Quantile regression is a powerful tool for detecting exposure-outcome associations given covariates across different parts of the outcome's distribution, but has two major limitations when the aim is to infer the effect of an exposure. Firstly, the exposure coefficient estimator may not converge to a meaningful quantity when the model is misspecified, and secondly, variable selection methods may induce bias and excess uncertainty, rendering inferences biased and overly optimistic. In this paper, we address these issues via partially linear quantile regression models which parametrize the conditional association of interest, but do not restrict the association with other covariates in the model. We propose consistent estimators for the unknown model parameter by mapping it onto a nonparametric main effect estimand that captures the (conditional) association of interest even when the quantile model is misspecified. This estimand is estimated using the efficient influence function under the nonparametric model, allowing for the incorporation of data-adaptive procedures such as variable selection and machine learning. Our approach provides a flexible and reliable method for detecting associations that is robust to model misspecification and excess uncertainty induced by variable selection methods. The proposal is illustrated using simulation studies and data on annual health care costs associated with excess body weight.
We demonstrate that the one-dimensional shallow water moment equations satisfy an auxiliary entropy conservation law, where the entropy function corresponds to the total energy. Additionally, we show that the classical Newtonian slip friction and Manning friction terms are entropy dissipative with respect to the developed entropy variables. The results from the continuous entropy analysis are used to construct an entropy stable and well-balanced nodal discontinuous Galerkin spectral element method for the spatial approximation. Key to ensure the entropy stability of the scheme is the derivation of entropy conservative numerical fluxes that satisfy a discrete version of the entropy flux compatibility condition. Finally, numerical examples demonstrate the performance of the scheme and validate the theoretical results.
Nanosecond pulsed plasmas show strong potential towards H-2 production via CH4 reforming, owing to their highly non-equilibrium nature. In this work, we investigate how the pulse repetition pattern, i.e. comparing single pulse operation vs. high-frequency pulse packages, correlates to the plasma properties and reforming process performance in atmospheric pressure pure CH4 using a combination of plasma diagnostics and gas chromatography. We show that the electrical properties (voltage, current, pulse energy), as well as gas temperature, electron density and plasma volume are significantly altered after the first pulse cycle in the pulse package as a result of the pronounced "memory effect" active at very short inter-pulse periods, during which the gas properties in the discharge gap (temperature, pressure, and composition) do not have enough time to return to the original conditions. These changes lead to a product selectivity shift towards highly unsaturated hydrocarbons, specifically C2H2, and energy cost reduction (from 480 to 400 kJ.mol(- 1)). In contrast, the overall CH4 conversion remains unaffected (similar to 21 %) as complete dissociation in the plasma region is already achieved after the first pulse cycle. These results demonstrate that tailoring the pulse repetition pattern provides an effective strategy to manipulate plasma properties and, thus, optimise CH4 conversion, energy efficiency, and control product selectivity in nanosecond pulsed CH4 plasmas.
OBJECTIVES:This study aimed to investigate the efficacy and safety of filgotinib, a JAK1 preferential inhibitor, in patients with axial spondyloarthritis (axSpA). METHODS:The phase 3 OLINGUITO trial comprises 2 international, randomised, double-blind, placebo (PBO)-controlled studies. Patients with an established diagnosis of radiographic (r) or nonradiographic (nr) axSpA and an inadequate response/intolerance to ≥2 nonsteroidal anti-inflammatory drugs were randomised 1:1 to filgotinib 200 mg or PBO once daily through week (W) 16 (double-blind period; stratified by high-sensitivity C-reactive protein [hs-CRP] level and prior biologic disease-modifying antirheumatic drug [bDMARD] use). After W16, patients received open-label filgotinib 200 mg through W52; patients ≥65 years and/or with prespecified risk factors received response-based dosing (100 or 200 mg). The primary (Assessment of SpondyloArthritis international Society ≥40% response [ASAS40 response]) and secondary efficacy endpoints were assessed at W16. Efficacy and safety were assessed through W52. RESULTS:At W16, the primary endpoint was met in both studies (ASAS40 response rates: r = axSpA [n = 258], 39.5% filgotinib vs 20.9% PBO [P = .001]; nr-axSpA [n = 237], 34.5% vs 17.8% [P = .003], respectively). ASAS40 improvements, irrespective of hs-CRP level/prior bDMARD use, were observed as early as W1. For secondary endpoints, significant improvements were seen in Axial Spondyloarthritis Disease Activity Score and Spondyloarthritis Research Consortium of Canada magnetic resonance imaging sacroiliac joint inflammation in both studies, and in Bath Ankylosing Spondylitis Functional Index and Ankylosing Spondylitis Quality of Life Questionnaire in patients with r-axSpA. Improvements with filgotinib were maintained/increased further through W52. Overall, 2 cases of myocardial infarction (PBO: n = 1; PBO-filgotinib: n = 1), 3 of herpes zoster (PBO-filgotinib), and 4 of malignancies (excluding nonmelanoma skin cancer; filgotinib: n = 3; PBO-filgotinib: n = 1) occurred. CONCLUSIONS:Across the whole spectrum of axSpA, filgotinib provided rapid and significant patient-relevant improvements in axSpA signs and symptoms and was well tolerated.
