Chlamydia control activities in Europe: cross-sectional survey

Background: Chlamydia is the most commonly reported bacterial sexually transmitted infection in Europe. The objective of the Screening for Chlamydia in Europe (SCREen) project was to describe current and planned chlamydia control activities in Europe. Methods: The authors sent a questionnaire asking about different aspects of chlamydia epidemiology and control to public health and clinical experts in each country in 2007. The principles of sexually transmitted infection control were used to develop a typology comprising five categories of chlamydia control activities. Each country was assigned to a category, based on responses to the questionnaire. Results: Experts in 29 of 33 (88%) invited countries responded. Thirteen of 29 countries (45%) had no current chlamydia control activities. Six countries in this group stated that there were plans to introduce chlamydia screening programmes. There were five countries (17%) with case management guidelines only. Three countries (10%) also recommended case finding amongst partners of diagnosed chlamydia cases or people with another sexually transmitted infection. Six countries (21%) further specified groups of asymptomatic people eligible for opportunistic chlamydia testing. Two countries (7%) reported a chlamydia screening programme. There was no consistent association between the per capita gross domestic product of a country and the intensity of chlamydia control activities (P = 0.816). Conclusion: A newly developed classification system allowed the breadth of ongoing national chlamydia control activities to be described and categorized. Chlamydia control strategies should ensure that clinical guidelines to optimize chlamydia diagnosis and case management have been implemented before considering the appropriateness of screening programmes

Introduction : analysing English syntax past and present

This book is an exploration of categories, constructions, and change in English syntax. A great many books are published on the syntax of English, both monographs and edited volumes, and yet another may seem unnecessary. However, we felt more than justified in adding to the sizeable literature here for two reasons. The first, to borrow from Richard M. Hogg and David Denison’s justification for A History of the English Language, is that ‘one of the beauties of the language is its ability to show continuous change and flexibility while in some sense remaining the same

Load-Balancing for Parallel Delaunay Triangulations

Computing the Delaunay triangulation (DT) of a given point set in $\mathbb{R}^D$ is one of the fundamental operations in computational geometry. Recently, Funke and Sanders (2017) presented a divide-and-conquer DT algorithm that merges two partial triangulations by re-triangulating a small subset of their vertices - the border vertices - and combining the three triangulations efficiently via parallel hash table lookups. The input point division should therefore yield roughly equal-sized partitions for good load-balancing and also result in a small number of border vertices for fast merging. In this paper, we present a novel divide-step based on partitioning the triangulation of a small sample of the input points. In experiments on synthetic and real-world data sets, we achieve nearly perfectly balanced partitions and small border triangulations. This almost cuts running time in half compared to non-data-sensitive division schemes on inputs exhibiting an exploitable underlying structure.Comment: Short version submitted to EuroPar 201

A small protein probe for correlated microscopy of endogenous proteins

Probes are essential to visualize proteins in their cellular environment, both using light microscopy as well as electron microscopy (EM). Correlated light microscopy and electron microscopy (CLEM) requires probes that can be imaged simultaneously by both optical and electron-dense signals. Existing combinatorial probes often have impaired efficiency, need ectopic expression as a fusion protein, or do not target endogenous proteins. Here, we present FLIPPER-bodies to label endogenous proteins for CLEM. Fluorescent Indicator and Peroxidase for Precipitation with EM Resolution (FLIPPER), the combination of a fluorescent protein and a peroxidase, is fused to a nanobody against a target of interest. The modular nature of these probes allows an easy exchange of components to change its target or color. A general FLIPPER-body targeting GFP highlights histone2B-GFP both in fluorescence and in EM. Similarly, endogenous EGF receptors and HER2 are visualized at nm-scale resolution in ultrastructural context. The small and flexible FLIPPER-body outperforms IgG-based immuno-labeling, likely by better reaching the epitopes. Given the modular domains and possibilities of nanobody generation for other targets, FLIPPER-bodies have high potential to become a universal tool to identify proteins in immuno-CLEM with increased sensitivity compared to current approaches

Discovery and Differential Processing of HLA Class II-Restricted Minor Histocompatibility Antigen LB-PIP4K2A-1S and Its Allelic Variant by Asparagine Endopeptidase

Minor histocompatibility antigens are the main targets of donor-derived T-cells after allogeneic stem cell transplantation. Identification of these antigens and understanding their biology are a key requisite for more insight into how graft vs. leukemia effect and graft vs. host disease could be separated. We here identified four new HLA class II-restricted minor histocompatibility antigens using whole genome association scanning. For one of the new antigens, i.e., LB-PIP4K2A-1S, we measured strong T-cell recognition of the donor variant PIP4K2A-1N when pulsed as exogenous peptide, while the endogenously expressed variant in donor EBV-B cells was not recognized. We showed that lack of T-cell recognition was caused by intracellular cleavage by a protease named asparagine endopeptidase (AEP). Furthermore, microarray gene expression analysis showed that PIP4K2A and AEP are both ubiquitously expressed in a wide variety of healthy tissues, but that expression levels of AEP were lower in primary acute myeloid leukemia (AML). In line with that, we confirmed low activity of AEP in AML cells and demonstrated that HLA-DRB1*03:01 positive primary AML expressing LB-PIP4K2A-1S or its donor variant PIP4K2A-1N were both recognized by specific T-cells. In conclusion, LB-PIP4K2A-1S not only represents a novel minor histocompatibility antigen but also provides evidence that donor T-cells after allogeneic stem cell transplantation can target the autologous allelic variant as leukemia-associated antigen. Furthermore, it demonstrates that endopeptidases can play a role in cell type-specific intracellular processing and presentation of HLA class II-restricted antigens, which may be explored in future immunotherapy of AML

Understanding the effect of an educational intervention to optimize HIV testing strategies in primary care in Amsterdam - results of a mixed-methods study.

