The sheep conceptus modulates proteome profiles in caruncular endometrium during early pregnancy

This project was funded by NHS Grampian R&D project number RG05/019Peer reviewedPostprin

Economics and public policy 0 NHS research and development as a public good

This paper analyses National Health Service R&D as a Samuelsonian public good. It also identifies other characteristics of NHS R&D: supplier-induced demand; information asymmetries; jointness in production of R&D, medical education and health care; multiplicity in research funding sources; uncertainty about research outcomes; the difficulty of measuring and valuing research outcomes; and the behavioural characteristics of the institutions which produce R&D. The principal conclusion is that a centrally planned approach is unlikely to solve the problems arising from these characteristics, whereas the creation of an appropriate institutional and behavioural framework is more promising. The recent reforms in the arrangements for supporting R&D in the NHS can be seen as a response consistent with this analysis, are outlined and set in their historical context.R&D; supply and demand

Evaluation of the NHS R & D implementation methods programme

Chapter 1: Background and introduction • Concern with research implementation was a major factor behind the creation of the NHS R&D Programme in 1991. In 1994 an Advisory Group was established to identify research priorities in this field. The Implementation Methods Programme (IMP) flowed from this and its Commissioning Group funded 36 projects. Funding for the IMP was capped before the second round of commissioning. The Commissioning Group was disbanded and eventually responsibility for the programme passed to the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D (NCCSDO) which, when most projects had finished, asked the Health Economics Research Group (HERG) to conduct an evaluation. This was intended to cover: the quality of outputs; lessons to be learnt about the communication strategy and the commissioning process; and the benefits or payback from the projects. As agreed, the evaluation also addresses the questions of whether there should be a synthesis of the findings from the IMP and any further assessment of payback. Chapter 2: Methods • We adopted a wide range of quantitative and qualitative methods in the evaluation. They included: documentary analysis; interviews with key actors; questionnaires to the funded lead researchers; questionnaires to potential users; and desk analysis. Chapter 3: The outputs from the programme • As in previous assessments of research programmes, we first examined the outputs in terms of knowledge production and various items related to capacity to conduct further research. Although there was a high response rate to the questionnaire to lead researchers (30/36), missing responses mean that the data given below are incomplete. In the case of publications, however, we also made some use of data previously gathered by the programme office. • We attempted to identify publications that were in some way a specific product of IMP funding. About half (59) of the publications from the IMP projects are articles in peer reviewed journals. The journal used most frequently for publication, the BMJ, is also the one with the highest journal impact factor score of those publishing articles specifically from the programme. The recent publication datesof many articles reduces the value of citation analysis. Nevertheless, one article, Coulter et al, 1999, has already been cited on 53 occasions. Important publications, including No Magic Bullets (Oxman et al, 1995), are also associated with preliminary work undertaken for the IMP to assist priority setting. • Fifteen projects, with grants of over £1.3 million, have been awarded to IMP researchers by other funders for follow-on studies connected in some way to the IMP. We also collected details about some non-IMP researchers who are building on the IMP projects. • Research training provided in at least nine of the funded IMP projects is associated with higher/research degrees, including three MDs and four PhDs, that have been awarded or are being completed. Chapter 4: Disseminating and using the research findings • Limited thought had been given by the Implementation Methods Programme to dissemination strategies, but many of the individual researchers were active here. In response to the questionnaires, lead researchers reported making 92 presentations to academic audiences and 104 to practitioner/service groups. Some lead researchers showed that their effective dissemination led to utilisation of the findings. • The Commissioning Group gave some thought to the likely use that could be made of individual research projects, but there was limited systematic analysis of how the findings as a whole would be taken forward. Achieving impact is difficult in this complex field and less than a third of lead researchers claimed to have done so, but about half thought impact could be expected. Based mainly on reports from lead researchers, we give a brief account of how the findings from six projects are being utilised. • We sent electronic questionnaires to groups of potential users of selected projects but this produced a very low response rate. Our postal survey to Heads of Midwifery/researchers in perinatal care produced a higher response of 44%. Amongst those who did respond, there is quite a high level of knowledge about some of the programme’s projects and some level of existing and potential utilisation. We suggest, however, that in some cases there are difficulties in identifying how far the respondent’s focus is on the findings from the original research projects, and it how far it is on the impact of the IMP study that is about ways of influencing the uptake of such findings. Comments from several respondents showed strong support for the cutting edge nature of some of the research. Others, however, also indicated why findings might not be utilised by some practitioners. Several respondents advocated greater dissemination of the IMP. Chapter 5: Comparing applications with outputs • We attempted to compare the scores given to project applications with those given to projects based on their outputs. This exercise faced various problems. The final reports from all completed projects had in theory already been reviewed and given scores for their quality and relevance. In practice, not all final reports received scores. We added a refinement by giving further scores that incorporated the additional information we gathered about both publications and any uptake of the research findings. • Various limitations meant that we conducted this analysis on just 19 of the 36 projects. Nevertheless, the wide range of scores given to the outputs from projects indicates that some were much more successful than others. Our rather limited evidence suggests that there is some correlation between the scores for applications and those for outputs but it is small, which could be related to the difficulties encountered during commissioning. Chapter 