importantly, those surveyed also identified the factors which constrain or prevent them from policing licensed premises. Study Two involved interviewing a small but comprehensive group (n=11) of senior managers from within the Queensland Police Service (QPS) who have responsibility for setting operational and strategic policy. The aim of this study was to examine the attitudes, perceptions and influence that senior officers (at the strategy and policy-setting level) had on the officers at the operational level. This qualitative study was carried out using a purposive sampling (Denzin & Lincoln, 2005; Guba & Lincoln, 1989), focused interview and thematic analytic approach. The interview participants were drawn from three tiers of management at district, regional as well as the whole-of-organisational level. The first key theme emerging from the study related to role, in terms of both the QPS broader organisational role, and the individual officer role with respect to the policing of licensed premises. For the QPS organisational role, participants at all three strategic levels had a high degree of congruity as to the organisations service role; that is, to enhance public safety. With respect to participants’ beliefs as to whether police officers have knowledge and understanding of their individual roles concerning licensed premises (as opposed to the QPS role), participants reported most commonly that officers had a reasonable to clear understanding of their role. Participant comments also were supportive of the view that officers operating in the research area, Brisbane Central District (BCD), had a clearer understanding of their role than police operating in other locations. The second key theme to emerge identified a disparity between the knowledge and capability of specialist police, compared with general duties police, to police licensed premises. In fact, a number of the responses to a variety of questions differentiated specialist and general police in a range of domains. One such example related to the clarity of understanding of officer role. Participants agreed that specialist police (Liquor Enforcement & Proactive Strategies [LEAPS] officers) had more clarity of understanding in terms of their role than generalist police. Participants also were strongly of the opinion that specialist police had higher skill levels to deal with issues both inside and outside licensed premises. Some participants expressed the view that general duty police undertook purely response-related activities, or alternatively, dealt with lower order matters. Conversely, it was viewed that specialist police undertook more complex tasks because of their higher levels of knowledge and skill. The third key theme to emerge concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Participant responses strongly indicated that there was a diversity of resourcing barriers that restrict police from undertaking their roles in licensed premises. Examples of such barriers were the lack of police and the low ratio of police to patrons, available officer time, and lack of organisational investment in skills and knowledge acquisition. However, some participants indicated that police resourcing in the BCD was appropriate and officers were equipped with sufficient powers (policy and legislation). Again, the issue of specialist police was raised by one participant who argued that increasing the numbers of specialist police would ameliorate the difficulties for police officers policing licensed premises. The fourth and last key theme to emerge from Study Two related to the perception of senior officers regarding the opportunity and capability of officers to leverage off external partnerships to reduce harms inside and outside licensed premises. Police working in partnership in BCD was seen as an effective harm reduction strategy and strongly supported by the participants. All participants demonstrated a high degree of knowledge as to who these partners were and could identify those government, non-government and community groups precisely. Furthermore, the majority of participants also held strong views that the partnerships were reasonably effective and worked to varying degrees depending on the nature of the partnership and issues such as resourcing. These senior officers identified better communication and coordination as factors that could potentially strengthen these partnerships. This research finding is particularly important for senior officers who have the capacity to shape the policy and strategic direction of the police service, not only in Queensland but throughout Australasia. Study Three examined the perceptions of those with links to the broader liquor industry (government, non-government and community but exclusive of police) concerning their understanding of the police role and the capacity of police to reduce alcohol-related harm inside and outside licensed premises, and their attitudes towards police. Participants (n=26) surveyed represented a range of areas including the liquor industry, business represenatives and government representatives from Queensland Fire and Rescue Service, Queensland Ambulance Service, Brisbane City Council and Queensland Health. The first key theme to emerge from Study Three related to participant understanding of the QPS organisational role, and importantly, individual officer role in policing licensed premises. In terms of participant understanding of the QPS role there was a clear understanding by the majority of participants that the police role was to act in ways consistent with the law and to otherwise engage in a range of enforcement-related activities. Participants saw such activities falling into two categories. The first category related to reactive policing, which included actions around responding to trouble