Distinct emphysema subtypes defined by quantitative CT analysis are associated with specific pulmonary matrix metalloproteinases.

BACKGROUND: Emphysema is characterised by distinct pathological sub-types, but little is known about the divergent underlying aetiology. Matrix-metalloproteinases (MMPs) are proteolytic enzymes that can degrade the extracellular matrix and have been identified as potentially important in the development of emphysema. However, the relationship between MMPs and emphysema sub-type is unknown. We investigated the role of MMPs and their inhibitors in the development of emphysema sub-types by quantifying levels and determining relationships with these sub-types in mild-moderate COPD patients and ex/current smokers with preserved lung function. METHODS: Twenty-four mild-moderate COPD and 8 ex/current smokers with preserved lung function underwent high resolution CT and distinct emphysema sub-types were quantified using novel local histogram-based assessment of lung density. We analysed levels of MMPs and tissue inhibitors of MMPs (TIMPs) in bronchoalveolar lavage (BAL) and assessed their relationship with these emphysema sub-types. RESULTS: The most prevalent emphysema subtypes in COPD subjects were mild and moderate centrilobular (CLE) emphysema, while only small amounts of severe centrilobular emphysema, paraseptal emphysema (PSE) and panlobular emphysema (PLE) were present. MMP-3, and -10 associated with all emphysema sub-types other than mild CLE, while MMP-7 and -8 had associations with moderate and severe CLE and PSE. MMP-9 also had associations with moderate CLE and paraseptal emphysema. Mild CLE occurred in substantial quantities irrespective of whether airflow obstruction was present and did not show any associations with MMPs. CONCLUSION: Multiple MMPs are directly associated with emphysema sub-types identified by CT imaging, apart from mild CLE. This suggests that MMPs play a significant role in the tissue destruction seen in the more severe sub-types of emphysema, whereas early emphysematous change may be driven by a different mechanism. TRIAL REGISTRATION: Trial registration number NCT01701869

Methods for the thematic synthesis of qualitative research in systematic reviews

<p>Abstract</p> <p>Background</p> <p>There is a growing recognition of the value of synthesising qualitative research in the evidence base in order to facilitate effective and appropriate health care. In response to this, methods for undertaking these syntheses are currently being developed. Thematic analysis is a method that is often used to analyse data in primary qualitative research. This paper reports on the use of this type of analysis in systematic reviews to bring together and integrate the findings of multiple qualitative studies.</p> <p>Methods</p> <p>We describe thematic synthesis, outline several steps for its conduct and illustrate the process and outcome of this approach using a completed review of health promotion research. Thematic synthesis has three stages: the coding of text 'line-by-line'; the development of 'descriptive themes'; and the generation of 'analytical themes'. While the development of descriptive themes remains 'close' to the primary studies, the analytical themes represent a stage of interpretation whereby the reviewers 'go beyond' the primary studies and generate new interpretive constructs, explanations or hypotheses. The use of computer software can facilitate this method of synthesis; detailed guidance is given on how this can be achieved.</p> <p>Results</p> <p>We used thematic synthesis to combine the studies of children's views and identified key themes to explore in the intervention studies. Most interventions were based in school and often combined learning about health benefits with 'hands-on' experience. The studies of children's views suggested that fruit and vegetables should be treated in different ways, and that messages should not focus on health warnings. Interventions that were in line with these suggestions tended to be more effective. Thematic synthesis enabled us to stay 'close' to the results of the primary studies, synthesising them in a transparent way, and facilitating the explicit production of new concepts and hypotheses.</p> <p>Conclusion</p> <p>We compare thematic synthesis to other methods for the synthesis of qualitative research, discussing issues of context and rigour. Thematic synthesis is presented as a tried and tested method that preserves an explicit and transparent link between conclusions and the text of primary studies; as such it preserves principles that have traditionally been important to systematic reviewing.</p

Student evaluation of an OSCE in paediatrics at the University of the West Indies, Jamaica

BACKGROUND: The Faculty of Medical Sciences, University of the West Indies first implemented the Objective Structured Clinical Examination (OSCE) in the final MB Examination in Medicine and Therapeutics during the 2000–2001 academic year. Simultaneously, the Child Health Department initiated faculty and student training, and instituted the OSCE as an assessment instrument during the Child Health (Paediatric) clerkship in year 5. The study set out to explore student acceptance of the OSCE as part of an evaluation of the Child Health clerkship. METHODS: A self-administered questionnaire was completed by successive groups of students immediately after the OSCE at the end of each clerkship rotation. Main outcome measures were student perception of examination attributes, which included the quality of instructions and organisation, the quality of performance, authenticity and transparency of the process, and usefulness of the OSCE as an assessment instrument compared to other formats. RESULTS: There was overwhelming acceptance of the OSCE in Child Health with respect to the comprehensiveness (90%), transparency (87%), fairness (70%) and authenticity of the required tasks (58–78%). However, students felt that it was a strong anxiety-producing experience. And concerns were expressed regarding the ambiguity of some questions and inadequacy of time for expected tasks. CONCLUSION: Student feedback was invaluable in influencing faculty teaching, curriculum direction and appreciation of student opinion. Further psychometric evaluation will strengthen the development of the OSCE

Image-guided Radiotherapy to Manage Respiratory Motion: Lung and Liver.