6: Lessons learnt about the commissioning process • Those who established the IMP were aware that it was a different type of research field from those previously addressed within the NHS R&D Programme, but one regarded nonetheless as important. Within the NHS R&D Programme at that time a standard clinical RCT approach was strongly favoured. There was also, as ever, a need for quick results. • In developing an understanding of implementation the Advisory Group (AG) conducted cutting edge analysis, consulted widely and drew on a wide range of disciplines. Our interviewees generally took the view that the AG worked well in setting priorities and went as far as it could at the time, especially given the time constraints. • Based on our field work and analysis we identified a series of lessons that might inform future exercises. More attention was required to ensure that all relevant background disciplines were adequately taken into account in setting priorities and commissioning research. Some of these processes needed to be given more time than was available. Consultation needed to be organised in a sufficiently selective way to be of maximum benefit in such a complex area. A time-limited programme was not the most appropriate way to cover a field such as this. • In relation to the commissioning of the projects, we identified issues about the composition of commissioning groups and how people from different backgrounds (researchers, practitioners, managers and patient representatives) should best be involved. • In this new field the Commissioning Group (CG) had to work closely with applicants to develop some of the research applications. This raised issues about how, and when, this process should be handled. • Despite its own rationale, and for a variety of reasons, including the disbanding of the CG, the Implementation Methods Programme never developed an implementation or communication strategy for its own findings. • The general conclusion of those who had been involved with the IMP was that it worked as well as it could at the time, and that various important projects were commissioned. But it was only a start. Chapter 7: Should a synthesis of the findings from the programme and further payback analysis be undertaken? • From interviews and questionnaires we identified widespread, but not total, agreement that there should be some type of synthesis of the findings from the IMP. There is more debate about the form such a synthesis should take. There is some support for a more limited type of stock taking, but also wider backing for the inclusion of many different elements. These could include: a conceptual map of the field of research implementation; an exploration of how the findings from the IMP fit into the context of research implementation today; and an assessment of how far work is still needed in those areas where no projects were funded. One possible suggestion that might incorporate much of this thinking is for the establishment of a group or commission of leading researchers in the field. Their investigation could incorporate all these elements and attempt to show how the issues could be advanced. • We suggest that further work on assessing the payback from the IMP is probably not worthwhile unless it is undertaken as part of a wide-ranging synthesis. Chapter 8: Conclusions, lessons and recommendations • We conclude that the IMP was seen by many of those involved as a new and exciting field. Looking back, they were generally positive about what was started through the IMP. It commissioned a series of projects that produced some important, rigorous, and cutting edge research, at least some of which is making an impact. But this is a complex area in which traditional clinical research, health services research and the social sciences all have a role to play. A unique set of difficulties, as well as opportunities, was faced by those responsible for taking the programme forward. The intellectual challenges of constructing a programme to cover such a vast area with diverse and sometimes conflicting conceptual and methodological perspectives, were compounded by practical problems. These included the capping of the programme’s funding and the premature winding up of the Commissioning Group. As a result, this complex programme, which arguably needed better support than its more clinically orientated predecessors, did not receive it at some stages. Those involved in the programme had a considerable task – the difficulties of which were not completely appreciated at the time. They are clearer in retrospect and feed into the lessons and recommendations presented here, but it is recognised that a programme such as the SDO is already adopting some of the steps. • In relation to research commissioning and communication strategies for research programmes in general, we suggest it could be helpful if protocols were drawn up to cover certain potential difficulties. These include the remit and role of the various stakeholders represented on commissioning groups and the extent to which commissioning groups should be expected to support applicants with their proposals. Perhaps the key general lesson from this evaluation is the need for research programmes to have a proper communication strategy. This should target dissemination at relevant audiences and stress the desirability for contact to be made with potential users as early as possible in the process of devising a project. • Our other recommendations are more specifically relevant when the SDO Programme is considering an area such as implementation methods research. It would be desirable for more time to be made available for preparatory work than was allowed for the IMP and also scope provided for the programme to be able to re-visit issues and learn from early results. It is difficult to incorporate all the analysis that is required if a programme is operating in a time-limited way. • Our conclusion that research implementation is a crucial area for the NHS R&D Programme leads to the recommendation that more R&D activity is needed in this field in order to assist delivery of some key NHS agenda items. As a preliminary step, there is certainly scope for a type of stock taking of the findings from the IMP. On balance there seems also to be an argument for conducting a synthesis of work in the implementation field that goes beyond a mere collation of findings from the specific projects funded. If undertaken, it should fundamentally examine the current NHS needs for research on implementation and how they could be addressed in the light of the findings from the IMP and elsewhere. • Finally, we recommend that more attention should be given to the timing of evaluations such as this and that a phased approach should be adopted. Furthermore, researchers should be informed at the outset of their project about the likely requirements that might be placed upon them in terms of responding to requests for information by those conducting an evaluation.National Co-ordinating Centre for NHS Service Delivery and Organisation R&D (NCCSDO

Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients

BACKGROUND: Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. METHODS: We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase "home-made" ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). RESULTS: We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). CONCLUSIONS: This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor

Nearly horizon skimming orbits of Kerr black holes

An unusual set of orbits about extreme Kerr black holes resides at the Boyer-Lindquist radius $r = M$, the coordinate of the hole's event horizon. These ``horizon skimming'' orbits have the property that their angular momentum $L_z$ {\it increases} with inclination angle, opposite to the familiar behavior one encounters at larger radius. In this paper, I show that this behavior is characteristic of a larger family of orbits, the ``nearly horizon skimming'' (NHS) orbits. NHS orbits exist in the very strong field of any black hole with spin a\agt 0.952412M. Their unusual behavior is due to the locking of particle motion near the event horizon to the hole's spin, and is therefore a signature of the Kerr metric's extreme strong field. An observational hallmark of NHS orbits is that a small body spiraling into a Kerr black hole due to gravitational-wave emission will be driven into orbits of progressively smaller inclination angle, toward the equator. This is in contrast to the ``normal'' behavior. For circular orbits, the change in inclination is very small, and unlikely to be of observational importance. I argue that the change in inclination may be considerably larger when one considers the evolution of inclined eccentric orbits. If this proves correct, then the gravitational waves produced by evolution through the NHS regime may constitute a very interesting and important probe of the strong-field nature of rotating black holes.Comment: 9 pages, 5 figures, accepted for publication in PR

A research and development strategy for Hillingdon Primary Care Trust (PCT) in North West London

Rationale: There were three notable milestones for health research in England during the 1990s. The NHS R&D programme was established and it prioritised research on themes such as the primary-secondary care interface and initiated regional R&D programmes. The Culyer Report led to the first comprehensive strategy for funding research within the NHS, while the Mant strategic review of research in primary care stimulated the setting up of primary care research networks. However, by the time the three waves of primary care trusts were introduced in 2000-02, 303 in all, opportunities for obtaining NHS funding for promoting R&D in primary care were much more restricted, especially from regional sources.Ye

In Vitro Complement-Binding on Cytoplasmic Structures in Normal Human Skin: I. Immunofluorescence Studies

