Costing in economic evaluation.
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Biomedical subjects
Publications and source records attributed to J Raftery.
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The correct positions of the deuterium (D) atoms of many of the bound waters in the protein concanavalin A are revealed by neutron Laue diffraction. The approach includes cases where these water D atoms show enough mobility to render them invisible even to ultra-high resolution synchrotron-radiation X-ray crystallography. The positions of the bound water H atoms calculated on the basis of chemical and energetic considerations are often incorrect. The D-atom positions for the water molecules in the Mn-, Ca- and sugar-binding sites of concanavalin A are described in detail.
The A1 subunit of the carotenoprotein alpha-crustacyanin, isolated from lobster carapace, has been crystallized using the vapour-diffusion method. The crystals, grown in solutions of ammonium sulfate containing methylpentanediol (MPD), diffracted to 2. 0 A. The crystals are stable to radiation. The space group of the crystals is P2(1)2(1)2(1). The unit-cell parameters are a = 41.9, b = 80.7, c = 110.8 A. 'Standard structure determination' has been unsuccessful within this crustacyanin family. Instead, an approach based on the S atoms is being undertaken involving softer X-rays at the SRS, Daresbury.
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The subunit C1 of the carotenoid-binding protein, V600, of the chondrophore Velella velella has been purified and crystallized. The crystals, which were grown by the vapour-diffusion method from ammonium sulfate as the major precipitant, diffract beyond 3 A and show little radiation damage over long periods (greater than 100 h) on a Cu Kalpha rotating-anode X-ray source. The space group of the crystals is P212121 with cell dimensions a = 42.0, b = 80.9, c = 110. 6 A.
This article reviews the methodological limitations identified in a recent authoritative US report by the Public Health Service, which provides the theoretical background to several other guidelines on cost effectiveness, such as those of the British Medical Journal. It places each limitation in context and discusses the implications of each individually and collectively. It concludes that while the report's interim solution by consensus agreement offers a way forward in the short term, the complexities identified reveal a range of limitations to the more heroic uses of cost effectiveness analysis in healthcare. More modest approaches, it is suggested, may have greater practical relevance.
The enzyme hydroxymethylbilane synthase (HMBS, E.C. 4.3.1.8) catalyzes the conversion of porphobilinogen into hydroxymethylbilane, a key intermediate for the biosynthesis of heme, chlorophylls, vitamin B12 and related macrocycles. The enzyme is found in all organisms, except viruses. The crystal structure of the selenomethionine-labelled enzyme ([SeMet]HMBS) from Escherichia coli has been solved by the multi-wavelength anomalous dispersion (MAD) experimental method using the Daresbury SRS station 9.5. In addition, [SeMet]HMBS has been studied by MAD at the Grenoble ESRF MAD beamline BM14 (BL19) and this work is described especially with respect to the use of the ESRF CCD detector. The structure at ambient temperature has been refined, the R factor being 16.8% at 2. 4 A resolution. The dipyrromethane cofactor of the enzyme is preserved in its reduced form in the crystal and its geometrical shape is in full agreement with the crystal structures of authentic dipyrromethanes. Proximal to the reactive C atom of the reduced cofactor, spherical density is seen consistent with there being a water molecule ideally placed to take part in the final step of the enzyme reaction cycle. Intriguingly, the loop with residues 47-58 is not ordered in the structure of this form of the enzyme, which carries no substrate. Direct experimental study of the active enzyme is now feasible using time-resolved Laue diffraction and freeze-trapping, building on the structural work described here as the foundation.
A number of methods can be used to improve the stability of the protein crystal-growth environment, including growth in microgravity without an air-liquid phase boundary, growth in gels and growth under oil ('microbatch'). In this study, X-ray data has been collected from and structures refined for crystals of hen egg-white lysozyme (HEWL) grown using four different methods, liquid-liquid dialysis on Earth and in microgravity using the European Space Agency's (ESA) Advanced Protein Crystallization Facility (APCF) on board the NASA Space Shuttle Life and Microgravity Spacelab (LMS) mission (STS-78), crystallization in agarose gel using a tube liquid-gel diffusion method and crystallization in microbatch under oil. A comparison of the overall quality of the X-ray data, the protein structures and especially the bound-water structures has been carried out at 1.8 A. The lysozyme protein structures corresponding to these four different crystallization methods remain similar. A small improvement in the bound-solvent structure is seen in lysozyme crystals grown in microgravity by liquid-liquid dialysis, which has a more stable fluid physics state in microgravity, and is consistent with a better formed protein crystal in microgravity.
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OBJECTIVES: To evaluate the reported achievements of the 52 first wave total purchasing pilot schemes in 1996-7 and the factors associated with these; and to consider the implications of these findings for the development of the proposed primary care groups. DESIGN: Face to face interviews with lead general practitioners, project managers, and health authority representatives responsible for each pilot; and analysis of hospital episode statistics. SETTING: England and Scotland for evaluation of pilots; England only for consideration of implications for primary care groups. MAIN OUTCOME MEASURES: The ability of total purchasers to achieve their own objectives and their ability specifically to achieve objectives in the service areas beyond fundholding included in total purchasing. RESULTS: The level of achievement between pilots varied widely. Achievement was more likely to be reported in primary than in secondary care. Reported achievements in reducing length of stay and emergency admissions were corroborated by analysis of hospital episode statistics. Single practice and small multipractice pilots were more likely than large multipractice projects to report achieving their objectives. Achievements were also associated with higher direct management costs per head and the ability to undertake independent contracting. Large multipractice pilots required considerable organisational development before progress could be made. CONCLUSION: The ability to create effective commissioning organisations the size of the proposed primary care groups should not be underestimated. To be effective commissioners, these care groups will need to invest heavily in their organisational development and in the short term are likely to need an additional development budget rather than the reduction in spending on NHS management that is planned by the government.
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