The genetic basis of human height : the role of estrogen

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

"Theatre of the dancing language" : new possibilities in contemporary Australian playwrighting

This study focuses on trends in contemporary Australian playwrighting, discussing recent investigations into the playwrighting process. The study analyses the current state of this country’s playwrighting industry, with a particular focus on programming trends since 1998. It seeks to explore the implications of this current theatrical climate, in particular the types of work most commonly being favoured for production. It argues that Australian plays are under-represented (compared to non-Australian plays) on ‘mainstream’ stages and that audiences might benefit from more challenging modes of writing than the popular three-act realist play models. The thesis argues that ‘New Lyricism’ might fill this position of offering an innovative Australian playwrighting mode. New Lyricism is characterised by a set of common aesthetics, including a non-linear narrative structure, a poetic use of language and magic realism. Several Australian playwrights who have adopted this mode of writing are identified and their works examined. The author’s play Floodlands is presented as a case study and the author’s creative process is examined in light of the published critical discussions about experimental playwriting work.

Innovation implementation effectiveness : a multiorganizational test of Klein Conn and Sorra’s model.

In an empirical test and extension of Klein Conn and Sorra’s model of innovation implementation effectiveness, we apply structural equation modelling to identify the generalizability of their data-modified model in comparison with their theorised model. We examined the implementation of various types of innovations in a sample of 135 organizations. We found that the data supported the original model rather than the data-modified model, such that implementation climate mediated polices and practices and implementation effectiveness, while implementation effectiveness partially mediated the relationship between implementation climate and innovation effectiveness. Furthermore, we extend their model to suggest that non-financial resources availability plays a critical role in implementation policies and practices.

Biochemical characterization of Aprataxin, the protein deficient in Ataxia with Oculomotor Apraxia type 1

Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

Mainstreaming sustainability into pre-service teacher edcuation in Australia

There is a growing interest in and support for education for sustainability in Australian schools. Australian Government schemes such as the Australian Sustainable Schools Initiative (AuSSI), along with strategies such as Educating for a Sustainable Future: A National Environmental Education Statement for Australian Schools(NEES(Australian Government and Curriculum Corporation (2005) and Living Sustainably: The Australian Government’s National Action Plan for Education for Sustainability (Australian Government 2009), recognise the need and offer support for education for sustainability in Australian schools. The number of schools that have engaged with AuSSI indicates that this interest also exists within Australian schools. Despite this, recent research indicates that pre-service teacher education institutions and programs are not doing all they can to prepare teachers for teaching education for sustainability or for working within sustainable schools. The education of school teachers plays a vital role in achieving changes in teaching and learning in schools. Indeed, the professional development of teachers in education for sustainability has been identified as ‘the priority of priorities’. Much has been written about the need to ‘reorient teacher education towards sustainability’. Teacher education is seen as a key strategy that is yet to be effectively utilised to embed education for sustainability in schools. Mainstreaming sustainability in Australian schools will not be achieved without the preparation of teachers for this task. The Mainstreaming Sustainability model piloted in this study seeks to engage a range of stakeholder organisations and key agents of change within a system to all work simultaneously to bring about a change, such as the mainstreaming of sustainability. The model is premised on the understanding that sustainability will be mainstreamed within teacher education if there is engagement with key agents of change across the wider teacher education system and if the key agents of change are ‘deeply’ involved in making the change. The model thus seeks to marry broad engagement across a system with the active participation of stakeholders within that system. Such a systemic approach is a way of bringing together diverse viewpoints to make sense of an issue and harness that shared interpretation to define boundaries, roles and relationships leading to a better defined problem that can be acted upon more effectively. Like action research, the systemic approach is also concerned with modelling change and seeking plausible solutions through collaboration between stakeholders. This is important in ensuring that outcomes are useful to the researchers/stakeholders and the system being researched as it creates partnerships and commitments to the outcomes by stakeholder participants. The study reported on here examines whether the ‘Mainstreaming Sustainability’ model might be effective as a means to mainstream sustainability in pre-service teacher education. This model, developed in an earlier study, was piloted in the Queensland teacher education system in order to examine its effectiveness in creating organisational and systemic change. The pilot project in Queensland achieved a number of outcomes. The project: • provided useful insights into the effectiveness of the Mainstreaming Sustainability model in bringing about change while also building research capacity within the system • developed capacities within the teacher education community: o developing competencies in education for sustainability o establishing more effective interactions between decision-makers and other stakeholders o establishing a community of inquiry • changed teaching and learning approaches used in participating teacher education institutions through: o curriculum and resource development o the adoption of education for sustainability teaching and learning processes o the development of institutional policies • improved networks within the teacher education system through: o identifying key agents of change within the system o developing new, and building on existing, partnerships between schools, teacher education institutions and government agencies • engaged relevant stakeholders such as government agencies and non-government organisations to understand and support the change Our findings indicate that the Mainstreaming Sustainability model is able to facilitate organisational and systemic change – over time – if: • the individuals involved have the conceptual and personal capacities needed to facilitate change, that is, to be a key agent of change • stakeholders are engaged as participants in the process of change, not simply as ‘interested parties’ • there is a good understanding of systemic change and the opportunities for leveraging change within systems. In particular, in seeking to mainstream sustainability in pre-service teacher education in Queensland it has become clear that one needs to build capacity for change within participants such as knowledge of education for sustainability, conceptual skills in systemic thinking, action research and organisational change, and leadership skills. It is also of vital importance that key agents of change – those individuals who are ‘hubs’ within a system and can leverage for change across a wide range of the system – are identified and engaged with as early as possible. Key agents of change can only be correctly identified, however, if the project leaders and known participants have clearly identified the boundary to their system as this enables the system, sub-system and environment of the system to be understood. Through mapping the system a range of key organisations and stakeholders will be identified, including government and nongovernment organisations, teacher education students, teacher education academics, and so on. On this basis, key agents of change within the system and sub-system can be identified and invited to assist in working for change. A final insight is that it is important to have time – and if necessary the funding to ‘buy time’ – in seeking to bring about system-wide change. Seeking to bring about system-wide change is an ambitious project, one that requires a great deal of effort and time. These insights provide some considerations for those seeking to utilise the Mainstreaming Sustainability model to bring about change within and across a pre-service teacher education system.

