Knee disorders in primary care: design and patient selection of the HONEUR knee cohort.

BACKGROUND: Knee complaints are a frequent reason for consultation in general practice. These patients constitute a specific population compared to secondary care patients. However, information to base treatment decisions on is generally derived from specialistic settings. Our cohort study is aimed at collecting knowledge about prognosis and prognostic factors of knee complaints presented in a primary care setting. This paper describes the methods used for data collection, and discusses potential selectiveness of patient recruitment. METHODS: This is a descriptive prospective cohort study with one-year follow-up. 40 Dutch GPs recruited consecutive patients with incident knee complaints aged 12 years and above from October 2001 to October 2003. Patients were assessed with questionnaires and standardised physical examinations. Additional measurements of subgroups included MRI for recent knee traumas and device assessed function measurements for non-traumatic patients. After the inclusion period we retrospectively searched the computerized medical files of participating GPs to obtain a sample to determine possible selective recruitment. We assessed differences in proportions of gender, traumatic onset of injury and age groups between participants and non-participants using Odds Ratios (OR) and 95% confidence intervals. RESULTS: We recruited 1068 patients. In a sample of 310 patients visiting the GP, we detected some selective recruitment, indicating an underrepresentation of patients aged 12 to 35 years (OR 1.70; 1.15-2.77), especially among men (OR 2.16; 1.12-4.18). The underrepresentation of patients with traumatic onset of injury was not statistically significant. CONCLUSION: This cohort is unique in its size, setting, and its range of both age and type of knee complaints. We believe the detected selective recruitment is unlikely to introduce significant bias, as the cohort will be divided into subgroups according to age group or traumatic onset of injury for future analyses. However, the underrepresentation of men in the age group of 12 to 35 years of age warrants caution. Based on the available data, we believe our cohort is an acceptable representation of patients with new knee complaints consulting the GP, and we expect no problems with extrapolation of the results to the general Dutch population

Explaining variability in ciclosporin exposure in adult kidney transplant recipients

International audienc

Chromosome-Biased Binding and Gene Regulation by the Caenorhabditis elegans DRM Complex

DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA–binding moieties together direct DRM to its target genes. Chromatin immunoprecipitation and gene expression profiling reveals conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find that LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, C. elegans DRM does not act uniformly throughout the genome: the DRM recruitment motif, DRM binding, and DRM-regulated embryonic genes are all under-represented on the X chromosome. However, germline genes down-regulated in lin-54 mutants are over-represented on the X chromosome. We discuss models for how loss of autosome-bound DRM may enhance germline X chromosome silencing. We propose that autosome-enriched binding of DRM arose in C. elegans as a consequence of germline X chromosome silencing and the evolutionary redistribution of germline-expressed and essential target genes to autosomes. Sex chromosome gene regulation may thus have profound evolutionary effects on genome organization and transcriptional regulatory networks.National Institutes of Health (U.S.) (grant GM24663)National Institutes of Health (U.S.) (grant DK068429)National Institutes of Health (U.S.) (grant GM082971)National Institutes of Health (U.S.) (grant GM076378

