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CD47 is an immune checkpoint molecule that downregulates key aspects of both the innate and adaptive anti-tumor immune response via its counter receptor SIRPα, and it is expressed at high levels in a wide variety of tumor types. This has led to the development of biologics that inhibit SIRPα engagement including humanized CD47 antibodies and a soluble SIRPα decoy receptor that are currently undergoing clinical trials. Unfortunately, toxicological issues, including anemia related to on-target mechanisms, are barriers to their clinical advancement. Another potential issue with large biologics that bind CD47 is perturbation of CD47 signaling through its high-affinity interaction with the matricellular protein thrombospondin-1 (TSP1). One approach to avoid these shortcomings is to identify and develop small molecule molecular probes and pretherapeutic agents that would (1) selectively target SIRPα or TSP1 interactions with CD47, (2) provide a route to optimize pharmacokinetics, reduce on-target toxicity and maximize tissue penetration, and (3) allow more flexible routes of administration. As the first step toward this goal, we report the development of an automated quantitative high-throughput screening (qHTS) assay platform capable of screening large diverse drug-like chemical libraries to discover novel small molecules that inhibit CD47-SIRPα interaction. Using time-resolved Fo¨rster resonance energy transfer (TR-FRET) and bead-based luminescent oxygen channeling assay formats (AlphaScreen), we developed biochemical assays, optimized their performance, and individually tested them in small-molecule library screening. Based on performance and low false positive rate, the LANCE TR-FRET assay was employed in a ~90,000 compound library qHTS, while the AlphaScreen oxygen channeling assay served as a cross-validation orthogonal assay for follow-up characterization. With this multi-assay strategy, we successfully eliminated compounds that interfered with the assays and identified five compounds that inhibit the CD47- SIRPα interaction; these compounds will be further characterized and later disclosed. Importantly, our results validate the large library qHTS for antagonists of CD47-SIRPα interaction and suggest broad applicability of this approach to screen chemical libraries for other protein-protein interaction modulators.

Globally, there is an urgent need for solutions that can support our aging populations to live well and reduce the associated economic, social and health burdens. Implementing smart technologies within homes and communities may assist people to live well and ‘age in place’. To date, there has been little consultation with older Australians addressing either the perceived benefits, or the potential social and ethical challenges associated with smart technology use. To address this, we conducted five World Cafés in two Australian states, aiming to capture citizen knowledge about the possibilities and challenges of smart technologies. The participants (n = 84) were aged 55 years and over, English-speaking, and living independently. Grounding our analysis in values-based social science and biomedical ethical principles, we identified the themes reflecting the participants’ understanding, resistance, and acceptance of smart technologies, and the ethical principles, including beneficence, non-maleficence, autonomy, privacy, confidentiality, and justice. Similar to other studies, many of the participants demonstrated cautious and conditional acceptance of smart technologies, while identifying concerns about social isolation, breaches of privacy and confidentiality, surveillance, and stigmatization. Attention to understanding and incorporating the values of older citizens will be important for the acceptance and effectiveness of smart technologies for supporting independent and full lives for older citizens.

Background: Current models of care for people with advanced chronic obstructive pulmonary disease (COPD) have been demonstrated to be inadequate, particularly in areas such as advance care planning, symptom control and psychosocial and spiritual care. Aim: This paper aims to explore how a model of patient-centred care can incorporate a palliative approach to form a practical and useful framework for care that meets the needs of people with advanced COPD. Discussion: There is increasing recognition of the need to provide active disease management at the same time as supportive care for people with chronic disease. A palliative approach can incorporate these two care imperatives but a number of barriers often make implementation problematic. A patient-centred care approach can help to address these barriers and is increasingly being seen as an appropriate framework for all healthcare service provision. Significant changes are required to health systems and service provision for this model of care to be implemented; specialist palliative care services can take a leading role in change management. Conclusion: Patient-centred care provides an appropriate framework for the development of a model of care for advanced COPD. It allows for a need-based approach to service provision, rather than the current prognosis-based system and brings patient and carer needs and concerns to the forefront of care. Refereed/Peer-reviewed

