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BACKGROUND AND PURPOSE To assess the frequency of plateaus in Amyotrophic Lateral Sclerosis (ALS) progression using a large population-based cohort. METHODS Data from the Piemonte and Valle d'Aosta ALS register (PARALS) were used. Patients who were diagnosed between 2007 and 2014 were considered. Follow-up period was extended until 31st December 2018. Visits after tracheostomy were excluded. A plateau was defined as a stable ALSFRS revised score lasting at least 6, 12 or 18 months. RESULTS Out of 1214 patients, 200 (16.5%), 93 (7.7%) and 52 (4.3%) showed at least one plateau lasting a minimum of 6, 12 and 18 months, respectively. Plateaus occurred mostly at high ALSFRSr scores and were more frequent during the initial phases of the disease course. Spinal onset (OR 1.83, 95% CI 1.16 - 2.95, p-value = 0.01) and predominant upper motor neuron phenotype (OR 2.18, 95% CI 1.36 - 3.48, p-value = 0.001) conferred a higher risk for the subsequent appearance of plateaus; conversely, older age at diagnosis (OR 0.25, 95% CI 0.11 - 0.54, p-value = 0.002 for >75 age class) reduced this risk. CONCLUSIONS Plateaus in ALS progression lasting at least 6 months appear in about one out of six patients and could last even 12, 18 months or more in a smaller subgroup of patients. Plateaus occurrence should not lead the neurologist to automatically reconsider ALS diagnosis and should be considered for future clinical trials design. This article is protected by copyright. All rights reserved.Treatment selection markers are generally sought for when the benefit of an innovative treatment in comparison with a reference treatment is considered, and this benefit is suspected to vary according to the characteristics of the patients. Classically, such quantitative markers are detected through testing a marker-by-treatment interaction in a parametric regression model. Most alternative methods rely on modeling the risk of event occurrence in each treatment arm or the benefit of the innovative treatment over the marker values, but with assumptions that may be difficult to verify. Herein, a simple non-parametric approach is proposed to detect and assess the general capacity of a quantitative marker for treatment selection when no overall difference in efficacy could be demonstrated between two treatments in a clinical trial. This graphical method relies on the area between treatment-arm-specific receiver operating characteristic curves (ABC), which reflects the treatment selection capacity of the marker. A simulation study assessed the inference properties of the ABC estimator and compared them with other parametric and non-parametric indicators. The simulations showed that the estimate of the ABC had low bias, power comparable to parametric indicators, and that its confidence interval had a good coverage probability (better than the other non-parametric indicator in some cases). Thus, the ABC is a good alternative to parametric indicators. The ABC method was applied to data of the PETACC-8 trial that investigated FOLFOX4 versus FOLFOX4 + cetuximab in stage III colon adenocarcinoma. It enabled the detection of a treatment selection marker the DDR2 gene. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.The potential role of home literacy environment (HLE) in children's language development has been widely studied. However, data on the HLE of children with familial risk (FR) of dyslexia are limited. In this longitudinal study, we examined (a) whether amount of book exposure and reading interest at age 4 were different in samples of Norwegian FR and no FR-children, respectively, (b) whether these home literacy-related factors exerted different effects depending on family-risk status on vocabulary and grammar skills at school entry age (6 years) and (c) whether they contributed independently to language outcomes at age 6, after controlling for the 4;6-year language skills. Zosuquidar clinical trial Results showed no significant between-group differences in book exposure and reading interest. Furthermore, while interest in reading did not affect vocabulary and grammar in either group, book exposure contributed to vocabulary skills only in the FR-group by school entry. However, this longitudinal association was mediated by lexical skills at age 4;6, implying that the HLE has a positive indirect effect on later language development through its effect on early language. Thus, these findings can be taken to suggest that early intervention including exposure to various book-reading activities for pre-school FR-children with poor expressive vocabulary is worth considering. © 2020 The Authors. Dyslexia published by John Wiley & Sons Ltd.Recently developed stem-cell-based in vitro models of morphogenesis can help shed light on the mechanisms involved in embryonic patterning. These models are showcased using traditional cell culture platforms and materials, which allow limited control over the biological system and usually do not support high-content imaging. In contrast, using advanced microengineered tools can help in microscale control, long-term culture, and real-time data acquisition from such biological models and aid in elucidating the underlying mechanisms. Here, a new culturing, manipulation and analysis platform is described to study in vitro morphogenesis using thin polycarbonate film-based microdevices. A pipeline consisting of open-source software to quantify 3D cell movement using 4D image acquisition is developed to analyze cell migration within the multicellular clusters. It is shown that the platform can be used to control and study morphogenesis in non-adherent cultures of the P19C5 mouse stem cell line and mouse embryonic stem cells (mESCs) that show symmetry breaking and axial elongation events similar to early embryonic development. Using the new platform, it is found that localized cell proliferation and coordinated cell migration result in elongation morphogenesis of the P19C5 aggregates. Further, it is found that polarization and elongation of mESC aggregates are dependent on directed cell migration. © 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.