Cisplatin treatment of primary and metastatic epithelial ovarian carcinomas generates residual cells with mesenchymal stem cell-like profile

Epithelial mesenchymal transition (EMT) and cancer stem cells (CSC) have been associated with resistance to chemotherapy. Eighty percent of ovarian cancer patients initially respond to platinum-based combination therapy but most return with recurrence and ultimate demise. To better understand such chemoresistance we have assessed the potential role of EMT in tumor cells collected from advanced-stage ovarian cancer patients and the ovarian cancer cell line OVCA 433 in response to cisplatin in vitro. We demonstrate that cisplatin-induced transition from epithelial to mesenchymal morphology in residual cancer cells correlated with reduced E-cadherin, and increased N-cadherin and vimentin expression. The mRNA expression of Snail, Slug, Twist, and MMP-2 were significantly enhanced in response to cisplatin and correlated with increased migration. This coincided with increased cell surface expression of CSC-like markers such as CD44, α2 integrin subunit, CD117, CD133, EpCAM, and the expression of stem cell factors Nanog and Oct-4. EMT and CSC-like changes in response to cisplatin correlated with enhanced activation of extracellular signal-regulated kinase (ERK)1/2. The selective MEK inhibitor U0126 inhibited ERK2 activation and partially suppressed cisplatin-induced EMT and CSC markers. In vivo xenotransplantation of cisplatin-treated OVCA 433 cells in zebrafish embryos demonstrated significantly enhanced migration of cells compared to control untreated cells. U0126 inhibited cisplatin-induced migration of cells in vivo, suggesting that ERK2 signaling is critical to cisplatin-induced EMT and CSC phenotypes, and that targeting ERK2 in the presence of cisplatin may reduce the burden of residual tumor, the ultimate cause of recurrence in ovarian cancer patients.

Laminin adhesion-selected primary human colon-cancer cells are more tumorigenic than the parenteral and nonadherent cells

Laminin has been shown to promote the malignant phenotype and the level of the 32/67 Kd laminin receptor has been found to correlate with Dukes' staging of colon cancer. A biopsy of a Dukes' stage B2 human colon carcinoma formed a tumor in a nude mouse after coinjection with Matrigel. The parental tumor and the murine tumor appeared identical at the histological level. A cell line LCC-C1 was established from the murine tumor. The cell line appeared moderately differentiated although it did not produce mucin in vitro; however, the xenograft in vivo did produce low levels of mucin. Laminin adherent and non-adherent cell lines were selected. The parental and the laminin-selected cell subclones adhered equally well to plastic and to fibronectin and showed similar growth rates on plastic. When injected subcutaneously into nude mice, the laminin-adherent cells formed relatively undifferentiated tumors that were twice as large as the parental cell tumors whereas the laminin non adherent cells formed very small, but highly differentiated tumors. These data demonstrate that subpopulations of tumor cells which differ in their tumorigenic properties can be selected based on their adhesion to laminin and thus provide models for studying the mechanisms of tumor growth.

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.

Time course analysis of hypoxia, granulation tissue and blood vessel growth, and remodeling in healing rat cutaneous incisional primary intention wounds

Hypoxia and the development and remodeling of blood vessels and connective tissue in granulation tissue that forms in a wound gap following full-thickness skin incision in the rat were examined as a function of time. A 1.5 cm-long incisional wound was created in rat groin skin and the opposed edges sutured together. Wounds were harvested between 3 days and 16 weeks and hypoxia, percent vascular volume, cell proliferation and apoptosis, α-smooth muscle actin, vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2, and transforming growth factor-β 1 expression in granulation tissue were then assessed. Hypoxia was evident between 3 and 7 days while maximal cell proliferation at 3 days (123.6 ± 22.2 cells/mm 2, p < 0.001 when compared with normal skin) preceded the peak percent vascular volume that occurred at 7 days (15.83 ± 1.10%, p < 0.001 when compared with normal skin). The peak in cell apoptosis occurred at 3 weeks (12.1 ± 1.3 cells/mm 2, p < 0.001 when compared with normal skin). Intense α-smooth muscle actin labeling in myofibroblasts was evident at 7 and 10 days. Vascular endothelial growth factor receptor-2 and vascular endothelial growth factor-A were detectable until 2 and 3 weeks, respectively, while transforming growth factor-β 1 protein was detectable in endothelial cells and myofibroblasts until 3-4 weeks and in the extracellular matrix for 16 weeks. Incisional wound granulation tissue largely developed within 3-7 days in the presence of hypoxia. Remodeling, marked by a decline in the percent vascular volume and increased cellular apoptosis, occurred largely in the absence of detectable hypoxia. The expression of vascular endothelial growth factor-A, vascular endothelial growth factor receptor-2, and transforming growth factor-β 1 is evident prior, during, and after the peak of vascular volume reflecting multiple roles for these factors during wound healing.