in licensed premises, monitoring crowd controllers and removing trouble-makers. In the second category, proactive approaches, participants identified the following activities as consistent with that approach: early intervention with offenders, support of licensed premises operators and high visibility policing. When participants were asked about their understanding of individual officer roles in the policing of licensed premises, a range of responses were received but the consistent message that emerged was that there is a different role to be played by general duty (uniformed) police compared to specialist (LEAPS Unit) police, which reflects differences in knowledge, skill and capability. The second key theme that emerged from the data related to the external participants’ views of the knowledge and capability of specialist police, compared with general duty police, to police licensed premises. As noted in the first key theme, participants were universally of the view that the knowledge, skill and capability of police in specialist units (LEAPS Unit) was at a higher level than that of general duty police. Participants observed that these specialist officers were better trained than their colleagues in generalist areas and were therefore better able to intervene knowledgeably and authoritatively to deal with problems and issues as they emerged. Participants also reported that officers working within BCD generally had a positive attitude to their duties and had important local knowledge that they could use in the resolution of alcohol-related issues. Participants also commented on the importance of sound and effective QPS leadership, as well as the quality of the leadership in BCD. On both these measures, there was general consensus from participants, who reported positively on the importance and effectiveness of such leadership in BCD. The third key theme to emerge from Study Three concerned the identification of barriers that serve to restrict or prevent police officers from policing licensed premises. Overwhelmingly, external participants reported the lack of human resources (i.e. police officers) as the key barrier. Other resourcing limitations, such as available officer time, police computer systems, and the time taken to charge offenders, were identified as barriers. Some participants identified barriers in the liquor industry such as ‘dodgy operators’ and negative media attention as limitations. Other constraints to emerge related to government and policy barriers. These were reflected in comments about the collection by government of fees from licensees and better ‘powers’ for police to deal with offenders. The fourth and final key theme that emerged from Study Three related to the opportunities for and capability of police to leverage off external partnerships to reduce harms inside and outside licensed premises. Not surprisingly, participants had a comprehensive knowledge of a broad range of stakeholders, from a diversity of contexts, influential in addressing issues in licensed premises. Many participants reported their relationships with the police and other stakeholders as effective, productive and consistent with the objectives of partnering to reduce alcohol-related harm. On the other hand, there were those who were concerned with their relationship with other stakeholders, particularly those with a compliance function (e.g. Office of Liquor & Gaming Regulation [OLGR]). The resourcing limitations of partners and stakeholders were also raised as an important constraining factor in fulfilling the optimum relationship. Again, political issues were mentioned in terms of the impact on partnerships, with participants stating that there is at times political interference and that politicians complicate the relationships of stakeholders. There are some significant strengths with respect to the methodology of this research. The research is distinguished from previous work in that it examines these critical issues from three distinct perspectives (i.e. police officer, senior manager and external stakeholder). Other strengths relate to the strong theoretical framework that guides and informs the research. There are also some identified limitations, including the subjective nature of self-report data as well as the potential for bias by the author, which was controlled for using a range of initiatives. A further limitation concerns the potential for transferability and generalisability of the findings to other locations given the distinctive nature of the BCD. These limitations and issues of transferability are dealt with at length in the thesis. Despite a growing body of literature about contextual harms associated with alcohol, and specific research concerning police intervention in such contextual harms, there is still much to learn. While research on the subject of police engaging in alcohol-related incidents has focused on police behaviours and strategies in response to such issues, there is a paucity of research that focuses on the knowledge and understanding of officers engaged in such behaviours and practices. Given the scarcity of research dealing with the knowledge, skills and attitudes of police officers responding to harms inside and outside licensed premises, this research contributes significantly to what is a recent and growing body of research and literature in the field. The research makes a practical contribution to police agencies’ understanding of officer knowledge and police practice in ways that have the potential to shape education and training agendas, policy approaches around generalist versus specialist policing, strategic and operational strategy, as well as partnership engagements. The research also makes a theoretical contribution given that the research design is informed by the Three Circle

