Immunogenicity and protective efficacy of an anti-Streptococcus pyogenes vaccine candidate in multiple animal species

Streptococcus pyogenes, also known as Group A Streptococcus (GAS) has been associated with a range of diseases from the mild pharyngitis and pyoderma to more severe invasive infections such as streptococcal toxic shock. GAS also causes a number of non-suppurative post-infectious diseases such as rheumatic fever, rheumatic heart disease and glomerulonephritis. The large extent of GAS disease burden necessitates the need for a prophylactic vaccine that could target the diverse GAS emm types circulating globally. Anti-GAS vaccine strategies have focused primarily on the GAS M-protein, an extracellular virulence factor anchored to GAS cell wall. As opposed to the hypervariable N-terminal region, the C-terminal portion of the protein is highly conserved among different GAS emm types and is the focus of a leading GAS vaccine candidate, J8-DT/alum. The vaccine candidate J8-DT/alum was shown to be immunogenic in mice, rabbits and the non-human primates, hamadryas baboons. Similar responses to J8-DT/alum were observed after subcutaneous and intramuscular immunization with J8-DT/alum, in mice and in rabbits. Further assessment of parameters that may influence the immunogenicity of J8-DT demonstrated that the immune responses were identical in male and female mice and the use of alum as an adjuvant in the vaccine formulation significantly increased its immunogenicity, resulting in a long-lived serum IgG response. Contrary to the previous findings, the data in this thesis indicates that a primary immunization with J8-DT/alum (50ƒÊg) followed by a single boost is sufficient to generate a robust immune response in mice. As expected, the IgG response to J8- DT/alum was a Th2 type response consisting predominantly of the isotype IgG1 accompanied by lower levels of IgG2a. Intramuscular vaccination of rabbits with J8-DT/alum demonstrated that an increase in the dose of J8-DT/alum up to 500ƒÊg does not have an impact on the serum IgG titers achieved. Similar to the immune response in mice, immunization with J8-DT/alum in baboons also established that a 60ƒÊg dose compared to either 30ƒÊg or 120ƒÊg was sufficient to generate a robust immune response. Interestingly, mucosal infection of naive baboons with a M1 GAS strain did not induce a J8-specific serum IgG response. As J8-DT/alum mediated protection has been previously reported to be due to the J8- specific antibody formed, the efficacy of J8-DT antibodies was determined in vitro and in vivo. In vitro opsonization and in vivo passive transfer confirmed the protective potential of J8-DT antibodies. A reduction in the bacterial burden after challenge with a bioluminescent M49 GAS strain in mice that were passively administered J8-DT IgG established that protection due to J8-DT was mediated by antibodies. The GAS burden in infected mice was monitored using bioluminescent imaging in addition to traditional CFU assays. Bioluminescent GAS strains including the ‘rheumatogenic’ M1 GAS could not be generated due to limitations with transformation of GAS, however, a M49 GAS strain was utilized during BLI. The M49 serotype is traditionally a ‘nephritogenic’ serotype associated with post-streptococcal glomerulonephritis. Anti- J8-DT antibodies now have been shown to be protective against multiple GAS strains such as M49 and M1. This study evaluated the immunogenicity of J8-DT/alum in different species of experimental animals in preparation for phase I human clinical trials and provided the ground work for the development of a rapid non-invasive assay for evaluation of vaccine candidates.

