The curious case of an internal pilot in a multicentre randomised trial-time for a rethink?

Acknowledgements The authors would like to acknowledge helpful discussions on this topic held with various colleagues in connection with a variety of projects. Funding No funding was received for this work.Peer reviewedPublisher PD

Non-compliance with randomised allocation and missing outcome data in randomised controlled trials evaluating surgical interventions : a systematic review

Acknowledgements JAC held MRC training (reference number: G0601938) and methodology (reference number: G1002292) fellowships while this research was undertaken. The Health Services Research Unit is core funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. The authors accept full responsibility for this manuscript.Peer reviewedPublisher PD

Striving for inclusive design in the built environment: learning strategy adopted by policy implementers at local authorities in England

The research will explore views on inclusive design policy implementation and learning strategy used in practice by Local Authorities’ planning, building control and policy departments in England. It reports emerging research findings. The research aim was developed from an extensive literature review, and informed by a pilot study with relevant Local Authority departments. The pilot study highlighted gaps within the process of policy implementation, a lack of awareness of the process and flaws in the design guidance policy. This has helped inform the development of a robust research design using both a survey and semi-structured interviews. The questionnaire targeted key employees within Local Authorities designed to establish how employees learn about inclusive design policy and to determine their views on current approaches of inclusive design policy implementation adopted by their Local Authorities. The questionnaire produces 117 responses. Interestingly approximately 9 out of 129 Local Authorities approached claimed that they were unable to participate either because an inclusive design policy was not adopted or they were faced with a high workload and thus unable to take part. An emerging finding is a lack of understanding of inclusive design problems, which may lead to problem with inclusive design policy implementation, and thus adversely affect how the built environment can be experienced. There is a strong indication from the survey respondents indicating that they are most likely to learn about inclusive design from policy guides produced by their Local Authorities and from their colleagues

Numerical Investigation Of The Leakage Flows In Twin Screw Compressor Rotors

Screw compressors are complex flow systems, but operate upon simple considerations: they are positive displacement machines consisting of meshing rotors contained in a casing to form a working chamber, whose volume depends only on the angle of rotation. Although the basic operation of twin screw compressors is well understood and the analytical methods for performance prediction are well established, the CFD analysis of such machines is still in its early days and requires more research in order to mature to the level of standardised application, as is the case with most turbomachinery applications. The performance of screw compressors is highly affected by leakages, which are dependent on various clearances and the pressure differences across these clearances. The numerical simulation of the leakage flows is the challenging aspect of running CFD in screw compressors, as the flow domain reduces in tip areas to the order of several microns. Commercial grid generators struggle in reproducing the flow path with good quality elements and user defined meshing techniques are currently available to allow the remeshing of the rotors domain to capture the modified aspect of the compression chamber at the start of each time step. This technique allows the full compressor performance prediction by means of CFD but does not allow for local mesh refinement in the tip area, where the turbulent character of the flow requires adequate boundary layer considerations. This is the area of concern in the present paper, where several means of investigating the flow in the very tight tip clearance area are proposed: 1) a three-dimensional model of all interacting compression chambers to investigate the effects of employing mesh-deforming techniques for the compressor simulation; 2) a simplified two-dimensional leakage model to identify the mesh refinement requirements for appropriate turbulence modelling. Keywords: screw compressors, CFD, leakage flows, tip sea

Exploiting genomics to improve the biological control potential of Pasteuria spp., an organisms with potential to control plant-parasitic nematodes

The Pasteuria group of Gram positive bacteria are invertebrate parasites with the potential to be developed into biological control agents of plant-parasitic nematodes. A key step in the infection process is the attachment of endospores to the cuticle of plant-parasitic nematodes, possibly through a Velcro-like attachment system involving the collagen-like fibres of the exosporium (Davies, 2009). Phylogenetically these bacteria are members of the Firmicutes and closely related to the members of genus Bacillus. Some of the genes involved in the construction of the endospore and in particular the exosporium in Bacillus spp. have already been identified. The Pasteuria sequences in the public databases and the complete genomes of Bacillus spp. were investigated for the genes linked with the endospore and associated exosporium. On the basis of our in silico studies we report the presence of genes putatively similar to bclA, exsJ and vrrB in Pasteuria.Non peer reviewedFinal Accepted Versio

Generic Utilization Rates, Real Pharmaceutical Prices, and Research and Development Expenditures

Generic utilization rates have risen substantially since the enactment of The Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman) in 1984. In the year Hatch-Waxman was enacted, generic utilization rates were 19 percent; in contrast, today, the generic utilization rate is approximately 70 percent. Striking a balance between access to existing medicines and access to yet-to-be-discovered (and developed) drugs, through research incentives, was the principal objective of this landmark legislation. However, given the current rate of generic utilization, it seems plausible, if not likely, that any balance achieved by the 1984 Act has since shifted away from research incentives and towards improved access, ceteris paribus. Among other factors, recent mandatory substitution laws in most states have driven up generic utilization rates. In the current paper, we employ semi-annual data from 1992 to 2008 to examine the link between generic utilization rates and real U.S. prescription drug prices. This link is important because previous research has identified a causal relationship between real drug prices in the U.S. and industry-level R&D investment intensity. We identify a statistically significant, positive relationship between generic utilization rates in the U.S. and real U.S. prescription drug prices. Specifically, we estimate an elasticity of real drug prices to generic utilization rates of -0.15. This finding, when coupled with previous empirical work on the determinants of pharmaceutical R&D intensity, suggests an elasticity of R&D to generic utilization rates of about 0.090. While the magnitude of this elasticity is modest, as theory would predict—the effect of greater generic erosion of brand sales at patent expiration is heavily discounted due to the long time horizon to generic erosion when an R&D project is in clinical development. However, because there has been a very substantial increase in generic utilization rates since 1984, the impact on R&D is nevertheless quite large. We explore this and other issues in the current paper.

Trichoderma koningii and Trichoderma harzianum as destructive mycoparasites of Sclerotinia slerotiorum.

Three T. koningii (Tk 3, 5 and 12) and one T. harzianum (Th 9) strain isolated from S. sclerotiorum sclerotia were found to reduce the growth of the patogens by over 60% relative to that of the control. These strains also hyperparasited the sclerotia. All were also highly competitive when assessed in the saprophytic competitiveness test. Extra cellular enzyme production was not particularly correlated with antagonistic activity, Tk 12 and Th 9 produced some Beta-glucosidase and no endoglucanase. In contrast, Tk3, 5 and 12 produced large amounts of antibiotics, causing between 30% and 80% inhibition of growth of the pathogen. The interactions between T. harzianum strain and S. sclerotiorum appeared to be mycoparasitism, and results from the sclerotial survival tests showed they were also capable of destroying sclerotia

A systematic review of the use of an expertise-based randomised controlled trial design

Acknowledgements JAC held a Medical Research Council UK methodology (G1002292) fellowship, which supported this research. The Health Services Research Unit, Institute of Applied Health Sciences (University of Aberdeen), is core-funded by the Chief Scientist Office of the Scottish Government Health and Social Care Directorates. Views express are those of the authors and do not necessarily reflect the views of the funders.Peer reviewedPublisher PD