Clinical Trial Readiness in Limb Girdle Muscular Dystrophy R1 (LGMDR1): A GRASP Consortium Study

\ua9 2025 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.Objective: Identifying functional measures that are both valid and reliable in the limb girdle muscular dystrophy (LGMD) population is critical for quantifying the level of functional impairment related to disease progression in order to establish clinical trial readiness in the context of anticipated therapeutic trials. Methods: Through the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP-LGMD) Consortium, 42 subjects with LGMDR1 were enrolled in a 12-month natural history study across 11 international sites. Each subject completed a battery of clinical outcome assessments (COA), including the North Star Assessment for Limb Girdle-Type Dystrophies (NSAD), 10-m walk/run, and Performance of the Upper Limb (PUL), in addition to several patient-reported outcome measures (PROM). Results: In this baseline cross-sectional analysis, significant correlations were found between COAs and PROMs, with significant differences in the performance of assessments based on subjects\u27 ambulatory status and genetic variant classification. Interpretation: The study has determined that the NSAD and other assessments are valid and reliable measures for quantifying the level of disease impairment in individuals with LGMDR1

Retest effects in operational selection settings: Development and test of a framework

This study proposes a framework for examining the effects of retaking tests in operational selection settings. A central feature of this frame-work is the distinction between within-person and between-person retest effects. This framework is used to develop hypotheses about retest ef-fects for exemplars of 3 types of tests (knowledge tests, cognitive ability tests, and situational judgment tests) and to test these hypotheses in a high stakes selection setting (admission to medical studies in Belgium). Analyses of within-person retest effects showed that mean scores of re-peat test takers were one-third of a standard deviation higher for the knowledge test and situational judgment test and one-half of a standard deviation higher for the cognitive ability test. The validity coefficients for the knowledge test differed significantly depending on whether ex-aminees ’ test scores on the first versus second administration were used, with the latter being more valid. Analyses of between-person retest ef-fects on the prediction of academic performance showed that the same test score led to higher levels of performance for those passing on the first attempt than for those passing on the second attempt. The implications of these results are discussed in light of extant retesting practice. In employment settings, the Uniform Guidelines on Employee Selec-tion Procedures (1978) state that organizations should provide a reasonable opportunity to test takers for retesting. Hence, most organizations in the private and public sector have installed retesting policies in promotion and hiring situations (e.g., Campbell, 2004; McElreath, Bayless, Reilly, & Hayes, 2004). In the educational domain, the Standards for Educational and Psychological Testing (APA/AERA/NCME, 1999) state that retest op-portunities should be provided for tests used for promotion or graduation decisions. The opportunity for retesting is also mandated for tests used in making admission, licensing, or certification decisions. A previous version of this manuscript was presented at the Annual Convention of th

The complex interplay between extracellular matrix and cells in tissues

Extracellular matrix (ECM) maintains the structural integrity of tissues and regulates cell and tissue functions. ECM is comprised of fibrillar proteins, proteoglycans (PGs), glycosaminoglycans, and glycoproteins, creating a heterogeneous but well-orchestrated network. This network communicates with resident cells via cell-surface receptors. In particular, integrins, CD44, discoidin domain receptors, and cell-surface PGs and additionally voltage-gated ion channels can interact with ECM components, regulating signaling cascades as well as cytoskeleton configuration. The interplay of ECM with recipient cells is enriched by the extracellular vesicles, as they accommodate ECM, signaling, and cytoskeleton molecules in their cargo. Along with the numerous biological properties that ECM can modify, autophagy and angiogenesis, which are critical for tissue homeostasis, are included. Throughout development and disease onset and progression, ECM endures rearrangement to fulfill cellular requirements. The main responsible molecules for tissue remodeling are ECM-degrading enzymes including matrix metalloproteinases, plasminogen activators, cathepsins, and hyaluronidases, which can modify the ECM structure and function in a dynamic mode. A brief summary of the complex interplay between ECM macromolecules and cells in tissues and the contribution of ECM in tissue homeostasis and diseases is given.Extracellular matrix (ECM) maintains the structural integrity of tissues and regulates cell and tissue functions. ECM is comprised of fibrillar proteins, proteoglycans (PGs), glycosaminoglycans, and glycoproteins, creating a heterogeneous but well-orchestrated network. This network communicates with resident cells via cell-surface receptors. In particular, integrins, CD44, discoidin domain receptors, and cell-surface PGs and additionally voltage-gated ion channels can interact with ECM components, regulating signaling cascades as well as cytoskeleton configuration. The interplay of ECM with recipient cells is enriched by the extracellular vesicles, as they accommodate ECM, signaling, and cytoskeleton molecules in their cargo. Along with the numerous biological properties that ECM can modify, autophagy and angiogenesis, which are critical for tissue homeostasis, are included. Throughout development and disease onset and progression, ECM endures rearrangement to fulfill cellular requirements. The main responsible molecules for tissue remodeling are ECM-degrading enzymes including matrix metalloproteinases, plasminogen activators, cathepsins, and hyaluronidases, which can modify the ECM structure and function in a dynamic mode. A brief summary of the complex interplay between ECM macromolecules and cells in tissues and the contribution of ECM in tissue homeostasis and diseases is given