Bayesian models for longitudinal data

Longitudinal data, where data are repeatedly observed or measured on a temporal basis of time or age provides the foundation of the analysis of processes which evolve over time, and these can be referred to as growth or trajectory models. One of the traditional ways of looking at growth models is to employ either linear or polynomial functional forms to model trajectory shape, and account for variation around an overall mean trend with the inclusion of random eects or individual variation on the functional shape parameters. The identification of distinct subgroups or sub-classes (latent classes) within these trajectory models which are not based on some pre-existing individual classification provides an important methodology with substantive implications. The identification of subgroups or classes has a wide application in the medical arena where responder/non-responder identification based on distinctly diering trajectories delivers further information for clinical processes. This thesis develops Bayesian statistical models and techniques for the identification of subgroups in the analysis of longitudinal data where the number of time intervals is limited. These models are then applied to a single case study which investigates the neuropsychological cognition for early stage breast cancer patients undergoing adjuvant chemotherapy treatment from the Cognition in Breast Cancer Study undertaken by the Wesley Research Institute of Brisbane, Queensland. Alternative formulations to the linear or polynomial approach are taken which use piecewise linear models with a single turning point, change-point or knot at a known time point and latent basis models for the non-linear trajectories found for the verbal memory domain of cognitive function before and after chemotherapy treatment. Hierarchical Bayesian random eects models are used as a starting point for the latent class modelling process and are extended with the incorporation of covariates in the trajectory profiles and as predictors of class membership. The Bayesian latent basis models enable the degree of recovery post-chemotherapy to be estimated for short and long-term followup occasions, and the distinct class trajectories assist in the identification of breast cancer patients who maybe at risk of long-term verbal memory impairment.

Disability, deinstitutionalisation and discourse : an analysis of institutional reform policies in Queensland, 1994-1996

The closure of large institutions for people with intellectual disability and the subsequent shift to community living has been a feature of social policies in most western democracies for more than two decades. While the move from congregated settings to homes in the community has been heralded as a positive and desirable strategy, deinstitutionalisation has continued to be a controversial policy and practice. This research critically analyses the implementation of a deinstitutionalisation policy called Institutional Reform in the state of Queensland from May 1994 until it was dismantled under a new government in the middle of 1996. A trajectory study of the policy from early conceptualisation through its development, implementation and final extinction was undertaken. Several methods were utilised in the research including the textual analyis of policy documents, discussion papers and newspaper articles, interviews with stakeholders and participant observation. The research draws on theories of discourse and focuses on how discourses of disability shape policy and practice. The thesis outlines a number of implications for policy implementation more generally as well as for disability services. In particular, the theoretical framework builds on Fulcher's (1989) disabling discourses - medical, charity, lay and rights - and identifies two additional discourses of economics and inclusion. The thesis argues that competing disability discourses operated in powerful ways to shape the implementation of the policy and illustrates how older discourses based on fear and prejudice were promoted to positions of dominance and power.

Osteopontin expression correlates with melanoma invasion

Melanoma is one of the most aggressive cancers affecting humans. Although early melanomas are curable with surgical excision, metastatic melanomas are associated with high mortality. The mechanism of melanoma development, progression, and metastasis is largely unknown. In order to uncover genes unique to melanoma cells, we used high-density DNA microarrays to examine the gene expression profiles of metastatic melanoma nodules using benign nevi as controls. Over 190 genes were significantly overexpressed in metastatic melanomas compared with normal nevi by at least 2-fold. One of the most abundantly expressed genes in metastatic melanoma nodules is osteopontin (OPN). Immunohistochemistry staining on tissue microarrays and individual skin biopsies representing different stages of melanoma progression revealed that OPN expression is first acquired at the step of melanoma tissue invasion. In addition, blocking of OPN expression by RNA interference reduced melanoma cell numbers in vitro. Our observations suggest that OPN may be acquired early in melanoma development and progression, and may enhance tumor cell growth in invasive melanoma.

Indigenous research and broader issues in the Academy

The Rudd Labour Government rode to power in Australia on the education promise of 'an education revolution'. The term 'education revolution' carries all the obligatory marketing metaphors that an aspirant government might want recognised by the general public on the eve government came to power however in revolutionary terms it fades into insignificance in comparison to the real revolution in Australian education. This revolution simply put is to elevate Indigenous Knowledge Systems, in Australian Universities. In the forty three years since the nation setting Referendum of 1967 a generation has made a beach head on the educational landscape. Now a further generation who having made it into the field of higher degrees yearn for the ways and means to authentically marshal Indigenous knowledge? The Institute of Koorie Education at Deakin has for over twenty years not only witnessed the transition but is also a leader in the field. With the appointment of two Chairs of Indigenous Knowledge Systems to build on to its already established research profile the Institute moved towards what is the 'real revolution' in education – the elevation of Indigenous Knowledge as a legitimate knowledge system. This paper lays out the Institute of Koorie Education‘s Research Plan and the basis of an argument put to the academy that will be the driver for this pursuit.

