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This article discusses a study that aimed to improve the sensitivity of brush cytology in patients with suspected perihilar or intrahepatic cholangiocarcinoma (pCCA/iCCA). The researchers implemented a new protocol for obtaining, handling, and rating brush cytology samples. They found that the sensitivity of brush cytology increased from 50.9% to 88.3% after the protocol implementation. The study also explored the use of next-generation sequencing (NGS), multiple brushes, and intraductal biopsies to further increase sensitivity. The findings suggest that these modifications can significantly improve the accuracy of diagnosing malignant disease in patients with suspected pCCA or iCCA. [Extracted from the article]

We describe a case of a boy with neurodevelopmental delay and a diffuse large B-cell lymphoma (DLBCL) in whom we discovered a germline de novo 2p16.3 deletion including MSH6 and part of the FBXO11 gene. A causative role for MSH6 in cancer development was excluded based on tumor characteristics. The constitutional FBXO11 deletion explains the neurodevelopmental delay in the patient. The FBXO11 protein is involved in BCL-6 ubiquitination and BCL-6 is required for the germinal center reaction resulting in B cell differentiation. Somatic loss of function alterations of FBXO11 result in BCL-6 overexpression which is a known driver in DLBCL. We therefore consider that a causative relationship between the germline FBXO11 deletion and the development of DLBCL in this boy is conceivable. [ABSTRACT FROM AUTHOR]

Background: Asthma is a chronic respiratory disease which is not curable, yet some patients experience spontaneous remission. We hypothesized that epigenetic mechanisms may be involved in asthma remission. Methods: Clinical remission (ClinR) was defined as the absence of asthma symptoms and medication for at least 12 months, and complete remission (ComR) was defined as ClinR with normal lung function and absence of airway hyperresponsiveness. We analyzed differential DNA methylation of ClinR and ComR comparing to persistent asthma (PersA) in whole blood samples (n = 72) and nasal brushing samples (n = 97) in a longitudinal cohort of well characterized asthma patients. Significant findings of whole blood DNA methylation were tested for replication in two independent cohorts, Lifelines and Epidemiological study on the Genetics and Environment of Asthma (EGEA). Results: We identified differentially methylated CpG sites associated with ClinR (7 CpG sites) and ComR (129 CpG sites) in whole blood. One CpG (cg13378519, Chr1) associated with ClinR was replicated and annotated to PEX11 (Peroxisomal Biogenesis Factor 11 Beta). The whole blood DNA methylation levels of this CpG were also different between ClinR and healthy subjects. One ComR-associated CpG (cg24788483, Chr10) that annotated to TCF7L2 (Transcription Factor 7 Like 2) was replicated and associated with expression of TCF7L2 gene. One out of seven ClinR-associated CpG sites and 8 out of 129 ComR-associated CpG sites identified from whole blood samples showed nominal significance (P < 0.05) and the same direction of effect in nasal brushes. Conclusion: We identified DNA methylation markers possibly associated with clinical and complete asthma remission in nasal brushes and whole blood, and two CpG sites identified from whole blood can be replicated in independent cohorts and may play a role in peroxisome proliferation and Wnt signaling pathway. [ABSTRACT FROM AUTHOR]

To the editor, Asthma, one of the most common chronic diseases in childhood, is caused by interactions between genes and environmental factors. Since the IL-33/IL1RL1 pathway has been associated with eosinophilic, type 2, inflammation, we hypothesized that I IL1RL1 i SNPs may affect corticosteroid treatment response in asthma patients. No association between I IL1RL1 i and questionnaire-based asthma control was found. [Extracted from the article]

