Application for the 4W Model of Drowning for Prevention, Rescue and Treatment, Research and Education

Previous research has been published about the 4W model of drowning and its four constituent variables (Avramidis, Butterly & Llewellyn, 2007; 2009a; 2009b; 2009c; 2009d; Avramidis, McKenna, Long, Butterly, & Llewellyn, 2010). We presently summarize and suggest applications of the model for the general public, aquatic safety professionals, injury epidemiologists and policy makers

Exploring differential item functioning in the SF-36 by demographic, clinical, psychological and social factors in an osteoarthritis population

The SF-36 is a very commonly used generic measure of health outcome in osteoarthritis (OA). An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items work in the same way across subgroup of a population. That is, if respondents have the same 'true' level of outcome, does the item give the same score in different subgroups or is it biased towards one subgroup or another. Differential item functioning (DIF) can identify items that may be biased for one group or another and has been applied to measuring patient reported outcomes. Items may show DIF for different conditions and between cultures, however the SF-36 has not been specifically examined in an osteoarthritis population nor in a UK population. Hence, the aim of the study was to apply the DIF method to the SF-36 for a UK OA population. The sample comprised a community sample of 763 people with OA who participated in the Somerset and Avon Survey of Health. The SF-36 was explored for DIF with respect to demographic, social, clinical and psychological factors. Well developed ordinal regression models were used to identify DIF items. Results: DIF items were found by age (6 items), employment status (6 items), social class (2 items), mood (2 items), hip v knee (2 items), social deprivation (1 item) and body mass index (1 item). Although the impact of the DIF items rarely had a significant effect on the conclusions of group comparisons, in most cases there was a significant change in effect size. Overall, the SF-36 performed well with only a small number of DIF items identified, a reassuring finding in view of the frequent use of the SF-36 in OA. Nevertheless, where DIF items were identified it would be advisable to analyse data taking account of DIF items, especially when age effects are the focus of interest

Biology of advanced uveal melanoma and next steps for clinical therapeutics

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation's ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherpies are reviewed, and next steps in the development of clinical therapeutics are discussed

Divergent trajectories of cellular bioenergetics, intermediary metabolism and systemic redox status in survivors and non-survivors of critical illness.

BACKGROUND: Numerous pathologies result in multiple-organ failure, which is thought to be a direct consequence of compromised cellular bioenergetic status. Neither the nature of this phenotype nor its relevance to survival are well understood, limiting the efficacy of modern life-support. METHODS: To explore the hypothesis that survival from critical illness relates to changes in cellular bioenergetics, we combined assessment of mitochondrial respiration with metabolomic, lipidomic and redox profiling in skeletal muscle and blood, at multiple timepoints, in 21 critically ill patients and 12 reference patients. RESULTS: We demonstrate an end-organ cellular phenotype in critical illness, characterized by preserved total energetic capacity, greater coupling efficiency and selectively lower capacity for complex I and fatty acid oxidation (FAO)-supported respiration in skeletal muscle, compared to health. In survivors, complex I capacity at 48 h was 27% lower than in non-survivors (p = 0.01), but tended to increase by day 7, with no such recovery observed in non-survivors. By day 7, survivors' FAO enzyme activity was double that of non-survivors (p = 0.048), in whom plasma triacylglycerol accumulated. Increases in both cellular oxidative stress and reductive drive were evident in early critical illness compared to health. Initially, non-survivors demonstrated greater plasma total antioxidant capacity but ultimately higher lipid peroxidation compared to survivors. These alterations were mirrored by greater levels of circulating total free thiol and nitrosated species, consistent with greater reductive stress and vascular inflammation, in non-survivors compared to survivors. In contrast, no clear differences in systemic inflammatory markers were observed between the two groups. CONCLUSION: Critical illness is associated with rapid, specific and coordinated alterations in the cellular respiratory machinery, intermediary metabolism and redox response, with different trajectories in survivors and non-survivors. Unravelling the cellular and molecular foundation of human resilience may enable the development of more effective life-support strategies