BACKGROUND: In the Netherlands, general practitioners (GPs) play a key role in provider-initiated HIV testing, but opportunities for timely diagnosis are regularly missed. We implemented an educational intervention to improve HIV testing by GPs from 2015 to 2020, and observed a 7% increase in testing in an evaluation using laboratory data. The objective for the current study was to gain a deeper understanding of whether and how practices and perceptions of GPs' HIV/sexually transmitted infection (STI) testing behaviour changed following the intervention. METHODS: We performed a mixed-methods study using questionnaires and semi-structured interviews to assess self-reported changes in HIV/STI testing by participating GPs. Questionnaires were completed by participants at the end of the final educational sessions from 2017 through 2020, and participating GPs were interviewed from January through March 2020. Questionnaire data were analysed descriptively, and open question responses were categorised thematically. Interview data were analysed following thematic analysis methods. RESULTS: In total, 101/103 participants completed questionnaires. Of 65 participants that were included in analyses on the self-reported effect of the programme, forty-seven (72%) reported it had changed their HIV/STI testing, including improved STI consultations, adherence to the STI consultation guideline, more proactive HIV testing, and more extragenital STI testing. Patients' risk factors, patients' requests and costs were most important in selecting STI tests ordered. Eight participants were interviewed and 15 themes on improved testing were identified, including improved HIV risk-assessment, more proactive testing for HIV/STI, more focus on HIV indicator conditions and extragenital STI testing, and tools to address HIV during consultations. However, several persistent barriers for optimal HIV/STI testing by GPs were identified, including HIV-related stigma and low perceived risk. CONCLUSIONS: Most GPs reported improved HIV/STI knowledge, attitude and testing, but there was a discrepancy between reported changes in HIV testing and observed increases using laboratory data. Our findings highlight challenges in implementation of effective interventions, and in their evaluation. Lessons learned from this intervention may inform follow-up initiatives to keep GPs actively engaged in HIV testing and care, on our way to zero new HIV infections

Quality of patient- and proxy-reported outcomes for children with impairment of the lower extremity:A systematic review using the COnsensus-based Standards for selection of health Measurement INstruments methodology

Background: Patient-reported outcome measures have become crucial in the clinical evaluation of patients. Appropriate selection, in a young population, of the instrument is vital to providing evidence-based patient-centered healthcare. This systematic review applies the COnsensus-based Standards for selection of health Measurement INstruments methodology to provide a critically appraised overview of patient-reported outcome measures targeted at pediatric orthopedic patients with lower limb impairment.Method: A systematic search of electronic databases was performed to identify original studies reporting the development and/or validation of patient-reported outcome measures evaluating children with impairment of the lower extremity. Data extraction, quality assessment, and risk of bias evaluation were performed following the COnsensus-based Standards for selection of health Measurement INstruments guidelines and Preferred Reporting Items for Systematic reviews and Meta-Analyses statement.Results: A total of 6919 articles were screened. Thirty-three studies were included, reporting evidence on the measurement properties of 13 different patient-reported outcome measures and 20 translations. Four studies reported on content validity and patient-reported outcome measure development. The methodological quality of studies on structural validity, content validity, or patient-reported outcome measure development was mostly rated as "doubtful" or "very good." The quality of evidence on measurement properties varied noticeably, with most studies needing to perform improve their methodological quality to justify their results.Conclusion: This review provides an extensive overview of all available patient-reported outcome measures for patients with lower extremity impairment within pediatric orthopedics. We cautiously advise the use of four patient-reported outcome measures. However, the scarce availability of research on content validity and patient-reported outcome measure development highlights an area for future research endeavors to improve our knowledge on the currently available patient-reported outcome measures.Level of evidence: Diagnostic level

IGLV3-21∗01 is an inherited risk factor for CLL through the acquisition of a single-point mutation enabling autonomous BCR signaling

© 2020 National Academy of Sciences. All rights reserved. The prognosis of chronic lymphocytic leukemia (CLL) depends on different markers, including cytogenetic aberrations, oncogenic mutations, and mutational status of the immunoglobulin (Ig) heavy-chain variable (IGHV) gene. The number of IGHV mutations distinguishes mutated (M) CLL with a markedly superior prognosis from unmutated (UM) CLL cases. In addition, B cell antigen receptor (BCR) stereotypes as defined by IGHV usage and complementaritydetermining regions (CDRs) classify ∼30% of CLL cases into prognostically important subsets. Subset 2 expresses a BCR with the combination of IGHV3-21-derived heavy chains (HCs) with IGLV3- 21-derived light chains (LCs), and is associated with an unfavorable prognosis. Importantly, the subset 2 LC carries a single-point mutation, termed R110, at the junction between the variable and constant LC regions. By analyzing 4 independent clinical cohorts through BCR sequencing and by immunophenotyping with antibodies specifically recognizing wild-type IGLV3-21 and R110-mutated IGLV3-21 (IGLV3-21R110), we show that IGLV3-21R110-expressing CLL represents a distinct subset with poor prognosis independent of IGHV mutations. Compared with other alleles, only IGLV3-21∗01 facilitates effective homotypic BCR-BCR interaction that results in autonomous, oncogenic BCR signaling after acquiring R110 as a single-point mutation. Presumably, this mutation acts as a standalone driver that transforms IGLV3-21∗01-expressing B cells to develop CLL. Thus, we propose to expand the conventional definition of CLL subset 2 to subset 2L by including all IGLV3-21R110-expressing CLL cases regardless of IGHV mutational status. Moreover, the generation ofmonoclonal antibodies recognizing IGLV3-21 or mutated IGLV3-21R110 facilitates the recognition of B cells carrying this mutation in CLL patients or healthy donors