Workplace design in the knowledge economy : a case of the NetWorkPlace™©

This thesis explores a way to inform the architectural design process for contemporary workplace environments. It reports on both theoretical and practical outcomes through an exclusively Australian case study of a network enterprise comprised of collaborative, yet independent business entities. The internet revolution, substantial economic and cultural shifts, and an increased emphasis on lifestyle considerations have prompted a radical re-ordering of organisational relationships and the associated structures, processes, and places of doing business. The social milieu of the information age and the knowledge economy is characterised by an almost instantaneous flow of information and capital. This has culminated in a phenomenon termed by Manuel Castells as the network society, where physical locations are joined together by continuous communication and virtual connectivity. A new spatial logic encompassing redefined concepts of space and distance, and requiring a comprehensive shift in the approach to designing workplace environments for today’s adaptive, collaborative organisations in a dynamic business world, provides the backdrop for this research. Within the duality of space and an augmentation of the traditional notions of place, organisational and institutional structures pose new challenges for the design professions. The literature revealed that there has always been a mono-organisational focus in relation to workplace design strategies. The phenomenon of inter-organisational collaboration has enabled the identification of a gap in the knowledge relative to workplace design. This new context generated the formulation of a unique research construct, the NetWorkPlace™©, which captures the complexity of contemporary employment structures embracing both physical and virtual work environments and practices, and provided the basis for investigating the factors that are shaping and defining interactions within and across networked organisational settings. The methodological orientation and the methods employed follow a qualitative approach and an abductively driven strategy comprising two distinct components, a cross-sectional study of the whole of the network and a longitudinal study, focusing on a single discrete workplace site. The complexity of the context encountered dictated that a multi-dimensional investigative framework was required to be devised. The adoption of a pluralist ontology and the reconfiguration of approaches from traditional paradigms into a collaborative, trans-disciplinary, multi-method epistemology provided an explicit and replicatable method of investigation. The identification and introduction of the NetWorkPlace™© phenomenon, by necessity, spans a number of traditional disciplinary boundaries. Results confirm that in this context, architectural research, and by extension architectural practice, must engage with what other disciplines have to offer. The research concludes that no single disciplinary approach to either research or practice in this area of design can suffice. Pierre Bourdieau’s philosophy of ‘practice’ provides a framework within which the governance and technology structures, together with the mechanisms enabling the production of social order in this context, can be understood. This is achieved by applying the concepts of position and positioning to the corporate power dynamics, and integrating the conflict found to exist between enterprise standard and ferally conceived technology systems. By extending existing theory and conceptions of ‘place’ and the ‘person-environment relationship’, relevant understandings of the tensions created between Castells’ notions of the space of place and the space of flows are established. The trans-disciplinary approach adopted, and underpinned by a robust academic and practical framework, illustrates the potential for expanding the range and richness of understanding applicable to design in this context. The outcome informs workplace design by extending theoretical horizons, and by the development of a comprehensive investigative process comprising a suite of models and techniques for both architectural and interior design research and practice, collectively entitled the NetWorkPlace™© Application Framework. This work contributes to the body of knowledge within the design disciplines in substantive, theoretical, and methodological terms, whilst potentially also influencing future organisational network theories, management practices, and information and communication technology applications. The NetWorkPlace™© as reported in this thesis, constitutes a multi-dimensional concept having the capacity to deal with the fluidity and ambiguity characteristic of the network context, as both a topic of research and the way of going about it.

The role of the health surveillance program in the Queensland coal mining industry

The Queensland Coal Industry Employees Health Scheme was implemented in 1993 to provide health surveillance for all Queensland coal industry workers. Tt1e government, mining employers and mining unions agreed that the scheme should operate for seven years. At the expiry of the scheme, an assessment of the contribution of health surveillance to meet coal industry needs would be an essential part of determining a future health surveillance program. This research project has analysed the data made available between 1993 and 1998. All current coal industry employees have had at least one health assessment. The project examined how the centralised nature of the Health Scheme benefits industry by identi~)jng key health issues and exploring their dimensions on a scale not possible by corporate based health surveillance programs. There is a body of evidence that indicates that health awareness - on the scale of the individual, the work group and the industry is not a part of the mining industry culture. There is also growing evidence that there is a need for this culture to change and that some change is in progress. One element of this changing culture is a growth in the interest by the individual and the community in information on health status and benchmarks that are reasonably attainable. This interest opens the way for health education which contains personal, community and occupational elements. An important element of such education is the data on mine site health status. This project examined the role of health surveillance in the coal mining industry as a tool for generating the necessary information to promote an interest in health awareness. The Health Scheme Database provides the material for the bulk of the analysis of this project. After a preliminary scan of the data set, more detailed analysis was undertaken on key health and related safety issues that include respiratory disorders, hearing loss and high blood pressure. The data set facilitates control for confounding factors such as age and smoking status. Mines can be benchmarked to identify those mines with effective health management and those with particular challenges. While the study has confirmed the very low prevalence of restrictive airway disease such as pneu"moconiosis, it has demonstrated a need to examine in detail the emergence of obstructive airway disease such as bronchitis and emphysema which may be a consequence of the increasing use of high dust longwall technology. The power of the Health Database's electronic data management is demonstrated by linking the health data to other data sets such as injury data that is collected by the Department of l\1mes and Energy. The analysis examines serious strain -sprain injuries and has identified a marked difference between the underground and open cut sectors of the industry. The analysis also considers productivity and OHS data to examine the extent to which there is correlation between any pairs ofJpese and previously analysed health parameters. This project has demonstrated that the current structure of the Coal Industry Employees Health Scheme has largely delivered to mines and effective health screening process. At the same time, the centralised nature of data collection and analysis has provided to the mines, the unions and the government substantial statistical cross-sectional data upon which strategies to more effectively manage health and relates safety issues can be based.

