Stochastic modelling of T cell homeostasis for two competing clonotypes via the master equation

Stochastic models for competing clonotypes of T cells by multivariate, continuous-time, discrete state, Markov processes have been proposed in the literature by Stirk, Molina-París and van den Berg (2008). A stochastic modelling framework is important because of rare events associated with small populations of some critical cell types. Usually, computational methods for these problems employ a trajectory-based approach, based on Monte Carlo simulation. This is partly because the complementary, probability density function (PDF) approaches can be expensive but here we describe some efficient PDF approaches by directly solving the governing equations, known as the Master Equation. These computations are made very efficient through an approximation of the state space by the Finite State Projection and through the use of Krylov subspace methods when evolving the matrix exponential. These computational methods allow us to explore the evolution of the PDFs associated with these stochastic models, and bimodal distributions arise in some parameter regimes. Time-dependent propensities naturally arise in immunological processes due to, for example, age-dependent effects. Incorporating time-dependent propensities into the framework of the Master Equation significantly complicates the corresponding computational methods but here we describe an efficient approach via Magnus formulas. Although this contribution focuses on the example of competing clonotypes, the general principles are relevant to multivariate Markov processes and provide fundamental techniques for computational immunology.

Understanding the legal implications of data sharing, access and reuse in the Australian research landscape

Researchers are increasingly involved in data-intensive research projects that cut across geographic and disciplinary borders. Quality research now often involves virtual communities of researchers participating in large-scale web-based collaborations, opening their earlystage research to the research community in order to encourage broader participation and accelerate discoveries. The result of such large-scale collaborations has been the production of ever-increasing amounts of data. In short, we are in the midst of a data deluge. Accompanying these developments has been a growing recognition that if the benefits of enhanced access to research are to be realised, it will be necessary to develop the systems and services that enable data to be managed and secured. It has also become apparent that to achieve seamless access to data it is necessary not only to adopt appropriate technical standards, practices and architecture, but also to develop legal frameworks that facilitate access to and use of research data. This chapter provides an overview of the current research landscape in Australia as it relates to the collection, management and sharing of research data. The chapter then explains the Australian legal regimes relevant to data, including copyright, patent, privacy, confidentiality and contract law. Finally, this chapter proposes the infrastructure elements that are required for the proper management of legal interests, ownership rights and rights to access and use data collected or generated by research projects.

The future of the internet economy : addressing challenges facing the implementation of the Australian national broadband network

Innovation is vital for the future of Australia.s internet economy. Innovations rely on businesses. ability to innovate. Businesses. ability to innovate relies on their employees. The more these individual end users engage in the internet economy, the better businesses. engagement will be. The less these individual end users engage, the less likely a business is to engage and innovate. This means, for the internet economy to function at its fullest potential, it is essential that individual Australians have the capacity to engage with it and participate in it. The Australian federal government is working to facilitate the internet economy through policies, legislation and practices that implement high-speed broadband. The National Broadband Network will be a vital tool for Australia.s internet economy. Its .chief importance¡® is that it will provide faster internet access speeds that will facilitate access to internet services and content. However, an appropriate infrastructure and internet speed is only part of the picture. As the Organisation for Economic Co-operation and Development identified, appropriate government policies are also needed to ensure that vital services are more accessible by consumers. The thesis identifies essential theories and principles underpinning the internet economy and from which the concept of connectedness is developed. Connectedness is defined as the ability of end users to connect with internet content and services, other individuals and organisations, and government. That is, their ability to operate in the internet economy. The NBN will be vital in ensuring connectedness into the future. What is not currently addressed by existing access regimes is how to facilitate end user access capacity and participation. The thesis concludes by making recommendations to the federal government as to what the governing principles of the Australian internet economy should include in order to enable individual end user access capacity.

