anystyle 1.0.0

data/res/finder/bj581pc8202.ttx

@@ -0,0 +1,2719 @@
+title         | COMPUTER MODELING OF MUSCLE COORDINATION STRATEGIES THAT
+              |                   DECREASE JOINT LOADS
+blank         | 
+              | 
+text          |                      A DISSERTATION
+              |  SUBMITTED TO THE DEPARTMENT OF MECHANICAL ENGINEERING
+              |          AND THE COMMITTEE ON GRADUATE STUDIES
+              |                  OF STANFORD UNIVERSITY
+              |        IN PARTIAL FULFILLMENT OF THE REQUIREMENTS
+              |                    FOR THE DEGREE OF
+              |                   DOCTOR OF PHILOSOPHY
+blank         | 
+              | 
+              | 
+              | 
+text          |                            By
+              |                     Matthew S. DeMers
+              |                       December 2015
+              |               © 2015 by Matthew Stephen DeMers. All Rights Reserved.
+              |          Re-distributed by Stanford University under license with the author.
+blank         | 
+              | 
+              | 
+text          |                          This work is licensed under a Creative Commons Attribution-
+              |                          Noncommercial 3.0 United States License.
+              |                          http://creativecommons.org/licenses/by-nc/3.0/us/
+blank         | 
+              | 
+              | 
+              | 
+text          | This dissertation is online at: http://purl.stanford.edu/bj581pc8202
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                            ii
+text          | I certify that I have read this dissertation and that, in my opinion, it is fully adequate
+              | in scope and quality as a dissertation for the degree of Doctor of Philosophy.
+blank         | 
+text          |                                                                 Scott Delp, Primary Adviser
+blank         | 
+              | 
+              | 
+text          | I certify that I have read this dissertation and that, in my opinion, it is fully adequate
+              | in scope and quality as a dissertation for the degree of Doctor of Philosophy.
+blank         | 
+text          |                                                                                    Garry Gold
+blank         | 
+              | 
+              | 
+text          | I certify that I have read this dissertation and that, in my opinion, it is fully adequate
+              | in scope and quality as a dissertation for the degree of Doctor of Philosophy.
+blank         | 
+text          |                                                                               Marc Levenston
+blank         | 
+              | 
+              | 
+              | 
+text          | Approved for the Stanford University Committee on Graduate Studies.
+              |                              Patricia J. Gumport, Vice Provost for Graduate Education
+blank         | 
+              | 
+              | 
+              | 
+text          | This signature page was generated electronically upon submission of this dissertation in
+              | electronic format. An original signed hard copy of the signature page is on file in
+              | University Archives.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                           iii
+              | iv
+title         | Abstract
+text          |        Musculoskeletal models allow us to study muscle coordination and joint injuries
+              | in ways that in vivo experiments cannot. Models and simulations can compute internal
+              | joint contact forces, explore unsafe conditions, and simulate injuries without risk of
+              | harming experimental subjects. Models also enable systematic variation of muscle
+              | activity to evaluate its effect on joint loading and injury. The goals of this dissertation
+              | were to systematically quantify the effects of varied muscle activity in three applications:
+              | (1) to decrease knee forces during walking, (2) to estimate increased knee forces due to
+              | crouch gait in subjects with cerebral palsy, and (3) to prevent ankle sprains during
+              | landing.
+              |        Muscles induce large forces in the tibiofemoral joint during walking and thereby
+              | influence the health or degradation of tissues like articular cartilage and menisci. It is
+              | possible to walk with a wide variety of muscle coordination patterns, but the effect of
+              | varied muscle coordination on tibiofemoral contact forces remains unclear. The first goal
+              | of this dissertation was to determine the effect of varied muscle coordination on
+              | tibiofemoral contact forces. We developed a musculoskeletal model of a subject walking
+              | with an instrumented knee implant. Using an optimization framework, we calculated the
+              | tibiofemoral forces resulting from muscle coordination that reproduced the subject’s
+              | walking dynamics. We performed a large set of optimizations in which we systematically
+              | varied the coordination of muscles to determine the influence on tibiofemoral force. Peak
+              | tibiofemoral forces during late stance could be reduced by increasing the activation of the
+              | gluteus medius, uniarticular hip flexors, and soleus and by decreasing the activation of
+              | the gastrocnemius and rectus femoris. These results suggest that retraining of muscle
+              | coordination could substantially reduce tibiofemoral forces during late stance.
+              |        Muscle coordination and the resulting tibiofemoral forces may vary dramatically
+              | due to changes in walking kinematics, especially for individuals with gait pathologies.
+              | Crouch gait, a common walking pattern in individuals with cerebral palsy, is
+              | characterized by excessive flexion of the hip and knee. Many subjects with crouch gait
+              | experience knee pain, perhaps because of elevated muscle forces and joint loading. The
+              | second goal of this dissertation was to examine how compressive tibiofemoral force
+              | change with the increasing knee flexion associated with crouch gait. Using our
+blank         | 
+meta          |                                                                                               v
+text          | musculoskeletal model, muscle forces and tibiofemoral force were computed for three
+              | unimpaired children and nine children with cerebral palsy who walked with varying
+              | degrees of knee flexion. Compressive tibiofemoral force increased quadratically with
+              | average stance phase knee flexion (i.e., crouch severity) during the stance phase of
+              | walking, primarily due to concomitant increases in quadriceps forces. These results
+              | revealed that walking in crouch generates increased knee loading which may contribute
+              | to knee pain in individuals with crouch gait.
+              |        Muscle coordination and pose are suspected causes and predictors of ankle
+              | inversion sprains. Interventions that retrain muscle coordination have helped rehabilitate
+              | injured ankles, but it is unclear which muscle coordination strategies, if any, can prevent
+              | ankle sprains. The third goal of this dissertation was to determine whether coordinated
+              | activity of the ankle muscles could prevent excessive ankle inversion during a simulated
+              | landing on a 30–degree incline. We used musculoskeletal simulations to evaluate two
+              | strategies for coordinating the ankle evertor and invertor muscles during simulated
+              | landing scenarios: planned co-activation and stretch reflex activation with physiologic
+              | latency (60-millisecond delay). Our simulations revealed that strong preparatory co-
+              | activation of the ankle evertors and invertors prior to ground contact prevented ankle
+              | inversion from exceeding injury thresholds by rapidly generating eversion moments after
+              | initial contact. Conversely, stretch reflexes were too slow to generate eversion moments
+              | before the simulations reached the threshold for inversion injury. These results suggest
+              | that training interventions to protect the ankle should focus on stiffening the ankle with
+              | muscle co-activation instead of increasing the speed or intensity of the evertor reflexes.
+              |        This dissertation examines the effects of varied muscle coordination on two of the
+              | most common musculoskeletal injuries: chronic degradation of the knee and acute ankle
+              | inversion sprains. Our results revealed key connections between specific changes in
+              | muscle coordination and improved function of the knee and ankle, suggesting exciting
+              | future research areas for designing and testing interventions that protect knee and ankle
+              | function. Additionally, this dissertation provides a computational foundation for
+              | systematically exploring muscle coordination in musculoskeletal models, and provides
+              | them, free and open source, to the broader research community.
