Smoking and response to rituximab in rheumatoid arthritis : results from an international European collaboration

Objectives: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). Method: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (Delta DAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. Results: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (Delta DAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). Conclusion: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.Peer reviewe

Superconductivity in multi-phase Mg-B-O compounds

Structures of MgB2-based materials manufactured under pressure (up to 2 GPa) by different methods having high superconducting performance and connectivity are multiphase and contain different Mg-B-O compounds. Some oxygen can be incorporated into MgB2 and boron into MgO structures, MgBx (X=4-20) inclusions contain practically no oxygen. Regulating manufacturing temperature, pressure, introducing additions one can influence oxygen and boron distribution in the materials and thus, affect the formation, amount and sizes of Mg-B-O and MgBx inclusions and changing type of pinning, pinning force and so affect critical current density jc. The boron concentration increase in initial Mg and B mixture allows obtaining sample containing 88.5 wt% of MgB12 with Tc of 37.4 K (estimated magnetically)

Design principles for riboswitch function

Scientific and technological advances that enable the tuning of integrated regulatory components to match network and system requirements are critical to reliably control the function of biological systems. RNA provides a promising building block for the construction of tunable regulatory components based on its rich regulatory capacity and our current understanding of the sequence–function relationship. One prominent example of RNA-based regulatory components is riboswitches, genetic elements that mediate ligand control of gene expression through diverse regulatory mechanisms. While characterization of natural and synthetic riboswitches has revealed that riboswitch function can be modulated through sequence alteration, no quantitative frameworks exist to investigate or guide riboswitch tuning. Here, we combined mathematical modeling and experimental approaches to investigate the relationship between riboswitch function and performance. Model results demonstrated that the competition between reversible and irreversible rate constants dictates performance for different regulatory mechanisms. We also found that practical system restrictions, such as an upper limit on ligand concentration, can significantly alter the requirements for riboswitch performance, necessitating alternative tuning strategies. Previous experimental data for natural and synthetic riboswitches as well as experiments conducted in this work support model predictions. From our results, we developed a set of general design principles for synthetic riboswitches. Our results also provide a foundation from which to investigate how natural riboswitches are tuned to meet systems-level regulatory demands

Perovskite CIGS Tandem Solar Cells From Certified 24.2 toward 30 and Beyond

We demonstrate a monolithic perovskite CIGS tandem solar cell with a certified power conversion efficiency PCE of 24.2 . The tandem solar cell still exhibits photocurrent mismatch between the subcells; thus optical simulations are used to determine the optimal device stack. Results reveal a high optical potential with the optimized device reaching a short circuit current density of 19.9 mA cm 2 and 32 PCE based on semiempirical material properties. To evaluate its energy yield, we first determine the CIGS temperature coefficient, which is at amp; 8722;0.38 K 1 notably higher than the one from the perovskite subcell amp; 8722;0.22 K 1 , favoring perovskite in the field operation at elevated cell temperatures. Both single junction cells, however, are significantly outperformed by the combined tandem device. The enhancement in energy output is more than 50 in the case of CIGS single junction device. The results demonstrate the high potential of perovskite CIGS tandem solar cells, for which we describe optical guidelines toward 30 PC