The role of property law in environmental management

Market-based environmental regulation is becoming increasingly common within international and national frameworks. In order for market-based regimes to attract sufficient levels of stakeholder engagement, participants within such schemes require an incentive to participate and furthermore need to feel a sense of security about investing in such processes. A sense of security is associated with property-based interests. This article explores the property-related issues connected with the operation of environmental markets. Relevant property-related considerations include examining the significant role that market-based regulation is playing in connection with the environment; examining the links between property rights and markets; exploring the legal definition of property; analysing the rights and powers associated with environmental interests in land; advancing theory on the need for landholder responsibilities in relation to land and examining the legal mechanisms used to recognise environmental property rights, including the registration thereof.

Advance directives, autonomy and the refusal of life-sustaining medical treatment

As Australian society 1s agemg, individuals are increasingly concerned about managing their future, including making decisions about the medical treatment they may wish to receive or refuse if they lose decision-making capacity. To date, there has been relatively little research into the extent to which legal regulation allows competent adults to make advance refusals of life-sustaining medical treatment that will bind health professionals and others when a decision needs to be made at a future time. This thesis aims to fill this gap in the research by presenting the results of research into the legal regulation of advance directives that refuse life-sustaining medical treatment. In the five papers that comprise this thesis, the law that governs this area is examined, and the ethical principle of autonomy is used to critically evaluate that law. The principal finding of this research is that the current scheme of regulation is ineffective to adequately promote the right of a competent adult to make binding advance directives about refusal of medical treatment. The research concludes that legislation should be enacted to enable individuals to complete an advance directive, only imposing restrictions to the extent that this is necessary to promote individual autonomy. The thesis first examines the principle of autonomy upon which the common law (and some statutory law) is expressed to be based, to determine whether that principle is an appropriate one to underpin regulation. 1 The finding of the research is that autonomy can be justified as an organising principle on a number of grounds: it is consistent with the values of a liberal democracy; over recent decades, it is a principle that has been even more prominent within the discipline of medical ethics; and it is the principle which underpins the legal regulation of a related topic, namely the contemporaneous refusal of medical treatment. Next, the thesis reviews the common law to determine whether it effectively achieves the goal of promoting autonomy by allowing a competent adult to make an advance directive refusing treatment that will operate if he or she later loses decision-making capacity. 2 This research finds that conunon law doctrine, as espoused by the judiciary, prioritises individual choice by recognising valid advance directives that refuse treatment as binding. However, the research also concludes that the common law, as applied by the judiciary in some cases, may not be effective to promote individual autonomy, as there have been a number of circumstances where advance directives that refuse treatment have not been followed. The thesis then examines the statutory regimes in Australia that regulate advance directives, with a focus on the regulation of advance refusals of life-sustaining medical treatment.3 This review commences with an examination ofparliamentary debates to establish why legislation was thought to be necessary. It then provides a detailed review of all of the statutory regimes, the extent to which the legislation regulates the form of advance directives, and the circumstances in which they can be completed, will operate and can be ignored by medical professionals. The research finds that legislation was enacted mainly to clarify the common law and bring a level of certainty to the field. Legislative regimes were thought to provide medical professionals with the assurance that compliance with an advance directive that refuses life-sustaining medical treatment will not expose them to legal sanction. However, the research also finds that the legislation places so many restrictions on when an advance directive refusing treatment can be made, or will operate, that they have not been successful in promoting individual autonomy.

Assessing performance capability in the work place

As universities worldwide begin to appreciate the value of authentic learning experiences, so they struggle with methods of assessing the outcomes from such experiences. This chapter describes the application of an assessment matrix developed by Queensland University of Technology(QUT) in Australia, to the assessment requirements and practices relating to work integrated learning at the University of Surrey in the UK. Despite the very different institutional contexts and independent way in which the assessment regimes have developed, it was found that the values and outcomes being assessed and the methods used to assess them were similar. The most important feature of assessing work integrated learning experiences is fitness for purpose, hence the learning objectives and assessment of outcomes for a WIL experience must be explicitly aligned to this objective.As universities worldwide begin to appreciate the value of authentic learning experiences, so they struggle with methods of assessing the outcomes from such experiences. This chapter describes the application of an assessment matrix developed by Queensland University of Technology (QUT) in Australia, to the assessment requirements and practices relating to work integrated learning at the University of Surrey in the UK. Despite the very different institutional contexts and independent way in which the assessment regimes have developed, it was found that the values and outcomes being assessed and the methods used to assess them were similar. The most important feature of assessing work integrated learning experiences is fitness for purpose, hence the learning objectives and assessment of outcomes for a WIL experience must be explicitly aligned to this objective.

