The Choice of Debt Source by UK Firms

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What can a participatory approach to evaluation contribute to the field of integrated care?

© 2017 BMJ Publishing Group. All rights reserved. Better integration of care within the health sector and between health and social care is seen in many countries as an essential way of addressing the enduring problems of dwindling resources, changing demographics and unacceptable variation in quality of care. Current research evidence about the effectiveness of integration efforts supports neither the enthusiasm of those promoting and designing integrated care programmes nor the growing efforts of practitioners attempting to integrate care on the ground. In this paper we present a methodological approach, based on the principles of participatory research, that attempts to address this challenge. Participatory approaches are characterised by a desire to use social science methods to solve practical problems and a commitment on the part of researchers to substantive and sustained collaboration with relevant stakeholders. We describe how we applied an emerging practical model of participatory research, the researcher-in-residence model, to evaluate a large-scale integrated care programme in the UK. We propose that the approach added value to the programme in a number of ways: by engaging stakeholders in using established evidence and with the benefits of rigorously evaluating their work, by providing insights for local stakeholders that they were either not familiar with or had not fully considered in relation to the development and implementation of the programme and by challenging established mindsets and norms. While there is still much to learn about the benefits and challenges of applying participatory approaches in the health sector, we demonstrate how using such approaches have the potential to help practitioners integrate care more effectively in their daily practice and help progress the academic study of integrated care

Do banks really monitor? : Evidence from CEO succession decisions

The authors are grateful to Dick Davies, Paul Draper, Robert Faff, David Hillier, Ike Mathur (the editor), Katrin Migliorati, Krishna Paudyal, our anonymous reviewer, and to seminar participants at the 2nd International Conference of the Financial Engineering and Banking Society (London) and 2013 Midwest Finance Association Annual Meeting (Chicago) for helpful comments on earlier versions of this work. We also thank Martin Kemmitt for helpful research assistance on this project. All errors remain our own.Peer reviewedPostprin

The identification and characterisation of novel antimicrobial targets in Burkholderia pseudomallei

The bacterium Burkholderia pseudomallei causes the disease melioidosis, a significant public health threat in endemic regions and is a potential biowarfare agent. Treatment of melioidosis is intensive and prolonged and there is no licensed vaccine to protect against it. The aim of this study was to characterise novel targets for antimicrobials to improve treatment of melioidosis. A holistic down selection process was undertaken in order to identify a range of possible novel and exploitable antimicrobial targets in Burkholderia pseudomallei. Four targets: FtsA, FtsZ, MraW and TonB were selected for characterisation by mutagenesis study. FtsA and FtsZ are early effectors of cell division and are considered potential antimicrobial drug targets in other pathogenic bacteria. Genes for both were shown likely to be essential for viability in Burkholderia pseudomallei, following attempted deletion of the genes, thus confirming their potential for drug targeting for treatment of melioidosis. MraW, a highly conserved methyltransferase, and TonB, the energiser for high affinity iron uptake in Gram negative bacteria, were also selected for characterisation as antimicrobial targets. In-frame deletions of the genes encoding these targets were constructed in B. pseudomallei K96243. In order to determine the roles played by MraW and TonB during infection, these mutants were characterised in several models of Burkholderia pseudomallei infection. Deletion of mraW rendered the bacteria non-motile and led to attenuation during infection of Balb/C mice. A small growth defect was seen early during infection of macrophages by this mutant, whilst no attenuation was seen on deletion of mraW in Galleria mellonella. Burkholderia pseudomallei ΔtonB required free iron supplementation for growth. This mutant had an improved ability to invade murine macrophages, though the mutant was attenuated in both Galleria mellonella and Balb/C mice. Attenuation of both mutants in a mammalian model of infection, support the strategy to target either of these proteins as novel targets for inhibition with small molecules during Burkholderia pseudomallei infection. However, an improved ability to infect macrophages by Burkholderia pseudomallei ΔtonB and non-complementation of this mutant by iron supplementation to Galleria mellonella suggests additional roles to iron uptake alone for TonB in Burkholderia pseudomallei, such as bacterial iron sensing and signalling.Dst

Novel methodology for the synthesis of ¹³C-Labelled phenols and its application to the total synthesis of polyphenols

Electronic version excludes material for which permission has not been granted by the rights holderThe base-catalysed reaction of 4H-pyran-4-one with a range of nucleophiles, namely diethyl malonate, ethyl acetoacetate, nitromethane, acetylacetone and ethyl cyanoacetate, was developed as a reliable, high yielding method for the preparation of para-substituted phenols. The methodology was extended to include the use of the substituted pyranones, maltol, 2,6-dimethyl-4H-pyran-4-one and diethyl chelidonate. Reactions were studied using conventional heating methods and microwave irradiation. Microwave irradiation had definite beneficial effects, with improved yields, reduced reaction times and cleaner reaction profiles. The potential of this methodology was examined for the regioselective placement of ¹³C-atoms into benzene rings using ¹³C-labelled nucleophiles or ¹³C-labelled 4H-pyran-4-ones. [3,5-13C₂]4H-Pyran-4-one and [2,6-13C₂]4H-pyran-4-one were prepared from various ¹³C-labelled versions of triethyl orthoformate and acetone. This methodology was applied to the synthesis of [1,3,5-¹³C₃]gallic acid, via the base-catalysed reaction of [3,5-¹³C₂]4H-pyran-4-one with diethyl [2-¹³C]malonate, followed by subsequent transformations to yield [1,3,5-¹³C₃]gallic acid. The preparation of [2-¹³C]phloroglucinol was carried out via [2-¹³C]resorcinol, with regioselective placement of a single ¹³C-atom into the aromatic ring. This was accomplished from non-aromatic precursors, with the source of the ¹³C-atom being [¹³C]methyl iodide. The key step in this synthesis was the introduction of the third hydroxyl group, which was achieved using a modified iridium-catalysed C-H activation/borylation/oxidation procedure. The scope of an existing C-H activation/borylation reaction was modified and expanded to include a range of protected resorcinol derivatives. A catalyst system was developed which allowed high conversion to the intermediate arylboronic acids, followed by oxidation using aqueous Oxone® to yield the corresponding phenols. Finally, to demonstrate the potential of these new methods for application in the synthesis of isotopically labelled natural products and polyphenols, the syntheses of ¹³C-labelled anthocyanins were studied. A route was developed that could be applied to the synthesis of either cyanidin-3-glucoside or delphinidin-3-glucoside. Only the final coupling/cyclisation step to yield the desired anthocyanin targets remains to be carried out