The BSR-PsA:study protocol for the British Society for Rheumatology psoriatic arthritis register

Acknowledgements We acknowledge contribution of BSR-PsA study staff, under the supervision of KFK: Maureen Heddle, Barry Morris, Jonathan Lock and Jane Brady. We also acknowledge the support from the Centre for Healthcare Randomised Trials (CHaRT) at the University of Aberdeen, especially Mark Forrest and Brian Taylor, for database and IT support. We would like to thank Professor Iain McInnes from the University of Glasgow, and our International Advisory Committee (Professors Merete Hetland, Oliver Fitzgerald and Philip Mease), for their comments when developing the protocol and for advice in harmonising data collection with other international studies, and the staff at the British Society for Rheumatology, in particular Alan Roach, Ross Matthews, Chris Hiley and Debbie MacDonald. Finally, we are indebted to the staff at all participating NHS trusts (details of which are available from www.abdn.ac.uk/bsr-psa) and especially the NIHR Clinical Research Network research nurses for their assistance with participant recruitment and data collection. Funding The BSR-PsA is funded by the BSR as part of its rheumatology registers portfolio and, in turn, receives funding for this from pharmaceutical companies. At the time of publication, only Amgen (previously Celgene) have contributed to the funding of the BSR-PsA. Pharmaceutical companies providing funds to BSR do not participant in the conduct or oversight of the study. However, they do receive advance notice of publications on which they are able to comment. Companies contributing to the funding of the register can request anonymised data on clinically confirmed serious adverse events and some events of special interest (e.g. pregnancy) among participants prescribed the specific bDMARD or tsDMARD agents that they manufacture. Other than this information, they do not have access to any raw data. They may, however, request specific analyses to be performed, for which a pre-specific analysis plan is discussed, and additional funds are provided.Peer reviewedPublisher PD

Estrogenic activity assessment of environmental chemicals using in vitro assays: identification of two new estrogenic compounds.

Environmental chemicals with estrogenic activities have been suggested to be associated with deleterious effects in animals and humans. To characterize estrogenic chemicals and their mechanisms of action, we established in vitro and cell culture assays that detect human estrogen receptor [alpha] (hER[alpha])-mediated estrogenicity. First, we assayed chemicals to determine their ability to modulate direct interaction between the hER[alpha] and the steroid receptor coactivator-1 (SRC-1) and in a competition binding assay to displace 17ss-estradiol (E(2)). Second, we tested the chemicals for estrogen-associated transcriptional activity in the yeast estrogen screen and in the estrogen-responsive MCF-7 human breast cancer cell line. The chemicals investigated in this study were o,p'-DDT (racemic mixture and enantiomers), nonylphenol mixture (NPm), and two poorly analyzed compounds in the environment, namely, tris-4-(chlorophenyl)methane (Tris-H) and tris-4-(chlorophenyl)methanol (Tris-OH). In both yeast and MCF-7 cells, we determined estrogenic activity via the estrogen receptor (ER) for o,p'-DDT, NPm, and for the very first time, Tris-H and Tris-OH. However, unlike estrogens, none of these xenobiotics seemed to be able to induce ER/SRC-1 interactions, most likely because the conformation of the activated receptor would not allow direct contacts with this coactivator. However, these compounds were able to inhibit [(3)H]-E(2) binding to hER, which reveals a direct interaction with the receptor. In conclusion, the test compounds are estrogen mimics, but their molecular mechanism of action appears to be different from that of the natural hormone as revealed by the receptor/coactivator interaction analysis

