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.

Gaussian process models for sensor-centric robot localisation

This paper presents an approach to building an observation likelihood function from a set of sparse, noisy training observations taken from known locations by a sensor with no obvious geometric model. The basic approach is to fit an interpolant to the training data, representing the expected observation, and to assume additive sensor noise. This paper takes a Bayesian view of the problem, maintaining a posterior over interpolants rather than simply the maximum-likelihood interpolant, giving a measure of uncertainty in the map at any point. This is done using a Gaussian process framework. To validate the approach experimentally, a model of an environment is built using observations from an omni-directional camera. After a model has been built from the training data, a particle filter is used to localise while traversing this environment

Identification of selection criteria for operational variations of the design-build system : a delphi study in China

The design-build (DB) system has been demonstrated as an effective delivery method and has gained popularity worldwide. However it is observed that a number of operational variations of DB system have emerged since the last decade to cater for different client’s requirements. After the client decides to procure his project through the DB system, he still has to choose an appropriate configuration to deliver their projects optimally. However, there is little research on the selection of DB operational variations. One of the main reasons for this is the lack of evaluation criteria for determining the appropriateness of each operational variation. To obtain such criteria, a three-round Delphi survey has been conducted with 20 construction experts in the People’s Republic of China (PRC). Seven top selection criteria were identified. These are: (1) availability of competent design-builders; (2) client’s capabilities; (3) project complexity; (4) client’s control of project; (5) early commencement & short duration; (6) reduced responsibility or involvement; and (7) clearly defined end user’s requirements. These selection criteria were found to have a statistically significant agreement. These findings may furnish various stakeholders, DB clients in particular, with better insight to understand and compare the different operational variations of the DB system.

Identification of key competences of design-builders in the construction market of the People’s Republic of China (PRC)

Design-builders play a vital role in the success of DB projects. In the construction market of the People’s Republic of China, most of the design-builders, however, lack adequate competences to conduct the DB projects successfully. The objective of this study is, therefore, to identify the key competences that design-builders should possess to not only ensure the success of DB projects but also acquire the competitive advantages in the DB market. Five semi-structured face-to-face interviews and two rounds of Delphi questionnaire survey were conducted to identify the key competences of design-builders. Rankings have been assigned to these key competences on the basis of their relative importance. Six ranked key competences of design-builders have been identified, which are, namely, (1) experience with similar DB projects; (2) capability of corporate management; (3) combination of building techniques and design expertise; (4) financial capability for DB projects; (5) enterprise qualification and scale; and (6) credit records and reputation in the industry. The design-builders can make use of the research findings as guidelines to improve their DB competence. These research findings will also be useful to clients during the selection of design-builders.

Identification of key competences of DB clients in the construction market of China

The design-build system has been demonstrated as an effective delivery method and gained popularity worldwide. Although there are an increasing number of clients adopting DB method in China, most of them remain inexperienced with method. The objective of this study is therefore to identify the key competences that a client or its consultant should possess to ensure the success of DB projects. Face-to-face interviews and a two-round Delphi questionnaire survey were conducted to find the following six key competences of clients, which include the (1) ability to clearly articulate project scope and objectives; (2) financial capacity for DB projects; (3) capability in contract management; (4) adequate staff or consulting team; (5) effective coordination with contractors and (6) experience with similar DB projects. This study will hopefully provide clients with measures to evaluate their DB competence and further promote their understanding of DB system in the PRC.

A longitudinal assessment of chronic wound fluid to detect biochemical indicators of healing