+blank         | 
+              | 
+meta          | vi
+title         | Acknowledgments
+text          |        Foremost among the lessons of my PhD, I’ve learned that great research and
+              | training new scientists is a collaborative, community endeavor. My doctoral development
+              | has been far from a singular, heroic effort to do science. Instead, I owe my development
+              | to my gracious peers, inspiring mentors, and the exhilarating atmosphere at Stanford. I
+              | dedicate the work in this dissertation to everyone in the hard working community that
+              | continues to nurture my lifelong learning.
+              |        Above all, I am grateful to Scott Delp, my principal advisor and mentor, for being
+              | the architect and visionary behind my research community. Scott has grown a laboratory
+              | full of driven yet nurturing peers, supported us to pursue difficult research questions, and
+              | compelled us to share our work and expertise with the world as often as possible. Scott,
+              | the storyteller, taught me to have great impact by conveying my research and expertise as
+              | meaningful stories, and I’ve learned much of my communication style by emulating him.
+              | I am most grateful to Scott for the freedom he granted me to learn what I wanted, and
+              | dive deep into technical virtuosity beyond the level required to publish our research.
+              | Sincerely, thank you.
+              |        I am thankful for the inspiring people of the Neuromuscular Biomechanics
+              | Laboratory (NMBL). Through ad hoc writing clubs, practice presentations, and design
+              | session on the whiteboard, you provided the driving drum beat for my learning and
+              | research progress. Thank you to Kat Steele, Saikat Pal, and Jen Hicks for your intense
+              | collaboration and mentorship on our shared research. Thank you to Sam Hamner, Edith
+              | Arnold, Gabriel Sanches, Melinda Cromie, Chand John, Tim Dorn, James Dunne, Tom
+              | Uchida, Chris Dembia, Carmichael Ong, and Apoorva Rajagopal. I notice how you
+              | consistently stay late to offer feedback on my presentations and donate your time to
+              | critique and augment my work. Thank you for being selfless and supportive. Thank you
+              | to Carolyn Mazenko and Diane Bush for your constant attention that glues NMBL
+              | together.
+              |        I have been incredibly lucky to learn from the extraordinary people of the NIH
+              | Center for physics-based Simulation of Biological Structures (Simbios) and the National
+              | Center for Simulation in Rehabilitation Research (NCSRR). These centers produce the
+              | highest quality of biomechanical modeling software, and give it away, so that myself and
+blank         | 
+meta          |                                                                                           vii
+text          | thousands more researchers can pursue their challenging research questions. However,
+              | more importantly to me, I must recognize the character demonstrated by Ajay Seth,
+              | Ayman Habib, Michael Sherman, Jen Hick, Joy Ku, and Scott Delp. All of you
+              | demonstrate elite expertise yet simultaneously conduct yourselves with grace and
+              | patience. It is humbling and I will strive to conduct myself with the same unique blend of
+              | character.
+              |        Thank you to my dissertation readers and defense committee, who were Marc
+              | Levenston, Garry Gold, Ellen Kuhl, and Lane Smith. I am fortunate to have your
+              | guidance at the end of my PhD as you review and critique my work. It was a new and fun
+              | experience to sit together, borrow your attention, and discuss my research. Also, thank
+              | you to Gary Beaupre for your support and enthusiasm for my research and serving as a
+              | sixth advisor in many ways. To all of you, thank you for that honor.
+              |        Substantial data used in this dissertation were provided by the ASME Grand
+              | Challenge to Predict In Vivo Knee Loads, the Gillette Children’s Specialty Healthcare,
+              | and the Human Performance Lab at Stanford University. Thank you to B.J. Fregly, Thor
+              | Besier, David Lloyd, Darryl D’Lima, Michael Schwartz, Rebecca Shultz, and Amy Silder
+              | for providing these unique data and enabling the research I pursued.
+              |        I was fortunate to have extensive financial support throughout my PhD. Thank
+              | you to the National Library of Medicine Training Grant in Biomedical Informatics, the
+              | Powell Foundation, and the DARPA Warrior Web for supporting my livelihood during
+              | my PhD and granting me numerous opportunities to travel and share my research
+              | worldwide.
+              |        Finally, thank you to my family and friends for sharing your curiosity and
+              | passion. Thank you to my parents, Freda Sharp and Stephen DeMers, my sister and her
+              | husband, Rachel and Brad Rice, and all my extended family who, time and again, rally in
+              | support of learning and growth. Thank you to Adam, Vanessa, Saikat, Tim, Jayodita, Adi,
+              | Anja, Vivian, Kathy, John, Brett, Min-Sun, Jaimie, Andrew, James, Billy, Takane, Mai,
+              | Sully, Caroline, Kelly, Brandon, and Gentry for your unique humor and the energy you
+              | gift to me. Thank you Jason Inay and his eskrimadors for being the crucible. Thank you
+              | Stanford for being the hammer and anvil. Thank you Kate for being the water stone.
+blank         | 
+              | 
+meta          | viii
+title         | Table of contents
+blank         | 
+text          | ABSTRACT                                                                          V
+blank         | 
+text          | ACKNOWLEDGMENTS                                                                  VII
+blank         | 
+text          | TABLE OF CONTENTS                                                                IX
+blank         | 
+text          | LIST OF TABLES                                                                   XI
+blank         | 
+text          | LIST OF ILLUSTRATIONS                                                            XI
+blank         | 
+text          | 1. INTRODUCTION                                                                    1
+              | 1.1. FOCUS OF THIS DISSERTATION                                                    3
+              | 1.2. SIGNIFICANCE OF THIS RESEARCH                                                 4
+              | 1.3. OVERVIEW OF THIS DISSERTATION                                                 5
+blank         | 
+text          | 2. CHANGES IN TIBIOFEMORAL FORCES DUE TO VARIATIONS IN
+              | MUSCLE ACTIVITY DURING WALKING                                                     7
+              | 2.1. INTRODUCTION                                                                  7
+              | 2.2. METHODS                                                                       8
+              | 2.2.1. HUMAN SUBJECT DATA                                                          8
+              | 2.2.2. OPENSIM MODEL                                                               8
+              | 2.2.3. OPTIMIZATION                                                               10
+              | 2.2.4. A MUSCLE COORDINATION PATTERN MINIMIZING MUSCLE ACTIVATIONS                11
+              | 2.2.5. A MUSCLE COORDINATION PATTERN MINIMIZING COMPRESSIVE TIBIOFEMORAL FORCE    12
+              | 2.2.6. CHANGES IN TIBIOFEMORAL FORCES DUE TO VARIED ACTIVATIONS OF INDIVIDUAL
+              | MUSCLES                                                                           12
+              | 2.3. RESULTS                                                                      13
+              | 2.4. DISCUSSION                                                                   17
+              | 2.5. CONCLUSION                                                                   21
+blank         | 
+text          | 3. COMPRESSIVE TIBIOFEMORAL FORCES DURING CROUCH GAIT                             23
+              | 3.1. INTRODUCTION                                                                 23
+              | 3.2. METHODS                                                                      24
+              | 3.2.1. SUBJECTS                                                                   24
+              | 3.2.2. MOTION ANALYSIS                                                            25
+              | 3.2.3. MUSCULOSKELETAL MODELING                                                   25
+blank         | 
+meta          |                                                                                   ix
+text          | 3.3. RESULTS                                                                 30
