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.

Streptococcus pneumoniae infection suppresses allergic airways disease by inducing regulatory T cells

An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD). Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed. Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment. Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae.

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.

Self-reported driving difficulty by persons with Hemianopia and Quadrantanopia

Purpose: To compare self-reported driving difficulty by persons with hemianopic or quadrantanopic field loss with that reported by age-matched drivers with normal visual fields; and to examine how their self- reported driving difficulty compares to ratings of driving performance provided by a certified driving rehabilitation specialist(CDRS). Method: Participants were 17 persons with hemianopic field loss, 7 with quadrantanopic loss, and 24 age-matched controls with normal visual fields, all of whom had current drivers’ licenses. Information was collected via questionnaire regarding driving difficulties experienced in 21 typical driving situations grouped into 3 categories(involvement of peripheral vision, low visibility conditions, and independent mobility). On-road driving performance was evaluated by a CDRS using a standard assessment scale. Results: Drivers with hemianopic and quadrantanopic field loss expressed significantly more difficulty with driving maneuvers involving peripheral vision and independent mobility, compared to those with normal visual fields. Drivers with hemianopia and quadrantanopia who were rated as unsafe to drive based upon an on-road assessment by the CDRS were no more likely to report driving difficulty than those rated as safe. Conclusion: This study highlights aspects of driving that hemianopic or quadrantanopic persons find particularly problematic, thus suggesting areas that could be focused on driving rehabilitation. Some drivers with hemianopia or quadrantanopia may inappropriately view themselves as good drivers when in fact their driving performance is unsafe as judged by a driving professional.

Risk of second cancer after lymphohematopoietic neoplasm

People living with lymphohematopoietic neoplasms (LHNs) are known to have increased risks of second cancer; however, the incidence of second cancers after LHNs has not been studied extensively in Australia. The Australian Cancer Database was used to analyze site-specific risk of second primary cancer after LHNs in 127,707 patients diagnosed between 1983 and 2005. Standardized incidence ratios (SIRs) were calculated using population rates. Overall, patients with an LHN had nearly twice the risk of developing a second cancer compared to the Australian population. Among 40,321 patients with non-Hodgkin's lymphoma (NHL), there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, connective tissue and peripheral nerves, eye, thyroid, Hodgkin's disease (HD) and myeloid leukemia. Among 6,396 patients with HD, there was over a fourfold significant increase in melanoma, Kaposi sarcoma, cancer of the lip, oral cavity and pharynx, female breast, uterine cervix, testis, thyroid, NHL and myeloid leukemia. Among the 33,025 patients with lymphoid and myeloid leukemia, significant excess were seen for cancers of the lip, eye, connective tissue and peripheral nerves, NHL and HD. Among the 13,856 patients with plasma cell tumors, there was over fourfold significant increase for melanoma, cancer of the connective tissue and peripheral nerves and myeloid leukemia. Our findings provide evidence of an increased risk of cancer, particularly ultraviolet radiation- and immunosuppression-related cancers, after an LHN in Australia. Copyright © 2010 UICC.

Interactive processes link the multiple symptoms of fatigue in sport competition

Muscle physiologists often describe fatigue simply as a decline of muscle force and infer this causes an athlete to slow down. In contrast, exercise scientists describe fatigue during sport competition more holistically as an exercise-induced impairment of performance. The aim of this review is to reconcile the different views by evaluating the many performance symptoms/measures and mechanisms of fatigue. We describe how fatigue is assessed with muscle, exercise or competition performance measures. Muscle performance (single muscle test measures) declines due to peripheral fatigue (reduced muscle cell force) and/or central fatigue (reduced motor drive from the CNS). Peak muscle force seldom falls by >30% during sport but is often exacerbated during electrical stimulation and laboratory exercise tasks. Exercise performance (whole-body exercise test measures) reveals impaired physical/technical abilities and subjective fatigue sensations. Exercise intensity is initially sustained by recruitment of new motor units and help from synergistic muscles before it declines. Technique/motor skill execution deviates as exercise proceeds to maintain outcomes before they deteriorate, e.g. reduced accuracy or velocity. The sensation of fatigue incorporates an elevated rating of perceived exertion (RPE) during submaximal tasks, due to a combination of peripheral and higher CNS inputs. Competition performance (sport symptoms) is affected more by decision-making and psychological aspects, since there are opponents and a greater importance on the result. Laboratory based decision making is generally faster or unimpaired. Motivation, self-efficacy and anxiety can change during exercise to modify RPE and, hence, alter physical performance. Symptoms of fatigue during racing, team-game or racquet sports are largely anecdotal, but sometimes assessed with time-motion analysis. Fatigue during brief all-out racing is described biomechanically as a decline of peak velocity, along with altered kinematic components. Longer sport events involve pacing strategies, central and peripheral fatigue contributions and elevated RPE. During match play, the work rate can decline late in a match (or tournament) and/or transiently after intense exercise bursts. Repeated sprint ability, agility and leg strength become slightly impaired. Technique outcomes, such as velocity and accuracy for throwing, passing, hitting and kicking, can deteriorate. Physical and subjective changes are both less severe in real rather than simulated sport activities. Little objective evidence exists to support exercise-induced mental lapses during sport. A model depicting mind-body interactions during sport competition shows that the RPE centre-motor cortex-working muscle sequence drives overall performance levels and, hence, fatigue symptoms. The sporting outputs from this sequence can be modulated by interactions with muscle afferent and circulatory feedback, psychological and decision-making inputs. Importantly, compensatory processes exist at many levels to protect against performance decrements. Small changes of putative fatigue factors can also be protective. We show that individual fatigue factors including diminished carbohydrate availability, elevated serotonin, hypoxia, acidosis, hyperkalaemia, hyperthermia, dehydration and reactive oxygen species, each contribute to several fatigue symptoms. Thus, multiple symptoms of fatigue can occur simultaneously and the underlying mechanisms overlap and interact. Based on this understanding, we reinforce the proposal that fatigue is best described globally as an exercise-induced decline of performance as this is inclusive of all viewpoints.