Psychometric performance of the CAMPHOR and SF-36 in pulmonary hypertension

BACKGROUND: The Cambridge Pulmonary Hypertension Outcome Review (CAMPHOR) and the Medical Outcomes Study Short Form 36 (SF-36) are widely used to assess patient-reported outcome in individuals with pulmonary hypertension (PH). The aim of the study was to compare the psychometric properties of the two measures. METHODS: Participants were recruited from specialist PH centres in Australia and New Zealand. Participants completed the CAMPHOR and SF-36 at two time points two weeks apart. The SF-36 is a generic health status questionnaire consisting of 36 items split into 8 sections. The CAMPHOR is a PH-specific measure consisting of 3 scales; symptoms, activity limitations and needs-based QoL. The questionnaires were assessed for distributional properties (floor and ceiling effects), internal consistency (Cronbach's alpha), test-retest reliability and construct validity (scores by World Health Organisation functional classification). RESULTS: The sample comprised 65 participants (mean (SD) age = 57.2 (14.5) years; n(%) male = 14 (21.5%)). Most of the patients were in WHO class 2 (27.7%) and 3 (61.5%). High ceiling effects were observed for the SF-36 bodily pain, social functioning and role emotional domains. Test-retest reliability was poor for six of the eight SF-36 domains, indicating high levels of random measurement error. Three of the SF-36 domains did not distinguish between WHO classes. In contrast, all CAMPHOR scales exhibited good distributional properties, test retest reliability and distinguished between WHO functional classes. CONCLUSIONS: The CAMPHOR exhibited superior psychometric properties, compared with the SF-36, in the assessment of PH patient-reported outcome

Preparation, structured deliberate practice and decision making in elite level football: The case study of Gary Neville (Manchester United FC and England)

Decision making in elite level sporting competition is often regarded as distinguishing success from failure. As an intricate brain-based process it is unlike other physical processes because it is invisible and is typically only evidenced after the event. This case study shows how an individual achieved great success in elite level professional football through consistent positive decision making on and off the field of play. Through prolonged interviewing, Gary Neville, a player from Manchester United Football Club, explored personal behaviours, the structure and activities of deliberate practice and his professional choices in match preparation. His career-long devotion to purposeful organised practice was focused on cognition, physical preparation, context-relative physical action and refined repetition to optimise his mental comfort while enhancing his match day performances. This approach was underpinned by diligent personal and collective organisation and by concerted action. Results provide an insight into the categorical nature of his deliberate practice, sport-specific information processing and match-based decision making. At the operational level, his process was mediated by a complex mental representation of ongoing and anticipated game situations; these representations were continuously updated during each match. Allowing for the limitations of the design, implications are provided for developmental and educational coaching, match preparation, deliberate practice activity and improved use of the performance analysis software packages in professional football

Exploring differential item functioning in the Western Ontario and McMaster Universities osteoarthritis index (WOMAC)

Background: The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) is a widely used patient reported outcome in osteoarthritis. An important, but frequently overlooked, aspect of validating health outcome measures is to establish if items exhibit differential item functioning (DIF). That is, if respondents have the same underlying level of an attribute, does the item give the same score in different subgroups or is it biased towards one subgroup or another. The aim of the study was to explore DIF in the Likert format WOMAC for the first time in a UK osteoarthritis population with respect to demographic, social, clinical and psychological factors. Methods: The sample comprised a community sample of 763 people with osteoarthritis who participated in the Somerset and Avon Survey of Health. The WOMAC was explored for DIF by gender, age, social deprivation, social class, employment status, distress, body mass index and clinical factors. Ordinal regression models were used to identify DIF items. Results: After adjusting for age, two items were identified for the physical functioning subscale as having DIF with age identified as the DIF factor for 2 items, gender for 1 item and body mass index for 1 item. For the WOMAC pain subscale, for people with hip osteoarthritis one item was identified with age-related DIF. The impact of the DIF items rarely had a significant effect on the conclusions of group comparisons. Conclusions: Overall, the WOMAC performed well with only a small number of DIF items identified. However, as DIF items were identified in for the WOMAC physical functioning subscale it would be advisable to analyse data taking into account the possible impact of the DIF items when weight, gender or especially age effects, are the focus of interest in UK-based osteoarthritis studies. Similarly for the WOMAC pain subscale in people with hip osteoarthritis it would be worthwhile to analyse data taking into account the possible impact of the DIF item when age comparisons are of primary interest