Humanised xenograft models of bone metastasis revisited : novel insights into species-specific mechanisms of cancer cell osteotropism

The determinants and key mechanisms of cancer cell osteotropism have not been identified, mainly due to the lack of reproducible animal models representing the biological, genetic and clinical features seen in humans. An ideal model should be capable of recapitulating as many steps of the metastatic cascade as possible, thus facilitating the development of prognostic markers and novel therapeutic strategies. Most animal models of bone metastasis still have to be derived experimentally as most syngeneic and transgeneic approaches do not provide a robust skeletal phenotype and do not recapitulate the biological processes seen in humans. The xenotransplantation of human cancer cells or tumour tissue into immunocompromised murine hosts provides the possibility to simulate early and late stages of the human disease. Human bone or tissue-engineered human bone constructs can be implanted into the animal to recapitulate more subtle, species-specific aspects of the mutual interaction between human cancer cells and the human bone microenvironment. Moreover, the replication of the entire "organ" bone makes it possible to analyse the interaction between cancer cells and the haematopoietic niche and to confer at least a partial human immunity to the murine host. This process of humanisation is facilitated by novel immunocompromised mouse strains that allow a high engraftment rate of human cells or tissue. These humanised xenograft models provide an important research tool to study human biological processes of bone metastasis.

Ruptures in the heterosexual matrix through teenage flows and multiplicities

This article analyzes a series of stories and artworks that were produced in a collective biography workshop. It explores Judith Butler’s concept of the heterosexual matrix combined with a Deleuzian theoretical framework. The article begins with an overview of Butler’s concept of the heterosexual matrix and her theorizations on how it might be disrupted. It then suggests how a Deleuzian framework offers other tools for analyzing these ruptures at the micro level of girls’ everyday interactions.

Preventing public sector corruption : the relationship between parliamentary committees and corruption commissions

Parliamentary committees fulfil several important functions within the Parliament, with one of these being the oversight of various agencies including those that are designed to reduce corruption within the police service and other public sector agencies. The cross-party nature of committees combined with the protections of Parliament make them powerful agencies. Prenzler & Faulkner (2010) suggest that the ideal system for an agency that has oversight of a public sector integrity commission should include monitoring by a parliamentary committee, with an inspector attached to the committee. This occurs in Queensland, New South Wales and Western Australia. There has been very little research conducted on the role of parliamentary committees with oversight responsibilities for public sector integrity agencies. This paper will address this gap by examining the relationship between a parliamentary committee, a parliamentary inspector and a corruption commission. Queensland’s Parliamentary Crime and Misconduct Committee (PCMC/the Committee) and the Parliamentary Crime and Misconduct Commissioner (the Commissioner) provide oversight of the Crime and Misconduct Commission (CMC). By focussing on the PCMC and the Commissioner, the paper will examine the legislative basis for the Committee and Commissioner and their respective roles in providing oversight of the CMC. One key method by which the PCMC provides oversight of the CMC is to conduct and publish a review of the CMC every three years. Additionally, the paper will identify some of the similarities and differences between the PCMC and other committees that operate within the Queensland Parliament. By doing so, the paper will provide insights into the relationships that exist between corruption commissions, parliamentary committees and parliamentary inspectors and demonstrate the important role of the parliamentary committee in preventing instances of public sector corruption.

Health complaints commissions in Australia : Time for a national approach to data collection

Health complaint commissions in Australia: Time for a national approach • There is considerable variation between jurisdictions in the ways complaint data are defined, collected and recorded by the Health complaint commissions. • Complaints from the public are an important accountability mechanism and an indicator of service quality. • The lack of a consistent approach leads to fragmentation of complaint data and a lost opportunity to use national data to assist policy development and identify the main areas causing consumers to complain. • We need a national approach to complaints data collection by the Health complaints commissions in order to better respond to patients’ concerns

Moving beyond traditional clinics : creating a new legal clinics through community partnerships

