Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice

The ability to activate pro-matrix metalloproteinase (pro-MMP)-2 via membrane type-MMP is a hallmark of human breast cancer cell lines that show increased invasiveness, suggesting that MMP-2 contributes to human breast cancer progression. To investigate this, we have stably transfected pro-MMP-2 into the human breast cancer cell line MDA-MB-231, which lacks MMP-2 expression but does express its cell surface activator, membrane type 1-MMP. Multiple clones were derived and shown to produce pro-MMP-2 and to activate it in response to concanavalin A. In vitro analysis showed that the pro-MMP-2-transfected clones exhibited an increased invasive potential in Boyden chamber and Matrigel outgrowth assays, compared with the parental cells or those transfected with vector only. When inoculated into the mammary fat pad of nude mice, each of the MMP-2-tranfected clones grew faster than each of the vector controls tested. After intracardiac inoculation into nude mice, pro-MMP-2-transfected clones showed a significant increase in the incidence of metastasis to brain, liver, bone, and kidney compared with the vector control clones but not lung. Increased tumor burden was seen in the primary site and in lung metastases, and a trend toward increased burden was seen in bone, however, no change was seen in brain, liver, or kidney. This data supports a role for MMP-2 in breast cancer progression, both in the growth of primary tumors and in their spread to distant organs. MMP-2 may be a useful target for breast cancer therapy when refinement of MMP inhibitors provides for MMP-specific agents.

Literacy assessment that counts : mediating, interpreting and contesting translocal policy in a primary school

In Australia, as in many western education systems over the last two decades, discourses of accountability and performativity have reshaped education policy that has in turn reorganised the work of school leaders and teachers. One of the effects of this reorganisation is increased attention to the production, analysis and display of student achievement data. In this paper we examine in detail a sequence of the production and reading of literacy assessment data in a small Catholic school. Our analysis uses institutional ethnography’s concept of the ‘active text’, the text as occurring in a specific place and time even as it is articulated to social relations beyond its immediate context. Through this process we learn from those involved how their everyday work brings into being formalised, textually authorised processes in a local site that ensure the school meets accountability requirements while enabling teachers to resist standardisation of literacy teaching and assessment.

Asthma interventions in primary schools : a review

Objective To explore, in depth, the literature for evidence supporting asthma interventions delivered within primary schools and to identify any “gaps” in this research area. Methods A literature search using electronic search engines (i.e. Medline, PubMed, Education Resources Information Center (ERIC), International Pharmaceutical Abstracts (IPA), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase and Informit) and the search terms “asthma”, “asthma intervention” and “school-based asthma education program” (and derivatives of these keywords) was conducted. Results Twenty-three articles met the inclusion criteria; of these eight were Randomised Controlled Trials. There was much variety in the type, content, delivery and outcome measures in these 23 studies. The most common intervention type was asthma education delivery. Most studies demonstrated improvement in clinical and humanistic markers, for example, asthma symptoms medication use (decrease in reliever medication use or decrease in the need for rescue oral steroid), inhaler use technique and spacer use competency, lung function and quality of life. Relatively few studies explored the effect of the intervention on academic outcomes. Most studies did not report on the sustainability or cost effectiveness of the intervention tested. Another drawback in the literature was the lack of details about the intervention and inconsistency in instruments selected for measuring outcomes. Conclusion School-based asthma interventions regardless of their heterogeneity have positive clinical, humanistic, health economical and academic outcomes.