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.

Securitizing infectious disease

Over the past decade there has been an increased awareness in the field of international relations of the potential impact of an infectious disease epidemic on national security. While states’ attempts to combat infectious disease have a long history, what is new in this area is the adoption at the international level of securitized responses regarding the containment of infectious disease. This article argues that the securitization of infectious disease by states and the World Health Organization (WHO) has led to two key developments. First, the WHO has had to assert itself as the primary actor that all states, particularly western states, can rely upon to contain the threat of infectious diseases. The WHO's apparent success in this is evidenced by the development of the Global Outbreak Alert Response Network (GOARN), which has led to arguments that the WHO has emerged as the key authority in global health governance. The second outcome that this article seeks to explore is the development of the WHO's authority in the area of infectious disease surveillance. In particular, is GOARN a representation of the WHO's consummate authority in the area of coordinating infectious disease response or is GOARN the product of the WHO's capitulation to western states’ concerns with preventing infectious disease outbreaks from reaching their borders and as a result, are arguments expressing the authority of the WHO in infectious disease response premature?

Characteristics of ultrafine particle sources and deposition rates in primary school classrooms

The aim of this work was to investigate changes in particle number concentration (PNC) within naturally ventilated primary school classrooms arising from local sources either within or adjacent to the classrooms. We quantify the rate at which ultrafine particles were emitted either from printing, grilling, heating or cleaning activities and the rate at which the particles were removed by both deposition and air exchange processes. At each of 25 schools in Brisbane, Australia, two weeks of measurements of PNC and CO2 were taken both outdoors and in the two classrooms. Bayesian regression modelling was employed in order to estimate the relevant rates and analyse the relationship between air exchange rate (AER), particle infiltration and the deposition rates of particle generated from indoor activities in the classrooms. During schooling hours, grilling events at the school tuckshop as well as heating and printing in the classrooms led to indoor PNCs being elevated by a factor of more than four, with emission rates of (2.51 ± 0.25) x 1011 p min-1, (8.99 ± 6.70) x 1011 p min-1 and (5.17 ± 2.00) x 1011 p min-1, respectively. During non-school hours, cleaning events elevated indoor PNC by a factor of above five, with an average emission rate of (2.09 ± 6.30) x 1011 p min-1. Particles were removed by both air exchange and deposition; chiefly by ventilation when AER > 0.7 h-1 and by deposition when AER < 0.7 h-1.

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.

Consumers persepctive on pharmacists integration into private primary healthcare clinics in Malaysia