+              | 3.2. DISCUSSION                                                              32
+              | 3.2. CONCLUSION                                                              36
+blank         | 
+text          | 4. PREPARATORY CO-ACTIVATION OF THE ANKLE MUSCLES MAY
+              | PREVENT ANKLE INVERSION INJURIES                                             37
+              | 4.1. INTRODUCTION                                                            37
+              | 4.2. METHODS                                                                 39
+              | 4.2.1. A NEW MUSCULOSKELETAL MODEL FOR SIMULATING ANKLE INVERSION INJURIES   39
+              | 4.2.2. GENERATING NOMINAL SIMULATIONS OF LANDING                             42
+              | 4.2.3. INDUCING ANKLE INVERSION IN SIMULATED LANDINGS                        44
+              | 4.2.4. QUANTIFYING THE EFFECT OF PLANNED CO-ACTIVATION                       45
+              | 4.2.5. QUANTIFYING THE EFFECT OF ANKLE STRETCH REFLEXES                      45
+              | 4.3. RESULTS                                                                 46
+              | 4.4. DISCUSSION                                                              49
+              | 4.5. CONCLUSION                                                              51
+blank         | 
+text          | 5. CONCLUSION                                                                52
+              | 5.1. CONTRIBUTIONS                                                           52
+              | 5.1.1. SCIENTIFIC FINDINGS                                                   52
+              | 5.1.2. TECHNOLOGICAL CONTRIBUTIONS TO THE RESEARCH COMMUNITY                 54
+              | 5.2. FUTURE WORK                                                             55
+              | 5.2.1. IMMEDIATE NEXT STEPS                                                  55
+              | 5.2.1. NEW LINES OF RESEARCH                                                 58
+blank         | 
+text          | LIST OF REFERENCES                                                           62
+blank         | 
+text          | APPENDIX A: OPEN SOURCE RESOURCES FROM THIS DISSERTATION 74
+blank         | 
+text          | APPENDIX B: CALCULATING JOINT CONTACT FORCES IN OPENSIM                      75
+blank         | 
+              | 
+              | 
+              | 
+meta          | x
+title         | List of Tables
+text          | Table 3.1: Characteristics of unimaired mild, moderate, and sever subjects. ................... 25
+              | Table 4.1: Parameters of the muscle stretch feedback controllers that coordinated the
+              |      trunk, hip, knee, and ankle plantar/dorsiflexor muscles. .......................................... 43
+blank         | 
+              | 
+title         | List of Illustrations
+text          | Figure 2.1: Musculoskeletal model of the human legs and torso, including a coupled
+              |      tibiofemoral and patellofemoral mechanism. ............................................................. 9
+              | Figure 2.2: Stance-phase tibiofemoral forces predicted in a musculoskeletal model by
+              |      minimize muscle activation squared or tibiofemoral forces, compared to in vivo
+              |      measurements. .......................................................................................................... 14
+              | Figure 2.3: The effect of varying activation of individual muscles on predicted
+              |      tibiofemoral forces shown for the most influential muscles. .................................... 15
+              | Figure 2.4: Maximum change in peak tibiofemoral force due to activation of a muscle or
+              |      muscle group during the late stance phase of walking. ............................................ 16
+              | Figure 2.5: Model predicted activations of the nine most influential muscles produced by
+              |      optimizations with varied muscle activity weights. .................................................. 18
+              | Figure 3.1: Tibiofemoral contact forces estimated in the computer model compared to
+              |      tibiofemoral forces measured in vivo. ....................................................................... 28
+              | Figure 3.2: Comparison of EMG and muscle activations from static optimization for
+              |      subjects with crouch gait. .......................................................................................... 29
+              | Figure 3.3: Average knee flexion angle, average compressive tibiofemoral force, and
+              |      average quadriceps force expressed as multiples of body-weight (xBW) during one
+              |      gait cycle for the subjects who walked with an unimpaired gait and mild, moderate,
+              |      and severe crouch gait. .............................................................................................. 31
+              | Figure 3.4: Correlation of average knee flexion angle during stance with average
+              |      compressive tibiofemoral force during stance, average quadriceps force during
+              |      stance, average hamstrings force during stance, and average gastrocnemius force
+              |      during stance. ............................................................................................................ 32
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                                                                 xi
+text          | Figure 3.5: Average tibiofemoral contact force, quadriceps force, hamstring force, and
+              |       gastrocnemius force during stance resulting from various objective functions. ....... 35
+              | Figure 4.1: Musculoskeletal model for simulating single-leg landing on level and inclined
+              |       surfaces, which included a torso, pelvis, and the right (landing) limb as well as
+              |       contact forces between the foot and floot. ................................................................ 40
+              | Figure 4.2: Load–deflection mechanics of passive ankle structures in the model compared
+              |       to soft tissue mechanics measured in cadavers (Chen et al., 1988). ......................... 41
+              | Figure 4.3: Simulated hip, knee, and ankle plantar flexion kinematics after initial ground
+              |       contact for a 0.3-meter landing onto level ground compared to kinematics measured
+              |       from a subject executing the same landing. .............................................................. 44
+              | Figure 4.4: Ankle inversion trajectories immediately after impact for various levels of
+              |       evertor and invertor muscle co-activation................................................................. 47
+              | Figure 4.5: Ankle inversion trajectories immediately after impact with ankle evertor and
+              |       invertor stretch reflexes of various intensities. ......................................................... 47
+              | Figure 4.6: Contributions of muscles and ligaments to the protective eversion moment
+              |       when adopting planned co-activation or strong stretch reflexes in the ankle evertor
+              |       and invertor muscles. ................................................................................................ 48
+blank         | 
+              | 
+              | 
+              | 
+meta          | xii
+title         | 1. Introduction
+text          |        Chronic knee degradation and acute ankle sprains occur at epidemic rates in
+              | humans and result in permanent deficits in function and health. Approximately 14% of
+              | Americans develop symptomatic osteoarthritis (OA) at the knee (Losina et al., 2013) and
+              | 12% experience ankle sprains during their lifetime (Doherty et al., 2014). These epidemic
+              | injuries are heavily influence by the loads in joint tissues and the muscle forces which
+              | generate them. For example, knee OA and pain have been linked to high tibiofemoral
+              | loads during walking (Baliunas, 2002; Schnitzer et al., 1993; Sharma et al., 1998),
+              | suggesting that changing the activity of muscles crossing the knee could decrease
+              | tibiofemoral loads and delay the onset and progression of OA. Similarly, ankle instability
+              | has been linked to slow or inactive ankle musculature, suggesting that increasing ankle
+              | muscle activity may prevent many ankle sprains (Delahunt, 2007; Konradsen and Bohsen
+              | Ravn, 1991; Löfvenberg et al., 1995). Therefor, delaying or even preventing chronic knee
+              | degradation, acute ankle sprains, and potentially many more joint tissue injuries require
+              | strategies for changing and optimizing muscle coordination to protect these tissues.
+              | Discovering these coordination strategies is only possible if we can safely and
+              | systematically control coordination and test the effect on the joints.
