Correlation of tumor- and stromal-derived MT1-MMP expression with progression of human ovarian tumors in SCID mice

Human ovarian carcinoma samples were orthotopically implanted into SCID mice to investigate the contribution of matrix metalloproteases (MMPs) to the spread of ovarian tumors. Mice were inoculated with patient tumor samples, and developed ovarian tumors over a 16-week period with metastasis occurring in some mice. Species-specific quantitative RT-PCR was used to identify the source of tumor-associated MMPs. Membrane-type (MT)1-MMP mRNA was significantly increased in high-grade tumors, tumors with evidence of serosal involvement, and tumors in which distant metastases were detected. The increase in MT1-MMP expression was predominantly from the human tumor cells, with a minor contribution from the mouse ovarian stroma. Neither human nor mouse MT2-MMP were correlated with tumor progression and MT3-MMP levels were negligible. While tumor cells did not produce significant amounts of MMP-2 or MMP-9, the presence of tumor was associated with increased levels of MMP-2 expression by mouse ovarian stroma. Stromal-derived MT1-MMP was greater in large tumors and was associated with stromal MMP-2 expression but neither was significantly linked with metastasis. These studies indicate that tumor-derived MT1-MMP, more so than other gelatinolytic MMPs, is strongly linked to aggressive tumor behavior. This orthotopic model of human ovarian carcinoma is appropriate for studying ovarian tumor progression, and will be valuable in the further investigation of the metastatic process.

More than a backchannel : Twitter and television

Twitter is a social media service that has managed very successfully to embed itself deeply in the daily lives of its users. Its short message length (140 characters), and one-way connections (‘following’ rather than ‘friending’), lead themselves effectively to random and regular updates on almost any form of personal or professional activity. Thus, it has found uses from the interpersonal (e.g. Boyd et al., 2010) through crisis communication (e.g. Bruns et al., 2012), to political debate (e.g. Burgess & Bruns, 2012). In such uses, Twitter does not necessarily replace existing media channels, such as broadcasting or online mainstream media, but often complements them, providing its users with alternative opportunities to contribute more actively to the wider media sphere. This is true especially where Twitter is used alongside television, as a simple backchannel to live programming or for more sophisticated uses. In this article, we outline four aspects and dimensions, of the way that the old medium of television intersects, and in some cases, interacts with the new medium of Twitter. Tweeting about the television has always been a social media form. It has also consistently provided key ‘talking points’ for western societies...

Outback institutions : an application of the Institutional Analysis and Development (IAD) framework to four case studies in Australia’s Outback -- Part 4 : Incentives for community participation and land use decisions in Etheridge Shire, Queensland

Natural resource management planning in the Northern Gulf region of Queensland is concerned with ‘how [natural assets] and community aspirations can be protected and enhanced to provide the Northern Gulf community with the economic, social and environmental means to meet the continuing growth of the region in an ecological and economically sustainable way’ (McDonald & Dawson 2004). In the Etheridge Shire, located in the tropical savanna of the Northern Gulf region, two of the activities that influence the balance between economic growth and long-term sustainable development are: 1. the land-use decisions people in the Shire make with regards to their own enterprises. 2. their decisions to engage in civically-minded activities aimed at improving conditions in the region. Land-use decision and engagement in community development activities were chosen for detailed analysis because they are activities for which policies can be devised to improve economic and sustainable development outcomes. Changing the formal and informal rules that guide and govern these two different kinds of decisions that people can make in the Etheridge Shire – the decision to improve one’s own situation and the decision to improve the situation for others in the community – may expand the set of available options for people in the Shire to achieve their goals and aspirations. Identifying appropriate and effective changes in rules requires, first, an understanding of the ‘action arena’, in this case comprised of a diversity of ‘participants’ from both within and outside the Etheridge Shire, and secondly knowledge of ‘action situations’ (land-use decisions and engagement in community development activities) in which stakeholders are involved and/or have a stake. These discussions are presented in sections 4.1.1.1 and 4.1.1.2.

