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.

Access and Quality of Heart Failure Management Programs in Australia

Background/aim In response to the high burden of disease associated with chronic heart failure (CHF), in particular the high rates of hospital admissions, dedicated CHF management programs (CHF-MP) have been developed. Over the past five years there has been a rapid growth of CHF-MPs in Australia. Given the apparent mismatch between the demand for, and availability of CHF-MPs, this paper has been designed to discuss the accessibility to and quality of current CHF-MPs in Australia. Methods The data presented in this report has been combined from the research of the co-authors, in particular a review of the inequities in access to chronic heart failure which utilised geographical information systems (GIS) and the survey of heterogeneity in quality and service provision in Australian. Results Of the 62 CHF-MPs surveyed in this study 93% (58) centres had been located areas that are rated as Highly Accessible. This result indicated that most of the CHF-MPs have been located in capital cities or large regional cities. Six percent (4 CHF-MPs) had been located in Accessible areas which were country towns or cities. No CHF-MPs had been established outside of cities to service the estimated 72,000 individuals with CHF living in rural and remote areas. 16% of programs recruited NYHA Class I patients and of these 20% lacked confirmation (echocardiogram) of their diagnosis. Conclusion Overall, these data highlight the urgent need to provide equitable access to CHF-MP's. When establishing CHF-MPs consideration of current evidence based models to ensure quality in practice.

Collaborative destination branding : planning for tourism development through design in the Waterfall Way, NSW, Australia

This thesis develops, applies and analyses a collaborative design methodology for branding a tourism destination. The area between the Northern Tablelands and the Mid-North Coast of New South Wales, Australia, was used as a case study for this research. The study applies theoretical concepts of systems thinking and complexity to the real world, and tests the use of design as a social tool to engage multiple stakeholders in planning. In this research I acknowledge that places (and destinations) are socially constructed through people's interactions with their physical and social environments. This study explores a methodology that is explicit about the uncertainties of the destination’s system, and that helps to elicit knowledge and system trends. The collective design process used the creation of brand concepts, elements and strategies as instruments to directly engage stakeholders in the process of reflecting about their places and the issues related to tourism activity in the region. The methods applied included individual conversations and collaborative design sessions to elicit knowledge from local stakeholders. Concept maps were used to register and interpret information released throughout the process. An important aspect of the methodology was to bring together different stakeholder groups and translate the information into a common language that was understandable by all participants. This work helped release significant information as to what kind of tourism activity local stakeholders are prepared to receive and support. It also helped the emergence of a more unified regional identity. The outcomes delivered by the project (brand, communication material and strategies) were of high quality and in line with the desires and expectation of the local hosts. The process also reinforced local sense of pride, belonging and conservation. Furthermore, interaction between participants from different parts of the region triggered some self organising activity around the brand they created together. A major contribution of the present work is the articulation of an inclusive methodology to facilitate the involvement of locals into the decision-making process related to tourism planning. Of particular significance is the focus on the social construction of meaning in and through design, showing that design exercises can have significant social impact – not only on the final product, but also on the realities of the people involved in the creative process.

High performance additive manufactured scaffolds for bone tissue engineering application

This study demonstrates the feasibility of additive manufactured poly(3-caprolactone)/silanized tricalcium phosphate (PCL/TCP(Si)) scaffolds coated with carbonated hydroxyapatite (CHA)-gelatin composite for bone tissue engineering. In order to reinforce PCL/TCP scaffolds to match the mechanical properties of cancellous bone, TCP has been modified with 3-glycidoxypropyl trimethoxysilane (GPTMS) and incorporated into PCL to synthesize a PCL/TCP(Si) composite. The successful modification is confirmed by X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) analysis. Additive manufactured PCL/TCP(Si) scaffolds have been fabricated using a screw extrusion system (SES). Compression testing demonstrates that both the compressive modulus and compressive yield strength of the developed PCL/TCP(Si) scaffolds fall within the lower ranges of mechanical properties for cancellous bone, with a compressive modulus and compressive yield strength of 6.0 times and 2.3 times of those of PCL/TCP scaffolds, respectively. To enhance the osteoconductive property of the developed PCL/TCP(Si) scaffolds, a CHA-gelatin composite has been coated onto the scaffolds via a biomimetic co-precipitation process, which is verified by using scanning electron microscopy (SEM) and XPS. Confocal laser microscopy and SEM images reveal a most uniform distribution of porcine bone marrow stromal cells (BMSCs) and cellsheet accumulation on the CHA-gelatin composite coated PCL/TCP(Si) scaffolds. The proliferation rate of BMSCs on the CHA-gelatin composite coated PCL/TCP(Si) scaffolds is 2.0 and 1.4 times higher compared to PCL/TCP(Si) and CHA coated PCL/TCP(Si) scaffolds, respectively, by day 10. Furthermore, the reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses reveal that CHA-gelatin composite coated PCL/TCP(Si) scaffolds stimulate osteogenic differentiation of BMSCs the most compared to the other scaffolds. In vitro results of SEM, confocal microscopy and proliferation rate also show that there is no detrimental effect of GPTMS modification on biocompatibility of the scaffolds.