Risky strategic behaviour : unintended consequences of good intentions in the homelessness service system

The delivery of human services occurs through a complex and often volatile system characterised by both competing and cooperating efforts. A recent strategic intention of government has been to integrate disparate service providers and programs into a more effective and efficient system using competitive funding regimes. A program of amalgamation has also been forecast and promoted as a further mechanism by which to link up smaller agencies thus creating economy and efficiency in the scale and scope of their service modes. Despite the current reliance on competitive funding models and amalgamation as the preferred ways forward for the sector little is known about their integrative capacity including their ability to predict outcomes and their consequences : the ‘unknown unknowns’. Drawing on an extensive data set of human services integration initiatives in Queensland, Australia, this paper examines the impact of government policy and service models and the risks arising from the tensions between competition and accountability on the one hand and the established good will and trust on the other. It is argued that unresolved, these tensions can lead to a weakening of the social infrastructure and make the system more vulnerable to inherent systemic risks. The paper finds that government’s efforts to externalise risk to the non-government sector leads to fragmentation of the service system and fractured collaborative capability. These unintended outcomes themselves have the unintended consequence of leaving governments disconnected from the service system and unable to provide the leadership role and direction necessary for sustained integration. Moreover, facilitating such a leadership role is undermined by behaviours that are directly contrary to collective integration models.

Facilitating Malaysia towards innovative society : arguing the case for open access policy

The Malaysian National Innovation Model blueprint states that there is an urgent need to pursue an innovation-oriented economy to improve the nation’s capacity for knowledge, creativity and innovation. In nurturing a pervasive innovation culture, the Malaysian government has declared the year 2010 as an Innovative Year whereby creativity among its population is highly celebrated. However, while Malaysian citizens are encouraged to be creative and innovative, scientific data and information generated from publicly funded research in Malaysia is locked up because of rigid intellectual property licensing regimes and traditional publishing models. Reflecting on these circumstances, this paper looks at, and argue why, scientific data and information should be made available, accessible and re-useable freely to promote the grassroots level of innovation in Malaysia. Using innovation theory as its platform of argument, this paper calls for an open access policy for publicly funded research output to be adopted and implemented in Malaysia. Simultaneously, a normative analytic approach is used to determine the types of open access policy that ought to be adopted to spur greater innovation among Malaysians.

The conceptual and operational compatibility of data breach notification and information privacy laws

