Identification of circulating tumour cells in early stage breast cancer patients using multi marker immunobead RT-PCR

Introduction The ability to screen blood of early stage operable breast cancer patients for circulating tumour cells is of potential importance for identifying patients at risk of developing distant relapse. We present the results of a study of the efficacy of the immunobead RT-PCR method in identifying patients with circulating tumour cells. Results Immunomagnetic enrichment of circulating tumour cells followed by RT-PCR (immunobead RT-PCR) with a panel of five epithelial specific markers (ELF3, EPHB4, EGFR, MGB1 and TACSTD1) was used to screen for circulating tumour cells in the peripheral blood of 56 breast cancer patients. Twenty patients were positive for two or more RT-PCR markers, including seven patients who were node negative by conventional techniques. Significant increases in the frequency of marker positivity was seen in lymph node positive patients, in patients with high grade tumours and in patients with lymphovascular invasion. A strong trend towards improved disease free survival was seen for marker negative patients although it did not reach significance (p = 0.08). Conclusion Multi-marker immunobead RT-PCR analysis of peripheral blood is a robust assay that is capable of detecting circulating tumour cells in early stage breast cancer patients.

Learning and teaching from the edge to centre stage : Critical factors in embedding sustainable university-wide engagement in external awards and grants funding initiatives.

Teaching awards, grants and fellowships are strategies used to recognise outstanding contributions to learning and teaching, encourage innovation, and to shift learning and teaching from the edge to centre stage. Examples range from school, faculty and institutional award and grant schemes to national schemes such as those offered by the Australian Learning and Teaching Council (ALTC), the Carnegie Foundation for the Advancement of Teaching in the United States, and the Fund for the Development of Teaching and Learning in higher education in the United Kingdom. The Queensland University of Technology (QUT) has experienced outstanding success in all areas of the ALTC funding since the inception of the Carrick Institute for Learning and Teaching in 2004. This paper reports on a study of the critical factors that have enabled sustainable and resilient institutional engagement with ALTC programs. As a lens for examining the QUT environment and practices, the study draws upon the five conditions of the framework for effective dissemination of innovation developed by Southwell, Gannaway, Orrell, Chalmers and Abraham (2005, 2010): 1. Effective, multi-level leadership and management 2. Climate of readiness for change 3. Availability of resources 4. Comprehensive systems in institutions and funding bodies 5. Funding design The discussion on the critical factors and practical and strategic lessons learnt for successful university-wide engagement offer insights for university leaders and staff who are responsible for learning and teaching award, grant and associated internal and external funding schemes.

A method for evaluating lean assembly process at design stage

Lean product design has the potential to reduce the overall product development time and cost and can improve the quality of a product. However, it has been found that no or little work has been carried out to provide an integrated framework of "lean design" and to quantitatively evaluate the effectiveness of lean practices/principles in product development process. This research proposed an integrated framework for lean design process and developed a dynamic decision making tool based on Methods Time Measurement (MTM) approach for assessing the impact of lean design on the assembly process. The proposed integrated lean framework demonstrates the lean processes to be followed in the product design and assembly process in order to achieve overall leanness. The decision tool consists of a central database, the lean design guidelines, and MTM analysis. Microsoft Access and C# are utilized to develop the user interface to use the MTM analysis as decision making tool. MTM based dynamic tool is capable of estimating the assembly time, costs of parts and labour of various alternatives of a design and hence is able to achieve optimum design. A case study is conducted to test and validate the functionality of the MTM Analysis as well as to verify the lean guidelines proposed for product development.

Broadening of transgenic adenocarcinoma of the mouse prostate (TRAMP) model to represent late stage androgen depletion independent cancer