Follow the leader if you can, hedge if you must

Follow-the-Leader (FTL) is an intuitive sequential prediction strategy that guarantees constant regret in the stochastic setting, but has poor performance for worst-case data. Other hedging strategies have better worst-case guarantees but may perform much worse than FTL if the data are not maximally adversarial. We introduce the FlipFlop algorithm, which is the first method that provably combines the best of both worlds. As a stepping stone for our analysis, we develop AdaHedge, which is a new way of dynamically tuning the learning rate in Hedge without using the doubling trick. AdaHedge refines a method by Cesa-Bianchi, Mansour, and Stoltz (2007), yielding improved worst-case guarantees. By interleaving AdaHedge and FTL, FlipFlop achieves regret within a constant factor of the FTL regret, without sacrificing AdaHedge’s worst-case guarantees. AdaHedge and FlipFlop do not need to know the range of the losses in advance; moreover, unlike earlier methods, both have the intuitive property that the issued weights are invariant under rescaling and translation of the losses. The losses are also allowed to be negative, in which case they may be interpreted as gains.

Tristate

"This work forms part of a much larger collaborative album project in progress between Tim Bruniges, Julian Knowles and David Trumpmanis which explores the intersections between traditional rock instrumentation and analogue and digital media. All of the creative team are performers, composers and producers. The material for the album was thus generated by a series of in studio improvisations and performances with each collaborator assuming a range of different and alternating roles – guitars, electronics, drums, percussion, bass, keyboards production. Thematically the work explores the intersection of instrumental (post) rock, ambient music, and historical electro-acoustic tape composition traditions. Over the past 10 years, musical practice has become increasingly hybrid, with the traditional boundaries between genre becoming progressively eroded. At the same time, digital tools have replaced many of the major analogue technologies that dominated music production and performance in the 20th century. The disappearance of analogue media in mainstream musical practice has had a profound effect on the sonic characteristics of contemporary music and the gestural basis for its production. Despite the increasing power of digital technologies, a small but dedicated group of practitioners has continued to prize and use analogue technology for its unique sounds and the non-linearity of the media, aestheticising its inherent limitations and flaws. At the most radical end of this spectrum lie glitch and lo-fi musical forms, seen in part as reactions to the clinical nature of digital media and the perceived lack of character associated with its transparency. Such developments have also problematised the traditional relationships between media and genre, where specific techniques and their associated sounds have become genre markers. Tristate is an investigation into this emerging set of dialogues between analogue and digital media across composition, production and performance. It employs analogue tape loops in performance, where a tape machine ‘performer’ records and hand manipulates loops of an electric guitar performer on ‘destroyed’ tape stock (intentionally damaged tape), processing the output of this analogue system in the digital domain with contemporary sound processors. In doing so it investigates how the most extreme sonic signatures of analogue media – tape dropout and noise – can be employed alongside contemporary digital sound gestures in both compositional and performance contexts and how the extremes of the two media signatures can brought together both compositionally and performatively. In respect of genre, the work established strategies for merging compositional techniques from the early musique concrete tradition of the 1940s with late 60s popular music experimentalism and the laptop glitch electronica movement of the early 2000s. Lastly, the work explores how analogue recording studio technologies can be used as performance tools, thus illuminating and foregrounding the performative/gestural dimensions of traditional analogue studio tools in use."

Mid-Aged Adults' Sitting Time in Three Contexts

BACKGROUND: To develop evidence-based approaches for reducing sedentary behavior, there is a need to identify the specific settings where prolonged sitting occurs, associated factors, and variations. PURPOSE: To examine the sociodemographic and health factors associated with mid-aged adults' sitting time in three contexts and variations between weekdays and weekend days. METHODS: A mail survey was sent to 17,000 adults (aged 40-65 years) in 2007; 11,037 responses were received (68.5%); and 7719 were analyzed in 2010. Respondents indicated time spent sitting on a usual weekday and weekend day for watching TV, general leisure, and home computer use. Multivariate linear mixed models with area-level random intercepts were used to examine (1) associations between sociodemographic and health variables and sitting time, and (2) interaction effects of weekday/weekend day with each of gender, age, education, and employment status, on sitting time. RESULTS: For each context, longer sitting times were reported by those single and living alone, and those whose health restricted activity. For watching TV, longer sitting times were reported by men; smokers; and those with high school or lower education, not in paid employment, in poor health, and with BMI ≥25. For general leisure, longer sitting times were reported by women, smokers, and those not employed full-time. For home computer use, longer sitting times were reported by men; and those aged 40-44 years, with university qualifications; in the mid-income range; and with BMI ≥30. Sitting times tended to be longer on weekend days than weekdays, although the extent of this differed among sociodemographic groups. CONCLUSIONS: Sociodemographic and health factors associated with sitting time differ by context and between weekdays and weekend days.

