Impacts of ‘change projects’ in Cumbria partnership trust’s Learning Leaders programme: Evaluating qualitative participant end-point reflections.

This paper reports findings arising from a broader evaluation of the first tranche of Cumbria Partnership Foundation Trust’s Learning Leaders Programme (LLP). At the final ‘Celebration Day’ of the LLP, all participants (N=15) were invited to fill a form in which they could self-assess the impacts of their projects, and results were analysed using Straussian Grounded Theory. Responses indicated that key concerns related to extant impacts, impact mechanisms (i.e. the manner through which impacts were effected) and obstacles to impact. The overwhelming consensus generated was that the projects had produced strong positive impacts at time of reporting, and had the potential to effect further affirmative change

25-Hydroxy vitamin-D, obesity, and associated variables as predictors of breast cancer risk and tamoxifen benefit in NSABP-P1.

Observational studies suggest that host factors are associated with breast cancer risk. The influence of obesity, vitamin-D status, insulin resistance, inflammation, and elevated adipocytokines in women at high risk of breast cancer is unknown. The NSABP-P1 trial population was used for a nested case-control study. Cases were drawn from those who developed invasive breast cancer and controls selected from unaffected participants (≤4 per case) matched for age, race, 5 year Gail score, and geographic location of clinical center as a surrogate for latitude. Fasting serum banked at trial enrolment was assayed for 25-hydroxy vitamin-D (25OHD), insulin, leptin (adipocytokine), and C-reactive protein (CRP, marker of inflammation). Logistic regression was used to test for associations between study variables and the risk of invasive breast cancer. Two hundred and thirty-one cases were matched with 856 controls. Mean age was 54, and 49% were premenopausal. There were negative correlations for 25OHD with body mass index (BMI), insulin, CRP, and leptin. BMI ≥ 25 kg/m(2) was associated with higher breast cancer risk (odds ratio [OR] 1.45, p = 0.02) and tamoxifen treatment was associated with lower risk (OR = 0.44, p < 0.001). Suboptimal 25OHD (<72 nmol/l) did not influence breast cancer risk (OR = 1.06, p = 0.76). When evaluated as continuous variables, 25OHD, insulin, CRP, and leptin levels were not associated with breast cancer risk (all p > 0.34). In this high risk population, higher BMI was associated with a greater breast cancer risk. Serum levels of 25OHD, insulin, CRP, and leptin were not independent predictors of either breast cancer risk or tamoxifen benefit

Development of an optimised 1:1 physiotherapy intervention post first-time lumbar discectomy:a mixed-methods study

Objectives To develop an optimised 1:1 physiotherapy intervention that reflects best practice, with flexibility to tailor management to individual patients, thereby ensuring patient-centred practice. Design Mixed-methods combining evidence synthesis, expert review and focus groups. Setting Secondary care involving 5 UK specialist spinal centres. Participants A purposive panel of clinical experts from the 5 spinal centres, comprising spinal surgeons, inpatient and outpatient physiotherapists, provided expert review of the draft intervention. Purposive samples of patients (n=10) and physiotherapists (n=10) (inpatient/outpatient physiotherapists managing patients with lumbar discectomy) were invited to participate in the focus groups at 1 spinal centre. Methods A draft intervention developed from 2 systematic reviews; a survey of current practice and research related to stratified care was circulated to the panel of clinical experts. Lead physiotherapists collaborated with physiotherapy and surgeon colleagues to provide feedback that informed the intervention presented at 2 focus groups investigating acceptability to patients and physiotherapists. The focus groups were facilitated by an experienced facilitator, recorded in written and tape-recorded forms by an observer. Tape recordings were transcribed verbatim. Data analysis, conducted by 2 independent researchers, employed an iterative and constant comparative process of (1) initial descriptive coding to identify categories and subsequent themes, and (2) deeper, interpretive coding and thematic analysis enabling concepts to emerge and overarching pattern codes to be identified. Results The intervention reflected best available evidence and provided flexibility to ensure patient-centred care. The intervention comprised up to 8 sessions of 1:1 physiotherapy over 8 weeks, starting 4 weeks postsurgery. The intervention was acceptable to patients and physiotherapists. Conclusions A rigorous process informed an optimised 1:1 physiotherapy intervention post-lumbar discectomy that reflects best practice. The developed intervention was agreed on by the 5 spinal centres for implementation in a randomised controlled trial to evaluate its effectiveness

Evaluating and Optimizing Fish Health and Welfare During Experimental Procedures.