+              |        In vivo measurement of muscle coordination and the resulting joint function is
+              | difficult, invasive, and rarely done. Directly measuring muscle tensions requires invasive
+              | procedures, such as severing tendons to install buckle transducers in living subjects
+              | (Fukashiro et al., 1993; Gregor et al., 1991). Direct measurement of joint loads requires
+              | implanting instrumented joint prostheses which measure the loads near the articulating
+              | surfaces (Graichen et al., 2007; Kirking et al., 2006). While these techniques provide
+              | valuable data, their invasiveness makes experiments on healthy individuals unethical,
+              | limiting the size and diversity of subject cohorts. For example, in vivo knee loads have
+              | been measured in fewer than 20 subjects, all of whom were middle aged or older and
+              | already experienced joint degradation and surgery (Fregly et al., 2012; Kutzner et al.,
+              | 2010). Similarly, systematic testing of in vivo ankle sprain mechanics is not possible
+              | because inducing or risking injuries in healthy subjects would be unethical. To date,
+              | experimental measurements of ankle mechanics are either restricted to conditions that are
+              | far from the thresholds of injury (Chan et al., 2008; Gutierrez et al., 2012) or are
+blank         | 
+meta          |                                                                                             1
+text          | performed on cadavers with no muscle activity (Lapointe et al., 1997; Siegler et al.,
+              | 1990). Therefore, systematic and comprehensive exploration of coordination strategies to
+              | protect joints is impractical in vivo.
+              |         Conversely, musculoskeletal models can quantify internal muscle and joint loads
+              | (Delp et al., 2007; Sasaki and Neptune, 2010; Shelburne et al., 2005) and serve as a non-
+              | invasive environment for inducing or mitigating joint injuries. Unlike in vivo
+              | measurement of human subjects, computational models and simulations can explore
+              | unsafe conditions and experience injury without risk. Musculoskeletal models can define
+              | individual muscle activations and how they change throughout an activity, enabling fine
+              | and systematic variation of muscle coordination. Therefore, it is feasible and practical to
+              | use musculoskeletal models to experiment with coordination strategies and quantify the
+              | effect on knee and ankle function. In the work presented in this dissertation, we
+              | developed and used musculoskeletal models to propose and explore variations in
+              | coordination that might improve the function and health of the knee and ankle joints.
+              |         Musculoskeletal models for simulating full-body motion typically capture rigid
+              | bone segments, joint kinematics, muscle geometry, and muscle dynamics. Researchers
+              | often obtain skeletal geometry by dissecting and digitizing cadavers to yield bone
+              | geometry (Delp et al., 1990) and the kinematics of articulating joints like the knee (Grood
+              | et al., 1984; Walker et al., 1988) and ankle (Isman and Inman, 1969; Siegler et al., 1988).
+              | Digitized cadaver geometry is also the most common source for muscle attachment
+              | points, moment arms, and fiber architecture (Klein Horsman et al., 2007; Ward et al.,
+              | 2009) used in musculoskeletal models (Arnold et al., 2010; Modenese et al., 2011). Bone,
+              | joint, and muscle geometry can also be quantified through medical imaging. Magnetic
+              | resonance imaging has been used to quantify muscle geometry and to validate and tune
+              | muscle moment arms (Arnold et al., 2000) and muscle volumes (Handsfield et al., 2014)
+              | in musculoskeletal models. Models of muscle architecture and dynamics capture the fiber
+              | length and velocity dependencies of muscle’s force-generating capacity (Millard et al.,
+              | 2013). In turn, the muscle force-generating capacity and skeletal geometry determine the
+              | moment-generating capacity, or strength, of the whole musculoskeletal model. The
+              | models described in this dissertation are based upon bone segments, joint kinematics, and
+              | muscle geometry derived from cadavers (Delp et al., 1990).
+meta          | 2
+text          |         Full-body musculoskeletal models have been used to estimate muscle and joint
+              | forces during walking, but have not been used to their full capacity for varying muscle
+              | activations and knee forces. Muscle activations that minimize effort or metabolic
+              | expenditure during walking have been estimated in models and used to compute the
+              | resulting knee forces (Sasaki and Neptune, 2010; Shelburne et al., 2005). Similar models
+              | minimizing muscle activity have accurately estimated knee forces in walking subjects,
+              | validated by in vivo knee forces measured in instrumented prostheses in the same
+              | subjects (Kim et al., 2009; Walter et al., 2014). These and other previous works to date
+              | (Winby et al., 2009) have primarily focused on accurately estimating the muscle forces
+              | that occurred during measured walking experiments and analyzing the resulting knee
+              | forces. However, the capacity to vary muscle activations and change the resulting knee
+              | forces during walking remained largely unexplored until the work described in this
+              | dissertation.
+              |         In contrast to models of walking, musculoskeletal models of ankle sprains are
+              | rare. Isolated models of the ankle have been developed to compute ankle ligament strains
+              | during measured motions (Wei et al., 2011b), but these models exclude muscles and
+              | ignore their capacity to protect the ankle (Wei et al., 2011a). Wright et al. used full-body,
+              | muscle-driven simulations of sidestepping to demonstrate that neutral ankle posture
+              | (Wright et al., 2000a) and increased passive ankle stiffness from braces or tape (Wright et
+              | al., 2000b) could decrease the likelihood of ankle sprains. However, these simulations
+              | only tested the effects of external stiffening. The effects of changes in muscle activity and
+              | the capacity of the intrinsic ankle muscles to prevent ankle inversion injuries remained
+              | unclear until the work described in this dissertation.
+blank         | 
+title         | 1.1. Focus of this dissertation
+text          |         The goal of this dissertation was to quantify and identify coordination strategies
+              | that might mitigate the most epidemic knee and ankle injuries by decreasing tibiofemoral
+              | forces during walking or resisting ankle inversion during landing. We created three-
+              | dimensional models of human walking and drop-landing which allowed us to probe and
+              | control the internal muscle forces, joint kinematics, and joint forces during walking and
+              | landings tasks. We used combinations of optimization and feedback control to
+blank         | 
+              | 
+meta          |                                                                                              3
+text          | systematically vary muscle coordination strategies and task kinematics, then observed the
+              | effects on tibiofemoral force during walking and ankle inversion during landing. We
+              | found that changing the distribution of muscle forces during walking can dramatically
+              | alter the tibiofemoral forces while still maintaining identical walking kinematics. We
+              | identified the muscles with the greatest effect on increasing or decreasing the
+              | tibiofemoral force and found that many influential muscles do not cross the knee. Next,
+              | we fixed the distribution of muscle forces and systematically varied the degree of crouch
+              | kinematics during walking. We found that increased degree of crouch requires larger
+              | muscle forces and results in increased tibiofemoral forces during walking. The
+              | compressive tibiofemoral forces increased quadratically with the degree of knee flexion
+              | during stance (a measure of crouch severity), and individuals walking in severe crouch
+              | experienced three-times the compressive tibiofemoral force of unimpaired individuals.
+              | Finally, we used musculoskeletal simulations of landing under muscle feedback control
+              | to induce ankle inversion injuries and test whether planned co-activation or unplanned
+              | stretch reflexes of the ankle evertors and invertors could prevent the injury. We found
+              | that planned co-activation at a sub-maximal level could rapidly generate protective forces
+              | and prevent injury. Conversely, even the fastest known stretch reflexes (60 millisecond
+              | latency) were too slow to resist the ankle injuries we simulated. These analyses identify
+              | specific coordination strategies that change tibiofemoral forces and prevent ankle
+              | inversion, which serve as a foundation for developing novel interventions for decreasing
+              | the epidemic rates of chronic knee pain and acute ankle sprains.