Assessment by interview and portfolio in a Graduate School Program

Assessment plays an integral role in teaching and learning in Higher Education and teachers have a strong interest in debates and commentaries on assessment as and for learning. In a one-year graduate entry teacher preparation program, the temptation is to emphasize assessment in an attempt to ensure students “cover” everything as part of a robust preparation for the profession. The risk is that, for students, assessment drives curriculum, and time spent in the completion of assignments is no guarantee of either effective learning or authentic preparation for teaching. Interviews as assessment provide an opportunity for a learning experience as well as an authentic task, since students will shortly be interviewing for employment in a “real world” situation. This paper reports on a project experimenting with interview panels as authentic assessment with pre-service early childhood teachers. At the end of their first semester of study, students enrolled in the Graduate Diploma of Education program at the Queensland University of Technology in Australia were required to participate in a panel interview where they were graded by a panel made up of three faculty staff and one undergraduate student enrolled in the four-year Bachelor of Education program. Students and panel members completed a questionnaire on their experience after the interview. Results indicated that both students and staff valued the experience and felt it was authentic. Results are discussed in terms of how the assessment interview and portfolio presentation supports graduating students in their preparation for employment interviews, and how this authentic assessment task has benefits for both students and teaching staff.

Biotribological assessment for artificial synovial joints : the role of boundary lubrication