Summary: Background: Asthma is a chronic respiratory disease without a cure, although there exists spontaneous remission. Genome‐wide association (GWA) studies have pinpointed genes associated with asthma development, but did not investigate asthma remission. Objective: We performed a GWA study to develop insights in asthma remission. Methods: Clinical remission (ClinR) was defined by the absence of asthma treatment and wheezing in the last year and asthma attacks in the last 3 years and complete remission (ComR) similarly but additionally with normal lung function and absence of bronchial hyperresponsiveness (BHR). A GWA study on both ClinR and ComR was performed in 790 asthmatics with initial doctor diagnosis of asthma and BHR and long‐term follow‐up. We assessed replication of the 25 top single nucleotide polymorphisms (SNPs) in 2 independent cohorts (total n = 456), followed by expression quantitative loci (eQTL) analyses of the 4 replicated SNPs in lung tissue and epithelium. Results: Of the 790 asthmatics, 178 (23%) had ClinR and 55 ComR (7%) after median follow‐up of 15.5 (range 3.3‐47.8) years. In ClinR, 1 of the 25 SNPs, rs2740102, replicated in a meta‐analysis of the replication cohorts, which was an eQTL for POLI in lung tissue. In ComR, 3 SNPs replicated in a meta‐analysis of the replication cohorts. The top‐hit, rs6581895, almost reached genome‐wide significance (P‐value 4.68 × 10−7) and was an eQTL for FRS2 and CCT in lung tissue. Rs1420101 was a cis‐eQTL in lung tissue for IL1RL1 and IL18R1 and a trans‐eQTL for IL13. Conclusions and Clinical Relevance: By defining a strict remission phenotype, we identified 3 SNPs to be associated with complete asthma remission, where 2 SNPs have plausible biological relevance in FRS2,CCT,IL1RL1, IL18R1 and IL13. [ABSTRACT FROM AUTHOR]

Wheezing is common in childhood. However, current prediction models of pediatric asthma have only modest accuracy. Novel biomarkers and definition of subphenotypes may improve asthma prediction. Interleukin-1-receptor-like-1 ( IL1RL1 or ST2) is a well-replicated asthma gene and associates with eosinophilia. We investigated whether serum sST2 predicts asthma and asthma with elevated exhaled NO (Fe NO), compared to the commonly used Asthma Prediction Index ( API). Using logistic regression modeling, we found that serum sST2 levels in 2-3 years-old wheezers do not predict doctors' diagnosed asthma at age 6 years. Instead, sST2 predicts a subphenotype of asthma characterized by increased levels of Fe NO, a marker for eosinophilic airway inflammation. Herein, sST2 improved the predictive value of the API ( AUC=0.70, 95% CI 0.56-0.84), but had also significant predictive value on its own ( AUC=0.65, 95% CI 0.52-0.79). Our study indicates that sST2 in preschool wheezers has predictive value for the development of eosinophilic airway inflammation in asthmatic children at school age. [ABSTRACT FROM AUTHOR]

Background European Union (EU) Directive 89/391 addressed occupational health surveillance, which recommends to provide workers with 'access to health surveillance at regular intervals', aiming to prevent work-related and occupational diseases. Aims To investigate how EU countries adopted this Directive. Methods We invited one selected representative per member state to complete a questionnaire. Results All 28 EU countries implemented the Directive in some form. Workers' health surveillance (WHS) is available to all workers in 15 countries, while in 12, only specific subgroups have access. In 21 countries, workers' participation is mandatory, and in 22, the employer covers the cost. In 13 countries, access to WHS is not available to all workers but depends on exposure to specific risk factors, size of the enterprise or belonging to vulnerable groups. In 26 countries, the employer appoints and revokes the physician in charge of WHS. Twelve countries have no recent figures, reports or costbenefit analyses of their WHS programmes. In 15 countries where reports exist, they are often in the native language. Conclusions Coverage and quality of occupational health surveillance should be evaluated to facilitate learning from good practice and from scientific studies. We propose a serious debate in the EU with the aim of protecting workers more effectively, including the use of evidence-based WHS programmes. [ABSTRACT FROM AUTHOR]

O01 Serum IL-1RL1-A levels predict an eosinophilic subtype of asthma in preschool wheezing ch... M. E. Ketelaar 1, K. Van De Kant 2, F. N. Dijk 1, E. M. M. Klaassen 3, N. Grotenboer 4,... 1 University Medical Center Groningen, Beatrix Children's Hospital, Groningen Research Instit... B Correspondence b : Maria Elizabeth Ketelaar - m.e.ketelaar@student.rug.nl I Clinical and Translational Allergy i 2017, B 7(Suppl 2) b :O01 B Introduction b : Respiratory symptoms are common in preschool children. The children were divided into four groups - 10 children with scoliosis without asthma (Sc),10 children with scoliosis and asthma (AS), 10 children with moderate asthma (BA), 10 children with severe asthma (SA) and 10 healthy children (HC). B Keywords b : Preschool Wheezing, Respiratory Viruses, Asthma Exacerbation, Severity P09 Tele-monitoring decreases unscheduled outpatient visits in pediatric patients with severe... Mihai Craiu, Iustina Violeta Stan INSMC Alessandrescu-Rusescu, Bucharest, Romania B Correspondence b : Mihai Craiu - mcraiu@yahoo.com I Clinical and Translational Allergy i 2017, B 7(Suppl 2) b :P09 B Introduction b : Pediatric asthma patients originating from poor-resource areas experience a significant increase of unscheduled and emergency department visits and most of medical care for them is delivered in such a facility. [Extracted from the article]