+blank         | 
+title         | 1.2. Significance of this research
+text          |        The work described in this dissertation yielded valuable biomechanical
+              | knowledge of joint loading and injury, as well as contributed models, simulations, and
+              | software tools that enable new research in the biomechanics community. We created
+              | sophisticated musculoskeletal models and simulations to explore how muscle
+              | coordination and kinematics could affect the internal loads of the knee during walking
+              | and protect the ankle from injury during landing. Our findings identified specific
+              | coordination strategies —and ruled out others— that could form the basis of much
+              | needed clinical interventions against musculoskeletal pain and injury. We also took great
+blank         | 
+meta          | 4
+text          | care to make our models and software tools reusable, extensible, and publicly available to
+              | enable and accelerate continuing work in the scientific community. The primary
+              | contributions of the research described in this dissertation are:
+              |    •! Identifying the primary muscles to recruit for decreasing or increasing
+              |        tibiofemoral forces during walking.
+              |    •! Quantifying how severity of crouch pathology affects the tibiofemoral forces
+              |        during walking in individuals with cerebral palsy.
+              |    •! Quantifying whether or not planned co-activation or physiologic stretch
+              |        reflexes of the ankle evertors and invertors can prevent ankle inversion
+              |        injuries during landing.
+              |    •! Designing and disseminating novel models and software to explore full-body
+              |        musculoskeletal dynamics, muscle coordination, and joint function.
+blank         | 
+title         | 1.3. Overview of this dissertation
+text          |        This dissertation is composed of three research studies that are presented as self-
+              | contained articles. Much of this work was performed in collaboration with others;
+              | therefore, I use the pronoun “we” throughout the dissertation to refer to myself and my
+              | coauthors. After this general introduction, Chapter 2 describes a three-dimensional
+              | modeling and optimization framework for studying walking gait and an analysis
+              | determining the changes in tibiofemoral forces due to variations in muscle activity. This
+              | work was previously published in the Journal of Orthopaedic Research in collaboration
+              | with my coauthors Saikat Pal and Scott Delp (DeMers et al., 2014). Chapter 3 describes
+              | an analysis using a similar modeling and optimization framework to determine the
+              | changes in tibiofemoral forces due to variations in knee flexion during walking in
+              | unimpaired versus crouch gaits. This work was previously published in the journal Gait
+              | & Posture in collaboration with my coauthors Katherine Steele and Scott Delp (Steele et
+              | al., 2012). Chapter 4 describes a landing model with foot-floor contact, passive ankle
+              | moments representing ligaments, and novel muscle feedback controllers as well as a
+              | battery of landing simulations that test the efficacy of two ankle coordination strategies
+              | for preventing ankle injury. This work has been submitted for peer review in
+              | collaboration with my coauthors Jennifer Hicks and Scott Delp. The final chapter
+blank         | 
+              | 
+meta          |                                                                                              5
+text          | highlights the important contributions of this dissertation to science and to the broader
+              | research community and outlines specific questions for future research.
+blank         | 
+              | 
+              | 
+              | 
+meta          | 6
+title         | 2. Changes in tibiofemoral forces due to variations in muscle
+              | activity during walking
+blank         | 
+title         | 2.1. Introduction
+text          |        The knee experiences large mechanical loads during activities of daily living.
+              | Walking, for example, induces forces as large as three bodyweights at the knee (Fregly et
+              | al., 2012; Kutzner et al., 2010). These loads affect the development, maintenance, and
+              | health of the joint tissues (Carter and Wong, 1988). The onset and progression of
+              | osteoarthritis can be associated with large loads at the knee (Baliunas, 2002; Sharma et
+              | al., 1998), and increased knee loads have been linked to pain in patients with
+              | osteoarthritis (Schnitzer et al., 1993). Since tibiofemoral loads during walking are
+              | produced primarily by muscle forces (Sasaki and Neptune, 2010; Shelburne et al., 2006),
+              | muscle coordination plays a pivotal role in determining tibiofemoral loads. Identifying
+              | muscle coordination patterns that alter tibiofemoral loads may assist in the design of
+              | rehabilitation programs to restore and maintain the health of the knee.
+              |        Training and rehabilitation programs can reduce tibiofemoral loads during
+              | walking by alteration of gait kinematics. Fregly et al. demonstrated that adopting a
+              | “medial thrust” gait reduced medial compartment forces measured in vivo using
+              | instrumented knee replacements (Fregly et al., 2009). Strategies altering foot progression
+              | angle and medio-lateral foot placement during the stance phase of walking reduce the net
+              | knee adduction moment (Chang et al., 2007; Guo et al., 2007; Shull et al., 2011) and knee
+              | pain (Shull et al., 2013). Exaggerated trunk sway in the medio-lateral direction during
+              | walking can reduce net knee adduction moments (Mündermann et al., 2008a). While
+              | previous work demonstrates that altering gait kinematics can reduce knee loads during
+              | walking, the effects of altered muscle coordination on tibiofemoral loads remain unclear.
+              |        Studying the effects of altered muscle coordination on tibiofemoral loads is
+              | challenging. Direct measurement of tibiofemoral loads during walking requires
+              | implanting instrumented knee prostheses in living subjects (D’Lima et al., 2005; Fregly et
+              | al., 2012; Kutzner et al., 2010). This technique provides valuable data, but is highly
+              | invasive, making measurement of tibiofemoral loads impractical in healthy subjects and
+              | limiting the number of subjects in which knee loads can be measured. An alternative to
+blank         | 
+meta          |                                                                                            7
+text          | direct measurement is calculating tibiofemoral loads using musculoskeletal modeling.
+              | Model-based studies have estimated tibiofemoral loads using a variety of muscle
+              | coordination strategies, including minimizing muscle activity (Sritharan et al., 2012;
+              | Steele et al., 2012), muscle stress (Glitsch and Baumann, 1997), or energy consumption
+              | (Shelburne et al., 2005). Previous studies have determined a single set of muscle forces
+              | during walking and the resulting tibiofemoral loads, but the changes in tibiofemoral loads
+              | arising from variations in muscle activations remains unknown.
+              |        The purpose of this study was to determine the changes in tibiofemoral forces due
+              | to variations in muscle activation patterns. We first evaluated whether a commonly
+              | assumed muscle coordination strategy, minimizing the sum of muscle activations
+              | squared, Thelen et al. (2003) produced tibiofemoral forces that were consistent with in
+              | vivo measurements. We next determined the potential for a subject to decrease
+              | tibiofemoral forces during walking by adopting a muscle coordination strategy that
+              | minimized tibiofemoral forces. Finally, we determined the changes in tibiofemoral forces
+              | due to varied activations of individual muscles of the lower limb and identified the
+              | muscles with the greatest potential to alter tibiofemoral loading.
+blank         | 
+title         | 2.2. Methods
+blank         | 
+title         | 2.2.1. Human Subject Data
+text          |        We used walking data of a subject implanted with an instrumented total knee
+              | replacement (TKR). These data are available from the ASME Grand Challenge
+              | Project(Fregly et al., 2012). The subject (83 year old male, 64 kg, 166 cm tall) had
+              | received bilateral TKR. The right TKR was instrumented to measure tibiofemoral forces
+              | normal to the tibial plateau (D’Lima et al., 2005). The data include three-dimensional
+              | marker positions, ground reaction forces, and tibiofemoral forces measured
+              | simultaneously during walking at the subject’s self-selected speed (1.3 m/s).