Organ motion as a result of respiratory and cardiac motion poses significant challenges for the accurate delivery of radiotherapy to both the thorax and the upper abdomen. Modern imaging techniques during radiotherapy simulation and delivery now permit better quantification of organ motion, which in turn reduces tumour and organ at risk position uncertainty. These imaging advances, coupled with respiratory correlated radiotherapy delivery techniques, have led to the development of a range of approaches to manage respiratory motion. This review summarises the key strategies of image-guided respiratory motion management with a focus on lung and liver radiotherapy

Amplification of Fluctuations in Unstable Systems with Disorder

We study the early-stage kinetics of thermodynamically unstable systems with quenched disorder. We show analytically that the growth of initial fluctuations is amplified by the presence of disorder. This is confirmed by numerical simulations of morphological phase separation (MPS) in thin liquid films and spinodal decomposition (SD) in binary mixtures. We also discuss the experimental implications of our results.Comment: 15 pages, 4 figure

Supporting disengaged children and young people living with diabetes to self-care: a qualitative study in a socially disadvantaged and ethnically diverse urban area

OBJECTIVE: To explore how to enhance services to support the self-care of children and young people (CYP) clinically considered 'disengaged' by diabetes services. DESIGN: Qualitative study. SETTING: Two diabetes clinics in an ethnically diverse and socially disadvantaged urban area in the UK. Eligible participants were CYP living with type 1 or type 2 diabetes aged between 10 and 25 years who did not attend their last annual hospital appointment. PARTICIPANTS: 22 CYP (14 female and 8 male) aged between 10 and 19 years old took part. The sample was diverse in terms of ethnicity, age at diagnosis, family composition and presence of diabetes among other family members. DATA COLLECTION: Semistructured interviews. DATA ANALYSIS: Data were analysed thematically. RESULTS: Analysis of participant accounts confirmed the crucial importance of non-medicalised care in CYP diabetes care. A life plan was considered as important to participants as a health plan. Participants valued the holistic support provided by friends, family members and school teachers. However, they found structural barriers in their health and educational pathways as well as disparities in the quality of support at critical moments along the life course. They actively tried to maximise their well-being by balancing life priorities against diabetes priorities. Combined, these features could undermine participants engagement with health services where personal strategies were often held back or edited out of clinical appointments in fear of condemnation. CONCLUSION: We demonstrate why diabetes health teams need to appreciate the conflicting pressures experienced by CYP and to coproduce more nuanced health plans for addressing their concerns regarding identity and risk taking behaviours in the context of their life-worlds. Exploring these issues and identifying ways to better support CYP to address them more proactively should reduce disengagement and set realistic health outcomes that make best use of medical resources

The Sac1 Lipid Phosphatase Regulates Cell Shape Change and the JNK Cascade during Dorsal Closure in Drosophila

AbstractThe Sac1 lipid phosphatase dephosphorylates several phosphatidylinositol (PtdIns) phosphates and, in yeast, regulates a diverse range of cellular processes including organization of the actin cytoskeleton and secretion [1]. We have identified mutations in the gene encoding Drosophila Sac1. sac1 mutants die as embryos with defects in dorsal closure (DC). DC involves the migration of the epidermis to close a hole in the dorsal surface of the embryo occupied by the amnioserosa. It requires cell shape change in both the epidermis and amnioserosa and activation of a Jun N-terminal kinase (JNK) MAPK cascade in the leading edge cells of the epidermis [2]. Loss of Sac1 leads to the improper activation of two key events in DC: cell shape change in the amnioserosa and JNK signaling. sac1 interacts genetically with other participants in these two events, and our data suggest that loss of Sac1 leads to upregulation of one or more signals controlling DC. This study is the first report of a role for Sac1 in the development of a multicellular organism

Physical activity self-management interventions for adults with spinal cord injury: Part 2 – Exploring the generalizability of findings from research to practice

Despite the benefits associated with regular participation in physical activity, individuals with spinal cord injury (SCI) remain insufficiently active. The ability to self-manage participation may increase physical activity levels, but only if self-management interventions can be implemented in the ‘real world’. The purpose of this review was to examine the degree to which authors of published studies of LTPA self-management interventions for individuals with SCI have reported on factors that could increase the likelihood of translating this research into practice. A systematic search of five databases was conducted, yielding 33 eligible studies representing 31 interventions. Each intervention was assessed using the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) Framework and the PRECIS-2 (PRagmatic-Explanatory Continuum Indicator Summary) tool. The most commonly reported RE-AIM dimensions were Effectiveness (51.0% of interventions) and Reach (18.5%), followed by Implementation (14.2%), Maintenance (13.8%), and Adoption (4.0%). Overall, interventions were scored as primarily explanatory in five of the nine PRECIS-2 domains (recruitment, primary analysis, organization, flexibility [delivery], follow-up) and primarily pragmatic in one domain (setting). These findings suggest that while some LTPA self-management interventions for individuals with SCI are intended to be translated to real world settings, limited information is available to understand the degree to which this has been accomplished. Enhanced reporting of factors that could increase the likelihood of translating these interventions into practice is recommended