Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative.

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.

Prior uncertainty impedes discrete locomotor adaptation.

The impact of environmental uncertainty on locomotor adaptation remains unclear. Environmental uncertainty could either aid locomotor adaptation by prompting protective control strategies that stabilize movements to assist learning or impede adaptation by reducing error sensitivity and fostering hesitance to pursue corrective movements. To explore this, we investigated participants' adaptation to a consistent force field after experiencing environmental uncertainty in the form of unpredictable balance perturbations. We compared the performance of this group (Perturbation) to the adaptive performance of a group that did not experience any unpredictable perturbations (Non-Perturbation). Perturbations were delivered using a cable-driven robotic device applying lateral forces to the pelvis. We assessed whole-body center of mass (COM) trajectory (COM signed deviation), anticipatory postural adjustments (COM lateral offset), and first step width. The Perturbation group exhibited larger disruptions in COM trajectory (greater COM signed deviations) than the Non-Perturbation group when first walking in the force field. While the COM signed deviations of both groups decreased towards baseline values, only the Non-Perturbation group returned to baseline levels. The Perturbation groups COM signed deviations remained higher, indicating they failed to fully adapt to the force field before the end. The Perturbation group also did not adapt their COM lateral offset to counter the predictable effects of the force field as the Non-Perturbation group did, and their first step width increased more slowly. Our findings suggest that exposure to unpredictable perturbations impeded future sensorimotor adaptations to consistent perturbations.

Optimism persists when walking in unpredictable environments.

Humans continuously modulate their control strategies during walking based on their ability to anticipate disturbances. However, how people adapt and use motor plans to create stable walking in unpredictable environments is not well understood. Our purpose was to investigate how people adapt motor plans when walking in a novel and unpredictable environment. We evaluated the whole-body center of mass (COM) trajectory of participants as they performed repetitions of a discrete goal-directed walking task during which a laterally-directed force field was applied to the COM. The force field was proportional in magnitude to forward walking velocity and randomly directed towards either the right or left each trial. We hypothesized that people would adapt a control strategy to reduce the COM lateral deviations created by the unpredictable force field. In support of our hypothesis, we found that with practice the magnitude of COM lateral deviation was reduced by 28% (force field left) and 44% (force field right). Participants adapted two distinct unilateral strategies, implemented regardless of if the force field was applied to the right or to the left, that collectively created a bilateral resistance to the unpredictable force field. These strategies included an anticipatory postural adjustment to resist against forces applied to the left, and a more lateral first step to resist against forces applied to the right. In addition, during catch trials when the force field was unexpectedly removed, participants exhibited trajectories similar to baseline trials. These findings were consistent with an impedance control strategy that provides a robust resistance to unpredictable perturbations. However, we also found evidence that participants made predictive adaptations in response to their immediate experience that persisted for three trials. Due to the unpredictable nature of the force field, this predictive strategy would sometimes result in greater lateral deviations when the prediction was incorrect. The presence of these competing control strategies may have long term benefits by allowing the nervous system to identify the best overall control strategy to use in a novel environment.

People adapt a consistent center-of-mass trajectory in a novel force field.

During human walking the whole body center-of-mass (COM) trajectory may be a control objective, a goal the central nervous system uses to plan and regulate movement. Our previous observation, that after practice walking in a novel laterally directed force field people adapt a COM trajectory similar to their normal trajectory, supports this idea. However, our prior work only presented data demonstrating changes in COM trajectory in response to a single force field. To evaluate whether this phenomena is robust, in the present study we present new data demonstrating that people adapt their COM trajectory in a similar manner when the direction of the external force field is changed resulting in drastically different lower limb joint dynamics. Specifically, we applied a continuous, left-directed force field (in the previous experiment the force field was applied to the right) to the COM as participants performed repeated trials of a discrete walking task. We again hypothesized that with practice walking in the force field people would adapt a COM trajectory that was similar to their baseline performance and exhibit aftereffects, deviation of their COM trajectory in the opposite direction of force field, when the field was unexpectedly removed. These hypotheses were supported and suggest that participants formed an internal model to control their COM trajectory. Collectively these findings demonstrate that people adapt their gait patterns to anticipate consistent aspects of the external environment. These findings suggest that this response is robust to force fields applied in multiple directions that may require substantially different neural control.NEW & NOTEWORTHY With experience people adapted a predictive internal model to control their whole body center-of-mass walking trajectory that anticipated the disruptive laterally directed forces of a novel and consistent external environment. Collectively these findings demonstrate that adaptation of gait to anticipate consistent aspects of the external environment is a response that is robust to force fields in multiple directions that require substantially different lower limb dynamics and neural control.

