Molecular diagnosis in allergy Sastre, J.
Clinical and experimental allergy,
October 2010, Volume:
40, Issue:
10
Journal Article
Peer reviewed
Summary
Development and progress made in the field of recombinant allergens have allowed for the development of a new concept in allergy diagnosis, molecular diagnosis (MD), which makes it possible ...to identify potential disease‐eliciting molecules. Microarray‐based testing performed with a small amount of serum sample enables clinicians to determine specific‐IgE antibodies against multiple recombinants or purified natural allergen components. Performance characteristics of allergens so far tested are comparable with current diagnostic tests, but have to be confirmed in larger studies. The use of allergen components and the successful interpretation of test results in the clinic require some degree of knowledge about the basis of allergen components and their clinical implications. Allergen components can be classified by protein families based on their function and structure. This review provides a brief overview of basic information on allergen components, recombinants or purified, currently available or soon to become commercially available in ImmunoCAP or ISAC® systems, including names, protein family and function. Special consideration is given to primary or species‐specific sensitization and possible cross‐reactivity, because one of the most important clinical utility of MD is its ability to reveal whether the sensitization is genuine in nature (primary, species‐specific) or if it is due to cross‐reactivity to proteins with similar protein structures, which may help to evaluate the risk of reaction on exposure to different allergen sources. MD can be a support tool for choosing the right treatment for the right patient with the right timing. Such information will eventually give clinicians the possibility to individualize the actions taken, including an advice on targeted allergen exposure reduction, selection of suitable allergens for specific immunotherapy, or the need to perform food challenges. Nevertheless, all in vitro tests should be evaluated together with the clinical history, because allergen sensitization does not necessarily imply clinical responsiveness.
Cite this as: J. Sastre, Clinical & Experimental Allergy, 2010 (40) 1442–1460.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
This paper presents a new family of methods for evaluating matrix polynomials more efficiently than the state-of-the-art Paterson–Stockmeyer method. Examples of the application of the methods to the ...Taylor polynomial approximation of matrix functions like the matrix exponential and matrix cosine are given. Their efficiency is compared with that of the best existing evaluation schemes for general polynomial and rational approximations, and also with a recent method based on mixed rational and polynomial approximants. For many years, the Paterson–Stockmeyer method has been considered the most efficient general method for the evaluation of matrix polynomials. In this paper we show that this statement is no longer true. Moreover, for many years rational approximations have been considered more efficient than polynomial approximations, although recently it has been shown that often this is not the case in the computation of the matrix exponential and matrix cosine. In this paper we show that in fact polynomial approximations provide a higher order of approximation than the state-of-the-art computational methods for rational approximations for the same cost in terms of matrix products.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Moderate and severe forms of allergic diseases such as atopic dermatitis and asthma are a challenge for clinicians. In these conditions, which severely affect the quality of life of the patient and ...frequently have associated allergic comorbidities, the therapeutic options are often very limited. Treatment with systemic corticosteroids and immunosuppressants has adverse effects in the long term, and a significant proportion of patients remain refractory to therapy. In this context, the emerging biological drugs constitute a truly innovative therapeutic approach. A leading example is dupilumab, a monoclonal antibody targeting the α chain of the interleukin (IL)-4 receptor. Dupilumab inhibits the biological effects of the cytokines IL-4 and IL-13, which are key drivers in the TH2 response. The efficacy and safety profile of dupilumab in the treatment of allergic diseases has been tested for more than 10 years in a variety of large clinical trials in atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyposis, and eosinophilic esophagitis. In 2017, the United States Food and Drug Administration and the European Medicines Agency approved the use of dupilumab for the treatment of adult patients with moderateto-severe atopic dermatitis whose disease is not adequately controlled with prescribed topical treatment. The results of phase III clinical studies of dupilumab in patients with persistent, uncontrolled asthma have been highly promising. The safety and tolerability profile of dupilumab has proven to be very favorable in long-term clinical trials. In this review, we focus on the mechanism of action of dupilumab, its development, and its impact on daily clinical practice in allergic diseases.
In this work, we address the problem of multi-vehicle detection and tracking for traffic monitoring applications. We preset a novel intelligent visual sensor for tracking-by-detection with ...simultaneous pose estimation. Essentially, we adapt an Extended Kalman Filter (EKF) to work not only with the detections of the vehicles but also with their estimated coarse viewpoints, directly obtained with the vision sensor. We show that enhancing the tracking with observations of the vehicle pose, results in a better estimation of the vehicles trajectories. For the simultaneous object detection and viewpoint estimation task, we present and evaluate two independent solutions. One is based on a fast GPU implementation of a Histogram of Oriented Gradients (HOG) detector with Support Vector Machines (SVMs). For the second, we adequately modify and train the Faster R-CNN deep learning model, in order to recover from it not only the object localization but also an estimation of its pose. Finally, we publicly release a challenging dataset, the GRAM Road Traffic Monitoring (GRAM-RTM), which has been especially designed for evaluating multi-vehicle tracking approaches within the context of traffic monitoring applications. It comprises more than 700 unique vehicles annotated across more than 40.300 frames of three videos. We expect the GRAM-RTM becomes a benchmark in vehicle detection and tracking, providing the computer vision and intelligent transportation systems communities with a standard set of images, annotations and evaluation procedures for multi-vehicle tracking. We present a thorough experimental evaluation of our approaches with the GRAM-RTM, which will be useful for establishing further comparisons. The results obtained confirm that the simultaneous integration of vehicle localizations and pose estimations as observations in an EKF, improves the tracking results.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Histamine, acting predominantly via the H1-receptor, is an important mediator of the symptoms of allergy. H1-antihistamines, which stabilize the receptor in its inactive form, are the treatment of ...choice for some chronic allergic conditions. Ebastine is a well-established secondgeneration oral H1-antihistamine that is administered once daily at a dose of 10-20 mg and is available both as a standard tablet and as a fast-dissolving tablet that disintegrates in the mouth. Ebastine has been shown to relieve symptoms in patients with allergic rhinitis or urticaria in multiple clinical trials. In addition to its antihistamine effects, the drug has modulating effects on the allergic inflammatory process, thus potentially explaining its beneficial effect on nasal obstruction in some patients. Ebastine is generally well tolerated at recommended doses and is one of the lowest-risk antihistamines with respect to adverse cognitive/psychomotor effects, as confirmed by decades of pharmacovigilance. New long-term data confirm its efficacy and tolerability during up to 1 year of treatment in patients with chronic urticaria.
