Dupilumab efficacy in uncontrolled, moderate-to-severe asthma with self-reported chronic rhinosinusitis

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4 and IL-13 signaling, key drivers of type 2 inflammation. In the phase 3 study (NCT02414854), add-on dupilumab 200 mg/300 mg every 2 weeks, versus placebo, significantly reduced severe asthma exacerbations and improved pre-bronchodilator forced expiratory volume in 1 second (FEV OBJECTIVE: To assess the efficacy and safety of dupilumab in patients with uncontrolled, moderate-to-severe asthma with or without self-reported comorbid chronic rhinosinusitis (CRS or non-CRS). METHODS: Comorbid CRS was self-reported by patients using an e-diary. Annualized severe exacerbation rates, changes from baseline in pre- and post-bronchodilator FEV RESULTS: CRS was self-reported by 382 of 1902 (20.1%) patients. Dupilumab 200 mg/300 mg reduced annualized severe exacerbation rates by 63%/61%, respectively, in patients with CRS, and by 42%/40% in patients without CRS (all P \u3c .001 vs placebo). Dupilumab also improved lung function and patient-reported asthma control and quality of life, and suppressed type 2 biomarkers versus placebo in both subgroups. Clinical responses were rapid, with near-maximal responses observed at the earliest measured time points and sustained at week 52. Improvements observed in the CRS subgroup were similar to or numerically greater than those in the non-CRS subgroup. CONCLUSION: Dupilumab showed efficacy and was generally well tolerated in patients with uncontrolled, moderate-to-severe asthma with or without CRS

Wigner instability analysis of the damped Hirota equation

We address the modulation instability of the Hirota equation in the presence of stochastic spatial incoherence and linear time-dependent amplification/attenuation processes via the Wigner function approach. We show that the modulation instability remains baseband type, though the damping mechanisms substantially reduce the unstable spectrum independent of the higher-order contributions (e.g. the higher-order nonlinear interaction and the third-order dispersion). Additionally, we find out that the unstable structure due to the Kerr interaction exhibits a significant resilience to the third-order-dispersion stabilizing effects in comparison with the higher-order nonlinearity, as well as a moderate Lorentzian spectrum damping may assist the rising of instability. Finally, we also discuss the relevance of our results in the context of current experiments exploring extreme wave events driven by the modulation instability (e.g. the generation of the so-called rogue waves).Comment: 7+4 pages. 3 figures. Comments are welcome. To appear in Physica

Prediction Markets to Forecast Electricity Demand

A preference is invariant with respect to a transformation tau if its ranking of acts is unaffected by a reshuffling of the states under tau. We show that any invariant preference must be parametric: there is a unique sufficient set of parameters such that the preference ranks acts according to their expected utility given the parameters. This property holds for all non-trivial preferences, provided only that they are reflexive, transitive, monotone, continuous and mixture linear.

Feasibility, Acceptability, and Preliminary Outcomes of a Culturally Adapted Evidence-Based Treatment for Latino Youth With ADHD

Objective: To advance our knowledge about the most effective way to treat Latino youth with ADHD, the current feasibility and pilot study compared a culturally adapted evidence-based treatment (CAT) for ADHD to standard evidence-based treatment (EBT). Method: Following a comprehensive ADHD assessment, 61 Latino families of school-aged children (mean age of 8 years) were randomly assigned to either CAT or standard EBT (i.e., parent management training). Results: CAT outperformed standard EBT when examining homework completion and mother-reported treatment satisfaction. Apart from two trends favoring CAT, CAT and EBT both resulted in significant improvements in parent- and teacher-reported ADHD symptoms and functional impairment, as well as mother- and father-reported parental functioning. Conclusion: CAT outperformed standard EBT when examining several engagement and acceptability outcomes. CAT and EBT were equally effective when examining traditional treatment outcomes, which is impressive considering the robustness of standard EBT, especially when delivered by culturally competent staff

Incremental Clinical Utility of ADHD Assessment Measures With Latino Families

Objective: This study examined the incremental clinical utility of parent and teacher reports of ADHD symptomatology and functional impairment in Latino youth, as well as parent and teacher agreement with the final clinical judgment on a diagnostic structured interview. Method: Participants included 70 Latino youth (47 males, 23 females; M age = 8.13 years, SD = 2.51 years) and their parents and teachers; 60 participants were diagnosed with ADHD. Correlations, percent agreement, kappas, and regressions were utilized. Results: Results demonstrated that teachers agreed with the final clinical judgment more often than did parents. Results additionally demonstrated that functional impairment did not statistically significantly improve diagnostic models already including ADHD symptoms; follow-up analyses were run and are discussed. Finally, results demonstrated that teacher reports statistically significantly improved diagnostic models already including parent reports. Conclusion: The current findings suggest the importance of including both parent and teacher reports of both ADHD symptomatology and functional impairment when assessing ADHD in Latino youth