This is the final version of the article. It first appeared from Mary Ann Liebert, Inc. via http://dx.doi.org/10.1089/zeb.2015.1165Many facilities house fish in separate static containers post-procedure, for example, while awaiting genotyping results. This ensures fish can be easily identified, but it does not allow for provision of continuous filtered water or diet. At the Wellcome Trust Sanger Institute, concern over the housing conditions led to the development of an individual housing system (GeneS) enabling feeding and water filtration. Trials to compare the water quality measures between the various systems found that fish housed in static containers experienced rapid deterioration in water quality. By day 1, measures of ammonia were outside the Institute's prescribed values and continued to rise until it was 25-fold higher than recommended levels. Nitrite levels were also outside recommended levels for all fish by day 9 and were twofold higher by the end of the trial. The water quality measures for tanks held on the recirculating system were stable even though food was provided. These results indicate that for housing zebrafish, running water or appropriately timed water changes are a critical component to ensure that the ethical obligations are met.We thank the staff from the Sanger Institute's Research Support Facility, Zebrafish Mutation Project, and Jacqui White for their support. This work was supported by the Wellcome Trust grant number 098051

Search for heavy neutral leptons decaying into muon-pion pairs in the MicroBooNE detector

We present upper limits on the production of heavy neutral leptons (HNLs) decaying to mu p pairs using data collected with the MicroBooNE liquid-argon time projection chamber (TPC) operating at Fermilab. This search is the first of its kind performed in a liquid-argon TPC. We use data collected in 2017 and 2018 corresponding to an exposure of 2.0 x 10(20) protons on target from the Fermilab Booster Neutrino Beam, which produces mainly muon neutrinos with an average energy of approximate to 800 MeV. HNLs with higher mass are expected to have a longer time of flight to the liquid-argon TPC than Standard Model neutrinos. The data are therefore recorded with a dedicated trigger configured to detect HNL decays that occur after the neutrino spill reaches the detector. We set upper limits at the 90% confidence level on the element vertical bar U-mu 4 vertical bar(2) of the extended PMNS mixing matrix in the range vertical bar U-mu 4 vertical bar(2) <(6.6-0.9) x 10(-7) for Dirac HNLs and vertical bar U-mu 4 vertical bar(2) <(4.7-0.7) x 10(-7) for Majorana HNLs, assuming HNL masses between 260 and 385 MeV and vertical bar U-e4 vertical bar(2) = vertical bar U-tau 4 vertical bar(2) = 0

The IBER study: study protocol for a feasibility randomised controlled trial of Imagery Based Emotion Regulation for the treatment of anxiety in bipolar disorder.

BACKGROUND: Anxiety is highly prevalent in people diagnosed with bipolar disorder (BD), and can persist between acute episodes of mania and depression. Recent studies indicate that people with BD are prone to experiencing frequent, intrusive and emotional mental images which further fuel their levels of anxiety and mood instability. These intrusive emotional mental images represent a specific target for treatment for this disorder with the potential to reduce anxiety and improve mood stability. A new brief structured psychological intervention for BD called Imagery Based Emotion Regulation (IBER) has been developed, which translates experimental work in the area of imagery and emotion into a skills training programme to improve the regulation of intrusive and distressing emotional mental images in BD. A feasibility trial is required in order to assess whether a full randomised controlled trial is indicated in order to evaluate this approach. METHODS: The design is a two-arm feasibility randomised controlled trial (RCT), with 1:1 randomisation stratified by trial site and minimised on medication status and anxiety severity. Participants are 60 individuals diagnosed with bipolar disorder and experiencing at least a mild level of anxiety. Sites are defined by the geographical boundaries of two National Health Service (NHS) Trusts, with recruitment from NHS teams, GP surgeries and self-referral. The intervention is up to 12 sessions of Imagery Based Emotion Regulation within 16 weeks. The comparator is NHS standard care. The primary aim is to assess the feasibility of conducting a powered multi-site RCT to evaluate effectiveness. Measures of anxiety, depression, mania, mood stability and health care use will be conducted at baseline, end of treatment and at 16-week follow-up. DISCUSSION: This is the first feasibility trial of an imagery-based intervention for the treatment of anxiety in bipolar disorder. If the trial proves feasible, a large multi-site trial will be required. TRIAL REGISTRATION: ISRCTN16321795. Registered on October 16, 2018. 10.1186/ISRCTN16321795