Biotribology, the study of lubrication, wear and friction within the body, has become a topic of high importance in recent times as we continue to encounter debilitating diseases and trauma that destroy function of the joints. A highly successful surgical procedure to replace the joint with an artificial equivalent alleviates dysfunction and pain. However, the wear of the bearing surfaces in prosthetic joints is a significant clinical problem and more patients are surviving longer than the life expectancy of the joint replacement. Revision surgery is associated with increased morbidity and mortality and has a far less successful outcome than primary joint replacement. As such, it is essential to ensure that everything possible is done to limit the rate of revision surgery. Past experience indicates that the survival rate of the implant will be influenced by many parameters, of primary importance, the material properties of the implant, the composition of the synovial fluid and the method of lubrication. In prosthetic joints, effective boundary lubrication is known to take place. The interaction of the boundary lubricant and the bearing material is of utmost importance. The identity of the vital active ingredient within synovial fluid (SF) to which we owe the near frictionless performance of our articulating joints has been the quest of researchers for many years. Once identified, tribo tests can determine what materials and more importantly what surfaces this fraction of SF can function most optimally with. Surface-Active Phospholipids (SAPL) have been implicated as the body’s natural load bearing lubricant. Studies in this thesis are the first to fully characterise the adsorbed SAPL detected on the surface of retrieved prostheses and the first to verify the presence of SAPL on knee prostheses. Rinsings from the bearing surfaces of both hip and knee prostheses removed from revision operations were analysed using High Performance Liquid Chromatography (HPLC) to determine the presence and profile of SAPL. Several common prosthetic materials along with a novel biomaterial were investigated to determine their tribological interaction with various SAPLs. A pin-on-flat tribometer was used to make comparative friction measurements between the various tribo-pairs. A novel material, Pyrolytic Carbon (PyC) was screened as a potential candidate as a load bearing prosthetic material. Friction measurements were also performed on explanted prostheses. SAPL was detected on all retrieved implant bearing surfaces. As a result of the study eight different species of phosphatidylcholines were identified. The relative concentrations of each species were also determined indicating that the unsaturated species are dominant. Initial tribo tests employed a saturated phosphatidylcholine (SPC) and the subsequent tests adopted the addition of the newly identified major constituents of SAPL, unsaturated phosphatidylcholine (USPC), as the test lubricant. All tribo tests showed a dramatic reduction in friction when synthetic SAPL was used as the lubricant under boundary lubrication conditions. Some tribopairs showed more of an affinity to SAPL than others. PyC performed superior to the other prosthetic materials. Friction measurements with explanted prostheses verified the presence and performance of SAPL. SAPL, in particular phosphatidylcholine, plays an essential role in the lubrication of prosthetic joints. Of particular interest was the ability of SAPLs to reduce friction and ultimately wear of the bearing materials. The identification and knowledge of the lubricating constituents of SF is invaluable for not only the future development of artificial joints but also in developing effective cures for several disease processes where lubrication may play a role. The tribological interaction of the various tribo-pairs and SAPL is extremely favourable in the context of reducing friction at the bearing interface. PyC is highly recommended as a future candidate material for use in load bearing prosthetic joints considering its impressive tribological performance.

Synthesis of orchestrators from service choreographies

With service interaction modelling, it is customary to distinguish between two types of models: choreographies and orchestrations. A choreography describes interactions within a collection of services from a global perspective, where no service plays a privileged role. Instead, services interact in a peer-to-peer manner. In contrast, an orchestration describes the interactions between one particular service, the orchestrator, and a number of partner services. The main proposition of this work is an approach to bridge these two modelling viewpoints by synthesising orchestrators from choreographies. To start with, choreographies are defined using a simple behaviour description language based on communicating finite state machines. From such a model, orchestrators are initially synthesised in the form of state machines. It turns out that state machines are not suitable for orchestration modelling, because orchestrators generally need to engage in concurrent interactions. To address this issue, a technique is proposed to transform state machines into process models in the Business Process Modelling Notation (BPMN). Orchestrations represented in BPMN can then be augmented with additional business logic to achieve value-adding mediation. In addition, techniques exist for refining BPMN models into executable process definitions. The transformation from state machines to BPMN relies on Petri nets as an intermediary representation and leverages techniques from theory of regions to identify concurrency in the initial Petri net. Once concurrency has been identified, the resulting Petri net is transformed into a BPMN model. The original contributions of this work are: an algorithm to synthesise orchestrators from choreographies and a rules-based transformation from Petri nets into BPMN.