Background Animal data have suggested that the transient receptor potential ankyrin-1 ( TRPA1) ion channel plays a key role in promoting airway inflammation in asthma and may mediate effects of paracetamol on asthma, yet confirmatory human data are lacking. To study associations of TRPA1 gene variants with childhood asthma and total IgE concentration, and interactions between TRPA1 and prenatal paracetamol exposure on these outcomes. Methods We analysed associations between 31 TRPA1 single nucleotide polymorphisms ( SNPs) and current doctor-diagnosed asthma and total IgE concentration at 7.5 years in the Avon Longitudinal Study of Parents and Children ( ALSPAC) birth cohort. We sought to confirm the most significant associations with comparable outcomes in the Prevention and Incidence of Asthma and Mite Allergy ( PIAMA) and Generation R birth cohorts. In ALSPAC, we explored interactions with prenatal paracetamol exposure. Results In ALSPAC, there was strong evidence for association between six SNPs and asthma: rs959974 and rs1384001 (per-allele odds ratio for both: 1.30 (95% CI: 1.15-1.47), p = 0.00001), rs7010969 ( OR 1.28 (1.13-1.46), p = 0.00004), rs3735945 ( OR 1.30 (1.09-1.55), p = 0.003), rs920829 ( OR 1.30 (1.09-1.54), p = 0.004) and rs4738202 ( OR 1.22 (1.07-1.39), p = 0.004). In a meta-analysis across the three cohorts, the pooled effect estimates confirmed that all six SNPs were significantly associated with asthma. In ALSPAC, TRPA1 associations with asthma were not modified by prenatal paracetamol, although associations with IgE concentration were. Conclusion This study suggests that TRPA1 may play a role in the development of childhood asthma. (249 words) [ABSTRACT FROM AUTHOR]

Introduction: Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation. Methods: A systematic search was performed in Pubmed, Embase and the Cochrane Library for original articles using IRE on pancreas, liver or surrounding structures in animal or human studies. Data on pathology and time between IRE and evaluation were extracted. Results: Of 2602 screened studies, 36 could be included, regarding IRE in liver (n = 24), pancreas (n = 4), blood vessels (n = 4) and nerves (n = 4) in over 440 animals (pig, rat, goat and rabbit). No eligible human studies were found. In liver and pancreas, the first signs of apoptosis and haemorrhage were observed 1–2 hours after treatment, and remained visible until 24 hours in liver and 7 days in pancreas after which the damaged tissue was replaced by fibrosis. In solitary blood vessels, the tunica media, intima and lumen remained unchanged for 24 hours. After 7 days, inflammation, fibrosis and loss of smooth muscle cells were demonstrated, which persisted until 35 days. In nerves, the median time until demonstrable histological changes was 7 days. Conclusions: Tissue damage after IRE is a dynamic process with remarkable time differences between tissues in animals. Whereas pancreas and liver showed the first damages after 1–2 hours, this took 24 hours in blood vessels and 7 days in nerves. [ABSTRACT FROM AUTHOR]

A single‐sideband opto‐RF oscillator based on a monolithic InGaAsP chip containing two distributed feedback (DFB) lasers is demonstrated. The heterodyne signal is stabilised by a hybrid method, combining optical and electronic feedback. It leads to a locking of the beating frequency onto a filtered version of itself. The table‐top setup provides a phase noise level down to −75 dBc/Hz at 1 kHz offset from a 10 GHz carrier. Potential phase noise improvement and integration scheme in a single component are discussed. [ABSTRACT FROM AUTHOR]

This paper describes the advantages that the introduction of photonic integration technologies can bring to the development of photonic-enabled wireless communications systems operating in the millimeter wave frequency range. We present two approaches for the development of dual wavelength sources for heterodyne-based millimeter wave generation realized using active/passive photonic integration technology. One approach integrates monolithically two distributed feedback semiconductor lasers along with semiconductor optical amplifiers, wavelength combiners, electro-optic modulators and broad bandwidth photodiodes. The other uses a generic photonic integration platform, developing narrow linewidth dual wavelength lasers based on arrayed waveguide gratings. Moreover, data transmission over a wireless link at a carrier wave frequency above 100 GHz is presented, in which the two lasers are free-running, and the modulation is directly applied to the single photonic chip without the requirement of any additional component. [ABSTRACT FROM PUBLISHER]

