Tensions in intergenerational practice guidance: intergroup contact versus community development

Intergenerational practice (IP) is an approach within community health promotion which aims to bring older and younger community members together in collaborative activity. Little research has critically examined the assumptions and values within IP and their implications for these communities. A sample of 15 IP planning documents were analysed using a social constructionist thematic analysis (Braun & Clarke2006) guided by Prior’s (2008) concept of documents as active agents. Three tensions were identified: a community-led model versus a contact model; old and young as targets versus older people as targets; and process-focused versus out­come-focused evaluation. IP has relied on contact theory as a mechanism of change, which has rooted IP to an overly individualistic practice tar­geted at older people (rather than all ages). In contrast, the community-led ethos of IP was also evident alongside values of mutual benefit for old and young, and a desire for more process-focused evaluation

Deep imaging: How much of the proteome does current top-down technology already resolve?

Effective proteome analyses are based on interplay between resolution and detection. It had been claimed that resolution was the main factor limiting the use of two-dimensional gel electrophoresis. Improved protein detection now indicates that this is unlikely to be the case. Using a highly refined protocol, the rat brain proteome was extracted, resolved, and detected. In order to overcome the stain saturation threshold, high abundance protein species were excised from the gel following standard imaging. Gels were then imaged again using longer exposure times, enabling detection of lower abundance, less intensely stained protein species. This resulted in a significant enhancement in the detection of resolved proteins, and a slightly modified digestion protocol enabled effective identification by standard mass spectrometric methods. The data indicate that the resolution required for comprehensive proteome analyses is already available, can assess multiple samples in parallel, and preserve critical information concerning post-translational modifications. Further optimization of staining and detection methods promises additional improvements to this economical, widely accessible and effective top-down approach to proteome analysis. © 2014 Wright et al

Representation of behaviour change interventions and their evaluation: Development of the Upper Level of the Behaviour Change Intervention Ontology [version 2; peer review: 1 approved, 1 approved with reservations]

Background: Behaviour change interventions (BCI), their contexts and evaluation methods are heterogeneous, making it difficult to synthesise evidence and make recommendations for real-world policy and practice. Ontologies provide a means for addressing this. They represent knowledge formally as entities and relationships using a common language able to cross disciplinary boundaries and topic domains. This paper reports the development of the upper level of the Behaviour Change Intervention Ontology (BCIO), which provides a systematic way to characterise BCIs, their contexts and their evaluations. Methods: Development took place in four steps. (1) Entities and relationships were identified by behavioural and social science experts, based on their knowledge of evidence and theory, and their practical experience of behaviour change interventions and evaluations. (2) The outputs of the first step were critically examined by a wider group of experts, including the study ontology expert and those experienced in annotating relevant literature using the initial ontology entities. The outputs of the second step were tested by (3) feedback from three external international experts in ontologies and (4) application of the prototype upper-level BCIO to annotating published reports; this informed the final development of the upper-level BCIO. Results: The final upper-level BCIO specifies 42 entities, including the BCI scenario, elaborated across 21 entities and 7 relationship types, and the BCI evaluation study comprising 10 entities and 9 relationship types. BCI scenario entities include the behaviour change intervention (content and delivery), outcome behaviour, mechanism of action, and its context, which includes population and setting. These entities have corresponding entities relating to the planning and reporting of interventions and their evaluations. Conclusions: The upper level of the BCIO provides a comprehensive and systematic framework for representing BCIs, their contexts and their evaluations. Keyword

Development of an Intervention Setting Ontology for behaviour change: Specifying where interventions take place