Disease progression and clinical outcomes in latent osteoarthritis phenotypes: Data from the Osteoarthritis Initiative.

The prevalence of knee osteoarthritis (OA) is widespread and the heterogeneous patient factors and clinical symptoms in OA patients impede developing personalized treatments for OA patients. In this study, we used unsupervised and supervised machine learning to organize the heterogeneity in knee OA patients and predict disease progression in individuals from the Osteoarthritis Initiative (OAI) dataset. We identified four distinct knee OA phenotypes using unsupervised learning that were defined by nutrition, disability, stiffness, and pain (knee and back) and were strongly related to disease fate. Interestingly, the absence of supplemental vitamins from an individual's diet was protective from disease progression. Moreover, we established a phenotyping tool and prognostic model from 5 variables (WOMAC disability score of the right knee, WOMAC total score of the right knee, WOMAC total score of the left knee, supplemental vitamins and minerals frequency, and antioxidant combination multivitamins frequency) that can be utilized in clinical practice to determine the risk of knee OA progression in individual patients. We also developed a prognostic model to estimate the risk for total knee replacement and provide suggestions for modifiable variables to improve long-term knee health. This combination of unsupervised and supervised data-driven tools provides a framework to identify knee OA phenotype in a clinical scenario and personalize treatment strategies.

American Society of Biomechanics Journal of Biomechanics Award 2018: Adaptive motor planning of center-of-mass trajectory during goal-directed walking in novel environments.

To aid in the successful execution of goal-directed walking (discrete movement from a start location to an end target) the central nervous system forms a predictive motor plan. For the motor plan to be effective, it must be adapted in response to environmental changes. Despite motor planning being inherent to goal-directed walking, it is not understood how the nervous system adapts these plans to interact with changing environments. Our objective was to understand how people adapt motor plans of center of mass (COM) trajectory during goal-directed walking in response to a consistent change in environmental dynamics. Participants preformed a series of goal-directed walking trials in a novel environment created by a cable robot that applied a lateral force field to their COM. We hypothesized that participants would adapt to the environment by forming an internal model of their COM trajectory within the force field. Our findings support this hypothesis. Initially, we found COM trajectory significantly deviated in the same direction as the applied field, relative to baseline (no field) (p = 0.002). However, with practice in the field, COM trajectory adapted back to the baseline (p = 0.6). When we unexpectedly removed the field, participants demonstrated after-effects, COM trajectory deviated in the direction opposite of the field relative to baseline (p < 0.001). Our findings suggest that when performing a goal-directed walking task, people adapt a motor plan that predicts the COM trajectory that will emerge from the interaction between a specific set of motor commands and the external environment.

Insertional achilles tendinopathy associated with altered transverse compressive and axial tensile strain during ankle dorsiflexion.

The purposes of this case-control study (N = 20) were to examine the effects of insertional Achilles tendinopathy (IAT) and tendon region on tendon strain in patients with IAT compared to a control group without tendinopathy. An ultrasound transducer was positioned over the Achilles tendon insertion during dorsiflexion tasks, which included standing and partial squat. A non-rigid image registration-based algorithm was used to estimate transverse compressive and axial tensile strains of the tendon from radiofrequency ultrasound images, which was segmented into two regions (superficial tendon and deep). For transverse compressive strain, two-way mixed effects ANOVAs demonstrated that there were interaction effects between group and tendon region for both dorsiflexion tasks (Heel lowering, p = 0.004; Partial squat, p = 0.008). For axial tensile strain, the IAT group demonstrated a main effect of lower tensile strain than the control group (Standing, p = 0.001; Partial squat, p = 0.033). There was also a main effect of greater tensile strain in the superficial region of the tendon compared to the deep during standing (p = 0.002), but not during partial squat (p = 0.603). Reduced transverse compressive and axial tensile strains in the IAT group indicate altered mechanical properties specific to the region of IAT pathology. Additionally, patterns of compressive strain are consistent with the theory of calcaneal impingement contributing to IAT pathology. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:910-915, 2017.