We present two different photonic integrated circuits aimed to generate electrical signals within the microwave and millimeter wave range with two different techniques. The first approach uses the heterodyne technique, implementing a monolithic dual wavelength source by integrating on a single chip two distributed feedback (DFB) lasers together with the high speed photodiode. The second approach, using mode locked lasers, describes a novel device structure based on multimode interference reflectors (MIR). [ABSTRACT FROM AUTHOR]

Purpose: General practitioners play or should play a role in occupational medicine (OM), either in diagnosing occupational diseases or in counseling on return to work. Nevertheless, their training has been reported to be insufficient in most single country studies. Aims: The objectives of this study were to analyze the content and extent of undergraduate teaching of OM in European medical schools. Methods: An e-mail questionnaire survey of the teaching of OM to undergraduates was undertaken from December 2010 to April 2011 in all medical schools and medical faculties listed in 27 European countries ( n = 305). Results: Among the 305 universities identified, 135 answered to the questionnaire, giving a response rate of 44 %. The mean number of hours given to formal instruction in occupational medicine to medical undergraduates was 25.5 h. Nevertheless, this number of hours varied widely between countries, but also within countries. Overall, 27 % of medical schools gave their students 10 h of teaching or less, 52 % 20 h or less and 69 % 30 h or less. Whereas occupational diseases and principles of prevention were covered in most schools, disability and return to work were very poorly represented among the topics that were taught to students. Conclusion: Dedicated undergraduate teaching on occupational health or OM in European medical schools is present in most medical schools, usually at a low level, but is very variable between and within countries. Medical schools across Europe are very unequal to provide qualifying doctors education on the topics they will frequently come across in their working lives. [ABSTRACT FROM AUTHOR]

Aberrant expression of human leukocyte antigens (HLA) class I has prognostic importance in various cancers. Here, we evaluated the prognostic value of classical (A/B/C) and nonclassical (G/E) HLA expression in 169 high grade epithelial ovarian cancer samples and linked that to clinicopathological characteristics and survival. Expression of HLA-A, -B/C, or -E was not correlated with survival. Survival was prolonged when tumours expressed HLA-G (P = 0.008) and HLA-G was an independent predictor for better survival (P = 0.011). In addition, HLA-G expression was associated with longer progression-free survival (P = 0.036) and response to chemotherapy {P = 0.014). Accordingly, high expression of HLA-G mRNA was associated with prolonged disease-free survival (P = 0.037) in 65 corresponding samples. Elevated serum-soluble HLA-G levels as measured by enzyme-linked immunosorbent assay in 50 matched patients were not correlated to HLA-G protein expression or gene expression nor with survival. During treatment, sHLA-G levels declined {P = 0.038). In conclusion, expression of HLA-G is an independent prognostic factor for improved survival in high grade epithelial ovarian cancer and a predictor for platinum sensitivity. [ABSTRACT FROM AUTHOR]

Purpose: Genetic research has opened up possibilities for identification of persons with an increased susceptibility for occupational disease. However, regulations considering the ethical issues that are inevitably associated with the use of genetic tests for susceptibility for occupational diseases are scarce. We investigated whether opinions of an intended stakeholder group, that is, student nurses, are sufficiently addressed by existing recommendations. Methods: Attitudes and opinions of Dutch student nurses toward a genetic test for susceptibility to occupational contact eczema were studied in a qualitative setup using focus groups, interviews and electronic questionnaires. The results were compared with guidelines and recommendations extracted from the literature. Results: Sixty-nine percent of the student nurses said they would partake in a genetic test for susceptibility to occupational contact eczema when available. Concerns were expressed regarding the difficulty of interpreting test results, the utility of the test result in practice and the necessity of genetic tests for non-severe diseases. For the issue of privacy and confidentiality, the students expressed few worries and much confidence. The existing guidelines largely covered the students' opinions. Still, the data emphasized the need for good individual risk communication both before and after testing, taking into account that the test concerns susceptibility. Conclusions: Comparing the students' statements with the issues addressed by the guidelines, we conclude that the guidelines should pay more attention to risk communication and practical advice accompanying the test results. [ABSTRACT FROM AUTHOR]