Consensus multivariate methods in gas chromatography mass spectrometry and denaturing gradient gel electrophoresis: MHC-congenic and other strains of mice can be classified according to the profiles of volatiles and microflora in their scent-marks

House mice (Mus domesticus) communicate using scent-marks, and the chemical and microbial composition of these 'extended phenotypes' are both influenced by genetics. This study examined how the genes of the major histocompatibility complex (MHC) and background genes influence the volatile compounds (analysed with Gas Chromatography Mass Spectrometry or GC/MS) and microbial communities (analysed using Denaturating Gradient Gel Electrophoresis or DGGE) in scent-marks produced by congenic strains of mice. The use of Consensus Principal Components Analysis is described and shows relationships between the two types of fingerprints (GC/MS and DGGE profiles). Classification methods including Support Vector Machines and Discriminant Partial Least Squares suggest that mice can be classified according to both background strain and MHC-haplotype. As expected, the differences among the mice were much greater between strains that vary at both MHC and background loci than the congenics, which differ only at the MHC. These results indicate that the volatiles in scent-marks provide information about genetic similarity of the mice, and support the idea that the production of these genetically determined volatiles is influenced by commensal microflora. This paper describes the application of consensus methods to relate two blocks of analytical data

Effectiveness and cost-effectiveness of a cardiovascular risk prediction algorithm for people with severe mental illness (PRIMROSE)

Objectives: To determine the cost-effectiveness of two bespoke severe mental illness (SMI)-specific risk algorithms compared to standard risk algorithms for primary cardiovascular disease (CVD) prevention in those with SMI. Setting: Primary care setting in the United Kingdom (UK). The analysis was from the National Health Service (NHS) perspective. Participants: 1000 individuals with SMI from The Health Improvement Network Database, aged 30-74 years and without existing CVD populated the model. Interventions: Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those considered high-risk (>10%) were assumed to be prescribed statin therapy whilst others received usual care. Primary and secondary outcome measures: Quality adjusted life years (QALYs) and costs were accrued for each algorithm including no algorithm, and cost-effectiveness was calculated using the net monetary benefit (NMB) approach. Deterministic and probabilistic sensitivity analyses were performed to test assumptions made and uncertainty around parameter estimates. Results: The SMI-specific BMI algorithm had the highest NMB resulting in 15 additional QALYs and a cost saving of approximately £53,000 per 1,000 patients with SMI over 10 years, followed by the general population lipid algorithm (13 additional QALYs and a cost saving of £46,000). Conclusions: The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of an SMI-specific BMI algorithm (blood tests not required), makes it an attractive algorithm to implement in clinical settings

Simulations and First RF Measurements of Coaxial HOM Coupler Prototypes for PERLE SRF Cavities

International audienceSuperconducting Radio-Frequency (SRF) linac cryomodules are foreseen for the high-current multi-turn energy recovery linac PERLE (Powerful Energy Recovery Linac for Experiments). Coaxial higher order mode (HOM) couplers are the primary design choice to absorb beam-induced power and avoid beam instabilities. We have used 3D-printed and copper-coated HOM couplers for the prototyping and bench RF measurements on the copper PERLE cavities. We have started a collaboration with JLab and CERN on this effort. This paper presents electromagnetic simulations of the cavity HOM-damping performance on those couplers. Bench RF measurements of the HOMs on an 801.58 MHz 2-cell copper cavity performed at JLab are detailed. The results are compared to eigenmode simulations in CST to confirm the design. RF-thermal simulations are conducted to investigate if the studied HOM couplers undergo quenching

Primary care management of cardiovascular risk for people with severe mental illnesses: the Primrose research programme including cluster RCT

