High nuclearity Ni(ii) cages from hydroxamate ligands

The synthesis, structural and magnetic characterisation of a family of Ni(ii) cages built from hydroxamate ligands is presented. Two pentanuclear 12-MCNi(ii)-4 metallacrowns [Ni5(L1) 4(MeOH)4](ClO4)2·2MeOH (1) and [Ni5(L1)4(py)5](ClO 4)2·H2O (2) (where L1H 2 = 2-(dimethylamino)phenylhydroxamic acid) share analogous, near-planar {Ni5(L1)4}2+ cores, but differ in the number and nature of the ligands located at the axial Ni(ii) sites; the addition of pyridine converting square planar Ni(ii) ions to square-based pyramidal and octahedral Ni(ii) ions, introducing extra paramagnetic metal centres which 'switch on' additional magnetic superexchange pathways. Subtle variations in the reaction scheme used to produce complexes 1 and 2 result in both a change of topology and an increase in nuclearity, through isolation of the hepta- and nonametallic complexes [Ni7(L 1H)8(L1)2(H2O) 6](SO4)·15H2O (3), [Ni 9(μ-H2O)2(L2)6(L 2H)4(H2O)2](SO4) ·29H2O (4) and [Ni9(μ-H2O) 2(L2)6(L2H)4(H 2O)2](ClO4)2·2MeOH· 18H2O (5) (where L2H2 = 2-(amino) phenylhydroxamic acid). Complementary dc magnetic susceptibility studies and DFT analysis indicate dominant antiferromagnetic exchange interactions in 1, 2, 4 and 5, but competing ferro- and antiferromagnetic exchange in 3. © the Partner Organisations 2014.EKB would like to thank the EPSRC for funding (SS). GR acknowledges financial support from the Government of India through the Department of Science and Technology (SR/S1/IC-41/2010; SR/NM/NS-1119/2011) and generous computational resources from the Indian Institute of Technology-Bombay. MKS thanks the University Grants Commission for a Junior Research Fellowship.Published versio

Recruitment to randomised trials : Strategies for Trial Enrolment and Participation Study. The STEPS study

Objectives: To identify factors associated with good and poor recruitment to multicentre trials. Data sources: Part A: database of trials started in or after 1994 and were due to end before 2003 held by the Medical Research Council and Health Technology Assessment Programmes. Part B: interviews with people playing a wide range of roles within four trials that their funders identified as ‘exemplars’. Part C: a large multicentre trial (the CRASH trial) of treatment for head injury. Review methods: The study used a number of different perspectives (‘multiple lenses’), and three components. Part A: an epidemiological review of a cohort of trials. Part B: case studies of trials that appeared to have particularly interesting lessons for recruitment. Part C: a single, in-depth case study to examine the feasibility of applying a businessorientated analytical framework as a reference model in future trials. Results: In the 114 trials found in Part A, less than one-third recruited their original target within the time originally specified, and around one-third had extensions. Factors observed more often in trials that recruited successfully were: having a dedicated trial manager, being a cancer or drug trial, and having interventions only available inside the trial. The most commonly reported strategies to improve recruitment were newsletters and mailshots, but it was not possible to assess whether they were causally linked to changes in recruitment. The analyses in Part B suggested that successful trials were those addressing clinically important questions at a timely point. The investigators were held in high esteem by the interviewees, and the trials were firmly grounded in existing clinical practices, so that the trial processes were not alien to clinical collaborators, and the results could be easily applicable to future practice. The interviewees considered that the needs of patients were well served by participation in the trials. Clinical collaborators particularly appreciated clear delineation of roles, which released them from much of the workload associated with trial participation. There was a strong feeling from interviewees that they were proud to be part of a successful team. This pride fed into further success. Good groundwork and excellent communications across many levels of complex trial structures were considered to be extremely important, including training components for learning about trial interventions and processes, and team building. All four trials had faced recruitment problems, and extra insights into the working of trials were afforded by strategies invoked to address them. The process of the case study in Part C was able to draw attention to a body of research and practice in a different discipline (academic business studies). It generated a reference model derived from a combination of business theory and work within CRASH. This enabled identification of weaker managerial components within CRASH, and initiatives to strengthen them. Although it is not clear, even within CRASH, whether the initiatives that follow from developing and applying the model will be effective in increasing recruitment or other aspects of the success of the trial, the reference model could provide a template, with potential for those managing other trials to use or adapt it, especially at foundation stages. The model derived from this project could also be used as a diagnostic tool if trials have difficulties and hence as a basis for deciding what type of remedial action to take. It may also be useful for auditing the progress of trials, such as during external review. Conclusions: While not producing sufficiently definitive results to make strong recommendations, the work here suggests that future trials should consider the different needs at different phases in the life of trials, and place greater emphasis on ‘conduct’ (the process of actually doing trials). This implies learning lessons from successful trialists and trial managers, with better training for issues relating to trial conduct. The complexity of large trials means that unanticipated difficulties are highly likely at some time in every trial. Part B suggested that successful trials were those flexible and robust enough to adapt to unexpected issues. Arguably, the trialists should also expect agility from funders within a proactive approach to monitoring ongoing trials. Further research into different recruitment patterns (including ‘failures’) may help to clarify whether the patterns seen in the ‘exemplar’ trials differ or are similar. The reference model from Part C needs to be further considered in other similar and different trials to assess its robustness. These and other strategies aimed at increasing recruitment and making trials more successful need to be formally evaluated for their effectiveness in a range of trials.Not peer reviewedPublisher PD

