Consenting to health record linkage: evidence from a multi-purpose longitudinal survey of a general population

Background: The British Household Panel Survey (BHPS) is the first long-running UK longitudinal survey with a non-medical focus and a sample covering the whole age range to have asked for permission to link to a range of administrative health records. This study determines whether informed consent led to selection bias and reflects on the value of the BHPS linked with health records for epidemiological research. Methods. Multivariate logistical regression is used, with whether the respondent gave consent to data linkage or not as the dependent variable. Independent variables were entered as four blocks; (i) a set of standard demographics likely to be found in most health registration data, (ii) a broader set of socio-economic characteristics, (iii) a set of indicators of health conditions and (iv) information about the use of health services. Results: Participants aged 16-24, males and those living in England were more likely to consent. Consent is not biased with respect to socio-economic characteristics or health. Recent users of GP services are underrepresented among consenters. Conclusions: Whilst data could only be linked for a minority of BHPS participants, the BHPS offers a great range of information on people's life histories, their attitudes and behaviours making it an invaluable source for epidemiological research. © 2012 Knies et al; licensee BioMed Central Ltd

Lehr- und lernrelevante Diversität an der Fachhochschule Köln

Studierende der Fachhochschule Köln unterscheiden sich in zunehmendem Maße in ihren sozio-kulturellen, bildungsbiografischen und kognitiven Voraussetzungen für einen hochschulischen Bildungsprozess. Lehre zeigt sich vor dem Hintergrund dieser Diversität zunehmend als Herausforderung. Ausgehend vom Ziel, studentisches Lern- und Arbeitsverhalten verstärkt auf Studienerfolg und die Gestaltung von Lehrveranstaltungen auf heterogene Zielgruppen auszurichten, wurde die Studie „Diversity Forschung“ durchgeführt, um Status quo der und Gestaltungsspielräume für Diversity-bezogene Aufmerksamkeit und Verständnis für lehr- und lernrelevante Effekte zu identifizieren. Die Studie wurde mit dem Forschungstypus Innerinstitutionelle Hochschulforschung durchgeführt. Was kann und was sollte eine Hochschule über ihr Kerngeschäft Studium und Lehre wissen, wie kommt sie zu diesem Wissen und was fängt sie damit an? Innerinstitutionelle Hochschulforschung macht Handlungen und Prozesse im Rahmen von Studium und Lehre in den Strukturen der Hochschule transparent und kann so die institutionelle Selbstaufklärung und das Qualitätsmanagement stützen. Gegenstand dieses Berichts sind Ansatz, Methoden und Befunde innerinstitutioneller hochschuldidaktischer Forschung an der Fachhochschule Köln. Schwerpunkt ist die Diversität der Lehrenden und Lernenden als Akteursgruppen und -gemeinschaft in Sachen Studium und Lehre. Ausgangspunkt war die Absicht, den Status lehr- und lernrelevanter Diversität zu erkennen, Gestaltungsspielräume für den Umgang mit Diversität auszuloten und Implementationen innovativer Lehrkonzepte für erfolgreiches Studieren mit einem Monitoring-Ansatz zu begleiten. Weiterer Gegenstand des Berichts sind die Einflüsse dieser Forschung als Selbstbeobachtung auf intendierte Change-Prozesse zur Verbesserung von Studium und Lehre und die Frage, wie Selbstbeobachtungsstrategien als hochschuldidaktische Hochschulforschung weiter elaboriert werden und deren Befunde in die hochschuldidaktische Praxis und die Lehr- und Lernkultur der Fachhochschule Köln gelangen können

CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis

Macrophages abundantly found in the tumor microenvironment enhance malignancy(1). At metastatic sites a distinct population of metastasis associated macrophages (MAMs) promote tumor cell extravasation, seeding and persistent growth(2). Our study has defined the origin of these macrophages by showing Gr1+ inflammatory monocytes (IMs) are preferentially recruited to pulmonary metastases but not primary mammary tumors, a process also found for human IMs in pulmonary metastases of human breast cancer cells. The recruitment of these CCR2 (receptor for chemokine CCL2) expressing IMs and subsequently MAMs and their interaction with metastasizing tumor cells is dependent on tumor and stromal synthesized CCL2 (FigS1). Inhibition of CCL2/CCR2 signaling using anti-CCL2 antibodies blocks IM recruitment and inhibits metastasis in vivo and prolongs the survival of tumor-bearing mice. Depletion of tumor cell-derived CCL2 also inhibits metastatic seeding. IMs promote tumor cell extravasation in a process that requires monocyte-derived VEGF. CCL2 expression and macrophage infiltration are correlated with poor prognosis and metastatic disease in human breast cancer (Fig S2)(3-6). Our data provides the mechanistic link between these two clinical associations and indicates new therapeutic targets for treating metastatic breast disease