Mandatory data breach notification laws are a novel and potentially important legal instrument regarding organisational protection of personal information. These laws require organisations that have suffered a data breach involving personal information to notify those persons that may be affected, and potentially government authorities, about the breach. The Australian Law Reform Commission (ALRC) has proposed the creation of a mandatory data breach notification scheme, implemented via amendments to the Privacy Act 1988 (Cth). However, the conceptual differences between data breach notification law and information privacy law are such that it is questionable whether a data breach notification scheme can be solely implemented via an information privacy law. Accordingly, this thesis by publications investigated, through six journal articles, the extent to which data breach notification law was conceptually and operationally compatible with information privacy law. The assessment of compatibility began with the identification of key issues related to data breach notification law. The first article, Stakeholder Perspectives Regarding the Mandatory Notification of Australian Data Breaches started this stage of the research which concluded in the second article, The Mandatory Notification of Data Breaches: Issues Arising for Australian and EU Legal Developments (‘Mandatory Notification‘). A key issue that emerged was whether data breach notification was itself an information privacy issue. This notion guided the remaining research and focused attention towards the next stage of research, an examination of the conceptual and operational foundations of both laws. The second article, Mandatory Notification and the third article, Encryption Safe Harbours and Data Breach Notification Laws did so from the perspective of data breach notification law. The fourth article, The Conceptual Basis of Personal Information in Australian Privacy Law and the fifth article, Privacy Invasive Geo-Mashups: Privacy 2.0 and the Limits of First Generation Information Privacy Laws did so for information privacy law. The final article, Contextualizing the Tensions and Weaknesses of Information Privacy and Data Breach Notification Laws synthesised previous research findings within the framework of contextualisation, principally developed by Nissenbaum. The examination of conceptual and operational foundations revealed tensions between both laws and shared weaknesses within both laws. First, the distinction between sectoral and comprehensive information privacy legal regimes was important as it shaped the development of US data breach notification laws and their subsequent implementable scope in other jurisdictions. Second, the sectoral versus comprehensive distinction produced different emphases in relation to data breach notification thus leading to different forms of remedy. The prime example is the distinction between market-based initiatives found in US data breach notification laws compared to rights-based protections found in the EU and Australia. Third, both laws are predicated on the regulation of personal information exchange processes even though both laws regulate this process from different perspectives, namely, a context independent or context dependent approach. Fourth, both laws have limited notions of harm that is further constrained by restrictive accountability frameworks. The findings of the research suggest that data breach notification is more compatible with information privacy law in some respects than others. Apparent compatibilities clearly exist as both laws have an interest in the protection of personal information. However, this thesis revealed that ostensible similarities are founded on some significant differences. Data breach notification law is either a comprehensive facet to a sectoral approach or a sectoral adjunct to a comprehensive regime. However, whilst there are fundamental differences between both laws they are not so great to make them incompatible with each other. The similarities between both laws are sufficient to forge compatibilities but it is likely that the distinctions between them will produce anomalies particularly if both laws are applied from a perspective that negates contextualisation.

The Law and Governance of Water Resources : The Challenge of Sustainability

To achieve the sustainable use and development of water resources is a daunting challenge for both the global and local communities. It requires commitments by all groups within the international, national and local communities from their own particular, possibly conflicting, perspectives. Without a set of coherent legal arrangements designed to ensure effective governance of water resources, their sustainable use and development are unlikely to be achieved. This study looks at how the legal arrangements for managing water resources have evolved across the continents over hundreds of years; their relevance for contemporary society; how the norms of current international and national legal regimes are responding; and, most importantly, how legal rights and duties should be structured so as to achieve sustainability in the future.

The resource boom's underbelly : criminological impacts of mining development

Australia is currently in the midst of a major resources boom. Resultant growing demands for labour in regional and remote areas have accelerated the recruitment of non resident workers, mostly contractors, who work extended block rosters of 12-hour shifts and are accommodated in work camps, often adjacent to established mining towns. Serious social impacts of these practices, including violence and crime, have generally escaped industry, government and academic scrutiny. This paper highlights some of these impacts on affected regional communities and workers and argues that post-industrial mining regimes serve to mask and privatize these harms and risks, shifting them on to workers, families and communities.

