Search

OBJECTIVE:To investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment. METHODS:A phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity. RESULTS:Of the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement. CONCLUSIONS:Efgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG. CLASSIFICATION OF EVIDENCE:This study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

I show equilibrium existence for a price‐setting game among multi‐product firms facing a nested logit/CES demand. As opposed to previous research I allow arbitrary firm/nest overlap, making the result relevant for applied work. Additionally, under easy‐to‐verify conditions, I show that there exist extreme equilibria, which are the most and least preferred by consumers, and provide an algorithm to find them. This allows researcher to numerically verify equilibrium uniqueness in applications, that is, if the extreme equilibria are equal to each other. As a by‐product, I show that inverting FOCs correctly identifies the marginal costs that rationalize observed prices. [ABSTRACT FROM AUTHOR]

Full-field optical techniques provide valuable information for the analysis of mode shapes thanks to their high density of measurement points, providing very detailed maps, in a non-invasive way that avoids alterations of the dynamic behaviour of the specimen. Digital image correlation and thermoelastic stress analysis are two of the most interesting ones. The first provides displacement fields that can be three-dimensional if a calibrated stereoscopic system is used. The second uses a thermographic camera to determine the stress invariant. Given the complementary nature of these magnitudes, this study deals with the integration of the displacement and stress fields by means of a calibrated set of a stereoscopic system and a thermographic camera which, through spatial triangulation, allow the association of the measurements to the same spatial point on the specimen. For this purpose, typical laboratory setups have been carried out for the characterisation of operational modal shapes of resonances. The integration has allowed a more accurate interpretation of the behaviour of the specimen, identifying the regions with the highest mechanical stress. This shows the advantages of integration compared to the isolated analysis of displacement and/or stress measurements that are usually carried out and proves the potential for the development of optical techniques at a scientific and industrial level, opening up new avenues of study. [ABSTRACT FROM AUTHOR]

This article explores how Francisco de Aguirre used the Copiapó Valley encomienda to negotiate political power during the transition from conquest to colonial rule in northern Chile. Simultaneously, we analyze the circumstances of how a native society was incorporated into the Spanish Empire after a decade of fighting and resistance on the fringes of the empire. The strategic use of the fear of native rebellions to close the road from Peru to Chile gave Aguirre enough power to negotiate an important political position, which in the future would clash with the colonial authorities. Copiapó Valley’s peripheral location in the southernmost Atacama Desert constituted a political gray zone for the colonial administration. This space contributed to consolidating power for Aguirre and enabled locals some negotiation power within the possibilities afforded by the colonial system. [ABSTRACT FROM AUTHOR]

Background: Friedreich's ataxia (FA) is a rare multisystemic disorder which can cause premature death. Objectives: To investigate predictors of survival in FA. Methods: Within a prospective registry established by the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS; ClinicalTrials.gov identifier NCT02069509) we enrolled genetically confirmed FA patients at 11 tertiary centers and followed them in yearly intervals. We investigated overall survival applying the Kaplan–Meier method, life tables, and log‐rank test. We explored prognostic factors applying Cox proportional hazards regression and subsequently built a risk score which was assessed for discrimination and calibration performance. Results: Between September 2010 and March 2017, we enrolled 631 FA patients. Median age at inclusion was 31 (range, 6–76) years. Until December 2022, 44 patients died and 119 terminated the study for other reasons. The 10‐year cumulative survival rate was 87%. In a multivariable analysis, the disability stage (hazard ratio [HR] 1.51, 95% CI 1.08–2.12, P = 0.02), history of arrhythmic disorder (HR 2.93, 95% CI 1.34–6.39, P = 0.007), and diabetes mellitus (HR 2.31, 95% CI 1.05–5.10, P = 0.04) were independent predictors of survival. GAA repeat lengths did not improve the survival model. A risk score built on the previously described factors plus the presence of left ventricular systolic dysfunction at echocardiography enabled identification of four trajectories to prognosticate up to 10‐year survival (log‐rank test P < 0.001). Conclusions: Arrhythmias, progressive neurological disability, and diabetes mellitus influence the overall survival in FA. We built a survival prognostic score which identifies patients meriting closer surveillance and who may benefit from early invasive cardiac monitoring and therapy. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]