231 research outputs found

    Factors Associated With Engagement With a Web-Based Lifestyle Intervention Following Provision of Coronary Heart Disease Risk: Mixed Methods Study

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    Background: Web-based interventions provide the opportunity to combine the tailored approach of face-to-face interventions with the scalability and cost-effectiveness of public health interventions. This potential is often limited by low engagement. A number of studies have described the characteristics of individuals who engage more in Web-based interventions but few have explored the reasons for these variations. Objective: We aimed to explore individual-level factors associated with different degrees of engagement with a Web-based behavior change intervention following provision of coronary heart disease (CHD) risk information, and the barriers and facilitators to engagement. Methods: This study involved the secondary analysis of data from the Information and Risk Modification Trial, a randomized controlled trial of a Web-based lifestyle intervention alone, or alongside information on estimated CHD risk. The intervention consisted of three interactive sessions, each lasting up to 60 minutes, delivered at monthly intervals. Participants were characterized as high engagers if they completed all three sessions. Thematic analysis of qualitative data from interviews with 37 participants was combined with quantitative data on usage of the Web-based intervention using a mixed-methods matrix, and data on the views of the intervention itself were analyzed across all participants. Results: Thirteen participants were characterized as low engagers and 24 as high engagers. There was no difference in age (P=.75), gender (P=.95), or level of risk (P=.65) between the groups. Low engagement was more often associated with: (1) reporting a negative emotional reaction in response to the risk score (P=.029), (2) perceiving that the intervention did not provide any new lifestyle information (P=.011), and (3) being less likely to have reported feeling an obligation to complete the intervention as part of the study (P=.019). The mixed-methods matrix suggested that there was also an association between low engagement and less success with previous behavior change attempts, but the statistical evidence for this association was weak (P=.16). No associations were seen between engagement and barriers or facilitators to health behavior change, or comments about the design of the intervention itself. The most commonly cited barriers related to issues with access to the intervention itself: either difficulties remembering the link to the site or passwords, a perceived lack of flexibility within the website, or lack of time. Facilitators included the nonjudgmental presentation of lifestyle information, the use of simple language, and the personalized nature of the intervention. Conclusions: This study shows that the level of engagement with a Web-based intervention following provision of CHD risk information is not influenced by the level of risk but by the individual’s response to the risk information, their past experiences of behavior change, the extent to which they consider the lifestyle information helpful, and whether they felt obliged to complete the intervention as part of a research study. A number of facilitators and barriers to Web-based interventions were also identified, which should inform future interventions.The INFORM study was funded by European Commission Framework 7 EPIC-CVD Grant agreement (No. 279233). NHS Blood and Transplant funded the INTERVAL trial. Deoxyribonucleic acid extraction and genotyping in INTERVAL/INFORM was funded by the United Kingdom National Institute of Health Research. The coordinating team for INTERVAL/INFORM at the Cardiovascular Epidemiology Unit of the University of Cambridge was supported by core funding from: United Kingdom Medical Research Council (G0800270), British Heart Foundation (SP/09/002), British Heart Foundation Cambridge Cardiovascular Centre of Excellence, and United Kingdom National Institute for Health Research Cambridge Biomedical Research Centre. JUS was funded by a National Institute for Health Clinical Lectureship and BS was supported by the Medical Research Council (MC_UU_12015/4)

    Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion

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    Danish Heart Foundation (Grant No. 15-R99-A5837-22920)Health Research Fund of Central Denmark RegionNational Institute for Health Research Biomedical Research Centre at Barts

    Influence of Cardiac CT based disease severity and clinical symptoms on the diagnostic performance of myocardial perfusion

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    Danish Heart Foundation (Grant No. 15-R99-A5837-22920)Health Research Fund of Central Denmark RegionNational Institute for Health Research Biomedical Research Centre at Barts

    Metabolic Stress Responses in Drosophila Are Modulated by Brain Neurosecretory Cells That Produce Multiple Neuropeptides

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    In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a): Drosophila tachykinin (DTK), short neuropeptide F (sNPF) and ion transport peptide (ITP). These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells

    The Atmosphere above Ny-Ålesund – Climate and global warming, ozone and surface UV radiation

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    The Arctic region is considered to be most sensitive to climate change, with warming in the Arctic occurring considerably faster than the global average due to several positive feedback mechanisms contributing to the “Arctic amplification”. Also the maritime and mountainous climate of Svalbard has undergone changes during the last decades. Here, the focus is set on the current atmospheric boundary conditions for the marine ecosystem in the Kongsfjorden area, discussed in the frame of long-term climatic observations in the larger regional and hemispheric context. During the last century, a general warming is found with temperature increases and precipitation changes varying in strength. During the last decades, a strong seasonality of the warming is observed in the Kongsfjorden area, with the strongest temperature increase occurring during the winter season. The winter warming is related to observed changes in the net longwave radiation. Moreover, changes in the net shortwave are observed during the summer period, attributed to the decrease in reflected radiation caused by the retreating snow cover. Another related aspect of radiation is the intensity of solar ultra-violet radiation that is closely coupled to the abundance of ozone in the column of air overhead. The long term evolution of ozone losses in the Arctic and their connection to climate change are discussed