Ultrastructural analysis of sequential Cyprinid herpesvirus 3 morphogenesis in vitro

Cyprinid herpesvirus 3 (CyHV-3) is an alloherpesvirus, and it is the aetiological agent of koi herpesvirus disease. Although the complex morphogenic stages of the replication cycle of CyHV-3 were shown to resemble that of other members of the Herpesvirales, detailed analysis of the sequence and timing of these events was not definitively determined. This study describes these features through a time course using cyprinid cell cultures (KF-1 and CCB) infected with CyHV-3 (KHV isolate, H361) and analysed by transmission electron microscopy. Rapid viral entry was noted, with high levels of intracellular virus within 1–4 h post-infection (hpi). Intranuclear capsid assembly, paracrystalline array formation and primary envelopment of capsids occurred within 4 hpi. Between 1 and 3 days post-infection (dpi), intracytoplasmic secondary envelopment occurred, as well as budding of infectious virions at the plasma membrane. At 5–7 dpi, the cytoplasm contained cytopathic vacuoles, enveloped virions within vesicles, and abundant non-enveloped capsids; also there was frequent nuclear deformation. Several morphological features are suggestive of inefficient viral assembly, with production of non-infectious particles, particularly in KF-1 cells. The timing of this alloherpesvirus morphogenesis is similar to other members of the Herpesvirales, but there may be possible implications of using different cell lines for CyHV-3 propagation

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives

Standardized Welfare Terms for the Zebrafish Community.

This is the final version of the article. It first appeared from Mary Ann Liebert via https://doi.org/10.1089/zeb.2016.1248Managing the welfare of laboratory animals is critical to animal health, vital in the understanding of phenotypes created by treatment or genetic alteration and ensures compliance of regulations. Part of an animal welfare assessment is the requirement to record observations, ensuring all those responsible for the animals are aware of their health status and can act accordingly. Although the use of zebrafish in research continues to increase, guidelines for conducting welfare assessments and the reporting of observations are considered unclear compared to mammalian species. To support the movement of zebrafish between facilities, significant improvement would be achieved through the use of standardized terms to ensure clarity and consistency between facilities. Improving the clarity of terminology around welfare not only addresses our ethical obligation but also supports the research goals and provides a searchable description of the phenotypes. A Collaboration between the Wellcome Trust Sanger Institute and Cambridge University (Department of Medicine-Laboratory of Molecular Biology) has led to the creation of the zebrafish welfare terms from which standardization of terminology can be achieved.This work was supported by the Wellcome Trust (grant no. 098051), the National Institutes of Health Office of Research Infrastructure Programs award (P40OD011021), the National Institutes of Health (grant no. A154503), National Institutes for Health Research to the Biomedical Research Centre (grant no. RG64229), and a Wellcome Trust Personal Research Fellowship (103950/Z/14/Z)

The Fire Within: Microbes Inflame Tumors

The immune system and the microbiota mutually interact to maintain homeostasis in the intestine. However, components of the microbiota can alter this balance and promote chronic inflammation, promoting intestinal tumor development. We review recent advances in understanding the complex interactions between the microbiota and the innate and adaptive immune systems and discuss their potential to lead us in new directions for understanding cancer biology and treatment