Crowded Diphosphinomethane Ligands in Catalysis: [(R2PCH2PR′2-κ2P)-NiR″]+ Cations for Ethylene Polymerization without Activators

The preparation of a series of nickel dichloride complexes with bulky diphosphinomethane chelate ligands R2PCH2PR′2 is reported. Reaction with the appropriate Grignard reagent leads to the corresponding dimethyl and dibenzyl complexes. Cationic monomethyl and mono-η3-benzyl complexes are generated from these dialkyl complexes by protonation with [H(OEt2)2]+[B(3,5-(CF3)2C6H3)4]−, while the complex [(dtbpm κ2P)Ni(η3-CH(CH2Ph)Ph]+[B(3,5-(CF3)2C6H3)4]−is obtained from protonation of the Ni(0) olefin complex (dtbpm-κ2P)N(η2-trans-stilbene). Crystal structures of examples of dichlorides, dimethyl, dibenzyl, cationic methyl, and cationic η3-benzyl complexes are reported. Solutions of the cations polymerize ethylene under mild conditions and without the necessity of an activating agent, to form polyethylene having high molecular weights and low degrees of chain branching. In comparison to the Ni methyl cations, the η3-benzyl cation complexes are more stable and somewhat less active but still very efficient in C2H4 polymerization. The effect on the resulting polyethylene of varying the substituents R, R′ on the phosphine ligand has been examined, and a clear trend for longer chain PE with less branching in the presence of more bulky substituents on the diphosphine has been found. Density functional calculations have been used to examine the rapid suprafacial η3 to η3 haptotropic shift processes of the[(R2PCH2PR′2)Ni] fragment and the η3−η1 change of the coordination mode of the benzyl group required for polymerization in those cations.

Chemopreventive effect of PSP through targeting of prostate cancer stem cell-like population

Recent evidence suggested that prostate cancer stem/progenitor cells (CSC) are responsible for cancer initiation as well as disease progression. Unfortunately, conventional therapies are only effective in targeting the more differentiated cancer cells and spare the CSCs. Here, we report that PSP, an active component extracted from the mushroom Turkey tail (also known as Coriolus versicolor), is effective in targeting prostate CSCs. We found that treatment of the prostate cancer cell line PC-3 with PSP led to the down-regulation of CSC markers (CD133 and CD44) in a time and dose-dependent manner. Meanwhile, PSP treatment not only suppressed the ability of PC-3 cells to form prostaspheres under non-adherent culture conditions, but also inhibited their tumorigenicity in vivo, further proving that PSP can suppress prostate CSC properties. To investigate if the anti-CSC effect of PSP may lead to prostate cancer chemoprevention, transgenic mice (TgMAP) that spontaneously develop prostate tumors were orally fed with PSP for 20 weeks. Whereas 100% of the mice that fed with water only developed prostate tumors at the end of experiment, no tumors could be found in any of the mice fed with PSP, suggesting that PSP treatment can completely inhibit prostate tumor formation. Our results not only demonstrated the intriguing anti-CSC effect of PSP, but also revealed, for the first time, the surprising chemopreventive property of oral PSP consumption against prostate cancer.

The obesity-associated polymorphisms FTO rs9939609 and MC4R rs17782313 and endometrial cancer risk in non-Hispanic white women

Overweight and obesity are strongly associated with endometrial cancer. Several independent genome-wide association studies recently identified two common polymorphisms, FTO rs9939609 and MC4R rs17782313, that are linked to increased body weight and obesity. We examined the association of FTO rs9939609 and MC4R rs17782313 with endometrial cancer risk in a pooled analysis of nine case-control studies within the Epidemiology of Endometrial Cancer Consortium (E2C2). This analysis included 3601 non-Hispanic white women with histologically-confirmed endometrial carcinoma and 5275 frequency-matched controls. Unconditional logistic regression models were used to assess the relation of FTO rs9939609 and MC4R rs17782313 genotypes to the risk of endometrial cancer. Among control women, both the FTO rs9939609 A and MC4R rs17782313 C alleles were associated with a 16% increased risk of being overweight (p = 0.001 and p = 0.004, respectively). In case-control analyses, carriers of the FTO rs9939609 AA genotype were at increased risk of endometrial carcinoma compared to women with the TT genotype [odds ratio (OR) = 1.17; 95% confidence interval (CI): 1.03–1.32, p = 0.01]. However, this association was no longer apparent after adjusting for body mass index (BMI), suggesting mediation of the gene-disease effect through body weight. The MC4R rs17782313 polymorphism was not related to endometrial cancer risk (per allele OR = 0.98; 95% CI: 0.91–1.06; p = 0.68). FTO rs9939609 is a susceptibility marker for white non-Hispanic women at higher risk of endometrial cancer. Although FTO rs9939609 alone might have limited clinical or public health significance for identifying women at high risk for endometrial cancer beyond that of excess body weight, further investigation of obesity-related genetic markers might help to identify the pathways that influence endometrial carcinogenesis.