A re-examination of the Ghrelin and Ghrelin receptor genes

The last few years have seen dramatic advances in genomics, including the discovery of a large number of non-coding and antisense transcripts. This has revolutionised our understanding of multifaceted transcript structures found within gene loci and their roles in the regulation of development, neurogenesis and other complex processes. The recent and continuing surge of knowledge has prompted researchers to reassess and further dissect gene loci. The ghrelin gene (GHRL) gives rise to preproghrelin, which in turn produces ghrelin, a 28 amino acid peptide hormone that acts via the ghrelin receptor (growth hormone secretagogue receptor/GHSR 1a). Ghrelin has many important physiological and pathophysiological roles, including the stimulation of growth hormone (GH) release, appetite regulation, and cancer development. A truncated receptor splice variant, GHSR 1b, does not bind ghrelin, but dimerises with GHSR 1a, and may act as a dominant negative receptor. The gene products of ghrelin and its receptor are frequently overexpressed in human cancer While it is well known that the ghrelin axis (ghrelin and its receptor) plays a range of important functional roles, little is known about the molecular structure and regulation of the ghrelin gene (GHRL) and ghrelin receptor gene (GHSR). This thesis reports the re-annotation of the ghrelin gene, discovery of alternative 5’ exons and transcription start sites, as well as the description of a number of novel splice variants, including isoforms with a putative signal peptide. We also describe the discovery and characterisation of a ghrelin antisense gene (GHRLOS), and the discovery and expression of a ghrelin receptor (growth hormone secretagogue receptor/GHSR) antisense gene (GHSR-OS). We have identified numerous ghrelin-derived transcripts, including variants with extended 5' untranslated regions and putative secreted obestatin and C-ghrelin transcripts. These transcripts initiate from novel first exons, exon -1, exon 0 and a 5' extended 1, with multiple transcription start sites. We used comparative genomics to identify, and RT-PCR to experimentally verify, that the proximal exon 0 and 5' extended exon 1 are transcribed in the mouse ghrelin gene, which suggests the mouse and human proximal first exon architecture is conserved. We have identified numerous novel antisense transcripts in the ghrelin locus. A candidate non-coding endogenous natural antisense gene (GHRLOS) was cloned and demonstrates very low expression levels in the stomach and high levels in the thymus, testis and brain - all major tissues of non-coding RNA expression. Next, we examined if transcription occurs in the antisense orientation to the ghrelin receptor gene, GHSR. A novel gene (GHSR-OS) on the opposite strand of intron 1 of the GHSR gene was identified and characterised using strand-specific RT-PCR and rapid amplification of cDNA ends (RACE). GHSR-OS is differentially expressed and a candidate non-coding RNA gene. In summary, this study has characterised the ghrelin and ghrelin receptor loci and demonstrated natural antisense transcripts to ghrelin and its receptor. Our preliminary work shows that the ghrelin axis generates a broad and complex transcriptional repertoire. This study provides the basis for detailed functional studies of the the ghrelin and GHSR loci and future studies will be needed to further unravel the function, diagnostic and therapeutic potential of the ghrelin axis.

Assessment of Health Impacts of Heatwaves in Brisbane, Australia : How to Best Define A Heatwave?

Background and Objective: As global warming continues, the frequency, intensity and duration of heatwaves are likely to increase. However, a heatwave is unlikely to be defined uniformly because acclimatisation plays a significant role in determining the heat-related impact. This study investigated how to best define a heatwave in Brisbane, Australia. Methods: Computerised datasets on daily weather, air pollution and health outcomes between 1996 and 2005 were obtained from pertinent government agencies. Paired t-tests and case-crossover analyses were performed to assess the relationship between heatwaves and health outcomes using different heatwave definitions. Results: The maximum temperature was as high as 41.5°C with a mean maximum daily temperature of 26.3°C. None of the five commonly-used heatwave definitions suited Brisbane well on the basis of the health effects of heatwaves. Additionally, there were pros and cons when locally-defined definitions were attempted using either a relative or absolute definition for extreme temperatures. Conclusion: The issue of how to best define a heatwave is complex. It is important to identify an appropriate definition of heatwave locally and to understand its health effects.

Exercise and cancer recovery workshop

Cancer represents a major public health concern in Australia, with 100,000 new cancer cases diagnosed each year. Physical activity level (specifically lack of physical activity) is considered a known risk factor, particularly for breast and colorectal cancers. Physical activity also plays a role following a cancer diagnosis; being regularly active during and following treatment for cancer has been associated with improvements in psychosocial and physical outcomes, as well as better compliance with treatment regimens, reduced impact of disease symptoms and treatment-related side effects, and survival benefits for particular cancers. This workshop will provide an overview of the work presented in the recently published AAESS position stand on exercise and cancer recovery. A summary of the cancer and exercise literature, in particular the purpose of exercise following diagnosis of cancer, the potential benefits derived by cancer patients and survivors from participating in exercise programs, and exercise prescription guidelines and contraindications or considerations for exercise prescription with this special population, will be given. A case summary will also be presented and discussed.

Augmenting competitiveness of cities through tourism planning : the role of collaborative decision support systems

Many cities around the globe are now considering tourism facilities and their remarkable revenues in order to become competitive in the global economy. In many of these cities a great emphasis is given to the cultural tourism as it plays an important role in the establishment of creative and knowledge-base of cities. The literature points out the importance of local community support in cultural tourism. In such context, the use of new approach and technologies in tourism planning in order to increase the community participation and competitiveness of cities’ cultural assets gains a great significance. This paper advocates a new planning approach for tourism planning, particularly for cultural tourism, to increase the competitiveness of cities. As part of this new approach, the paper introduces the joined up planning approach integrated with a collaborative decision support system: ‘the community-oriented decision support system’. This collaborative planning support system is an effective and efficient tool for cultural tourism planning, which provides a platform for local communities’ participation in the development decision process.