BACKGROUND The transgenic adenocarcinoma of the mouse prostate (TRAMP) model closely mimics PC-progression as it occurs in humans. However, the timing of disease incidence and progression (especially late stage) makes it logistically difficult to conduct experiments synchronously and economically. The development and characterization of androgen depletion independent (ADI) TRAMP sublines are reported. METHODS Sublines were derived from androgen-sensitive TRAMP-C1 and TRAMP-C2 cell lines by androgen deprivation in vitro and in vivo. Epithelial origin (cytokeratin) and expression of late stage biomarkers (E-cadherin and KAI-1) were evaluated using immunohistochemistry. Androgen receptor (AR) status was assessed through quantitative real time PCR, Western blotting, and immunohistochemistry. Coexpression of AR and E-cadherin was also evaluated. Clonogenicity and invasive potential were measured by soft agar and matrigel invasion assays. Proliferation/survival of sublines in response to androgen was assessed by WST-1 assay. In vivo growth of subcutaneous tumors was assessed in castrated and sham-castrated C57BL/6 mice. RESULTS The sublines were epithelial and displayed ADI in vitro and in vivo. Compared to the parental lines, these showed (1) significantly faster growth rates in vitro and in vivo independent of androgen depletion, (2) greater tumorigenic, and invasive potential in vitro. All showed substantial downregulation in expression levels of tumor suppressor, E-cadherin, and metastatis suppressor, KAI-1. Interestingly, the percentage of cells expressing AR with downregulated E-cadherin was higher in ADI cells, suggesting a possible interaction between the two pathways. CONCLUSIONS The TRAMP model now encompasses ADI sublines potentially representing different phenotypes with increased tumorigenicity and invasiveness.

A two-stage decision model for information filtering

Information mismatch and overload are two fundamental issues influencing the effectiveness of information filtering systems. Even though both term-based and pattern-based approaches have been proposed to address the issues, neither of these approaches alone can provide a satisfactory decision for determining the relevant information. This paper presents a novel two-stage decision model for solving the issues. The first stage is a novel rough analysis model to address the overload problem. The second stage is a pattern taxonomy mining model to address the mismatch problem. The experimental results on RCV1 and TREC filtering topics show that the proposed model significantly outperforms the state-of-the-art filtering systems.

Identification of early-stage colorectal cancer patients at risk of relapse post-resection by immunobead reverse transcription-PCR analysis of peritoneal lavage fluid for malignant cells

Purpose: Colorectal cancer patients diagnosed with stage I or II disease are not routinely offered adjuvant chemotherapy following resection of the primary tumor. However, up to 10% of stage I and 30% of stage II patients relapse within 5 years of surgery from recurrent or metastatic disease. The aim of this study was to determine if tumor-associated markers could detect disseminated malignant cells and so identify a subgroup of patients with early-stage colorectal cancer that were at risk of relapse. Experimental Design: We recruited consecutive patients undergoing curative resection for early-stage colorectal cancer. Immunobead reverse transcription-PCR of five tumor-associated markers (carcinoembryonic antigen, laminin γ2, ephrin B4, matrilysin, and cytokeratin 20) was used to detect the presence of colon tumor cells in peripheral blood and within the peritoneal cavity of colon cancer patients perioperatively. Clinicopathologic variables were tested for their effect on survival outcomes in univariate analyses using the Kaplan-Meier method. A multivariate Cox proportional hazards regression analysis was done to determine whether detection of tumor cells was an independent prognostic marker for disease relapse. Results: Overall, 41 of 125 (32.8%) early-stage patients were positive for disseminated tumor cells. Patients who were marker positive for disseminated cells in post-resection lavage samples showed a significantly poorer prognosis (hazard ratio, 6.2; 95% confidence interval, 1.9-19.6; P = 0.002), and this was independent of other risk factors. Conclusion: The markers used in this study identified a subgroup of early-stage patients at increased risk of relapse post-resection for primary colorectal cancer. This method may be considered as a new diagnostic tool to improve the staging and management of colorectal cancer. © 2006 American Association for Cancer Research.

A first stage test of Dunning's framework on multinational contracting into Australia : reviewing secondary data.

