Calprotectin instability may lead to undertreatment in children with IBD

BACKGROUND: Treatment decisions in children with inflammatory bowel disease (IBD) are increasingly based on longitudinal tracking of faecal calprotectin concentrations, but there is little known about the stability of this protein in stool. METHODS: We stored aliquots of homogenised stool at room temperature and at 4°C, and measured the calprotectin concentration for 6 consecutive days with three different assays. In addition, we assessed calprotectin stability in assay-specific extraction buffers kept at room temperature. RESULTS: After 6 days of storage at room temperature, mean percentage change from baseline calprotectin concentrations in stool and extraction buffer was 35% and 46%, respectively. The stability of calprotectin was significantly better preserved in samples stored at 4°C (p=0.0066 and 0.0011, respectively). CONCLUSIONS: Calprotectin is not stable at room temperature. Children with IBD and their caretakers may be falsely reassured by low calprotectin values. The best advisable standard for preanalytical calprotectin handling is refrigeration of the stool sample until delivery at the hospital laboratory

Discrete Control of Response for Cybersecurity in Industrial Control

International audienceCybersecurity in Industrial Control Systems (ICS) is a crucial problem, as recent history has shown. A notable characteristic of ICS, compared to Information Technology, is the necessity to take into account the physical process, and its specific dynamics and effects on the environment, when considering cybersecurity issues. Intrusion Detection Systems have been studied extensively. In our work, we address the less classic topic of response mechanisms, and their automation in a self-protection feedback loop. More precisely, we address self-protection seen as resilience, where the functionality of the system is maintained under attacks, be it in a degraded mode. We model this as a Discrete Event Systems supervisory control problem, involving a model of the plant's possible behaviors, a model of considered attacks, and a formulation of the control objectives. We consider a case study, and perform a prototype implementation and simulation, using the Heptagon/BZR programming language and compiler/code generator, and targeting a multi-PLC experimental platform

Developing a French FrameNet: Methodology and First results

International audienceThe Asfalda project aims to develop a French corpus with frame-based semantic annotations and automatic tools for shallow semantic analysis. We present the first part of the project: focusing on a set of notional domains, we delimited a subset of English frames, adapted them to French data when necessary, and developed the corresponding French lexicon. We believe that working domain by domain helped us to enforce the coherence of the resulting resource, and also has the advantage that, though the number of frames is limited (around a hundred), we obtain full coverage within a given domain

Prenatal Environmental Exposure to Persistent Organic Pollutants and Reproductive Hormone Profile and Pubertal Development in Dutch Adolescents

Persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs), may interfere with hormonal processes. Knowledge about the effects of prenatal exposure to PCBs and their hydroxylated metabolites (OH-PCBs) on pubertal development is limited. Therefore, the aim of the current study was to determine whether prenatal environmental PCB and OH-PCB exposure are associated with reproductive hormone levels and pubertal characteristics in 13- to 15-year-old children. In this Dutch observational cohort study, 194 mother-infant pairs were included (1998-2002). Maternal pregnancy serum levels of PCBs, OH-PCBs, and other POPs were measured. At follow-up (2014-2016), we measured serum or plasma levels of reproductive hormones in their children. We assessed Tanner stages and testicular volume (by clinician or standardized self-assessment), and participants completed questionnaires on pubertal onset. In total, 101 adolescents (14.4 ± 0.8 years; 53.7% of invited) participated, and 55 were boys. In boys, higher prenatal PCB levels were associated with higher testosterone levels, higher pubic hair stage, larger testicular volume, and younger age at onset of growth spurt and voice break. In girls, higher prenatal PCB levels were associated with higher stages for breast development. In conclusion, higher prenatal PCB exposure could be associated with more advanced pubertal development in 13- to 15-year-old children

Reference values of fecal calgranulin C (S100A12) in school aged children and adolescents

Background: Calgranulin C (S100A12) is an emerging marker of inflammation. It is exclusively released by activated neutrophils which makes this marker potentially more specific for inflammatory bowel disease (IBD) compared to established stool markers including calprotectin and lactoferrin. We aimed to establish a reference value for S100A12 in healthy children and investigated whether S100A12 levels can discriminate children with IBD from healthy controls. Methods: In a prospective community-based reference interval study we collected 122 stool samples from healthy children aged 5-19 years. Additionally, feces samples of 41 children with suspected IBD (who were later confirmed by endoscopy to have IBD) were collected. Levels of S100A12 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) (Inflamark (R)). The limit of detection was 0.22 mu g/g. Results: The upper reference limit in healthy children was 0.75 mu g/g (90% confidence interval: 0.30-1.40). Median S100A12 levels were significantly higher in patients with IBD (8.00 mu g/g [interquartile range (IQR) 2.5-11.6] compared to healthy controls [0.22 mu g/g (IQR <0.22); p <0.001]). The best cutoff point based on receiver operating characteristic curve was 0.33 mu g/g (sensitivity 93%; specificity 97%). Conclusions: Children and teenagers with newly diagnosed IBD have significantly higher S100A12 results compared to healthy individuals. We demonstrate that fecal S100A12 shows diagnostic promise under ideal testing conditions. Future studies need to address whether S100A12 can discriminate children with IBD from nonorganic disease in a prospective cohort with chronic gastrointestinal complaints, and how S100A12 performs in comparison with established stool markers