Innovative Visualizations Shed Light on Avian Nocturnal Migration

We acknowledge the support provided by COST–European Cooperation in Science and Technology through the Action ES1305 ‘European Network for the Radar Surveillance of Animal Movement’ (ENRAM) in facilitating this collaboration. We thank ENRAM members and researchers attending the EOU round table discussion ‘Radar aeroecology: unravelling population scale patterns of avian movement’ for feedback on the visualizations. We thank Arie Dekker for his feedback as jury member of the bird migration visualization challenge & hackathon hosted at the University of Amsterdam, 25–27 March 2015. We thank Willem Bouten and Kevin Winner for discussion of methodological design. We thank Kevin Webb and Jed Irvine for assistance with downloading, managing, and reviewing US radar data. We thank the Royal Meteorological Institute of Belgium for providing weather radar data.Globally, billions of flying animals undergo seasonal migrations, many of which occur at night. The temporal and spatial scales at which migrations occur and our inability to directly observe these nocturnal movements makes monitoring and characterizing this critical period in migratory animals’ life cycles difficult. Remote sensing, therefore, has played an important role in our understanding of large-scale nocturnal bird migrations. Weather surveillance radar networks in Europe and North America have great potential for long-term low-cost monitoring of bird migration at scales that have previously been impossible to achieve. Such long-term monitoring, however, poses a number of challenges for the ornithological and ecological communities: how does one take advantage of this vast data resource, integrate information across multiple sensors and large spatial and temporal scales, and visually represent the data for interpretation and dissemination, considering the dynamic nature of migration? We assembled an interdisciplinary team of ecologists, meteorologists, computer scientists, and graphic designers to develop two different flow visualizations, which are interactive and open source, in order to create novel representations of broad-front nocturnal bird migration to address a primary impediment to long-term, large-scale nocturnal migration monitoring. We have applied these visualization techniques to mass bird migration events recorded by two different weather surveillance radar networks covering regions in Europe and North America. These applications show the flexibility and portability of such an approach. The visualizations provide an intuitive representation of the scale and dynamics of these complex systems, are easily accessible for a broad interest group, and are biologically insightful. Additionally, they facilitate fundamental ecological research, conservation, mitigation of human–wildlife conflicts, improvement of meteorological products, and public outreach, education, and engagement.Yeshttp://www.plosone.org/static/editorial#pee

Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study

Contains fulltext : 108565.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: To get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort study METHODS: In a longitudinal, observational cohort of RA patients treated with infliximab for at least 6 months, treatment interval, DAS28, infliximab trough levels and anti-infliximab antibodies were assessed. Prevalence of low (5 mg/l) infliximab serum trough levels and anti-infliximab antibodies was recorded. Relationship of a change in anti-infliximab antibodies and treatment interval was described. Reliability of consecutive infliximab serum trough levels and anti-infliximab antibodies in patients with stable DAS28 and treatment was analysed with Spearman correlation and kappa-analysis. RESULTS: 147 patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3) at baseline were followed during 1.5 years. Inter-individual variability in infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR 3.35), with 31% (95%CI: 20-42%) having low (5 mg/L). Interestingly also in RA patients with DAS28 </= 3.2, anti-infliximab antibodies were found in one-third of the patients, with half of them having antibodies every visit during a median of more than one year. Agreement for consecutive measurements of serum trough levels and anti-infliximab antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0 (SE 0.14) Anti-infliximab antibody appearance was influenced by interval increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low infliximab levels. CONCLUSIONS: Low (and high) infliximab serum trough levels are prevalent, interestingly also in patients with low disease activity. Consecutive measurements of serum trough levels and anti-infliximab antibodies are reliable in stable patients. These test could be used to lower or stop infliximab in selected patients

Differential Expression of the Middle East Respiratory Syndrome Coronavirus Receptor in the Upper Respiratory Tracts of Humans and Dromedary Camels

Middle East respiratory syndrome coronavirus (MERS-CoV) is not efficiently transmitted between humans, but it is highly prevalent in dromedary camels. Here we report that the MERS-CoV receptor-dipeptidyl peptidase 4 (DPP4)-is expressed in the upper respiratory tract epithelium of camels but not in that of humans. Lack of DPP4 expression may be the primary cause of limited MERS-CoV replication in the human upper respiratory tract and hence restrict transmission

Adenosine Deaminase Acts as a Natural Antagonist for Dipeptidyl Peptidase 4-Mediated Entry of the Middle East Respiratory Syndrome Coronavirus

Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in cells of different species using dipeptidyl peptidase 4 (DPP4) as a functional receptor. Here we show the resistance of ferrets to MERS-CoV infection and inability of ferret DDP4 to bind MERS-CoV. Site-directed mutagenesis of amino acids variable in ferret DPP4 thus revealed the functional human DPP4 virus binding site. Adenosine deaminase (ADA), a DPP4 binding protein, competed for virus binding, acting as a natural antagonist for MERS-CoV infection