Antenatal screening for Group B Streptococcus: A diagnostic cohort study

BACKGROUND: A range of strategies have been adopted to prevent early onset Group B Streptococcal (EOGBS) sepsis, as a consequence of Group B Streptococcal (GBS) vertically acquired infection. This study was designed to provide a scientific basis for optimum timing and method of GBS screening in an Australian setting, to determine whether screening for GBS infection at 35–37 weeks gestation has better predictive values for colonisation at birth than screening at 31–33 weeks, to examine the test characteristics of a risk factor strategy and to determine the test characteristics of low vaginal swabs alone compared with a combination of perianal plus low vaginal swabs per colonisation during labour. METHODS: Consented women received vaginal and perianal swabs at 31–33 weeks gestation, 35–38 weeks gestation and during labour. Swabs were cultured on layered horse blood agar and inoculated into selective broth prior to analysis. Test characteristics were calculated with exact confidence intervals for a high risk strategy and for antenatal screening at 31–33 and 35–37 weeks gestation for vaginal cultures alone, perianal cultures alone and combined low vaginal and perianal cultures. RESULTS: The high risk strategy was not informative in predicting GBS status during labour. There is an unequivocal benefit for the identification of women colonised with GBS during labour associated with delaying screening until 36 weeks however the results for method of screening were less definitive with no clear advantage in using a combined low vaginal and perianal swabbing regimen over the use of a low vaginal swab alone. CONCLUSION: This study can contribute to the development of prevention strategies in that it provides clear evidence for optimal timing of swabs. The addition of a perianal swab does not confer clear benefit. The quantification of advantages and disadvantages provided in this study will facilitate communication with clinicians and pregnant women alike

CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

Incorporating ‘recruitment’ in matrix projection models : estimation, parameters, and the influence of model structure

Author Posting. © The Author(s), 2010. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Journal of Ornithology 152, Suppl.2 (2012):585-595, doi:10.1007/s10336-010-0573-1.Advances in the estimation of population parameters using encounter data from marked individuals have made it possible to include estimates of the probability of recruitment in population projection models. However, the projected growth rate of the population, and the sensitivity of projected growth to changes in recruitment, can vary significantly depending upon both the structural form of the model and how recruitment is parameterized. We show that the common practices of (1) collapsing some age classes into a single, terminal ‘aggregated’ age-class, and (2) parameterizing recruitment using the proportion of recruited individuals (breeders) in a given age-class may confound analysis of age-based (Leslie) matrix projection models in some instances, relative to state-based projection models where recruited and pre-recruited individuals are treated as separate states. Failing to account for these differences can lead to misinterpretation of the relative role of recruitment in the dynamics of an age-structured population.We show that such problems can be avoided, either by structural changes to the terminal aggregated age-class in age-based models, or by using using a state-based model instead. Since all the metrics of general interest from a classical age-based matrix models are readily derived from a state-based model equivalent, this suggests there may be little reason to use the classical age-based approach in situations where recruitment is a parameter of interest

Patient and public involvement in patient safety research: a workshop to review patient information, minimise psychological risk and inform research

Background Patient safety has attracted increasing attention in recent years. This paper explores patients’ contributions to informing patient safety research at an early stage, within a project on intravenous infusion errors. Currently, there is little or no guidance on how best to involve patients and the wider public in shaping patient safety research, and indeed, whether such efforts are worthwhile. Method We ran a 3-hour workshop involving nine patients with experience of intravenous therapy in the hospital setting. The first part explored patients’ experiences of intravenous therapy. We derived research questions from the resulting discussion through qualitative analysis. In the second part, patients were asked for feedback on patient information sheets considering both content and clarity, and on two potential approaches to framing our patient information: one that focused on research on safety and error, the other on quality improvement. Results The workshop led to a thorough review of how we should engage with patients. Importantly, there was a clear steer away from terms such as ‘error’ and ‘safety’ that could worry patients. The experiences that patients revealed were also richer than we had anticipated, revealing different conceptions of how patients related to their treatment and care, their role in safety and use of medical devices, the different levels of information they preferred, and broader factors impacting perceptions of their care. Conclusion Involving patients at an early stage in patient safety research can be of great value. Our workshop highlighted sensitivities around potentially worrying patients about risks that they might not have considered previously, and how to address these. Patient representatives also emphasised a need to expand the focus of patient safety research beyond clinicians and error, to include factors affecting perceptions of quality and safety for patients more broadly