In response to the need to leverage private finance and the lack of competition in some parts of the Australian public sector infrastructure market, especially in the very large economic infrastructure sector procured using Pubic Private Partnerships, the Australian Federal government has demonstrated its desire to attract new sources of in-bound foreign direct investment (FDI). This paper aims to report on progress towards an investigation into the determinants of multinational contractors’ willingness to bid for Australian public sector major infrastructure projects. This research deploys Dunning’s eclectic theory for the first time in terms of in-bound FDI by multinational contractors into Australia. Elsewhere, the authors have developed Dunning’s principal hypothesis to suit the context of this research and to address a weakness arising in this hypothesis that is based on a nominal approach to the factors in Dunning's eclectic framework and which fails to speak to the relative explanatory power of these factors. In this paper, a first stage test of the authors' development of Dunning's hypothesis is presented by way of an initial review of secondary data vis-à-vis the selected sector (roads and bridges) in Australia (as the host location) and with respect to four selected home countries (China; Japan; Spain; and US). In doing so, the next stage in the research method concerning sampling and case studies is also further developed and described in this paper. In conclusion, the extent to which the initial review of secondary data suggests the relative importance of the factors in the eclectic framework is considered. It is noted that more robust conclusions are expected following the future planned stages of the research including primary data from the case studies and a global survey of the world’s largest contractors and which is briefly previewed. Finally, and beyond theoretical contributions expected from the overall approach taken to developing and testing Dunning’s framework, other expected contributions concerning research method and practical implications are mentioned.

Cohabitation : placing disability centre stage

The play Cohabitation places disability centre stage by creating a three dimensional protagonist who is also a wheelchair user. The accompanying exegesis examines the challenges associated with creating such a character for theatre, using a practice-led methodology. During the process of writing my case study play, I have investigated the international literature, reflected on my experience as a physician specialising in rehabilitation and collaborated with members of the Australian and international disability communities. I have also reflected on the historical stereotypes associated with disability and integrated the contemporary experience of wheelchair users into my script. By organising a production of the play in Australia and directing a rehearsed reading of the play in New York, I was able to scrutinise my additional goal of casting an actor who was also a wheelchair user. My research illuminates the issues involved in writing and producing a play in which the lead character also has a physical disability, and I would hope, offers insight into the creation of such a character and script.

Productivity performance of Singapore’s retail sector : a two-stage non-parametric approach

This paper seeks to identify and quantify sources of the lagging productivity in Singapore’s retail sector as reported in the Economic Strategies Committee 2010 report. A two-stage analysis is adopted. In the first stage, the Malmquist productivity index is employed which provides measures of productivity change, technological change and efficiency change. In the second stage, technical efficiency estimates are regressed against explanatory variables based on a truncated regression model. Sources of technical efficiency were attributed to quality of workers while product assortment and competition negatively impacted on efficiency.

The use of virtual prototyping for hazard identification in the early design stage

Purpose: The construction industry is well known for its high accident rate and many practitioners consider a preventative approach to be the most important means of bringing about improvements. This paper addresses previous research and the weaknesses of existing preventative approaches and a new application is described and illustrated involving the use of a multi-dimensional simulation tool - Construction Virtual Prototyping (CVP). Methodology: A literature review was conducted to investigate previous studies of hazard identification and safety management and to develop the new approach. Due to weaknesses in current practice, the research study explored the use of computer simulation techniques to create virtual environments where users can explore and identify construction hazards. Specifically, virtual prototyping technology was deployed to develop typical construction scenarios in which unsafe or hazardous incidents occur. In a case study, the users’ performance was evaluated their responses to incidents within the virtual environment and the effectiveness of the computer simulation system established though interviews with the safety project management team. Findings: The opinions and suggestions provided by the interviewees led to the initial conclusion that the simulation tool was useful in assisting the safety management team’s hazard identification process during the early design stage. Originality: The research introduces an innovative method to support the management teams’ reviews of construction site safety. The system utilises three-dimensional modelling and four-dimensional simulation of worker behaviour, a configuration that has previously not been employed in construction simulations. An illustration of the method’s use is also provided, together with a consideration of its strengths and weaknesses.

Spectrum sensing using two-stage detection to compensate for reduced primary user duty cycle

Spectrum sensing is considered to be one of the most important tasks in cognitive radio. One of the common assumption among current spectrum sensing detectors is the full presence or complete absence of the primary user within the sensing period. In reality, there are many situations where the primary user signal only occupies a portion of the observed signal and the assumption of primary user duty cycle not necessarily fulfilled. In this paper we show that the true detection performance can degrade from the assumed achievable values when the observed primary user exhibits a certain duty cycle. Therefore, a two-stage detection method incorporating primary user duty cycle that enhances the detection performance is proposed. The proposed detector can improve the probability of detection under low duty cycle at the expense of a small decrease in performance at high duty cycle.