"New" and distributed leadership in quality and safety in healthcare, or "old" and hierarchical? : An interview study with strategic stakeholders

Peer reviewedPostprin

The friends and family test : a qualitative study of concerns that influence the willingness of English National Health Service staff to recommend their organisation

Peer reviewedPublisher PD

Ellipticine derivatives: targeting cell proliferation by a structured approach

Ellipticine and its derivatives are molecules which possess potent anticancer activity. This thesis explores the synthesis of novel ellipticine derivatives, as well as modifications of the template, and evaluates their biological activity as anticancer agents. The first section of this work, expands on previous work within the group, exploring derivatisation at the 9-position of the ellipticine template. This methodology was then extended to encompass isoellipticine and neoellipticine, two of the isomeric forms of ellipticine. This range of analogues allows for assessment of the role of the pyridine nitrogen for bioactivity and explores the theme of D-ring modification. A panel of novel ellipticinium salts were generated, which encompass a range of substituents at the N-2, N-6 and C-9 position. To further explore the role of the D-ring, three anhydrides were subjected to the methodology for the synthesis of ellipticine but none of the coupling reactions proved successful. However, by implementing an alternative synthetic route, new maleimide-type D-rings were successfully introduced, maintaining the carbazole core. This work was extended further, examining the use of benzofuran as a starting material, in place of indole, allowing for the generation of new tetracyclic scaffolds and corresponding derivatives. Substitution of 2-position of the D-ring took a fragment based approach, generating a panel of the novel analogues of the tetracyclic dibenzofuran fused imide compounds. A panel of 27 novel derivatives was prepared encompassing derivatives of ellipticine and its isomers. A further 43 novel benzofuran derivatives and 7 novel maleic anhydride intermediates were generated across 7 different templates. From both families, a total of 66 compounds were sent for biological evaluation, with the primary source of information gathered from the NCI 60-human tumour cell lines screen. This in vitro information allowed the identification of new lead compounds, highlighting compounds with nanomolar GI50 values and selectivity for specific cell lines. One isoellipticine analogue displayed a mean growth of −5.64% and on progression to five-dose screening, a mean GI50 of 0.42 μM was obtained with selectivity observed for the renal cell line A498 (GI50 0.02 μM). Novel ellipticinium salts were biologically evaluated by our collaborators in the University of Newcastle, Australia, identifying long chain alkyl ellipticinium salts with very good bioactivity, which is corroborated by findings from the NCI, where a mean GI50 value of 3.09 μM was recorded for one such derivative. In the benzofuran series, preliminary results have shown excellent activity, with diethylamino propyl and diethylamino ethyl substituents generating mean growths as low as 3.77% and have progressed to five-dose screenin

Beyond metrics? Utilizing 'soft intelligence' for healthcare quality and safety.

Formal metrics for monitoring the quality and safety of healthcare have a valuable role, but may not, by themselves, yield full insight into the range of fallibilities in organizations. 'Soft intelligence' is usefully understood as the processes and behaviours associated with seeking and interpreting soft data-of the kind that evade easy capture, straightforward classification and simple quantification-to produce forms of knowledge that can provide the basis for intervention. With the aim of examining current and potential practice in relation to soft intelligence, we conducted and analysed 107 in-depth qualitative interviews with senior leaders, including managers and clinicians, involved in healthcare quality and safety in the English National Health Service. We found that participants were in little doubt about the value of softer forms of data, especially for their role in revealing troubling issues that might be obscured by conventional metrics. Their struggles lay in how to access softer data and turn them into a useful form of knowing. Some of the dominant approaches they used risked replicating the limitations of hard, quantitative data. They relied on processes of aggregation and triangulation that prioritised reliability, or on instrumental use of soft data to animate the metrics. The unpredictable, untameable, spontaneous quality of soft data could be lost in efforts to systematize their collection and interpretation to render them more tractable. A more challenging but potentially rewarding approach involved processes and behaviours aimed at disrupting taken-for-granted assumptions about quality, safety, and organizational performance. This approach, which explicitly values the seeking out and the hearing of multiple voices, is consistent with conceptual frameworks of organizational sensemaking and dialogical understandings of knowledge. Using soft intelligence this way can be challenging and discomfiting, but may offer a critical defence against the complacency that can precede crisis

