Systematic inference of the long-range dependence and heavy-tail distribution parameters of ARFIMA models

Long-Range Dependence (LRD) and heavy-tailed distributions are ubiquitous in natural and socio-economic data. Such data can be self-similar whereby both LRD and heavy-tailed distributions contribute to the self-similarity as measured by the Hurst exponent. Some methods widely used in the physical sciences separately estimate these two parameters, which can lead to estimation bias. Those which do simultaneous estimation are based on frequentist methods such as Whittle’s approximate maximum likelihood estimator. Here we present a new and systematic Bayesian framework for the simultaneous inference of the LRD and heavy-tailed distribution parameters of a parametric ARFIMA model with non-Gaussian innovations. As innovations we use the α-stable and t-distributions which have power law tails. Our algorithm also provides parameter uncertainty estimates. We test our algorithm using synthetic data, and also data from the Geostationary Operational Environmental Satellite system (GOES) solar X-ray time series. These tests show that our algorithm is able to accurately and robustly estimate the LRD and heavy-tailed distribution parameters

Food allergy enhances allergic asthma in mice

BackgroundAtopic march refers to the typical transition from a food allergy in early childhood to allergic asthma in older children and adults. However the precise interplay of events involving gut, skin and pulmonary inflammation in this process is not completely understood.ObjectivesTo develop a mouse model of mixed food and respiratory allergy mimicking the atopic march and better understand the impact of food allergies on asthma.MethodsFood allergy to ovalbumin (OVA) was induced through intra-peritoneal sensitization and intra-gastric challenge, and/or a respiratory allergy to house dust mite (HDM) was obtained through percutaneous sensitization and intra-nasal challenges with dermatophagoides farinae (Der f) extract. Digestive, respiratory and systemic parameters were analyzed.ResultsOVA-mediated gut allergy was associated with an increase in jejunum permeability, and a worsening of Der f-induced asthma with stronger airway hyperresponsiveness and pulmonary cell infiltration, notably eosinophils. There was overproduction of the pro-eosinophil chemokine RANTES in broncho-alveolar lavages associated with an enhanced Th2 cytokine secretion and increased total and Der f-specific IgE when the two allergies were present. Both AHR and lung inflammation increased after a second pulmonary challenge.ConclusionGut sensitization to OVA amplifies Der f-induced asthma in mice

CD9+ Regulatory B Cells Induce T Cell Apoptosis via IL-10 and Are Reduced in Severe Asthmatic Patients

CD9 was recently identified as a marker of murine IL-10-competent regulatory B cells. Functional impairments or defects in CD9+ IL-10-secreting regulatory B cells are associated with enhanced asthma-like inflammation and airway hyperresponsiveness. In mouse models, all asthma-related features can be abrogated by CD9+ B cell adoptive transfer. We aimed herein to decipher the profiles, features, and molecular mechanisms of the regulatory properties of CD9+ B cells in human and mouse. The profile of CD9+ B cells was analyzed using blood from severe asthmatic patients and normal and asthmatic mice by flow cytometry. The regulatory effects of mouse CD9+ B cells on effector T cell death, cell cycle arrest, apoptosis, and mitochondrial depolarization were determined using yellow dye, propidium iodide, Annexin V, and JC-1 staining. MAPK phosphorylation was analyzed by western blotting. Patients with severe asthma and asthmatic mice both harbored less CD19+CD9+ B cells, although these cells displayed no defect in their capacity to induce T cell apoptosis. Molecular mechanisms of regulation of CD9+ B cells characterized in mouse showed that they induced effector T cell cycle arrest in sub G0/G1, leading to apoptosis in an IL-10-dependent manner. This process occurred through MAPK phosphorylation and activation of both the intrinsic and extrinsic pathways. This study characterizes the molecular mechanisms underlying the regulation of CD9+ B cells to induce effector T cell apoptosis in mice and humans via IL-10 secretion. Defects in CD9+ B cells in blood from patients with severe asthma reveal new insights into the lack of regulation of inflammation in these patients

Holographic Vitrification

We establish the existence of stable and metastable stationary black hole bound states at finite temperature and chemical potentials in global and planar four-dimensional asymptotically anti-de Sitter space. We determine a number of features of their holographic duals and argue they represent structural glasses. We map out their thermodynamic landscape in the probe approximation, and show their relaxation dynamics exhibits logarithmic aging, with aging rates determined by the distribution of barriers.Comment: 100 pages, 25 figure

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Political, mythological and philosophical inspiration in Pindar and Horace : thoughts on ancient lyricism

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Endogenous polyclonal anti-IL-1 antibody responses potentiate IL-1 activity during pathogenic inflammation

BACKGROUND Particular neutralizing mAbs to certain cytokines act as agonists in vivo through protection of the cytokine's active site and prolongation of its half-life. Although this principle might be useful for targeted immunotherapy, its role in the pathogenesis of inflammation and autoimmunity is unclear. OBJECTIVE We sought to determine whether slight, structurally nonrelevant modifications of the prototypic proinflammatory cytokine IL-1β during an immune response could elicit polyclonal anti-IL-1β antibody responses that modulated IL-1β's in vivo activity. METHODS We engineered 2 different IL-1β variants, thereby mimicking the process of cytokine modification occurring during inflammation, and conjugated them to virus-like particles, followed by immunization of mice. The resulting polyclonal anti-IL-1β antibody responses were assessed by using in vitro and in vivo assays, as well as 2 relevant (auto-) inflammatory murine models. RESULTS Although antibody responses generated to one variant were potently inhibiting IL-1β, antibody responses induced by the other variant even potentiated the in vivo effects of IL-1β; the latter led to enhanced morbidity in 2 different IL-1β-mediated mouse models, including a model of inflammatory bowel disease and an inflammatory arthritis model. CONCLUSION These data demonstrate that endogenous polyclonal anti-cytokine antibody responses can enhance the cytokine's activity in inflammatory and autoimmune diseases

Hypothèse hygiéniste : où en est-on ? Compte rendu de l’atelier « Allergies » du DHU 2020 « Médecine personnalisées des maladies chroniques »

National audienceAllergic diseases have been increasing constantly over the past few years. With the population aging, the rising cost of healthcare is inevitable.The increasing cost of curative medicine, which has developed considerably during recent decades, will no longer be accepted. Thus, the treatmentof many chronic diseases, including allergies, must be reconsidered. Current treatments such as allergen immunotherapy are not effective enoughfor all the different types of allergies and no valid preventive treatment exists. New strategies for the treatment of chronic diseases are now beingfocused on the development of personalized medicine and on 4P (preventive, personalized, predictive, and participative) medicine. For instance,vaccines or health food products are currently being developed for populations at risk.Les maladies allergiques sont en constante augmentation depuis quelques années. Avec le vieillissement de la population, les dépenses de santévont s’accroître également. Le coût de la médecine curative, qui a considérablement été développée ces dernières décennies ne pourra plus êtresupporté demain. Ainsi les traitements de nombreuses maladies chroniques telles que les allergies doivent être reconsidérés. Les thérapies existantestelles que l’immunothérapie ne sont pas efficaces pour tous les types d’allergies et il n’existe aucun moyen validé de prévenir ces maladies. Lesnouvelles stratégies thérapeutiques des maladies chroniques se focalisent aujourd’hui sur le développement de la médecine personnalisée oumédecine 4P (prédictive, préventive, personnalisée et participative). Ainsi, l’élaboration de vaccins ou encore d’aliment-santé à destination despopulations à risque est en cours