Youth Alcohol and Drug Practice Guide 3 : Practice Strategies and Interventions

This guide canvasses a range of practice strategies and interventions utilised by workers and services who engage with young people experiencing problematic AOD use whilst also exploring the many and varied challenges associated with this type of work.

Validation and consistency in the application of a trauma team activation system at a level 1 trauma centre

- The RAH was activated over 2500 trauma calls in 2009. This figure is over twice the number of calls put out by similar services. - Many trauma calls (in particular L2 trauma calls) from the existing system do not warrant activation of the trauma team - Sometimes trauma calls are activated for nontrauma reasons (eg rapid access to radiology, departmental pressures etc) - The excess of trauma calls has several deleterious effects particularly on time management for the trauma service staff: ward rounds/tertiary survey rounds, education, quality improvement, research

Determination of vertical hydraulic conductivity of aquitards in a multilayered leaky system using water-level signals in adjacent aquifers

This paper presents a methodology for determining the vertical hydraulic conductivity (Kv) of an aquitard, in a multilayered leaky system, based on the harmonic analysis of arbitrary water-level fluctuations in aquifers. As a result, Kv of the aquitard is expressed as a function of the phase-shift of water-level signals measured in the two adjacent aquifers. Based on this expression, we propose a robust method to calculate Kv by employing linear regression analysis of logarithm transformed frequencies and phases. The frequencies, where the Kv are calculated, are identified by coherence analysis. The proposed methods are validated by a synthetic case study and are then applied to the Westbourne and Birkhead aquitards, which form part of a five-layered leaky system in the Eromanga Basin, Australia.

Factors associated with common mental disorders during the transition to adulthood : do emerging adults and ‘early starters’ differ? Findings from an Australian birth cohort study