Background: Contextual factors such as an intervention's setting are key to understanding how interventions to change behaviour have their effects and patterns of generalisation across contexts. The intervention's setting is not consistently reported in published reports of evaluations. Using ontologies to specify and classify intervention setting characteristics enables clear and reproducible reporting, thus aiding replication, implementation and evidence synthesis. This paper reports the development of a Setting Ontology for behaviour change interventions as part of a Behaviour Change Intervention Ontology, currently being developed in the Wellcome Trust funded Human Behaviour-Change Project. Methods: The Intervention Setting Ontology was developed following methods for ontology development used in the Human Behaviour-Change Project: 1) Defining the ontology's scope, 2) Identifying key entities by reviewing existing classification systems (top-down) and 100 published behaviour change intervention reports (bottom-up), 3) Refining the preliminary ontology by literature annotation of 100 reports, 4) Stakeholder reviewing by 23 behavioural science and public health experts to refine the ontology, 5) Assessing inter-rater reliability of using the ontology by two annotators familiar with the ontology and two annotators unfamiliar with it, 6) Specifying ontological relationships between setting entities and 7) Making the Intervention Setting Ontology machine-readable using Web Ontology Language (OWL) and publishing online. Results: The Intervention Setting Ontology consists of 72 entities structured hierarchically with two upper-level classes: Physical setting including Geographic location, Attribute of location (including Area social and economic condition, Population and resource density sub-levels) and Intervention site (including Facility, Transportation and Outdoor environment sub-levels), as well as Social setting. Inter-rater reliability was found to be 0.73 (good) for those familiar with the ontology and 0.61 (acceptable) for those unfamiliar with it. Conclusion: The Intervention Setting Ontology can be used to code information from diverse sources, annotate the setting characteristics of existing intervention evaluation reports and guide future reporting

Mouse hypothalamic GT1-7 cells demonstrate AMPK-dependent intrinsic glucose-sensing behaviour.

AIMS/HYPOTHESIS: Hypothalamic glucose-excited (GE) neurons contribute to whole-body glucose homeostasis and participate in the detection of hypoglycaemia. This system appears defective in type 1 diabetes, in which hypoglycaemia commonly occurs. Unfortunately, it is at present unclear which molecular components required for glucose sensing are produced in individual neurons and how these are functionally linked. We used the GT1-7 mouse hypothalamic cell line to address these issues. METHODS: Electrophysiological recordings, coupled with measurements of gene expression and protein levels and activity, were made from unmodified GT1-7 cells and cells in which AMP-activated protein kinase (AMPK) catalytic subunit gene expression and activity were reduced. RESULTS: Hypothalamic GT1-7 neurons express the genes encoding glucokinase and ATP-sensitive K(+) channel (K(ATP)) subunits K ( ir ) 6.2 and Sur1 and exhibit GE-type glucose-sensing behaviour. Lowered extracellular glucose concentration hyperpolarised the cells in a concentration-dependent manner, an outcome that was reversed by tolbutamide. Inhibition of glucose uptake or metabolism hyperpolarised cells, showing that energy metabolism is required to maintain their resting membrane potential. Short hairpin (sh)RNA directed to Ampkα2 (also known as Prkaa2) reduced GT1-7 cell AMPKα2, but not AMPKα1, activity and lowered the threshold for hypoglycaemia-induced hyperpolarisation. shAmpkα1 (also known as Prkaa1) had no effect on glucose-sensing or AMPKα2 activity. Decreased uncoupling protein 2 (Ucp2) mRNA was detected in AMPKα2-reduced cells, suggesting that AMPKα2 regulates UCP2 levels. CONCLUSIONS/INTERPRETATION: We have demonstrated that GT1-7 cells closely mimic GE neuron glucose-sensing behaviour, and reducing AMPKα2 blunts their responsiveness to hypoglycaemic challenge, possibly by altering UCP2 activity. These results show that suppression of AMPKα2 activity inhibits normal glucose-sensing behaviour and may contribute to defective detection of hypoglycaemia.This study was funded by: grants from the Wellcome Trust (grant numbers 068692 and 086989) and Diabetes UK (grant number RD08/0003681) to M.L.J. Ashford; a Juvenile Diabetes Research Foundation (JDRF) Postdoctoral Fellowship to C. Beall (grant number 3-576-2010); grants from JDRF and European Foundation for the study of Diabetes to R.J. McCrimmon, and from the British Heart Foundation to A. Jovanović

Defining emergency department episodes by severity and intensity: A 15-year study of Medicare beneficiaries

