Aditional Ultra-High-Resolution Observations of Ca+ Ions in the Local Insterstellar Medium

We present ultra-high-resolution (0.35 km s−1 FWHM) observations of the interstellar Ca K line towards seven nearby stars. The spectral resolution was sufficient to resolve the line profiles fully, thereby enabling us to detect hitherto unresolved velocity components, and to obtain accurate measurements of the velocity dispersions (b values). Absorption components with velocities similar to those expected for the Local Interstellar Cloud (LIC) and the closely associated ‘G cloud’ were identified towards six of the seven stars. However, in most cases the b values deduced for these components were significantly larger than the b ≈ 2.2 km s−1 (i.e. Tk ≈ 7000 K, vt ≈ 1 km s−1) expected for the LIC, and it is argued that this results from the presence of additional, spectrally unresolved, components having similar velocities and physical conditions. For two stars (δ Vel and α Pav) we detect interstellar components with much smaller b values (1.1 ± 0.3 and 0.8 ± 0.1 km s−1, respectively) than are expected for low-density clouds within the Local Bubble. In the case of the narrow α Pav component, we also find an anomalously large Na i/Ca ii column density ratio, which is indicative of a relatively high density. Thus it is possible that, in addition to LIC-type clouds, the local interstellar medium contains a population of previously undetected cooler and denser interstellar clouds

Improving well-being and equality outcomes: Aligning processes, supporting implementation and creating new opportunities

This report for Welsh Government considers the existing statutory duties in Wales, and how imoroved outcomes for equality and well-being might be improved by integrating engagement, setting objectives, delivery and reporting. The report also sets recommendations for reviewing Wales' specific duties, reflexive learning and practices and joint working opportunities between Wales' staturtory Commission

Circumstellar discs: What will be next?

This prospective chapter gives our view on the evolution of the study of circumstellar discs within the next 20 years from both observational and theoretical sides. We first present the expected improvements in our knowledge of protoplanetary discs as for their masses, sizes, chemistry, the presence of planets as well as the evolutionary processes shaping these discs. We then explore the older debris disc stage and explain what will be learnt concerning their birth, the intrinsic links between these discs and planets, the hot dust and the gas detected around main sequence stars as well as discs around white dwarfs.Comment: invited review; comments welcome (32 pages

Cross-national mixed methods comparative case study of recovery-focused mental health care planning and coordination in acute inpatient mental health settings (COCAPP-A)

Background: Serious concerns have been identified in relation to care planning, patient involvement and consent to treatment in mental health wards, including for those patients detained under the Mental Health Act. Further evidence is needed to develop care planning interventions that embed dignity, recovery and participation for all people using inpatient mental health care. Design: We propose to undertake a cross-national comparative study of recovery-focused mental health care planning in inpatient settings. This two-phase exploratory mixed methods study will produce theory and empirical evidence to complement that developed in our current study of community mental health services to inform a future whole systems intervention study. The study is guided by a theoretical framework emphasising the connections between different 'levels' of organisation (macro/meso/micro). In phase 1 we study the macro-level through the comparative analysis of English and Welsh policy contexts. In phase 2 concurrent quantitative and qualitative data will be collected at 6 NHS Trust/Health Board case study sites (meso-level) and within each site, a single micro-level mental health ward will be selected to provide in-depth qualitative data related to care planning processes. Phase 1: We will extend our current meta-narrative mapping review (Wong et al 2013) of English and Welsh policies and the international literature on personalised recovery-oriented care planning and coordination in community settings to include inpatient settings. We will provide a review of evidence that is useful, rigorous and relevant for service providers and decision-makers and to inform Phase 2. Phase 2: We are employing a concurrent transformative mixed methods approach with embedded case studies (Creswell 2009: 215). We will conduct six in-depth meso-level case study investigations across contrasting NHS Trusts in England (n=4) and Local Health Boards in Wales (n=2), selected to reflect variety in geography and population and include a mix of rural, urban and inner city settings providing routine inpatient care. A large sample of service users (total n=300), inpatient staff (n=300) and informal carers (n=150) will be surveyed about perceptions of acute mental health care and care planning, recovery oriented practices, therapeutic relationships and empowerment using validated questionnaires. Documents and interviews with managers, consultant psychiatrists, ward staff and informal carers (n=60) will also be generated relating to local contexts, policies and practices. In each site we will also select a single inpatient ward and conduct a series of case studies embedded within each organisational case study, to explore care planning in detail. We will invite a sample of service users (total n=36) to participate in in-depth interviews about care planning and structured narrative reviews of their care plans; undertake a structured review of anonymised care plans for a further sample (n=60) of consecutively discharged patients; and conduct observation of care planning processes (n= 18). Framework method will be employed to integrate and compare textual and statistical summaries of qualitative and quantitative analyses within each case study site, informed by the theoretical framework focused on recovery and personalisation. Armed with our set of six within-case analyses we will then conduct a cross-case analysis to draw out key findings from across all sites

Accessibility and implementation in the UK NHS services of an effective depression relapse prevention programme:learning from mindfulness-based cognitive therapy through a mixed-methods study

