Evidence for a dual function of EphB4 as tumor promoter and suppressor regulated by the absence or presence of the ephrin-B2 ligand

Overexpression of the receptor tyrosine kinase EphB4 is common in epithelial cancers and linked to tumor progression by promoting angiogenesis, increasing survival and facilitating invasion and migration. However, other studies have reported loss of EphB4 suggesting a tumor suppressor function in some cancers. These opposing roles may be regulated by (i) the presence of the primary ligand ephrin-B2 that regulates pathways involved in tumor suppression or (ii) the absence of ephrin-B2 that allows EphB4 signaling via ligand-independent pathways that contribute to tumor promotion. To explore this theory, EphB4 was overexpressed in the prostate cancer cell line 22Rv1 and the mammary epithelial cell line MCF-10A. Overexpressed EphB4 localized to lipid-rich regions of the plasma membrane and confirmed to be ligand-responsive as demonstrated by increased phosphorylation of ERK1/2 and internalization. EphB4 overexpressing cells demonstrated enhanced anchorage-independent growth, migration and invasion, all characteristics associated with an aggressive phenotype, and therefore supporting the hypothesis that overexpressed EphB4 facilitates tumor promotion. Importantly, these effects were reversed in the presence of ephrin-B2 which led to a reduction in EphB4 protein levels, demonstrating that ligand-dependent signaling is tumor suppressive. Furthermore, extended ligand stimulation caused a significant decrease in proliferation that correlated with a rise in caspase-3/7 and -8 activities. Together, these results demonstrate that overexpression of EphB4 confers a transformed phenotype in the case of MCF-10A cells and an increased metastatic phenotype in the case of 22Rv1 cancer cells and that both phenotypes can be restrained by stimulation with ephrin-B2, in part by reducing EphB4 levels.

Kallikrein 14 is down-regulated by androgen receptor signalling and harbours genetic variation that is associated with prostate tumour aggressiveness

Kallikrein 14 (KLK14) has been proposed as a useful prognostic marker in prostate cancer, with expression reported to be associated with tumour characteristics such as higher stage and Gleason score. KLK14 tumour expression has also shown the potential to predict prostate cancer patients at risk of disease recurrence after radical prostatectomy. The KLKs are a remarkably hormone-responsive family of genes, although detailed studies of androgen regulation of KLK14 in prostate cancer have not been undertaken to date. Using in vitro studies, we have demonstrated that unlike many other prostatic KLK genes that are strictly androgen responsive, KLK14 is more broadly expressed and inversely androgen regulated in prostate cancer cells. Given these results and evidence that KLK14 may play a role in prostate cancer prognosis, we also investigated whether common genetic variants in the KLK14 locus are associated with risk and/or aggressiveness of prostate cancer in approximately 1200 prostate cancer cases and 1300 male controls. Of 41 single nucleotide polymorphisms assessed, three were associated with higher Gleason score (≥7): rs17728459 and rs4802765, both located upstream of KLK14, and rs35287116, which encodes a p.Gln33Arg substitution in the KLK14 signal peptide region. Our findings provide further support for KLK14 as a marker of prognosis in prostate cancer.

A systematic review of psychological interventions for excessive alcohol consumption among people with psychotic disorders

Objective: Excessive alcohol consumption is common among people with psychotic disorders. While there is an extensive literature on the efficacy of psychological treatments for excessive drinking, few studies have examined interventions addressing this issue among people with psychotic disorders. Method: Systematic searches in PubMed and PsycINFO were conducted to identify randomized controlled trials comparing manual guided psychological interventions for excessive alcohol consumption among individuals with psychotic disorders. Of the 429 articles identified, 7 met inclusion criteria. Data were extracted from each study regarding study sample characteristics, design, results, clinical significance of alcohol consumption results, and methodological limitations. Results: Assessment interviews, brief motivational interventions and lengthier cognitive behavior therapy have been associated with reductions in alcohol consumption among people with psychosis. While brief interventions (i.e., 1-2 sessions) were generally as effective as longer duration psychological interventions (i.e., 10 session) for reducing alcohol consumption, longer interventions provided additional benefits for depression, functioning and other alcohol outcomes. Conclusion: Excessive alcohol consumption among people with psychotic disorders is responsive to psychological interventions. It is imperative that such approaches are integrated within standard care for people with psychosis.

