A Methodology to Engineer and Validate Dynamic Multi-level Multi-agent Based Simulations

This article proposes a methodology to model and simulate complex systems, based on IRM4MLS, a generic agent-based meta-model able to deal with multi-level systems. This methodology permits the engineering of dynamic multi-level agent-based models, to represent complex systems over several scales and domains of interest. Its goal is to simulate a phenomenon using dynamically the lightest representation to save computer resources without loss of information. This methodology is based on two mechanisms: (1) the activation or deactivation of agents representing different domain parts of the same phenomenon and (2) the aggregation or disaggregation of agents representing the same phenomenon at different scales.Comment: Presented at 3th International Workshop on Multi-Agent Based Simulation, Valencia, Spain, 5th June 201

Dendritic Cells in Human Atherosclerosis: From Circulation to Atherosclerotic Plaques

Background. Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory infiltrates predominantly consisting of monocytes/macrophages and activated T cells. More recent is the implication of dendritic cells (DCs) in the disease. Since DCs were demonstrated in human arteries in 1995, numerous studies in humans suggest a role for these professional antigen-presenting cells in atherosclerosis. Aim. This paper focuses on the observations made in blood and arteries of patients with atherosclerosis. In principal, flow cytometric analyses show that circulating myeloid (m) and plasmacytoid (p) DCs are diminished in coronary artery disease, while immunohistochemical studies describe increased intimal DC counts with evolving plaque stages. Moreover, mDCs and pDCs appear to behave differently in atherosclerosis. Yet, the origin of plaque DCs and their relationship with blood DCs are unknown. Therefore, several explanations for the observed changes are postulated. In addition, the technical challenges and discrepancies in the research field are discussed. Future. Future studies in humans, in combination with experimental animal studies will unravel mechanisms leading to altered blood and plaque DCs in atherosclerosis. As DCs are crucial for inducing but also dampening immune responses, understanding their life cycle, trafficking and function in atherosclerosis will determine potential use of DCs in antiatherogenic therapies

Cardiopulmonary Exercise Testing in Pediatrics

Aerobic fitness is an important determinant of overall health. Higher aerobic fitness has been associated with many health benefits. Because myocardial ischemia is rare in children, indications for exercise testing differ in children compared to adults. Pediatric exercise testing is imperative to unravel the physiological mechanisms of a reduced aerobic fitness and to evaluate intervention effects in children and adolescents with a chronic disease or disability. Cardiopulmonary exercise testing includes the measurement of respiratory gas exchange and is the gold standard for determining aerobic fitness, as well as for examining the integrated physiological responses to exercise in pediatric medicine. As the physiological responses to exercise change during growth and development, appropriate pediatric reference values are essential for an adequate interpretation of the cardiopulmonary exercise test

Identification of Novel Astroviruses in the Gastrointestinal Tract of Domestic Cats

Astroviruses, isolated from numerous avian and mammalian species including humans, are commonly associated with enteritis and encephalitis. Two astroviruses have previously been identified in cats, and while definitive evidence is lacking, an association with enteritis is suggested. Using metagenomic next-generation sequencing of viral nucleic acids from faecal samples, we identified two novel feline astroviruses termed Feline astrovirus 3 and 4. These viruses were isolated from healthy shelter-housed kittens (Feline astrovirus 3; 6448 bp) and from a kitten with diarrhoea that was co-infected with Feline parvovirus (Feline astrovirus 4, 6549 bp). Both novel astroviruses shared a genome arrangement of three open reading frames (ORFs) comparable to that of other astroviruses. Phylogenetic analysis of the concatenated ORFs, ORF1a, ORF1b and capsid protein revealed that both viruses were phylogenetically distinct from other feline astroviruses, although their precise evolutionary history could not be accurately determined due to a lack of resolution at key nodes. Large-scale molecular surveillance studies of healthy and diseased cats are needed to determine the pathogenicity of feline astroviruses as single virus infections or in co-infections with other enteric viruses

Physical activity in relation to motor performance, exercise capacity, sports participation, parental perceptions, and overprotection in school aged children with a critical congenital heart defect