Perspectives of healthcare providers, service users, and family members about mental illness stigma in primary care settings: A multi-site qualitative study of seven countries in Africa, Asia, and Europe

Background: Stigma among healthcare providers is a barrier to the effective delivery of mental health services in primary care. Few studies have been conducted in primary care settings comparing the attitudes of healthcare providers and experiences of people with mental illness who are service users in those facilities. Such research is necessary across diverse global settings to characterize stigma and inform effective stigma reduction. Methods: Qualitative research was conducted on mental illness stigma in primary care settings in one low-income country (Nepal), two lower-middle income countries (India, Tunisia), one upper-middle-income country (Lebanon), and three high-income countries (Czech Republic, Hungary, Italy). Qualitative interviews were conducted with 248 participants: 64 primary care providers, 11 primary care facility managers, 111 people with mental illness, and 60 family members of people with mental illness. Data were analyzed using framework analysis. Results: Primary care providers endorsed some willingness to help persons with mental illness but reported not having appropriate training and supervision to deliver mental healthcare. They expressed that people with mental illness are aggressive and unpredictable. Some reported that mental illness is incurable, and mental healthcare is burdensome and leads to burnout. They preferred mental healthcare to be delivered by specialists. Service users did not report high levels of discrimination from primary care providers; however, they had limited expectations of support from primary care providers. Service users reported internalized stigma and discrimination from family and community members. Providers and service users reported unreliable psychiatric medication supply and lack of facilities for confidential consultations. Limitations of the study include conducting qualitative interviews in clinical settings and reliance on clinician-researchers in some sites to conduct interviews, which potentially biases respondents to present attitudes and experiences about primary care services in a positive manner. Conclusions: Primary care providers' willingness to interact with people with mental illness and receive more training presents an opportunity to address stigmatizing beliefs and stereotypes. This study also raises important methodological questions about the most appropriate strategies to accurately understand attitudes and experiences of people with mental illness. Recommendations are provided for future qualitative research about stigma, such as qualitative interviewing by non-clinical personnel, involving non-clinical staff for recruitment of participants, conducting interviews in non-clinical settings, and partnering with people with mental illness to facilitate qualitative data collection and analysis

Characterization of a new simian immunodeficiency virus strain in a naturally infected Pan troglodytes troglodytes chimpanzee with AIDS related symptoms

<p>Abstract</p> <p>Background</p> <p>Data on the evolution of natural SIV infection in chimpanzees (SIVcpz) and on the impact of SIV on local ape populations are only available for Eastern African chimpanzee subspecies (<it>Pan troglodytes schweinfurthii</it>), and no data exist for Central chimpanzees (<it>Pan troglodytes troglodytes</it>), the natural reservoir of the ancestors of HIV-1 in humans. Here, we report a case of naturally-acquired SIVcpz infection in a <it>P.t.troglodytes </it>chimpanzee with clinical and biological data and analysis of viral evolution over the course of infection.</p> <p>Results</p> <p>A male chimpanzee (Cam155), 1.5 years, was seized in southern Cameroon in November 2003 and screened SIV positive during quarantine. Clinical follow-up and biological analyses have been performed for 7 years and showed a significant decline of CD4 counts (1,380 cells/mm³in 2004 vs 287 in 2009), a severe thrombocytopenia (130,000 cells/mm³in 2004 vs 5,000 cells/mm³in 2009), a weight loss of 21.8% from August 2009 to January 2010 (16 to 12.5 kg) and frequent periods of infections with diverse pathogens.</p> <p>DNA from PBMC, leftover from clinical follow-up samples collected in 2004 and 2009, was used to amplify overlapping fragments and sequence two full-length SIVcpz<it>Ptt</it>-Cam155 genomes. SIVcpz<it>Ptt</it>-Cam155 was phylogenetically related to other SIVcpz<it>Ptt </it>from Cameroon (SIVcpz<it>Ptt</it>-Cam13) and Gabon (SIVcpz<it>Ptt</it>-Gab1). Ten molecular clones 5 years apart, spanning the V1V4 gp120 <it>env </it>region (1,100 bp), were obtained. Analyses of the <it>env </it>region showed positive selection (dN-dS >0), intra-host length variation and extensive amino acid diversity between clones, greater in 2009. Over 5 years, N-glycosylation site frequency significantly increased (p < 0.0001).</p> <p>Conclusions</p> <p>Here, we describe for the first time the clinical history and viral evolution of a naturally SIV infected <it>P.t.troglodytes </it>chimpanzee. The findings show an increasing viral diversity over time and suggest clinical progression to an AIDS-like disease, showing that SIVcpz can be pathogenic in its host, as previously described in <it>P.t.schweinfurthii</it>. Although studying the impact of SIV infection in wild apes is difficult, efforts should be made to better characterize the pathogenicity of the ancestors of HIV-1 in their natural host and to find out whether SIV infection also plays a role in ape population decline.</p