Cloning of a novel insulin-regulated ghrelin transcript in prostate cancer

Ghrelin is a multifunctional hormone, with roles in stimulating appetite and regulating energy balance, insulin secretion and glucose homeostasis. The ghrelin gene locus (GHRL) is highly complex and gives rise to a range of novel transcripts derived from alternative first exons and internally spliced exons. The wild-type transcript encodes a 117 amino acid preprohormone that is processed to yield the 28 amino acid peptide ghrelin. Here, we identified insulin-responsive transcription corresponding to cryptic exons in intron 2 of the human ghrelin gene. A transcript, termed in2c-ghrelin (intron 2-cryptic), was cloned from the testis and the LNCaP prostate cancer cell line. This transcript may encode an 83 AA preproghrelin isoform that codes for the ghrelin, but not obestatin. It is expressed in a limited number of normal tissues and in tumours of the prostate, testis, breast and ovary. Finally, we confirmed that in2c-ghrelin transcript expression, as well as the recently described in1-ghrelin transcript, is significantly upregulated by insulin in cultured prostate cancer cells. Metabolic syndrome and hyperinsulinaemia has been associated with prostate cancer risk and progression. This may be particularly significant after androgen deprivation therapy for prostate cancer, which induces hyperinsulinaemia, and this could contribute to castrate resistant prostate cancer growth. We have previously demonstrated that ghrelin stimulates prostate cancer cell line proliferation in vitro. This study is the first description of insulin regulation of a ghrelin transcript in cancer, and should provide further impetus for studies into the expression, regulation and function of ghrelin gene products.

How much do residential aged care staff members know about the nutritional needs of residents?

Background Undernutrition, weight loss and dehydration are major clinical issues for people with dementia in residential care, with excessive weight loss contributing to increased risk of frailty, immobility, illness and premature morbidity. This paper discusses a nutritional knowledge and attitudes survey conducted as part of a larger project focused on improving nutritional intake of people with dementia within a residential care facility in Brisbane, Australia. Aims The specific aims of the survey were to identify (i) knowledge of the nutritional needs of aged care facility residents; (ii) mealtime practices; and (iii) attitudes towards mealtime practices and organisation. Methods A survey based on those used in other healthcare settings was completed by 76 staff members. The survey included questions about nutritional knowledge, opinions of the food service, frequency of feeding assistance provided and feeding assessment practices. Results Nutritional knowledge scores ranged from 1 to 9 of a possible 10, with a mean score of 4.67. While 76% of respondents correctly identified risk factors associated with malnutrition in nursing home residents, only 38% of participants correctly identified the need for increased protein and energy in residents with pressure ulcers, and just 15% exhibited correct knowledge of fluid requirements. Further, while nutritional assessment was considered an important part of practice by 83% of respondents, just 53% indicated that they actually carried out such assessments. Identified barriers to promoting optimal nutrition included insufficient time to observe residents (56%); being unaware of residents' feeding issues (46%); poor knowledge of nutritional assessments (44%); and unappetising appearance of food served (57%). Conclusion An important step towards improving health and quality of life for residents of aged care facilities would be to enhance staff nutritional awareness and assessment skills. This should be carried out through increased attention to both preservice curricula and on-the-job training. Implications for practice The residential facility staff surveyed demonstrated low levels of nutrition knowledge, which reflects findings from the international literature. This has implications for the provision of responsive care to residents of these facilities and should be explored further.

Learning landscapes 2.0 : warning - assembly required

Twenty first century learners operate in organic, immersive environments. A pedagogy of student-centred learning is not a recipe for rooms. A contemporary learning environment is like a landscape that grows, morphs, and responds to the pressures of the context and micro-culture. There is no single adaptable solution, nor a suite of off-the-shelf answers; propositions must be customisable and infinitely variable. They must be indeterminate and changeable; based on the creation of learning places, not restrictive or constraining spaces. A sustainable solution will be un-fixed, responsive to the life cycle of the components and materials, able to be manipulated by the users; it will create and construct its own history. Learning occurs as formal education with situational knowledge structures, but also as informal learning, active learning, blended learning social learning, incidental learning, and unintended learning. These are not spatial concepts but socio-cultural patterns of discovery. Individual learning requirements must run free and need to be accommodated as the learner sees fit. The spatial solution must accommodate and enable a full array of learning situations. It is a system not an object. Three major components: 1. The determinate landscape: in-situ concrete 'plate' that is permanent. It predates the other components of the system and remains as a remnant/imprint/fossil after the other components of the system have been relocated. It is a functional learning landscape in its own right; enabling a variety of experiences and activities. 2. The indeterminate landscape: a kit of pre-fabricated 2-D panels assembled in a unique manner at each site to suit the client and context. Manufactured to the principles of design-for-disassembly. A symbiotic barnacle like system that attaches itself to the existing infrastructure through the determinate landscape which acts as a fast growth rhizome. A carapace of protective panels, infinitely variable to create enclosed, semi-enclosed, and open learning places. 3. The stations: pre-fabricated packages of highly-serviced space connected through the determinate landscape. Four main types of stations; wet-room learning centres, dry-room learning centres, ablutions, and low-impact building services. Entirely customised at the factory and delivered to site. The stations can be retro-fitted to suit a new context during relocation. Principles of design for disassembly: material principles • use recycled and recyclable materials • minimise the number of types of materials • no toxic materials • use lightweight materials • avoid secondary finishes • provide identification of material types component principles • minimise/standardise the number of types of components • use mechanical not chemical connections • design for use of common tools and equipment • provide easy access to all components • make component size to suite means of handling • provide built in means of handling • design to realistic tolerances • use a minimum number of connectors and a minimum number of types system principles • design for durability and repeated use • use prefabrication and mass production • provide spare components on site • sustain all assembly and material information

