Modeling prostate cancer: a perspective on transgenic mouse models

Despite considerable success in treatment of early stage localized prostate cancer (PC), acute inadequacy of late stage PC treatment and its inherent heterogeneity poses a formidable challenge. Clearly, an improved understanding of PC genesis and progression along with the development of new targeted therapies are warranted. Animal models, especially, transgenic immunocompetent mouse models, have proven to be the best ally in this respect. A series of models have been developed by modulation of expression of genes implicated in cancer-genesis and progression; mainly, modulation of expression of oncogenes, steroid hormone receptors, growth factors and their receptors, cell cycle and apoptosis regulators, and tumor suppressor genes have been used. Such models have contributed significantly to our understanding of the molecular and pathological aspects of PC initiation and progression. In particular, the transgenic mouse models based on multiple genetic alterations can more accurately address the inherent complexity of PC, not only in revealing the mechanisms of tumorigenesis and progression but also for clinically relevant evaluation of new therapies. Further, with advances in conditional knockout technologies, otherwise embryonically lethal gene changes can be incorporated leading to the development of new generation transgenics, thus adding significantly to our existing knowledge base. Different models and their relevance to PC research are discussed.

Long term survival following the detection of circulating tumour cells in head and neck squamous cell carcinoma

Background Techniques for detecting circulating tumor cells in the peripheral blood of patients with head and neck cancers may identify individuals likely to benefit from early systemic treatment. Methods Reconstruction experiments were used to optimise immunomagnetic enrichment and RT-PCR detection of circulating tumor cells using four markers (ELF3, CK19, EGFR and EphB4). This method was then tested in a pilot study using samples from 16 patients with advanced head and neck carcinomas. Results Seven patients were positive for circulating tumour cells both prior to and after surgery, 4 patients were positive prior to but not after surgery, 3 patients were positive after but not prior to surgery and 2 patients were negative. Two patients tested positive for circulating cells but there was no other evidence of tumor spread. Given this patient cohort had mostly advanced disease, as expected the detection of circulating tumour cells was not associated with significant differences in overall or disease free survival. Conclusion For the first time, we show that almost all patients with advanced head and neck cancers have circulating cells at the time of surgery. The clinical application of techniques for detection of spreading disease, such as the immunomagnetic enrichment RT-PCR analysis used in this study, should be explored further.

