Circulating tumour cells, their role in metastasis and their clinical utility in lung cancer

Circulating tumour cells (CTCs) have attracted much recent interest in cancer research as a potential biomarker and as a means of studying the process of metastasis. It has long been understood that metastasis is a hallmark of malignancy, and conceptual theories on the basis of metastasis from the nineteenth century foretold the existence of a tumour "seed" which is capable of establishing discrete tumours in the "soil" of distant organs. This prescient "seed and soil" hypothesis accurately predicted the existence of CTCs; microscopic tumour fragments in the blood, at least some of which are capable of forming metastases. However, it is only in recent years that reliable, reproducible methods of CTC detection and analysis have been developed. To date, the majority of studies have employed the CellSearch™ system (Veridex LLC), which is an immunomagnetic purification method. Other promising techniques include microfluidic filters, isolation of tumour cells by size using microporous polycarbonate filters and flow cytometry-based approaches. While many challenges still exist, the detection of CTCs in blood is becoming increasingly feasible, giving rise to some tantalizing questions about the use of CTCs as a potential biomarker. CTC enumeration has been used to guide prognosis in patients with metastatic disease, and to act as a surrogate marker for disease response during therapy. Other possible uses for CTC detection include prognostication in early stage patients, identifying patients requiring adjuvant therapy, or in surveillance, for the detection of relapsing disease. Another exciting possible use for CTC detection assays is the molecular and genetic characterization of CTCs to act as a "liquid biopsy" representative of the primary tumour. Indeed it has already been demonstrated that it is possible to detect HER2, KRAS and EGFR mutation status in breast, colon and lung cancer CTCs respectively. In the course of this review, we shall discuss the biology of CTCs and their role in metastagenesis, the most commonly used techniques for their detection and the evidence to date of their clinical utility, with particular reference to lung cancer.

Defining reference service life : an open innovation approach

The endeavour to obtain estimates of durability of components for use in lifecycle assessment or costing and infrastructure and maintenance planning systems is large. The factor method and the reference service life concept provide a very valuable structure, but do not resolve the central dilemma of the need to derive an extensive database of service life. Traditional methods of estimating service life, such as dose functions or degradation models, can play a role in developing this database, however the scale of the problem clearly indicates that individual dose functions cannot be derived for each component in each different local and geographic setting. Thus, a wider range of techniques is required in order to devise reference service life. This paper outlines the approaches being taken in the Cooperative Research Centre for Construction Innovation project to predict reference service life. Approaches include the development of fundamental degradation and microclimate models, the development of a situation-based reasoning ‘engine’ to vary the ‘estimator’ of service life, and the development of a database on expert performance (Delphi study). These methods should be viewed as complementary rather than as discrete alternatives. As discussed in the paper, the situation-based reasoning approach in fact has the possibility of encompassing all other methods.

Configurable reference modeling languages

This chapter discusses reference modelling languages for business systems analysis and design. In particular, it reports on reference models in the context of the design-for/by-reuse paradigm, explains how traditional modelling techniques fail to provide adequate conceptual expressiveness to allow for easy model reuse by configuration or adaptation and elaborates on the need for reference modelling languages to be configurable. We discuss requirements for and the development of reference modelling languages that reflect the need for configurability. Exemplarily, we report on the development, definition and configuration of configurable event-driven process chains. We further outline how configurable reference modelling languages and the corresponding design principles can be used in future scenarios such as process mining and data modelling.

QoS-aware reference station placement for regional network RTK

Network RTK (Real-Time Kinematic) is a technology that is based on GPS (Global Positioning System) or more generally on GNSS (Global Navigation Satellite System) measurements to achieve centimeter-level accuracy positioning in real-time. Reference station placement is an important problem in the design and deployment of network RTK systems as it directly affects the quality of the positioning service and the cost of the network RTK systems. This paper identifies a new reference station placement for network RTK, namely QoS-aware regional network RTK reference station placement problem, and proposes an algorithm for the new reference station placement problem. The algorithm can always produce a reference station placement solution that completely covers the region of network RTK.

University library virtual reference services : best practices and continuous improvement

The inclusion or not of chat services within Virtual Reference (VR) is an important topic for university libraries. Increasingly, email supported by a Frequently Asked Questions (FAQ) database is suggested in the scholarly literature as the preferred, cost-effective means for providing university VR services. This paper examines these issues and identifies some best practices for university library VR services relating to chat and email service, collaborative service provision, services staffing, and staff training. Further studies are required to more completely identify best practices for the complete range of VR services.

Towards a reference model for SOA governance (extended version)

Although the lack of elaborate governance mechanisms is often seen as the main reason for failures of SOA projects, SOA governance is still very low in maturity. In this paper, we follow a design science approach to address this drawback by presenting a framework that can guide organisations in implementing a governance approach for SOA more successfully. We have reviewed the highly advanced IT governance frameworks Cobit and ITIL and mapped them to the SOA domain. The resulting blueprint for an SOA governance framework was refined based on a detailed literature review, expert interviews and a practical application in a government organisation. The proposed framework stresses the need for business representatives to get involved in SOA decisions and to define benefits ownership for services.

On the use of different spatial reference frames for movement control

Previous work has shown that amplitude and direction are two independently controlled parameters of aimed arm movements, and performance, therefore, suffers when they must be decomposed into Cartesian coordinates. We now compare decomposition into different coordinate systems. Subjects pointed at visual targets in 2-D with a cursor, using a two-axis joystick or two single-axis joysticks. In the latter case, joystick axes were aligned with the subjects’ body axes, were rotated by –45°, or were oblique (i.e., one axis was in an egocentric frame and the other was rotated by –45°). Cursor direction always corresponded to joystick direction. We found that compared with the two-axis joystick, responses with single-axis joysticks were slower and less accurate when the axes were oriented egocentrically; the deficit was even more pronounced when the axes were rotated and was most pronounced when they were oblique. This confirms that decomposition of motor commands is computationally demanding and documents that this demand is lowest for egocentric, higher for rotated, and highest for oblique coordinates. We conclude that most current vehicles use computationally demanding man–machine interfaces.