Static optimization underestimates antagonist muscle activity at the glenohumeral joint: A musculoskeletal modeling study

Static optimization is commonly employed in musculoskeletal modeling to estimate muscle and joint loading; however, the ability of this approach to predict antagonist muscle activity at the shoulder is poorly understood. Antagonist muscles, which contribute negatively to a net joint moment, are known to be important for maintaining glenohumeral joint stability. This study aimed to compare muscle and joint force predictions from a subject-specific neuromusculoskeletal model of the shoulder driven entirely by measured muscle electromyography (EMG) data with those from a musculoskeletal model employing static optimization. Four healthy adults performed six sub-maximal upper-limb contractions including shoulder abduction, adduction, flexion, extension, internal rotation and external rotation. EMG data were simultaneously measured from 16 shoulder muscles using surface and intramuscular electrodes, and joint motion evaluated using video motion analysis. Muscle and joint forces were calculated using both a calibrated EMG-driven neuromusculoskeletal modeling framework, and musculoskeletal model simulations that employed static optimization. The EMG-driven model predicted antagonistic muscle function for pectoralis major, latissimus dorsi and teres major during abduction and flexion; supraspinatus during adduction; middle deltoid during extension; and subscapularis, pectoralis major and latissimus dorsi during external rotation. In contrast, static optimization neural solutions showed little or no recruitment of these muscles, and preferentially activated agonistic prime movers with large moment arms. As a consequence, glenohumeral joint force calculations varied substantially between models. The findings suggest that static optimization may under-estimate the activity of muscle antagonists, and therefore, their contribution to glenohumeral joint stability.     

A regression model predicting isometric shoulder muscle activities from arm postures and shoulder joint moments

Tissue overloading is a major contributor to shoulder musculoskeletal injuries. Previous studies attempted to use regression-based methods to predict muscle activities from shoulder kinematics and shoulder kinetics. While a regression-based method can address co-contraction of the antagonist muscles as opposed to the optimization method, most of these regression models were based on limited shoulder postures. The purpose of this study was to develop a set of regression equations to predict the 10th percentile, the median, and the 90th percentile of normalized electromyography (nEMG) activities from shoulder postures and net shoulder moments. Forty participants generated various 3-D shoulder moments at 96 static postures. The nEMG of 16 shoulder muscles was measured and the 3-D net shoulder moment was calculated using a static biomechanical model. A stepwise regression was used to derive the regression equations. The results indicated the measured range of the 3-D shoulder moment in this study was similar to those observed during work requiring light physical capacity. The r² of all the regression equations ranged between 0.228 and 0.818. For the median of the nEMG, the average r² among all 16 muscles was 0.645, and the five muscles with the greatest r² were the three deltoids, supraspinatus, and infraspinatus. The results can be used by practitioners to estimate the range of the shoulder muscle activities given a specific arm posture and net shoulder moment.     

Agreement of measured and calculated muscle activity during highly dynamic movements modelled with a spherical knee joint

The inclusion of muscle forces into the analysis of joint contact forces has improved their accuracy. But it has not been validated if such force and activity calculations are valid during highly dynamic multidirectional movements. The purpose of this study was to validate calculated muscle activation of a lower extremity model with a spherical knee joint for running, sprinting and 90°-cutting. Kinematics, kinetics and lower limb muscle activation of ten participants were investigated in a 3D motion capture setup including EMG. A lower extremity rigid body model was used to calculate the activation of these muscles with an inverse dynamics approach and a cubic cost function. Correlation coefficients were calculated to compare measured and calculated activation. The results showed good correlation of the modelled and calculated data with a few exceptions. The highest average correlations were found during walking (r = 0.81) and the lowest during cutting (r = 0.57). Tibialis anterior had the lowest average correlation (r = 0.33) over all movements while gastrocnemius medius had the highest correlation (r = 0.9). The implementation of a spherical knee joint increased the agreement between measured and modelled activation compared to studies using a hinge joint knee. Although some stabilizing muscles showed low correlations during dynamic movements, the investigated model calculates muscle activity sufficiently.     

Contribution of muscle short-range stiffness to initial changes in joint kinetics and kinematics during perturbations to standing balance: A simulation study

Simulating realistic musculoskeletal dynamics is critical to understanding neural control of muscle activity evoked in sensorimotor feedback responses that have inherent neural transmission delays. Thus, the initial mechanical response of muscles to perturbations in the absence of any change in muscle activity determines which corrective neural responses are required to stabilize body posture. Muscle short-range stiffness, a history-dependent property of muscle that causes a rapid and transient rise in muscle force upon stretch, likely affects musculoskeletal dynamics in the initial mechanical response to perturbations. Here we identified the contributions of short-range stiffness to joint torques and angles in the initial mechanical response to support surface translations using dynamic simulation. We developed a dynamic model of muscle short-range stiffness to augment a Hill-type muscle model. Our simulations show that short-range stiffness can provide stability against external perturbations during the neuromechanical response delay. Assuming constant muscle activation during the initial mechanical response, including muscle short-range stiffness was necessary to account for the rapid rise in experimental sagittal plane knee and hip joint torques that occurs simultaneously with very small changes in joint angles and reduced root mean square errors between simulated and experimental torques by 56% and 47%, respectively. Moreover, forward simulations lacking short-range stiffness produced unreasonably large joint angle changes during the initial response. Using muscle models accounting for short-range stiffness along with other aspects of history-dependent muscle dynamics may be important to advance our ability to simulate inherently unstable human movements based on principles of neural control and biomechanics.     

Process development of a New Haemophilus influenzae type b conjugate vaccine and the use of mathematical modeling to identify process optimization possibilities

Vaccination is one of the most successful public health interventions being a cost‐effective tool in preventing deaths among young children. The earliest vaccines were developed following empirical methods, creating vaccines by trial and error. New process development tools, for example mathematical modeling, as well as new regulatory initiatives requiring better understanding of both the product and the process are being applied to well‐characterized biopharmaceuticals (for example recombinant proteins). The vaccine industry is still running behind in comparison to these industries. A production process for a new Haemophilus influenzae type b (Hib) conjugate vaccine, including related quality control (QC) tests, was developed and transferred to a number of emerging vaccine manufacturers. This contributed to a sustainable global supply of affordable Hib conjugate vaccines, as illustrated by the market launch of the first Hib vaccine based on this technology in 2007 and concomitant price reduction of Hib vaccines. This paper describes the development approach followed for this Hib conjugate vaccine as well as the mathematical modeling tool applied recently in order to indicate options for further improvements of the initial Hib process. The strategy followed during the process development of this Hib conjugate vaccine was a targeted and integrated approach based on prior knowledge and experience with similar products using multi‐disciplinary expertise. Mathematical modeling was used to develop a predictive model for the initial Hib process (the ‘baseline’ model) as well as an ‘optimized’ model, by proposing a number of process changes which could lead to further reduction in price. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:568–580, 2016