+blank         | 
+title         | 2.2.2. OpenSim Model
+text          |        We created a full-body gait model in OpenSim (Delp et al., 2007) to analyze knee
+              | loads. The 10 segment, 19 degree of freedom (dof) model (Figure 2.1 A) was adapted
+              | from a musculoskeletal model of the lower limb published by Delp et al. (1990) (Figure
+blank         | 
+meta          | 8
+text          | 2.1 A). The model was driven by 92 muscle-tendon actuators (Thelen et al., 2003) that
+              | captured force-length-velocity properties, with muscle geometry and architecture based
+              | on adult cadaver data (Delp et al., 1990). A ball-and-socket joint connected the torso to
+              | the pelvis. The right and left lower limbs consisted of a ball-and-socket hip joint, a
+              | revolute ankle joint, and a coupled knee mechanism (1 dof) with translations of the tibia
+              | and patella prescribed by the knee flexion angle. We refined the knee mechanism of the
+              | generic model so that the patella articulated with the femur, and the quadriceps wrapped
+              | around the patella before attaching to the tibial tuberosity (Figure 2.1 B). The patella
+              | functioned as a frictionless pulley that redirected the quadriceps forces to act along the
+              | line of action of the patellar ligament. This refined knee mechanism reproduced the
+              | patellofemoral kinematics in Delp et al. (1990) and enabled resultant tibiofemoral forces
+              | to be computed.
+blank         | 
+              | 
+              | 
+              | 
+text          | Figure 2.1: (A) Musculoskeletal model of the human legs and torso. The tibiofemoral and patellofemoral
+              | joints were modeled as planar joints with translations and rotations coupled to the knee flexion angle (B).
+              | Forces in the quadriceps (B, dark red) were transmitted through the patella to the tibia (see Methods for
+              | details).
+blank         | 
+meta          |                                                                                                               9
+text          |        We used the full-body model to simulate 3D walking dynamics of the
+              | instrumented subject. All joint kinematics, muscle attachments, and the resulting muscle
+              | moment arms were scaled to match the segment lengths of the subject. Additionally, the
+              | optimal fiber length and tendon slack length of each muscle were scaled according to the
+              | muscle’s total change in muscle-tendon length. Other muscle parameters, including peak
+              | isometric forces and pennation angles, were not altered. We determined joint kinematics
+              | for five trials of normal walking by minimizing error between the experimentally
+              | measured marker positions and the corresponding markers on the model. A residual
+              | reduction algorithm (Delp et al., 2007) adjusted the model mass properties and joint
+              | kinematics for each trial to ensure that the ground reaction forces and body segment
+              | accelerations were dynamically consistent. After residual reduction the model segment
+              | masses differed by less than 2% from the scaled model, and the resulting joint kinematics
+              | differed by less than 2 degrees from the kinematics tracked by the residual reduction
+              | algorithm.
+blank         | 
+title         | 2.2.3. Optimization
+text          |        We developed a static optimization framework in OpenSim to calculate individual
+              | muscle forces and resulting tibiofemoral forces for each trial. This optimization
+              | minimized a sum of muscle activations and joint loads by combining them in a single
+              | objective function:
+              |                                                            Equation 2.1
+              |                                                              6                                  *7
+              |                                           )<=&)>,          %4 7    0      0                    %4     0      0
+              |              )*+,-./,
+              |                                                                     69                                 *9
+              |    min $                %& '&   (
+              |                                     $+$             $345    0     %4      0     34 $ + $ ;45    0    %4      0     ;4 $ $ $
+              |              &01
+              |                                              4                             6                                  *
+              |                                                             0      0     %4 :                   0     0     %4 :
+blank         | 
+              | 
+              | 
+text          | subject to the constraint
+              |       )*+,-./,
+              |                  3& ('& ) +          3/A>/B)C. = E F F + G F, F +                              3-=),>BC&)> $$$Equation$2.2
+              |       &01
+blank         | 
+              | 
+              | 
+text          |        In the objective function, ai was the activation of the ith muscle, which could vary
+              | between 0 and 1. The activation weight, wi, was a weighting constant set to penalize
+meta          | 10
+text          |                                                                              6      6             6
+              | activation of the ith muscle. The joint force weighting constants, %4 7 , %4 9 , and %4 : were
+blank         | 
+text          | set to penalize the vector components of the jth joint reaction force, 34 . Similarly, the joint
+              |                                   *     *            *:
+              | moment weighting constants, %4 7 , %4 9 , and %4          were set to penalize the vector
+blank         | 
+text          | components of the jth joint reaction moment,$;4 . The joint reaction forces and moments
+              | represented the resultant loads carried by the articulating joint structures, and were
+              | calculated using the JointReaction analysis in OpenSim (Steele et al., 2012).
+              |         We constrained the optimization such that the calculated muscle forces and
+              | measured external forces balanced all inertial forces to reproduce the measured walking
+              | motion (Equation 2.2). 3& ('& ) represented the force applied by muscle i due to its
+              | activation, '& . The external forces included forces due to gravity and ground reactions at
+              | the feet. The system mass matrix, E F , was a function of the measured generalized
+              | coordinates, F. The velocity dependent forces, G(F, F), included centripetal and Coriolis
+              | forces. The kinematic constraint forces included forces due to coupling between
+              | patellofemoral and tibiofemoral kinematics. Equation 2.2 guaranteed that the optimized
+              | muscle activations reproduced the walking kinematics and ground reaction forces
+              | measured from the instrumented TKR subject.
+blank         | 
+title         | 2.2.4. A muscle coordination pattern minimizing muscle activations
+text          |         We simulated the five trials of normal walking with a muscle coordination pattern
+              | that minimized muscle activations. In this case, the generalized objective function
+              | (Equation 2.1) simplified to
+              |                                           )*+,-./,
+              |                                                              (
+              |                                min $                 1×'&        $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$Equation$2.3$$$
+              |                                           &01
+blank         | 
+text          | The activation weight, w, was set to 1 for all muscles to penalize all muscle activations
+              | uniformly. The joint force and moment weighting constants were set to zero so that joint
+              | loads were not penalized. This optimization strategy was used in previous
+              | studies.(Anderson and Pandy, 2001; Sritharan et al., 2012)
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                                            11
+title         | 2.2.5. A muscle coordination pattern minimizing compressive tibiofemoral force
+text          |        We simulated the five trials of normal walking with a muscle coordination pattern
+              | that minimized the compressive force in the tibiofemoral joint of the instrumented leg. In
+              | this case, the generalized objective function (Equation 2.1) simplified to
+blank         | 
+              | 
+text          |                                % 67 = 0    0    0
+              |                           5
+              |                 min      356       0     69
+              |                                         % =1    0 356 $$$$$$$$$$$$$$$$$$$$Equation$2.4
+              |                                               6:
+              |                                    0       0 % =0
+blank         | 
+              | 
+text          | which is equivalent to
+blank         | 
+              | 
+text          |                                             (
+              |                                        min 356,U $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$Equation$2.5
+blank         | 
+              | 
+text          |        The activation weight, w, was set to zero for all muscles so that muscle activations
+              | were not penalized. The compressive tibiofemoral force was defined as the vector
+              | component of the tibiofemoral force acting normal to the tibial plateau, 356,U . The
+              | compressive tibiofemoral force was penalized by setting its weighting constant, % 69 ,
+              | equal to 1; all other joint force and moment weighting constants were set to zero. This
+              | strategy determined the muscle coordination pattern that minimized the tibiofemoral
+              | forces and matched the measured walking dynamics.
