V_H replacement in rearranged immunoglobulin genes

Examples suggesting that all or part of the V<sub>H</sub> segment of a rearranged V<sub>H</sub>DJ<sub>H</sub> may be replaced by all or part of another V<sub>H</sub> have been appearing since the 1980s. Evidence has been presented of two rather different types of replacement. One of these has gained acceptance and has now been clearly demonstrated to occur. The other, proposed more recently, has not yet gained general acceptance because the same effect can be produced by polymerase chain reaction artefact. We review both types of replacement including a critical examination of evidence for the latter. The first type involves RAG proteins and recombination signal sequences (RSS) and occurs in immature B cells. The second was also thought to be brought about by RAG proteins and RSS. However, it has been reported in hypermutating cells which are not thought to express RAG proteins but in which activation-induced cytidine deaminase (AID) has recently been shown to initiate homologous recombination. Re-examination of the published sequences reveals AID target sites in V<sub>H</sub>-V<sub>H</sub> junction regions and examples that resemble gene conversion

Perceived risk, anxiety, and behavioural responses of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands: results of three consecutive online surveys

Background: Research into risk perception and behavioural responses in case of emerging infectious diseases is still relatively new. The aim of this study was to examine perceptions and behaviours of the general public during the early phase of the Influenza A (H1N1) pandemic in the Netherlands. Methods: Two cross-sectional and one follow-up online survey (survey 1, 30 April-4 May; survey 2, 15-19 June; survey 3, 11-20 August 2009). Adults aged 18 years and above participating in a representative Internet panel were invited (survey 1, n = 456; survey 2, n = 478; follow-up survey 3, n = 934). Main outcome measures were 1) time trends in risk perception, feelings of anxiety, and behavioural responses (survey 1-3) and 2) factors associated with taking preventive measures and strong intention to comply with government-advised preventive measures in the future (survey 3). Results: Between May and August 2009, the level of knowledge regarding Influenza A (H1N1) increased, while perceived severity of the new flu, perceived self-efficacy, and intention to comply with preventive measures decreased. The perceived reliability of information from the government decreased from May to August (62% versus 45%). Feelings of anxiety decreased from May to June, and remained stable afterwards. From June to August 2009, perceived vulnerability increased and more respondents took preventive measures (14% versus 38%). Taking preventive measures was associated with no children in the household, high anxiety, high self-efficacy, more agreement with statements on avoidance, and paying much attention to media information regarding Influenza A (H1N1). Having a strong intention to comply with government-advised preventive measures in the future was associated with higher age, high perceived severity, high anxiety, high perceived efficacy of measures, high self-efficacy, and finding governmental information to be reliable. Conclusions: Decreasing trends over time in perceived severity and anxiety are consistent with the reality: the clinical picture of influenza turned out to be mild in course of time. Although (inter) national health authorities initially overestimated the case fatality rate, the public stayed calm and remained to have a relatively high intention to comply with preventive measures

QRTEngine: An easy solution for running online reaction time experiments using Qualtrics

Performing online behavioral research is gaining increased popularity among researchers in psychological and cognitive science. However, the currently available methods for conducting online reaction time experiments are often complicated and typically require advanced technical skills. In this article, we introduce the Qualtrics Reaction Time Engine (QRTEngine), an open-source JavaScript engine that can be embedded in the online survey development environment Qualtrics. The QRTEngine can be used to easily develop browser-based online reaction time experiments with accurate timing within current browser capabilities, and it requires only minimal programming skills. After introducing the QRTEngine, we briefly discuss how to create and distribute a Stroop task. Next, we describe a study in which we investigated the timing accuracy of the engine under different processor loads using external chronometry. Finally, we show that the QRTEngine can be used to reproduce classic behavioral effects in three reaction time paradigms: a Stroop task, an attentional blink task, and a masked-priming task. These findings demonstrate that QRTEngine can be used as a tool for conducting online behavioral research even when this requires accurate stimulus presentation times

