Definition of valid proteomic biomarkers: a bayesian solution

Clinical proteomics is suffering from high hopes generated by reports on apparent biomarkers, most of which could not be later substantiated via validation. This has brought into focus the need for improved methods of finding a panel of clearly defined biomarkers. To examine this problem, urinary proteome data was collected from healthy adult males and females, and analysed to find biomarkers that differentiated between genders. We believe that models that incorporate sparsity in terms of variables are desirable for biomarker selection, as proteomics data typically contains a huge number of variables (peptides) and few samples making the selection process potentially unstable. This suggests the application of a two-level hierarchical Bayesian probit regression model for variable selection which assumes a prior that favours sparseness. The classification performance of this method is shown to improve that of the Probabilistic K-Nearest Neighbour model

Reply: SUN vs BEVþIFN in first-line mRCC therapy: no evidence for a statistically significant difference in progression-free survival

Copyright © 2015 Cancer Research UKThis is an BJC Open articleLetter to the Edito

Patient initiated clinics for patients with chronic or recurrent conditions managed in secondary care: a systematic review of patient reported outcomes and patient and clinician satisfaction

This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: The cost to the NHS of missed or inappropriate hospital appointments is considerable. Alternative methods of appointment scheduling might be more flexible to patients' needs without jeopardising health and service quality. The objective was to systematically review evidence of patient initiated clinics in secondary care on patient reported outcomes among patients with chronic/recurrent conditions. METHODS: Seven databases were searched from inception to June 2013. Hand searching of included studies references was also conducted. Studies comparing the effects of patient initiated clinics with traditional consultant led clinics in secondary care for patients with long term chronic or recurrent diseases on health related quality of life and/or patient satisfaction were included. Data was extracted by one reviewer and checked by a second. Results were synthesised narratively. RESULTS: Seven studies were included in the review, these covered a total of 1,655 participants across three conditions: breast cancer, inflammatory bowel disease and rheumatoid arthritis. Quality of reporting was variable. Results showed no significant differences between the intervention and control groups for psychological and health related quality of life outcomes indicating no evidence of harm. Some patients reported significantly more satisfaction using patient-initiated clinics than usual care (p < 0.001). CONCLUSIONS: The results show potential for patient initiated clinics to result in greater patient and clinician satisfaction. The patient-consultant relationship appeared to play an important part in patient satisfaction and should be considered an important area of future research as should the presence or absence of a guidebook to aid self-management. Patient initiated clinics fit the models of care suggested by policy makers and so further research into long term outcomes for patients and service use in this area of practice is both relevant and timely.This systematic review was funded by the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health

The clinical effectiveness of patient initiated clinics for patients with chronic or recurrent conditions managed in secondary care: a systematic review

This is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Missed or inappropriate hospital appointments cost the UK National Health Service millions of pounds each year and delay treatment for other patients. Innovative methods of appointment scheduling that are more flexible to patient needs, may improve service quality and preserve resources. METHODS: A systematic review of the evidence for the clinical effectiveness of patient initiated clinics in managing long term care for people with chronic or recurrent conditions in secondary care. Seven databases were searched including MEDLINE, Embase and PsycINFO (using the OVID interface), the Cochrane Library of Systematic Reviews and CENTRAL, Science Citation Index Expanded, Social Sciences Citation Index, and Conference Proceedings Citation Index (via the Web of Science interface) from inception to June 2013. Studies comparing patient initiated clinics with traditional consultant-led clinics in secondary care for people with long term chronic or recurrent diseases were included. Included studies had to provide data on clinical or resource use outcomes. Data were extracted and checked by two reviewers using a piloted, standardised data extraction form. RESULTS: Eight studies (n = 1927 individuals) were included. All were conducted in the UK. There were few significant differences in clinical outcomes between the intervention and control groups. In some instances, using the patient initiated clinics model was associated with savings in time and resource use. The risk of harm from using the patient initiated clinic model of organising outpatient care is low. Studies with longer follow-up periods are needed to assess the long term costs and the ongoing risk of potential harms. CONCLUSIONS: The UK policy context is ripe for evidence-based, patient-centred services to be implemented, especially where the use of health care resources can be optimised without reducing the quality of care. Implementation of patient initiated clinics should remain cautious, with importance placed on ongoing evaluation of long term outcomes and costs.This systematic review was funded by the National Institute of Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care for the South West. The views expressed in this publication are those of the author(s) and not necessarily those of the National Health Service, the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Whole-system approaches to improving the health and wellbeing of healthcare workers: A systematic review