Chronic venous leg ulcers are a detrimental health issue plaguing our society, resulting in long term pain, immobility and decreased quality of life for a large proportion of sufferers. The frequency of these chronic wounds has led current research to focus on the wound environment to provide important information regarding the prolonged, fluctuated or static healing patterns of these wounds. Disruption to the normal wound healing process results in release of multiple factors in the wound environment that could correlate to wound chronicity. These biochemical factors can often be detected through non-invasively sampling chronic wound fluid (CWF) from the site of injury. Of note, whilst there are numerous studies comparing acute and chronic wound fluids, there have not been any reports in the literature employing a longitudinal study in order to track biochemical changes in wound fluid as patients transition from a non-healing to healed state. Initially the objective of this study was to identify biochemical changes in CWF associated with wound healing using a proteomic approach. The proteomic approach incorporated a multi-dimensional liquid chromatography fractionation technique coupled with mass spectrometry (MS) to enable identification of proteins present in lower concentrations in CWF. Not surprisingly, many of the proteins identified in wound fluid were acute phase proteins normally expressed during the inflammatory phase of healing. However, the number of proteins positively identified by MS was quite low. This was attributed to the diverse range in concentration of protein species in CWF making it challenging to detect the diagnostically relevant low molecular weight proteins. In view of this, SELDI-TOF MS was also explored as a means to target low molecular weight proteins in sequential patient CWF samples during the course of healing. Unfortunately, the results generated did not yield any peaks of interest that were altered as wounds transitioned to a healed state. During the course of proteomic assessment of CWF, it became evident that a fraction of non-proteinaceous compounds strongly absorbed at 280 nm. Subsequent analyses confirmed that most of these compounds were in fact part of the purine catabolic pathway, possessing distinctive aromatic rings and which results in high absorbance at 254 nm. The accumulation of these purinogenic compounds in CWF suggests that the wound bed is poorly oxygenated resulting in a switch to anaerobic metabolism and consequently ATP breakdown. In addition, the presence of the terminal purine catabolite, uric acid (UA), indicates that the enzyme xanthine oxidoreductase (XOR) catalyses the reaction of hypoxanthine to xanthine and finally to UA. More importantly, the studies provide evidence for the first time of the exogenous presence of XOR in CWF. XOR is the only enzyme in humans capable of catalysing the production of UA in conjunction with a burst of the highly reactive superoxide radical and other oxidants like H2O2. Excessive release of these free radicals in the wound environment can cause cellular damage disrupting the normal wound healing process. In view of this, a sensitive and specific assay was established for monitoring low concentrations of these catabolites in CWF. This procedure involved combining high performance liquid chromatography (HPLC) with tandem mass spectrometry and multiple reaction monitoring (MRM). This application was selective, using specific MRM transitions and HPLC separations for each analyte, making it ideal for the detection and quantitation of purine catabolites in CWF. The results demonstrated that elevated levels of UA were detected in wound fluid obtained from patients with clinically worse ulcers. This suggests that XOR is active in the wound site generating significant amounts of reactive oxygen species (ROS). In addition, analysis of the amount of purine precursors in wound fluid revealed elevated levels of purine precursors in wound fluid from patients with less severe ulcers. Taken together, the results generated in this thesis suggest that monitoring changes of purine catabolites in CWF is likely to provide valuable information regarding the healing patterns of chronic venous leg ulcers. XOR catalysis of purine precursors not only provides a method for monitoring the onset, prognosis and progress of chronic venous leg ulcers, but also provides a potential therapeutic target by inhibiting XOR, thus blocking UA and ROS production. Targeting a combination of these purinogenic compounds and XOR could lead to the development of novel point of care diagnostic tests. Therefore, further investigation of these processes during wound healing will be worthwhile and may assist in elucidating the pathogenesis of this disease state, which in turn may lead to the development of new diagnostics and therapies that target these processes.

A process evaluation of a comprehensive school based injury prevention program

A process evaluation enables understanding of critical issues that can inform the improved, ongoing implementation of an intervention program. This study describes the process evaluation of a comprehensive, multi-level injury prevention program for adolescents. The program targets change in injury associated with violence, transport and alcohol risks and incorporates two primary elements: an 8-week, teacher delivered attitude and behaviour change curriculum for Grade 8 students; and a professional development program for teachers on school level methods of protection, focusing on strategies to increase students’ connectedness to school.

A sequence analytic model of entrepreneurial discovery and exploitation process

This study examined the effect that temporal order within the entrepreneurial discovery exploitation process has on the outcomes of venture creation. Consistent with sequential theories of discovery-exploitation, the general flow of venture creation was found to be directed from discovery toward exploitation in a random sample of nascent ventures. However, venture creation attempts which specifically follow this sequence derive poor outcomes. Moreover, simultaneous discovery-exploitation was the most prevalent temporal order observed, and venture attempts that proceed in this manner more likely become operational. These findings suggest that venture creation is a multi-scale phenomenon that is at once directional in time, and simultaneously driven by symbiotically coupled discovery and exploitation.

