849 research outputs found

    IL‐13, periostin and dipeptidyl‐peptidase‐4 reveal endotype‐phenotype associations in atopic dermatitis

    Get PDF
    Background: The heterogeneous (endo)phenotypes of atopic dermatitis (AD) require precision medicine. Currently, systemic therapy is recommended to patients with an Eczema Area and Severity Index (EASI) ≥ 16. Previous studies have demonstrated an improved treatment response to the anti‐interleukin (IL)‐13 antibody tralokinumab in AD subgroups with elevated levels of the IL‐13‐related biomarkers dipeptidyl‐peptidase (DPP)‐4 and periostin. Methods: Herein, 373 AD patients aged ≥12 years were stratified by IL‐13high^{high}, periostinhigh^{high} and DPP‐4high^{high} endotypes using cross‐sectional data from the ProRaD cohort Bonn. “High” was defined as >80th quantile of 47 non‐atopic controls. We analyzed endotype‐phenotype associations using machine‐learning gradient boosting compared to logistic regression. Results: Atopic dermatitis severity and eosinophils correlated with IL‐13 and periostin levels. Correlations of IL‐13 with EASI were stronger in patients with increased (rs = 0.482) than with normal (rs = 0.342) periostin levels. We identified eosinophilia >6% and an EASI range of 5.5–17 dependent on the biomarker combination to be associated with increasing probabilities of biomarkerhigh^{high} endotypes. Also patients with mild‐to‐low‐moderate severity (EASI < 16) featured increased biomarkers (IL‐13high^{high}: 41%, periostinhigh^{high}: 48.4%, DPP‐4high^{high}: 22.3%). Herthoge sign (adjusted Odds Ratio (aOR) = 1.89, 95% Confidence Interval (CI) [1.14–3.14]) and maternal allergic rhinitis (aOR = 2.79–4.47) increased the probability of an IL‐13high^{high}‐endotype, “dirty neck” (aOR = 2.83 [1.32–6.07]), orbital darkening (aOR = 2.43 [1.08–5.50]), keratosis pilaris (aOR = 2.21 [1.1–4.42]) and perleche (aOR = 3.44 [1.72–6.86]) of a DPP‐4high^{high}‐endotype. Conclusions: A substantial proportion of patients with EASI < 16 featured high biomarker levels suggesting systemic impact of skin inflammation already below the current cut‐off for systemic therapy. Our findings facilitate the identification of patients with distinct endotypes potentially linked to response to IL‐13‐targeted therapy

    Atopic dermatitis: Correlation of distinct risk factors with age of onset in adulthood compared to childhood

    Full text link
    Background: Atopic dermatitis (AD) has long been regarded as a primarily pediatric disease. However, there is growing evidence for a high rate of adult-onset AD. We aimed to characterize factors associated with adult-onset versus childhood-onset AD and controls. Methods: We analyzed cross-sectional data of the CK-CARE-ProRaD cohorts Bonn, Augsburg, Davos, Zürich of 736 adult patients stratified by age of AD onset (childhood-onset <18 years: 76.4% (subsets: 0 to 2; ≥2 to 6; ≥7 to 11; ≥12 to 18); adult-onset ≥18 years: 23.6% (subsets: ≥18 to 40; ≥41 to 60; ≥61) and 167 controls (91 atopic, 76 non-atopic)). Results: We identified active smoking to be associated with adult-onset AD versus controls (adjusted Odds Ratio (aOR) = 5.54 [95% Confidence Interval: 1.06-29.01] vs. controlsnonatopic^{non-atopic} , aOR = 4.03 [1.20-13.45] vs. controlsatopic^{atopic} ). Conjunctivitis showed a negative association versus controlsatopic^{atopic} (aOR = 0.36 [0.14-0.91]). Food allergy (aOR = 2.93 [1.44-5.96]), maternal food allergy (aOR = 9.43 [1.10-80.95]), palmar hyperlinearity (aOR = 2.11 [1.05-4.25]), and academic background (aOR = 2.14 [1.00-4.54]) increased the odds of childhood-onset AD versus controlsatopic^{atopic}. Shared AD-associated factors were maternal AD (4-34x), increased IgE (2-20x), atopic stigmata (2-3x) with varying effect sizes depending on AD onset and control group. Patients with adult-compared to childhood-onset had doubled odds of allergic rhinitis (aOR = 2.15 [1.12-4.13]), but reduced odds to feature multiple (3-4) atopic comorbidities (aOR = 0.34 [0.14-0.84]). Adult-onset AD, particularly onset ≥61 years, grouped mainly in clusters with low contributions of personal and familial atopy and high frequencies of physical inactivity, childhood-onset AD, particularly infant-onset, mainly in "high-atopic"-clusters. Conclusions: The identified associated factors suggest partly varying endo- and exogeneous mechanisms underlying adult-onset versus childhood-onset AD. Our findings might contribute to better assessment of the individual risk to develop AD throughout life and encourage prevention by non-smoking and physical activity as modifiable lifestyle factors

    Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

    Full text link
    Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

    Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

    Get PDF
    Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio
    corecore