Objective To explore service availability and accessibility for people with advanced chronic obstructive pulmonary disease (COPD) and their carers and strategies for improvement, including the potential role of a COPD care co-ordinator in ensuring best-practice care in the Australian context. Methods This qualitative study used focus groups and interviews with health professionals, carers and consumers to explore gaps and restrictions in services, barriers to access and the functioning of services. Data were analysed deductively. Results Key themes arising from the data included difficulties around access to care, lack of continuity of care, poor care co-ordination, the need for active disease management as well as supportive care, and poor communication. A COPD care co-ordinator was suggested as an effective strategy for ensuring best-practice care. Conclusions People with advanced COPD often have difficulty navigating the acute, primary and community care systems to deal with the multiple services that they may require. Lack of communication between health professionals and services is frequently a significant issue. A COPD care co-ordinator, encompassing advanced nursing skills, could ensure that care is centred on the needs of the person and their carer and that they receive continuing, appropriate and accessible care as they approach the end of their life. What is known about the topic? The importance of care co-ordination as a quality care indicator in chronic disease is growing, and the care co-ordinator role as a facilitator of quality care is increasingly being recognised in the UK and US. There is currently little information in the Australian context about how a COPD care co-ordinator role could be implemented, where it could be situated and the level of skill required. What does this paper add? This paper explores the specific issues in developing a COPD care co-ordinator role and provides a detailed model of care for the introduction of care co-ordinators into the Australian setting. What are the implications for practitioners? The proposed COPD care co-ordinator role has the potential to improve quality, continuing care for people with advanced COPD. It could facilitate the linkage of multidisciplinary teams across acute, primary and community care settings and promote timely and effective communication. The role would provide a clear point of contact for all practitioners and the opportunity for nurses to develop an advanced practice role in COPD care co-ordination, combining a palliative care approach with a chronic disease management framework.

Advance care-planning conversations with people who have chronic obstructive pulmonary disease (COPD) are important because of the severity of the disease and the unpredictable timing of death. Advance care-planning is a process involving conversations about future wishes, including end-of-life care and the appointment of a substitute decision-maker. This qualitative research explored issues relating to end-of-life decisions with 15 individuals and their carers living in the community who had severe COPD. Findings indicated that, although patients and carers would welcome the opportunity to discuss end-of-life decisions, almost no conversation about care-planning had been initiated by health professionals with any of the participants. It also demonstrated that professional support is required to assist with advance care-planning and the completion of the legal advance directive documents. Refereed/Peer-reviewed

This project has demonstrated that neither respiratory nor palliative care services alone can adequately support people with COPD. There is little doubt that a new model of care for people with advanced COPD is required in Australia. The findings of this project reflect both the international evidence and the Australian context and demonstrate clearly that the health care system must change for best practice care to be provided for people with advanced COPD and for their carers and families.There is a need for a model of care that assists these people to navigate the health care and community support systems, that is patient-centred and reflects a palliative approach and which is co-ordinated across the primary, acute and community sectors. The integration of a multidisciplinary palliative approach within a chronic disease management strategy, as well as the recognition thatDeveloping a model of care for people with end stage COPD and their carers, 2011 119active disease management and palliation are complimentary, not mutually exclusive, will be central for the best care for people living with advanced COPD.

AIMS To determine general practitioners’ research training needs, and the barriers to involvement in research. METHOD Semi-structured interviews with 11 GPs in rural and metropolitan South Australia, analysed using a grounded theory approach. RESULTS General practitioners’ perceptions about their research needs were limited by their own experience and focussed at an individual level. Overlapping needs and barriers emerged, categorised as: ‘individual issues’ (a lack of research training or experience, concepts and attitudes to research, and research interest) and ‘systems issues’ (funding arrangements for general practice, access to resources, opportunity for publication and the role of The Royal Australian College of General Practitioners [RACGP]). DISCUSSION Our data provide an exploratory model that may assist in developing suitable strategies for research capacity building programs. General practitioners perceived both individual and systems solutions to building research capacity, including multifaceted interventions.