Acquisition of estrogen independence and antiestrogen resistance in breast cancer : association with the invasive and metastatic phenotype

A significant percentage of human breast cancer (HBC) is dependent upon the ovarian hormone estrogen for its onset and progression. The presence or lack of estrogen receptors (ERs) in human breast cancer is an important determinant both of prognosis and of choice of treatment - a poorer prognosis being associated with ER–ve disease. Cell lines established from human breast cancer provide models for breast cancer in various stages of progression (Engel & Young 1978). When grown as tumors in athymic nude mice, these lines represent the major in vivo experimental model for HBC studies (Brünner et al 1987). The ease of both in vitro and in vivo maintenance, the human derivation of the tissue, and the similarities in plasma estrogen levels between ovariectomized nude mice and postmenopausal women (Seibert et al. 1983, Brünner et al. 1986), make the growth of human breast cancer cell lines in nude mice an attractive...

Vimentin expression in cervical carcinomas : association with invasive and migratory potential

Vimentin is an intermediate filament protein normally expressed in mesenchymal cells, but evidence is accumulating in the literature which suggests that the aberrant expression of vimentin in epithelial cancer cells might be related to local invasiveness and metastatic potential. Vimentin expression has previously been associated with invasive properties in an in vitro model consisting of a set of HPV-33-transformed cervical keratinocyte cell lines. In the present study, in order to emphasize those in vitro findings, the expression of vimentin has been investigated in cervical neoplasms of different grades, using immunohistochemistry. A clear association is reported between vimentin expression and metastatic progression, since vimentin was detected in all invasive carcinomas and lymph node metastases, but not in CIN III lesions. These in vivo results are compared with present and previous data obtained in vitro on cervical keratinocyte cell lines, where vimentin expression also correlated with in vitro invasiveness.

Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production

Background: Expression of matrix metalloproteinase-2 (MMP-2), the 72-kd type IV collagenase/gelatinase, by cancer cells has been implicated in metastasis through cancer cell invasion of basement membranes mediated by degradation of collagen IV. However, the abundance of this latent proenzyme in normal tissues and fluids suggests that MMP-2 proenzyme utilization is limited by its physiological activation rather than expression alone. We previously reported activation of this proenzyme by normal and malignant fibroblastoid cells cultured on collagen I (vitrogen) gels. Purpose: Our purposes in this study were 1) to determine whether MMP-2 activation is restricted to the more invasive human breast cancer cell lines and 2) to localize the activating mechanism. Methods: Zymography was used to monitor MMP-2 activation through detection of latent MMP-2 (72 kd) and mature species of smaller molecular weight (59 or 62 kd). Human breast cancer cell lines cultured on plastic, vitrogen, and other matrices were thus screened for MMP- 2 activation. Collagen I-cultured cells were exposed to cycloheximide, a protein synthesis inhibitor, or to protease inhibitors to determine the nature of the MMP-2-activating mechanism. Triton X-114 (TX-114) detergent extracts from cells cultured on collagen I or plastic were incubated with latent MMP-2 and analyzed by zymography to localize the MMP-2 activator. Results: MMP-2 activation was only induced by collagen I culture in the more aggressive, highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines (Hs578T, MDA-MB-436, BT549, MDA-MB-231, MDA- MB-435, MCF-7(ADR)) and was independent of MMP-2 production. MMP-2 activation was detected in cells cultured on collagen I gels but not in those cultured on gelatin gels, Matrigel, or thin layers of collagen I or IV, gelatin, or fibronectin. Collagen-induced activation was specific for the enzyme species MMP-2, since MMP-9, the 92-kd type IV collagenase/gelatinase, was not activatable under similar conditions. MMP-2 activation was inhibited by cycloheximide and was sensitive to a metalloproteinase inhibitor but not to aspartyl, serine, or cysteinyl protease inhibitors. MMP-2 activation was detected in the hydrophobic, plasma membrane-enriched, TX-114 extracts from invasive collagen I-cultured cells. Conclusion: Collagen I-induced MMP-2 activation is restricted to highly invasive estrogen receptor-negative, vimentin-positive human breast cancer cell lines, is independent of MMP-2 production, and is associated with metastatic potential. Our findings are consistent with plasma membrane localization of the activator. Implications: The MMP-2 activation mechanism may represent a new target for diagnosis, prognosis, and treatment of human breast cancer.

