CDKN2A is not the principal target of deletions on the short arm of chromosome 9 in neuroendocrine (Merkel cell) carcinoma of the skin

The majority of small-cell lung cancers (SCLCs) express p16 but not pRb. Given our previous study showing loss of pRb in Merkel cell carcinoma (MCC)/neuroendocrine carcinoma of the skin and the clinicopathological similarities between SCLC and MCC, we wished to determine if this was also the case in MCC. Twenty-nine MCC specimens from 23 patients were examined for deletions at 10 loci on 9p and 1 on 9q. No loss of heterozygosity (LOH) was seen in 9 patients including 2 for which tumour and cell line DNAs were examined. Four patients had LOH for all informative loci on 9p. Ten tumours showed more limited regions of loss on 9p, and from these 2 common regions of deletion were determined. Half of all informative cases had LOH at D9S168, the most telomeric marker examined, and 3 specimens showed loss of only D9S168. A second region (IFNA-D9S126) showed LOH in 10 (44%) cases, and case MCC26 showed LOH for only D9S126, implicating genes centromeric of the CDKN2A locus. No mutations in the coding regions of p16 were seen in 7 cell lines tested, and reactivity to anti-p16 antibody was seen in all 11 tumour specimens examined and in 6 of 7 cell lines from 6 patients. Furthermore, all cell lines examined reacted with anti-p14(ARF) antibody. These results suggest that neither transcript of the CDKN2A locus is the target of deletions on 9p in MCC and imply the existence of tumour-suppressor genes mapping both centromeric and telomeric of this locus.

FGFR2 as a molecular target in endometrial cancer

Although molecularly targeted therapies have been effective in some cancer types, no targeted therapy is approved for use in endometrial cancer. The recent identification of activating mutations in fibroblast growth factor receptor 2 (FGFR2) in endometrial tumors has generated a new avenue for the development of targeted therapeutic agents. The majority of the mutations identified are identical to germline mutations in FGFR2 and FGFR3 that cause craniosynostosis and hypochondroplasia syndromes and result in both ligand-independent and ligand-dependent receptor activation. Mutations that predominantly occur in the endometrioid subtype of endometrial cancer, are mutually exclusive with KRAS mutation, but occur in the presence of PTEN abrogation. In vitro studies have shown that endometrial cancer cell lines with activating FGFR2 mutations are selectively sensitive to a pan-FGFR inhibitor, PD173074. Several agents with activity against FGFRs are currently in clinical trials. Investigation of these agents in endometrial cancer patients with activating FGFR2 mutations is warranted.

An assessment of development funding for new housing post GFC in Queensland, Australia

Purpose: The purpose of this paper is to identify changes in bank lending criteria due to the GFC and to explore the associated impacts on new housing supply in Queensland, Australia. Design/methodology/approach: This research involves a survey of each of Australia’s big four banks, as well as two prominent arrangers of development finance. Data on key lending criteria was collected: Pre GFC, during the GFC, and GFC recovery stage. Findings: The GFC has resulted in a retraction of funds available for residential development. The few institutions lending are filtering out only the best credit risks by way of constrictive loan covenants including: low loan to value ratios, high cash equity requirements, regional “no go” zones, and demonstrated borrower track record. The ability of developers to proceed with new housing developments is being constrained by their inability to obtain sufficient finance. Research limitations/implications: This research uses survey data, together with an understanding of the project finance process to extrapolate impacts on the residential development industry across Queensland. No regional or sub-market analysis is included. Future research will include subsequent surveys to track any loosening of credit policies over time and sub-market sector analysis. Practical implications: The inability to obtain project finance is identified as a key constraint to new housing supply. This research will inform policy makers and provide important quantitative evidence of the importance of availability of development finance in the housing supply chain. Social implications: Queensland is facing a supply shortfall, which if not corrected, may lead to upward pressure on house prices and falling housing affordability. Originality/value: There is very little academic research on development funding. This research is unique in linking bank lending criteria to new housing supply and demonstrating the impact on the development industry.

Detection versus false alarm characterisation of a vision-based airborne dim-target collision detection system

This paper presents a preliminary flight test based detection range versus false alarm performance characterisation of a morphological-hidden Markov model filtering approach to vision-based airborne dim-target collision detection. On the basis of compelling in-flight collision scenario data, we calculate system operating characteristic (SOC) curves that concisely illustrate the detection range versus false alarm rate performance design trade-offs. These preliminary SOC curves provide a more complete dim-target detection performance description than previous studies (due to the experimental difficulties involved, previous studies have been limited to very short flight data sample sets and hence have not been able to quantify false alarm behaviour). The preliminary investigation here is based on data collected from 4 controlled collision encounters and supporting non-target flight data. This study suggests head-on detection ranges of approximately 2.22 km under blue sky background conditions (1.26 km in cluttered background conditions), whilst experiencing false alarms at a rate less than 1.7 false alarms/hour (ie. less than once every 36 minutes). Further data collection is currently in progress.

Managing financial implications for sustainable highway infrastructure delivery

Highway construction works have significant bearings on all aspects of sustainability. As they typically involve huge capital funds, stakeholders tend to place all interests on the financial justifications of the project, especially when embedding sustainability principles and practices may demand significant initial investment. Increasing public awareness and government policies demand that infrastructure projects respond to environmental challenges and people start to realise the negative consequences of not to pursue sustainability. Stakeholders are now keen to identify sustainable alternatives and financial implications of including them on a whole lifecycle basis. Therefore tools that aid the evaluation of investment options, such as provision of environmentally sustainable features in roads and highways, are highly desirable. Life-cycle cost analysis (LCCA) is generally recognised as a valuable approach for investment decision making for construction works. However to date it has limited application because the current LCCA models tend to focus on economic issues alone and are not able to deal with sustainability factors. This paper reports a research on identifying sustainability related factors in highway construction projects, in quantitative and qualitative forms of a multi-criteria analysis. These factors are then incorporated into existing LCCA models to produce a new sustainability based LCCA model with cost elements specific to sustainability measures. This presents highway project stakeholders a practical tool to evaluate investment decisions and reach an optimum balance between financial viability and sustainability deliverables.

An investigation of market segmentation theory and its impact on effective fundraising

This paper presents the findings of an indepth study into the effects and success of marketing segmentation, target marketing and fundraising. Organisations are constantly seeking new ways and more efficient means to raise funds so that they can fulfill their objectives. These organisations review and evaluate their resources to gain competitive advantage and increased fundraising success...

Mathematics funds of knowledge : sotmaute and sermaute fish in a Torres Strait Islander community

The purpose of this article is to describe a project with one Torres Strait Islander Community. It provides some insights into parents’ funds of knowledge that are mathematical in nature, such as sorting shells and giving fish. The idea of funds of knowledge is based on the premise that people are competent and have knowledge that has been historically and culturally accumulated into a body of knowledge and skills essential for their functioning and well-being. This knowledge is then practised throughout their lives and passed onto the next generation of children. Through adopting a community research approach, funds of knowledge that can be used to validate the community’s identities as knowledgeable people, can also be used as foundations for future learnings for teachers, parents and children in the early years of school. They can be the bridge that joins a community’s funds of knowledge with schools validating that knowledge.