Integrated genomic characterization of endometrial carcinoma

We performed an integrated genomic, transcriptomic and proteomic characterization of 373 endometrial carcinomas using array- and sequencing-based technologies. Uterine serous tumours and ∼25% of high-grade endometrioid tumours had extensive copy number alterations, few DNA methylation changes, low oestrogen receptor/progesterone receptor levels, and frequent TP53 mutations. Most endometrioid tumours had few copy number alterations or TP53 mutations, but frequent mutations in PTEN, CTNNB1, PIK3CA, ARID1A and KRAS and novel mutations in the SWI/SNF chromatin remodelling complex gene ARID5B. A subset of endometrioid tumours that we identified had a markedly increased transversion mutation frequency and newly identified hotspot mutations in POLE. Our results classified endometrial cancers into four categories: POLE ultramutated, microsatellite instability hypermutated, copy-number low, and copy-number high. Uterine serous carcinomas share genomic features with ovarian serous and basal-like breast carcinomas. We demonstrated that the genomic features of endometrial carcinomas permit a reclassification that may affect post-surgical adjuvant treatment for women with aggressive tumours.

Aliens, borders and social citizens : Health and community services for trafficked women

Australian policy makers recognise women who are trafficked to Australia (and these are largely for the purposes of sexual exploitation) primarily as victims of crime. The main public mechanism by which the "problem" of trafficked people in Australia is managed is the criminal law. At the same time, however, as a signatory to the UN Protocol on Trafficking and the Declaration of Human Rights, the Australian Government also recognises the rights of women trafficked to Australia to access health and community services in the wake of the health damage and trauma they often incur as a consequence of their experience. Current evidence suggests that trafficked women in Australia face considerable barriers in being able to avail themselves of such a right and of the services that accompany it. This paper explores the tensions posed by Australian policy and service approaches to trafficked women in light of the concept of social citizenship and the ways in which it is mediated in the Australian context by national border protection policy.

New and young firms Entrepreneurship policy and the role of government – evidence from the Federation of Small Businesses survey

Purpose – The purpose of this paper is to investigate whether new and young firms are different from older firms. This analysis is undertaken to explore general characteristics, use of external resources and growth orientation. Design/methodology/approach – Data from the 2008 UK Federation of Small Businesses survey provided 8,000 responses. Quantitative analysis identified significantly different characteristics of firms from 0-4, 4-9, 9-19 and 20+ years. Factor analysis was utilised to identify the advice sets, finance and public procurement customers of greatest interest, with ANOVA used to statistically compare firms in the identified age groups with different growth aspirations. Findings – The findings reveal key differences between new, young and older firms in terms of characteristics including business sector, owner/manager age, education/business experience, legal status, intellectual property and trading performance. New and young firms were more able to access beneficial resources in terms of finance and advice from several sources. New and young firms were also able to more easily access government and external finance, as well as government advice, but less able to access public procurement. Research limitations/implications – New and young firms are utilising external networks to access several resources for development purposes, and this differs for older firms. This suggests that a more explicit age-differentiated focus is required for government policies aimed at supporting firm growth. Originality/value – The study provides important baseline data for future quantitative and qualitative studies focused on the impact of firm age and government policy.

Does preoperative oral carbohydrate reduce hospital stay?

Background Carbohydrate-rich fluids are used to improve postoperative recovery but the effectiveness of the product for reducing length of hospital stay is uncertain. Objective To assess the effectiveness of preoperative loading with carbohydrates on postoperative outcomes. Participants Forty six patients booked for elective colorectal surgery. Methods Participants were allocated to a Carbohydrate-rich fluid group or Usual Care group during their pre-admission clinic visit. The primary outcome was ‘Time to readiness for discharge’. Results Patients in the control group spent on average 4.3 days (95% confidence interval 3.2 to 5.7) and the Carbohydrate-rich fluid group spent 4.1 days (95% confidence interval 3.2 to 5.4) until the primary outcome was met (p=0.824). Conclusion The safety of preoperative high carbohydrate fluids is supported but we were unable to confirm or refute the benefit of CHO for shorter hospital stay following elective colorectal surgery.

Proteomics science and society :the role of knowledge translation in moving towards clinical applications

Gaining support for proteomics science requires effective knowledge translation. Knowledge translation (KT) processes turn the evidence generated by scientific discovery into recommendations for clinical applications, funding priorities, and policy/regulatory reforms. Clinicians, regulators, and funders need to understand why emerging proteomics knowledge is relevant, and what are the potential applications of that knowledge. A lack of clarity remains about what KT means.