This is the final version of the article. Available from Public Library of Science via the DOI in this record.BACKGROUND: Healthcare professionals throughout the developed world report higher levels of sickness absence, dissatisfaction, distress, and "burnout" at work than staff in other sectors. There is a growing call for the 'triple aim' of healthcare delivery (improving patient experience and outcomes and reducing costs; to include a fourth aim: improving healthcare staff experience of healthcare delivery. A systematic review commissioned by the United Kingdom's (UK) Department of Health reviewed a large number of international healthy workplace interventions and recommended five whole-system changes to improve healthcare staff health and wellbeing: identification and response to local need, engagement of staff at all levels, and the involvement, visible leadership from, and up-skilling of, management and board-level staff. OBJECTIVES: This systematic review aims to identify whole-system healthy workplace interventions in healthcare settings that incorporate (combinations of) these recommendations and determine whether they improve staff health and wellbeing. METHODS: A comprehensive and systematic search of medical, education, exercise science, and social science databases was undertaken. Studies were included if they reported the results of interventions that included all healthcare staff within a healthcare setting (e.g. whole hospital; whole unit, e.g. ward) in collective activities to improve physical or mental health or promote healthy behaviours. RESULTS: Eleven studies were identified which incorporated at least one of the whole-system recommendations. Interventions that incorporated recommendations to address local need and engage the whole workforce fell in to four broad types: 1) pre-determined (one-size-fits-all) and no choice of activities (two studies); or 2) pre-determined and some choice of activities (one study); 3) A wide choice of a range of activities and some adaptation to local needs (five studies); or, 3) a participatory approach to creating programmes responsive and adaptive to local staff needs that have extensive choice of activities to participate in (three studies). Only five of the interventions included substantial involvement and engagement of leadership and efforts aimed at up-skilling the leadership of staff to support staff health and wellbeing. Incorporation of more of the recommendations did not appear to be related to effectiveness. The heterogeneity of study designs, populations and outcomes excluded a meta-analysis. All studies were deemed by their authors to be at least partly effective. Two studies reported statistically significant improvement in objectively measured physical health (BMI) and eight in subjective mental health. Six studies reported statistically significant positive changes in subjectively assessed health behaviours. CONCLUSIONS: This systematic review identified 11 studies which incorporate at least one of the Boorman recommendations and provides evidence that whole-system healthy workplace interventions can improve health and wellbeing and promote healthier behaviours in healthcare staff.Funding provided in part to the European Centre for Environment and Human Health (part of the University of Exeter Medical School) by the European Regional Development Fund Programme 2007 to 2013 (https://www.gov.uk/guidance/erdf-programmes-and-resources) and European Social Fund Convergence Programme for Cornwall and the Isles of Scilly (http://www.erdfconvergence.org.uk/esf). This research was also funded in part by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South West Peninsula (http://clahrc-peninsula.nihr.ac.uk/) at the Royal Devon and Exeter NHS Foundation Trust (http://www.rdehospital.nhs.uk/). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Sleep positioning systems for children with cerebral palsy

PublishedArticleThis review is published as a Cochrane Review in the Cochrane Database of Systematic Reviews 2015, Issue 11. Cochrane Reviews are regularly updated as new evidence emerges and in response to comments and criticisms, and the Cochrane Database of Systematic Reviews should be consulted for the most recent version of the Review.Background Sleep positioning systems can be prescribed for children with cerebral palsy to help reduce or prevent hip migration, provide comfort to ease pain and/or impr ove sleep. As sleep disturbance is common in children with developmental disabilities, with impact on their carers’ sleep, and as sleep positioning systems can be expensive, guidance is needed to support decisions as to their use. Objectives To determine whether commercially-available sleep positioning systems, compared with usual care, reduce or prevent hip migration in children with cerebral palsy. Any negative effect of sleep positioning systems on hip migration will be considered within this objective. Secondary objective s were to determine the effect of sleep positioning systems on: (1) number or frequency of hip problems; (2) sleep patterns and quality; (3) quality of life of the child and family; (4) pain; and (5) physical functioning. We also sought to identify any adverse effects from using sleep positioning systems. Search methods In December 2014, we se arched CENTRAL, Ovid MEDLINE, Embase, and 13 other databases. We also searched two trials registers. We applied no restrictions on date of publication, language, publication status or study design. We checked references and contacted manufacturers and authors for potentially relevant literature , and searched the internet using Google. Selection criteria We included all randomised controlled trials (RCTs) evaluating whole body sleep positioning systems for children and adolescents (up to 18 years of age) with cerebral palsy. Data collection and analysis Two review authors independently screened reports retrieved from the search against pre-determined inclusion criteria and assessed the quality of eligible studies. Members of the public (parent carers of children with neurodisability) contributed to this review by suggesting the topic, refining the research objectives, interpreting the findings, and reviewing the plain language summaryNIHRCerebra, U

