A study of the of ytterbium disilicates undergoing water vapour corrosion for environmental barrier coating applications

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Does a monetary incentive improve the response to a postal questionnaire in a randomised controlled trial? : the MINT incentive study

Background: Sending a monetary incentive with postal questionnaires has been found to improve the proportion of responders, in research in non-healthcare settings. However, there is little research on use of incentives to improve follow-up rates in clinical trials, and existing studies are inconclusive. We conducted a randomised trial among participants in the Managing Injuries of the Neck Trial (MINT) to investigate the effects on the proportion of questionnaires returned and overall non-response of sending a £5 gift voucher with a follow-up questionnaire. Methods: Participants in MINT were randomised to receive either: (a) a £5 gift voucher (incentive group) or (b) no gift voucher (no incentive group), with their 4 month or 8 month follow-up questionnaire. We recorded, for each group, the number of questionnaires returned, the number returned without any chasing from the study office, the overall number of non-responders (after all chasing efforts by the study office), and the costs of following up each group. Results: 2144 participants were randomised, 1070 to the incentive group and 1074 to the no incentive group. The proportion of questionnaires returned (RR 1.10 (95% CI 1.05, 1.16)) and the proportion returned without chasing (RR 1.14 (95% CI 1.05, 1.24) were higher in the incentive group, and the overall non-response rate was lower (RR 0.68 (95% CI 0.53, 0.87)). Adjustment for injury severity and hospital of recruitment to MINT made no difference to these results, and there were no differences in results between the 4-month and 8-month follow up questionnaires. Analysis of costs suggested a cost of £67.29 per additional questionnaire returned. Conclusion: Monetary incentives may be an effective way to increase the proportion of postal questionnaires returned and minimise loss to follow-up in clinical trials

A national survey of clinical practice for the management of whiplash-associated disorders in UK emergency departments

Objective: To undertake a national survey to determine current practice for the management of whiplash injuries in UK emergency departments (ED). Methods: Postal questionnaire survey. 316 lead consultants from all UK ED with annual new attendances of over 50 000 people were asked to indicate the use of a range of treatments and the frequency with which these treatments were used. Samples of written advice were requested and content analysis was conducted and compared with survey responses. Results: The response rate was 79% (251/316). The intervention most frequently used was verbal advice to exercise, reported by 84% of respondents for most or all cases, and advice against the use of a collar (83%). Other treatments reported as being used frequently were written advice and anti-inflammatory medication. 106 consultants (42%) provided a sample of written materials. Reference to expected recovery and encouragement for early return to activities were included in less than 6%. Nearly 50% of written materials contained information on how to use a soft collar and 61% contained information on solicitors and pursuing a personal injury claim. There were important differences between reported verbal behaviours and written advice. Conclusion: Verbal advice is the primary method for managing whiplash injuries in ED and is usually supplemented by written advice. Within individual hospitals there is a lack of consistency between verbal and written advice. The promotion of personal injury claims is a common feature of written advice. Research is required to develop effective and consistent models of advice

Managing Injuries of the Neck Trial (MINT) : design of a randomised controlled trial of treatments for whiplash associated disorders

Background: A substantial proportion of patients with whiplash injuries develop chronic symptoms. However, the best treatment of acute injuries to prevent long-term problems is uncertain. A stepped care treatment pathway has been proposed, in which patients are given advice and education at their initial visit to the emergency department (ED), followed by review at three weeks and physiotherapy for those with persisting symptoms. MINT is a two-stage randomised controlled trial to evaluate two components of such a pathway: 1. use of The Whiplash Book versus usual advice when patients first attend the emergency department; 2. referral to physiotherapy versus reinforcement of advice for patients with continuing symptoms at three weeks. Methods: Evaluation of the Whiplash Book versus usual advice uses a cluster randomised design in emergency departments of eight NHS Trusts. Eligible patients are identified by clinicians in participating emergency departments and are sent a study questionnaire within a week of their ED attendance. Three thousand participants will be included. Patients with persisting symptoms three weeks after their ED attendance are eligible to join an individually randomised study of physiotherapy versus reinforcement of the advice given in ED. Six hundred participants will be randomised. Follow-up is at 4, 8 and 12 months after their ED attendance. Primary outcome is the Neck Disability Index (NDI), and secondary outcomes include quality of life and time to return to work and normal activities. An economic evaluation is being carried out. Conclusion: This paper describes the protocol and operational aspects of a complex intervention trial based in NHS emergency and physiotherapy departments, evaluating two components of a stepped-care approach to the treatment of whiplash injuries. The trial uses two randomisations, with the first stage being cluster randomised and the second individually randomised