Homelessness and leaving care : the experiences of young adults in Queensland and Victoria, and implications for practice

This research first asks ‘What happens when young people leave state care?’ in respect of Victoria and Queensland and second ‘What are the service support implications of this?’ A number of methods were used to explore these questions including semi-structured interviews with 27 young adults aged 19-23 years who had been homeless or at risk of homelessness, and focus groups with young people and service providers. This study provides support for the proposition that young people should be proactively and voluntarily involved in periodic monitoring of their lived experience post care and linkage of this monitoring to the activation of timely support. The great majority of young people involved in this study thought this was not only desirable but important. Whilst some young people will be in close contact with leaving care services many others will not. New research is recommended to develop a mentoring and support activation process using participatory monitoring and action research methods. This type of approach reflects the importance of utilising processes with young people in care and leaving care which acknowledge their personhood and capacity to contribute voluntarily to the processes which seek to support them.

Enhancing the capacity of kin caregivers and their families to meet the needs of children left behind

Based on qualitative research of the experiences of 23 kin caregivers and five school personnel, this article explores the role of informal kinship care in addressing the needs of school-age children left behind in rural China. The findings of this study suggest that kin caregivers' child-rearing capacity is limited in the rural context, and they are often overwhelmed by children's diverse and complex needs, particularly their emotional ones. In view of the huge population and their vulnerability, it is imperative for the state to take up its responsibilities and develop specific social work services and other support for children left behind and their families. 根据对23位亲属照顾者和5位学校人员的质性研究，文章探讨在处理中国留守学龄儿童的需要时，非正式亲属照料所担当的角色。研究发现，在农村的亲属照料者的抚养儿童能力有限，而且他们时常在面对儿童众多复杂的需求时应接不暇，问题又以情绪需要尤甚。有见于留守儿童的数目众多和易受伤害，政府急切需要承担相关的责任，为留守儿童及其家庭发展专门的社会工作服务和其他支援。

Current trends and challenges for sport and exercise psychology – What now for our discipline?

With an ever changing landscape including National Registration, endorsed areas of practice, establishment of Sport and Exercise Psychology coordinators within National Sporting Organisations, changes to the National and State Sporting Insitutions, this forum looks to explore through collegiate discussion the impacts, current and future implications for our profession across training, supervision, research and applied practice in Australia.

New country market feasibility analyses

Opportunity screening is also known as feasibility testing, which is the process of assessing whether a particular business opportunity is within the capacity of either an entrepreneur or an intrapreneur, and also whether it can create sustainable revenues. As the funnel diagram shows, the number of opportunities diminishes as we move to the right through the diagram. This is because not every idea identified in the opportunity identification stage as potentially interesting, and then framed into a business opportunity in the opportunity development stage, will satisfy the formal and informal screening criteria. The informal screening process occurs in all stages of the development process. For example, not every idea that has been identified will be converted into a business opportunity; similarly, not every business opportunity progresses to a feasibility test. Subsequently, only the best business opportunities are screened, and only the very best of those screened then progress to the business plan step.

Managing growth and entry strategies across borders

Should the firm move successfully into a growth or expansion phase the owner manager will be required to increase the scale and scope of its operations. Part of this expansion will involve hiring additional employees, and increasing the overall complexity of the firm's activities. It is likely that the need for greater levels of professional management will be required to operate the firm, along with the need for enhanced planning and the introduction of systems to support the new levels of complexity. The transition from a small, owner-managed firm to a large systems-managed business will require the development of a team-based management approach with greater specialisation within the management team. Corporate governance is also likely to change as the growth cycle takes place. As it grows, the business will become more formalised in its accounting, management and other systems. The need for greater quantities of capital is likely to lead the business towards equity finance. As new equity partner are taken into the company the original owner managers may find their level of control diminished. The larger the firm becomes the more likely its management structure will become decentralised with greater separation between the owner and the firm in terms of operational and financial matters.

