151 research outputs found

    Choosing a screening tool to assess disordered eating in adolescents with type 1 diabetes mellitus

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    [Extract] Disturbed eating behaviours and insulin omission in adolescents with type 1 diabetes mellitus have concerned diabetes clinicians for decades, yet screening and management protocols using validated tools for this high risk group are lacking. Clinical eating disorders and milder forms of disordered eating can impact negatively on glycaemic control and are associated with serious health consequences (Rydall et al., 1997). Early detection and treatment of disturbed eating thoughts and behaviours is important (Goebel-Fabbri, 2009)

    Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures.

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    BACKGROUND: Neural circuits can spontaneously generate complex spatiotemporal firing patterns during development. This spontaneous activity is thought to help guide development of the nervous system. In this study, we had two aims. First, to characterise the changes in spontaneous activity in cultures of developing networks of either hippocampal or cortical neurons dissociated from mouse. Second, to assess whether there are any functional differences in the patterns of activity in hippocampal and cortical networks. RESULTS: We used multielectrode arrays to record the development of spontaneous activity in cultured networks of either hippocampal or cortical neurons every 2 or 3 days for the first month after plating. Within a few days of culturing, networks exhibited spontaneous activity. This activity strengthened and then stabilised typically around 21 days in vitro. We quantified the activity patterns in hippocampal and cortical networks using 11 features. Three out of 11 features showed striking differences in activity between hippocampal and cortical networks: (1) interburst intervals are less variable in spike trains from hippocampal cultures; (2) hippocampal networks have higher correlations and (3) hippocampal networks generate more robust theta-bursting patterns. Machine-learning techniques confirmed that these differences in patterning are sufficient to classify recordings reliably at any given age as either hippocampal or cortical networks. CONCLUSIONS: Although cultured networks of hippocampal and cortical networks both generate spontaneous activity that changes over time, at any given time we can reliably detect differences in the activity patterns. We anticipate that this quantitative framework could have applications in many areas, including neurotoxicity testing and for characterising the phenotype of different mutant mice. All code and data relating to this report are freely available for others to use.PC and AM were supported by the Wellcome Trust Genes to Cognition programme. PC received additional support from the Biotechnology and Biological Sciences Research Council (BB/H008608/1). EC was supported by a Wellcome Trust PhD studentship and Cambridge Biomedical Research Centre studentship. SJE was supported by an Engineering and Physical Sciences Research Council grant (EP/E002331/1).This is the final published version. It first appeared at http://link.springer.com/article/10.1186%2Fs13064-014-0028-0

    Suppressor of cytokine signalling protein SOCS3 expression is increased at sites of acute and chronic inflammation.

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    Treatment of cells with cytokines and growth factors leads to the synthesis of Suppressor of Cytokine Signalling (SOCS) proteins that act as potent negative regulators of signalling via the Jak/STAT pathway. We used immunohistochemistry to identify cells and pathologies where SOCS3 expression might influence acute and chronic inflammatory responses in human tissues. Epitope and GFP tagged SOCS3 fusion proteins were localised predominantly in the nucleus of transfected cells and a validated anti SOCS3 antiserum revealed the expression of SOCS3 in the nucleus and cytoplasm of macrophages, endothelial and epithelial cells in a wide range of normal tissues in tissue microarrays (n = 31 different tissues). Nuclear SOCS3 was only seen in cells expressing a high level of the protein. Comparative immunostaining of acute, chronically and granulomatously inflamed human tissues revealed higher levels of nuclear and cytoplasmic SOCS3 expression in inflamed than in corresponding normal tissues, particularly in recruited leukocyte populations, but also in epithelia. The staining appeared more intense, suggesting higher expression levels, in areas where inflammation was more acute, consistent with the time course of SOCS3 induction described in vitro. Expression of SOCS3 protein by leucocytes and other cell types in tissue sections could be a useful marker of cells undergoing acute or chronic stimulation by cytokines in vivo

    Diet, Physical Activity, and Obesity in School-Aged Indigenous Youths in Northern Australia