Het Rijksvaccinatieprogramma in Nederland. Ontwikkelingen in 2006

In 2006 several changes were made in the Dutch National Immunisation Programme (NIP): Hepatitis B vaccination at birth was added for children born to mothers positive for hepatitis B surface antigen; a new vaccine for diphtheria, tetanus, pertussis (a-cellular), poliomyelitis and Haemophilus influenzae (DTaP-IPV/Hib) was introduced; vaccination against pneumococcal disease was added at two, three, four and eleven months; risk groups for hepatitis B receive a combined vaccine for DTaP-IPV/Hib and HBV at the same ages; DT-IPV and aP at the age of four years were combined in one vaccine; and new MMR vaccines were introduced. As new information became available in 2006, the desirability to introduce vaccinations in the NIP for the following diseases could be (re)considered: hepatitis B (universal vaccination), rotavirus, varicella and human papillomavirus. For respiratory syncytial virus and meningococcal serogroup B disease no candidate vaccines are available yet. Extension of the programme with available vaccines for hepatitis A, influenza and tuberculosis is not (yet) recommended. The NIP in the Netherlands is effective and safe. However, continued monitoring of the effectiveness and safety of the NIP is important as changes are made regularly. Maintaining high vaccine uptake is vital to prevent (re)emergence of diseases. Furthermore, the programme should be regularly reviewed as new vaccines become available.In 2006 traden verschillende veranderingen op in het Rijksvaccinatieprogramma (RVP) in Nederland: kinderen die geboren worden uit moeders die chronisch geinfecteerd zijn met hepatitis B krijgen vlak na de geboorte een hepatitis B vaccinatie; er is een ander vaccin geintroduceerd voor difterie, kinkhoest (a-cellulair), tetanus, poliomyelitis en Haemophilus influenzae (DaKTP/Hib); vaccinatie tegen pneumokokken is toegevoegd op de leeftijd van 2, drie, vier en elf maanden; risicogroepen voor hepatitis B krijgen op diezelfde leeftijden een combinatievaccin voor DaKTP/Hib en hepatitis B; DTP en aK zijn gecombineerd in een vaccin op vierjarige leeftijd; en er zijn nieuwe BMR vaccins geintroduceerd. Op basis van informatie die in 2006 beschikbaar is gekomen wordt geadviseerd de introductie van vaccinaties voor de volgende ziekten te overwegen: hepatitis B (universele vaccinatie), rotavirus, waterpokken en humaan papillomavirus. Voor respiratoir syncytieel virus en meningokokken B zijn nog geen kandidaatvaccins beschikbaar en uitbreiding van het RVP met beschikbare vaccins voor hepatitis A, influenza en tuberculose wordt nog niet aanbevolen. Het RVP is effectief en veilig, maar voortdurende bewaking hiervan is groot belang, omdat er regelmatig veranderingen optreden. Handhaven van de hoge vaccinatiegraad is essentieel om terugkeer van ziekten te voorkomen. Verder moet regelmatig bekeken worden of het RVP aangepast moet worden aangezien er steeds nieuwe vaccins beschikbaar komen

Cost-effectiveness of a screening strategy for Q fever among pregnant women in risk areas: a clustered randomized controlled trial

Contains fulltext : 87399.pdf (publisher's version ) (Open Access)BACKGROUND: In The Netherlands the largest human Q fever outbreak ever reported in the literature is currently ongoing with more than 2300 notified cases in 2009. Pregnant women are particularly at risk as Q fever during pregnancy may cause maternal and obstetric complications. Since the majority of infected pregnant women are asymptomatic, a screening strategy might be of great value to reduce Q fever related complications. We designed a trial to assess the (cost-)effectiveness of a screening program for Q fever in pregnant women living in risks areas in The Netherlands. METHODS/DESIGN: We will conduct a clustered randomized controlled trial in which primary care midwife centres in Q fever risk areas are randomized to recruit pregnant women for either the control group or the intervention group. In both groups a blood sample is taken around 20 weeks postmenstrual age. In the intervention group, this sample is immediately analyzed by indirect immunofluorescence assay for detection of IgG and IgM antibodies using a sensitive cut-off level of 1:32. In case of an active Q fever infection, antibiotic treatment is recommended and serological follow up is performed. In the control group, serum is frozen for analysis after delivery. The primary endpoint is a maternal (chronic Q fever or reactivation) or obstetric complication (low birth weight, preterm delivery or fetal death) in Q fever positive women. Secondary aims pertain to the course of infection in pregnant women, diagnostic accuracy of laboratory tests used for screening, histo-pathological abnormalities of the placenta of Q fever positive women, side effects of therapy, and costs. The analysis will be according to the intention-to-screen principle, and cost-effectiveness analysis will be performed by comparing the direct and indirect costs between the intervention and control group. DISCUSSION: With this study we aim to provide insight into the balance of risks of undetected and detected Q fever during pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov, protocol record NL30340.042.09

