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.

Hot Summers and Heart Failure: Seasonal Variations in Morbidity and Mortality in Australian Heart Failure Patients (1994-2005)

Background There are minimal reports of seasonal variations in chronic heart failure (CHF)-related morbidity and mortality beyond the northern hemisphere. Aims and methods We examined potential seasonal variations with respect to morbidity and all-cause mortality over more than a decade in a cohort of 2961 patients with CHF from a tertiary referral hospital in South Australia subject to mild winters and hot summers. Results Seasonal variation across all event-types was observed. CHF-related morbidity peaked in winter (July) and was lowest in summer (February): 70 (95% CI: 65 to 76) vs. 33 (95% CI: 30 to 37) admissions/1000 at risk (p<0.005). All-cause admissions (113 (95% CI: 107 to 120) vs. 73 (95% CI 68 to 79) admissions/1000 at risk, p<0.001) and concurrent respiratory disease (21% vs. 12%,p<0.001) were consistently higher in winter. 2010 patients died, mortality was highest in August relative to February: 23 (95% CI: 20 to 27) vs. 12 (95% CI: 10 to 15) deaths per 1000 at risk, p<0.001. Those aged 75 years or older were most at risk of seasonal variations in morbidity and mortality. Conclusion Seasonal variations in CHF-related morbidity and mortality occur in the hot climate of South Australia, suggesting that relative (rather than absolute) changes in temperature drive this global phenomenon.

Renal and genitourinary emergencies

Genitourinary (GU) problems are a common complaint in the community and to the emergency department (ED). Urinary tract infections (UTIs) are the second most common bacterial disease. UTIs rank as the sixteenth most frequently reported problem to general practitioners in Australia1 and between 10% and 20% of women will experience at least one UTI in their lifetime. Over 1,000,000 Australians are currently suffering with nephrolithiasis (renal calculi) and it is hy-pothesised that Australia’s hot, dry climate causes more stone formation than many other coun-tries in the world. Acute kidney injury (AKI) is a common complication of any trauma. Hypovol-aemia results in severe hypotension and this precipitates the development of acute tubular necrosis and subsequent AKI. The incidence of chronic kidney disease (CKD) is rising across the world. CKD is classified into five stages with those in stage 5 being classified as being in end stage kidney disease (ESKD). It is estimated that there are over 1.5 million people in Australia with CKD and there were over 16,000 Australians and over 2900 individuals in New Zealand with ESKD.2 Indigenous populations from both countries (Aboriginals, Torres Strait Islanders, Maoris, and Pacific Islanders) are over-represented in the number of people with all stages of CKD in both countries. Patients with compromised renal function often require the assistance of paramedics and will arrive at the ED with life-threatening fluid and electrolyte imbalances. Spe-cific GU emergencies discussed in this chapter are acute renal failure, rhabdomyolysis, chronic kidney disease, UTIs, acute urinary retention, urinary calculi, testicular torsion, epididymitis, and priapism. Refer to Chapter 31 for discussion of sexually transmitted infections (STIs) in women and to Chapter X for discussion of genitourinary trauma.

Daily average temperature and mortality among the elderly : a meta-analysis and systematic review of epidemiological evidence

The impact of climate change on the health of vulnerable groups such as the elderly has been of increasing concern. However, to date there has been no meta-analysis of current literature relating to the effects of temperature fluctuations upon mortality amongst the elderly. We synthesised risk estimates of the overall impact of daily mean temperature on elderly mortality across different continents. A comprehensive literature search was conducted using MEDLINE and PubMed to identify papers published up to December 2010. Selection criteria including suitable temperature indicators, endpoints, study-designs and identification of threshold were used. A two-stage Bayesian hierarchical model was performed to summarise the percent increase in mortality with a 1°C temperature increase (or decrease) with 95% confidence intervals in hot (or cold) days, with lagged effects also measured. Fifteen studies met the eligibility criteria and almost 13 million elderly deaths were included in this meta-analysis. In total, there was a 2-5% increase for a 1°C increment during hot temperature intervals, and a 1-2 % increase in all-cause mortality for a 1°C decrease during cold temperature intervals. Lags of up to 9 days in exposure to cold temperature intervals were substantially associated with all-cause mortality, but no substantial lagged effects were observed for hot intervals. Thus, both hot and cold temperatures substantially increased mortality among the elderly, but the magnitude of heat-related effects seemed to be larger than that of cold effects within a global context.

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.