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    Purpose. To examine the relationship between diet, physical activity, and obesity in Indigenous youths from northern Australia. Methods. In a cross-sectional study, physical activity and dietary intake (“short nutrition questionnaire”) were assessed among all youths during a face-to-face interview. For 92 high school youths, additional dietary information was assessed using a food-frequency questionnaire. Height and weight were measured and BMI was calculated. Multiple logistic regression was used to assess associations. Results. Of the 277 youths included, 52% had ≤2 servings of fruit and 84% had <4 servings of vegetables per day; 65% ate fish and 27%, take-away food (“fast food”) at least twice a week. One in four ate local traditional sea food including turtle and dugong (a local sea mammal) at least twice a week. Overweight/obese youths engaged in fewer days of physical activity in the previous week than normal weight youths (OR = 2.52, 95% CI 1.43–4.40), though patterns of physical activity differed by sex and age (P < 0.001). Overweight/obese youths were 1.89 times (95% CI 1.07–3.35) more likely to eat dugong regularly than nonobese youths. Analysis of food-frequency data showed no difference by weight assessment among high-school students. Conclusions. Low fruit and vegetable intake were identified in these Indigenous youths. Regular consumption of fried dugong and low frequency of physical activity were associated with overweight/obesity reinforcing the need to devise culturally appropriate health promotion strategies and interventions for Indigenous youths aimed at improving their diet and increasing their physical activity

    Peripheral blood monocyte gene expression profile clinically stratifies patients with recent-onset type 1 diabetes

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    Novel biomarkers of disease progression after type 1 diabetes onset are needed. We profiled peripheral blood (PB) monocyte gene expression in six healthy subjects and 16 children with type 1 diabetes diagnosed ∼3 months previously and analyzed clinical features from diagnosis to 1 year. Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy control subjects, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA 1clevels during the first year, compared with patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g., induction of HIF1A, DDIT3, DDIT4, and GRP78). Quantitative PCR (qPCR) of a 9-gene panel correlated with glycemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. A PB gene expression signature correlates with glycemic control in the first year after diabetes diagnosis and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and post-onset and systemic stresses as contributors to innate immune function in type 1 diabetes. © 2012 by the American Diabetes Association

    The overlap between randomised evaluations of recruitment and retention interventions:An updated review of recruitment (Online Resource for Recruitment in Clinical triAls) and retention (Online Resource for Retention in Clinical triAls) literature

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    Background: The Online Resource for Recruitment in Clinical triAls (ORRCA) and the Online Resource for Retention in Clinical triAls (ORRCA2) were established to organise and map the literature addressing participant recruitment and retention within clinical research. The two databases are updated on an ongoing basis using separate but parallel systematic reviews. However, recruitment and retention of research participants is widely acknowledged to be interconnected. While interventions aimed at addressing recruitment challenges can impact retention and vice versa, it is not clear how well they are simultaneously considered within methodological research. This study aims to report the recent update of ORRCA and ORRCA2 with a special emphasis on assessing crossover of the databases and how frequently randomised studies of methodological interventions measure the impact on both recruitment and retention outcomes. Methods: Two parallel systematic reviews were conducted in line with previously reported methods updating ORRCA (recruitment) and ORRCA2 (retention) with publications from 2018 and 2019. Articles were categorised according to their evidence type (randomised evaluation, non-randomised evaluation, application and observation) and against the recruitment and retention domain frameworks. Articles categorised as randomised evaluations were compared to identify studies appearing in both databases. For randomised studies that were only in one database, domain categories were used to assess whether the methodological intervention was likely to impact on the alternate construct. For example, whether a recruitment intervention might also impact retention. Results: In total, 806 of 17,767 articles screened for the recruitment database and 175 of 18,656 articles screened for the retention database were added as result of the update. Of these, 89 articles were classified as ‘randomised evaluation’, of which 6 were systematic reviews and 83 were randomised evaluations of methodological interventions. Ten of the randomised studies assessed recruitment and retention and were included in both databases. Of the randomised studies only in the recruitment database, 48/55 (87%) assessed the content or format of participant information which could have an impact on retention. Of the randomised studies only in the retention database, 6/18 (33%) assessed monetary incentives, 4/18 (22%) assessed data collection location and methods and 3/18 (17%) assessed non-monetary incentives, all of which could have an impact on recruitment. Conclusion: Only a small proportion of randomised studies of methodological interventions assessed the impact on both recruitment and retention despite having a potential impact on both outcomes. Where possible, an integrated approach analysing both constructs should be the new standard for these types of evaluations to ensure that improvements to recruitment are not at the expense of retention and vice versa.</p