Background: Pharmacists are considered medication experts but are underutilised mainly at the periphery of the primary healthcare team. General medical practitioners (GPs) in Malaysian private healthcare clinics are granted rights to prescribe and dispense medications, thus furhter limiting pharmacists involvement in ensuring safe use of medicines. The integration of pharmacist into private primary healthcare clinics has the potential to reduce medication-relation problems. Objective: To explore the views of consumers on the integration of pharmacists within private primary healthcare clinics in Malaysia. Method: A purposive sample of healthcare consumers in Selangor and Kuala Lumpur, Malaysia were invited to participate in focus groups and semi-structured interviews. Sessions were audio recorded and transcribed verbatim and thematically analysed using NVivo 10. Results: A total of 24 healthcare consumers particpated in two focus groups and six semi-structured interviews. Four major themes were identified: (1) Pharmacists role viewed mainly as supplying medications, (2) Readiness to accept pharmacists in private healthcare clinics, (3) Willingness to pay for pharmacy services, and (4) Concerns about GPs resistance to pharmacist integration. Consumers felt that a pharmacist integrated into private prumary healthcare clinics could offer potential benefits such as counter-checking prescriptions to ensure correct medication is supplied and counselling consumers on their medications and the potential side effects. The potential to increase in costs to consumers and GPs reluctance were perceived as barriers to integration. Conclusion: This study provides insights into consumers perspectives on the roles of pharmacists within private primary healthcare clinics in Malaysia. Consumers generally supported pharmacist integration into private primary healthcare clinics. However, for pharmacists to expand their capacity in providing integrated and collaborative primary care services to consumers, barriers to pharmacist integration need to be addressed.

The expression profiles of the galectin gene family in primary and metastatic papillary thyroid carcinoma with particular emphasis on galectin-1 and galectin-3 expression

INTRODUCTION: Galectin family members have been demonstrated to be abnormally expressed in cancer at the protein and mRNA level. This study investigated the levels of galectin proteins and mRNA expression in a large cohort of patients with papillary thyroid carcinoma and matched lymph node metastases with particular emphasis on galectin-1 and galectin-3. METHODS: mRNA expression of galectin family members (1, 2, 3, 4, 7, 8, 9, 10 and 12) were analysed by real-time polymerase chain reaction in 65 papillary thyroid carcinomas, 30 matched lymph nodes with metastatic papillary thyroid carcinoma and 5 non-cancer thyroid tissues. Galectin-1 and 3 protein expression was determined by immunohistochemistry in these samples. RESULTS: Significant expression differences in all tested galectin family members (1, 2, 3, 4, 7, 8, 9, 10 and 12) were noted for mRNA in papillary thyroid carcinomas, with and without lymph node metastasis. Galectin-1 protein was more strongly expressed than galectin-3 protein in papillary thyroid carcinoma. Galectin-1 protein was found to be overexpressed in 32% of primary papillary thyroid carcinomas. A majority of lymph nodes with metastatic papillary thyroid carcinoma (53%) had significantly increased expression of galectin-1 protein, as did 47% of primaries with metastases. Galectin-1 mRNA levels were decreased in the vast majority (94%) of primary thyroid carcinomas that did not have metastases present. Galectin-3 protein levels were noted to be overexpressed in 15% of primary papillary thyroid carcinomas. In primary papillary thyroid carcinoma with lymph node metastases, 32% had over expression of galectin-3 protein. Overexpression of galectin-3 mRNA was noted in 58% of papillary thyroid carcinomas and 64% of lymph nodes bearing metastatic papillary thyroid carcinoma. Also, primary papillary thyroid carcinoma with lymph node metastases had significantly higher expression of galectin-3 mRNA compared to those without lymph node metastases. CONCLUSION: Galectin family members show altered expression at the mRNA level in papillary thyroid cancers. Overexpression of galectin-1 and 3 proteins were noted in papillary thyroid carcinoma with lymph node metastases. The results presented here demonstrated that galectin-1 and galectin-3 expression have important roles in clinical progression of papillary thyroid carcinoma.

What are pregnant women told about models of maternity care in Australia? A retrospective study of women's reports

Objective To describe women’s reports of the model of care options General Practitioners (GPs) discussed with them at the first pregnancy consultation and women’s self-reported role in decisionmaking about model of care. Methods Women who had recently given birth responded to survey items about the models of care GPs discussed, their role in final decision-making, and socio-demographic, obstetric history, and early pregnancy characteristics. Results The proportion of women with whom each model of care was discussed varied between 8.2% (for private midwifery care with home birth) and 64.4% (GP shared care). Only 7.7% of women reported that all seven models were discussed. Exclusive discussion about private obstetric care and about all public models was common, and women’s health insurance status was the strongest predictor of the presence of discussions about each model. Most women (82.6%) reported active involvement in final decision-making about model of care. Conclusion Although most women report involvement in maternity model of care decisions, they remain largely uninformed about the breadth of available model of care options. Practical implications Strategies that facilitate women’s access to information on the differentiating features and outcomes for all models of care should be prioritized to better ensure equitable and quality decisions.