A soliton menagerie in AdS

We explore the behaviour of charged scalar solitons in asymptotically global AdS4 spacetimes. This is motivated in part by attempting to identify under what circumstances such objects can become large relative to the AdS length scale. We demonstrate that such solitons generically do get large and in fact in the planar limit smoothly connect up with the zero temperature limit of planar scalar hair black holes. In particular, for given Lagrangian parameters we encounter multiple branches of solitons: some which are perturbatively connected to the AdS vacuum and surprisingly, some which are not. We explore the phase space of solutions by tuning the charge of the scalar field and changing scalar boundary conditions at AdS asymptopia, finding intriguing critical behaviour as a function of these parameters. We demonstrate these features not only for phenomenologically motivated gravitational Abelian-Higgs models, but also for models that can be consistently embedded into eleven dimensional supergravity.Comment: 62 pages, 21 figures. v2: added refs and comments and updated appendice

Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes.

The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. We report that, just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte

Tumour-retained activated CCR7⁺ dendritic cells are heterogeneous and regulate local anti-tumour cytolytic activity

Tumour dendritic cells (DCs) internalise antigen and upregulate CCR7, which directs their migration to tumour-draining lymph nodes (dLN). CCR7 expression is coupled to an activation programme enriched in regulatory molecule expression, including PD-L1. However, the spatio-temporal dynamics of CCR7+ DCs in anti-tumour immune responses remain unclear. Here, we use photoconvertible mice to precisely track DC migration. We report that CCR7+ DCs are the dominant DC population that migrate to the dLN, but a subset remains tumour-resident despite CCR7 expression. These tumour-retained CCR7+ DCs are phenotypically and transcriptionally distinct from their dLN counterparts and heterogeneous. Moreover, they progressively downregulate the expression of antigen presentation and pro-inflammatory transcripts with more prolonged tumour dwell-time. Tumour-residing CCR7+ DCs co-localise with PD-1+CD8+ T cells in human and murine solid tumours, and following anti-PD-L1 treatment, upregulate stimulatory molecules including OX40L, thereby augmenting anti-tumour cytolytic activity. Altogether, these data uncover previously unappreciated heterogeneity in CCR7+ DCs that may underpin a variable capacity to support intratumoural cytotoxic T cells.</p

Minimizing the impact of biologging devices: Using computational fluid dynamics for optimizing tag design and positioning

Biologging devices are used ubiquitously across vertebrate taxa in studies of movement and behavioural ecology to record data from organisms without the need for direct observation. Despite the dramatic increase in the sophistication of this technology, progress in reducing the impact of these devices to animals is less obvious, notwithstanding the implications for animal welfare. Existing guidelines focus on tag weight (e.g. the ‘5% rule'), ignoring aero/hydrodynamic forces in aerial and aquatic organisms, which can be considerable. Designing tags to minimize such impact for animals moving in fluid environments is not trivial, as the impact depends on the position of the tag on the animal, as well as its shape and dimensions. We demonstrate the capabilities of computational fluid dynamics (CFD) modelling to optimize the design and positioning of biologgers on marine animals, using the grey seal (Halichoerus grypus) as a model species. Specifically, we investigate the effects of (a) tag form, (b) tag size, and (c) tag position and quantify the impact under frontal hydrodynamic forces, as encountered by seals swimming at sea. By comparing a conventional versus a streamlined tag, we show that the former can induce up to 22% larger drag for a swimming seal; to match the drag of the streamlined tag, the conventional tag would have to be reduced in size by 50%. For the conventional tag, the drag induced can differ by up to 11% depending on the position along the seal's body, whereas for the streamlined tag this difference amounts to only 5%. We conclude by showing how the CFD simulation approach can be used to optimize tag design to reduce drag for aerial and aquatic species, including issues such as the impact of lateral currents (unexplored until now). We also provide a step-by-step guide to facilitate the implementation of CFD in biologging tag design

Probing host pathogen cross-talk by transcriptional profiling of both Mycobacterium tuberculosis and infected human dendritic cells and macrophages

This study provides the proof of principle that probing the host and the microbe transcriptomes simultaneously is a valuable means to accessing unique information on host pathogen interactions. Our results also underline the extraordinary plasticity of host cell and pathogen responses to infection, and provide a solid framework to further understand the complex mechanisms involved in immunity to M. tuberculosis and in mycobacterial adaptation to different intracellular environments