Bouncing Back : Recovery through Design + Making

Architectural education is beginning to recognise the potential of a more intensive relationship between the tasks of designing and building (Erdman et al., 2002) within a work integrated learning environment. The Bouncing Back Project, began after the Queensland, Australia floods in January 2011, and has organically grown through a number of architectural student exhibitions, initially displaying flood responsive designs. In September 2011, 10 Queensland University of Technology architecture students travelled to Sydney to work together in helping to construct a shelter in the Emergency Shelter Exhibition, at Customs House in Circular Quay. The construction and making of the shelter, was filmed. This film documents the student experience, of making, working with industry professionals, community engagement and it reveals how this activity promotes informal work integrated learning in a real world context.

Custom digital workflows : a new framework for design analysis integration

Flexible information exchange is critical to successful design-analysis integration, but current top-down, standards-based and model-oriented strategies impose restrictions that contradicts this flexibility. In this article we present a bottom-up, user-controlled and process-oriented approach to linking design and analysis applications that is more responsive to the varied needs of designers and design teams. Drawing on research into scientific workflows, we present a framework for integration that capitalises on advances in cloud computing to connect discrete tools via flexible and distributed process networks. We then discuss how a shared mapping process that is flexible and user friendly supports non-programmers in creating these custom connections. Adopting a services-oriented system architecture, we propose a web-based platform that enables data, semantics and models to be shared on the fly. We then discuss potential challenges and opportunities for its development as a flexible, visual, collaborative, scalable and open system.

Custom digital workflows : a new framework for design analysis integration

Flexible information exchange is critical to successful design integration, but current top-down, standards-based and model-oriented strategies impose restrictions that are contradictory to this flexibility. In this paper we present a bottom-up, user-controlled and process-oriented approach to linking design and analysis applications that is more responsive to the varied needs of designers and design teams. Drawing on research into scientific workflows, we present a framework for integration that capitalises on advances in cloud computing to connect discrete tools via flexible and distributed process networks. Adopting a services-oriented system architecture, we propose a web-based platform that enables data, semantics and models to be shared on the fly. We discuss potential challenges and opportunities for the development thereof as a flexible, visual, collaborative, scalable and open system.

"Please touch the plant on your way up the stairs..."

We are aware of global concerns of sustainability and are encouraged on many fronts to modify our behaviour to save the planet but sometimes this understanding is more intellectual than motivated. An opportunity was identified within the university environment to activate a pilot study to investigate the level of voluntary student engagement in saving energy if a plant/digital interface were introduced. We postulate that people may be more inclined to participate in a "green" activity if they are more directly aware of the benefits. This project also seeks to discover if the introduction of nature (green plants) as the interface would encourage users to increase participation in socially responsive activities. Using plants as the interface offers an immediate sensory connection between the participants and the outcome of their chosen actions. This may generate a deeper awareness of the environment by enabling the participant to realise that their one small action in an ordinary day can contribute positively to larger global issues.

In pursuit of tourism destination brand loyalty : visitor relationship management orientation of destination marketing organisations

The proposition underpinning this study is engaging in meaningful dialogue with previous visitors represents an efficient and effective use of resources for a destination marketing organization (DMO), compared to above the line advertising in broadcast media. However there has been a lack of attention in the tourism literature relating to destination switching, loyalty and customer relationship management (CRM) to test such a proposition. This paper reports an investigation of visitor relationship marketing (VRM) orientation among DMOs. A model of CRM orientation, which was developed from the wider marketing literature and a prior qualitative study, was used to develop a scale to operationalise DMO visitor relationship orientation. Due to a small sample, the Partial Least Squares (PLS) method of structural equation modelling was used to analyse the data. Although the sample limits the ability to generalise, the results indicated the DMOs’ visitor orientation is generally responsive and reactive rather than proactive.

Regulating for corporate human rights abuses : the emergence of corporate reporting on the ILO’s human rights standards within the global garment manufacturing and retail industry

Despite the ubiquitous nature of the discourse on human rights there is currently little research on the emergence of disclosure by multinational corporations on their human rights obligations or the regulatory dynamic that may lie behind this trend. In an attempt to begin to explore the extent to which, if any, the language of human rights has entered the discourse of corporate accountability, this paper investigates the adoption of the International Labour Organisation's (ILO) human rights standards by major multinational garment retail companies that source products from developing countries, as disclosed through their reporting media. The paper has three objectives. Firstly, to empirically explore the extent to which a group of multinational garment retailers invoke the language of human rights when disclosing their corporate responsibilities. The paper reviews corporate reporting media including social responsibility codes of conduct, annual reports and stand-alone social responsibility reports released by 18 major global clothing and retail companies during a period from 1990 to 2007. We find that the number of companies adopting and disclosing on the ILO's workplace human rights standards has significantly increased since 1998 – the year in which the ILO's standards were endorsed and accepted by the global community (ILO, 1998). Secondly, drawing on a combination of Responsive Regulation theory and neo-institutional theory, we tentatively seek to understand the regulatory space that may have influenced these large corporations to adopt the language of human rights obligations. In particular, we study the role that International Governmental Organisation's (IGO) such as ILO may have played in these disclosures. Finally, we provide some critical reflections on the power and potential within the corporate adoption of the language of human rights.

Meta-regulation approach of law : a potential legal strategy to develop socially responsible business self-regulation in least developed common law countries

In the corporate regulation landscape, 'meta-regulation' is a comparatively new legal approach. The sketchy role of state promulgated authoritative laws in pluralized society and scepticism in corporate self-regulation's role have resulted in the development of this legal approach. It has opened up possibilities to synthesize corporate governance to add social values in corporate self-regulation. The core of this approach is the fusion of responsive and reflexive legal strategies to combine regulators and regulatees for reaching a particular goal. This paper argues that it is a potential strategy that can be successfully deployed to develop a socially responsible corporate culture for the business enterprises, so that they will be able to acquire social, environmental and ethical values in their self-regulation sustainably. Taking Bangladeshi corporate laws as an instance, this paper also evaluates the scope of incorporating this approach in laws of the least developed common law countries in general.

Securities market regulators’ use of the ‘please explain’ queries sanction and its power of compliance

The aim of this study is to investigate the compliance impact of price queries issued by a securities market operator to its participating firms. Market operators in Australia and New Zealand, such as the Australian Securities Exchange and the New Zealand Securities Exchange, have the regulatory power in their rules to issue queries to its market participants to explain unusual fluctuations in trading price or volume in the market. The operator will issue a price query where it believes that the market has not been fully informed as to price relevant information. Responsive regulation has informed much of the regulatory debate in securities laws in our region. We posit that price queries are one strategy that a market operator can use in communicating its enforcement expectations to its stakeholder. However, whilst responsive regulation informs regulatory choices, an alternate view seeks to explain why participants respond to these regulatory strategies, and we use disclosure behaviour after price queries to test compliance behaviour

Linking Karumba : Creating Sustainable Connections

Linking Karumba: Creating Sustainable Connections This exhibition showcases the work of 3rd -4th year undergraduate landscape architecture, architecture, Industrial Design, Environmental Engineering, Civil Engineering students in response to issues of sustainability in the Gulf of Carpentaria town of Karumba. It presented the work to the Karumba and Carpentaria Shire community. 16 students and four staff set off on a 2488km journey to undertake the first half of the Carpentaria Project: a fortnight-long strategic planning project entitled Linking Karumba to encourage social, economic, environmental and cultural linkages across the town. Karumba, along with the nearby town of Normanton, is one of Queensland’s most remote settlements. Its economy is based on fishing, tourism, and mining. It has two centres, 2.5km apart by river, or 9km by road. This physical disconnect was identified by Carpentaria Shire Council (CSC) and the Karumba Progress Association (KPA) as a source of socio-cultural disconnection, which formed the basis of our project brief. Student designs were highly responsive to the character of Karumba’s culture and environment, indicating remarkable levels of immersion, and attracting $830 000 in Qld. state government funding for implementation. The Exhibition Four groups of four students produced four strategic planning and design options toward this future: Make the Switch: Alice Anonuevo, Michael Marriott, Carla Priestley & Grant Harvey Realigning the Systems: Claudia Bergs, Rebecca Stephens, Anna Coulson & Lois Kerrigan Diversification of Experience: Rebecca North, Kyle Bush, Debra Sullivan & Jenna Green The River is the Main Street: Ashley Nicholson, Monica Kuiken, Dean Bowen & Bill Schild