Origins of Australian Football: Victoria's Early History. Volume 2 : A golden era begins : Football in 'Marvellous Melbourne', 1877 to 1885

This is the second volume of a five volume series that describes, assesses, and analyses football in Victoria during the nineteenth century. This volume looks at the cultural contexts of the sport in the late 1870s and early 1880s, describes the important matches played, and provides a full statistical account of this time period. This book is the first comprehensive discussion of the early period in Australian football's development.

Detection of dynamic primary user with cooperative spectrum sensing

In this paper we demonstrate that existing cooperative spectrum sensing formulated for static primary users cannot accurately detect dynamic primary users regardless of the information fusion method. Performance error occurs as the sensing parameters calculated by the conventional detector result in sensing performance that violates the sensing requirements. Furthermore, the error is accumulated and compounded by the number of cooperating nodes. To address this limitation, we design and implement the duty cycle detection model for the context of cooperative spectrum sensing to accurately calculate the sensing parameters that satisfy the sensing requirements. We show that longer sensing duration is required to compensate for dynamic primary user traffic.

Using a visually-based assignment to reinforce and assess design history knowledge and understanding

This paper presents a visual timeline-based assignment used in an undergraduate Industrial Design History, Theory and Critcism unit. The assignment was developed in order to find a better way of supporting design history learning than an exam or essay assessment. It was developed using constructive alignment and it allows design students to use their strong visual thinking skills to understand unfamiliar content, develop their visual literacy of design history, and think deeply about the links between the designs, styles, movements, events and people in their timeline. The task produced a variety of responses, from websites and electronic presentations to large paper timelines, scrolls and 3D models. These have been admired by peers and used for end of year shows and permanent displays. Questionnaires were issued to students to gain feedback about the assessment. Students stated that the visual nature of the assignment helped them to understand how different aspects of design history related to each other, assisted with retaining the information, and that it was more interesting and fun than a report or an exam. This paper explores the theories behind and the benefits of using such methods of assessment for design history courses.

Investigating early childhood education for sustainability : insights from history and literature

Seemingly straightforward tasks often have a way of becoming complex. This was the case for our guest editorial team charged with creating Early Childhood Australia’s Best of Sustainability publication drawn from the the Australasian Journal of Early Childhood and Every Child. The complexities we encountered ranged from the varied terminologies and understandings of constructs such as education for sustainable development, environmental education and education for sustainability, through to the fundamental lack of published research on which to draw as the basis for a special issue. It is timely to explore these complexities as we face the global challenges of The Critical Decade (DCCEE, 2011) including rising sea levels, extreme weather events and food security. At a local level, the early childhood field in Australia is seeking to interpret sustainability with systemic support from the National Quality Standards(NQS) (ACECQA, 2011), while elsewhere environmental/sustainability education is encouraged through national curricula documents (for example, Singapore Ministry of Education, 2008; Swedish National Agency for Education,2010; Ministry of Education of Korea, 2011). Both The Critical Decade and the NQS provide imperatives to drive early childhood education’s engagement with sustainability. In other words, sustainability in early childhood education is no longer optional, but essential (Elliott, 2010). While some twenty years of advocacy has led to this somewhat subdued celebratory position, in this publication we do recognise the historical contexts that have led to early childhood education for sustainability (ECEfS), as we (Elliott & Davis) phrase it, becoming almost ‘mainstream not marginal’ (Davis, 1999)— a stitching together of the isolated ‘patches of green’, first identified a decade ago by Elliott (NSW EPA, 2003). Here we weave together, through these articles, a story of the evolving history of ECEfS from our particular perspective. In so doing, we also acknowledge that there are other perspectives or ‘paths’ for this field as identified by Edwards and Cutter-McKenzie in their concluding paper to this compilation.