Equity in the twenty-first century

Issues of equity and inequity have always been part of employment relations and are a fundamental part of the industrial landscape. For example, in most countries in the nineteenth century and a large part of the twentieth century women and members of ethnic groups (often a minority in the workforce) were barred from certain occupations, industries or work locations, and received less pay than the dominant male ethnic group for the same work. In recent decades attention has been focused on issues of equity between groups, predominantly women and different ethnic groups in the workforce. This has been embodied in industrial legislation, for example in equal pay for women and men, and frequently in specific equity legislation. In this way a whole new area of law and associated workplace practice has developed in many countries. Historically, employment relations and industrial relations research has not examined employment issues disaggregated by gender or ethnic group. Born out of concern with conflict and regulation at the workplace, studies tended to concentrate on white, male, unionized workers in manufacturing and heavy industry (Ackers, 2002, p. 4). The influential systems model crafted by Dunlop (1958) gave rise to The discipline’s preoccupation with the ‘problem of order’ [which] ensures the invisibility of women, not only because women have generally been less successful in mobilizing around their own needs and discontents, but more profoundly because this approach identifies the employment relationship as the ultimate source of power and conflict at work (Forrest, 1993, p. 410). While ‘the system approach does not deliberately exclude gender . . . by reproducing a very narrow research approach and understanding of issues of relevance for the research, gender is in general excluded or looked on as something of peripheral interest’ (Hansen, 2002, p. 198). However, long-lived patterns of gender segregation in occupations and industries, together with discriminatory access to work and social views about women and ethnic groups in the paid workforce, mean that the employment experience of women and ethnic groups is frequently quite different to that of men in the dominant ethnic group. Since the 1980s, research into women and employment has figured in the employment relations literature, but it is often relegated to a separate category in specific articles or book chapters, with women implicitly or explicitly seen as the atypical or exceptional worker (Hansen, 2002; Wajcman, 2000). The same conclusion can be reached for other groups with different labour force patterns and employment outcomes. This chapter proposes that awareness of equity issues is central to employment relations. Like industrial relations legislation and approaches, each country will have a unique set of equity policies and legislation, reflecting their history and culture. Yet while most books on employment and industrial relations deal with issues of equity in a separate chapter (most commonly on equity for women or more recently on ‘diversity’), the reality in the workplace is that all types of legislation and policies which impact on the wages and working conditions interact, and their impact cannot be disentangled one from another. When discussing equity in workplaces in the twenty-first century we are now faced with a plethora of different terms in English. Terms used include discrimination, equity, equal opportunity, affirmative action and diversity with all its variants (workplace diversity, managing diversity, and so on). There is a lack of agreed definitions, particularly when the terms are used outside of a legislative context. This ‘shifting linguistic terrain’ (Kennedy-Dubourdieu, 2006b, p. 3) varies from country to country and changes over time even within the one country. There is frequently a division made between equity and its related concepts and the range of expressions using the term ‘diversity’ (Wilson and Iles, 1999; Thomas and Ely, 1996). These present dilemmas for practitioners and researchers due to the amount and range of ideas prevalent – and the breadth of issues that are covered when we say ‘equity and diversity in employment’. To add to these dilemmas, the literature on equity and diversity has become bifurcated: the literature on workplace diversity/management diversity appears largely in the business literature while that on equity in employment appears frequently in legal and industrial relations journals. Workplaces of the twenty-first century differ from those of the nineteenth and twentieth century not only in the way they deal with individual and group differences but also in the way they interpret what are fair and equitable outcomes for different individuals and groups. These variations are the result of a range of social conditions, legislation and workplace constraints that have influenced the development of employment equity and the management of diversity. Attempts to achieve employment equity have primarily been dealt with through legislative means, and in the last fifty years this legislation has included elements of anti-discrimination, affirmative action, and equal employment opportunity in virtually all OECD countries (Mor Barak, 2005, pp. 17–52). Established on human rights and social justice principles, this legislation is based on the premise that systemic discrimination has and/or continues to exist in the labour force and particular groups of citizens have less advantageous employment outcomes. It is based on group identity, and employment equity programmes in general apply across all workplaces and are mandatory. The more recent notions of diversity in the workplace are based on ideas coming principally from the USA in the 1980s which have spread widely in the Western world since the 1990s. Broadly speaking, diversity ideas focus on individual differences either on their own or in concert with the idea of group differences. The diversity literature is based on a business case: that is diversity is profitable in a variety of ways for business, and generally lacks a social justice or human rights justification (Burgess et al., 2009, pp. 81–2). Managing diversity is represented at the organizational level as a voluntary and local programme. This chapter discusses some major models and theories for equity and diversity. It begins by charting the history of ideas about equity in employment and then briefly discusses what is meant by equality and equity. The chapter then analyses the major debates about the ways in which equity can be achieved. The more recent ideas about diversity are then discussed, including the history of these ideas and the principles which guide this concept. The following section discusses both major frameworks of equity and diversity. The chapter then raises some ways in which insights from the equity and diversity literature can inform employment relations. Finally, the future of equity and diversity ideas is discussed.

Performance analysis of business process models with advanced constructs

The importance of actively managing and analysing business processes is acknowledged more than ever in organisations nowadays. Business processes form an essential part of an organisation and their application areas are manifold. Most organisations keep records of various activities that have been carried out for auditing purposes, but they are rarely used for analysis purposes. This paper describes the design and implementation of a process analysis tool that replays, analyses and visualises a variety of performance metrics using a process definition and its corresponding execution logs. The replayer uses a YAWL process model example to demonstrate its capacity to support advanced language constructs.

Fourier active appearance models

Gaining invariance to camera and illumination variations has been a well investigated topic in Active Appearance Model (AAM) fitting literature. The major problem lies in the inability of the appearance parameters of the AAM to generalize to unseen conditions. An attractive approach for gaining invariance is to fit an AAM to a multiple filter response (e.g. Gabor) representation of the input image. Naively applying this concept with a traditional AAM is computationally prohibitive, especially as the number of filter responses increase. In this paper, we present a computationally efficient AAM fitting algorithm based on the Lucas-Kanade (LK) algorithm posed in the Fourier domain that affords invariance to both expression and illumination. We refer to this as a Fourier AAM (FAAM), and show that this method gives substantial improvement in person specific AAM fitting performance over traditional AAM fitting methods.

The impact of software-as-a-service on business models of leading software vendors : experiences from three exploratory case studies

The number of software vendors offering ‘Software-as-a-Service’ has been increasing in recent years. In the Software-as-a-Service model software is operated by the software vendor and delivered to the customer as a service. Existing business models and industry structures are challenged by the changes to the deployment and pricing model compared to traditional software. However, the full implications on the way companies create, deliver and capture value are not yet sufficiently analyzed. Current research is scattered on specific aspects, only a few studies provide a more holistic view of the impact from a business model perspective. For vendors it is, however, crucial to be aware of the potentially far reaching consequences of Software-as-a-Service. Therefore, a literature review and three exploratory case studies of leading software vendors are used to evaluate possible implications of Software-as-a-Service on business models. The results show an impact on all business model building blocks and highlight in particular the often less articulated impact on key activities, customer relationship and key partnerships for leading software vendors and show related challenges, for example, with regard to the integration of development and operations processes. The observed implications demonstrate the disruptive character of the concept and identify future research requirements.