Tetraspanins as regulators of the tumour microenvironment : implications for metastasis and therapeutic strategies

One of the hallmarks of cancer is the ability to activate invasion and metastasis (Hanahan et al., 2011). Cancer morbidity and mortality are largely related to the spread of the primary, localised tumour to adjacent and distant sites (Pantel et al., 2004). Appropriate management and treatment decisions of predicting metastatic disease at the time of diagnosis is thus crucial, which supports better understanding of the metastatic process. There are common events that occur during metastasis: dissociation from the primary tumour mass, reorganisation/remodelling of extracellular matrix, cell migration, recognition and transversal of endothelial cells and the vascular circulation and lodgement and proliferation within ectopic stroma (Wells, 2006). One of the key and initial events is the increased capability of cancer cells to move, escaping the regulation of normal physiological control. The cellular cytoskeleton plays an important role in cancer cell motility and active cytoskeletal rearrangement can result in metastatic disease. This active change in cytoskeletal dynamics results in manipulation of plasma membrane and cellular balance between cellular adhesion and motility which in turn determines cancer cell movement. Members of the tetraspanins play important roles in regulation of cancer migration and cancer-endothelial cell interactions, which are critical for cancer invasion and metastasis. Their involvements in active cytoskeletal dynamics, cancer metastasis and potential clinical application will be discussed in this review. In particular, tetraspanin member, CD151, is highlighted for its major role in cancer invasion and metastasis

Trait resilience fosters adaptive coping when control opportunities are high : implications for the motivating potential of active work

Purpose: We examine the interaction between trait resilience and control in predicting coping and performance. Drawing on a person–environment fit perspective, we hypothesized resilient individuals would cope and perform better in demanding work situations when control was high. In contrast, those low in resilience would cope and perform better when control was low. Recognizing the relationship between trait resilience and performance also could be indirect, adaptive coping was examined as a mediating mechanism through which high control enables resilient individuals to demonstrate better performance. Methodology: In Study 1 (N = 78) and Study 2 (N = 94), participants completed a demanding inbox task in which trait resilience was measured and high and low control was manipulated. Study 3 involved surveying 368 employees on their trait resilience, control, and demand at work (at Time 1), and coping and performance 1 month later at Time 2. Findings: For more resilient individuals, high control facilitated problem-focused coping (Study 1, 2, and 3), which was indirectly associated with higher subjective performance (Study 1), mastery (Study 2), adaptive, and proficient performance (Study 3). For more resilient individuals, high control also facilitated positive reappraisal (Study 2 and 3), which was indirectly associated with higher adaptive and proficient performance (Study 3). Implications: Individuals higher in resilience benefit from high control because it enables adaptive coping. Originality/value: This research makes two contributions: (1) an experimental investigation into the interaction of trait resilience and control, and (2) investigation of coping as the mechanism explaining better performance.

Person-Centred Approaches to Private Housing for People with Disability : Impediments, Difficulties and Opportunities

Objective The main objective of the project was to explore the barriers and obstacles impeding a person-centred approach to planning and private housing for people with disability. Method Methodologically, the project involved explanation building using a multiple case study approach supported by a contextual study. It focussed initially on three organisations and their attempts to integrate innovative and what they regarded as person-centred models of housing into the private housing market for people with disability. It also included a fourth case highlighting the experiences of individuals with disability in accessing suitable and affordable housing. Results Using an ecological framework, the project found that: • Challenges exist within systems (such as the macro cultural, economic, regulatory systems through to local community, family and intra personal systems) as well as with interaction between systems • Reaching across systems is a key role for organisations and individuals but is very challenging with distance from the individual as well as from the policy/funding/service systems being a key aspect of the nature and extent by which they are challenged • In the case of housing for people with disability a ‘disability space’ is assumed and maintained disparately within each system and is separate from the ‘mainstream space’ with the established policy, legal, funding structures making it difficult to move between the two spaces. Conclusions Based on these findings, the project makes recommendations for government, community organisations, the housing industry, people with disability and their families and support networks, as well as for future research. An overarching recommendation is the need to address housing stock availability and suitability by adopting a mainstream approach rather than a disability-first/disability-specific approach.

Functions and therapeutic roles of exosomes in cancer

The role of exosomes in cancer development has become the focus of much research, due to the many emerging roles possessed by exosomes. These micro-vesicles that are ubiquitously released in to the extracellular milieu, have been found to regulate immune system function, particularly in tumorigenesis, as well as conditioning future metastatic sites for the attachment and growth of tumor tissue. Through an interaction with a range of host tissue, exosomes are able to generate a pro-tumor environment that is essential for carcinogenesis. Herein, we discuss the contents of exosomes and their contribution to tumorigenesis, as well as their role in chemotherapeutic resistance and the development of novel cancer treatments and the identification of cancer biomarkers.