Mining and (sustainable) local communities : transforming Ravensthorpe, Western Australia

This chapter examines local community experiences, understandings and changes attending the presence of mining activity, in particular as occurred in the Shire of Ravensthorpe in the South West of Western Australia (WA). It does so by drawing on an extensive ethnographic study spanning the development, opening, and closure of BHP Billiton’s Ravensthorpe Nickel Operation (RNO). Given that the negative consequences of mining activity are most evident and complex at the local level, it is crucial that we understand and address how communities (and the individuals and families who are both part of and are shaped by communities) experience the impacts of mining. Though difficult to measure, social and cultural dimensions of mining at the local scale, as this chapter demonstrates, are central to our understanding of mining as a curse or cure.

Analysis of the needs of the East Coast cluster regional natural resource management bodies in relation to planning for climate change adaptation

The Climate Change Adaptation for Natural Resource Management (NRM) in East Coast Australia Project aims to foster and support an effective “community of practice” for climate change adaptation within the East Coast Cluster NRM regions that will increase the capacity for adaptation to climate change through enhancements in knowledge and skills and through the establishment of long‐term collaborations. It is being delivered by six consortium research partners: * The University of Queensland (project lead) * Griffith University * University of the Sunshine Coast * CSIRO * New South Wales Office of Environment and Heritage * Queensland Department of Science, IT, Innovation and the Arts (Queensland Herbarium). The project relates to the East Coast Cluster, comprising the six coastal NRM regions and regional bodies between Rockhampton and Sydney: * Fitzroy Basin Association (FBA) * Burnett‐Mary Regional Group (BMRG) * SEQ Catchments (SEQC) * Northern Rivers Catchment Management Authority (CMA) (NRCMA) * Hunter‐Central Rivers CMA (HCRCMA) * Hawkesbury Nepean CMA (HNCMA). The aims of this report are to summarise the needs of the regional bodies in relation to NRM planning for climate change adaptation, and provide a basis for developing the detailed work plan for the research consortium. Two primary methods were used to identify the needs of the regional bodies: (1) document analysis of the existing NRM/ Catchment Action Plans (CAPs) and applications by the regional bodies for funding under Stream 1 of the Regional NRM Planning for Climate Change Fund, and; (2) a needs analysis workshop, held in May 2013 involving representatives from the research consortium partners and the regional bodies. The East Coast Cluster includes five of the ten largest significant urban areas in Australia, world heritage listed natural environments, significant agriculture, mining and extensive grazing. The three NSW CMAs have recently completed strategic level CAPs, with implementation plans to be finalised in 2014/2015. SEQC and FBA are beginning a review of their existing NRM Plans, to be completed in 2014 and 2015 respectively; while BMRG is aiming to produce a NRM and Climate Variability Action Strategy. The regional bodies will receive funding from the Australian Government through the Regional NRM Planning for Climate Change Fund (NRM Fund) to improve regional planning for climate change and help guide the location of carbon and biodiversity activities, including wildlife corridors. The bulk of the funding will be available for activities in 2013/2014, with smaller amounts available in subsequent years. Most regional bodies aim to have a large proportion of the planning work complete by the end of 2014. In addition, NSW CMAs are undergoing major structural change and will be incorporated into semi‐autonomous statutory Local Land Services bodies from 2014. Boundaries will align with local government boundaries and there will be significant change in staff and structures. The regional bodies in the cluster have a varying degree of climate knowledge. All plans recognise climate change as a key driver of change, but there are few specific actions or targets addressing climate change. Regional bodies also have varying capacity to analyse large volumes of spatial or modelling data. Due to the complex nature of natural resource management, all regional bodies work with key stakeholders (e.g. local government, industry groups, and community groups) to deliver NRM outcomes. Regional bodies therefore require project outputs that can be used directly in stakeholder engagement activities, and are likely to require some form of capacity building associated with each of the outputs to maximise uptake. Some of the immediate needs of the regional bodies are a summary of information or tools that are able to be used immediately; and a summary of the key outputs and milestone dates for the project, to facilitate alignment of planning activities with research outputs. A project framework is useful to show the linkages between research elements and the relevance of the research to the adaptive management cycle for NRM planning in which the regional bodies are engaged. A draft framework is proposed to stimulate and promote discussion on research elements and linkages; this will be refined during and following the development of the detailed project work plan. The regional bodies strongly emphasised the need to incorporate a shift to a systems based resilience approach to NRM planning, and that approach is included in the framework. The regional bodies identified that information on climate projections would be most useful at regional and subregional scale, to feed into scenario planning and impact analysis. Outputs should be ‘engagement ready’ and there is a need for capacity building to enable regional bodies to understand and use the projections in stakeholder engagement. There was interest in understanding the impacts of climate change projections on ecosystems (e.g. ecosystem shift), and the consequent impacts on the production of ecosystem services. It was emphasised that any modelling should be able to be used by the regional bodies with their stakeholders to allow for community input (i.e. no black box models). The online regrowth benefits tool was of great interest to the regional bodies, as spatial mapping of carbon farming opportunities would be relevant to their funding requirements. The NSW CMAs identified an interest in development of the tool for NSW vegetation types. Needs relating to socio‐economic information included understanding the socio‐economic determinants of carbon farming uptake and managing community expectations. A need was also identified to understand the vulnerability of industry groups as well as community to climate change impacts, and in particular understanding how changes in the flow of ecosystem services would interact with the vulnerability of these groups to impact on the linked ecologicalsocio‐economic system. Responses to disasters (particularly flooding and storm surge) and recovery responses were also identified as being of interest. An ecosystem services framework was highlighted as a useful approach to synthesising biophysical and socioeconomic information in the context of a systems based, resilience approach to NRM planning. A need was identified to develop processes to move towards such an approach to NRM planning from the current asset management approach. Examples of best practice in incorporating climate science into planning, using scenarios for stakeholder engagement in planning and processes for institutionalising learning were also identified as cross‐cutting needs. The over‐arching theme identified was the need for capacity building for the NRM bodies to best use the information available at any point in time. To this end a planners working group has been established to support the building of a network of informed and articulate NRM agents with knowledge of current climate science and capacity to use current tools to engage stakeholders in NRM planning for climate change adaptation. The planners working group would form the core group of the community of practice, with the broader group of stakeholders participating when activities aligned with their interests. In this way, it is anticipated that the Project will contribute to building capacity within the wider community to effectively plan for climate change adaptation.