Examination of relationships between urban form, household activities, and time allocation in the Atlanta Metropolitan Region

A substantial body of research is focused on understanding the relationships between socio-demographics, land-use characteristics, and mode specific attributes on travel mode choice and time-use patterns. Residential and commercial densities, inter-mixing of land uses, and route directness in conjunction with transportation performance characteristics interact to influence accessibility to destinations as well as time spent traveling and engaging in activities. This study uniquely examines the activity durations undertaken for out-of-home subsistence; maintenance, and discretionary activities. Also examined are total tour durations (summing all activity categories within a tour). Cross-sectional activities are obtained from household activity travel survey data from the Atlanta Metropolitan Region. Time durations allocated to weekdays and weekends are compared. The censoring and endogeneity between activity categories and within individuals are captured using multiple equations Tobit models. The analysis and modeling reveal that land-use characteristics such as net residential density and the number of commercial parcels within a kilometer of a residence are associated with differences in weekday and weekend time-use allocations. Household type and structure are significant predictors across the three activity categories, but not for overall travel times. Tour characteristics such as time-of-day and primary travel mode of the tours also affect traveler's out-of-home activity-tour time-use patterns.

The role of nature-based experiences in the development and maintenance of wellness

Wellness is now seen as central to redefining the National Health agenda. There is growing evidence that contact with nature and physical activity in nature has considerable positive effects on human health. At the most basic level humanity is reliant on the natural world for resources such as air and water. However, a growing body of research is finding that beyond this fundamental relationship exposure to the non-human natural world can also positively enhance perceptions of physiological, emotional, psychological and spiritual health in ways that cannot be satisfied by alternate means. Theoretical explanations for this have posited that non-human nature might 1) restore mental fatigue, 2) trigger deep reflections, 3) provide an opportunity for nurturing and 4) rekindle innate connections. In this paper the authors show how human wellness is strongly connected to their relationship with the natural world. This paper points to how non-human nature could be better utilised for enhancing human health and wellness.

The regulation of insurance intermediaries in the Australian financial services market

The insurance industry discharges a critical role in the Australian economy and is a significant part of the Australian financial services market. The industry relies upon intermediaries, the principal types being brokers and agents, to promote, arrange and distribute their products and services in the market. The pivotal role that they play in this context and sensitivities associated with the consumer oriented products, such as house and contents insurance, has ensured close regulatory attention. Of particular importance was the passage of the Insurance (Agents and Brokers) Act 1984 (Cth), a comprehensive attempt to address the responsibilities of intermediaries as well as particular problem areas associated with the handling of money. However, with the introduction of financial services and market reform early in the new millennium this insurance intermediary specific regulatory approach was abandoned in favour of a market-wide strategy; that is, market reform was based upon across-the-board licensing, disclosure, conduct and fairness standards, and all financial products and services are now regulated at a generic level under Ch 7 of the Corporations Act 2001 (Cth). This article briefly explores the categories of insurance intermediaries and the relevant distinctions between them but focuses mainly upon the regulatory context in which they operate. This context transcends a strictly legal framework as the regulatory body, the Australian Securities and Investments Commission (ASIC), has sought to inform and guide the market through Policy Statements and Regulatory Guides. The usefulness of these guides as an adjunct to the legislation in explaining the scope and operation of regulatory framework is examined. In addition, the article looks at the self-regulatory and dispute resolution practices in this area and their impact. In conclusion an assessment of this across-the-board regulatory regime is advanced.

Mum, why are the potholes 8 feet apart? Repetitive wheel loads from heavy vehicles in the spatial domain

This paper presents the results of testing to determine pavement forces from three heavy vehicles (HVs). The HVs were instrumented to measure their wheel forces. A “novel roughness” value of the roads during testing is also derived. The various dynamic pavement forces are presented according to the range of novel roughness of pavement surfacings encountered during testing. The paper then examines the relationship between the two derived wavelengths predominant within the HV suspensions; those of axle hop and body-bounce. How these may be considered as contributing to spatial repetition of pavement forces from HVs is discussed. The paper concludes that pavement models need to be revised since dynamic forces from HVs in particular are not generally considered in current pavement design.

