Understanding innovators' experiences of barriers and facilitators in implementation and diffusion of healthcare service innovations: A qualitative study

This article is made available through the Brunel Open Access Publishing Fund - Copyright @ 2011 Barnett et al.Background: Healthcare service innovations are considered to play a pivotal role in improving organisational efficiency and responding effectively to healthcare needs. Nevertheless, healthcare organisations encounter major difficulties in sustaining and diffusing innovations, especially those which concern the organisation and delivery of healthcare services. The purpose of the present study was to explore how healthcare innovators of process-based initiatives perceived and made sense of factors that either facilitated or obstructed the innovation implementation and diffusion. Methods: A qualitative study was designed. Fifteen primary and secondary healthcare organisations in the UK, which had received health service awards for successfully generating and implementing service innovations, were studied. In-depth, semi structured interviews were conducted with the organisational representatives who conceived and led the development process. The data were recorded, transcribed and thematically analysed. Results: Four main themes were identified in the analysis of the data: the role of evidence, the function of inter-organisational partnerships, the influence of human-based resources, and the impact of contextual factors. "Hard" evidence operated as a proof of effectiveness, a means of dissemination and a pre-requisite for the initiation of innovation. Inter-organisational partnerships and people-based resources, such as champions, were considered an integral part of the process of developing, establishing and diffusing the innovations. Finally, contextual influences, both intra-organisational and extra-organisational were seen as critical in either impeding or facilitating innovators' efforts. Conclusions: A range of factors of different combinations and co-occurrence were pointed out by the innovators as they were reflecting on their experiences of implementing, stabilising and diffusing novel service initiatives. Even though the innovations studied were of various contents and originated from diverse organisational contexts, innovators' accounts converged to the significant role of the evidential base of success, the inter-personal and inter-organisational networks, and the inner and outer context. The innovators, operating themselves as important champions and being often willing to lead constructive efforts of implementation to different contexts, can contribute to the promulgation and spread of the novelties significantly.This research was supported financially by the Multidisciplinary Assessment of Technology Centre for Healthcare (MATCH)

A repurposing strategy for Hsp90 inhibitors demonstrates their potency against filarial nematodes

Novel drugs are required for the elimination of infections caused by filarial worms, as most commonly used drugs largely target the microfilariae or first stage larvae of these infections. Previous studies, conducted in vitro, have shown that inhibition of Hsp90 kills adult Brugia pahangi. As numerous small molecule inhibitors of Hsp90 have been developed for use in cancer chemotherapy, we tested the activity of several novel Hsp90 inhibitors in a fluorescence polarization assay and against microfilariae and adult worms of Brugia in vitro. The results from all three assays correlated reasonably well and one particular compound, NVP-AUY922, was shown to be particularly active, inhibiting Mf output from female worms at concentrations as low as 5.0 nanomolar after 6 days exposure to drug. NVP-AUY922 was also active on adult worms after a short 24 h exposure to drug. Based on these in vitro data, NVP-AUY922 was tested in vivo in a mouse model and was shown to significantly reduce the recovery of both adult worms and microfilariae. These studies provide proof of principle that the repurposing of currently available Hsp90 inhibitors may have potential for the development of novel agents with macrofilaricidal properties

Assay strategies for the discovery and validation of therapeutics targeting <i>Brugia pahangi</i> Hsp90

The chemotherapy of lymphatic filariasis relies upon drugs such as diethylcarbamazine and ivermectin that largely target the microfilarial stages of the parasite, necessitating continued treatment over the long reproductive life span of the adult worm. The identification of compounds that target adult worms has been a long-term goal of WHO. Here we describe a fluorescence polarization assay for the identification of compounds that target Hsp90 in adult filarial worms. The assay was originally developed to identify inhibitors of Hsp90 in tumor cells, and relies upon the ability of small molecules to inhibit the binding of fluorescently labelled geldanamycin to Hsp90. We demonstrate that the assay works well with soluble extracts of Brugia, while extracts of the free-living nematode C. elegans fail to bind the probe, in agreement with data from other experiments. The assay was validated using known inhibitors of Hsp90 that compete with geldanamycin for binding to Hsp90, including members of the synthetic purine-scaffold series of compounds. The efficacy of some of these compounds against adult worms was confirmed in vitro. Moreover, the assay is sufficiently sensitive to differentiate between binding of purine-scaffold compounds to human and Brugia Hsp90. The assay is suitable for high-throughput screening and provides the first example of a format with the potential to identify novel inhibitors of Hsp90 in filarial worms and in other parasitic species where Hsp90 may be a target

Understanding barriers to decision making in the UK energy-food-water nexus: The added value of interdisciplinary approaches

The nexus represents a multi-dimensional means of scientific enquiry which seeks to describe the complex and non-linear interactions between energy, food and water with the climate, whilst furthering understanding of wider implications for society. These resources are fundamental for human life but are negatively affected by shocks such as climate change and characterize some of the main challenges for global sustainable development. Given the multidimensional and complex nature of the nexus, a transdisciplinary approach to knowledge development through co-production is needed to timely and effectively inform decision making processes to build societal resilience to these shocks going beyond the sectorality of current research practice. The paper presents findings from five themed workshops (shocks and hazards, infrastructure, local economy, governance and governments, finance and insurance) with 80 stakeholders from academia, government and industry in the UK to explore the impact of climate and weather shocks across the energy-food-water nexus and barriers to related responses. The research identified key stakeholders’ concerns, opportunities and barriers to better inform decision-making centred on four themes: communication and collaboration, decision making processes, social and cultural dimensions, and the nature of responses to nexus shocks. We discuss implications of these barriers and how addressing these can better facilitate constructive dialogue and more efficient decision-making in response to nexus shocks

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals

Connecting climate action with other sustainable development goals

The international community has committed to combat climate change and achieve 17 Sustainable Development Goals (SDGs). Here we explore (dis)connections in evidence and governance between these commitments. Our structured evidence review suggests that climate change can undermine 16 SDGs, while combatting climate change can reinforce all 17 SDGs but undermine efforts to achieve 12. Understanding these relationships requires wider and deeper interdisciplinary collaboration. Climate change and sustainable development governance should be better connected to maximize the effectiveness of action in both domains. The emergence around the world of new coordinating institutions and sustainable development planning represents promising progress

University–industry collaboration: using meta-rules to overcome barriers to knowledge transfer

This is the final version of the article. Available from Springer Verlag via the DOI in this record.University–industry knowledge transfer is an important source wealth of creation for all partners; however, the practical management of this activity within universities is often hampered by procedural rigidity either through the absence of decision-making protocols to reconcile conflicting priorities or through the inconsistent implementation of existing policies. This is problematic, since it can impede operational effectiveness, prevent inter-organisational knowledge-creation and hamper organisational learning. This paper addresses this issue by adopting a cross-discipline approach and presenting meta-rules as a solution to aid organisational decision making. It is proposed that meta-rules can help resolve tensions arising from conflicting priorities between academics, knowledge transfer offices and industry and help facilitate strategic alignment of processes and policies within and between organisations. This research contributes to the growing debate on the strategic challenges of managing knowledge transfer and presents meta-rules as a practical solution to facilitate strategic alignment of internal and external stakeholder tensions. Meta-rules has previously only been applied in a computer intelligence context however, this research proves the efficacy of meta rules in a university–industry knowledge transfer context. This research also has practical implications for knowledge transfer office managers who can use meta-rules to help overcome resource limitations, conflicting priorities and goals of diverse internal and external stakeholders