Global outsourcing, production and logistics

Supply chains are the core of most industrial networks in which your business operates. They provide the pipeline through which the products and services flow from supplier to customer across each element within the business activity system. Global supply chain relationships have become the basis for many industries with an international network of firms engaged in the supply of goods and services that must be produced to quality standards in one country and delivered just-in-time for assembly or integration into further production processes in another country, frequently many thousands of miles apart. This topic examines the nature of supply chain management and their role in strategic networking. The previous learning tasks have focused on having the correct internal mechanism to effectively manage the inputs and outputs of the organisation by implementing an effective and transparent management system. This learning task takes a look at how management intent strategy and innovation are used to measure the external factors that influence the overall performance of the organisation and develop new strategies by understanding the business cycle and the people within your market environment.

Physical activity, walking and quality of life in women with depressive symptoms

Background Physical activity (PA) has a positive association with health-related quality of life (HRQL) in the general population. The association between PA and HRQL in those with poor mental health is less clear. Purpose To examine the concurrent and prospective dose-response relationships between total physical activity (TPA) and walking only with HRQL in women aged 50-55 with depressive symptoms in 2001. Methods Participants were 1904 women born in 1946-1951 who completed mailed surveys for the Australian Longitudinal Study on Women's Health in 2001, 2004, 2007 and 2010 and who, in 2001, reported depressive symptoms. At each time point, they reported their weekly minutes of walking, moderate PA, and vigorous PA. A summary TPA score was created that accounted for differences in energy expenditure among the three PA types. Mixed models were used to examine associations between TPA and HRQL (SF-36 component and subscale scores) and between walking and HRQL, for women who reported walking as their only PA. Analyses were conducted in 2013-2014. Results Concurrently, higher levels of TPA and walking were associated with better HRQL (p<0.05). The strongest associations were found for physical functioning, vitality, and social functioning subscales. In prospective models, associations were attenuated, yet compared with women doing no TPA or walking, women doing “sufficient” TPA or walking had significantly better HRQL over time for most SF-36 scales. Conclusions This study extends previous work by demonstrating trends between both TPA and walking and HRQL in women reporting depressive symptoms.

Transcriptional pathway signatures predict MEK addiction and response to selumetinib (AZD6244)

Selumetinib (AZD6244, ARRY-142886) is a selective, non-ATP-competitive inhibitor of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-1/2. The range of antitumor activity seen preclinically and in patients highlights the importance of identifying determinants of response to this drug. In large tumor cell panels of diverse lineage, we show that MEK inhibitor response does not have an absolute correlation with mutational or phospho-protein markers of BRAF/MEK, RAS, or phosphoinositide 3-kinase (PI3K) activity. We aimed to enhance predictivity by measuring pathway output through coregulated gene networks displaying differential mRNA expression exclusive to resistant cell subsets and correlated to mutational or dynamic pathway activity. We discovered an 18-gene signature enabling measurement of MEK functional output independent of tumor genotype. Where the MEK pathway is activated but the cells remain resistant to selumetinib, we identified a 13-gene signature that implicates the existence of compensatory signaling from RAS effectors other than PI3K. The ability of these signatures to stratify samples according to functional activation of MEK and/or selumetinib sensitivity was shown in multiple independent melanoma, colon, breast, and lung tumor cell lines and in xenograft models. Furthermore, we were able to measure these signatures in fixed archival melanoma tumor samples using a single RT-qPCR-based test and found intergene correlations and associations with genetic markers of pathway activity to be preserved. These signatures offer useful tools for the study of MEK biology and clinical application of MEK inhibitors, and the novel approaches taken may benefit other targeted therapies.

Dancing through the Air (parts one and 2) - Spirit of Akasha

Recording for ARIA nominated Film Soundtrack for Spirit of Akasha. Recorded, Mixed, and Co-produced by Phil Graham. Published by Warner Music Australia