Whole-genome multiparametric screening to identify modulators of epithelial-to-mesenchymal transition

Metastasis accounts for the poor prognosis of the majority of solid tumors. The phenotypic transition of nonmotile epithelial tumor cells to migratory and invasive “mesenchymal” cells (epithelial-to-mesenchymal transition [EMT]) enables the transit of cancer cells from the primary tumor to distant sites. There is no single marker of EMT; rather, multiple measures are required to define cell state. Thus, the multiparametric capability of high-content screening is ideally suited for the comprehensive analysis of EMT regulators. The aim of this study was to generate a platform to systematically identify functional modulators of tumor cell plasticity using the bladder cancer cell line TSU-Pr1-B1 as a model system. A platform enabling the quantification of key EMT characteristics, cell morphology and mesenchymal intermediate filament vimentin, was developed using the fluorescent whole-cell-tracking reagent CMFDA and a fluorescent promoter reporter construct, respectively. The functional effect of genome-wide modulation of protein-coding genes and miRNAs coupled with those of a collection of small-molecule kinase inhibitors on EMT was assessed using the Target Activation Bioapplication integrated in the Cellomics ArrayScan platform. Data from each of the three screens were integrated to identify a cohort of targets that were subsequently examined in a validation assay using siRNA duplexes. Identification of established regulators of EMT supports the utility of this screening approach and indicated capacity to identify novel regulators of this plasticity program. Pathway analysis coupled with interrogation of cancer-related expression profile databases and other EMT-related screens provided key evidence to prioritize further experimental investigation into the molecular regulators of EMT in cancer cells.

Becoming a pharmacist : students' perceptions of their curricular experience and professional identity formation

Introduction Student professional identity formation is important for enabling the successful transition between academic education and professional practice. Recognition of this has resulted in significant changes in professional education (e.g., the inclusion of experiential placements and authentic learning experiences). There is limited research that examines how the curricular experience influences pharmacy studentsʼ professional identity formation. Methods Using focus groups, comprising 82 students from all levels of a four-year Australian undergraduate pharmacy course, this study examined studentsʼ perceptions of their overall curricular experience and examined how these experiences influenced the construction of their professional identities. Results Our analysis found that the pharmacy students struggled with their professional identity formation. Many were entering the degree with little understanding of what being a pharmacist entailed. Once in the educational context, the nature of the role became both apparent and idealistic but not enacted. Students experienced dissonance between the idealistic notion of pharmacy practice and the realities of placements, and this may have been enhanced by a lack of patient-centered care role models. This struggle left them concluding that the role of the pharmacist was constrained and limited. Conclusions We argue that professional identity formation needs to be in the foreground from commencement of the degree and throughout the curriculum.

Negotiating futility, managing emotions : nursing the transition to palliative care

Nurses play a pivotal role in caring for patients during the transition from life-prolonging care to palliative care. This is an area of nursing prone to emotional difficulty, interpersonal complexity, and interprofessional conflict. It is situated within complex social dynamics, including those related to establishing and accepting futility and reconciling the desire to maintain hope. Here, drawing on interviews with 20 Australian nurses, we unpack their accounts of nursing the transition to palliative care, focusing on the purpose of nursing at the point of transition; accounts of communication and strategies for representing palliative care; emotional engagement and burden; and key interprofessional challenges. We argue that in caring for patients approaching the end of life, nurses occupy precarious interpersonal and interprofessional spaces that involve a negotiated order around sentimental work, providing them with both capital (privileged access) and burden (emotional suffering) within their day-to-day work.

On resilience and acceptance in the transition to palliative care at the end of life

Specialist palliative care is a prominent and expanding site of health service delivery, providing highly specialised care to people at the end of life. Its focus on the delivery of specialised life-enhancing care stands in contrast to biomedicine's general tendency towards life-prolonging intervention. This philosophical departure from curative or life-prolonging care means that transitioning patients can be problematic, with recent work suggesting a wide range of potential emotional, communication and relational difficulties for patients, families and health professionals. Yet, we know little about terminally ill patients' lived experiences of this complex transition. Here, through interviews with 40 inpatients in the last few weeks of life, we explore their embodied and relational experiences of the transition to inpatient care, including their accounts of an ethic of resilience in pre-palliative care and an ethic of acceptance as they move towards specialist palliative care. Exploring the relationship between resilience and acceptance reveals the opportunities, as well as the limitations, embedded in the normative constructs that inflect individual experience of this transition. This highlights a contradictory dynamic whereby participants' experiences were characterised by talk of initiating change, while also acquiescing to the terminal progression of their illness.

Growth factors in induction of epithelial-mesenchymal transition and metastasis

Epithelial to mesenchymal transition (EMT) has gained widespread acceptance over recent years as a mechanism by which normally sessile epithelial tumour cells can move away from the primary tumour and metastasize. This review article examines the role of a number of growth factors in inducing EMT, and the reverse process mesenchymal to epithelial transition. Unique and common intracellular signalling pathways are highlighted. A comprehensive understanding of the regulation of EMT will be critical in manipulating this process to develop novel anti-metastasis therapies.