Children's Literature Digital Resource (CLDR)

Children’s Literature Digital Resources incorporates primary texts published from white settlement to 1945, including children’s and young adult fiction, poetry, short stories, and picture books. This collection is supported by selected secondary material. The objective is to provide a centralised access point for information about Australian children's literature and writers and a growing body of full-text primary resources. Four key aims are: * To establish an important digital facility for research, teaching, and information provision around Australian children’s literature; * To provide access to a wide range of high-quality full-text data, both primary and secondary resources; * To provide access to essential library and research information infrastructure and facilities for established and emerging researchers in the fields of Humanities and Education; To enable research while preserving important heritage material. The collection contains texts digitised for AustLit through cooperation with various Australian libraries. The collection includes children’s and young adult fiction, poetry, picture books, short stories, and critical articles relating to relevant primary texts. Authors of primary sources include Irene Cheyne, E. W. Cole, Richard Rowe, Lillian M. Pyke, and Dorothy Wall. Secondary sources include critical works by Clare Bradford, Heather Scutter, Kerry White, Sharyn Pearce, and Marcie Muir. These full-text materials are keyword searchable (both within individual texts and across the CLDR corpus) and can be downloaded for research purposes. As well as digitising primary and secondary material, the project locates and provides pathways to existing online resources or internet publications to enhance AustLit's Children's Literature subset. These resources include both primary and secondary texts.

Australian learning and teaching council projects in the mathematical sciences : a retrospective

Since 2004, the Australian Learning and Teaching Council (ALTC) and its predecessor, the Carrick Institute for Learning and Teaching in Higher Education, have funded numerous teaching and educational research-based projects in the Mathematical Sciences. In light of the Commonwealth Government’s decision to close the ALTC in 2011, it is appropriate to take account of the ALTCs input into the Mathe- matical Sciences in higher education. Here we present an overview of ALTC projects in the Mathematical Sciences, as well as report on the contributions they have made to the Discipline.

Advertising and promotion : an integrated marketing communications perspective

This text explores the area of advertising and promotion practice. It shows how real organisations coordinate the various elements of the promotional mix with other marketing activities."--Provided by publisher

Long-term azithromycin for Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease (Bronchiectasis Intervention Study) : a multicentre, double-blind, randomised controlled trial

Background Indigenous children in high-income countries have a heavy burden of bronchiectasis unrelated to cystic fibrosis. We aimed to establish whether long-term azithromycin reduced pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. Methods Between Nov 12, 2008, and Dec 23, 2010, we enrolled Indigenous Australian, Maori, and Pacific Island children aged 1—8 years with either bronchiectasis or chronic suppurative lung disease into a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial. Eligible children had had at least one pulmonary exacerbation in the previous 12 months. Children were randomised (1:1 ratio, by computer-generated sequence with permuted block design, stratified by study site and exacerbation frequency [1—2 vs ≥3 episodes in the preceding 12 months]) to receive either azithromycin (30 mg/kg) or placebo once a week for up to 24 months. Allocation concealment was achieved by double-sealed, opaque envelopes; participants, caregivers, and study personnel were masked to assignment until after data analysis. The primary outcome was exacerbation (respiratory episodes treated with antibiotics) rate. Analysis of the primary endpoint was by intention to treat. At enrolment and at their final clinic visits, children had deep nasal swabs collected, which we analysed for antibiotic-resistant bacteria. This study is registered with the Australian New Zealand Clinical Trials Registry; ACTRN12610000383066. Findings 45 children were assigned to azithromycin and 44 to placebo. The study was stopped early for feasibility reasons on Dec 31, 2011, thus children received the intervention for 12—24 months. The mean treatment duration was 20·7 months (SD 5·7), with a total of 902 child-months in the azithromycin group and 875 child-months in the placebo group. Compared with the placebo group, children receiving azithromycin had significantly lower exacerbation rates (incidence rate ratio 0·50; 95% CI 0·35—0·71; p<0·0001). However, children in the azithromycin group developed significantly higher carriage of azithromycin-resistant bacteria (19 of 41, 46%) than those receiving placebo (four of 37, 11%; p=0·002). The most common adverse events were non-pulmonary infections (71 of 112 events in the azithromycin group vs 132 of 209 events in the placebo group) and bronchiectasis-related events (episodes or investigations; 22 of 112 events in the azithromycin group vs 48 of 209 events in the placebo group); however, study drugs were well tolerated with no serious adverse events being attributed to the intervention. Interpretation Once-weekly azithromycin for up to 24 months decreased pulmonary exacerbations in Indigenous children with non-cystic-fibrosis bronchiectasis or chronic suppurative lung disease. However, this strategy was also accompanied by increased carriage of azithromycin-resistant bacteria, the clinical consequences of which are uncertain, and will need careful monitoring and further study.