Who selects the 'right' directors? An examination of the association between board selection, gender diversity and outcomes

Using a sample of companies from the top 500 listed firms in Australia, we investigate whether the presence of a designated nomination committee and female representation on the nomination committee affect board gender diversity. We also examine whether gender diversity on the board affects firm risk and financial performance. We find that board gender diversity is significantly and positively associated with the presence of a designated nomination committee and that female representation on the nomination committee is a significant explanatory factor of increasing board gender diversity following the release of the 2010 Australian Securities Exchange Corporate Governance Council (ASXCGC) recommendations. Further, our results support the business case for board gender diversity as we find greater gender diversity moderates excessive firm risk which in turn improves firms’ financial performance. Our results are robust after correcting for selection bias and controlling for other board, firm and industry characteristics.

The association between social support and levels of psychological distress in pregnant women in Australia

The purpose of this study was to explore associations between forms of social support and levels of psychological distress during pregnancy. Methods: A cross-sectional analysis of 2,743 pregnant women from south-east Queensland, Australia, was conducted utilising data collected between 2007-2011 as part of the Environments for Healthy Living (EFHL) project, Griffith University. Psychological distress was measured using the Kessler 6; social support was measured using the following four factors: living with a partner, living with parents or in-laws, self-perceived social network, and area satisfaction. Data were analysed using an ordered logistic regression model controlling for a range of socio-demographic factors. Results: There was an inverse association between self-perceived strength of social networks and levels of psychological distress (OR = 0.77; 95%CI: 0.70, 0.85) and between area satisfaction and levels of psychological distress (OR = 0.77; 95%CI: 0.69, 0.87). There was a direct association between living with parents or in-laws and levels of psychological distress (OR = 1.50; 95%CI: 1.16, 1.96). There was no statistically significant association between living with a partner and the level of psychological distress of the pregnant woman after accounting for household income. Conclusion: Living with parents or in-laws is a strong marker for psychological distress. Strategies aiming to build social support networks for women during pregnancy have the potential to provide a significant benefit. Policies promoting stable family relationships and networks through community development could also be effective in promoting the welfare of pregnant women.