+blank         | 
+title         | 2.2.6. Changes in tibiofemoral forces due to varied activations of individual muscles
+text          |        We determined the change in tibiofemoral forces due to varied activations of
+              | individual muscles of the lower limb by performing optimizations with varied activation
+              | weighting constants, wi, for each muscle. For these optimizations, the generalized
+              | objective function (Equation 2.1) was simplified:
+blank         | 
+              | 
+text          |                                          )*+,-./,
+              |                                                              (
+              |                                 min                  %& '&       $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$Equation$2.6
+              |                                          &01
+blank         | 
+text          | In Equation 6, w = 0 represented no penalty to activate a muscle during walking, while w
+              | = 100 prohibited activation of a muscle.
+blank         | 
+              | 
+meta          | 12
+text          |         To investigate the change in tibiofemoral forces due to varied activation of a
+              | muscle, we performed two static optimizations for each trial of normal walking. First, to
+              | prohibit activation of a particular muscle, we performed a static optimization with w =
+              | 100 for that muscle while w for all other muscles was held at 1. Second, to promote
+              | activation of a particular muscle, we performed a static optimization with w = 0 for that
+              | muscle while w for all other muscles was held at 1. Performing two static optimizations
+              | for each muscle of the lower limb determined the range of tibiofemoral forces due to
+              | varying activation of that muscle. We determined the change in peak tibiofemoral force
+              | due to activation of a muscle by calculating the difference between peak tibiofemoral
+              | forces obtained from the static optimizations with w = 0 and w = 100.
+              |         Our methods produced similar joint moments, muscle activations, and
+              | tibiofemoral forces for all five walking trials; thus, we have included results from one
+              | representative trial for clarity.
+blank         | 
+title         | 2.3. Results
+text          |         A muscle coordination strategy that minimized muscle activations produced
+              | greater tibiofemoral forces than forces measured in vivo (Figure 2.2). During late stance
+              | (33-66% gait), a muscle coordination strategy that minimized the sum of muscle
+              | activations squared produced a peak tibiofemoral force that was 1.7 bodyweights larger
+              | than the peak force measured in vivo. This difference was less pronounced during early
+              | stance (0-33% gait), when minimizing muscle activations squared produced a peak
+              | tibiofemoral force that was 0.4 bodyweights larger than the peak force measured in vivo.
+              | During the swing phase (not shown), differences between the model-predicted and
+              | measured forces were less than 0.2 bodyweights.
+              |         A muscle coordination strategy that minimized tibiofemoral forces produced
+              | lower model-predicted forces than forces measured in vivo (Figure 2.2). During late
+              | stance, a muscle coordination strategy that minimized tibiofemoral force produced a peak
+              | model-predicted force that was 1.5 bodyweights lower than the peak force measured in
+              | vivo. During early stance, this strategy produced a peak tibiofemoral force that was
+              | similar to the peak force measured in vivo.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                             13
+text          | Figure 2.2: Stance-phase tibiofemoral forces predicted using a musculoskeletal model and muscle
+              | coordination strategies that minimize muscle activation squared (dashed black line) and tibiofemoral
+              | forces (solid grey line). The minimum tibiofemoral force represents the smallest compressive tibiofemoral
+              | force the model generated while still reproducing the measured walking kinematics and kinetics. Measured
+              | in vivo forces (solid black line) are shown.
+blank         | 
+              | 
+              | 
+text          |          Tibiofemoral forces were sensitive to activations of muscles of the lower limb,
+              | especially during the late stance phase of walking (Figure 2.3). Tibiofemoral forces were
+              | sensitive to activations of the gastrocnemius and the rectus femoris but only during late
+              | stance. Tibiofemoral forces were also sensitive to activations of the psoas major, iliacus,
+              | and soleus muscles during late stance. Tibiofemoral forces were sensitive to activations
+              | of the biarticular hamstrings during early stance, and were sensitive to activations of the
+meta          | 14
+text          | biceps femoris short head during late stance. Tibiofemoral forces were insensitive to
+              | activations of the vasti muscles; this occurred because producing the dynamics of the
+              | subject’s walking required activation of the vasti, even when activation of these muscles
+              | was penalized in the optimization. Varying activations of the gluteus medius muscle
+              | produced large changes in tibiofemoral forces throughout stance phase.
+blank         | 
+              | 
+              | 
+              | 
+text          | Figure 2.3: The effect of varying activation of individual muscles on predicted tibiofemoral forces shown
+              | for the most influential muscles. The shaded area represents the range of predicted tibiofemoral forces due
+              | to varying the activation of each muscle. For each muscle, the boundary indicated by w = 0 corresponded
+              | to the optimization for which the muscle activity weight of that muscle was set to zero in the objective
+              | function. This objective function permitted the muscle to activate without penalty. The model predictions
+              | that minimize uniformly weighted muscle activations squared (dashed black lines) are shown.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                                             15
+text          | Figure 2.4: Maximum change in peak tibiofemoral force due to activation of a muscle or muscle group
+              | during the late stance phase of walking. The maximum change was calculated as the difference between
+              | peak tibiofemoral forces obtained from the static optimizations with w = 0 (promote activity) and w = 100
+              | (prohibit activity) for that muscle or muscle group. Note that increasing the activation of gluteus medius
+              | greatly decreased the tibiofemoral force, whereas increasing the activation of the gastrocnemius increased
+              | tibiofemoral force. The changes in peak tibiofemoral force during the late stance of walking were minimal
+              | for the muscles not shown.
+blank         | 
+              | 
+              | 
+text          |          Promoting activation of the gluteus medius produced the largest decrease in peak
+              | tibiofemoral force during late stance (Figure 2.4). Promoting activation of the psoas,
+              | iliacus, and soleus muscles also decreased peak tibiofemoral force during late stance.
+              | Promoting activation of the gastrocnemius produced the largest increase in peak
+              | tibiofemoral force during late stance. Promoting activation of the rectus femoris and
+blank         | 
+meta          | 16
+text          | biceps femoris short head also increased peak tibiofemoral force during late stance. The
+              | vasti remained inactive after 30% of gait and had little effect on peak tibiofemoral force
+              | during late stance. Changing the activation of other muscles of the lower limb had little
+              | effect on peak tibiofemoral force during late stance.
+blank         | 
+title         | 2.4. Discussion
+text          |        Our results demonstrate that altering muscle activation patterns during walking
+              | can induce large changes in compressive forces at the tibiofemoral joint. Tibiofemoral
+              | forces were sensitive to activations of a small subset of lower limb muscles, including the
+              | gluteus medius, gastrocnemius, and rectus femoris, indicating that these muscles have the
+              | greatest potential to affect knee loading. This suggests that interventions aimed at
+              | retraining muscle coordination should target these muscles to reduce tibiofemoral loads.
+              |        Our first goal was to evaluate whether a strategy minimizing the sum of muscle
+              | activations squared produced tibiofemoral forces that were consistent with in vivo
+              | measurements. When adopting this strategy, our model over-predicted tibiofemoral
+              | forces during the late stance phase. The discrepancy was due to over-activity of the rectus
+              | femoris and gastrocnemius, which were the largest contributors to the over-predicted
+              | tibiofemoral force. The model activated the rectus femoris during late stance, while
+              | electromyography (EMG) measured from the subject suggest that the rectus femoris may
+              | have been inactive at this time (Figure 2.5). Similarly, the strategy minimizing muscle
+              | activations squared activated the gastrocnemius earlier and more than the soleus;
+              | however, EMG data show that the subject activated the gastrocnemius and soleus
+              | muscles equitably during late stance. Optimization objectives that penalized activity of
+              | the rectus femoris and gastrocnemius produced lower tibiofemoral forces that better
+              | matched in vivo measurements.