The challenges faced in the design, conduct and analysis of surgical randomised controlled trials

Randomised evaluations of surgical interventions are rare; some interventions have been widely adopted without rigorous evaluation. Unlike other medical areas, the randomised controlled trial (RCT) design has not become the default study design for the evaluation of surgical interventions. Surgical trials are difficult to successfully undertake and pose particular practical and methodological challenges. However, RCTs have played a role in the assessment of surgical innovations and there is scope and need for greater use. This article will consider the design, conduct and analysis of an RCT of a surgical intervention. The issues will be reviewed under three headings: the timing of the evaluation, defining the research question and trial design issues. Recommendations on the conduct of future surgical RCTs are made. Collaboration between research and surgical communities is needed to address the distinct issues raised by the assessmentof surgical interventions and enable the conduct of appropriate and well-designed trials.The Health Services Research Unit is funded by the Scottish Government Health DirectoratesPeer reviewedPublisher PD

Development of an occupational advice intervention for patients undergoing lower limb arthroplasty (the OPAL study)

Background: There are an increasing number of patients of working age undergoing hip and knee replacements. Currently there is variation in the advice and support given about sickness absence, recovery to usual activities and return to work after these procedures. Earlier, sustainable, return to work improves the health of patients and benefits their employers and society. An intervention that encourages and supports early recovery to usual activities, including work, has the potential to reduce the health and socioeconomic burden of hip and knee replacements. Methods/design: A two-phase research programme delivered over 27 months will be used to develop and subsequently test the feasibility of an occupational advice intervention to facilitate return to work and usual activities in patients undergoing lower limb arthroplasty. The 2 phases will incorporate a six-stage intervention mapping process: Phase 1: Intervention mapping stages 1–3: 1 Needs assessment (including rapid evidence synthesis, prospective cohort analysis and structured stakeholder interviews) 2 Identification of intended outcomes and performance objectives 3 Selection of theory-based methods and practical strategies Phase 2: Intervention mapping stages 4–6: 4 Development of components and materials for the occupational advice intervention using a modified Delphi process 5 Adoption and implementation of the intervention 6 Evaluation and feasibility testing The study will be undertaken in four National Health Service (NHS) hospitals in the United Kingdom and two Higher Education Institution. Discussion: OPAL (Occupational advice for Patients undergoing Arthroplasty of the Lower limb) aims to develop an occupational advice intervention to support early recovery to usual activities including work, which is tailored to the requirements of patients undergoing hip and knee replacements. The developed intervention will then be assessed with a specific focus on evaluating its feasibility as a potential trial intervention to improve speed of recovery to usual activities including work

What are the postoperative experiences of patients who have undergone hip and knee joint replacement? A literature review

Background: There are an increasing number of people undergoing hip and knee joint replacement each year; approximately 68,000 hip and 76,000 knee replacements, respectively, are performed in England and Wales. Joint replacements serve to reduce pain and improve function. Objectives: The purpose of this qualitative literature review is to gain an in depth understanding into participants’ postoperative experiences following hip and knee replacement in order to establish if participants can be better supported post joint replacement and whether preoperative education can be enhanced. Methods: Searches were carried out in 13 online scientific databases (January 1995 to October 2016) to identify relevant studies. The quality of studies was assessed, data were extracted and analysed using thematic synthesis. Results: A total of 197 studies were identified and screened against the inclusion/exclusion criteria. Seven studies met the inclusion criteria. Three broad themes were identified; coping with pain, recovering function and the challenges of discharge. In general, pain was poorly understood and difficulties arose with the appropriate management postoperatively. The recovery process took commitment and required individuals to have realistic expectations. Participants also felt the need for individualised care as they approached discharge. Conclusions: Overall qualitative evidence surrounding postoperative views of participants is limited. It appears current preoperative education does not fulfil the majority of participants’ needs. Utilising the views of participants may help to tailor preoperative education or provide alternative support postoperatively. Future research should focus on clarifying the effect of a well-constructed and well-delivered preoperative education sessions