Incubation of cryostat sections of normal human skin with normal human serum (NHS) at 37°C followed by fluorescein isothiocyanate labeled rabbit antihuman C3 (FITC-R/Hu-C3) yields cytoplasmic staining of various cell types including keratinocytes of the upper epidermal layers, melanocytes, fibroblasts, smooth muscle cells, and cells lining vascular structures.Deposition of C3 on the respective cytoplasmic structures is most likely due to activation of the classical complement (C) cascade on these structures since no fluorescent staining is observed when serum of patients with hereditary C4-deficiency is used instead of NHS or when incubation with NHS is performed in the presence of EDTA or EGTA in concentrations known to inhibit classical C pathway activation. Further evidence suggesting the involvement of the classical C pathway comes from the finding that incubation of cryostat skin sections with NHS followed by FITC labeled rabbit antihuman Clq (FITC-R/Hu-Clq) results in a fluorescent staining pattern remarkably similar to that seen after exposure of cryostat skin sections to NHS and FITC-R/ Hu-C3.Although formal proof is lacking, our investigations strongly indicate that binding to and activation of C components on cytoplasmic structures occur independently of the presence of circulating antibodies. This assumption is based on the finding that in 17 out of 20 NHS we were not able to detect any skin reactive antibodies by indirect immunofluorescence (IF) techniques. More conclusive evidence for a direct, antibody-independent interaction between C components and cytoplasmic structures is provided by the observation that incubation of the substrate with purified Clq followed by FITC-R/ Hu-Clq results in cytoplasmic staining of some of the skin cell populations described above.The phenomenon of C-binding adn activation on cytoplasmic structures of normal human skin cells may be a critical event in the initiation of complement mediated pathopysiological reactions of the skin

Lessons from the evaluation of the UK's NHS R&D Implementation Methods Programme

Background: Concern about the effective use of research was a major factor behind the creation of the NHS R&D Programme in 1991. In 1994, an advisory group was established to identify research priorities in research implementation. The Implementation Methods Programme (IMP) flowed from this, and its commissioning group funded 36 projects. In 2000 responsibility for the programme passed to the National Co-ordinating Centre for NHS Service Delivery and Organisation R&D, which asked the Health Economics Research Group (HERG), Brunel University, to conduct an evaluation in 2002. By then most projects had been completed. This evaluation was intended to cover: the quality of outputs, lessons to be learnt about the communication strategy and the commissioning process, and the benefits from the projects. Methods: We adopted a wide range of quantitative and qualitative methods. They included: documentary analysis, interviews with key actors, questionnaires to the funded lead researchers, questionnaires to potential users, and desk analysis. Results: Quantitative assessment of outputs and dissemination revealed that the IMP funded useful research projects, some of which had considerable impact against the various categories in the HERG payback model, such as publications, further research, research training, impact on health policy, and clinical practice. Qualitative findings from interviews with advisory and commissioning group members indicated that when the IMP was established, implementation research was a relatively unexplored field. This was reflected in the understanding brought to their roles by members of the advisory and commissioning groups, in the way priorities for research were chosen and developed, and in how the research projects were commissioned. The ideological and methodological debates associated with these decisions have continued among those working in this field. The need for an effective communication strategy for the programme as a whole was particularly important. However, such a strategy was never developed, making it difficult to establish the general influence of the IMP as a programme. Conclusion: Our findings about the impact of the work funded, and the difficulties faced by those developing the IMP, have implications for the development of strategic programmes of research in general, as well as for the development of more effective research in this field

Best practice statement : use of ankle-foot orthoses following stroke

NHS Quality Improvement Scotland (NHSQIS) leads the use of knowledge to promote improvement in the quality of health care for the people of Scotland and performs three key functions. It provides advice and guidance on effective clinical practice, including setting standards; drives and supports implementation of improvements in quality, and assessing the performance of the NHS, reporting and publishing findings

Forced residential mobility and social support: impacts on psychiatric disorders among Somali migrants

This study was funded by London Region NHS R&D Projectreference no: RCC01924; Prof Bhui is the PI