The "Historical Materials BAG": A New Facilitated Access to Synchrotron X-ray Diffraction Analyses for Cultural Heritage Materials at the European Synchrotron Radiation Facility.

The European Synchrotron Radiation Facility (ESRF) has recently commissioned the new Extremely Brilliant Source (EBS). The gain in brightness as well as the continuous development of beamline instruments boosts the beamline performances, in particular in terms of accelerated data acquisition. This has motivated the development of new access modes as an alternative to standard proposals for access to beamtime, in particular via the "block allocation group" (BAG) mode. Here, we present the recently implemented "historical materials BAG": a community proposal giving to 10 European institutes the opportunity for guaranteed beamtime at two X-ray powder diffraction (XRPD) beamlines-ID13, for 2D high lateral resolution XRPD mapping, and ID22 for high angular resolution XRPD bulk analyses-with a particular focus on applications to cultural heritage. The capabilities offered by these instruments, the specific hardware and software developments to facilitate and speed-up data acquisition and data processing are detailed, and the first results from this new access are illustrated with recent applications to pigments, paintings, ceramics and wood.

The use of liraglutide 3.0 mg daily in the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first episode psychosis: Results of a pilot randomized, double-blind, placebo-controlled trial.

AIM: To investigate the feasibility and acceptability of using liraglutide 3.0 mg daily in the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first episode psychosis. MATERIALS AND METHODS: A double-blind, randomized, placebo-controlled pilot trial took place in mental health centres and primary care within Southern Health NHS Foundation Trust. The participants were adults with schizophrenia, schizoaffective or first-episode psychosis prescribed antipsychotic medication who were overweight or obese. The intervention was once-daily subcutaneous liraglutide or placebo, titrated to 3.0 mg daily, for 6 months. The primary outcomes were recruitment, consent, retention and adherence. The secondary exploratory outcomes were weight, HbA1c and Brief Psychiatric Rating Scale. RESULTS: Seven hundred and ninety-nine individuals were screened for eligibility. The most common reasons for exclusion were ineligibility (44%) and inability to make contact (28%). The acceptance rate, as a proportion of all eligible participants, was 12.2%. The most commonly stated reason why eligible candidates declined to participate related to the study-specific medication and protocol (n = 50). Forty-seven participants were randomized, with 79% completing the trial. Participants in the liraglutide arm lost a mean 5.7 ± 7.9 kg compared with no significant weight change in the placebo group (treatment difference -6.0 kg, p = .015). Body mass index, waist circumference and HbA1c were reduced in the intervention group. CONCLUSIONS: This study supports the need for a larger randomized controlled trial to evaluate the use of liraglutide (maximum dose 3.0 mg daily) in the management of obesity in people with severe mental illness.

Measles outbreak linked to European B3 outbreaks, Wales, United Kingdom, 2017.

The United Kingdom achieved interrupted endemic measles transmission for 36 months in 2016. Despite this, ongoing challenges from sporadic measles cases typically imported from abroad remain. We summarise a B3 measles genotype outbreak in south-east Wales occurring between May and September 2017, linked with other European outbreaks, and lessons learnt. Seventeen confirmed cases and one probable case occurred principally in education and healthcare-settings. Six confirmed cases attended healthcare settings when infectious, without being isolated.

Feasibility and acceptability of transcranial stimulation in obsessive-compulsive symptoms (FEATSOCS): study protocol for a randomised controlled trial of transcranial direct current stimulation (tDCS) in obsessive-compulsive disorder (OCD).