The knock-on from the knock-off : recent shifts within Australian mass market fashion design practice

Australia’s mass market fashion labels have traditionally benefitted from their peripheral location to the world’s fashion centres. Operating a season behind, Australian mass market designers and buyers were well-placed to watch trends play out overseas before testing them in the Australian marketplace. For this reason, often a designer’s role was to source and oversee the manufacture of ‘knock-offs’, or close copies of Northern hemisphere mass market garments. Both Weller (2007) and Walsh (2009) have commented on this practice. The knock-on effect from this continues to be a cautious, derivative fashion sensibility within Australian mass market fashion design, where any new trend or product is first tested and proved overseas months earlier. However, there is evidence that this is changing. The rapid online dissemination of global fashion trends, coupled with the Australian consumer’s willingness to shop online, has meant that the ‘knock-off’ is less viable. For this reason, a number of mass market companies are moving away from the practice of direct sourcing and are developing product in-house under a Northern hemisphere model. This shift is also witnessed in the trend for mass market companies to develop collections in partnership with independent Australian designers. This paper explores the current and potential effects of these shifts within Australian mass market design practice, and discusses how they may impact on designers, consumers and on the wider culture of Australian fashion.

Inward internationalization of services : Exploring satisfaction and dissatisfaction of overseas students in Australia

Most research has assessed the outward internationalization process of service firms and less is known in the literature about the inward internationalization of services, or companies that provide the service to overseas customers in the domestic market (i.e., tourism, education, healthcare). Specifically, there is scant research looking at the overseas customer perspective. This study attempts to identify the main drivers of satisfaction and dissatisfaction for overseas customers. The critical incident technique (CIT) method was used to collect and analyse the data. A total of 107 critical incidents regarding drivers of satisfaction and dissatisfaction for overseas customers in a higher educational service context were collected. Findings of this study show that drivers of service satisfaction and dissatisfaction for overseas customers derive from elements of the core service and peripheral service. However, the findings show that elements of the peripheral service (living environment, socialization and interaction with others, and personal performance) are more important for international students.

The ghrelin signalling system is involved in the consumption of sweets

The gastric-derived orexigenic peptide ghrelin affects brain circuits involved in energy balance as well as in reward. Indeed, ghrelin activates an important reward circuit involved in natural- as well as drug-induced reward, the cholinergic-dopaminergic reward link. It has been hypothesized that there is a common reward mechanism for alcohol and sweet substances in both animals and humans. Alcohol dependent individuals have higher craving for sweets than do healthy controls and the hedonic response to sweet taste may, at least in part, depend on genetic factors. Rat selectively bred for high sucrose intake have higher alcohol consumption than non-sucrose preferring rats and vice versa. In the present study a group of alcohol-consuming individuals selected from a population cohort was investigated for genetic variants of the ghrelin signalling system in relation to both their alcohol and sucrose consumption. Moreover, the effects of GHS-R1A antagonism on voluntary sucrose- intake and operant self-administration, as well as saccharin intake were investigated in preclinical studies using rodents. The effects of peripheral grelin administration on sucrose intake were also examined. Here we found associations with the ghrelin gene haplotypes and increased sucrose consumption, and a trend for the same association was seen in the high alcohol consumers. The preclinical data show that a GHS-R1A antagonist reduces the intake and self-administration of sucrose in rats as well as saccharin intake in mice. Further, ghrelin increases the intake of sucrose in rats. Collectively, our data provide a clear indication that the GHS-R1A antagonists reduces and ghrelin increases the intake of rewarding substances and hence, the central ghrelin signalling system provides a novel target for the development of drug strategies to treat addictive behaviours. © 2011 Landgren et al.