To overcome the challenge of finding placements for large student numbers, QUT has partnered with community organisations to enable students to work on community-based projects addressing a community need. Students work in interdisciplinary teams with the community organisation to resolve issues and identify solutions to suit the organisation and client base. This paper will describe the community engaged learning pedagogy that is employed in the subject and will consider the benefits and challenges to law students of working collaboratively and developing community relationships. Critical appraisal of the legal system and the role of lawyers and analysis of the professional and ethical responsibilities legal practitioners is a focus of the subject. Explicit emphasis is placed on developing a sense of social responsibility and inculcating a pro bono ethos. Students attend workshops on topics such as reflective practice, cultural competencies, client solutions, collaborative practice and ethical obligations. This paper will discuss the challenges in creating the new legal clinic subject, benefits to students and community partners, and the results of initial student evaluation of the subject.

Valuing student and community voices in the university : action research as a framework for community service-learning

The Community Service-learning Lab (the Lab) was initiated as a university-wide service-learning experience at an Australian university. The Lab engages students, academics, and key community organisations in interdisciplinary action research projects to support student learning and to explore complex and ongoing problems nominated by the community partners. The current study uses feedback from the first offering of the Lab and focuses on exploring student experiences of the service learning project using an action research framework. Student reflections on this experience have revealed some positive outcomes of the Lab such as an appreciation for positive and strengths-based change. These outcomes are corroborated by collected reflections from community partners and academics. The students also identified challenges balancing the requirements for assessment and their goals to serve the community partner’s needs. This feedback has provided vital information for the academic team, highlighting the difficulties in balancing the agenda of the academic framework and the desire to give students authentic experiences.

Combining elicited expert knowledge into Bayesian priors

Information that is elicited from experts can be treated as `data', so can be analysed using a Bayesian statistical model, to formulate a prior model. Typically methods for encoding a single expert's knowledge have been parametric, constrained by the extent of an expert's knowledge and energy regarding a target parameter. Interestingly these methods have often been deterministic, in that all elicited information is treated at `face value', without error. Here we sought a parametric and statistical approach for encoding assessments from multiple experts. Our recent work proposed and demonstrated the use of a flexible hierarchical model for this purpose. In contrast to previous mathematical approaches like linear or geometric pooling, our new approach accounts for several sources of variation: elicitation error, encoding error and expert diversity. Of interest are the practical, mathematical and philosophical interpretations of this form of hierarchical pooling (which is both statistical and parametric), and how it fits within the subjective Bayesian paradigm. Case studies from a bioassay and project management (on PhDs) are used to illustrate the approach.

A polymorphism in the HLA-DPB1 gene is associated with susceptibility to multiple sclerosis

We conducted an association study across the human leukocyte antigen (HLA) complex to identify loci associated with multiple sclerosis (MS). Comparing 1927 SNPs in 1618 MS cases and 3413 controls of European ancestry, we identified seven SNPs that were independently associated with MS conditional on the others (each ). All associations were significant in an independent replication cohort of 2212 cases and 2251 controls () and were highly significant in the combined dataset (). The associated SNPs included proxies for HLA-DRB1*15:01 and HLA-DRB1*03:01, and SNPs in moderate linkage disequilibrium (LD) with HLA-A*02:01, HLA-DRB1*04:01 and HLA-DRB1*13:03. We also found a strong association with rs9277535 in the class II gene HLA-DPB1 (discovery set , replication set , combined ). HLA-DPB1 is located centromeric of the more commonly typed class II genes HLA-DRB1, -DQA1 and -DQB1. It is separated from these genes by a recombination hotspot, and the association is not affected by conditioning on genotypes at DRB1, DQA1 and DQB1. Hence rs9277535 represents an independent MS-susceptibility locus of genome-wide significance. It is correlated with the HLA-DPB1*03:01 allele, which has been implicated previously in MS in smaller studies. Further genotyping in large datasets is required to confirm and resolve this association.