Theorizing in design science research : an abstraction layers framework

For Design Science Research (DSR) to gain wide credence as a research paradigm in Information Systems (IS), it must contribute to theory. “Theory cannot be improved until we improve the theorizing process, and we cannot improve the theorizing process until we describe it more explicitly, operate it more self-consciously, and decouple it from validation more deliberately” (Weick 1989, p. 516). With the aim of improved design science theorizing, we propose a DSR abstraction-layers framework that integrates, interlates, and harmonizes key methodological notions, primary of which are: 1) the Design Science (DS), Design Research (DR), and Routine Design (RD) distinction (Winter 2008); 2) Multi Grounding in IS Design Theory (ISDT) (Goldkuhl & Lind 2010); 3) the Idealized Model for Theory Development (IM4TD) (Fischer & Gregor 2011); and 4) the DSR Theorizing Framework (Lee et al. 2011). Though theorizing, or the abstraction process, has been the subject of healthy discussion in DSR, important questions remain. With most attention to date having focused on theorizing for Design Research (DR), a key stimulus of the layered view was the realization that Design Science (DS) produces abstract knowledge at a higher level of generality. The resultant framework includes four abstraction layers: (i) Design Research (DR) 1st Abstract Layer, (ii) Design Science (DS) 2nd Abstract Layer, (iii) DSR Incubation 3rd Layer, and (iv) Routine Design 4th Layer. Differentiating and inter-relating these layers will aid DSR researchers to discover, position, and amplify their DSR contributions. Additionally, consideration of the four layers can trigger creative perspectives that suggest unplanned outputs. The first abstraction layer, including its alternative patterns of activity, is well recognized in the literature. The other layers, however, are less well recognized; and the integrated representation of layers is novel.

Development and pilot study of the Primary Care Practice Improvement Tool (PC-PIT) : an innovative approach

Objective To assess the usability and validity of the Primary Care Practice Improvement Tool (PC-PIT), a practice performance improvement tool based on 13 key elements identified by a systematic review. It was co-created with a range of partners and designed specifically for primary health care. Design This pilot study examined the PC-PIT using a formative assessment framework and mixed-methods research design. Setting and participants Six high-functioning general practices in Queensland, Australia, between February and July 2013. A total of 28 staff participated — 10 general practitioners, six practice or community nurses, 12 administrators (four practice managers; one business manager and eight reception or general administrative staff). Main outcome measures Readability, content validity and staff perceptions of the PC-PIT. Results The PC-PIT offers an appropriate and acceptable approach to internal quality improvement in general practice. Quantitative assessment scores and qualitative data from all staff identified two areas in which the PC-PIT required modification: a reduction in the indicative reading age, and simplification of governance-related terms and concepts. Conclusion The PC-PIT provides an innovative approach to address the complexity of organisational improvement in general practice and primary health care. This initial validation will be used to develop a suite of supporting, high-quality and free-to-access resources to enhance the use of the PC-PIT in general practice. Based on these findings, a national trial is now underway.

An orientation to early childhood education for sustainability and research : framing the text

This publication arose from the interests of the chapter authors, ‘a small group of thoughtful people’ almost all of whom participated in one or both Transnational Dialogues in Research in Early Childhood Education for Sustainability, held in Stavanger, Norway in 2010 and Brisbane, Australia in 2011 (Refer Appendix 1 for list of participants). These meetings were the first time that a critical mass of researchers from vastly different parts of the globe - Norway, Sweden, Australia and New Zealand at the inaugural meeting, with additional participants from Korea, Japan and Singapore attending the second - had come together to debate, discuss and share ideas about research and theory in the emerging field of Early Childhood Education for Sustainability (ECEfS. Some of the researchers who joined these Transnational Dialogues, had met serendipitously at earlier conferences and meetings, or corresponded via email, but many had never met face-to-face. Now a significant number are contributing authors in this text. It is a testament to these researchers’ interest in this agenda that they mostly self-funded their travel and other costs to attend the Transnational Dialogues research meetings. While most chapter authors come from the field of early childhood education, a few are more aligned with education for sustainability/environmental education, while a much smaller number are already working at the intersection of early childhood education and education for sustainability. What we share as a group is a range of perspectives and orientations to research and to the research focus at the heart of this book - young children and their actual and potential capabilities as agents of change for sustainability. As researchers, regardless of experience and perspectives, participants knew they had something extra to offer - their expertise as researchers - providing scholarly insights into the work of practitioners, applying critically reflective lenses to curricula, pedagogies and assumptions, testing of ideas and theories, and presenting a sense for where ECEfS might fit or, indeed, go beyond norms and orthodoxies. This is a text, then, for both researchers and those whose primary interests lie in daily interactions with children, families and communities.