The internet and the changing global media environment

This chapter describes current trends in the global media environment, with a focus on their implications for the management of public agendas and political processes. It assesses the extent to which trends such as the growth of the blogosphere, "citizen journalism," and other forms if user-generated content, have complicated and problematized news and agenda management as engaged in by both media and political elites. It argues that, in large part due to the rise of the internet and the proliferation if online producers of information and commentary, alongside 24-hour news channels such as CNN and Al Jazeera, political and social actors today face a much more complex, chaotic communication environment than ever bifore, an environment characterized as one of cultural chaos. Having outlined the roots of this trend in the emergence of an expanded, globalized public sphere, the chapter goes on to ask if elite control over the political agenda has been eroded, and if it has, what the consequences for governmmt and the exercise if power might be. Can authoritarian regimes in China, the Middle East, and elsewhere survive the onset if internet-fueled global journalism, for example? In a political environment where public opinion is driven and buffeted by news coverage if unprecedented speed and volume, can democratic governments retain sufficient control over decision- and policy-making processes to enable competent social administration al'ld political management? Can the citizens of contemporary democracies use the emerging media environment to enhance elite accountability and strengthen the democratic process? The chapter concludes that the changing global media environment has the potmtial to strengthen democratic processes, though there is no sil'lgle template for the impact of the internet and other new media on specific countries.

Violent urbanism is us

This paper explores violent urbanism in the recent science-fiction filem District 9 whhich depicts an alien immigration camp, filmed on location in Soweto in 2008 in the midst of a series of violent clashed between indigenous South Africans and the new wave of African immigrants. Violent Urbanism is the State of method of control of bodies and populations by those precise biological techniques that determine geopolitical sites for the control of cities. This film while presented as cinema verite speaks the real invasion of traditional, spatio-disciplinary regimes such as corporate-run detention centres, refugee camps, border control and enforced relocation by those imperceptible techniques which violate the body by reducing it to a biological datum, tool, or specimen to serve the security agenda of the twenty-first century nation-state. These techniques are chemical and biological warfare proliferation; genetic engineering; and surveillance systems, such as biometrics, whose purview is no longer limited to the specular but includes the molecular. District 9 evinces a compelling urban image of contemporary biopolitics that disturbs the received historiography of post-apartheid urbanism. Clearly Johannesburg is not the only place this could or is happening - the reach of biopolitics is worldwide. District 9 visualises with utter precision the corporate hijacking of the biological realm in contemporary cites, just as it asks the unsettling question, who exactly is the "audience" of Violent Urbanism?

Design and implementation of a virtual world training simulation of ICU first hour handover processes

Nursing training for an Intensive Care Unit (ICU) is a resource intensive process. High demands are made on staff, students and physical resources. Interactive, 3D computer simulations, known as virtual worlds, are increasingly being used to supplement training regimes in the health sciences; especially in areas such as complex hospital ward processes. Such worlds have been found to be very useful in maximising the utilisation of training resources. Our aim is to design and develop a novel virtual world application for teaching and training Intensive Care nurses in the approach and method for shift handover, to provide an independent, but rigorous approach to teaching these important skills. In this paper we present a virtual world simulator for students to practice key steps in handing over the 24/7 care requirements of intensive care patients during the commencing first hour of a shift. We describe the modelling process to provide a convincing interactive simulation of the handover steps involved. The virtual world provides a practice tool for students to test their analytical skills with scenarios previously provided by simple physical simulations, and live on the job training. Additional educational benefits include facilitation of remote learning, high flexibility in study hours and the automatic recording of a reviewable log from the session. To the best of our knowledge, we believe this is a novel and original application of virtual worlds to an ICU handover process. The major outcome of the work was a virtual world environment for training nurses in the shift handover process, designed and developed for use by postgraduate nurses in training.

Development of novel vaccine strategies to prevent genital tract chlamydial infections