In this paper, we introduce a numerical method based on Artificial Neural Networks (ANNs) for the analysis of black hole solutions to the Einstein-axion-dilaton system in a high dimensional parabolic ...class. Leveraging a profile root-finding technique based on General Relativity we describe an ANN solver to directly tackle the system of ordinary differential equations. Through our extensive numerical analysis, we demonstrate, for the first time, that there is no self-similar critical solution for the parabolic class in the high dimensions of space-time. Specifically, we develop 95% ANN-based confidence intervals for all the solutions in their domains. At the 95% confidence level, our ANN estimators confirm that there is no black hole solution in higher dimensions, hence the gravitational collapse does not occur. Results provide some doubts about the universality of the Choptuik phenomena. Therefore, we conclude that the fastest-growing mode of the perturbations that determine the critical exponent does not exist for the parabolic class in the high dimensions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A
bstract
In this paper, we study the black hole solution of self-similar gravitational collapse in the Einstein-axion-dilaton system for the elliptic class in four dimensions. The solution is ...invariant under space-time dilation, which is combined with internal SL(2,R) transformations. Due to the complex and highly nonlinear pattern of the equations of motion in the physics of black holes, researchers typically have to use various numerical techniques to make the equations tractable to estimate the parameters and the critical solutions. To this end, they have to ignore the numerical measurement errors in estimating the parameters. To our knowledge, for the first time in the literature on axion-dilation systems, we propose to estimate the critical collapse functions in a Bayesian framework. We develop a novel methodology to translate the modelling of the complexity of the elliptic black hole to a sampling problem using Hamiltonian Monte Carlo with stacked neural networks. Unlike methods in the literature, this probabilistic approach enables us not only to recover the available deterministic solution but also to explore possibly all physically distinguishable self-similar solutions that may occur due to numerical measurement errors.
EAACI Molecular Allergology User's Guide Matricardi, P. M.; Kleine-Tebbe, J.; Hoffmann, H. J. ...
Pediatric allergy and immunology,
20/May , Volume:
27, Issue:
S23
Journal Article
Peer reviewed
Open access
The availability of allergen molecules (‘components’) from several protein families has advanced our understanding of immunoglobulin E (IgE)‐mediated responses and enabled ‘component‐resolved ...diagnosis’ (CRD). The European Academy of Allergy and Clinical Immunology (EAACI) Molecular Allergology User's Guide (MAUG) provides comprehensive information on important allergens and describes the diagnostic options using CRD. Part A of the EAACI MAUG introduces allergen molecules, families, composition of extracts, databases, and diagnostic IgE, skin, and basophil tests. Singleplex and multiplex IgE assays with components improve both sensitivity for low‐abundance allergens and analytical specificity; IgE to individual allergens can yield information on clinical risks and distinguish cross‐reactivity from true primary sensitization. Part B discusses the clinical and molecular aspects of IgE‐mediated allergies to foods (including nuts, seeds, legumes, fruits, vegetables, cereal grains, milk, egg, meat, fish, and shellfish), inhalants (pollen, mold spores, mites, and animal dander), and Hymenoptera venom. Diagnostic algorithms and short case histories provide useful information for the clinical workup of allergic individuals targeted for CRD. Part C covers protein families containing ubiquitous, highly cross‐reactive panallergens from plant (lipid transfer proteins, polcalcins, PR‐10, profilins) and animal sources (lipocalins, parvalbumins, serum albumins, tropomyosins) and explains their diagnostic and clinical utility. Part D lists 100 important allergen molecules. In conclusion, IgE‐mediated reactions and allergic diseases, including allergic rhinoconjunctivitis, asthma, food reactions, and insect sting reactions, are discussed from a novel molecular perspective. The EAACI MAUG documents the rapid progression of molecular allergology from basic research to its integration into clinical practice, a quantum leap in the management of allergic patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
The safety and efficacy of intranasal corticosteroids (INCs) are well established for the management of allergic rhinitis, rhinosinusitis, and nasal polyps. As seen in numerous studies, INCs ...demonstrate markedly reduced systemic bioavailability compared with oral and even inhaled corticosteroids and have shown an excellent safety profile over 3 decades of use. Nonetheless, concerns remain among some prescribers and patients that these agents may reach the systemic circulation in sufficient concentration to produce adverse effects (AEs). Available evidence does not support these concerns. A review of the published literature indicates that the side effect profiles of INCs consist primarily of a low incidence of mostly mild and often transient local AEs, such as nasal irritation and epistaxis.The second-generation INC agents currently in use (mometasone furoate nasal spray, fluticasone propionate, ciclesonide, and fluticasone furoate) have favorable pharmacokinetic characteristics that further minimize systemic bioavailability (< 1%) compared with older INCs and compared with oral agents, thereby limiting the risk for systemic adverse events.
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