Background: Despite increasing diversity in pathways to adulthood, choices available to young people are influenced by environmental, familial and individual factors, namely access to socioeconomic resources, family support and mental and physical health status. Young people from families with higher socioeconomic position (SEP) are more likely to pursue tertiary education and delay entry to adulthood, whereas those from low socioeconomic backgrounds are less likely to attain higher education or training, and more likely to partner and become parents early. The first group are commonly termed ‘emerging adults’ and the latter group ‘early starters’. Mental health disorders during this transition can seriously disrupt psychological, social and academic development as well as employment prospects. Depression, anxiety and most substance use disorders have early onset during adolescence and early adulthood with approximately three quarters of lifetime psychiatric disorders having emerged by 24 years of age. Aims: This thesis aimed to explore the relationships between mental health, sociodemographic factors and family functioning during the transition to adulthood. Four areas were investigated: 1) The key differences between emerging adults and ‘early starters’, were examined and focused on a series of social, economic, and demographic factors as well as DSM-IV diagnoses; 2) Methodological issues associated with the measurement of depression and anxiety in young adults were explored by comparing a quantitative measure of symptoms of anxiety and depression (Achenbach’s YSR and YASR internalising scales) with DSM-IV diagnosed depression and anxiety. 3) The association between family SEP and DSM-IV depression and anxiety was examined in relation to the different pathways to adulthood. 4) Finally, the association between pregnancy loss, abortion and miscarriage, and DSM-IV diagnoses of common psychiatric disorders was assessed in young women who reported early parenting, experiencing a pregnancy loss, or who had never been pregnant. Methods: Data were taken from the Mater University Study of Pregnancy (MUSP), a large birth cohort started in 1981 in Brisbane, Australia. 7223 mothers and their children were assessed five times, at 6 months, 5, 14 and 21 years after birth. Over 3700 young adults, aged 18 to 23 years, were interviewed at the 21-year phase. Respondents completed an extensive series of self-reported questionnaires and a computerised structured psychiatric interview. Three outcomes were assessed at the 21-year phase. Mental health disorders diagnosed by a computerised structured psychiatric interview (CIDI-Auto), the prevalence of DSM-IV depression, anxiety and substance use disorders within the previous 12-month, during the transition (between ages of 18 and 23 years) or lifetime were examined. The primary outcome “current stage in the transition to adulthood” was developed using a measure conceptually constructed from the literature. The measure was based on important demographic markers, and these defined four independent groups: emerging adults (single with no children and living with parents), and three categories of ‘early starter’, singles (with no children or partner, living independently), those with a partner (married or cohabitating but without children) and parents. Early pregnancy loss was assessed using a measure that also defined four independent groups and was based on pregnancy outcomes in the young women This categorised the young women into those who were never pregnant, women who gave birth to a live child, and women who reported some form of pregnancy loss, either an abortion or a spontaneous miscarriage. A series of analyses were undertaken to test the study aims. Potential confounding and mediating factors were prospectively measured between the child’s birth and the 21-year phase. Binomial and multinomial logistic regression was used to estimate the risk of relevant outcomes, and the associations were reported as odds ratios (OR) and 95% confidence intervals (95%CI). Key findings: The thesis makes a number of important contributions to our understanding of the transition to adulthood, particularly in relation to the mental health consequences associated with different pathways. Firstly, findings from the thesis clearly showed that young people who parented or partnered early fared worse across most of the economic and social factors as well as the common mental disorders when compared to emerging adults. That is, young people who became early parents were also more likely to experience recent anxiety (OR=2.0, 95%CI 1.5-2.8) and depression (OR=1.7, 95%CI 1.1-2.7) than were emerging adults after taking into account a range of confounding factors. Singles and those partnering early also had higher rates of lifetime anxiety and depression than emerging adults. Young people who partnered early, but were without children, had decreased odds of recent depression; this may be due to the protective effect of early marriage against depression. It was also found that young people who form families early had an increased risk of cigarette smoking (parents OR=3.7, 95%CI 2.9-4.8) compared to emerging adults, but not heavy alcohol (parents OR=0.4, 95%CI 0.3-0.6) or recent illicit drug use. The high rates of cigarette smoking and tobacco use disorders in ‘early starters’ were explained by common risk factors related to early adversity and lower SEP. Having a child and early marriage may well function as a ‘turning point’ for some young people, it is not clear whether this is due to a conscious decision to disengage from a previous ‘substance using’ lifestyle or simply that they no longer have the time to devote to such activities because of child caring. In relation to the methodological issues associated with assessing common mental disorders in young adults, it was found that although the Achenbach empirical internalising scales successfully predicted both later DSM-IV depression (YSR OR=2.3, 95%CI 1.7-3.1) and concurrently diagnosed depression (YASR OR=6.9, 95%CI 5.0- 9.5) and anxiety (YASR OR=5.1, 95%CI 3.8- 6.7), the scales discriminated poorly between young people with or without DSM-IV diagnosed mood disorder. Sensitivity values (the proportion of true positives) for the internalising scales were surprisingly low. Only a third of young people with current DSM-IV depression (range for each of the scales was between 34% to 42%) were correctly identified as cases by the YASR internalising scales, and only a quarter with current anxiety disorder (range of 23% to 31%) were correctly identified. Also, use of the DSM-oriented scales increased sensitivity only marginally (for depression between 2-8%, and anxiety between 2-6%) above the standard Achenbach scales. This is despite the fact that the DSM-oriented scales were originally developed to overcome the poor prediction of DSM-IV diagnoses by the Achenbach scales. The internalising scales, both standard and DSM-oriented, were much more effective at identifying young people with comorbid depression and anxiety, with OR’s 10.1 to 21.7 depending on the internalising scale used. SEP is an important predictor of both an early transition to adulthood and the experience of anxiety during that time Family income during adolescence was a strong predictor of early parenting and partnering before age 24 but not early independent living. Compared to families in the upper quintile, young people from families with low income were nearly twice as likely to live with a partner and four times more likely to become parents (OR ranged from 2.6 to 4.0). This association remained after adjusting for current employment and education level. Children raised in low income families were 30% more likely to have an anxiety disorder (OR=1.3, 95%CI 0.9-1.9), but not depression, as young adults when compared to children from wealthier families. Emerging adults and ‘early starters’ from low income families did not differ in their likelihood of having a later anxiety disorder. Young women reporting a pregnancy loss had nearly three times the odds of experiencing a lifetime illicit drug disorder (excluding cannabis) [abortion OR=3.6, 95%CI 2.0-6.7 and miscarriage OR=2.6, 95%CI 1.2-5.4]. Abortion was associated with alcohol use disorder (OR=2.1, 95%CI 1.3- 3.5) and 12-month depression (OR=1.9, 95%CI 1.1- 3.1). These finding suggest that the association identified by Fergusson et al between abortion and later psychiatric disorders in young women may be due to pregnancy loss and not to abortion, per se. Conclusion: Findings from this thesis support the view that young people who parent or partner early have a greater burden of depression and anxiety when compared to emerging adults. As well, young women experiencing pregnancy loss, from either abortion or miscarriage, are more likely to experience depression and anxiety than are those who give birth to a live infant or who have never been pregnant. Depression, anxiety and substance use disorders often go unrecognised and untreated in young people; this is especially true in young people from lower SEP. Early identification of these common mental health disorders is important, as depression and anxiety experienced during the transition to adulthood have been found to seriously disrupt an individual’s social, educational and economic prospects in later life.