One-year follow-up of patients of the ongoing Dutch Q fever outbreak: clinical, serological and echocardiographic findings

Contains fulltext : 89915.pdf (publisher's version ) (Open Access)PURPOSE: In 2007, a large goat-farming-associated Q fever outbreak occurred in the Netherlands. Data on the clinical outcome of Dutch Q fever patients are lacking. The current advocated follow-up strategy includes serological follow-up to detect evolution to chronic disease and cardiac screening at baseline to identify and prophylactically treat Q fever patients in case of valvulopathy. However, serological follow-up using commercially available tests is complicated by the lack of validated cut-off values. Furthermore, cardiac screening in the setting of a large outbreak has not been implemented previously. Therefore, we report here the clinical outcome, serological follow-up and cardiac screening data of the Q fever patients of the current ongoing outbreak. METHODS: The implementation of a protocol including clinical and serological follow-up at baseline and 3, 6 and 12 months after acute Q fever and screening echocardiography at baseline. RESULTS: Eighty-five patients with acute Q fever were identified (male 62%, female 38%). An aspecific, flu-like illness was the most common clinical presentation. Persistent symptoms after acute Q fever were reported by 59% of patients at 6 months and 30% at 12 months follow-up. We observed a typical serological response to Coxiella burnetii infection in both anti-phase I and anti-phase II IgG antibodies, with an increase in antibody titres up to 3 months and a subsequent decrease in the following 9 months. Screening echocardiography was available for 66 (78%) out of 85 Q fever patients. Cardiac valvulopathy was present in 39 (59%) patients. None of the 85 patients developed chronic Q fever. CONCLUSIONS: Clinical, serological and echocardiographic data of the current ongoing Dutch Q fever outbreak cohort are presented. Screening echocardiography is no longer part of the standard work-up of Q fever patients in the Netherlands.1 december 201

Cognition and bimanual performance in children with unilateral cerebral palsy: Protocol for a multicentre, cross-sectional study

© 2018 The Author(s). Background: Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. Methods/Design: This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. Discussion: This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy

Counting on the mental number line to make a move: sensorimotor ('pen') control and numerical processing

Mathematics is often conducted with a writing implement. But is there a relationship between numerical processing and sensorimotor ‘pen’ control? We asked participants to move a stylus so it crossed an unmarked line at a location specified by a symbolic number (1–9), where number colour indicated whether the line ran left–right (‘normal’) or vice versa (‘reversed’). The task could be simplified through the use of a ‘mental number line’ (MNL). Many modern societies use number lines in mathematical education and the brain’s representation of number appears to follow a culturally determined spatial organisation (so better task performance is associated with this culturally normal orientation—the MNL effect). Participants (counter-balanced) completed two consistent blocks of trials, ‘normal’ and ‘reversed’, followed by a mixed block where line direction varied randomly. Experiment 1 established that the MNL effect was robust, and showed that the cognitive load associated with reversing the MNL not only affected response selection but also the actual movement execution (indexed by duration) within the mixed trials. Experiment 2 showed that an individual’s motor abilities predicted performance in the difficult (mixed) condition but not the easier blocks. These results suggest that numerical processing is not isolated from motor capabilities—a finding with applied consequences