The Fixed-Cycle Traffic-Light queue with multiple lanes and temporary blockages

Traffic-light modelling is a complex task, because many factors have to be taken into account. In particular, capturing all traffic flows in one model can significantly complicate the model. Therefore, several realistic features are typically omitted from most models. We introduce a mechanism to include pedestrians and focus on situations where they may block vehicles that get a green light simultaneously. More specifically, we consider a generalization of the Fixed-Cycle Traffic-Light (FCTL) queue. Our framework allows us to model situations where (part of the) vehicles are blocked, e.g. by pedestrians that block turning traffic and where several vehicles might depart simultaneously, e.g. in case of multiple lanes receiving a green light simultaneously. We rely on probability generating function and complex analysis techniques which are also used to study the regular FCTL queue. We study the effect of several parameters on performance measures such as the mean delay and queue-length distribution

Prevalence of Defecation Disorders and their Symptoms is Comparable in Children and Young Adults:Cross-Sectional Study

Purpose: We aimed to compare the prevalence rates and associated symptoms of constipation and fecal incontinence in children and young adults and evaluate how these patient groups cope with these disorders. Methods: A cross-sectional study was performed in which 212 children (8-17 years) and 149 young adults (18-29 years) from the general Dutch population completed a questionnaire about defecation disorders. Results: Constipation occurred in 15.6% of children and 22.8% of young adults (p=0.55), while the prevalence of fecal incontinence was comparable between groups (7%, p=0.91). The symptoms associated with constipation occurred as often in children as in young adults, while most fecal incontinence symptoms occurred more often in young adults. Approximately 43% of children had constipation for more than 5 years, while 26% of young adults experienced constipation since childhood. Only 27% of constipated children and 21% of constipated young adults received treatment (mostly laxatives). For fecal incontinence, 13% of children and 36% of young adults received treatment (mostly antidiarrheal medications or incontinence pads). Conclusion: In contrast to the general belief, the prevalence of defecation disorders and associated symptoms seem to be comparable in children and young adults. Only a few people with defecation disorders receive adequate treatment

Puzzled by GRB 060218

We study the optical-UV/X-ray spectral energy distribution of GRB 060218 during the prompt phase and during what seems to be the afterglow phase. The results are puzzling, since if the opt-UV and the X-ray emission belong to a single backbody (BB), then its luminosity is too large, and this BB cannot be interpreted as the signature of the shock breakout of the supernova. There are also serious problems in associating the emission expected by the supernova shock breakout with either the opt-UV or the X-ray emission. In the former case we derive too small ejecta velocities; in the latter case, on the contrary, the required velocity is too large, corresponding to the large radius of a BB required to peak close to the UV band. We then present what we think is the most conservative alternative explanation, namely a synchrotron spectrum, self-absorbed in the opt-UV and extending up to the X-ray band, where we observe the emission of the most energetic electrons, which are responsible for the exponential roll-over of the spectrum. The obtained fit can explain the entire spectrum except the BB observed in the X-rays, which must be a separate component. The puzzling feature of this interpretation is that the same model is required to explain the spectrum also at later times, up to 1e5 s, because the opt-UV emission remains constant in shape and also (approximately) in normalisation. In this case the observed X-ray flux is produced by self-Compton emission. Thus the prompt emission phase should last for ~1e5 s or more. Finally, we show that the BB observed in X-rays, up to 7000 seconds, can be photospheric emission from the cocoon or stellar material, energized by the GRB jet at radii comparable to the stellar radius (i.e. 1e10-1e11 cm), not very far from where this material becomes transparent (e.g. 1e12 cm).Comment: revised version accepted for publication in MNRAS (Letters

Using laxatives and/or enemas to accelerate the diagnosis in children presenting with acute abdominal pain:a randomised controlled trial study protocol

Introduction: Many children with acute abdominal pain and suspicion of appendicitis are diagnosed with constipation. Nevertheless, it can be difficult to differentiate between acute constipation and acute appendicitis because of similar symptoms and lack of diagnostic criteria. Consequently, constipation is often missed despite repeated consultations at the emergency department. We hypothesise that the diagnostic process can be improved and adequate treatment accelerated by supporting faecal evacuation in children with acute abdominal pain. Methods and analysis: An unblinded randomised controlled trial including children aged between 5 years and 18 years with acute abdominal pain and suspicion of acute appendicitis. Children who do not have a definitive diagnosis after the first consultation and who need to return for a second consultation will be randomised. The intervention group will receive laxatives and enemas, while the control group will receive no medication. If, after the second consultation, still no diagnosis is established, and a third consultation is needed, then the intervention group will receive only laxatives, and the control group will again not receive medication. The primary outcome will be the differences in abdominal pain scores obtained with FACES Pain Rating Scale and the visual analogue scale at first, second and possibly third consultation. The secondary outcome will be the number of consultations needed to reach final diagnosis. Ethics and dissemination: Laxatives and enemas have proven to be safe and effective treatments for constipation in children. Adverse events are therefore not expected, however, should they occur, then the child concerned shall be properly followed and treated until the event is over. The local Medical Research Ethics Committee approved of this study and waived the otherwise mandatory insurance for human test subjects. Trial registration numbers: Pre-results: CCMO NL44710.042.12 andEudraCT 2013-000498-56