BACKGROUND: Obsessive-compulsive disorder (OCD) is a neuropsychiatric disorder which often proves refractory to current treatment approaches. Transcranial direct current stimulation (tDCS), a noninvasive form of neurostimulation, with potential for development as a self-administered intervention, has shown potential as a safe and efficacious treatment for OCD in a small number of trials. The two most promising stimulation sites are located above the orbitofrontal cortex (OFC) and the supplementary motor area (SMA). METHODS: The aim of this feasibility study is to inform the development of a definitive trial, focussing on the acceptability, safety of the intervention, feasibility of recruitment, adherence and tolerability to tDCS and study assessments and the size of the treatment effect. To this end, we will deliver a double-blind, sham-controlled, crossover randomised multicentre study in 25 adults with OCD. Each participant will receive three courses of tDCS (SMA, OFC and sham), randomly allocated and given in counterbalanced order. Each course comprises four 20-min stimulations, delivered over two consecutive days, separated by at least 4 weeks' washout period. We will collect information about recruitment, study conduct and tDCS delivery. Blinded raters will assess clinical outcomes before, during and up to 4 weeks after stimulation using validated scales. We will include relevant objective neurocognitive tasks, testing cognitive flexibility, motor disinhibition, cooperation and habit learning. DISCUSSION: We will analyse the magnitude of the effect of the interventions on OCD symptoms alongside the standard deviation of the outcome measure, to estimate effect size and determine the optimal stimulation target. We will also measure the duration of the effect of stimulation, to provide information on spacing treatments efficiently. We will evaluate the usefulness and limitations of specific neurocognitive tests to determine a definitive test battery. Additionally, qualitative data will be collected from participants to better understand their experience of taking part in a tDCS intervention, as well as the impact on their overall quality of life. These clinical outcomes will enable the project team to further refine the methodology to ensure optimal efficiency in terms of both delivering and assessing the treatment in a full-scale trial. TRIAL REGISTRATION: ISRCTN17937049 . (date applied 08/07/2019). Recruitment (ongoing) began 23rd July 2019 and is anticipated to complete 30th April 2021.

MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments.

The design and features of a beamline control software system for macromolecular crystallography (MX) experiments developed at the European Synchrotron Radiation Facility (ESRF) are described. This system, MxCuBE, allows users to easily and simply interact with beamline hardware components and provides automated routines for common tasks in the operation of a synchrotron beamline dedicated to experiments in MX. Additional functionality is provided through intuitive interfaces that enable the assessment of the diffraction characteristics of samples, experiment planning, automatic data collection and the on-line collection and analysis of X-ray emission spectra. The software can be run in a tandem client-server mode that allows for remote control and relevant experimental parameters and results are automatically logged in a relational database, ISPyB. MxCuBE is modular, flexible and extensible and is currently deployed on eight macromolecular crystallography beamlines at the ESRF. Additionally, the software is installed at MAX-lab beamline I911-3 and at BESSY beamline BL14.1.

Liraglutide and the management of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis: protocol for a pilot trial.

BACKGROUND: People with severe mental illness (SMI) are two to three times more likely to be overweight and obese than the general population and this is associated with significant morbidity and premature mortality. Although lifestyle interventions can support people with SMI to lose weight, some are unable to make the necessary lifestyle changes or, despite making the changes, continue to gain weight. OBJECTIVE: To assess the feasibility and acceptability of delivering a full-scale trial evaluating whether liraglutide 3.0 mg, a once-daily injectable therapy, may be an effective treatment of overweight and obesity in people with schizophrenia, schizoaffective disorder and first-episode psychosis. METHODS: Design: a single-centre, double-blind, randomised, placebo-controlled trial. SETTING: mental health facilities within Southern Health NHS Trust. PARTICIPANTS: 60 adults with schizophrenia, schizoaffective or first-episode psychosis prescribed antipsychotic medication will be recruited. Participants will be overweight or obese, defined by their baseline BMI which will be: • BMI ≥ 30 kg/m2 or • BMI ≥ 27 kg/m2 to < 30 kg/m2 in the presence of at least one weight-related consequence. This is in concordance with the current EU licence for liraglutide (maximum dosage 3.0 mg). INTERVENTION: participants will be allocated in a 1:1 ratio using a computer-based randomisation programme to either once-daily subcutaneously administered liraglutide or placebo, titrated to 3.0 mg daily, for 6 months. All participants will receive standardised written information about healthy eating and exercise at their randomisation visit. OUTCOMES: the main aim of the study is to gather data on recruitment, consent, retention and adherence. Qualitative interviews with a purposive sub-sample of participants and healthcare workers will provide data on intervention feasibility and acceptability. Secondary clinical outcome measurements will be assessed at 3 and 6 months and will include: weight, fasting plasma glucose, lipid profile, HbA1c level; and the Brief Psychiatric Rating Scale. DISCUSSION: This study should provide evidence of the potential benefits of liraglutide (maximum dosage 3.0 mg daily) on body weight and metabolic variables in people with schizophrenia, schizoaffective disorder and first-episode psychosis. It will also address the feasibility and acceptability of the use of liraglutide in mental health settings. This will inform the design of a longer outcome study that will be needed to determine whether any weight loss can be maintained in the long term. TRIAL REGISTRATION: Universal Trial Number (UTN), ID: U1111-1203-0068. Registered on on 2/10/2017. European Clinical Trials Database (EudraCT), ID: 2017-004064-35. Registered on 3/10/2017.

