Fragility curves for non-ductile reinforced concrete frames that exhibit different component response mechanisms

Around the world, a large percentage of buildings in regions of high seismicity are older, non-ductile reinforced concrete. To assess the risk posed by these buildings, fragility functions are required to define the likelihood that these buildings will sustain damage and collapse under earthquake loading. This paper presents the initial phase of a research effort to develop fragility functions for non-ductile concrete frames using numerical simulation; the research presented in this paper focuses on development of the numerical model and application of the model to develop fragility functions for a prototype non-ductile concrete frame. To enable numerical simulation of concrete frame buildings, response models for beam–column joints and columns are developed to provide (1) appropriate simulation of component response and, thereby, reliable assessment of risk and (2) computational efficiency and robustness. These new models are developed using existing experimental data, build on response models proposed by others, and employ component and material models available in the OpenSees analysis platform (http://opensees.berkeley.edu). A new beam–column joint model combines a new expression for joint strength and newly developed cyclic response parameters; a new column response model includes a new shear-strength model and newly developed cyclic response parameters. Numerical models of a prototype non-ductile concrete frame are developed that include simulation of one or more of the following characteristics: (1) rigid beam–column joint, (2) nonlinear joint shear response, (3) nonlinear joint shear and bond–slip response, and (4) column shear failure. Dynamic analyses are performed using these frame models and a suite of ground motions; analysis results are used to develop fragility curves. Fragility curves quantify the vulnerability of the frame and provide understanding of the impact of different component failure mechanisms on frame vulnerability.This research was supported by the National Science Foundation under NSF Grant # 1000700.This is the accepted manuscript of a paper published in Engineering Structures (J-S Jeon, LN Lowes, R DesRoches, I Brilakis, Engineering Structures 2015, 85, 127–143

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

Prospective observational study of FKRP-related limb-girdle muscular dystrophy R9: A GRASP consortium study

\ua9 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association. Objective: Limb-girdle muscular dystrophy R9 (LGMDR9, formerly known as LGMD2I), caused by variants in the fukutin-related protein (FKRP) gene leads to progressive muscle weakness of the shoulder and pelvic limb-girdles and loss of motor function over time. Clinical management and future trial design are improved by determining which standardized clinical outcome assessments (COA) of function are most appropriate to capture disease presentation and progression, informing endpoint selection and enrollment criteria. The purpose of our study was to evaluate the cross-sectional validity and reliability of clinical outcome assessments in patients with FKRP-related LGMDR9 participating in the Genetic Resolution and Assessments Solving Phenotypes in LGMD (GRASP) natural history study. Methods: Enrolled patients completed a battery of COA on two consecutive days, including the North Star Assessment for limb girdle-type dystrophies (NSAD), the 100-m timed test (100 m), and the Performance of Upper Limb 2.0 (PUL). Results: A total of 101 patients with FKRP-related LGMDR9 completed COA evaluations. All functional COA were highly and significantly correlated even across constructs, except for the 9-hole peg test. Similarly, all tests demonstrated excellent test–retest reliability across 2-day visits. The NSAD and PUL demonstrate robust psychometrics with good targeting, ordered response thresholds, fit and stability, and limited dependency of items across the scales. Conclusions: This study has determined the suitability of several functional COA, cross-sectionally, in LGMDR9 to inform future trial design and clinical care

Performance of upper limb entry item to predict forced vital capacity in dysferlin-deficient limb girdle muscular dystrophy

\ua9 2024 The Authors. Dysferlin-deficient limb girdle muscular dystrophy (LGMD R2), also referred to as dysferlinopathy, can be associated with respiratory muscle weakness as the disease progresses. Clinical practice guidelines recommend biennial lung function assessments in patients with dysferlinopathy to screen for respiratory impairment. However, lack of universal access to spirometry equipment and trained specialists makes regular monitoring challenging. This study investigated the use of the Performance of Upper Limb (PUL) clinical scale entry item as a low-cost screening tool to identify patients with dysferlinopathy at risk of respiratory impairment. Using data from 193 patients from the Jain Foundation\u27s International Clinical Outcomes Study, modelling identified a significant positive relationship between the PUL entry item and forced vital capacity (FVC). Eighty-eight percent of patients with the lowest PUL entry item score of 1 presented with FVC % predicted values of <60 %, suggestive of respiratory impairment. By contrast, only 10 % of the remainder of the cohort (PUL entry item of 2 or more) had an FVC of <60 %. This relationship also held true when accounting for ambulatory status, age, and sex as possible confounding factors. In summary, our results suggest that the PUL entry item could be implemented in clinical practice to screen for respiratory impairment where spirometry is not readily available

Numerical modeling of the tension stiffening in reinforced concrete members via discontinuum models