Three-Nucleon Photodisintegration of 3He

The three-nucleon photodisintegration of 3He has been calculated in the whole phase space using consistent Faddeev equations for the three-nucleon bound and scattering states. Modern nucleon-nucleon and 3N forces have been applied as well as different approaches to nuclear currents. Phase space regions are localized where 3N force effects are especially large. In addition semi-exclusive cross sections for 3He(gamma,N) have been predicted which carry interesting peak structures. Finally some data for the exclusive 3N breakup process of 3He and its total breakup cross section have been compared to theory.Comment: 28 pages, 6 png figures, 11 ps figures, modified version with changed figures, conclusions unchanged, to appear in Phys.Rev.

Charge-Asymmetry of the Nucleon-Nucleon Interaction

Based upon the Bonn meson-exchange model for the nucleon-nucleon ($NN$) interaction, we study systematically the charge-symmetry-breaking (CSB) of the $NN$ interaction due to nucleon mass splitting. Particular attention is payed to CSB generated by the $2\pi$-exchange contribution to the $NN$ interaction, $\pi\rho$ diagrams, and other multi-meson-exchanges. We calculate the CSB differences in the $^1S_0$ effective range parameters as well as phase shift differences in $S$, $P$ and higher partial waves up to 300 MeV lab. energy. We find a total CSB difference in the singlet scattering length of 1.6 fm which explains the empirical value accurately. The corresponding CSB phase-shift differences are appreciable at low energy in the $^1S_0$ state. In the other partial waves, the CSB splitting of the phase shifts is small and increases with energy, with typical values in the order of 0.1 deg at 300 MeV in $P$ and $D$ waves.Comment: 11 pages, RevTex, 14 figure

Three-Nucleon Force Effects in Nucleon Induced Deuteron Breakup: Predictions of Current Models (I)

An extensive study of three-nucleon force effects in the entire phase space of the nucleon-deuteron breakup process, for energies from above the deuteron breakup threshold up to 200 MeV, has been performed. 3N Faddeev equations have been solved rigorously using the modern high precision nucleon-nucleon potentials AV18, CD Bonn, Nijm I, II and Nijm 93, and also adding 3N forces. We compare predictions for cross sections and various polarization observables when NN forces are used alone or when the two pion-exchange Tucson-Melbourne 3NF was combined with each of them. In addition AV18 was combined with the Urbana IX 3NF and CD Bonn with the TM' 3NF, which is a modified version of the TM 3NF, more consistent with chiral symmetry. Large but generally model dependent 3NF effects have been found in certain breakup configurations, especially at the higher energies, both for cross sections and spin observables. These results demonstrate the usefulness of the kinematically complete breakup reaction in testing the proper structure of 3N forces.Comment: 42 pages, 20 ps figures, 2 gif figure

The one-pion-exchange three-nucleon force and the AyA_y puzzle

We consider a new three-nucleon force generated by the exchange of one pion in the presence of a 2N correlation. The underlying irreducible diagram has been recently suggested by the authors as a possible candidate to explain the puzzle of the vector analyzing powers $A_y$ and $iT_{11}$ for nucleon-deuteron scattering. Herein, we have calculated the elastic neutron-deuteron differential cross section, $A_y$, $iT_{11}$, $T_{20}$, $T_{21}$, and $T_{22}$ below break-up threshold by accurately solving the Alt-Grassberger-Sandhas equations with realistic interactions. We have also studied how $A_y$ evolves below 30 MeV. The results indicate that this new 3NF diagram provides one possible additional contribution, with the correct spin-isospin structure, for the explanation of the origin of this puzzle.Comment: revised version: We have also studied how Ay evolves below 30 MeV, 4 Pages (twocolumn), 2 figures, uses psfig, RevTe