Investigation of the [−/A]8 and C1236T genetic variations within the human toll-like receptor 3 gene for association with multiple sclerosis

Multiple sclerosis (MS) is a serious cause of neurological disability among young adults. The clinical course remains difficult to predict, and the pathogenesis of the disease is still modestly understood. Autoimmunity is thought to be a key aspect of the disease, with autoreactive T cells thought to mediate central nervous system (CNS) inflammation to some extent. Toll-like receptors are known to mediate cellular recognition of pathogens by way of patterns of molecular presentation. Toll-like receptor 3 is coded by the gene TLR3 and is recognized as an important factor in virus recognition and is known to be involved in the expression of neuroprotective mediators. We set out to investigate two variations within the TLR3 gene, an 8 bp insertion-deletion \[-/A](8) and a single base-pair variation C1236T, in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We used capillary gel electrophoresis and TaqMan genotyping assay techniques to resolve genotypes for each marker, respectively. Our work found no significant difference between frequencies for TLR3 \[-/A](8) by genotype (chi(2)=1.03, p=0.60) or allele (chi(2)=1.09, p=0.30). Similarly, we found no evidence for the association of TLR3 C1236T by genotype (chi(2)=0.35, p=0.84) or allele frequency (chi(2)=0.31, p=0.58). This work reveals no evidence to suggest that these markers are associated with MS in the tested population. Although the role of TLR3 and the wider toll-like receptor family remain significant in neurological and CNS inflammatory disorders, our current work does not support a role for the two tested variants in this gene with regard to MS susceptibility.

Multiple sclerosis susceptibility-associated SNPs do not influence disease severity measures in a cohort of Australian MS patients

Recent association studies in multiple sclerosis (MS) have identified and replicated several single nucleotide polymorphism (SNP) susceptibility loci including CLEC16A, IL2RA, IL7R, RPL5, CD58, CD40 and chromosome 12q13–14 in addition to the well established allele HLA-DR15. There is potential that these genetic susceptibility factors could also modulate MS disease severity, as demonstrated previously for the MS risk allele HLA-DR15. We investigated this hypothesis in a cohort of 1006 well characterised MS patients from South-Eastern Australia. We tested the MS-associated SNPs for association with five measures of disease severity incorporating disability, age of onset, cognition and brain atrophy. We observed trends towards association between the RPL5 risk SNP and time between first demyelinating event and relapse, and between the CD40 risk SNP and symbol digit test score. No associations were significant after correction for multiple testing. We found no evidence for the hypothesis that these new MS disease risk-associated SNPs influence disease severity.

An investigation of the C77G and C772T variations within the human protein tyrosine phosphatase receptor type C gene for association with multiple sclerosis in an Australian population

Multiple sclerosis (MS) is a common cause of neurological disability in young adults. The disease generally manifests in early to middle adulthood and causes various neurological deficits. Autoreactive T lymphocytes and their associated antigens have long been presumed important features of MS pathogenesis. The Protein tyrosine phosphatase receptor type C gene (PTPRC) encodes the T-cell receptor CD45. Variations within PTPRC have been previously associated with diseases of autoimmune origin such as type 1 diabetes mellitus and Graves' disease. We set out to investigate two variants within the PTPRC gene, C77G and C772T in subjects with MS and matched healthy controls to determine whether significant differences exist in these markers in an Australian population. We employed high resolution melt analysis (HRM) and restriction length polymorphism (RFLP) techniques to determine genotypic and allelic frequencies. Our study found no significant difference between frequencies for PTPRC C77G by either genotype (Χ2 = 0.65, P = 0.72) or allele (Χ2 = 0.48, P = 0.49). Similarly, we did not find evidence to suggest an association between PTPRC C772T by genotype (Χ2 = 1.06, P = 0.59) or allele (Χ2 = 0.20, P = 0.66). Linkage disequilibrium (LD) analysis showed strong linkage disequilibrium between the two tested markers (D' = 0.9970, SD = 0.0385). This study reveals no evidence to suggest that these markers are associated with MS in the tested Australian Caucasian population. Although the PTPRC gene has a significant role in regulating CD4+ and CD8+ autoreactive T-cells, interferon-beta responsiveness, and potentially other important processes, our study does not support a role for the two tested variants of this gene in MS susceptibility in the Australian population.