Antimicrobial stewardship activities : a survey of Queensland hospitals

Objective: In 2011, the Australian Commission on Safety and Quality in Health Care (ACSQHC) recommended that all hospitals in Australia must have an Antimicrobial Stewardship (AMS) program by 2013. Nevertheless, little is known about current AMS activities. This study aimed to determine the AMS activities currently undertaken, and to identify gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. Methods: The AMS activities of 26 facilities from 15 hospital and health services in Queensland were surveyed during June 2012 to address strategies for effective AMS: implementing clinical guidelines, formulary restriction, reviewing antimicrobial prescribing, auditing antimicrobial use and selective reporting of susceptibility results. Results: The response rate was 62%. Nineteen percent had an AMS team (a dedicated multidisciplinary team consisting of a medically trained staff member and a pharmacist). All facilities had access to an electronic version of Therapeutic Guidelines: Antibiotic, with a further 50% developing local guidelines for antimicrobials. One-third of facilities had additional restrictions. Eighty-eight percent had advice for restricted antimicrobials from in-house infectious disease physicians or clinical microbiologists. Antimicrobials were monitored with feedback given to prescribers at point of care by 76% of facilities. Deficiencies reported as barriers to establishing AMS programs included: pharmacy resources, financial support by hospital management, and training and education in antimicrobial use. Conclusions: Several areas for improvement were identified: reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use. There also appears to be a lack of resources to support AMS programs in some facilities. What is known about the topic? The ACSQHC has recommended that all hospitals implement an AMS program by 2013 as a requirement of Standard 3 (Preventing and Controlling Healthcare-Associated Infections) of the National Safety and Quality Health Service Standards. The intent of AMS is to ensure appropriate prescribing of antimicrobials as part of the broader systems within a health service organisation to prevent and manage healthcare-associated infections, and improve patient safety and quality of care. This criterion also aligns closely with Standard 4: Medication Safety. Despite this recommendation, little is known about what AMS activities are undertaken in these facilities and what additional resources would be required in order to meet these national standards. What does the paper add? This is the first survey that has been conducted of public hospital and health services in Queensland, a large decentralised state in Australia. This paper describes what AMS activities are currently being undertaken, identifies practice gaps, barriers to implementation and opportunities for improvement in Queensland hospitals. What are the implications for practitioners? Several areas for improvement such as reviewing antimicrobial prescribing with feedback to the prescriber, auditing, and training and education in antimicrobial use have been identified. In addition, there appears to be a lack of resources to support AMS programs in some facilities.

Building energy simulation and parallel computing : opportunities and challenges

Increased focus on energy cost savings and carbon footprint reduction efforts improved the visibility of building energy simulation, which became a mandatory requirement of several building rating systems. Despite developments in building energy simulation algorithms and user interfaces, there are some major challenges associated with building energy simulation; an important one is the computational demands and processing time. In this paper, we analyze the opportunities and challenges associated with this topic while executing a set of 275 parametric energy models simultaneously in EnergyPlus using a High Performance Computing (HPC) cluster. Successful parallel computing implementation of building energy simulations will not only improve the time necessary to get the results and enable scenario development for different design considerations, but also might enable Dynamic-Building Information Modeling (BIM) integration and near real-time decision-making. This paper concludes with the discussions on future directions and opportunities associated with building energy modeling simulations.

Beyond the Producer/Consumer Divide : Key Principles of Produsage and Opportunities for Innovation

Though popular, concepts such as Toffler's 'prosumer' (1970; 1980; 1990) are inherently limited in their ability to accurately describe the makeup and dynamics of current co-creative environments, from fundamentally non-profit initiatives like the Wikipedia to user-industry partnerships that engage in crowdsourcing and the development of collective intelligence. Instead, the success or failure of such projects can be understood best if the traditional producer/consumer divide is dissolved, allowing for the emergence of the produser (Bruns, 2008). A close investigation of leading spaces for produsage makes it possible to extract the key principles which underpin and guide such content co-creation, and to identify how innovative pro-am partnerships between commercial entities and user communities might be structured in order to maximise the benefits that both sides will be able to draw from such collaboration. This chapter will outline these principles, and point to successes and failures in applying them to pro- am initiatives.

Opportunities and challenges in engaging citizens in the co-production of infrastructure-based public services in Australia

Research and practice have observed a shift towards service-oriented approaches that depend on input from citizens as co-producers of services. Yet in the delivery of public infrastructure the focus is still on managing assets rather than services. Using a Policy Delphi approach, we found that although experts advocate service-centric approaches guidelines and policies lack a service-centric perspective. Findings revealed a range of impediments to effective stakeholder involvement. The paper contributes to co-production and new public governance literature and offers directions for public infrastructure decision-makers to support and reconnect disengaged government–citizen relations, and determine ways of understanding optimal service outcomes.

Mapping futures for news: Trends, opportunities and challenges for Scotland

The Mapping Futures of News research and seminar programme, sponsored by the Institute for Advanced Studies in 2009-10, addressed those questions, as well as the many more immediate issues facing the Scottish news industry, such as how to survive the current period of often traumatic transition. This document summarises that work, and identifies: Mapping Futures for News: Programme Report iii • Where the main Scottish print and broadcast news media are in 2010, in terms of circulation and ratings figures; • the key trends currently impacting on Scottish news media; • the responses up to now of government and regulators to assist the Scottish media through the present problems; • the responses of the news media themselves.

Therapeutic options for metastatic castration resistant prostate cancer : has the situation improved?

Limited treatment options for Castration Resistant Prostate Cancer (CRPC) still remain a major challenge. Despite therapeutic advances, most patients with malignant PCa have a poor prognosis. Since the year 2000, we have rapidly expanded our understanding of the molecular mechanisms underlying CRPC and this has led to an unprecedented number of new drug approvals within a short span of time. Recently, four new agents namely Abiraterone Acetate, Enzalutamide, Cabazitaxel, and Radium-223 have been shown to be effective in the post-chemotherapy setting in CRPC. The continued dependency of CRPC on androgen synthesis has seen the development of a number of new anti-androgen therapies, with abiraterone acetate and Enzalutamide being the most promising discoveries. Immunotherapeutic approaches have also found their niche in PCa with Sipuleucel-T shown to be effective in minimally asymptomatic CRPC. Research focussed on bone-targeting therapies has witnessed the arrival of promising new drugs with Denosumab and Radium-223 displaying improved survival of patients with CRPC. This review briefly discusses the findings and limitations from ongoing and completed clinical trials of novel treatments and regimens. In addition, potential mechanisms of therapy resistance and future challenges are discussed.