Braving a New World : Design Interventions for Changing Climates. Papers from the Subtropical Cities 2013 Fall Conference of the Association of Collegiate Schools of Architecture (ACSA)

We no longer have the luxury of time as the effects of climate change are being felt, according to the latest Intergovernmental Panel on Climate Change report, on every continent and in every ocean. More than 50% of the population of the United States and 85% of Australians live in coastal regions. The number of people living in the world’s coastal regions is expected to increase along with the need to improve capacity to mitigate hazards , and manage the multiple risks that have been identified by the scientific community. Under the auspices of the Association of Collegiate Schools of Architecture (ACSA) design academics and practitioners from the Americas, Asia, and Australia met in Fort Lauderdale, Florida for the fourth Subtropical Cities international conference to share outcomes of research and new pedagogies to address the critical transformation of the physical environments and infrastructures of the world’s vulnerable coastal communities. The theme of Subtropical Cities, adopted by the ACSA for its Fall 2014 Conference, is not confined entirely to a latitudinal or climatic frame of reference. The paper and project presentations addressed a range of theoretical, practice-led, and education-oriented research topics in architecture and urban design related to the subtropics, with emphasis on urban and coastal regions. More than half the papers originate from universities and practices in coastal regions. Threads emerged from a tapestry of localized investigations to reveal a more global understanding about possible futures we are designing for current and future generations. The one hundred-plus conference delegates and presenters represented 33 universities and institutions from across the United States, Mexico, Canada, Australia, the Middle East, Peru and China. Case studies from India, Morocco, Tahiti, Indonesia, Jordan, and Cambodia were also presented, expanding the global knowledge base. Co-authored submissions presented new directions for architecture and design, with a resounding theme of collaboration across diverse disciplines. The ability to deal with abstraction and complexity, and the capacity to develop synthesis and frameworks for defining problem boundaries can be considered key attributes of architectural thinking. Such a unique set of abilities can forge collaboration with different professional disciplines to achieve extraordinary outcomes. As the broad range of papers presented at this conference suggest, existing architectural and urban typologies and practices are increasingly considered part of the cause and not the solution to adapting to climate change and sea level rise. Design responses and the actions needed to generate new and unfamiliar forms of urbanism and infrastructure for defense, adaptation, and retreat in subtropical urban regions are being actively explored in academic design studios and research projects around the world. Many presentations propose provocative and experimental strategies as global climate moves beyond our “comfort zone”. The ideas presented at the Subtropical Cities conference are timely as options for low-energy passive climatic design are becoming increasingly limited in the context of changing climate. At the same time, ways of reducing or obsoleting energy intensive mechanical systems in densely populated urban centres present additional challenges for designers and communities as a whole. The conference was marked by a common theme of trans-disciplinary research, where design integration with emerging technologies resonate with a reaffirmation of the centrality of design thinking, expanding the scope of the traditional architecture studio pedagogy to integrate knowledge from other disciplines and the participation of diverse communities.

Measuring patient flow variations : a cross-organisational process mining approach

Variations that exist in the treatment of patients (with similar symptoms) across different hospitals do substantially impact the quality and costs of healthcare. Consequently, it is important to understand the similarities and differences between the practices across different hospitals. This paper presents a case study on the application of process mining techniques to measure and quantify the differences in the treatment of patients presenting with chest pain symptoms across four South Australian hospitals. Our case study focuses on cross-organisational benchmarking of processes and their performance. Techniques such as clustering, process discovery, performance analysis, and scientific workflows were applied to facilitate such comparative analyses. Lessons learned in overcoming unique challenges in cross-organisational process mining, such as ensuring population comparability, data granularity comparability, and experimental repeatability are also presented.

Rabobank : a process mining case study BPI Challenge 2014 report

The increased interest in the area of process improvement persuaded Rabobank Group ICT in examining its own Change-process in order to improve its competitiveness. The group is looking for answers about the effectiveness of changes applied as part of this process, with particular interest toward the presence of predictive patterns and their parameters. We conducted an analysis of the log using well established process mining techniques (i.e. Fuzzy Miner). The results of the analysis conducted on the log of the process show that a visible impact is missing.

Head and neck squamous-cell cancer and its association with polymorphic enzymes of xenobiotic metabolism and repair