Genome-wide analysis in a murine Dnmt1 knockdown model identifies epigenetically silenced genes in primary human pituitary tumors

DNA methylation at promoter CpG islands (CGI) is an epigenetic modification associated with inappropriate gene silencing in multiple tumor types. In the absence of a human pituitary tumor cell line, small interfering RNA-mediated knockdown of the maintenance methyltransferase DNA methyltransferase (cytosine 5)-1 (Dnmt1) was used in the murine pituitary adenoma cell line AtT-20. Sustained knockdown induced reexpression of the fully methylated and normally imprinted gene neuronatin (Nnat) in a time-dependent manner. Combined bisulfite restriction analysis (COBRA) revealed that reexpression of Nnat was associated with partial CGI demethylation, which was also observed at the H19 differentially methylated region. Subsequent genome-wide microarray analysis identified 91 genes that were significantly differentially expressed in Dnmt1 knockdown cells (10% false discovery rate). The analysis showed that genes associated with the induction of apoptosis, signal transduction, and developmental processes were significantly overrepresented in this list (P < 0.05). Following validation by reverse transcription-PCR and detection of inappropriate CGI methylation by COBRA, four genes (ICAM1, NNAT, RUNX1, and S100A10) were analyzed in primary human pituitary tumors, each displaying significantly reduced mRNA levels relative to normal pituitary (P < 0.05). For two of these genes, NNAT and S100A10, decreased expression was associated with increased promoter CGI methylation. Induced expression of Nnat in stable transfected AtT-20 cells inhibited cell proliferation. To our knowledge, this is the first report of array-based "epigenetic unmasking" in combination with Dnmt1 knockdown and reveals the potential of this strategy toward identifying genes silenced by epigenetic mechanisms across species boundaries.

Conceptions of learning held by Aboriginal students in a tertiary program in Indigenous primary health care

This paper is a description of a pilot investigation into conceptions of learning held by a sample of 10 Aboriginal students in a Bachelors degree courses. Results from this study suggest that this group of students view and approach learning in much the same way as other university students. They mostly hold quantitative conceptions of learning and use repetitive strategies which are potentially at odds with the objectives and procedures of the problems based program in which they are studying.

Q-RARA : a rapid and rigorous method for researching small, primary health care organisations

Understanding the organisational processes driving quality primary care is crucial to the maintaining and improving practice. Qualitative methods are increasingly popular in health services research, but this area is dominated by interview studies. Multiple qualitative methods are rarely used in a systematically integrated fashion. We developed a method to study small primary health care organizations using rapid appraisal and qualitative mixed methods: Q-RARA – Qualitative Rapid Appraisal, Rigorous Analysis

Technical Action Research

This entry into the SAGE Encyclopedia of Action Research outlines the history, purpose and orientation of what has been termed 'technical action research'. The primary purpose of technical action research (commonly referred to as TAR) is improving the outcomes of a practice or intervention, with the focus of the inquiry process typically determined by parties external to those directly involved in the practice.

Dismantling worker categories: the primary duty of care, and worker consultation, participation and representation, in the model Work Health and Safety Bill 2009

Late in 2009, the Australian Workplace Relations Ministers' Council endorsed the model Work Health and Safety Bill 2009, which is to be adopted by all Australian governments (federal, state and territory) from 01 January 2012. This paper describes and analyses two key sets of provisions in this model legislation. The first establishes a 'primary' duty of care imposed not on 'employers' but on persons conducting a business or undertaking, and owed to all kinds of workers engaged, directed or influenced by the person conducting the business or undertaking. The second encompasses broad duties on all persons conducting a business or undertaking to consult with workers who carry out work for the business or undertaking and who are directly affected by a work health and safety issue, and to facilitate the election of health and safety representatives representing all workers who carry out work for the business or undertaking. These provisions arguably make a significant contribution to solving a problem faced by occupational safety and health regulators around the world – modifying regulation to accommodate all forms of precarious work.

Primary school teachers' conceptions of pedagogical responses to concepts of diverse sexualities

This thesis reports on a social constructionist study that identified teachers' conceptions of their pedagogical responses to concepts of diverse sexualities in primary schools in Queensland. The study shows that teachers face a range of scenarios in which students raise awareness of diverse sexualities as part of their everyday experiences, yet teachers have little guidance about how to respond.