From supply to demand-driven opportunities : unravelling the role of the customer in opportunity identification processes

Successful identification and exploitation of opportunities has been an area of interest to many entrepreneurship researchers. Since Shane and Venkataraman’s seminal work (e.g. Shane and Venkataraman, 2000; Shane, 2000), several scholars have theorised on how firms identify, nurture and develop opportunities. The majority of this literature has been devoted to understanding how entrepreneurs search for new applications of their technological base or discover opportunities based on prior knowledge (Zahra, 2008; Sarasvathy et al., 2003). In particular, knowledge about potential customer needs and problems that may present opportunities is vital (Webb et al., 2010). Whereas the role of prior knowledge of customer problems (Shane, 2003; Shepherd and DeTienne, 2005) and positioning oneself in a so-called knowledge corridor (Fiet, 1996) has been researched, the role of opportunity characteristics and their interaction with customer-related mechanisms that facilitate and hinder opportunity identification has received scant attention.

Do balanced skills help nascent entrepreneurs to make progress in the venture creation process?

We apply Lazear’s jack-of-all-trades theory to investigate the effect of nascent entrepreneurs´ balanced skill set across various functional areas on the performance of nascent projects. Analyzing longitudinal data on innovative nascent projects, we find that nascent entrepreneurs with a more balanced skill set are more successful in that they progress faster in the venture creation process.

Context-aware methods for process modeling

Recent studies have started to explore context-awareness as a driver in the design of adaptable business processes. The emerging challenge of identifying and considering contextual drivers in the environment of a business process are well understood, however, typical methods used in business process modeling do not yet consider this additional contextual information in their process designs. In this chapter, we describe our research towards innovative and advanced process modeling methods that include mechanisms to incorporate relevant contextual drivers and their impacts on business processes in process design models. We report on our ongoing work with an Australian insurance provider and describe the design science we employed to develop these innovative and useful artifacts as part of a context-aware method framework. We discuss the utility of these artifacts in an application in the claims handling process at the case organization.

Research process management

Though the value of a process-centred view for the understanding and (re-)design of corporations has been widely accepted, our understanding of the research process in Information Systems (IS) remains superficial. A process-centred view on IS research considers the conduct of a research project as a sequence of activities involving resources, data and research artifacts. As such, it helps to reflect on more effective ways to conduct IS research, to consolidate and compare diverse practices and to complement the focus on research methodologies with research project practices. This paper takes a first step towards the discipline of ‘Research Process Management’ by exploring the features of research processes and by presenting a preliminary approach for research process design that can facilitate modelling IS research. The case study method and the design science research method are used as examples to demonstrate the potential of such reference research process models.

Source characterisation of road dust based on chemical and mineralogical composition

Road dust contain potentially toxic pollutants originating from a range of anthropogenic sources common to urban land uses and soil inputs from surrounding areas. The research study analysed the mineralogy and morphology of dust samples from road surfaces from different land uses and background soil samples to characterise the relative source contributions to road dust. The road dust consist primarily of soil derived minerals (60%) with quartz averaging 40-50% and remainder being clay forming minerals of albite, microcline, chlorite and muscovite originating from surrounding soils. About 2% was organic matter primarily originating from plant matter. Potentially toxic pollutants represented about 30% of the build-up. These pollutants consist of brake and tire wear, combustion emissions and fly ash from asphalt. Heavy metals such as Zn, Cu, Pb, Ni, Cr and Cd primarily originate from vehicular traffic while Fe, Al and Mn primarily originate from surrounding soils. The research study confirmed the significant contribution of vehicular traffic to dust deposited on urban road surfaces.