Report on SHAFE policies, strategies and funding

The objective of Working Group (WG) 4 of the COST Action NET4Age-Friendly is to examine existing policies, advocacy, and funding opportunities and to build up relations with policy makers and funding organisations. Also, to synthesize and improve existing knowledge and models to develop from effective business and evaluation models, as well as to guarantee quality and education, proper dissemination and ensure the future of the Action. The Working Group further aims to enable capacity building to improve interdisciplinary participation, to promote knowledge exchange and to foster a cross-European interdisciplinary research capacity, to improve cooperation and co-creation with cross-sectors stakeholders and to introduce and educate students SHAFE implementation and sustainability (CB01, CB03, CB04, CB05). To enable the achievement of the objectives of Working Group 4, the Leader of the Working Group, the Chair and Vice-Chair, in close cooperation with the Science Communication Coordinator, developed a template (see annex 1) to map the current state of SHAFE policies, funding opportunities and networking in the COST member countries of the Action. On invitation, the Working Group lead received contributions from 37 countries, in a total of 85 Action members. The contributions provide an overview of the diversity of SHAFE policies and opportunities in Europe and beyond. These were not edited or revised and are a result of the main areas of expertise and knowledge of the contributors; thus, gaps in areas or content are possible and these shall be further explored in the following works and reports of this WG. But this preliminary mapping is of huge importance to proceed with the WG activities. In the following chapters, an introduction on the need of SHAFE policies is presented, followed by a summary of the main approaches to be pursued for the next period of work. The deliverable finishes with the opportunities of capacity building, networking and funding that will be relevant to undertake within the frame of Working Group 4 and the total COST Action. The total of country contributions is presented in the annex of this deliverable

FGFR3, HRAS, KRAS, NRAS and PIK3CA Mutations in Bladder Cancer and Their Potential as Biomarkers for Surveillance and Therapy

Background: Fifty percent of patients with muscle-invasive bladder cancer (MI-BC) die from their disease and current chemotherapy treatment only marginally increases survival. Novel therapies targeting receptor tyrosine kinases or activated oncogenes may improve outcome. Hence, it is necessary to stratify patients based on mutations in relevant oncogenes. Patients with non-muscle-invasive bladder cancer (NMI-BC) have excellent survival, however two-thirds develop recurrences. Tumor specific mutations can be used to detect recurrences in urine assays, presenting a more patient-friendly diagnostic procedure than cystoscopy. Methodology/Principal Findings: To address these issues, we developed a mutation assay for the simultaneous detection of 19 possible mutations in the HRAS, KRAS, and NRAS genes. With this assay and mutation assays for the FGFR3 and PIK3CA oncogenes, we screened primary bladder tumors of 257 patients and 184 recurrences from 54 patients. Additionally, in primary tumors p53 expression was obtained by immunohistochemistry. Of primary tumors 64% were mutant for FGFR3, 11% for RAS, 24% for PIK3CA, and 26% for p53. FGFR3 mutations were mutually exclusive with RAS mutations (p = 0.001) and co-occurred with PIK3CA mutations (p = 0.016). P53 overexpression was mutually exclusive with PIK3CA and FGFR3 mutations (p≤0.029). Mutations in the RAS and PIK3CA genes were not predictors for recurrence-free, progression-free and disease-specific survival. In patients presenting with NMI-BC grade 3 and MI-BC, 33 and 36% of the primary tumors were mutant. In patients with low-grade NMI-BC, 88% of the primary tumors carried a mutation and 88% of the recurrences were mutant. Conclusions/Significance: The mutation assays present a companion diagnostic to define patients for targeted therapies. In addition, the assays are a potential biomarker to detect recurrences during surveillance. We showed that 88% of patients presenting with low-grade NMI-BC are eligible for such a follow-up. This may contribute to a reduction in the number of cystoscopical examinations