    The overlap between randomised evaluations of recruitment and retention interventions:An updated review of recruitment (Online Resource for Recruitment in Clinical triAls) and retention (Online Resource for Retention in Clinical triAls) literature

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    Background: The Online Resource for Recruitment in Clinical triAls (ORRCA) and the Online Resource for Retention in Clinical triAls (ORRCA2) were established to organise and map the literature addressing participant recruitment and retention within clinical research. The two databases are updated on an ongoing basis using separate but parallel systematic reviews. However, recruitment and retention of research participants is widely acknowledged to be interconnected. While interventions aimed at addressing recruitment challenges can impact retention and vice versa, it is not clear how well they are simultaneously considered within methodological research. This study aims to report the recent update of ORRCA and ORRCA2 with a special emphasis on assessing crossover of the databases and how frequently randomised studies of methodological interventions measure the impact on both recruitment and retention outcomes. Methods: Two parallel systematic reviews were conducted in line with previously reported methods updating ORRCA (recruitment) and ORRCA2 (retention) with publications from 2018 and 2019. Articles were categorised according to their evidence type (randomised evaluation, non-randomised evaluation, application and observation) and against the recruitment and retention domain frameworks. Articles categorised as randomised evaluations were compared to identify studies appearing in both databases. For randomised studies that were only in one database, domain categories were used to assess whether the methodological intervention was likely to impact on the alternate construct. For example, whether a recruitment intervention might also impact retention. Results: In total, 806 of 17,767 articles screened for the recruitment database and 175 of 18,656 articles screened for the retention database were added as result of the update. Of these, 89 articles were classified as ‘randomised evaluation’, of which 6 were systematic reviews and 83 were randomised evaluations of methodological interventions. Ten of the randomised studies assessed recruitment and retention and were included in both databases. Of the randomised studies only in the recruitment database, 48/55 (87%) assessed the content or format of participant information which could have an impact on retention. Of the randomised studies only in the retention database, 6/18 (33%) assessed monetary incentives, 4/18 (22%) assessed data collection location and methods and 3/18 (17%) assessed non-monetary incentives, all of which could have an impact on recruitment. Conclusion: Only a small proportion of randomised studies of methodological interventions assessed the impact on both recruitment and retention despite having a potential impact on both outcomes. Where possible, an integrated approach analysing both constructs should be the new standard for these types of evaluations to ensure that improvements to recruitment are not at the expense of retention and vice versa.</p

    Refining and testing the diagnostic accuracy of an assessment tool (PAT-POPS) to predict admission and discharge of children and young people who attend an emergency department : protocol for an observational study

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    Background: Increasing attendances by children (aged 0–16 years) to United Kingdom Emergency Departments (EDs) challenges patient safety within the National Health Service (NHS) with health professionals required to make complex judgements on whether children attending urgent and emergency care services can be sent home safely or require admission. Health regulation bodies have recommended that an early identification systems should be developed to recognise children developing critical illnesses. The Pennine Acute Hospitals NHS Trust Paediatric Observation Priority Score (PAT-POPS) was developed as an ED-specific tool for this purpose. This study aims to revise and improve the existing tool and determine its utility in determining safe admission and discharge decision making. Methods/design: An observational study to improve diagnostic accuracy using data from children and young people attending the ED and Urgent Care Centre (UCC) at three hospitals over a 12 month period. The data being collected is part of routine practice; therefore opt-out methods of consent will be used. The reference standard is admission or discharge. A revised PAT-POPs scoring tool will be developed using clinically guided logistic regression models to explore which components best predict hospital admission and safe discharge. Suitable cut-points for safe admission and discharge will be established using sensitivity and specificity as judged by an expert consensus meeting. The diagnostic accuracy of the revised tool will be assessed, and it will be compared to the former version of PAT-POPS using ROC analysis. Discussion: This new predictive tool will aid discharge and admission decision-making in relation to children and young people in hospital urgent and emergency care facilities. Trial registration: NIHR RfPB Grant: PB-PG-0815-20034. ClinicalTrials.gov: 213469. Retrospectively registered on 11 April 2018. Keywords: Paediatric, Emergency department, Diagnostic accuracy, Early identification systems, screening tool, Observational, Early warning score, Early warning system, hospital admission
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