Moment inequalities for functions of independent random variables

A general method for obtaining moment inequalities for functions of independent random variables is presented. It is a generalization of the entropy method which has been used to derive concentration inequalities for such functions [Boucheron, Lugosi and Massart Ann. Probab. 31 (2003) 1583-1614], and is based on a generalized tensorization inequality due to Latala and Oleszkiewicz [Lecture Notes in Math. 1745 (2000) 147-168]. The new inequalities prove to be a versatile tool in a wide range of applications. We illustrate the power of the method by showing how it can be used to effortlessly re-derive classical inequalities including Rosenthal and Kahane-Khinchine-type inequalities for sums of independent random variables, moment inequalities for suprema of empirical processes and moment inequalities for Rademacher chaos and U-statistics. Some of these corollaries are apparently new. In particular, we generalize Talagrand's exponential inequality for Rademacher chaos of order 2 to any order. We also discuss applications for other complex functions of independent random variables, such as suprema of Boolean polynomials which include, as special cases, subgraph counting problems in random graphs.Comment: Published at http://dx.doi.org/10.1214/009117904000000856 in the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

Growth rate regulated genes and their wide involvement in the Lactococcus lactis stress responses

International audienc

Investigation of the adaptation of Lactococcus lactis to isoleucine starvation integrating dynamic transcriptome and proteome information

Background: Amino acid assimilation is crucial for bacteria and this is particularly true for Lactic Acid Bacteria (LAB) that are generally auxotroph for amino acids. The global response of the Lmodel Lactococcus lactis ssp. lactis was characterized during progressive isoleucine starvation in batch culture using a chemically defined medium in which isoleucine concentration was fixed so as to become the sole limiting nutriment. Dynamic analyses were performed using transcriptomic and proteomic approaches and the results were analysed conjointly with fermentation kinetic data. Results: The response was first deduced from transcriptomic analysis and corroborated by proteomic results. It occurred progressively and could be divided into three major mechanisms: (i) a global down-regulation of processes linked to bacterial growth and catabolism (transcription, translation, carbon metabolism and transport, pyrimidine and fatty acid metabolism), (ii) a specific positive response related to the limiting nutrient (activation of pathways of carbon or nitrogen metabolism and leading to isoleucine supply) and (iii) an unexpected oxidative stress response (positive regulation of aerobic metabolism, electron transport, thioredoxin metabolism and pyruvate dehydrogenase). The involvement of various regulatory mechanisms during this adaptation was analysed on the basis of transcriptomic data comparisons. The global regulator CodY seemed specifically dedicated to the regulation of isoleucine supply. Other regulations were massively related to growth rate and stringent response. Conclusion: This integrative biology approach provided an overview of the metabolic pathways involved during isoleucine starvation and their regulations. It has extended significantly the physiological understanding of the metabolism of L. lactis ssp. lactis. The approach can be generalised to other conditions and will contribute significantly to the identification of the biological processes involved in complex regulatory networks of micro-organisms

Omalizumab as alternative to chronic use of oral corticosteroids in severe asthma

Systemic/oral corticosteroids (OCS) have been used for decades in the management of acute asthma exacerbations and chronically in patients with uncontrolled severe asthma. However, while OCS are effective at treating acute exacerbations, there is only empirical evidence regarding the efficacy of OCS at reducing the rate of exacerbations. Evidence, although scarce, is suggestive of high exacerbation rates in severe asthma patients even when receiving maintenance treatment with OCS. In addition, use of OCS is associated with undesirable effects. Despite all this, physicians have continued to use OCS for managing severe asthma and acute exacerbation due to the lack of availability of effective alternatives. Fortunately, in the last decade several biologics have been proven safe and effective for patients with uncontrolled severe asthma. This has led to the Global Initiative for Asthma (GINA) recommending the use of biologics, instead of maintenance OCS, in patients with severe asthma (GINA Step 5). These include one biologic targeting immunoglobulin E (IgE) (omalizumab), and different biologics targeting interleukin-5 (IL-5), the IL-5 receptor (IL-5R) or IL-4 receptor alpha-unit (IL-4R alpha), including mepolizumab (subcutaneous), reslizumab (intravenous), benralizumab (subcutaneous) and dupilumab (subcutaneous). Omalizumab for the treatment of severe allergic asthma reduces exacerbations, irrespective of blood eosinophil levels. Anti-IL-5/IL-5R biologics are indicated in patients with severe eosinophilic asthma and repetitive exacerbations, irrespective of the presence or absence of allergy. Recently, an anti-IL4R alpha biologic has been approved by the FDA for eosinophilic phenotype or oral corticosteroid-dependent asthma. Finally, physicians should consider using biologics as an alternative to chronic OCS therapy

A common language to assess allergic rhinitis control : results from a survey conducted during EAACI 2013 Congress

Peer reviewedPublisher PD

IgE-Mediated Multimorbidities in Allergic Asthma and the Potential for Omalizumab Therapy

Allergic asthma often coexists with different pathological conditions, called multimorbidities, that are mostly of allergic nature and share a common underlying inflammatory pathophysiological mechanism. Multimorbidities of allergic asthma may influence asthma control, its severity, and patients' response to treatment, and contribute to the overall socioeconomic burden of the disease. Immunoglobulin E (IgE) is known to play a central role in the pathogenesis of various allergic diseases, including asthma. Thus, IgE-mediated immunologic pathways present an attractive target for intervention in asthma and multimorbidities. In this review, we discuss the most frequently reported IgE-mediated multimorbidities in allergic asthma, including allergic rhinitis, rhinoconjunctivitis, atopic dermatitis, vernal keratoconjunctivitis, chronic rhinosinusitis with nasal polyps, food allergies, and allergic bronchopulmonary aspergillosis. Omalizumab is a recombinant humanized monoclonal antibody against IgE and has been in use to treat allergic asthma for more than a decade. We comprehensively review the clinical evidence for omalizumab in the treatment of the aforementioned multimorbidities in allergic asthma