Innovation networks in the construction arena : the strategic management of mixed enterprises

The building and construction sector is one of the five largest contributors to the Australian economy and is a key performance component in the economy of many other jurisdictions. However, the ongoing viability of this sector is increasingly reliant on its ability to foster and transfer innovated products and practices. Interorganisational networks, which bring together key industry stakeholders and facilitate the flows of information, resources and trust necessary to secure innovation, have emerged as a key growth strategy within this and other arenas. The blending of organisations, resources and purposes creates new, hybrid institutional forms that draw on a mix of contract, structure and interpersonal relationship as integration processes. This paper argues that hybrid networked arrangements, because they incorporate relational elements, require management strategies and techniques that not always synonymous with conventional management approaches, including those used within the building and construction sector. It traces the emergence of the Construction Innovation Project in Australia as a hybrid institutional arrangement moulding public, private and academic stakeholders of the building and construction industry into a coherent collective force aimed at fostering innovation and its application within all levels of the industry. Specifically, the paper examines the Construction Innovation Project to ascertain the impact of relational governance and its management to harness and leverage the skills, resources and capacities of members to secure innovative outcomes. Finally, the paper offers some prospects to guide the ongoing work of this body and any other charged with a similar integrative responsibility.

Comparison of koala LPCoLN and human strains of Chlamydia pneumoniae highlights extended genetic diversity in the species

Background Chlamydia pneumoniae is a widespread pathogen causing upper and lower respiratory tract infections in addition to a range of other diseases in humans and animals. Previous whole genome analyses have focused on four essentially clonal (> 99% identity) C. pneumoniae human genomes (AR39, CWL029, J138 and TW183), providing relatively little insight into strain diversity and evolution of this species. Results We performed individual gene-by-gene comparisons of the recently sequenced C. pneumoniae koala genome and four C. pneumoniae human genomes to identify species-specific genes, and more importantly, to gain an insight into the genetic diversity and evolution of the species. We selected genes dispersed throughout the chromosome, representing genes that were specific to C. pneumoniae, genes with a demonstrated role in chlamydial biology and/or pathogenicity (n = 49), genes encoding nucleotide salvage or amino acid biosynthesis proteins (n = 6), and extrachromosomal elements (9 plasmid and 2 bacteriophage genes). Conclusions We have identified strain-specific differences and targets for detection of C. pneumoniae isolates from both human and animal origin. Such characterisation is necessary for an improved understanding of disease transmission and intervention.

Independent cinema in the Chinese film industry

Chinese independent cinema has developed for more than twenty years. Two sorts of independent cinema exist in China. One is underground cinema, which is produced without official approvals and cannot be circulated in China, and the other are the films which are legally produced by small private film companies and circulated in the domestic film market. This sort of ‘within-system’ independent cinema has played a significant role in the development of Chinese cinema in terms of culture, economics and ideology. In contrast to the amount of comment on underground filmmaking in China, the significance of ‘within-system’ independent cinema has been underestimated by most scholars. This thesis is a study of how political management has determined the development of Chinese independent cinema and how Chinese independent cinema has developed during its various historical trajectories. This study takes media economics as the research approach, and its major methods utilise archive analysis and interviews. The thesis begins with a general review of the definition and business of American independent cinema. Then, after a literature review of Chinese independent cinema, it identifies significant gaps in previous studies and reviews issues of traditional definition and suggests a new definition. After several case studies on the changes in the most famous Chinese directors’ careers, the thesis shows that state studios and private film companies are two essential domestic backers for filmmaking in China. After that, the body of the thesis provides an examination of the development of ‘within-system’ independent cinema. Specifically, three factors: government intervention, the majors’ performance (state studios and, later, the conglomerates) and the market conduct of independent cinema at various points in their trajectories are studied. The key findings of the study are as follows: First, most scholars have overlooked the existence and the significance of within-system Chinese independent cinema. Drawing on an American definition of the independent sector, this thesis proposes a definition of the sector in China: namely, any film that has not been financed, produced, and/or distributed by majors. The thesis also notes important contradictions in applying this definition: i.e. film-making is still dependent on policies that frame industry development. The thesis recognises that major tensions apply to filmmaking in China, which significantly differentiates the Chinese independents from those in the US. Second, the development of Chinese independent cinema is the result the rise of the private sector and the decline of the state studio system. As state studios encountered difficulties the private sector moved forward; consequently the environment improved for independent cinema. Third, before 2003, the film industry in China had little commercialisation. The government controlled independent cinema by means of license and censorship. State studios produced main melody films and Hollywood attracted most of the audiences. Many independent filmmakers focused on commercial films, thus contributing to film commercialisation. Fourth, after 2003, the film industry became increasingly fragmented. The government created distribution and exhibition opportunities for main melody films; conglomerates collaborated with Hong Kong players; Hong Kong co-productions and Hollywood occupied the film market; and small private film companies produced main melody films in order to earn meagre profits. The original contribution of the thesis is to advance the study of Chinese independent cinema. The study suggests a reasonable and practical definition of Chinese independent cinema. It shows how the Chinese government authorities have implemented economic measures to gain ideological control in the film industry. Finally, this the first study on Chinese independent cinema applying a synthesis of economic, political and historical perspectives.