Ontology-based support for taxonomic functions

This paper reports on an investigation into the use of ontology technologies to support taxonomic functions. Support for taxonomy is imperative given several recent discussions and publications that voiced concern over the taxonomic impediment within the broader context of the life sciences. Taxonomy is defined as the scientific classification, description and grouping of biological organisms into hierarchies based on sets of shared characteristics, and documenting the principles that enforce such classification. Under taxonomic functions we identified two broad categories: the classification functions concerned with identification and naming of organisms, and secondly classification functions concerned with categorization and revision (i.e. grouping and describing, or revisiting existing groups and descriptions). Ontology technologies within the broad field of artificial intelligence include computational ontologies that are knowledge representation mechanisms using standardized representations that are based on description logics (DLs). This logic base of computational ontologies provides for the computerized capturing and manipulation of knowledge. Furthermore, the set-theoretical basis of computational ontologies ensures particular suitability towards classification, which is considered as a core function of systematics or taxonomy. Using the specific case of Afrotropical bees, this experimental research study represents the taxonomic knowledge base as an ontology, explore the use of available reasoning algorithms to draw the necessary inferences that support taxonomic functions (identification and revision) over the ontology and implement a Web-based application (the WOC). The contributions include the ontology, a reusable and standardized computable knowledge base of the taxonomy of Afrotropical bees, as well as the WOC and the evaluation thereof by experts

The predictability of the extratropical stratosphere on monthly time-scales and its impact on the skill of tropospheric forecasts

This is the final version of the article. Available from Wiley via the DOI in this record.Extreme variability of the winter- and spring-time stratospheric polar vortex has been shown to affect extratropical tropospheric weather. Therefore, reducing stratospheric forecast error may be one way to improve the skill of tropospheric weather forecasts. In this review, the basis for this idea is examined. A range of studies of different stratospheric extreme vortex events shows that they can be skilfully forecasted beyond 5 days and into the sub-seasonal range (0–30 days) in some cases. Separate studies show that typical errors in forecasting a stratospheric extreme vortex event can alter tropospheric forecast skill by 5–7% in the extratropics on sub-seasonal time-scales. Thus understanding what limits stratospheric predictability is of significant interest to operational forecasting centres. Both limitations in forecasting tropospheric planetary waves and stratospheric model biases have been shown to be important in this context.This work is supported by the Natural Environmental Research Council (NERC) funded project Stratospheric Network for the Assessment of Predictability (SNAP) (Grant H5147600) and partially supported by the SPARC. ACP and RGH acknowledge funding through the EU ARISE project (Grant 284387) (EU-FP7). We also acknowledge Steven Pawson and Lawrence Coy from NASA for providing Figure 1. We wish to thank Lorenzo Polvani from Columbia University for providing Figure 4 and Amy Butler from NOAA for her contribution to Figure 5. We thank Adrian Simmons of ECMWF for his insightful review and two anonymous reviewers for their comments and suggestions that improved the quality of the manuscript

VEGF receptors on PC12 cells mediate transient activation of ERK1/2 and Akt: comparison of nerve growth factor and vascular endothelial growth factor

Vascular endothelial growth factor (VEGF) and endostatin are angiogenic and anti-angiogenic molecules, respectively, that have been implicated in neurogenesis and neuronal survival. Using alkaline phosphatase fusion proteins, we show that the PC12 neuronal cell line contains cell membrane receptors for VEGF but not for endostatin and the collagen XV endostatin homologue. Immunocytochemistry confirmed that proliferating and differentiated PC12 cells express VEGF receptors 1, 2 and neuropilin-1. While no functional effects of VEGF on PC12 cell proliferation and differentiation could be observed, a slight VEGF-induced reduction of caspase-3 activity in differentiated apoptotic PC12 cells was paralleled by transient activation of ERK1/2 and Akt. In direct comparison, nerve growth factor proved to be a strikingly more potent neuroprotective agent than VEGF

Spectrum and Inoculum Size Effect of a Rapid Antigen Detection Test for Group A Streptococcus in Children with Pharyngitis