Chlamydia trachomatis is the most prevalent bacterial sexually transmitted infection in the developed world and the leading cause of preventable blindness worldwide. As reported by the World Health Organization in 2001, there are approximately 92 million new infections detected annually, costing health systems billions of dollars to treat not only the acute infection, but also to treat infection-associated sequelae. The majority of genital infections are asymptomatic, with 50-70% going undetected. Genital tract infections can be easily treated with antibiotics when detected. Lack of treatment can lead to the development of pelvic inflammatory disease, ectopic pregnancies and tubal factor infertility in women and epididymitis and prostatitis in men. With infection rates on the continual rise and the large number of infections going undetected, there is a need to develop an efficacious vaccine which prevents not only infection, but also the development of infection-associated pathology. Before a vaccine can be developed and administered, the pathogenesis of chlamydial infections needs to be fully understood. This includes the kinetics of ascending infection and the effects of inoculating dose on ascension and development of pathology. The first aim in this study was to examine these factors in a murine model. Female BALB/c mice were infected intravaginally with varying doses of C. muridarum, the mouse variant of human C. trachomatis, and the ascension of infection along the reproductive tract and the time-course of infection-associated pathology development, including inflammatory cell infiltration, pyosalpinx and hydrosalpinx, were determined. It was found that while the inoculating dose did affect the rate and degree of infection, it did not affect any of the pathological parameters examined. This highlighted that the sexual transmission dose may have minimal effect on the development of reproductive sequelae. The results of the first section enabled further studies presented here to use an optimal inoculating dose that would ascend the reproductive tract and cause pathology development, so that vaccine efficacy could be determined. There has been a large amount of research into the development of an efficacious vaccine against genital tract chlamydial infections, with little success. However, there have been no studies examining the effects of the timing of vaccination, including the effects of vaccination during an active genital infection, or after clearance of a previous infection. These are important factors that need to be examined, as it is not yet known whether immunization will enhance not only the individual's immune response, but also pathology development. It is also unknown whether any enhancement of the immune responses will cause the Chlamydia to enter a dormant, persistent state, and possibly further enhance any pathology development. The second section of this study aimed to determine if vaccination during an active genital tract infection, or after clearance of a primary infection, enhanced the murine immune responses and whether any enhanced or reduced pathology occurred. Naïve, actively infected, or previously infected animals were immunized intranasally or transcutaneously with the adjuvants cholera toxin and CpG-ODN in combination with either the major outer membrane protein (MOMP) of C. muridarum, or MOMP and ribonucleotide reductase small chain protein (NrdB) of C. muridarum. It was found that the systemic immune responses in actively or previously infected mice were altered in comparison to animals immunized naïve with the same combinations, however mucosal antibodies were not enhanced. It was also found that there was no difference in pathology development between any of the groups. This suggests that immunization of individuals who may have an asymptomatic infection, or may have been previously exposed to a genital infection, may not benefit from vaccination in terms of enhanced immune responses against re-exposure. The final section of this study aimed to determine if the vaccination regimes mentioned above caused in vivo persistence of C. muridarum in the upper reproductive tracts of mice. As there has been no characterization of C. muridarum persistence in vitro, either ultrastructurally or via transcriptome analysis, this was the first aim of this section. Once it had been shown that C. muridarum could be induced into a persistent state, the gene transcriptional profiles of the selected persistent marker genes were used to determine if persistent infections were indeed present in the upper reproductive tracts of the mice. We found that intranasal immunization during an active infection induced persistent infections in the oviducts, but not the uterine horns, and that intranasal immunization after clearance of infection, caused persistent infections in both the uterine horns and the oviducts of the mice. This is a significant finding, not only because it is the first time that C. muridarum persistence has been characterized in vitro, but also due to the fact that there is minimal characterization of in vivo persistence of any chlamydial species. It is possible that the induction of persistent infections in the reproductive tract might enhance the development of pathology and thereby enhance the risk of infertility, factors that need to be prevented by vaccination, not enhanced. Overall, this study has shown that the inoculating dose does not affect pathology development in the female reproductive tract of infected mice, but does alter the degree and rate of ascending infection. It has also been shown that intranasal immunization during an active genital infection, or after clearance of one, induces persistent infections in the uterine horns and oviducts of mice. This suggests that potential vaccine candidates will need to have these factors closely examined before progressing to clinical trials. This is significant, because if the same situation occurs in humans, a vaccine administered to an asymptomatic, or previously exposed individual may not afford any extra protection and may in fact enhance the risk of development of infection-associated sequelae. This suggests that a vaccine may serve the community better if administered before the commencement of sexual activity.