High-density lipoprotein and the risk of recurrent venous thromboembolism

BACKGROUND - High-density lipoprotein (HDL) protects against arterial atherothrombosis, but it is unknown whether it protects against recurrent venous thromboembolism. METHODS AND RESULTS - We studied 772 patients after a first spontaneous venous thromboembolism (average follow-up 48 months) and recorded the end point of symptomatic recurrent venous thromboembolism, which developed in 100 of the 772 patients. The relationship between plasma lipoprotein parameters and recurrence was evaluated. Plasma apolipoproteins AI and B were measured by immunoassays for all subjects. Compared with those without recurrence, patients with recurrence had lower mean (±SD) levels of apolipoprotein AI (1.12±0.22 versus 1.23±0.27 mg/mL, P<0.001) but similar apolipoprotein B levels. The relative risk of recurrence was 0.87 (95% CI, 0.80 to 0.94) for each increase of 0.1 mg/mL in plasma apolipoprotein AI. Compared with patients with apolipoprotein AI levels in the lowest tertile (<1.07 mg/mL), the relative risk of recurrence was 0.46 (95% CI, 0.27 to 0.77) for the highest-tertile patients (apolipoprotein AI >1.30 mg/mL) and 0.78 (95% CI, 0.50 to 1.22) for midtertile patients (apolipoprotein AI of 1.07 to 1.30 mg/mL). Using nuclear magnetic resonance, we determined the levels of 10 major lipoprotein subclasses and HDL cholesterol for 71 patients with recurrence and 142 matched patients without recurrence. We found a strong trend for association between recurrence and low levels of HDL particles and HDL cholesterol. CONCLUSIONS - Patients with high levels of apolipoprotein AI and HDL have a decreased risk of recurrent venous thromboembolism. © 2007 American Heart Association, Inc.

High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men

Background-Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients. Methods and Results-We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoproteins AI and B in blood samples from 49 male venous thrombosis patients and matched controls aged <55 years. Venous thrombosis patients had significantly lower levels of HDL particles, large HDL particles, HDL cholesterol, and apolipoprotein AI and significantly higher levels of LDL particles and small LDL particles. The quartile-based odds ratios for decreased HDL particle and apolipoprotein AI levels in patients compared with controls were 6.5 and 6.0 (95% CI, 2.3 to 19 and 2.1 to 17), respectively. Odds ratios for apolipoprotein B/apolipoprotein AI ratio and LDL cholesterol/HDL cholesterol ratio were 6.3 and 2.7 (95% CI, 1.9 to 21 and 1.1 to 6.5), respectively. When polymorphisms in genes for hepatic lipase, endothelial lipase, and cholesteryl ester transfer protein were analyzed, patients differed significantly from controls in the allelic frequency for the TaqI B1/B2 polymorphism in cholesteryl ester transfer protein, consistent with the observed pattern of lower HDL and higher LDL. Conclusions-Venous thrombosis in men aged <55 years old is associated with dyslipoproteinemia involving lower levels of HDL particles, elevated levels of small LDL particles, and an elevated ratio of apolipoprotein B/apolipoprotein AI. This dyslipoproteinemia seems associated with a related cholesteryl ester transfer protein genotype difference. © 2005 American Heart Association, Inc.

Use of virtual index for measuring efficiency of innovation systems : a cross-country study

In this study we propose a virtual index for measuring the relative innovativeness of countries. Using a multistage virtual benchmarking process, the best and rational benchmark is extracted for inefficient ISs. Furthermore, Tobit and Ordinary Least Squares (OLS) regression models are used to investigate the likelihood of changes in inefficiencies by investigating country-specific factors. The empirical results relating to the virtual benchmarking process suggest that the OLS regression model would better explain changes in the performance of innovation- inefficient countries.

Unlicensed drivers : are they high risk?

- Road safety implications of unlicensed driving - Present results from three studies examining: the crash involvement of unlicensed drivers; the impact of licence disqualification on offending; characteristics of unlicensed driving offenders - Countermeasure implications - Discussion of high-risk groups and innovative countermeasure options

Closing the gap between bandit and full-information online optimization : high-probability regret bound

We demonstrate a modification of the algorithm of Dani et al for the online linear optimization problem in the bandit setting, which allows us to achieve an O( \sqrt{T ln T} ) regret bound in high probability against an adaptive adversary, as opposed to the in expectation result against an oblivious adversary of Dani et al. We obtain the same dependence on the dimension as that exhibited by Dani et al. The results of this paper rest firmly on those of Dani et al and the remarkable technique of Auer et al for obtaining high-probability bounds via optimistic estimates. This paper answers an open question: it eliminates the gap between the high-probability bounds obtained in the full-information vs bandit settings.