Background. Episodes of Emergency Department (ED) service use among older adults previously have not been constructed, or evaluated as multi-dimensional phenomena. In this study, we constructed episodes of ED service use among a cohort of older adults over a 15-year observation period, measured the episodes by severity and intensity, and compared these measures in predicting subsequent hospitalization. Methods. We conducted a secondary analysis of the prospective cohort study entitled the Survey on Assets and Health Dynamics among the Oldest Old (AHEAD). Baseline (1993) data on 5,511 self-respondents 70 years old were linked to their Medicare claims for 1991-2005. Claims then were organized into episodes of ED care according to Medicare guidelines. The severity of ED episodes was measured with a modified-NYU algorithm using ICD9-CM diagnoses, and the intensity of the episodes was measured using CPT codes. Measures were evaluated against subsequent hospitalization to estimate comparative predictive validity. Results. Over 15 years, three-fourths (4,171) of the 5,511 AHEAD participants had at least 1 ED episode, with a mean of 4.5 episodes. Cross-classification indicated the modified-NYU severity measure and the CPT-based intensity measure captured different aspects of ED episodes (kappa = 0.18). While both measures were significant independent predictors of hospital admission from ED episodes, the CPT measure had substantially higher predictive validity than the modified-NYU measure (AORs 5.70 vs. 3.31; p < .001). Conclusions. We demonstrated an innovative approach for how claims data can be used to construct episodes of ED care among a sample of older adults. We also determined that the modified-NYU measure of severity and the CPT measure of intensity tap different aspects of ED episodes, and that both measures were predictive of subsequent hospitalization. © 2010 Kaskie et al; licensee BioMed Central Ltd

KCa1.1, a calcium-activated potassium channel subunit alpha 1, is targeted by miR-17-5p and modulates cell migration in malignant pleural mesothelioma

© 2016 Lin et al. Background: Malignant pleural mesothelioma (MPM) is an aggressive, locally invasive, cancer elicited by asbestos exposure and almost invariably a fatal diagnosis. To date, we are one of the leading laboratory that compared microRNA expression profiles in MPM and normal mesothelium samples in order to identify dysregulated microRNAs with functional roles in mesothelioma. We interrogated a significant collection of MPM tumors and normal pleural samples in our biobank in search for novel therapeutic targets. Methods: Utilizing mRNA-microRNA correlations based on differential gene expression using Gene Set Enrichment Analysis (GSEA), we systematically combined publicly available gene expression datasets with our own MPM data in order to identify candidate targets for MPM therapy. Results: We identified enrichment of target binding sites for the miR-17 and miR-30 families in both MPM tumors and cell lines. RT-qPCR revealed that members of both families were significantly downregulated in MPM tumors and cell lines. Interestingly, lower expression of miR-17-5p (P = 0.022) and miR-20a-5p (P = 0.026) was clearly associated with epithelioid histology. We interrogated the predicted targets of these differentially expressed microRNA families in MPM cell lines, and identified KCa1.1, a calcium-activated potassium channel subunit alpha 1 encoded by the KCNMA1 gene, as a target of miR-17-5p. KCa1.1 was overexpressed in MPM cells compared to the (normal) mesothelial line MeT-5A, and was also upregulated in patient tumor samples compared to normal mesothelium. Transfection of MPM cells with a miR-17-5p mimic or KCNMA1-specific siRNAs reduced mRNA expression of KCa1.1 and inhibited MPM cell migration. Similarly, treatment with paxilline, a small molecule inhibitor of KCa1.1, resulted in suppression of MPM cell migration. Conclusion: These functional data implicating KCa1.1 in MPM cell migration support our integrative approach using MPM gene expression datasets to identify novel and potentially druggable targets

Early Life Socioeconomic Circumstance and Late Life Brain Hyperintensities : A Population Based Cohort Study

Funding: Image acquisition and image analysis for this study was funded by the Alzheimer's Research Trust (now Alzheimer's Research UK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36), without whom this research would not have been possible.Peer reviewedPublisher PD