Case Study 4: Education Doctoral Student - "An Exploratory Study of Online Social Networking within a Doctorate of Education Program"

Introduction The professional doctorate is specifically designed for professionals investigating real-world problems and relevant issues for a profession, industry, and/or the community. The focus is scholarly research into professional practices. The research programme bridges academia and the professions, and offers doctoral candidates the opportunity to investigate issues relevant to their own practices and to apply these understandings to their professional contexts. The study on which this article is based sought to track the scholarly skill development of a cohort of professional doctoral students who commenced the course in January 2008 at an Australian university. Because they hold positions of responsibility and are time-poor, many doctoral students have difficulty transitioning from professional practitioner to researcher and scholar. The struggle many experience is in the development of a theoretical or conceptual standpoint for argumentation (Lesham, 2007; Weese et al., 1999). It was thought that the use of a scaffolded learning environment that drew upon a blended learning approach incorporating face to face intensive blocks and collaborative knowledge-building tools such as wikis would provide a data source for understanding the development of scholarly skills. Wikis, weblogs and similar social networking software have the potential to support communities to share, learn, create and collaborate. The development of a wiki page by each candidate in the 2008 cohort was encouraged to provide the participants and the teaching team members with textual indicators of progress. Learning tasks were scaffolded with the expectation that the candidates would complete these tasks via the wikis. The expectation was that cohort members would comment on each other’s work, together with the supervisor and/or teaching team member who was allocated to each candidate. The supervisor is responsible for supervising the candidate’s work through to submission of the thesis for examination and the teaching team member provides support to both the supervisor and the candidate through to confirmation. This paper reports on the learning journey of a cohort of doctoral students during the first seven months of their professional doctoral programme to determine if there had been any qualitative shifts in understandings, expectations and perceptions regarding their developing knowledge and skills. The paper is grounded in the literature pertaining to doctoral studies and examines the structure of the professional doctoral programme. Following this is a discussion of the qualitative study that helped to unearth key themes regarding the participants’ learning journey.

Adaptive estimation of HMM transition probabilities

This paper presents new schemes for recursive estimation of the state transition probabilities for hidden Markov models (HMM's) via extended least squares (ELS) and recursive state prediction error (RSPE) methods. Local convergence analysis for the proposed RSPE algorithm is shown using the ordinary differential equation (ODE) approach developed for the more familiar recursive output prediction error (RPE) methods. The presented scheme converges and is relatively well conditioned compared with the ...

Adaptive estimation of hidden semi-Markov chains with parameterised transition probabilities and exponential decaying states

This paper develops maximum likelihood (ML) estimation schemes for finite-state semi-Markov chains in white Gaussian noise. We assume that the semi-Markov chain is characterised by transition probabilities of known parametric from with unknown parameters. We reformulate this hidden semi-Markov model (HSM) problem in the scalar case as a two-vector homogeneous hidden Markov model (HMM) problem in which the state consist of the signal augmented by the time to last transition. With this reformulation we apply the expectation Maximumisation (EM ) algorithm to obtain ML estimates of the transition probabilities parameters, Markov state levels and noise variance. To demonstrate our proposed schemes, motivated by neuro-biological applications, we use a damped sinusoidal parameterised function for the transition probabilities.

Improving criteria and feedback in student assessment in law

Spurred on by both the 1987 Pearce Report1 and the general changes to higher education spawned by the “Dawkins revolution” from 1988, there has been much critical self-evaluation leading to profound improvements to the quality of teaching in Australian law schools.2 Despite the changes there are still areas of general law teaching practice which have lagged behind recent developments in our understanding of what constitutes high quality teaching. One such area is assessment criteria and feedback. The project Improving Feedback in Student Assessment in Law is an attempt to remedy this. It aims to produce a manual containing key principles for the design of assessment and the provision of feedback, with practical yet flexible ideas and illustrations which law teachers may adopt or modify. Most of the examples have been developed by teachers at the University of Melbourne Law School. The project was supported in 1996 by a Committee for the Advancement of University Teaching grant and the manual will be published late in 1997.3 This note summarises the core principles which are elaborated further in the manual.

Whole-of-Curriculum Design in Law

In this book teaching professionalism is characterised by the scholarly underpinning of each contribution; and every contribution provides a rich resource for enhancing teaching practice. The critical concerns for legal education have been identified and discussed: curriculum design that includes graduate attributes; embedding specific attributes across the curriculum; empowering students to learn; academic teamwork to manage large student cohorts; first year and final year transition strategies; tracking students' personal development through the use of ePortfolio; assessment strategies; improving student well-being and promoting resilience; teaching practice to achieve deep learning; flexibility in delivery; the use of Web 2.0 technology; and understanding the 21st century student.