A delicate dance: autoethnography, curriculum, and the semblance of intimacy

Have you ever had a dream that you shared an intimate moment—grew close—with someone who in your waking life you barely knew; or that you knew a language that outside of your dream you did not understand? Or if you are a teacher, have you ever dreamt that you connected with a student—actually taught them something? If upon waking you have felt the residual yet potent ephemeral as-ifness of such closeness, you have experienced what is the focus of this study: the semblance of intimacy. This dissertation, via autoethnography, couples experiences teaching multicultural education and learning to zydeco dance in order to explore semblances of intimacy across self and other; also, to consider the implications of such semblances in terms of thinking about curriculum and research. I use the term “semblance” to suggest that the intimacy at work in the embodied virtual worlds of zydeco, autoethnography, and curriculum can be a powerful as-ifness, or what Jerome Bruner (1985) might describe as a “truth likeness” (p. 97). Thrift (1997) explores dance as “as an example of play; a kind of exaggeration of everyday embodied joint action which contains within it the capacity to hint at different experiential frames, ‘elsewheres’ which are here” (p. 150). Thrift (1997) calls these hints to elsewhere “semblances,” which he describes as an embodied meaning that is “not taken for real, but it is enacted as if it were” (p. 145). In what follows, I borrow Thrift’s (1997) notion of semblance to look specifically at semblances of intimacy embodied on the dance floor, and the implications such intimacy might have for thinking about curriculum and autoethnographic research. What might it mean to envision curriculum as an embodied locale much like zydeco dancing: where the play of epistemological forces replaces technocratic force, and where students experience the relative weight of desire, fear, and knowledge; the reciprocal touch of self and other; and the mysterious momentum of the semblance of intimacy

Quantifying Ecosystem Trajectories: Tree Growth Response to Biophysical Gradients and Disturbance

Disturbance and climate are important drivers of tree physiological functioning, community assemblages and trends in recruitment and species presence across time and space. Fire exclusion-driven changes to the disturbance regime of frequent fire-adapted forests of the southern Rocky Mountains, North America, followed by modern megafires has strongly influenced stand structure and led to density increases in many forest types. Recent decadal drought has led to widespread mortality of some tree species, exacerbated fire extent and effects, and contributed to insect outbreaks. With climate change ongoing, hotter and drier conditions and droughts are expected, leading to increased risk of widespread tree mortality and vegetation type change. Forest ecosystem changes result from compounding effects on individual tree establishment, growth, and survival, which leads to changes in stand structure and composition, and drives patterns appreciable at the broadest scale. Here I focus on tree-environment interactions in the context of disturbance and climate across three scales, from tree-stand, to stand-watershed, to forest-ecosystem. By working across scales we can observe how fine-scale tree responses to interact with the environment to create broad patterns. At the tree scale, I considered the influence of increased forest density on tradeoffs of water and nutrient limitation affecting growth and physiological functioning in old-growth ponderosa pine (Pinus ponderosa Douglas ex C. Lawson) (Appendix A). I identified a novel interaction in which lower leaf nitrogen in dense stands was associated with lower tree-ring growth yet higher carbon isotope discrimination, rather than the expected negative relationship between discrimination and density-driven water stress. Reduced leaf nitrogen likely limited photosynthetic capacity, resulting in discrimination values more decoupled from water stress than is expected in the Southern Rockies. At the stand level to watershed scale, I investigated climate-growth relationships and species distributions across a biophysical gradient in southwestern mixed-conifer forest (Appendix B). I used model selection to find how climate drivers of tree-ring growth varied by species, elevation, and aspect, and found differences were in accordance with relative species drought tolerance. I combined this with stand-level regeneration patterns to predict shifts in species dominance across the watershed. In the absence of fire, I found increased regeneration in pinyon pine (Pinus edulis Engelm.) at low elevations and white fir (Abies concolor (Gord. & Glend.) Lindl. ex Hildebr.) at high elevations, while regeneration of ponderosa pine and Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco) decreased everywhere across the study area. At the ecosystem scale I used Forest Inventory and Analysis (FIA) data to derive the novel Community Mean Tolerance Index, based on relating species shade and drought tolerance to ecosystem changes and applied it to investigate demographic trends within and across forest types (Appendix C). With the index I mapped responses within and across forest ecosystems in the southern Rocky Mountains, and found areas at risk for vegetation type conversion to oak woodland following severe fire. Substantial shifts in mean drought and shade tolerance in tree regeneration was found in forest types that had exceeded their historic fire interval. Across forest types, drought tolerance in seedling groups increased at lower elevation sites, while shade tolerance increased at higher elevation sites. The difference in drought tolerance across demographic groups was significantly associated with PRISM-derived recent temperature and precipitation means, indicating the potential for climate-driven community shifts. Investigating the effects of disturbance and climate on trees, watersheds, and ecosystems allows for a holistic view across scales of the current state of southwestern forests, and the potential for future changes