A micro-level indexing model for the assessment of sustainable urban ecosystems

During the last several decades, the quality of natural resources and their services have been exposed to significant degradation from increased urban populations combined with the sprawl of settlements, development of transportation networks and industrial activities (Dorsey, 2003; Pauleit et al., 2005). As a result of this environmental degradation, a sustainable framework for urban development is required to provide the resilience of natural resources and ecosystems. Sustainable urban development refers to the management of cities with adequate infrastructure to support the needs of its population for the present and future generations as well as maintain the sustainability of its ecosystems (UNEP/IETC, 2002; Yigitcanlar, 2010). One of the important strategic approaches for planning sustainable cities is „ecological planning‟. Ecological planning is a multi-dimensional concept that aims to preserve biodiversity richness and ecosystem productivity through the sustainable management of natural resources (Barnes et al., 2005). As stated by Baldwin (1985, p.4), ecological planning is the initiation and operation of activities to direct and control the acquisition, transformation, disruption and disposal of resources in a manner capable of sustaining human activities with a minimum disruption of ecosystem processes. Therefore, ecological planning is a powerful method for creating sustainable urban ecosystems. In order to explore the city as an ecosystem and investigate the interaction between the urban ecosystem and human activities, a holistic urban ecosystem sustainability assessment approach is required. Urban ecosystem sustainability assessment serves as a tool that helps policy and decision-makers in improving their actions towards sustainable urban development. There are several methods used in urban ecosystem sustainability assessment among which sustainability indicators and composite indices are the most commonly used tools for assessing the progress towards sustainable land use and urban management. Currently, a variety of composite indices are available to measure the sustainability at the local, national and international levels. However, the main conclusion drawn from the literature review is that they are too broad to be applied to assess local and micro level sustainability and no benchmark value for most of the indicators exists due to limited data availability and non-comparable data across countries. Mayer (2008, p. 280) advocates that by stating "as different as the indices may seem, many of them incorporate the same underlying data because of the small number of available sustainability datasets". Mori and Christodoulou (2011) also argue that this relative evaluation and comparison brings along biased assessments, as data only exists for some entities, which also means excluding many nations from evaluation and comparison. Thus, there is a need for developing an accurate and comprehensive micro-level urban ecosystem sustainability assessment method. In order to develop such a model, it is practical to adopt an approach that uses a method to utilise indicators for collecting data, designate certain threshold values or ranges, perform a comparative sustainability assessment via indices at the micro-level, and aggregate these assessment findings to the local level. Hereby, through this approach and model, it is possible to produce sufficient and reliable data to enable comparison at the local level, and provide useful results to inform the local planning, conservation and development decision-making process to secure sustainable ecosystems and urban futures. To advance research in this area, this study investigated the environmental impacts of an existing urban context by using a composite index with an aim to identify the interaction between urban ecosystems and human activities in the context of environmental sustainability. In this respect, this study developed a new comprehensive urban ecosystem sustainability assessment tool entitled the „Micro-level Urban-ecosystem Sustainability IndeX‟ (MUSIX). The MUSIX model is an indicator-based indexing model that investigates the factors affecting urban sustainability in a local context. The model outputs provide local and micro-level sustainability reporting guidance to help policy-making concerning environmental issues. A multi-method research approach, which is based on both quantitative analysis and qualitative analysis, was employed in the construction of the MUSIX model. First, a qualitative research was conducted through an interpretive and critical literature review in developing a theoretical framework and indicator selection. Afterwards, a quantitative research was conducted through statistical and spatial analyses in data collection, processing and model application. The MUSIX model was tested in four pilot study sites selected from the Gold Coast City, Queensland, Australia. The model results detected the sustainability performance of current urban settings referring to six main issues of urban development: (1) hydrology, (2) ecology, (3) pollution, (4) location, (5) design, and; (6) efficiency. For each category, a set of core indicators was assigned which are intended to: (1) benchmark the current situation, strengths and weaknesses, (2) evaluate the efficiency of implemented plans, and; (3) measure the progress towards sustainable development. While the indicator set of the model provided specific information about the environmental impacts in the area at the parcel scale, the composite index score provided general information about the sustainability of the area at the neighbourhood scale. Finally, in light of the model findings, integrated ecological planning strategies were developed to guide the preparation and assessment of development and local area plans in conjunction with the Gold Coast Planning Scheme, which establishes regulatory provisions to achieve ecological sustainability through the formulation of place codes, development codes, constraint codes and other assessment criteria that provide guidance for best practice development solutions. These relevant strategies can be summarised as follows: • Establishing hydrological conservation through sustainable stormwater management in order to preserve the Earth’s water cycle and aquatic ecosystems; • Providing ecological conservation through sustainable ecosystem management in order to protect biological diversity and maintain the integrity of natural ecosystems; • Improving environmental quality through developing pollution prevention regulations and policies in order to promote high quality water resources, clean air and enhanced ecosystem health; • Creating sustainable mobility and accessibility through designing better local services and walkable neighbourhoods in order to promote safe environments and healthy communities; • Sustainable design of urban environment through climate responsive design in order to increase the efficient use of solar energy to provide thermal comfort, and; • Use of renewable resources through creating efficient communities in order to provide long-term management of natural resources for the sustainability of future generations.

