Destabilisation of hydrogen bonding and the phase stability of aniline at high pressure

Two crystalline phases of aniline have been investigated by a combination of single crystal X-ray diffraction data on aniline-h7 and neutron powder diffraction data on aniline-d7. Phase-I, which is formed on cooling the liquid at ambient pressure, is monoclinic (P21Ic). Orthorhombic (Pna21) phase-II was crystallised at 0.84 GPa at room temperature and structurally characterised at pressures up to 7.3 GPa. The strongest intermolecular interactions in both structures are NH···π contacts and NH···N H-bonds. These interactions occur within layers in both phases, and the phases differ in the way the layers are stacked. The structures of both phases have been obtained under two sets of identical conditions, at 0.84 GPa and 0.35 GPa and studied at room temperature by neutron powder and X-ray single-crystal diffraction. At 0.84 GPa phase-II is the thermodynamically stable form because it has a lower molar volume than phase-I, but as the pressure is reduced the volume of phase-I becomes less than that of phase-II, and at 0.35 GPa phase-II partially transformed into phase-I. PIXEL calculations indicate that the intermolecular interaction energy for pairs of molecules connected by H-bonds is -9 to -16 kJ mol-1 in phase-I and II at 0.84 GPa, but one of these becomes destabilising in phase-II at 7.3 GPa, with an energy of +1 kJ mol-1, making it similar to several compressed CH center···π contacts. The results demonstrate how the hierarchy of intermolecular interaction energies can be manipulated with pressure, driving a H-bond beyond its ambient-pressure distance limit into repulsive region of its potential, and trapping it within a compressed crystal structure.</p

Protective efficacy of a recombinant plague vaccine when co-administered with another sub-unit or live attenuated vaccine.

Vaccines against bioterrorism agents offer the prospect of providing high levels of protection against airborne pathogens. However, the diversity of the bioterrorism threat means that it may be necessary to use several vaccines simultaneously. In this study we have investigated whether there are changes to the protective immune response to a recombinant sub-unit plague vaccine when it is co-administered with other sub-unit or live attenuated vaccines. Our results indicate that the co-administration of these vaccines did not influence the protection afforded by the plague vaccine. However, the co-administration of the plague sub-unit vaccine with a live vaccine resulted in markedly increased levels of IgG2a subclass antibodies, and markedly reduced levels of IgG1 subclass antibodies, to the plague sub-unit vaccine. This finding might have implications when considering the co-administration of other vaccine combinations

Genome sequence of Burkholderia pseudomallei NCTC 13392

Here, we describe the draft genome sequence of Burkholderia pseudomallei NCTC 13392. This isolate has been distributed as K96243, but distinct genomic differences have been identified. The genomic sequence of this isolate will provide the genomic context for previously conducted functional studies

Consensus on the development of vaccines against naturally acquired melioidosis.

Several candidates for a vaccine against Burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and a rational approach is now needed to select and advance candidates for testing in relevant nonhuman primate models and in human clinical trials. Development of such a vaccine was the topic of a meeting in the United Kingdom in March 2014 attended by international candidate vaccine developers, researchers, and government health officials. The focus of the meeting was advancement of vaccines for prevention of natural infection, rather than for protection from the organism's known potential for use as a biological weapon. A direct comparison of candidate vaccines in well-characterized mouse models was proposed. Knowledge gaps requiring further research were identified. Recommendations were made to accelerate the development of an effective vaccine against melioidosis

The distortion of two FePO₄ polymorphs with high pressure

Both the trigonal (Berlinite-type, phase-I), and orthorhombic (CrVO4-type, phase-II) forms of FePO4 have been studied at high-pressure using neutron powder diffraction. Phase-II was prepared by a high-pressure, high-temperature synthetic route, and recovered to ambient conditions. We report the first high-pressure structural study of this phase up to 8.4GPa at room temperature. It is shown that with increasing pressure, the FeO6 octahedra become more regular and decrease in volume, while the PO4 tetrahedra become less regulars and increase in volume. For phase-I, similar changes in volume are determined, though without changes in distortion. At 2GPa a signature of amorphisation has been observed for phase-I with the appearance of broad phase-II reflections. To support the results of the high-pressure study, Raman spectroscopic and SQUID magnetometry studies have been performed

Supporting self-management after attending a structured education programme: a qualitative longitudinal investigation of type 1 diabetes patients’ experiences and views