Genome-wide association study identifies new multiple sclerosis susceptibility loci on chromosomes 12 and 20

To identify multiple sclerosis (MS) susceptibility loci, we conducted a genome-wide association study (GWAS) in 1,618 cases and used shared data for 3,413 controls. We performed replication in an independent set of 2,256 cases and 2,310 controls, for a total of 3,874 cases and 5,723 controls. We identified risk-associated SNPs on chromosome 12q13-14 (rs703842, P = 5.4 x 10(-11); rs10876994, P = 2.7 x 10(-10); rs12368653, P = 1.0 x 10(-7)) and upstream of CD40 on chromosome 20q13 (rs6074022, P = 1.3 x 10(-7); rs1569723, P = 2.9 x 10(-7)). Both loci are also associated with other autoimmune diseases. We also replicated several known MS associations (HLA-DR15, P = 7.0 x 10(-184); CD58, P = 9.6 x 10(-8); EVI5-RPL5, P = 2.5 x 10(-6); IL2RA, P = 7.4 x 10(-6); CLEC16A, P = 1.1 x 10(-4); IL7R, P = 1.3 x 10(-3); TYK2, P = 3.5 x 10(-3)) and observed a statistical interaction between SNPs in EVI5-RPL5 and HLA-DR15 (P = 0.001).

Study of leukemia inhibitory factor polymorphism within an Australian multiple sclerosis population

OBJECTIVE: To examine a polymorphism within the 3' untranslated region of the leukemia inhibitory factor gene for an association with multiple sclerosis within an Australian case-control population. METHODS: A test group of 121 unrelated multiple sclerosis patients, of Caucasian origin, and 121 controls, matched for ethnicity, sex and age (+/-5 years) were included in the study. The LIF 3' UTR StuI polymorphism was genotyped by restriction fragment length polymorphism analysis. Statistical analysis of genotype and allele frequencies included Hardy-Weinberg law and conventional contingency table analysis incorporating the standard chi-squared test for independence. RESULTS: Allelic and genotype frequencies did not demonstrate a significant association between the case and control groups for the tested LIF 3' UTR StuI polymorphism. CONCLUSION: The results indicate that the LIF 3' UTR StuI polymorphism is not associated with multiple sclerosis, however we cannot exclude the hypothesis that other polymorphic alleles of LIF could be implicated in MS susceptibility.

Animated Kolam Patterns

The brief for the creative work was to produce a digital backdrop that would be projected behind and enhance a dance performance. The animation needed to display a static kolam pattern that would then dissolve at a choreographed point in the performance. The dissolving mimics the fragmentation that occurs to physical kolam patterns throughout the day as people interact with the drawings. The final animated work was incorporated into Vanessa Mafe-Keane’s performance titled “Paired Back” performed at the Judith Wright Centre, Brisbane 2013 as part of “Dance. Indie Dance. Through the use of motion capture technology the process of dissolving the pattern is a direct result of the performer’s movements allowing visual and temporal connection between motion of performer and digital graphic to be observed. This creative work presented an opportunity to expand upon experiments conducted in the production of experimental visual forms undertaken at QUT using the Xsens MVN Inertial Motion Capture System. The project took on the form of an investigation into practice with a focus on the additional complexities of capturing, then applying multiple data sources into the production of animated visuals along with bringing to light the considerations taken into account when producing this type of generative art work for live performance. The reported outcomes from this investigation have contributed to a larger study on the use of motion capture in the generative arts, furthering the understanding of and generating theories on practice.