EBF recommendation on practical management of critical reagents for antidrug antibody ligand-binding assays

Immunogenicity assays are required to measure antidrug antibodies that are generated against biotherapeutic modalities. As for any ligand-binding assays, critical reagents (CR) play a crucial role in immunogenicity assays, as the robustness and reliability of an assay are defined by the quality and long-term availability of these reagents. The current regulatory guidelines do not provide clear directions on how to implement and verify lot-to-lot changes of CR during an assay life cycle, or the acceptance criteria that should be used when implementing new lots of CR. These aspects were extensively discussed within the European Bioanalysis Forum community. In this paper, CR for immunogenicity assays are identified and the minimum requirements for introducing new lots of CR in immunogenicity assays are described

The problem of defecation disorders in children is underestimated and easily goes unrecognized:A cross-sectional study

We aimed to study constipation and fecal incontinence in terms of prevalence, recognizing the disorders, help-seeking behavior, and associated symptoms. In this cross-sectional study, 240 children (8 to 18 years) from the general Dutch population completed a questionnaire about defecation disorders. After exclusions for anorectal/pelvic surgery or comorbidities, we analyzed 212 children. The prevalence of constipation was 15.6%; in a quarter of the cases, it co-occurred with fecal incontinence. We found 3% fecal incontinence without constipation. Even though children with a defecation disorder rated their bowel habits worse compared to children without defecation disorders (P < 0.001), 46% constipated children and 67% fecally incontinent children rated their bowel habits as good or very good. Moreover, 21 to 50% of children with a defecation disorder did not mention their symptoms to anybody. Interestingly, most constipated children had "normal" stool frequencies (64%) and consistencies (49%). Conclusion: The prevalence of constipation and fecal incontinence is quite high in children. Stool frequency and consistency is normal in half the constipated children, which may complicate the recognition of constipation. Finally, a considerable number of children does not recognize their disorders as constituting a problem and does not seek help, which leads to an underestimation of these disorders. What is Known: • Constipation and fecal incontinence are common in children, but their prevalence rates may be underestimated due to a variety of reasons. • Diagnosing these disorders remains challenging owing to the variety of symptoms and co-existence with other diseases. What is New: • The prevalence of constipation and fecal incontinence in children is high. • Many children do not recognize their defecation disorders as constituting a problem and do not seek help, which leads to an underestimation of the problem of these disorders

Strategies to diagnose ovarian cancer: new evidence from phase 3 of the multicentre international IOTA study

Background: To compare different ultrasound-based international ovarian tumour analysis (IOTA) strategies and risk of malignancy index (RMI) for ovarian cancer diagnosis using a meta-analysis approach of centre-specific data from IOTA3. Methods: This prospective multicentre diagnostic accuracy study included 2403 patients with 1423 benign and 980 malignant adnexal masses from 2009 until 2012. All patients underwent standardised transvaginal ultrasonography. Test performance of RMI, subjective assessment (SA) of ultrasound findings, two IOTA risk models (LR1 and LR2), and strategies involving combinations of IOTA simple rules (SRs), simple descriptors (SDs) and LR2 with and without SA was estimated using a meta-analysis approach. Reference standard was histology after surgery. Results: The areas under the receiver operator characteristic curves of LR1, LR2, SA and RMI were 0.930 (0.917–0.942), 0.918 (0.905–0.930), 0.914 (0.886–0.936) and 0.875 (0.853–0.894). Diagnostic one-step and two-step strategies using LR1, LR2, SR and SD achieved summary estimates for sensitivity 90–96%, specificity 74–79% and diagnostic odds ratio (DOR) 32.8–50.5. Adding SA when IOTA methods yielded equivocal results improved performance (DOR 57.6–75.7). Risk of Malignancy Index had sensitivity 67%, specificity 91% and DOR 17.5. Conclusions: This study shows all IOTA strategies had excellent diagnostic performance in comparison with RMI. The IOTA strategy chosen may be determined by clinical preference