Bifocal lens control of myopia progression in children

This research investigated underlying issues that were critical to the success of the bifocal trial and comprised of three studies. The first study evaluated if Chinese-Canadian children were suitable subjects for the bifocal trial. The high prevalence of myopia in Chinese children suggests that genetic input plays a role in myopia development, but the rapid increase in prevalence over the last few decades indicates environmental factors are also important. Since this bifocal trial was conducted in Canada, this work aimed to determine whether Chinese children who had migrated to Canada would still have high myopia prevalence and a high rate of myopia progression. The second study determined the optimal bifocal lens power for myopia treatment and the effect of incorporating base-in prism into the bifocal. In the majority of published myopia control studies, the power of the prescribed near addition was usually predetermined in the belief that the near addition would always help to improve the near focus. In fact, the effect of near addition on the accommodative error might be quite different even for individuals in which the same magnitude of accommodation lag had been measured. Therefore, this work was necessary to guide the selection of bifocal and prism powers most suitable for the subsequent bifocal trial. The third study, the ultimate goal of this research, was to conduct a longitudinal clinical trial to determine if bifocals and prismatic bifocals could control myopia progression in children.

Collaborative Filtering Recommender Systems based on Popular Tags

The social tags in web 2.0 are becoming another important information source to profile users' interests and preferences for making personalized recommendations. However, the uncontrolled vocabulary causes a lot of problems to profile users accurately, such as ambiguity, synonyms, misspelling, low information sharing etc. To solve these problems, this paper proposes to use popular tags to represent the actual topics of tags, the content of items, and also the topic interests of users. A novel user profiling approach is proposed in this paper that first identifies popular tags, then represents users’ original tags using the popular tags, finally generates users’ topic interests based on the popular tags. A collaborative filtering based recommender system has been developed that builds the user profile using the proposed approach. The user profile generated using the proposed approach can represent user interests more accurately and the information sharing among users in the profile is also increased. Consequently the neighborhood of a user, which plays a crucial role in collaborative filtering based recommenders, can be much more accurately determined. The experimental results based on real world data obtained from Amazon.com show that the proposed approach outperforms other approaches.

A psychosocial approach to understanding young Australians' mobile phone behaviour