Background: Structured education programmes for patients with diabetes and other chronic conditions are being widely adopted. However, follow-up studies suggest that course graduates may struggle to sustain the self-care practices taught on their courses over time. This study explored the support needs of patients with type 1 diabetes after attending a structured education programme promoting an empowerment approach and training in use of flexible intensive insulin therapy, a regimen now widely advocated and used to manage this condition. The objective was to inform future support offered to course graduates. Methods: Repeat, in-depth interviews with 30 type 1 diabetes patients after attending Dose Adjustment for Normal Eating (DAFNE) courses in the UK, and six and 12 months later. Data were analysed using an inductive, thematic approach. Results: While the flexible intensive insulin treatment approach taught on DAFNE courses was seen as a logical and effective way of managing one’s diabetes, it was also considered more technically complex than other insulin regimens. To sustain effective disease self-management using flexible intensive insulin treatment over time, patients often expected, and needed, on-going input and support from health care professionals trained in the approach. This included: help determining insulin dose adjustments; reassurance; and, opportunities to trouble-shoot issues of concern. While some benefits were identified to receiving follow-up support in a group setting, most patients stated a preference or need for tailored and individualised support from appropriately-trained clinicians, accessible on an ‘as and when needed’ basis. Conclusions: Our findings highlight potential limitations to group-based forms of follow-up support for sustaining diabetes self-management. To maintain the clinical benefits of structured education for patients with type 1 diabetes over time, course graduates may benefit from and prefer ongoing, one-to-one support from health care professionals trained in the programme’s practices and principles. This support should be tailored and personalised to reflect patients’ specific and unique experiences of applying their education and training in the context of their everyday lives, and could be the subject of future research

Neurosurgical team acceptability of brain-computer interfaces: a two-stage international cross-sectional survey

OBJECTIVE: Invasive brain-computer interfaces (BCIs) require neurosurgical implantation, which confers a range of risks. Despite this, no studies have assessed the acceptability of invasive BCIs amongst the neurosurgical team. This study aims to establish baseline knowledge of BCIs within the neurosurgical team and identify attitudes towards different applications of invasive BCI. METHOD: A two-stage cross-sectional international survey of the neurosurgical team (neurosurgeons, anaesthetists, and operating room nurses) was conducted. Results from the first, qualitative, survey were used to guide the second stage quantitative survey, which assessed acceptability of invasive BCI applications. 5-part Likert Scales were used to collect quantitative data. Surveys were distributed internationally via social media and collaborators. RESULTS: 108 qualitative responses were collected. Themes included the promise of BCIs positively impacting disease targets, concerns regarding stability, and an overall positive emotional reaction to BCI technology. The quantitative survey generated 538 responses from 32 countries. Baseline knowledge of BCI technology was poor, with 9% claiming to have a ‘good’ or ‘expert’ knowledge of BCIs. Acceptability of invasive BCI for rehabilitative purposes was >80%. Invasive BCI for augmentation in healthy populations divided opinion. CONCLUSION: The neurosurgical team’s view of the acceptability of BCI was divided across a range of indications. Some applications (for example stroke rehabilitation) were viewed as more appropriate than other applications (such as augmentation for military use). This range in views highlights the need for stakeholder consultation on acceptable use cases along with regulation and guidance to govern initial BCI implantations if patients are to realise the potential benefits

An extended thermal pressure equation of state for sodium fluoride

The effect of pressure and temperature on the unit-cell volume of NaF has been measured by X-ray powder diffraction at ambient pressure between 12 and 300 K and neutron powder diffraction up to 5 GPa between 140 and 350 K. These data have been combined with high-pressure volume data at 300 and 950 K to 25 GPa and adiabatic bulk modulus data to 650 K to define an equation of state for NaF relating molar volume to both temperature and pressure. The model combines a fourth-order Birch-Murnaghan equation of state at 295 K with a Mie-Grüneisen-Debye model for thermal pressure. The parameters of the model set at 295 K and ambient pressure are as follows: reference unit-cell volume V0 = 14.9724 (5) cm3 mol-1, isothermal bulk modulus K0T = 46.79 (14) GPa, first derivative of the bulk modulus K′0T = 5.72 (12), second derivative of the bulk modulus K′0T = -0.43 (4) GPa-1, Debye temperature TMGD = 459 (3) K, and Anderson Grüneisen parameters γ0 = 1.547 (11) and q = 0.94 (18).</p

Process analysis of the patient pathway for automated data collection: an exemplar using pituitary surgery