Ultrasound strain mapping of Achilles tendon compressive strain patterns during dorsiflexion.

Heel lifts are commonly prescribed to patients with Achilles tendinopathy, yet little is known about the effect on tendon compressive strain. The purposes of the current study were to (1) develop a valid and reliable ultrasound elastography technique and algorithm to measure compressive strain of human Achilles tendon in vivo, (2) examine the effects of ankle dorsiflexion (lowering via controlled removal of a heel lift and partial squat) on compressive strain of the Achilles tendon insertion and (3) examine the relative compressive strain between the deep and superficial regions of the Achilles tendon insertion. All tasks started in a position equivalent to standing with a 30mm heel lift. An ultrasound transducer positioned over the Achilles tendon insertion was used to capture radiofrequency images. A non-rigid image registration-based algorithm was used to estimate compressive strain of the tendon, which was divided into 2 regions (superficial, deep). The bland-Altman test and intraclass correlation coefficient were used to test validity and reliability. One-way repeated measures ANOVA was used to compare compressive strain between regions and across tasks. Compressive strain was accurately and reliably (ICC>0.75) quantified. There was greater compressive strain during the combined task of lowering and partial squat compared to the lowering (P=.001) and partial squat (P<.001) tasks separately. There was greater compressive strain in the deep region of the tendon compared to the superficial for all tasks (P=.001). While these findings need to be examined in a pathological population, heel lifts may reduce tendon compressive strain during daily activities.

An Ankle-Foot Orthosis With a Lateral Extension Reduces Forefoot Abduction in Subjects With Stage II Posterior Tibial Tendon Dysfunction.

STUDY DESIGN: Controlled laboratory, repeated measures. BACKGROUND: Posterior tibial tendon dysfunction is a common musculoskeletal problem that includes tendon degeneration and collapse of the medial arch of the foot (flatfoot deformity). Ankle-foot orthoses (AFOs) typically are used to correct flatfoot deformity. Correction of flatfoot deformity involves increasing forefoot adduction, forefoot plantar flexion, and hindfoot inversion. OBJECTIVES: To test whether a foot orthosis with a lateral extension reduces forefoot abduction in patients with stage II posterior tibial tendon dysfunction while walking. METHODS: The gait of 15 participants with stage II posterior tibial tendon dysfunction was evaluated under 3 conditions: a standard AFO, an AFO with a lateral extension, and a shoe-only control condition. Kinematic variables of interest were evaluated at designated time points in the gait cycle and included hindfoot inversion/eversion, forefoot plantar flexion/dorsiflexion, and forefoot abduction/adduction. A 3-by-4, repeated-measures analysis of variance (brace condition by gait phase) was used to compare variables across conditions. RESULTS: The AFO with a lateral extension resulted in a significantly greater change in forefoot adduction compared to the standard AFO (2.6°, P = .02) and shoe-only conditions (4.1°, P<.01) across all phases of stance. Forefoot plantar flexion was significantly increased when comparing the standard AFO and AFO with a lateral extension to the shoe-only condition. The AFO with the lateral extension also demonstrated significantly increased hindfoot inversion during the loading response and terminal stance phases. CONCLUSION: Off-the-shelf and standard AFOs have been shown to improve forefoot plantar flexion and hindfoot eversion, but not forefoot adduction. A lateral extension added to a standard AFO along the forefoot significantly improved forefoot adduction in participants with posterior tibial tendon dysfunction while walking.