This thesis by publication contributes to our knowledge of psychological factors underlying a modern day phenomenon, young people’s mobile phone behaviour. Specifically, the thesis reports a PhD program of research which adopted a social psychological approach to explore mobile phone behaviour among young Australians aged between 15 and 24 years. A particular focus of the research program was to explore both the cognitive and behavioural aspects of young people’s mobile phone behaviour which for the purposes of this thesis is defined as mobile phone involvement. The research program comprised three separate stages which were developmental in nature, in that, the findings of each stage of the research program informed the next. The overarching goal of the program of research was to improve our understanding of the psychosocial factors influencing young people’s mobile phone behaviour. To achieve this overall goal, there were a number of aims to the research program which reflect the developmental nature of this thesis. Given the limited research into the mobile phone behaviour in Australia, the first two aims of the research program were to explore patterns of mobile phone behaviour among Australian youth and explore the social psychological factors relating to their mobile phone behaviour. Following this exploration, the research program sought to develop a measure which captures the cognitive and behavioural aspects of mobile phone behaviour. Finally, the research program aimed to examine and differentiate the psychosocial predictors of young people’s frequency of mobile phone use and their level of involvement with their mobile phone. Both qualitative and quantitative methodologies were used throughout the program of research. Five papers prepared during the three stages of the research program form the bulk of this thesis. The first stage of the research program was a qualitative investigation of young people’s mobile phone behaviour. Thirty-two young Australians participated in a series of focus groups in which they discussed their mobile phone behaviour. Thematic data analysis explored patterns of mobile phone behaviour among young people, developed an understanding of psychological factors influencing their use of mobile phones, and identified that symptoms of addiction were emerging in young people’s mobile phone behaviour. Two papers (Papers 1 and 2) emanated from this first stage of the research program. Paper 1 explored patterns of mobile phone behaviour and revealed that mobile phones were perceived as being highly beneficial to young people’s lives, with the ability to remain in constant contact with others being particularly valued. The paper also identified that symptoms of behavioural addiction including withdrawal, cognitive and behavioural salience, and loss of control, emerged in participants’ descriptions of their mobile phone behaviour. Paper 2 explored how young people’s need to belong and their social identity (two constructs previously unexplored in the context of mobile phone behaviour) related to their mobile phone behaviour. It was revealed that young people use their mobile phones to facilitate social attachments. Additionally, friends and peers influenced young people’s mobile phone behaviour; for example, their choice of mobile phone carrier and their most frequent type of mobile phone use. These papers laid the foundation for the further investigation of addictive patterns of behaviour and the role of social psychological factors on young people’s mobile behaviour throughout the research program. Stage 2 of the research program focussed on developing a new parsimonious measure of mobile phone behaviour, the Mobile Phone Involvement Questionnaire (MPIQ), which captured the cognitive and behavioural aspects of mobile phone use. Additionally, the stage included a preliminary exploration of factors influencing young people’s mobile phone behaviour. Participants (N = 946) completed a questionnaire which included a pool of items assessing symptoms of behavioural addiction, the uses and gratifications relating to mobile phone use, and self-identity and validation from others in the context of mobile phone behaviour. Two papers (Papers 3 & 4) emanated from the second stage of the research program. Paper 3 provided an important link between the qualitative and quantitative components of the research program. Qualitative data from Stage 1 indicated the reasons young people use their mobile phones and identified addictive characteristics present in young people’s mobile phone behaviour. Results of the quantitative study conducted in Stage 2 of the research program revealed the uses and gratifications relating to young people’s mobile phone behaviour and the effect of these gratifications on young people’s frequency of mobile phone use and three indicators of addiction, withdrawal, salience, and loss of control. Three major uses and gratifications: self (such as feeling good or as a fashion item), social (such as contacting friends), and security (such as use in an emergency) were found to underlie much of young people’s mobile phone behaviour. Self and social gratifications predicted young people’s frequency of mobile phone use and the three indicators of addiction but security gratifications did not. These results provided an important foundation for the inclusion of more specific psychosocial predictors in the later stages of the research program. Paper 4 reported the development of the mobile phone involvement questionnaire and a preliminary exploration of the effect of self-identity and validation from others on young people’s mobile phone behaviour. The MPIQ assessed a unitary construct and was a reliable measure amongst this cohort. Results found that self-identity influenced the frequency of young people’s use whereas self-identity and validation from others influenced their level of mobile phone involvement. These findings provided an important indication that, in addition to self factors, other people have a strong influence on young people’s involvement with their mobile phone and that mobile phone involvement is conceptually different to frequency of mobile phone use. Stage 3 of the research program empirically examined the psychosocial predictors of young people’s mobile behaviour and one paper, Paper 5, emanated from this stage. Young people (N = 292) from throughout Australia completed an online survey assessing the role of self-identity, ingroup norm, the need to belong, and self-esteem on their frequency of mobile phone use and their mobile phone involvement. Self-identity was the only psychosocial predictor of young people’s frequency of mobile phone use. In contrast, self-identity, ingroup norm, and need to belong all influenced young people’s level of involvement with their mobile phone. Additionally, the effect of self-esteem on young people’s mobile phone involvement was mediated by their need to belong. These results indicate that young people who perceive their mobile phone to be an integral part of their self-identity, who perceive that mobile phone is common amongst friends and peers, and who have a strong need for attachment to others, in some cases driven by a desire to enhance their self-esteem, are most likely to become highly involved with their mobile phones. Overall, this PhD program of research has provided an important contribution to our understanding of young Australians’ mobile phone behaviour. Results of the program have broadened our knowledge of factors influencing mobile phone behaviour beyond the approaches used in previous research. The use of various social psychological theories combined with a behavioural addiction framework provided a novel examination of young people’s mobile behaviour. In particular, the development of a new measure of mobile phone behaviour in the research program facilitated the differentiation of the psychosocial factors influencing frequency of young people’s mobile phone behaviour and their level of involvement with their mobile phone. Results of the research program indicate the important role that mobile phone behaviour plays in young people’s social development and also signals the characteristics of those people who may become highly involved with their mobile phone. Future research could build on this thesis by exploring whether mobile phones are affecting traditional social psychological processes and whether the results in this research program are generalisable to other cohorts and other communication technologies.