INTRODUCTION: Automation of routine clinical data shows promise in relieving health systems of the burden associated with manual data collection. Identifying consistent points of documentation in the electronic health record (EHR) provides salient targets to improve data entry quality. Using our pituitary surgery service as an exemplar, we aimed to demonstrate how process mapping can be used to identify reliable areas of documentation in the patient pathway to target structured data entry interventions. MATERIALS AND METHODS: Automation of routine clinical data shows promise in relieving health systems of the burden associated with manual data collection. Identifying consistent points of documentation in the electronic health record (EHR) provides salient targets to improve data entry quality. Using our pituitary surgery service as an exemplar, we aimed to demonstrate how process mapping can be used to identify reliable areas of documentation in the patient pathway to target structured data entry interventions. This mixed methods study was conducted in the largest pituitary centre in the UK. Purposive snowball sampling identified frontline stakeholders for process mapping to produce a patient pathway. The final patient pathway was subsequently validated against a real-world dataset of 50 patients who underwent surgery for pituitary adenoma. Events were categorized by frequency and mapped to the patient pathway to determine critical data points. RESULTS: Eighteen stakeholders encompassing all members of the multidisciplinary team (MDT) were consulted for process mapping. The commonest events recorded were neurosurgical ward round entries (N = 212, 14.7%), pituitary clinical nurse specialist (CNS) ward round entries (N = 88, 6.12%) and pituitary MDT treatment decisions (N = 88, 6.12%) representing critical data points. Operation notes and neurosurgical ward round entries were present for every patient. 43/44 (97.7%) had a pre-operative pituitary MDT entry, pre-operative clinic letter, a post-operative clinic letter, an admission clerking entry, a discharge summary, and a post-operative histopathology pituitary multidisciplinary (MDT) team entries. CONCLUSION: This is the first study to produce a validated patient pathway of patients undergoing pituitary surgery, serving as a comparison to optimise this patient pathway. We have identified salient targets for structured data entry interventions, including mandatory datapoints seen in every admission and have also identified areas to improve documentation adherence, both of which support movement towards automation

Aquatic therapy for children with Duchenne muscular dystrophy: a pilot feasibility randomised controlled trial and mixed-methods process evaluation.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare disease that causes the progressive loss of motor abilities such as walking. Standard treatment includes physiotherapy. No trial has evaluated whether or not adding aquatic therapy (AT) to land-based therapy (LBT) exercises helps to keep muscles strong and children independent. OBJECTIVES: To assess the feasibility of recruiting boys with DMD to a randomised trial evaluating AT (primary objective) and to collect data from them; to assess how, and how well, the intervention and trial procedures work. DESIGN: Parallel-group, single-blind, randomised pilot trial with nested qualitative research. SETTING: Six paediatric neuromuscular units. PARTICIPANTS: Children with DMD aged 7-16 years, established on corticosteroids, with a North Star Ambulatory Assessment (NSAA) score of 8-34 and able to complete a 10-m walk without aids/assistance. Exclusions: > 20% variation between baseline screens 4 weeks apart and contraindications. INTERVENTIONS: Participants were allocated on a 1 : 1 ratio to (1) optimised, manualised LBT (prescribed by specialist neuromuscular physiotherapists) or (2) the same plus manualised AT (30 minutes, twice weekly for 6 months: active assisted and/or passive stretching regime; simulated or real functional activities; submaximal exercise). Semistructured interviews with participants, parents (n = 8) and professionals (n = 8) were analysed using Framework analysis. An independent rater reviewed patient records to determine the extent to which treatment was optimised. A cost-impact analysis was performed. Quantitative and qualitative data were mixed using a triangulation exercise. MAIN OUTCOME MEASURES: Feasibility of recruiting 40 participants in 6 months, participant and therapist views on the acceptability of the intervention and research protocols, clinical outcomes including NSAA, independent assessment of treatment optimisation and intervention costs. RESULTS: Over 6 months, 348 children were screened - most lived too far from centres or were enrolled in other trials. Twelve (30% of target) were randomised to AT (n = 8) or control (n = 4). People in the AT (n = 8) and control (n = 2: attrition because of parental report) arms contributed outcome data. The mean change in NSAA score at 6 months was -5.5 [standard deviation (SD) 7.8] for LBT and -2.8 (SD 4.1) in the AT arm. One boy suffered pain and fatigue after AT, which resolved the same day. Physiotherapists and parents valued AT and believed that it should be delivered in community settings. The independent rater considered AT optimised for three out of eight children, with other children given programmes that were too extensive and insufficiently focused. The estimated NHS costs of 6-month service were between £1970 and £2734 per patient. LIMITATIONS: The focus on delivery in hospitals limits generalisability. CONCLUSIONS: Neither a full-scale frequentist randomised controlled trial (RCT) recruiting in the UK alone nor a twice-weekly open-ended AT course delivered at tertiary centres is feasible. Further intervention development research is needed to identify how community-based pools can be accessed, and how families can link with each other and community physiotherapists to access tailored AT programmes guided by highly specialised physiotherapists. Bayesian RCTs may be feasible; otherwise, time series designs are recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN41002956. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 27. See the NIHR Journals Library website for further project information