The Large Allen Cognitive Level Screen as an indicator for medication adherence among adults accessing community mental health services

Background: Medication remains the cornerstone treatment for mental illness. Cognition is one of the strongest predictors of non-adherence. The aim of this preliminary investigation was to examine the association between the Large Allen Cognitive Level Screen (LACLS) and medication adherence among a small sample of mental health service users to determine whether the LACLS has potential as a screening tool for capacity to manage medication regimens. Method: Demographic and clinical information was collected from a small sample of people who had recently accessed community mental health services. Participants then completed the LACLS and the Medication Adherence Rating Scale (MARS) at a single time point. The strength of association between the LACLS and MARS was examined using Spearman rank-order correlation. Results: A strong positive correlation between the LACLS and medication adherence (r = 0.71, p = 0.01) was evident. No participants reported the use of medication aids despite evidence of impaired cognitive functioning. Conclusion: This investigation has provided the first empirical evidence indicating that the LACLS may have utility as a screening instrument for capacity to manage medication adherence among this population. While promising, this finding should be interpreted with caveats given its preliminary nature.

Multi-level information fusion for environment aware robotic navigation

This thesis develops the hardware and software framework for an integrated navigation system. Dynamic data fusion algorithms are used to develop a system with a high level of resistance to the typical problems that affect standard navigation systems.

Metabolomics coupled with proteomics advancing drug discovery toward more agile development of targeted combination therapies

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.