The role of near adaptation in myopia development

Prolonged near work is associated with myopia development in children and young adults but the reason underlying this association is unknown. Two potentially important factors are the near work induced ocular adaptations of contrast and accommodative adaptation. This study measured the degrees of contrast and accommodative adaptation during and following reading in myopic and emmetropic children and young adults in Singapore, where myopia is highly prevalent. Reading caused significantly greater contrast and accommodative adaptations in myopic children and myopic young adults compared to that measured in emmetropes of comparable ages. The adaptations were greater in magnitude in children than young adults, suggesting that children are more susceptible to ocular changes induced by reading and thus are potentially at greater risk of adverse refractive outcomes from these adaptations. In addition to the magnitude of the adaptations the regression time of these adaptations, (i.e. their durations) are also important. Longer accommodative adaptation regression times were measured for myopic children than for emmetropic children. Although the regression of contrast adaptation was not measured, its duration may likewise be important. The refractive effects of both of these adaptations are likely to be cumulative across the day and this could promote myopia in susceptible individuals performing considerable amounts of near work. Whether the type of text read affected the magnitude of the adaptations was also explored. Given the high prevalence of myopia in Chinese children and the fact that Chinese text is more complicated to write than English text, it was hypothesized that Chinese text would induce greater adaptation. However, both Chinese and English text produced similar amounts of accommodative and contrast adaptation in young adult subjects. We propose that children who spend prolonged periods reading at a young age are most vulnerable to near work induced adaptations and hence near work induced myopia. Both Chinese and English texts produce these effects and we propose that these adaptations are likely to occur for all types of common reading texts.

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.

Action research as foresight methodology

To the action researcher, who laboriously spends his or her hours working within the local contexts of communities or organisations to co-generate meaningful research, and who’s theories are hardened on the anvil of creating meaningful social change; futures studies might seem the discipline the most peripheral to its interests, and the most ill equipped to deal with the local and intimate domain of community existence. To the futurist, who laboriously spends his or her hours understanding the nuances of history and social change, who through persistent work, begins to make sense of the weak signals and the subtle shifts, action research would seem as simply an auxiliary field, inappropriate for understanding the greater scheme. I invite the reader, however, whether they belong to one camp or the other, to let go of their respective disciplinary perspectives, and see both belonging to each other. [Introduction] .

Investigation to enhance high speed rail accessibility

High Speed Rail (HSR) is rapidly gaining popularity worldwide as a safe and efficient transport option for long-distance travel. Designed to win market shares from air transport, HSR systems optimise their productivity between increasing speeds and station spacing to offer high quality service and gain ridership. Recent studies have investigated the effects that the deployment of HSR infrastructure has on spatial distribution and the economic development of cities and regions. Findings appear mostly positive at higher geographical scales, where HSR links connect major urban centres several hundred kilometres apart and already well positioned within a national or international context. Also, at the urban level, studies have shown regeneration and concentration effects around HSR station areas with positive returns on city’s image and economy. However, doubts persist on the effects of HSR at an intermediate scale, where the accessibility trade off on station spacing limits access to many small and medium agglomerations. Thereby, their ability to participate in the development opportunities facilitated by HSR infrastructure is significantly reduced. The locational advantages deriving from transport improvements appear contrasting especially in regions that tend to have a polycentric structure, where cities may present greater accessibility disparities between those served by HSR and those left behind. This thesis fits in this context where intermediate and regional cities do not directly enjoy the presence of an HSR station while having an existing or planned proximate HSR corridor. With the aim of understanding whether there might be a solution to this apparent incongruity, the research investigates strategies to integrate HSR accessibility at the regional level. While current literature recommends to commit with ancillary investments to the uplift of station areas and the renewal of feeder systems, I hypothesised the interoperability between the HSR and the conventional networks to explore the possibilities offered by mixed traffic and infrastructure sharing. Thus, I developed a methodology to quantify the exchange of benefits deriving from this synergistic interaction. In this way, it was possible to understand which level of service quality offered by alternative transit strategies best facilitates the distribution of accessibility benefits for areas far from actual HSR stations. Therefore, strategies were selected for their type of service capable of regional extensions and urban penetrations, while incorporating a combination of specific advantages (e.g. speed, sub-urbanity, capacity, frequency and automation) in order to emulate HSR quality with increasingly efficient services. The North-eastern Italian macro region was selected as case study to ground the research offering concurrently a peripheral polycentric metropolitan form, the presence of a planned HSR corridor with some portions of HSR infrastructure implementation, and the project to develop a suburban rail service extended regionally. Results show significant distributive potential, in terms of network effects produced in relation with HSR, in increasing proportions for all the strategies considered: a regional metro rail strategy (abbreviated RMR), a regional high speed rail strategy (abbreviated RHSR), a regional light rail transit (abbreviated LRT) strategy, and a non-stopping continuous railway system (abbreviated CRS) strategy. The provision of additional tools to value HSR infrastructure against its accessibility benefits and their regional distribution through alternative strategies beyond the actual HSR stations, would have great implications, both politically and technically, in moving towards new dimensions of HSR evaluation and development.