890 research outputs found
Listening to Birds in the Anthropocene : The Anxious Semiotics of Sound in a Human-Dominated World
ACKNOWLEDGEMENTS Funding for much of the research on which this article is based was provided by the Arts and Humanities Research Council of the UK. I thank them and Tim Ingold for their support.Peer reviewedPublisher PD
Stable and Unstable Operations in mod p Cohomology Theories
We consider operations between two multiplicative, complex orientable
cohomology theories. Under suitable hypotheses, we construct a map from
unstable to stable operations, left-inverse to the usual map from stable to
unstable operations. In the main example, where the target theory is one of the
Morava K-theories, this provides a simple and explicit description of a
splitting arising from the Bousfield-Kuhn functorComment: 28 pages; corrected proof of proposition 3.2, other minor
improvement
Exploring Taskscapes : an introduction
Open Access via the Wiley Jisc AgreementPeer reviewedPublisher PD
Managing uncertainty - A qualitative study of surgeons' decision-making for one-stage and two-stage revision surgery for prosthetic hip joint infection
Abstract Background Approximately 88,000 primary hip replacements are performed in England and Wales each year. Around 1% go on to develop deep prosthetic joint infection. Between one-stage and two-stage revision arthroplasty best treatment options remain unclear. Our aims were to characterise consultant orthopaedic surgeonsā decisions about performing either one-stage or two-stage revision surgery for patients with deep prosthetic infection (PJI) after hip arthroplasty, and to identify whether a randomised trial comparing one-stage with two-stage revision would be feasible. Methods Semi-structured interviews were conducted with 12 consultant surgeons who perform revision surgery for PJI after hip arthroplasty at 5 high-volume National Health Service (NHS) orthopaedic departments in England and Wales. Surgeons were interviewed before the development of a multicentre randomised controlled trial. Data were analysed using a thematic approach. Results There is no single standardised surgical intervention for the treatment of PJI. Surgeons balance multiple factors when choosing a surgical strategy which include multiple patient-related factors, their own knowledge and expertise, available infrastructure and the infecting organism. Surgeons questioned whether it was appropriate that the two-stage revision remained the best treatment, and some surgeons' willingness to consider more one-stage revisions had increased over recent years and were influenced by growing evidence showing equivalence between surgical techniques, and local observations of successful one-stage revisions. Custom-made articulating spacers was a practice that enabled uncertainty to be managed in the absence of definitive evidence about the superiority of one surgical technique over the other. Surgeons highlighted the need for research evidence to inform practice and thought that a randomised trial to compare treatments was needed. Most surgeons thought that patients who they treated would be eligible for trial participation in instances where there was uncertainty about the best treatment option. Conclusions Surgeons highlighted the need for evidence to support their choice of revision. Some surgeons' willingness to consider one-stage revision for infection had increased over time, largely influenced by evidence of successful one-stage revisions. Custom-made articulating spacers also enabled surgeons to manage uncertainty about the superiority of surgical techniques. Surgeons thought that a prospective randomised controlled trial comparing one-stage with two-stage joint replacement is needed and that randomisation would be feasible
Senses of being : The atmospheres of listening to birds in Britain, Australia and New Zealand
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Inhibition of enzymes from mycobacteria using fragment-based approaches
The work described in this thesis is focused on the application of fragment-based approaches for two essential mycobacterial target proteins, fumarate hydratase (fumarase) from Mycobacterium tuberculosis (Mtb) and tRNA (m1G37) methyltransferase (TrmD) from Mycobacterium abscessus (Mab). With Mtb fumarase a high-throughput screening (HTS) hit was used to design a small library of fragments in a deconstruction-reconstruction approach. These fragments were screened using a range of both biochemical and biophysical methods. The resultant fragments showed evidence of weak protein binding. As an alternative strategy, derivatives of the HTS hit were synthesised and screened by a biochemical assay, which identified nanomolar inhibitors of this enzyme. In addition, X-ray crystallography was also carried out with a range of these compounds. Selected compounds were subsequently screened by collaborators at the NIH against Mtb.
With the enzyme TrmD from Mab, the fragment hits identified were used as the basis of a fragment-merging approach to develop potent inhibitors, guided by structural biology. In the implementation of this approach, synthesis and biophysical techniques were extensively utilised, including both differential scanning fluorimetry and isothermal titration calorimetry. This approach led to the development of novel inhibitors with low nanomolar affinity. Select compounds were screened by collaborators against both Mab and Mtb in vitro. In light of encouraging activity against Mtb, the TrmD homolog in Mtb was expressed and screened against select compounds to demonstrate the broader applicability of the lead series.EPSR
Pensions policy in the UK: An economic analysis
An attempt to unravel the complexities of pension policy in the UK, including financial, fiscal, labour-market and income-distribution analyses of the retirement-income system. This book, drawing on five yearsā IFS research, was widely praised. A Financial Times editorial observed that āThe IFSās pioneering attempt to quantify the different returns to pensioners is welcomeā. The Independent reported that āThis book challenges the common assumption that personal pension plans are inherently more risky than occupational or state provisionā.
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