International tax and the Australian wine industry: Is your client’s product destined to sail the seven seas?

The export market for Australian wine continues to grow at a rapid rate, with imported wines also playing a role in market share in sales in Australia. It is estimated that over 60 per cent of all Australian wine is exported, while 12 per cent of wine consumed in Australia has overseas origins. In addition to understanding the size and direction (import or export) of wines, the foreign locales also play an important role in any tax considerations. While the export market for Australian produced alcohol continues to grow, it is into the Asian market that the most significant inroads are occurring. Sales into China of bottled wine over $7.50 per litre recently overtook the volume sold our traditional partners of the United States and Canada. It is becoming easier for even small to medium sized businesses to export their services or products overseas. However, it is vital for those businesses to understand the tax rules applying to any international transactions. Specifically, one of the first tax regimes that importers and exporters need to understand once they decide to establish a presence overseas is transfer pricing. These are the rules that govern the cross-border prices of goods, services and other transactions entered into between related parties. This paper is Part 2 of the seminar presented on transfer pricing and international tax issues which are particularly relevant to the wine industry. The predominant focus of Part 2 is to discuss four key areas likely to affect international expansion. First, the use of the available transfer pricing methodologies for international related party transactions is discussed. Second, the affects that double tax agreements will have on taking a business offshore are considered. Third, the risks associated with aggressive tax planning through tax information exchange agreements is reviewed. Finally, the paper predicts future ‘trip-wires’ and areas to ‘watch out for’ for practitioners dealing with clients operating in the international arena.

The Cube : a very large-scale interactive engagement space

“The Cube” is a unique facility that combines 48 large multi-touch screens and very large-scale projection surfaces to form one of the world’s largest interactive learning and engagement spaces. The Cube facility is part of the Queensland University of Technology’s (QUT) newly established Science and Engineering Centre, designed to showcase QUT’s teaching and research capabilities in the STEM (Science, Technology, Engineering, and Mathematics) disciplines. In this application paper we describe, the Cube, its technical capabilities, design rationale and practical day-to-day operations, supporting up to 70,000 visitors per week. Essential to the Cube’s operation are five interactive applications designed and developed in tandem with the Cube’s technical infrastructure. Each of the Cube’s launch applications was designed and delivered by an independent team, while the overall vision of the Cube was shepherded by a small executive team. The diversity of design, implementation and integration approaches pursued by these five teams provides some insight into the challenges, and opportunities, presented when working with large distributed interaction technologies. We describe each of these applications in order to discuss the different challenges and user needs they address, which types of interactions they support and how they utilise the capabilities of the Cube facility.

Fire safety of buildings based on realistic fire time-temperature curves

In recent times, fire has become a major disaster in buildings due to the increase in fire loads, as a result of modern furniture and light weight construction. This has caused problems for safe evacuation and rescue activities, and in some instances lead to the collapse of buildings (Lewis, 2008 and Nyman, 2002). Recent research has shown that the actual fire resistance of building elements exposed to building fires can be less than their specified fire resistance rating (Lennon and Moore, 2003, Jones, 2002, Nyman, 2002 and Abecassis-Empis et al. 2008). Conventionally the fire rating of building elements is determined using fire tests based on the standard fire time-temperature curve given in ISO 834. This ISO 834 curve was developed in the early 1900s, where wood was the basic fuel source. In reality, modern buildings make use of thermoplastic materials, synthetic foams and fabrics. These materials are high in calorific values and increase both the speed of fire growth and heat release rate, thus increasing the fire severity beyond that of the standard fire curve. Hence it suggests the need to use realistic fire time-temperature curves in tests. Real building fire temperature profiles depend on the fuel load representing the combustible building contents, ventilation openings and thermal properties of wall lining materials. Fuel load is selected based on a review and suitable realistic fire time-temperature curves were developed. Fire tests were then performed for plasterboard lined light gauge steel framed walls for the developed realistic fire curves. This paper presents the details of the development of suitable realistic building fire curves, and the fire tests using them. It describes the fire performance of tested walls in comparison to the standard fire tests and highlights the differences between them. This research has shown the need to use realistic fire exposures in assessing the fire resistance rating of building elements.