BACKGROUND: The stability of the accuracy of a diagnostic test is critical to whether clinicians can rely on its result. We aimed to assess whether the performance of a rapid antigen detection test (RADT) for group A streptococcus (GAS) is affected by the clinical spectrum and/or bacterial inoculum size. METHODS: Throat swabs were collected from 785 children with pharyngitis in an office-based, prospective, multicenter study (2009-2010). We analysed the effect of clinical spectrum (i.e., the McIsaac score and its components) and inoculum size (light or heavy GAS growth) on the accuracy (sensitivity, specificity, likelihood ratios and predictive values) of a RADT, with laboratory throat culture as the reference test. We also evaluated the accuracy of a McIsaac-score-based decision rule. RESULTS: GAS prevalence was 36% (95CI: 33%-40%). The inoculum was heavy for 85% of cases (81%-89%). We found a significant spectrum effect on sensitivity, specificity, likelihood ratios and positive predictive value (p<0.05) but not negative predictive value, which was stable at about 92%. RADT sensitivity was greater for children with heavy than light inoculum (95% vs. 40%, p<0.001). After stratification by inoculum size, the spectrum effect on RADT sensitivity was significant only in patients with light inoculum, on univariate and multivariate analysis. The McIsaac-score-based decision rule had 99% (97%-100%) sensitivity and 52% (48%-57%) specificity. CONCLUSIONS: Variations in RADT sensitivity only occur in patients with light inocula. Because the spectrum effect does not affect the negative predictive value of the test, clinicians who want to rule out GAS can rely on negative RADT results regardless of clinical features if they accept that about 10% of children with negative RADT results will have a positive throat culture. However, such a policy is more acceptable in populations with very low incidence of complications of GAS infection

Northern winter climate change: assessment of uncertainty in CMIP5 projections related to stratosphere-troposphere coupling

Journal ArticlePublished versionFuture changes in the stratospheric circulation could have an important impact on northern winter tropospheric climate change, given that sea level pressure (SLP) responds not only to tropospheric circulation variations but also to vertically coherent variations in troposphere-stratosphere circulation. Here we assess northern winter stratospheric change and its potential to influence surface climate change in the Coupled Model Intercomparison Project-Phase 5 (CMIP5) multimodel ensemble. In the stratosphere at high latitudes, an easterly change in zonally averaged zonal wind is found for the majority of the CMIP5 models, under the Representative Concentration Pathway 8.5 scenario. Comparable results are also found in the 1% CO2 increase per year projections, indicating that the stratospheric easterly change is common feature in future climate projections. This stratospheric wind change, however, shows a signi fi cant spread among the models. By using linear regression, we quantify the impact of tropical upper troposphere warming, polar amplification, and the stratospheric wind change on SLP. We find that the intermodel spread in stratospheric wind change contributes substantially to the intermodel spread in Arctic SLP change. The role of the stratosphere in determining part of the spread in SLP change is supported by the fact that the SLP change lags the stratospheric zonally averaged wind change. Taken together, these findings provide further support for the importance of simulating the coupling between the stratosphere and the troposphere, to narrow the uncertainty in the future projection of tropospheric circulation changes

Localisation of RNAs into the germ plasm of vitellogenic xenopus oocytes

We have studied the localisation of mRNAs in full-grown Xenopus laevis oocytes by injecting fluorescent RNAs, followed by confocal microscopy of the oocyte cortex. Concentrating on RNA encoding the Xenopus Nanos homologue, nanos1 (formerly Xcat2), we find that it consistently localised into aggregated germ plasm ribonucleoprotein (RNP) particles, independently of cytoskeletal integrity. This implies that a diffusion/entrapment-mediated mechanism is active, as previously reported for previtellogenic oocytes. Sometimes this was accompanied by localisation into scattered particles of the “late”, Vg1/VegT pathway; occasionally only late pathway localisation was seen. The Xpat RNA behaved in an identical fashion and for neither RNA was the localisation changed by any culture conditions tested. The identity of the labelled RNP aggregates as definitive germ plasm was confirmed by their inclusion of abundant mitochondria and co-localisation with the germ plasm protein Hermes. Further, the nanos1/Hermes RNP particles are interspersed with those containing the germ plasm protein Xpat. These aggregates may be followed into the germ plasm of unfertilized eggs, but with a notable reduction in its quantity, both in terms of injected molecules and endogenous structures. Our results conflict with previous reports that there is no RNA localisation in large oocytes, and that during mid-oogenesis even germ plasm RNAs localise exclusively by the late pathway. We find that in mid oogenesis nanos1 RNA also localises to germ plasm but also by the late pathway. Late pathway RNAs, Vg1 and VegT, also may localise into germ plasm. Our results support the view that mechanistically the two modes of localisation are extremely similar, and that in an injection experiment RNAs might utilise either pathway, the distinction in fates being very subtle and subject to variation. We discuss these results in relation to their biological significance and the results of others

Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons

Metabotropic glutamate receptors (mGluRs), including mGluR5, play a central role in regulating the strength and plasticity of synaptic connections in the brain. However, the signaling pathways that connect mGluRs to their downstream effectors are not yet fully understood. Here, we report that stimulation of mGluR5 in hippocampal cultures and slices results in phosphorylation of protein kinase D (PKD) at the autophosphorylation site Ser-916. This phosphorylation event occurs within 30 s of stimulation, persists for at least 24 h, and is dependent on activation of phospholipase C and protein kinase C. Our data suggest that activation of PKD may represent a novel signaling pathway linking mGluR5 to its downstream targets. These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity.Howard Hughes Medical InstituteFRAXA Research FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.