Tobacco smoking, alcohol drinking, and occupational exposures to polycyclic aromatic hydrocarbons are the major proven risk factors for human head and neck squamous-cell cancer (HNSCC). Major research focus on gene-environment interactions concerning HNSCC has been on genes encoding enzymes of metabolism for tobacco smoke constituents and repair enzymes. To investigate the role of genetically determined individual predispositions in enzymes of xenobiotic metabolism and in repair enzymes under the exogenous risk factor tobacco smoke in the carcinogenesis of HNSCC, we conducted a case-control study on 312 cases and 300 noncancer controls. We focused on the impact of 22 sequence variations in CYP1A1, CYP1B1, CYP2E1, ERCC2/XPD, GSTM1, GSTP1, GSTT1, NAT2, NQO1, and XRCC1. To assess relevant main and interactive effects of polymorphic genes on the susceptibility to HNSCC we used statistical models such as logic regression and a Bayesian version of logic regression. In subgroup analysis of nonsmokers, main effects in ERCC2 (Lys751Gln) C/C genotype and combined ERCC2 (Arg156Arg) C/A and A/A genotypes were predominant. When stratifying for smokers, the data revealed main effects on combined CYP1B1 (Leu432Val) C/G and G/G genotypes, followed by CYP1B1 (Leu432Val) G/G genotype and CYP2E1 (-70G>T) G/T genotype. When fitting logistic regression models including relevant main effects and interactions in smokers, we found relevant associations of CYP1B1 (Leu432Val) C/G genotype and CYP2E1 (-70G>T) G/T genotype (OR, 10.84; 95% CI, 1.64-71.53) as well as CYP1B1 (Leu432Val) G/G genotype and GSTM1 null/null genotype (OR, 11.79; 95% CI, 2.18-63.77) with HNSCC. The findings underline the relevance of genotypes of polymorphic CYP1B1 combined with exposures to tobacco smoke.

Social water assessment protocol : a step towards connecting mining, water and human rights

The human right to water has recently been recognised by both the United Nations General Assembly and the Human Rights Council. As the mining industry interacts with water on multiple levels, it is important that these interactions respect the human right to water. Currently, a disconnect exists between mine site water management practices and the recognition of water from a human rights perspective. The Minerals Council of Australia (MCA) Water Accounting Framework (WAF) has previously been used to strengthen the connection between water management and human rights. This article extends this connection through the use of a Social Water Assessment Protocol (SWAP). The SWAP is scoping tool consisting of a set of questions classified into taxonomic themes under leading topics with suggested sources of data that enable mine sites to better understand the local water context in which they operate. Three of the themes contained in the SWAP – gender, Indigenous peoples and health – are discussed to demonstrate how the protocol may be useful in assisting mining companies to consider their impacts on the human right to water.

Social licence to operate and the coal seam gas industry : lessons from social issues in established mining operations?

The recent growth of the coal seam gas industry has increased pressure on regional communities. Debate surrounding the industry is intense and a social licence to operate has yet to be granted to the industry in its entirety. This article presents an analysis of social issues surrounding the coal seam gas industry, making comparisons between two case studies: the Ranger and Jabiluka mines and the Yandicoogina mine. It presents the results of a desktop study, focussed on three topics: community identity; procedural justice and distributive justice, which provides a means for comparison and draws attention to central concerns. It is found that: power imbalances; changing community identities; potentially inequitable distributions of long term benefits and the process to distribute those benefits and negative perceptions of the industry as a whole serve to undermine the provision of a social licence to operate by communities and has the potential to impose significant negative impacts on companies within the industry.

Mining business process deviance : a quest for accuracy

This paper evaluates the suitability of sequence classification techniques for analyzing deviant business process executions based on event logs. Deviant process executions are those that deviate in a negative or positive way with respect to normative or desirable outcomes, such as non-compliant executions or executions that undershoot or exceed performance targets. We evaluate a range of feature types and classification methods in terms of their ability to accurately discriminate between normal and deviant executions both when deviances are infrequent (unbalanced) and when deviances are as frequent as normal executions (balanced). We also analyze the ability of the discovered rules to explain potential causes and contributing factors of observed deviances. The evaluation results show that feature types extracted using pattern mining techniques only slightly outperform those based on individual activity frequency. The results also suggest that more complex feature types ought to be explored to achieve higher levels of accuracy.

On the operationalisation of conceptions of learning in higher education and their association with students’ knowledge and experiences of their learning

Conceptions of learning, as well as other associated aspects of prior knowledge, are theoretically important factors in influencing the manner in which the content and context of learning are engaged. The present study reports on: (a) the operationalisation of some of these factors aimed at isolating sources of explanatory variation that can be used for modelling purposes; and (b) a conservative exploration of the discriminatory power of, and exhibited patterns of association between, such sources of variation as have been isolated. Based on a conservative analytical approach, the results of the present study do not support a single clearly defined empirical model of conceptions of learning and associated constructs. Instead, there is consistent evidence that underlying empirical structures appear to be sensitive to the response context and other factors.