Background: Effective interventions are needed to prevent cardiovascular disease (CVD) in people with severe mental illnesses (SMI) because their risk of CVD is higher than that of the general population. Objectives: (1) Develop and validate risk models for predicting CVD events in people with SMI and evaluate their cost-effectiveness, (2) develop an intervention to reduce levels of cholesterol and CVD risk in SMI and (3) test the clinical effectiveness and cost-effectiveness of this new intervention in primary care. Design: Mixed methods with patient and public involvement throughout. The mixed methods were (1) a prospective cohort and risk score validation study and cost-effectiveness modelling, (2) development work (focus groups, updated systematic review of interventions, primary care database studies investigating statin prescribing and effectiveness) and (3) cluster randomised controlled trial (RCT) assessing the clinical effectiveness and cost-effectiveness of a new practitioner-led intervention, and fidelity assessment of audio-recorded appointments. Setting: General practices across England. Participants: All studies included adults with SMI (schizophrenia, bipolar disorder or other non-organic psychosis). The RCT included adults with SMI and two or more CVD risk factors. Interventions: The intervention consisted of 8–12 appointments with a practice nurse/health-care assistant over 6 months, involving collaborative behavioural approaches to CVD risk factors. The intervention was compared with routine practice with a general practitioner (GP). Main outcome measures: The primary outcome for the risk score work was CVD events, in the cost-effectiveness modelling it was quality-adjusted life-years (QALYs) and in the RCT it was level of total cholesterol. Data sources: Databases studies used The Health Improvement Network (THIN). Intervention development work included focus groups and systematic reviews. The RCT collected patient self-reported and routine NHS GP data. Intervention appointments were audio-recorded. Results: Two CVD risk score models were developed and validated in 38,824 people with SMI in THIN: the Primrose lipid model requiring cholesterol levels, and the Primrose body mass index (BMI) model with no blood test. These models performed better than published Cox Framingham models. In health economic modelling, the Primrose BMI model was most cost-effective when used as an algorithm to drive statin prescriptions. Focus groups identified barriers to, and facilitators of, reducing CVD risk in SMI including patient engagement and motivation, staff confidence, involving supportive others, goal-setting and continuity of care. Findings were synthesised with evidence from updated systematic reviews to create the Primrose intervention and training programme. THIN cohort studies in 16,854 people with SMI demonstrated that statins effectively reduced levels of cholesterol, with similar effect sizes to those in general population studies over 12–24 months (mean decrease 1.2 mmol/l). Cluster RCT: 76 GP practices were randomised to the Primrose intervention (n = 38) or treatment as usual (TAU) (n = 38). The primary outcome (level of cholesterol) was analysed for 137 out of 155 participants in Primrose and 152 out of 172 in TAU. There was no difference in levels of cholesterol at 12 months [5.4 mmol/l Primrose vs. 5.5 mmol/l TAU; coefficient 0.03; 95% confidence interval (CI) –0.22 to 0.29], nor in secondary outcomes related to cardiometabolic parameters, well-being or medication adherence. Mean cholesterol levels decreased over 12 months in both arms (–0.22 mmol/l Primrose vs. –0.39 mmol/l TAU). There was a significant reduction in the cost of inpatient mental health attendances (–£799, 95% CI –£1480 to –£117) and total health-care costs (–£895, 95% CI –£1631 to –£160; p = 0.012) in the intervention group, but no significant difference in QALYs (–0.011, 95% CI –0.034 to 0.011). A total of 69% of patients attended two or more Primrose appointments. Audiotapes revealed moderate fidelity to intervention delivery (67.7%). Statin prescribing and adherence was rarely addressed. Limitations: RCT participants and practices may not represent all UK practices. CVD care in the TAU arm may have been enhanced by trial procedures involving CVD risk screening and feedback. Conclusions: SMI-specific CVD risk scores better predict new CVD if used to guide statin prescribing in SMI. Statins are effective in reducing levels of cholesterol in people with SMI in UK clinical practice. This primary care RCT evaluated an evidence-based practitioner-led intervention that was well attended by patients and intervention components were delivered. No superiority was shown for the new intervention over TAU for level of cholesterol, but cholesterol levels decreased over 12 months in both arms and the intervention showed fewer inpatient admissions. There was no difference in cholesterol levels between the intervention and TAU arms, which might reflect better than standard general practice care in TAU, heterogeneity in intervention delivery or suboptimal emphasis on statins. Future work: The new risk score should be updated, deployed and tested in different settings and compared with the latest versions of CVD risk scores in different countries. Future research on CVD risk interventions should emphasise statin prescriptions more. The mechanism behind lower costs with the Primrose intervention needs exploring, including SMI-related training and offering frequent support to people with SMI in primary care. Trial registration: Current Controlled Trials ISRCTN13762819. Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 7, No. 2. See the NIHR Journals Library website for further project information. Professor David Osborn is supported by the University College London Hospital NIHR Biomedical Research Centre and he was also in part supported by the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) North Thames at Barts Health NHS Trust

First expert elicitation of knowledge on possible drivers of observed increasing human cases of Tick-Borne Encephalitis in Europe

International audienceTick-borne encephalitis (TBE) is a viral disease endemic in Eurasia. The virus is mainly transmitted to humans via ticks and occasionally via the consumption of unpasteurized milk products. The European Centre for Disease Prevention and Control reported an increase in TBE incidence over the past years in Europe as well as the emergence of the disease in new areas. To better understand this phenomenon, we investigated the drivers of TBE emergence and increase in incidence in humans through an expert knowledge elicitation. We listed 59 possible drivers grouped in eight domains and elicited forty European experts to: (i) allocate a score per driver, (ii) weight this score within each domain, and (iii) weight the different domains and attribute an uncertainty level per domain. An overall weighted score per driver was calculated, and drivers with comparable scores were grouped into three terminal nodes using a regression tree analysis. The drivers with the highest scores were: (i) changes in human behavior/activities; (ii) changes in eating habits or consumer demand; (iii) changes in the landscape; (iv) influence of humidity on the survival and transmission of the pathogen; (v) difficulty to control reservoir(s) and/or vector(s); (vi) influence of temperature on virus survival and transmission; (vii) number of wildlife compartments/groups acting as reservoirs or amplifying hosts; (viii) increase of autochthonous wild mammals; and (ix) number of tick species vectors and their distribution. Our results support researchers in prioritizing studies targeting the most relevant drivers of emergence and increasing TBE incidence