Microbial colonisation of human follicular fluid and adverse in vitro fertilisation outcomes

This study, investigating 263 women undergoing trans-vaginal oocyte retrieval for in vitro fertilisation (IVF) found that microorganisms colonising follicular fluid contributed to adverse IVF (pre-implantation) and pregnancy (post-implantation) outcomes including poor quality embryos, failed pregnancy and early pregnancy loss (< 37 weeks gestation). Some microorganisms also showed in vitro growth patterns in liquid media that appeared to be enhanced by the hormonal stimulation protocol used for oocyte retrieval. Elaborated cytokines within follicular fluid were also associated with adverse IVF outcomes. This study is imperative because infertility affects 16% of the human population and the numbers of couples needing assistance continues to increase. Despite significant improvements in the technical aspects of assisted reproductive technologies (ART), the live birth rate has not increased proportionally. Overt genital tract infection has been associated with both infertility and adverse pregnancy outcomes (including miscarriage and preterm birth) as a direct result of the infection or the host response to it. Importantly, once inflammation had become established, medical treatment often failed to prevent these significant adverse outcomes. Current evaluations of fertility focus on the ovary as a site of steroid hormone production and ovulation. However, infertility as a result of subclinical colonisation of the ovary has not been reported. Furthermore, identification of the microorganisms present in follicular fluid and the local cytokine profile may provide clinicians with an early indication of the prognosis for IVF treatment in infertile couples, thus allowing antimicrobial treatment and/or counselling about possible IVF failure. During an IVF cycle, multiple oocytes undergo maturation in vivo in response to hormonal hyperstimulation. Oocytes for in vitro insemination are collected trans-vaginally. The follicular fluid that bathes the maturing oocyte in vivo, usually is discarded as part of the IVF procedure, but provides a unique opportunity to investigate microbial causes of adverse IVF outcomes. Some previous studies have identified follicular fluid markers that predict IVF pregnancy outcomes. However, there have not been any detailed microbiological studies of follicular fluid. For this current study, paired follicular fluid and vaginal secretion samples were collected from women undergoing IVF cycles to determine whether microorganisms in follicular fluid were associated with adverse IVF outcomes. Microorganisms in follicular fluid were regarded as either "colonisers" or "contaminants"; colonisers, if they were unique to the follicular fluid sample, and contaminants if the same microorganisms were detected in the vaginal and follicular fluid samples indicating that the follicular fluid was merely contaminated during the oocyte retrieval process. Quite unexpectedly, by these criteria, we found that follicular fluid from approximately 30% of all subjects was colonised with bacteria. Fertile and infertile women with colonised follicular fluid had decreased embryo transfer rates and decreased pregnancy rates compared to women with contaminated follicular fluids. The observation that follicular fluid was not always sterile, but contained a diverse range of microorganisms, is novel. Many of the microorganisms we detected in follicular fluid are known opportunistic pathogens that have been detected in upper genital tract infections and are associated with adverse pregnancy outcomes. Bacteria were able to survive for at least 28 weeks in vitro, in cultures of follicular fluid. Within 10 days of establishing these in vitro cultures, several species (Lactobacillus spp., Bifidobacterium spp., Propionibacterium spp., Streptococcus spp. and Salmonella entericus) had formed biofilms. Biofilms play a major role in microbial pathogenicity and persistence. The propensity of microbial species to form biofilms in follicular fluid suggests that successful treatment of these infections with antimicrobials may be difficult. Bifidobacterium spp. grew, in liquid media, only if concentrations of oestradiol and progesterone were similar to those achieved in vivo during an IVF cycle. In contrast, the growth of Streptococcus agalactiae and Escherichia coli was inhibited or abolished by the addition of these hormones to culture medium. These data suggest that the likelihood of microorganisms colonising follicular fluid and the species of bacteria involved is influenced by the stage of the menstrual cycle and, in the case of IVF, the nature and dose of steroid hormones administered for the maturation of multiple oocytes in vivo. Our findings indicate that the elevated levels of steroid hormones during an IVF cycle may influence the microbial growth within follicular fluid, suggesting that the treatment itself will impact on the microflora present in the female upper genital tract during pre-conception and early post-conception phases of the cycle. The effect of the host immune response on colonising bacteria and on the outcomes of IVF also was investigated. White blood cells reportedly compose between 5% and 15% of the cell population in follicular fluid. The follicular membrane is semi-permeable and cells are actively recruited as part of the normal menstrual cycle and in response to microorganisms. A previous study investigated follicular fluid cytokines from infertile women and fertile oocyte donors undergoing IVF, and concluded that there were no significant differences in the cytokine concentrations between the two groups. However, other studies have reported differences in the follicular fluid cytokine levels associated with infertile women with endometriosis or polycystic ovary syndrome. In this study, elevated levels of interleukin (IL)-1 á, IL-1 â and vascular endothelial growth factor (VEGF) in vaginal fluid were associated with successful fertilisation, which may be useful marker for successful fertilisation outcomes for women trying to conceive naturally or prior to oocyte retrieval for IVF. Elevated levels of IL-6, IL-12p40, granulocyte colony stimulating factor (GCSF) and interferon-gamma (IFN ã) in follicular fluid were associated with successful embryo transfer. Elevated levels of pro-inflammatory IL-18 and decreased levels of anti-inflammatory IL-10 were identified in follicular fluid from women with idiopathic infertility. Successful fertilisation and implantation is dependent on a controlled pro-inflammatory environment, involving active recruitment of pro-inflammatory mediators to the genital tract as part of the menstrual cycle and early pregnancy. However, ongoing pregnancy requires an enhanced anti-inflammatory environment to ensure that the maternal immune system does not reject the semi-allergenic foetus. The pro-inflammatory skew in the follicular fluid of women with idiopathic infertility, correlates with normal rates of fertilisation, embryo discard and embryo transfer, observed for this cohort, which were similar to the outcomes observed for fertile women. However, their pregnancy rate was reduced compared to fertile women. An altered local immune response in follicular fluid may provide a means of explaining infertility in this cohort, previously defined as 'idiopathic'. This study has found that microorganisms colonising follicular fluid may have contributed to adverse IVF and pregnancy outcomes. Follicular fluid bathes the cumulus oocyte complex during the in vivo maturation process, and microorganisms in the fluid, their metabolic products or the local immune response to these microorganisms may result in damage to the oocytes, degradation of the cumulus or contamination of the IVF culture system. Previous studies that have discounted bacterial contamination of follicular fluid as a cause of adverse IVF outcomes failed to distinguish between bacteria that were introduced into the follicular fluid at the time of trans-vaginal oocyte retrieval and those that colonised the follicular fluid. Those bacteria that had colonised the fluid may have had time to form biofilms and to elicit a local immune response. Failure to draw this distinction has previously prevented consideration of bacterial colonisation of follicular fluid as a cause of adverse IVF outcomes. Several observations arising from this study are of significance to IVF programs. Follicular fluid is not always sterile and colonisation of follicular fluid is a cause of adverse IVF and pregnancy outcomes. Hormonal stimulation associated with IVF may influence whether follicular fluid is colonised and enhance the growth of specific species of bacteria within follicular fluid. Bacteria in follicular fluid may form biofilms and literature has reported that this may influence their susceptibility to antibiotics. Monitoring the levels of selected cytokines within vaginal secretions may inform fertilisation outcomes. This study has identified novel factors contributing to adverse IVF outcomes and that are most likely to affect also natural conception outcomes. Early intervention, possibly using antimicrobial or immunological therapies may reduce the need for ART and improve reproductive health outcomes for all women.

Organizational rhetoric in the prospectuses of elite private schools: unpacking strategies of persuasion

The way in which private schools use rhetoric in their communications offers important insights into how these organizational sites persuade audiences and leverage marketplace advantage in the context of contemporary educational platforms. Through systemic analysis of rhetorical strategies employed in 65 ‘elite’ school prospectuses in Australia, this paper contributes to understandings of the ways schools’ communications draw on broader cultural politics in order to shape meanings and interactions among organizational actors. We identify six strategies consistently used by schools to this end: identification, juxtapositioning, bolstering or self-promotion, partial reporting, self-expansion, and reframing or reversal. We argue that, in the context of marketization and privatization discourses in twenty-first-century western education, these strategies attempt to subvert potentially threatening discourses, in the process actively reproducing broader economic and social privilege and inequalities.