Background: Depression affects as many as one in five people in their lifetime and often runs a recurrent lifetime course. Mindfulness-based cognitive therapy (MBCT) is an effective psychosocial approach that aims to help people at risk of depressive relapse to learn skills to stay well. However, there is an ‘implementation cliff’: access to those who could benefit from MBCT is variable and little is known about why that is the case, and how to promote sustainable implementation. As such, this study fills a gap in the literature about the implementation of MBCT. Objectives: To describe the existing provision of MBCT in the UK NHS, develop an understanding of the perceived costs and benefits of MBCT implementation, and explore the barriers and critical success factors for enhanced accessibility. We aimed to synthesise the evidence from multiple data sources to create an explanatory framework of the how and why of implementation, and to co-develop an implementation resource with key stakeholders. Design: A two-phase qualitative, exploratory and explanatory study, which was conceptually underpinned by the Promoting Action on Research Implementation in Health Services framework. Setting: UK NHS services. Methods: Phase 1 involved interviews with participants from 40 areas across the UK about the current provision of MBCT. Phase 2 involved 10 case studies purposively sampled with differing degrees of MBCT provision, and from each UK country. Case study methods included interviews with key stakeholders, including commissioners, managers, MBCT practitioners and teachers, and service users. Observations were conducted and key documents were also collected. Data were analysed using a modified approach to framework analysis. Emerging findings were verified through stakeholder discussions and workshops. Results: Phase 1: access to and the format of MBCT provision across the NHS remains variable. NHS services have typically adapted MBCT to their context and its integration into care pathways was also highly variable even within the same trust or health board. Participants’ accounts revealed stories of implementation journeys that were driven by committed individuals that were sometimes met by management commitment. Phase 2: a number of explanations emerged that explained successful implementation. Critically, facilitation was the central role of the MBCT implementers, who were self-designated individuals who ‘championed’ implementation, created networks and over time mobilised top-down organisational support. Our explanatory framework mapped out a prototypical implementation journey, often over many years. This involved implementers working through grassroots initiatives and over time mobilising top-down organisational support, and a continual fitting of evidence, with the MBCT intervention, contextual factors and the training/supervision of MBCT teachers. Key pivot points in the journey provided windows of challenge or opportunity. Limitations: The findings are largely based on informants’ accounts and, therefore, are at risk of the bias of self-reporting. Conclusions: Although access to MBCT across the UK is improving, it remains very patchy. This study provides an explanatory framework that helps us understand what facilitates and supports sustainable MBCT implementation. Future work: The framework and stakeholder workshops are being used to develop online implementation guidance

Perturbing Dynamin Reveals Potent Effects on the Drosophila Circadian Clock

BACKGROUND: Transcriptional feedback loops are central to circadian clock function. However, the role of neural activity and membrane events in molecular rhythms in the fruit fly Drosophila is unclear. To address this question, we expressed a temperature-sensitive, dominant negative allele of the fly homolog of dynamin called shibire(ts1) (shi(ts1)), an active component in membrane vesicle scission. PRINCIPAL FINDINGS: Broad expression in clock cells resulted in unexpectedly long, robust periods (>28 hours) comparable to perturbation of core clock components, suggesting an unappreciated role of membrane dynamics in setting period. Expression in the pacemaker lateral ventral neurons (LNv) was necessary and sufficient for this effect. Manipulation of other endocytic components exacerbated shi(ts1)'s behavioral effects, suggesting its mechanism is specific to endocytic regulation. PKA overexpression rescued period effects suggesting shi(ts1) may downregulate PKA pathways. Levels of the clock component PERIOD were reduced in the shi(ts1)-expressing pacemaker small LNv of flies held at a fully restrictive temperature (29 degrees C). Less restrictive conditions (25 degrees C) delayed cycling proportional to observed behavioral changes. Levels of the neuropeptide PIGMENT-DISPERSING FACTOR (PDF), the only known LNv neurotransmitter, were also reduced, but PERIOD cycling was still delayed in flies lacking PDF, implicating a PDF-independent process. Further, shi(ts1) expression in the eye also results in reduced PER protein and per and vri transcript levels, suggesting that shibire-dependent signaling extends to peripheral clocks. The level of nuclear CLK, transcriptional activator of many core clock genes, is also reduced in shi(ts1) flies, and Clk overexpression suppresses the period-altering effects of shi(ts1). CONCLUSIONS: We propose that membrane protein turnover through endocytic regulation of PKA pathways modulates the core clock by altering CLK levels and/or activity. These results suggest an important role for membrane scission in setting circadian period

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

The Magpie Trial follow up study: outcome after discharge from hospital for women and children recruited to a trial comparing magnesium sulphate with placebo for pre-eclampsia

Contributing member: Caroline Crowther is listed as a member of the Magpie Trial Follow Up Study Collaborative GroupBACKGROUND: The Magpie Trial compared magnesium sulphate with placebo for women with pre-eclampsia. 10,141 women were recruited, 8804 before delivery. Overall, 9024 children were included in the analysis of outcome at discharge from hospital. Magnesium sulphate more than halved the risk of eclampsia, and probably reduced the risk of maternal death. There did not appear to be any substantive harmful effects on the baby, in the short term. It is now important to assess whether these benefits persist, and to provide adequate reassurance about longer term safety. The main objective of the Magpie Trial Follow Up Study is to assess whether in utero exposure to magnesium sulphate has a clinically important effect on the child's chance of surviving without major neurosensory disability. Other objectives are to assess long term outcome for the mother, and to develop and assess appropriate strategies for following up large numbers of children in perinatal trials. STUDY DESIGN: Follow up is only feasible in selected centres. We therefore anticipate contacting 2800–3350 families, for 2435–2915 of whom the woman was randomised before delivery. A further 280–335 children would have been eligible for follow up if they had survived. The total sample size for the children is therefore 3080–3685, 2680–3210 of whom will have been born to women randomised before delivery. Families eligible for the follow up will be contacted, and surviving children screened using the Ages and Stages Questionnaires. Children who screen positive, and a sample of those who screen negative, will whenever possible have a paediatric and neurodevelopmental assessment. When women are contacted to ask how their child is, they will also be asked about their own health. The primary outcome is a composite measure of death or neurosensory disability for the child at 18 months. DISCUSSION: The Follow Up Study began in 2002, and now involves collaborators in 19 countries. Data collection will close at the end of 2003

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified