A review of the economic consequences of a policy of universal leucodepletion as compared to existing practices

Leucodepletion, the removal of leucocytes from blood products improves the safety of blood transfusion by reducing adverse events associated with the incidental non-therapeutic transfusion of leucocytes. Leucodepletion has been shown to have clinical benefit for immuno-suppressed patients who require transfusion. The selective leucodepletion of blood products by bed side filtration for these patients has been widely practiced. This study investigated the economic consequences in Queensland of moving from a policy of selective leucodepletion to one of universal leucodepletion, that is providing all transfused patients with blood products leucodepleted during the manufacturing process. Using an analytic decision model a cost-effectiveness analysis was conducted. An ICER of $16.3M per life year gained was derived. Sensitivity analysis found this result to be robust to uncertainty in the parameters used in the model. This result argues against moving to a policy of universal leucodepletion. However during the course of the study the policy decision for universal leucodepletion was made and implemented in Queensland in October 2008. This study has concluded that cost-effectiveness is not an influential factor in policy decisions regarding quality and safety initiatives in the Australian blood sector.

Protein complementation assay as a display system for screening protein libraries in the intracellular environment

A wide range of screening strategies have been employed to isolate antibodies and other proteins with specific attributes, including binding affinity, specificity, stability and improved expression. However, there remains no high-throughput system to screen for target-binding proteins in a mammalian, intracellular environment. Such a system would allow binding reagents to be isolated against intracellular clinical targets such as cell signalling proteins associated with tumour formation (p53, ras, cyclin E), proteins associated with neurodegenerative disorders (huntingtin, betaamyloid precursor protein), and various proteins crucial to viral replication (e.g. HIV-1 proteins such as Tat, Rev and Vif-1), which are difficult to screen by phage, ribosome or cell-surface display. This study used the β-lactamase protein complementation assay (PCA) as the display and selection component of a system for screening a protein library in the cytoplasm of HEK 293T cells. The colicin E7 (ColE7) and Immunity protein 7 (Imm7) *Escherichia coli* proteins were used as model interaction partners for developing the system. These proteins drove effective β-lactamase complementation, resulting in a signal-to-noise ratio (9:1 – 13:1) comparable to that of other β-lactamase PCAs described in the literature. The model Imm7-ColE7 interaction was then used to validate protocols for library screening. Single positive cells that harboured the Imm7 and ColE7 binding partners were identified and isolated using flow cytometric cell sorting in combination with the fluorescent β-lactamase substrate, CCF2/AM. A single-cell PCR was then used to amplify the Imm7 coding sequence directly from each sorted cell. With the screening system validated, it was then used to screen a protein library based the Imm7 scaffold against a proof-of-principle target. The wild-type Imm7 sequence, as well as mutants with wild-type residues in the ColE7- binding loop were enriched from the library after a single round of selection, which is consistent with other eukaryotic screening systems such as yeast and mammalian cell-surface display. In summary, this thesis describes a new technology for screening protein libraries in a mammalian, intracellular environment. This system has the potential to complement existing screening technologies by allowing access to intracellular proteins and expanding the range of targets available to the pharmaceutical industry.

Introduction

The production of knowledge has become central to economic life. Competitiveness in the 21st century market place is now characterized by the ability to translate scientific and technological knowledge into innovation. But does this render cultural and social knowledge unimportant? This unique book advocates a broader epistemological base for the term ‘knowledge’ and develops policy implications from this perspective. By examining long-term challenges, the volume argues that fresh policy thinking is needed not only in the obviously knowledge-intensive portfolios but across all areas of knowledge production and questions how the different dynamics of the knowledge era affect defence, employment, environment, indigenous and international relations, multiculturalism and urban policy.

Realistic yet humanitarian? The comprehensive plan of action and refugee policy in Southeast Asia

The 1989 Comprehensive Plan of Action (CPA) has recently been described as a successful example of how to manage large protracted refugee flows. However, this article revisits the circumstances surrounding the CPA used to resolve the prolonged Indo-Chinese refugee crisis to highlight that part of its development was linked to the fact that Southeast Asian states refused to engage with proposed solutions, which did not include repatriation for the majority of the Indo-Chinese asylum seekers who were deemed to be ‘non-genuine’1 ( UNGA, 1989a) refugees. This resulted in the CPA often forcibly repatriating ‘non-genuine’ refugees, particularly near the end of its program. This article reviews the CPA in order to assess whether its practices and results should be repeated.

Vitronectin modulates human mesenchymal stem cell response to insulin-like growth factor-I and transforming growth factor beta 1 in a serum-free environment

The use of animal sera for the culture of therapeutically important cells impedes the clinical use of the cells. We sought to characterize the functional response of human mesenchymal stem cells (hMSCs) to specific proteins known to exist in bone tissue with a view to eliminating the requirement of animal sera. Insulin-like growth factor-I (IGF-I), via IGF binding protein-3 or -5 (IGFBP-3 or -5) and transforming growth factor-beta 1 (TGF-beta(1)) are known to associate with the extracellular matrix (ECM) protein vitronectin (VN) and elicit functional responses in a range of cell types in vitro. We found that specific combinations of VN, IGFBP-3 or -5, and IGF-I or TGF-beta(1) could stimulate initial functional responses in hMSCs and that IGF-I or TGF-beta(1) induced hMSC aggregation, but VN concentration modulated this effect. We speculated that the aggregation effect may be due to endogenous protease activity, although we found that neither IGF-I nor TGF-beta(1) affected the functional expression of matrix metalloprotease-2 or -9, two common proteases expressed by hMSCs. In summary, combinations of the ECM and growth factors described herein may form the basis of defined cell culture media supplements, although the effect of endogenous protease expression on the function of such proteins requires investigation.

Facial feature detection for in-car environment

Acoustically, vehicles are extremely noisy environments and as a consequence audio-only in-car voice recognition systems perform very poorly. Seeing that the visual modality is immune to acoustic noise, using the visual lip information from the driver is seen as a viable strategy in circumventing this problem. However, implementing such an approach requires a system being able to accurately locate and track the driver’s face and facial features in real-time. In this paper we present such an approach using the Viola-Jones algorithm. Using this system, we present our results which show that using the Viola-Jones approach is a suitable method of locating and tracking the driver’s lips despite the visual variability of illumination and head pose.

Open Access and Public Sector Information : Policy Developments in Australia and Key Jurisdictions

This book chapter considers recent developments in Australia and key jurisdictions both in relation to the formation of a national information strategy and the management of legal rights in public sector information.

Mobility and safety are conflicting goals for transport policy makers when making decisions about graduated driver licensing

Policy decisions are frequently influenced by more than research results alone. This review examines one road safety countermeasure, graduated driver licensing, in three jurisdictions and identifies how the conflict between mobility and safety goals can influence policy decisions relating to this countermeasure. Evaluations from around the world of graduated driver licensing have demonstrated clear reductions in crashes for young drivers. However, the introduction of this countermeasure may be affected, both positively and negatively, by the conflict some policy makers experience between ensuring individuals remain both mobile and safe as drivers. This review highlights how this conflict in policy decision making can serve to either facilitate or hinder the introduction of graduated driver licensing systems. However, policy makers whose focus on mobility is too strong when compared with safety may be mistaken, with evidence suggesting that after a graduated driver licensing system is introduced young drivers adapt their behaviour to the new system and remain mobile. As a result, policy makers should consciously acknowledge the conflict between mobility and safety and consider an appropriate balance in order to introduce these systems. Improvements to the licensing system can then be made in an incremental manner as the balance between these two priorities change. Policy makers can achieve an appropriate balance by using empirical evidence as a basis for their decisions.

Testing the effectiveness of a Practice Development intervention on changing the culture of evidence based practice in an acute care environment

In this age of evidence-based practice, nurses are increasingly expected to use research evidence in a systematic and judicious way when making decisions about patient care practices. Clinicians recognise the role of research when it provides valid, realistic answers in practical situations. Nonetheless, research is still perceived by some nurses as external to practice and implementing research findings into practice is often difficult. Since its conceptual platform in the 1960s, the emergence and growth of Nursing Development Units, and later, Practice Development Units has been described in the literature as strategic, organisational vehicles for changing the way nurses think about nursing by promoting and supporting a culture of inquiry and research-based practice. Thus, some scholars argue that practice development is situated in the gap between research and practice. Since the 1990s, the discourse has shifted from the structure and outcomes of developing practice to the process of developing practice, using a Practice Development methodology; underpinned by critical social science theory, as a vehicle for changing the culture and context of care. The nursing and practice development literature is dominated by descriptive reports of local practice development activity, typically focusing on reflection on processes or outcomes of processes, and describing perceived benefits. However, despite the volume of published literature, there is little published empirical research in the Australian or international context on the effectiveness of Practice Development as a methodology for changing the culture and context of care - leaving a gap in the literature. The aim of this study was to develop, implement and evaluate the effectiveness of a Practice Development model for clinical practice review and change on changing the culture and context of care for nurses working in an acute care setting. A longitudinal, pre-test/post-test, non-equivalent control group design was used to answer the following research questions: 1. Is there a relationship between nurses' perceptions of the culture and context of care and nurses' perceptions of research and evidence-based practice? 2. Is there a relationship between engagement in a facilitated process of Practice Development and change in nurses' perceptions of the culture and context of care? 3. Is there a relationship between engagement in a facilitated process of Practice Development and change in nurses' perceptions of research and evidence-based practice? Through a critical analysis of the literature and synthesis of the findings of past evaluations of Nursing and Practice Development structures and processes, this research has identified key attributes consistent throughout the chronological and theoretical development of Nursing and Practice Development that exemplify a culture and context of care that is conducive to creating a culture of inquiry and evidence-based practice. The study findings were then used in the development, validation and testing of an instrument to measure change in the culture and context of care. Furthermore, this research has also provided empirical evidence of the relationship of the key attributes to each other and to barriers to research and evidence-based practice. The research also provides empirical evidence regarding the effectiveness of a Practice Development methodology in changing the culture and context of care. This research is noteworthy in its contribution to advancing the discipline of nursing by providing evidence of the degree to which attributes of the culture and context of care, namely autonomy and control, workplace empowerment and constructive team dynamics, can be connected to engagement with research and evidence-based practice.

Impromptu : an interactive programming environment for composition and performance

Interactive development environments are making a resurgence. The traditional batch style of programming, edit -> compile -> run, is slowly being reevaluated by the development community at large. Languages such as Perl, Python and Ruby are at the heart of a new programming culture commonly described as extreme, agile or dynamic. Musicians are also beginning to embrace these environments and to investigate the opportunity to use dynamic programming tools in live performance. This paper provides an introduction to Impromptu, a new interactive development environment for musicians and sound artists.