Blood exposure risk during procedural dermatology.

BACKGROUND: Dermatologists are at risk of body-fluid contamination during procedures. OBJECTIVE: We sought to determine the frequency of blood splash during procedural dermatology. METHODS: In all, 500 consecutive excisions were performed. Postoperatively, blood droplets on face shields and surgical gowns were counted. A survey regarding universal precautions during procedures was also conducted with members of the American College of Mohs Surgery (ACMS). RESULTS: Contamination from blood splashes during dermatologic procedures (Mohs micrographic surgery, excision, repair) occurred in 66.4%. Reconstruction type, anticoagulation use, wound location, and wound size correlated with a higher blood splash rate. Our survey showed that face shields and goggles are used inconsistently. LIMITATIONS: The 4 participating dermatologists do not represent all practicing dermatologists. It may be possible to generalize the survey results directed at physicians in the ACMS. CONCLUSION: Physician body-fluid contamination risk with procedural dermatology is clinically significant. Dermatologists and their assistants should wear preventive barriers during procedures to minimize the risk of viral transmission.

Automation of macromolecular crystallography beamlines.

The production of three-dimensional crystallographic structural information of macromolecules can now be thought of as a pipeline which is being streamlined at every stage from protein cloning, expression and purification, through crystallisation to data collection and structure solution. Synchrotron X-ray beamlines are a key section of this pipeline as it is at these that the X-ray diffraction data that ultimately leads to the elucidation of macromolecular structures are collected. The burgeoning number of macromolecular crystallography (MX) beamlines available worldwide may be enhanced significantly with the automation of both their operation and of the experiments carried out on them. This paper reviews the current situation and provides a glimpse of how a MX beamline may look in the not too distant future.

Structure of the manganese superoxide dismutase from Deinococcus radiodurans in two crystal forms.

The structure of the manganese superoxide dismutase (Mn-SOD; DR1279) from Deinococcus radiodurans has been determined in two different crystal forms. Both crystal forms are monoclinic with space group P2(1). Form I has unit-cell parameters a = 44.28, b = 83.21, c = 59.52 angstroms, beta = 110.18 degrees and contains a homodimer in the asymmetric unit, with structure refinement (R = 16.8%, R(free) = 23.6%) carried out using data to d(min) = 2.2 angstroms. Form II has unit-cell parameters a = 43.57, b = 87.10, c = 116.42 angstroms, beta = 92.1 degrees and an asymmetric unit containing two Mn-SOD homodimers; structure refinement was effected to a resolution of 2.0 angstroms (R = 17.2%, R(free) = 22.3%). The resulting structures are compared with that of Mn-SOD from Escherichia coli, with which they are shown to be essentially isostructural.