David Chambers

Understanding the role of opinion leaders in improving clinical effectiveness.

We present findings from evaluations of two government-funded initiatives exploring the transfer of research evidence into clinical practice--the PACE Programme (Promoting Action on Clinical Effectiveness), and the Welsh Clinical Effectiveness Initiative National Demonstration Projects. We situate the findings within the context of available research evidence from healthcare and other settings on the role of opinion leaders or product champions in innovation and change--evidence which leaves a number of problems and unanswered questions. A major concern is the difficulty of achieving a single replicable description of what opinion leaders are and what they do--subjective understandings of their role differ from one setting to another, and we identify a range of very different types of opinion leadership. What makes someone a credible and influential authority is derived not just from their own personality and skills and the dynamic of their relationship with other individuals, but also from other context-specific factors. We examine the question of expert versus peer opinion leaders, and the potential for these different categories to be more or less influential at different stages in the innovation process. An often neglected area is the impact of opinion leaders who are ambivalent or hostile to an innovation. Finally, we note that the interaction between individual opinion leaders and the collective process of negotiating a change and reorienting professional norms remains poorly understood. This raises a number of methodological concerns which need to be considered in further research in this area.

Implementation of evidence-based medicine: evaluation of the Promoting Action on Clinical Effectiveness programme

Objectives: To evaluate the Promoting Action on Clinical Effectiveness (PACE) programme, which sought to implement clinically effective practice in 16 local sites. Methods: 182 semi-structured interviews, usually by telephone, with project team members, clinicians, and senior managers and representatives from the Department of Health and the Kings Fund. Results: The most influential factors were strong evidence, supportive opinion leaders and integration within a committed organization; without these factors, projects had little chance of success. Other factors (context analysis, professional involvement and good project management) emerged as important, supporting processes; their presence might be an additional help, but on their own they would not be enough to initiate change. A serious problem with any of them could have a strong adverse impact. Conclusions: Although there is no simple formula for the factors that ensure successful implementation of research-based improvements to clinical practice, certain principles do seem to help. Time and resource need to be devoted to a period of local negotiation and adaptation of good research evidence based on a careful understanding of the local context, in which opinion leader influence is an important component of a well managed and preferably well integrated process of change.

Stereoselective 1,2‐cis Glycosylation of 2‐O‐Allyl Protected Thioglycosides

The technique of intramolecular aglycon delivery (IAD), whereby a glycosyl acceptor is temporarily appended to a hydroxyl group of a glycosyl donor is an attractive method that can allow the synthesis of 1,2-cis glycosides in an entirely stereoselective fashion. 2-O-Allyl protected thioglycoside donors are excellent substrates for IAD, and may be glycosylated stereoselectively through a three-step reaction sequence. This sequence consists of quantitative yielding allyl bond isomerisation, to produce vinyl ethers that can then undergo N-iodosuccinimide mediated tethering of the desired glycosyl acceptor, and subsequent intramolecular glycosylation, to yield either alpha-glucosides or beta-mannosides accordingly. Although attempted one-pot tethering and glycosylation is hampered by competitive intermolecular reaction with excess glycosyl acceptor, this problem can be simply overcome by the use of excess glycosyl donor. Allyl mediated IAD is a widely applicable practical alternative to other IAD approaches for the synthesis of beta-mannosides, that is equally applicable for alpha-gluco linkages. It is advantageous in terms of both simplicity of application and yield, and in addition has no requirement for cyclic 4,6-protection of the glycosyl donor.

The Norway Model

The Norwegian Government Pension Fund Global was recently ranked the largest fund on the planet. It is also highly rated for its professional, low-cost, transparent, and socially responsible approach to asset management. Investment professionals increasingly refer to Norway as a model for managing financial assets. We present and evaluate the strategies followed by the Fund, review long-term performance, and describe how it responded to the financial crisis. We conclude with some lessons that investors can draw from Norway’s approach to asset management, contrasting the Norway Model with the Yale Model.

HOW GOOD WAS THE PROFITABILITY OF BRITISH RAILWAYS, 1870-1912?

This article provides new estimates of the return on capital employed (ROCE) for major British railway companies. It shows that ROCE was generally below the cost of capital after the mid-1870s and fell until the turn of the century. Addressing cost inefficiency issues could have restored ROCE to an adequate level in the late 1890s but not in 1910. Declines in ROCE hit share prices and investors made little or no money in real terms after 1897. Optimal portfolio analysis shows that, while railway securities were attractive to investors before this date, they would have been justified in rushing to the exits thereafter.

Going public in interwar Britain

Utilising a new sample of interwar initial public offerings (IPOs), I consider the effectiveness of the interwar stock market for firms going public. Consistent with the pecking order theory, IPO proceeds contributed only modestly to domestic industrys capital expenditure needs. IPOs of capital-hungry new manufacturing industries raised no more finance than did the rest of manufacturing. This was in part attributable to the detrimental effect of weak financial regulation on investor appetite for newer, riskier enterprises. In terms of the quality of firms allowed onto the market, IPO survival rates of the early and late 1920s were shockingly low, just as earlier research has shown. However, survival rates rebounded strongly in the following decade due not only to the economic recovery but also to tougher scrutiny of listing applications by the London Stock Exchange.

Gentlemanly Capitalism Revisited: A Case Study of the Underpricing of Initial Public Offerings on the London Stock Exchange, 1946–86

Allegations of British capital market failure are numerous, but frequently contentious. This paper revisits the literature by highlighting the post-1945 market for initial public offerings (IPOs) as a clear instance of capital market failure. Despite the tender method delivering substantially lower underpricing than the traditional fixed-price offer method, it was adopted by only one in 10 firms going public. This missed opportunity cost issuing firms between £1.7 billion and £3.5 billion in real proceeds forgone between 1960 and 1986, excluding privatizations, and was symptomatic of a lack of competition in equity underwriting before Big Bang.

Stereoselective synthesis of C-glycosides from carboxylic acids: the tandem Tebbe–Claisen approach

A variety of beta- or alpha-C-glycosides may be readily accessed in an entirely stereoselective fashion from esters derived from the reaction of carboxylic acids and 3-hydroxy glycals, by way of a tandem reaction sequence of Tebbe methylenation and Claisen rearrangement. Though of wide scope, for example allowing the synthesis of 1-6 linked C-disaccharides, the methodology does not currently allow the synthesis of C-glycosyl alpha-amino acids.

A facile synthesis of 4,6-O-benzylidene glucal

Abstract 4,6-O-Benzylidene protected d -glucal, a useful synthetic intermediate, may be accessed from the extremely cheap and readily available starting material α-methyl glucopyranoside, via a simple four-step reaction sequence involving selective triflation and iodide displacement at C-2.

Efficient one-step synthesis of 2-hydroxy and 2-aminoglycals from selenoglycosides

2-Hydroxy and 2-aminoglycals are readily synthesised in one step from selenoglycosides by a Sharpless-type oxidation, which is then followed by spontaneous selenoxide elimination.