Negotiating freedom in the circum-Caribbean : the Jamaican Maroons and Creek Nation compared

PhD ThesisBuilt on an investigation of a large number of archival sources in three different countries, this study analyses free, non-white communities in the circum-Caribbean. Using the comparative method, I assess how the Maroons and Creeks negotiated a role for themselves in an inter-war context, exploring their interactions with four main groups. First, I consider the Maroon and Creek relationship with the enslaved population of Jamaica and the United States, respectively. This allows me to demonstrate that the signing of the peace treaties with white society had little impact on interactions with slaves. Maroon and Creek attitudes towards slaves continued in much the same manner as before peace, it was the contexts in which these interactions that took place which changed. Second, I scrutinise how the two communities navigated the potentially inflammatory situation of peace with their former white enemies. I argue that the Maroons enjoyed a more amicable relationship than the Creeks did with the local white settlers. This was largely a result of the fact that the Maroons and local whites shared a mutual usefulness whereas the Creeks and local whites did not. Third, I compare the Maroon alliance with the colonial government of Jamaica with that of the Creek and federal government. I show that, initially, both governments appreciated the usefulness of such an allegiance but, as time passed and the Maroons and Creeks showed no indication of submissiveness, both soon moved to restrict, and ultimately reduce, the independence of the societies. This attitude was exacerbated following the Haitian Revolution when the perceived threat to white stability from the Maroons was at its height and the white desire for Creek lands was increased with the Louisiana Purchase. Finally, I examine the degree of Maroon and Creek interactions outside the borders of Jamaica and the United States. I show that both were fully incorporated into the circum-Caribbean region both before and after the peace treaties. Whilst the Maroons encountered European powers prior to the treaties, this ceased with the coming of peace and their alliance was focused on the British. However, the fears of the colonial government, particularly after the Haitian Revolution, ensured that the Maroons would be plagued by rumours of foreign collusion throughout the eighteenth century. In ii contrast, the Creeks continued their numerous communications with European powers after the ending of hostilities. American fears were based on very real events. As a whole, my PhD thesis challenges the current strict hierarchical conception of race in the circum-Caribbean. The similarities between the Maroons and Creeks highlight the fact that non-white experiences were often determined by free status and the cause of many of the differences was the different ‘frontier’ context of the two rather than their divergent racial backgrounds.Arts and Humanities Research Council in the form of a doctoral awar

A light and transmission electron microscopical characterization of contact sensitivity in the mouse.

Dept. of Biological Sciences. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1983 .M344. Source: Masters Abstracts International, Volume: 40-07, page: . Thesis (M.Sc.)--University of Windsor (Canada), 1983

"For how long are we going to take the tablets?" Kenyan stakeholders' views on priority investments to sustainably tackle soil-transmitted helminths.

Recent global commitments to shift responsibility for Neglected Tropical Disease (NTD) control to affected countries reflect a renewed emphasis on sustainability, away from aid-dependency. This calls for a better understanding of how domestic stakeholders perceive investments in different strategies for NTD control. Soil transmitted helminths (STH) are among the NTDs targeted for elimination as a public health problem by international agencies through mass drug administration, provided periodically to at-risk population groups, often using drugs donated by pharmaceutical companies. This study was conducted in Kenya at a time when responsibilities for long running STH programmes were transitioning from external to national and sub-national agencies. Following an initial assessment in which we identified key domestic stakeholders and reviewed relevant scientific and government documents, the perspectives of stakeholders working in health, education, community engagement and sanitation were investigated through semi-structured interviews with national level policymakers, county level policymakers, and frontline implementers in one high-STH burden county, Kwale. Our conceptual framework on sustainability traced a progression in thinking, from ensuring financial stability through the technical ability to adapt to changing circumstances, and ultimately to a situation where a programme is prioritised by domestic policymakers because empowered communities demand it. It was clear from our interviews that most Kenyan stakeholders sought to be at the final stage in this progression. Interviewees criticised long-term investment in mass drug administration, the approach favoured predominantly by external agencies, for failing to address underlying causes of STH. Instead they identified three synergistic priority areas for investment: changes in institutional structures and culture to reduce working in silos; building community demand and ownership; and increased policymaker engagement on underlying socioeconomic and environmental causes of STH. Although challenging to implement, the shift in responsibility from external agencies to domestic stakeholders may lead to emergence of new strategic directions