[prova tipográfica]This study presents a numerical investigation on the fracture mechanism of tension stiffening phenomenon in reinforced concrete members. A novel approach using the discrete element method (DEM) is proposed, where three-dimensional randomly generated distinct polyhedral blocks are used, representing concrete and one-dimensional truss elements are utilized, representing steel reinforcements. Thus, an explicit representation of reinforced concrete members is achieved, and the mechanical behavior of the system is solved by integrating the equations of motion for each block using the central difference algorithm. The inter-block interactions are taken into consideration at each contact point with springs and cohesive frictional elements. Once the applied modeling strategy is validated, based on previously published experimental findings, a sensitivity analysis is performed for bond stiffness, cohesion strength, and the number of truss elements. Hence, valuable inferences are made regarding discontinuum analysis of reinforced concrete members, including concrete-steel interaction and their macro behavior. The results demonstrate that the proposed phenomenological modeling strategy successfully captures the concrete-steel interaction and provides an accurate estimation of the macro behavior

INCEPTUS Natural History, Run-in Study for Gene Replacement Clinical Trial in X-Linked Myotubular Myopathy

Supplementary Material: The supplementary material is available in the electronic version of this article: https://doi.org/10.3233/JND-210871.Copyright © 2022 The authors. Background X-linked myotubular myopathy (XLMTM) is a life-threatening congenital myopathy that, in most cases, is characterized by profound muscle weakness, respiratory failure, need for mechanical ventilation and gastrostomy feeding, and early death. Objective We aimed to characterize the neuromuscular, respiratory, and extramuscular burden of XLMTM in a prospective, longitudinal study. Methods Thirty-four participants 16 hours/day); 20% required non-invasive support (6–16 hours/day). Median age at tracheostomy was 3.5 months (95% CI: 2.5, 9.0). Thirty-three participants (97%) required gastrostomy. Thirty-one (91%) participants had histories of hepatic disease and/or prospectively experienced related adverse events or laboratory or imaging abnormalities. CHOP INTEND scores ranged from 19–52 (mean: 35.1). Seven participants (21%) could sit unsupported for≥30 seconds (one later lost this ability); none could pull to stand or walk with or without support. These parameters remained static over time across the INCEPTUS cohort. Conclusions INCEPTUS confirmed high medical impact, static respiratory, motor and feeding difficulties, and early death in boys with XLMTM. Hepatobiliary disease was identified as an under-recognized comorbidity. There are currently no approved disease-modifying treatments.The INCEPTUS and ASPIRO studies are sponsored by Astellas Gene Therapies

Emerging therapeutic options for sporadic inclusion body myositis

Lindsay N Alfano, Linda P Lowes Nationwide Children’s Hospital, Center for Gene Therapy, Columbus, OH, USA Abstract: Sporadic inclusion body myositis is the most common inflammatory muscle disorder preferentially affecting males over the age of 40 years. Progressive muscle weakness of the finger flexors and quadriceps muscles results in loss of independence with activities of daily living and eventual wheelchair dependence. Initial signs of disease are often overlooked and can lead to mis- or delayed diagnosis. The underlying cause of disease is unknown, and disease progression appears refractory to available treatment options. This review discusses the clinical presentation of inclusion body myositis and the current efforts in diagnosis, and focuses on the current state of research for both nonpharmacological and pharmacological treatment options for this patient group. Keywords: myositis, inclusion body myositis, inflammatory myopathy, treatment, function, outcome

Modelling and Fragility Analysis of Non-Ductile Reinforced Concrete Buildings in Low-to-Moderate Seismic Zones

Reinforced concrete buildings in low-to-moderate seismic zones are often designed only for gravity loads in accordance with the non-seismic detailing provisions. Deficient detailing of columns and beam-column joints can lead to unpredictable brittle failures even under moderate earthquakes. Therefore, a reliable estimate of structural response is required for the seismic evaluation of these structures. For this purpose, analytical models for both interior and exterior slab-beam-column subassemblages and for a 1/3 scale model frame were implemented into the nonlinear finite element platform OpenSees. Comparison between the analytical results and experimental data available in the literature is carried out using nonlinear pushover analyses and nonlinear time history analysis for the subassemblages and the model frame, respectively. Furthermore, the seismic fragility assessment of reinforced concrete buildings is performed on a set of non-ductile frames using nonlinear time history analyses. The fragility curves, which are developed for various damage states for the maximum interstory drift ratio are characterized in terms of peak ground acceleration and spectral acceleration using a suite of ground motions representative of the seismic hazard in the region

Comparison of Fragility Curves for an Older RC Frame with Column and Beam-Column Joint Shear Models

The paper aims to develop fragility curves for old reinforced concrete (RC) frames by accounting for their potential failure modes, particularly shear failure of columns and beam-column connections. For this purpose, the analytical models capturing column nonlinear flexure-shear behavior and joint shear behavior are compared with experimental results available in the literature for the validation. Accordingly, to investigate the effect of joint and column shear failure behaviors on frames, a four-story, three-bay ordinary moment frame, one of typical older RC office buildings in California, was selected in this paper. For the subject frame, three types of analytical frame models are taken into account in order to examine its potential failure responses: (1) joint shear, (2) column shear, and (3) joint and column shears. Fragility curves are developed for three frame models and the probability of exceeding a damage state is computed to compare the seismic vulnerability of those frame models