OBJECTIVE: To depict objectively measured moderate-to-vigorous physical activity (MVPA), motor performance (MP), cardiorespiratory fitness (CRF), organized sports participation, parental perceptions of vulnerability and parenting style in children with a Critical Congenital Heart Disease (CCHD), and to explore whether these factors are associated with MVPA. STUDY DESIGN: A prospective observational cohort study in 62 7-10 years old children with a CCHD. RESULTS: On average, children with CCHD spent 64 min on MVPA per day (accelerometry), 61 % met the international WHO physical activity guideline. Only 12 % had >60 min of MVPA daily. Eighteen percent had a motor delay (movement-assessment-battery-for children-II) and 38 % showed a below average CRF (cardiopulmonary exercise test using the Godfrey ramp protocol). Seventy-seven percent participated in organized sports activities at least once a week. Twenty-one percent of the parents are classified as overprotective (parent protection scale) and 7.3 % consider their child as being vulnerable (child vulnerability scale). A significant positive association was found between MVPA and MP (rs = 0.359), CRF(V̇O 2peak/ml/kg: rs = 0.472 and W peak/kg: rs = 0.396) and sports participation (rs = 0.286). Children who were perceived as vulnerable by their parents showed a significantly lower MVPA (rs = -0.302). No significant associations were found between mean MVPA and parental overprotection. CONCLUSION: Even though the majority of school aged children with a CCHD is sufficiently active, counseling parents regarding the importance of sufficient MVPA and sports participation, especially in parents who consider their child being vulnerable, could be useful. Since motor delays can be detected at an early age, motor development could be an important target to improve exercise capacity and sports participation to prevent inactivity in children with a CCHD

Feline calicivirus virulent systemic disease: Clinical epidemiology, analysis of viral isolates and in vitro efficacy of novel antivirals in australian outbreaks

Feline calicivirus (FCV) causes upper respiratory tract disease (URTD) and sporadic outbreaks of virulent systemic disease (FCV-VSD). The basis for the increased pathogenicity of FCVVSD viruses is incompletely understood, and antivirals for FCV-VSD have yet to be developed. We investigated the clinicoepidemiology and viral features of three FCV-VSD outbreaks in Australia and evaluated the in vitro efficacy of nitazoxanide (NTZ), 2′-C-methylcytidine (2CMC) and NITD008 against FCV-VSD viruses. Overall mortality among 23 cases of FCV-VSD was 39%. Metagenomic sequencing identified five genetically distinct FCV lineages within the three outbreaks, all seemingly evolving in situ in Australia. Notably, no mutations that clearly distinguished FCVURTD from FCV-VSD phenotypes were identified. One FCV-URTD strain likely originated from a recombination event. Analysis of seven amino-acid residues from the hypervariable E region of the capsid in the cultured viruses did not support the contention that properties of these residues can reliably differentiate between the two pathotypes. On plaque reduction assays, dose–response inhibition of FCV-VSD was obtained with all antivirals at low micromolar concentrations; NTZ EC50, 0.4–0.6 µM, TI = 21; 2CMC EC50, 2.7–5.3 µM, TI > 18; NITD-008, 0.5 to 0.9 µM, TI > 111. Investigation of these antivirals for the treatment of FCV-VSD is warranted

Open Problems on Central Simple Algebras

We provide a survey of past research and a list of open problems regarding central simple algebras and the Brauer group over a field, intended both for experts and for beginners.Comment: v2 has some small revisions to the text. Some items are re-numbered, compared to v

Distinct lineages of feline parvovirus associated with epizootic outbreaks in Australia, New Zealand and the United Arab Emirates

Feline panleukopenia (FPL), a frequently fatal disease of cats, is caused by feline parvovirus (FPV) or canine parvovirus (CPV). We investigated simultaneous outbreaks of FPL between 2014 and 2018 in Australia, New Zealand and the United Arab Emirates (UAE) where FPL outbreaks had not been reported for several decades. Case data from 989 cats and clinical samples from additional 113 cats were obtained to determine the cause of the outbreaks and epidemiological factors involved. Most cats with FPL were shelter-housed, 9 to 10 weeks old at diagnosis, unvaccinated, had not completed a primary vaccination series or had received vaccinations noncompliant with current guidelines. Analysis of parvoviral VP2 sequence data confirmed that all FPL cases were caused by FPV and not CPV. Phylogenetic analysis revealed that each of these outbreaks was caused by a distinct FPV, with two virus lineages present in eastern Australia and virus movement between different geographical locations. Viruses from the UAE outbreak formed a lineage of unknown origin. FPV vaccine virus was detected in the New Zealand cases, highlighting the difficulty of distinguishing the co-incidental shedding of vaccine virus in vaccinated cats. Inadequate vaccination coverage in shelter-housed cats was a common factor in all outbreaks, likely precipitating the multiple re-emergence of infection events