    Structural Properties of MHC Class II Ligands, Implications for the Prediction of MHC Class II Epitopes

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    Major Histocompatibility class II (MHC-II) molecules sample peptides from the extracellular space allowing the immune system to detect the presence of foreign microbes from this compartment. Prediction of MHC class II ligands is complicated by the open binding cleft of the MHC class II molecule, allowing binding of peptides extending out of the binding groove. Furthermore, only a few HLA-DR alleles have been characterized with a sufficient number of peptides (100–200 peptides per allele) to derive accurate description of their binding motif. Little work has been performed characterizing structural properties of MHC class II ligands. Here, we perform one such large-scale analysis. A large set of SYFPEITHI MHC class II ligands covering more than 20 different HLA-DR molecules was analyzed in terms of their secondary structure and surface exposure characteristics in the context of the native structure of the corresponding source protein. We demonstrated that MHC class II ligands are significantly more exposed and have significantly more coil content than other peptides in the same protein with similar predicted binding affinity. We next exploited this observation to derive an improved prediction method for MHC class II ligands by integrating prediction of MHC- peptide binding with prediction of surface exposure and protein secondary structure. This combined prediction method was shown to significantly outperform the state-of-the-art MHC class II peptide binding prediction method when used to identify MHC class II ligands. We also tried to integrate N- and O-glycosylation in our prediction methods but this additional information was found not to improve prediction performance. In summary, these findings strongly suggest that local structural properties influence antigen processing and/or the accessibility of peptides to the MHC class II molecule

    The emerging structure of the Extended Evolutionary Synthesis: where does Evo-Devo fit in?

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    The Extended Evolutionary Synthesis (EES) debate is gaining ground in contemporary evolutionary biology. In parallel, a number of philosophical standpoints have emerged in an attempt to clarify what exactly is represented by the EES. For Massimo Pigliucci, we are in the wake of the newest instantiation of a persisting Kuhnian paradigm; in contrast, Telmo Pievani has contended that the transition to an EES could be best represented as a progressive reformation of a prior Lakatosian scientific research program, with the extension of its Neo-Darwinian core and the addition of a brand-new protective belt of assumptions and auxiliary hypotheses. Here, we argue that those philosophical vantage points are not the only ways to interpret what current proposals to ‘extend’ the Modern Synthesis-derived ‘standard evolutionary theory’ (SET) entail in terms of theoretical change in evolutionary biology. We specifically propose the image of the emergent EES as a vast network of models and interweaved representations that, instantiated in diverse practices, are connected and related in multiple ways. Under that assumption, the EES could be articulated around a paraconsistent network of evolutionary theories (including some elements of the SET), as well as models, practices and representation systems of contemporary evolutionary biology, with edges and nodes that change their position and centrality as a consequence of the co-construction and stabilization of facts and historical discussions revolving around the epistemic goals of this area of the life sciences. We then critically examine the purported structure of the EES—published by Laland and collaborators in 2015—in light of our own network-based proposal. Finally, we consider which epistemic units of Evo-Devo are present or still missing from the EES, in preparation for further analyses of the topic of explanatory integration in this conceptual framework

    Insulin Production and Signaling in Renal Tubules of Drosophila Is under Control of Tachykinin-Related Peptide and Regulates Stress Resistance

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    The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone

    Neuroarchitecture of Peptidergic Systems in the Larval Ventral Ganglion of Drosophila melanogaster

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    Recent studies on Drosophila melanogaster and other insects have revealed important insights into the functions and evolution of neuropeptide signaling. In contrast, in- and output connections of insect peptidergic circuits are largely unexplored. Existing morphological descriptions typically do not determine the exact spatial location of peptidergic axonal pathways and arborizations within the neuropil, and do not identify peptidergic in- and output compartments. Such information is however fundamental to screen for possible peptidergic network connections, a prerequisite to understand how the CNS controls the activity of peptidergic neurons at the synaptic level. We provide a precise 3D morphological description of peptidergic neurons in the thoracic and abdominal neuromeres of the Drosophila larva based on fasciclin-2 (Fas2) immunopositive tracts as landmarks. Comparing the Fas2 “coordinates” of projections of sensory or other neurons with those of peptidergic neurons, it is possible to identify candidate in- and output connections of specific peptidergic systems. These connections can subsequently be more rigorously tested. By immunolabeling and GAL4-directed expression of marker proteins, we analyzed the projections and compartmentalization of neurons expressing 12 different peptide genes, encoding approximately 75% of the neuropeptides chemically identified within the Drosophila CNS. Results are assembled into standardized plates which provide a guide to identify candidate afferent or target neurons with overlapping projections. In general, we found that putative dendritic compartments of peptidergic neurons are concentrated around the median Fas2 tracts and the terminal plexus. Putative peptide release sites in the ventral nerve cord were also more laterally situated. Our results suggest that i) peptidergic neurons in the Drosophila ventral nerve cord have separated in- and output compartments in specific areas, and ii) volume transmission is a prevailing way of peptidergic communication within the CNS. The data can further be useful to identify colocalized transmitters and receptors, and develop peptidergic neurons as new landmarks
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