Influence of osteocytes in the in vitro and in vivo β-tricalcium phosphate-stimulated osteogenesis

Osteocytes, known to act as the main regulators of bone homeostasis, have become a major focus in the field of bone research. Bioactive ceramics have been widely used for bone regeneration. However, there are few studies about the interaction of osteocytes with bioceramics. The effects of osteocytes on the in vitro and in vivo osteogenesis of bioceramics are also unclear. The aim of this study was to investigate the role of osteocytes on the b-tricalcium phosphate (b-TCP) stimulated osteogenesis. It was found that osteocytes responded to the b-TCP stimulation, leading to the release of Wnt (wingless-related MMTV integration site), which enhanced osteogenic differentiation of bone marrow stromal cells via Wnt signaling pathway. Receptor activator of nuclear factor kappa B ligand, an osteoclast inducer, was also upregulated, indicating that osteocytes would also participated in activation of osteoclasts, which played a major role in the degradation process of b-TCP and new bone remodeling. In vivo studies further demonstrated that when the material was completely embedded by newly formed bone, the only cell contacting with the material was osteocyte. However, the material would eventually be degraded and replaced by the new bone, requiring the participation of osteoclasts and osteoblasts, which were demonstrated by using immunostaining in this study. As the only cell contacting with the material, osteocytes probably acted in a regulatory role to regulate the surrounding osteoclasts and osteoblasts. Osteocytes were also found to participate in the maturation of osteoblasts and the mineralization process of biomaterials, by upregulating E11 (podoplanin) and dentin matrix protein 1 expression. These findings indicated that osteocytes involved in bone biomaterial-mediated osteogenesis and biomaterial degradation, providing valuable insights into the mechanism of material-stimulated osteogenesis, and a novel strategy to optimize the evaluating system for the biological properties of biomaterials.

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.

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.

Single-nucleotide polymorphism alleles in the insulin receptor gene are associated with typical migraine

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and association analysis. We isolated 48 single-nucleotide polymorphisms within the locus, of which we genotyped 24 in a Caucasian population comprising 827 unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the insulin receptor gene showed significant association with migraine. This association was independently replicated in a case-control population collected separately. We used experiments with insulin receptor RNA and protein to investigate functionality for the migraine-associated single-nucleotide polymorphisms. We suggest possible functions for the insulin receptor in migraine pathogenesis.

Understanding the actualization of affordances: A study in the process modeling context

The affordances concept describes the possibilities for goal-oriented action that technical objects offer to specified users. This notion has received growing attention from IS researchers. However, few studies have gone beyond contextualizing parts of the concept to a specific setting – the tip of the iceberg. In this research-in-progress paper, we report on our efforts to further develop the IS discipline’s understanding of affordances from informational objects. Specifically, we seek to extend extant theory on the origin and actualization of affordances. We develop a model that describes the process by which affordances are perceived and actualized and their dependence on information and actualization effort. We illustrate our emergent theory in the context of conceptual process models used by analysts for purposes of information systems analysis and design. We offer suggestions for operationalizing and testing this model empirically, and provide details about our design of a mixed-methods study currently in progress.

Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly expresses EBNA3A with conserved CD8+ T-cell epitopes

Post-transplantation lymphoproliferative disorders (PTLD) arise in the immunosuppressed and are frequently Epstein-Barr virus (EBV) associated. The most common PTLD histological sub-type is diffuse large B-cell lymphoma (EBV+DLBCL-PTLD). Restoration of EBV-specific T-cell immunity can induce EBV+DLBCL-PTLD regression. The most frequent B-cell lymphoma in the immunocompetent is also DLBCL. ‘EBV-positive DLBCL of the elderly’ (EBV+DLBCL) is a rare but well-recognized DLBCL entity that occurs in the overtly immunocompetent, that has an adverse outcome relative to EBV-negative DLBCL. Unlike PTLD (which is classified as viral latency III), literature suggests EBV+DLBCL is typically latency II, i.e. expression is limited to the immuno-subdominant EBNA1, LMP1 and LMP2 EBV-proteins. If correct, this would be a major impediment for T-cell immunotherapeutic strategies. Unexpectedly we observed EBV+DLBCL-PTLD and EBV+DLBCL both shared features consistent with type III EBV-latency, including expression of the immuno-dominant EBNA3A protein. Extensive analysis showed frequent polymorphisms in EBNA1 and LMP1 functionally defined CD8+ T-cell epitope encoding regions, whereas EBNA3A polymorphisms were very rare making this an attractive immunotherapy target. As with EBV+DLBCL-PTLD, the antigen presenting machinery within lymphomatous nodes was intact. EBV+DLBCL express EBNA3A suggesting it is amenable to immunotherapeutic strategies.