+              |        Our second goal was to determine the potential for a subject to decrease
+              | tibiofemoral forces during walking by altering muscle coordination. Our model achieved
+              | tibiofemoral forces that were lower than in vivo measurements during late stance by
+              | adopting different muscle activation patterns compared to the TKR subject (Figure 2.2).
+              | For example, the model minimized tibiofemoral forces by deactivating the gastrocnemius
+              | and hamstrings during late stance, whereas the TKR subject activated these muscles
+blank         | 
+              | 
+meta          |                                                                                             17
+text          | during late stance (Fregly et al., 2012), resulting in higher tibiofemoral forces. Thus, the
+              | model demonstrated a lower bound for the subject’s tibiofemoral forces during late
+              | stance.
+blank         | 
+              | 
+              | 
+              | 
+text          | Figure 2.5: Model predicted activations of the nine most influential muscles produced by optimizations
+              | with varied muscle activity weights. For each muscle, activity ranged from 0 (no activity) to 1 (maximum
+              | activity). A muscle activity weight of w = 100 (dotted blue) prohibited the muscle from activating, while w
+              | = 0 (solid red) allowed the muscle to activate freely. The range of muscle activity used by the model (the
+              | area between the dotted blue and solid red lines) resulted in a corresponding variation in tibiofemoral
+              | forces (Figure 3). Filtered electromyography (EMG) signals, measured from the subject during the same
+              | trial of normal walking, are provided for comparison. EMG was not measured from the psoas major or
+              | iliacus muscles.
+blank         | 
+              | 
+meta          | 18
+text          |        Increasing the activation of gluteus medius, a muscle crossing the hip, had the
+              | greatest potential to reduce tibiofemoral forces during walking. The gluteus medius
+              | produced the largest hip abduction moment throughout the stance phase of walking. In
+              | our simulations, increased activation of the gluteus medius resulted in a compensatory
+              | decrease in activation of the rectus femoris, tensor fasciae latae, and sartorius muscles to
+              | maintain the required hip abduction moment. The decrease in activations of the rectus
+              | femoris muscle in turn resulted in a compensatory decrease in activations of the
+              | gastrocnemius and biceps femoris short head muscles to maintain net knee moments.
+              | These decreased activations of the rectus femoris, gastrocnemius, and biceps femoris
+              | short head muscles resulted in decreased tibiofemoral forces. Conversely, decreasing
+              | activations of the gluteus medius muscle increased activations of the rectus femoris,
+              | gastrocnemius, and biceps femoris short head muscles, thereby increasing tibiofemoral
+              | forces. Thus, while the gluteus medius does not cross the knee, changes in activity or
+              | forces generated by this muscle produce substantial compensations from other muscles
+              | and have a potent effect on tibiofemoral forces. Our results may seem inconsistent with
+              | studies that have reported minimal contributions of the gluteus medius to tibiofemoral
+              | force (Sasaki and Neptune, 2010; Sritharan et al., 2012); however, these studies reported
+              | the contributions of individual muscles to tibiofemoral force based on a single muscle
+              | activation pattern and did not account for compensatory muscle activity. In contrast, we
+              | selectively changed activations of individual muscles and allowed other muscle
+              | activations to compensate to reproduce the walking motion.
+              |        Increasing the activation of the gastrocnemius and rectus femoris, two biarticular
+              | muscles crossing the knee, had the greatest potential to increase tibiofemoral forces
+              | during the late stance phase of walking. In addition to generating moments about the
+              | knee, the gastrocnemius and rectus femoris muscles produce ankle plantarflexion and hip
+              | flexion moments, respectively, in preparation for swinging the leg. During late stance,
+              | increased activation of the gastrocnemius generated a large knee flexion moment, causing
+              | compensatory co-activation of the rectus femoris to balance the net knee moment.
+              | Conversely, increased activation of the rectus femoris generated a knee extension
+              | moment, causing compensatory co-activation of the gastrocnemius and biceps femoris
+blank         | 
+meta          |                                                                                           19
+text          | short head. Co-activation of the gastrocnemius, rectus femoris, and biceps femoris short
+              | head increased tibiofemoral forces. Previous studies have shown that the gastrocnemius
+              | and rectus femoris muscles contribute a higher proportion of the tibiofemoral force than
+              | the soleus and the uniarticular hip flexors (Sasaki and Neptune, 2010; Sritharan et al.,
+              | 2012). Sasaki and Neptune (2010) postulated that decreasing activations of the biarticular
+              | knee muscles may decrease tibiofemoral loading; our results support this idea. We also
+              | found that promoting activations of the soleus and uniarticular hip flexors could reduce
+              | tibiofemoral force. These results suggest that training to strengthen and activate the
+              | soleus and uniarticular hip flexors may decrease tibiofemoral forces and associated knee
+              | pain.
+              |         Tibiofemoral forces were most sensitive to muscle activations during the late
+              | stance phase of walking. During late stance, net knee flexion-extension moments are
+              | small compared to early stance (Liu et al., 2008; McClelland et al., 2010). Low net knee
+              | flexion-extension moments during late stance allow a large range of muscle activations
+              | while still reproducing the measured walking motion. Since minimal muscle forces are
+              | required to generate the low net knee moments, the model can minimally activate
+              | muscles crossing the knee, especially the quadriceps (Figure 2.5). However, the model
+              | can also co-activate the knee muscles, using a large portion of their force-generating
+              | capacity to generate co-contraction. This permits substantial freedom to vary muscle
+              | activations and tibiofemoral forces during late stance without altering the walking
+              | motion. In contrast, larger knee extension moments during early stance demand larger
+              | activations of the knee extensors. Therefore, muscle activations that reproduce walking
+              | are constrained to a narrow range, allowing only small variations in tibiofemoral forces
+              | during early stance.
+              |         A limitation of this study was that we used walking kinematics measured from
+              | one subject with bilateral TKR, and it is unclear if this dataset adequately represents a
+              | healthy or osteoarthritic population with intact knees. Subjects with TKR have been
+              | shown to walk with a straighter leg and reduced knee moments during stance (Bolanos et
+              | al., 1998; McClelland et al., 2010), presumably to reduce quadriceps forces and
+              | tibiofemoral loading. In our case, the TKR subject displayed stance phase knee moments
+              | that are similar to pain free subjects. Peak knee moments of from 2-5% bodyweight times
+meta          | 20
+text          | height are typically reported for pain free subjects walking at self-selected speed (Liu et
+              | al., 2008; McClelland et al., 2010; Pandy et al., 2010); in comparison, our TKR subject
+              | generated peak knee moments of 4% bodyweight times height. The knee moments were
+              | similar across five walking trials; hence, our reported results from a single trial are
+              | representative of the remaining four normal walking trials. A second limitation of this
+              | study was that our simplified tibiofemoral joint did not permit knee abduction-adduction
+              | or internal-external rotation. Including these degrees of freedom would require the knee
+              | muscles to balance net moments in these directions. We speculate that producing these
+              | moments would increase muscle activations and tibiofemoral forces reported in this
+              | study. Tibiofemoral forces also depend on muscle geometry and strength; therefore,
+              | changes in the model’s muscle attachments and architecture would affect the reported
+              | results as well. A fourth limitation was that we permitted all muscles to activate
+              | independently. This may result in compensatory muscle coordination strategies that may
+              | be physiologically difficult for a patient to adopt. For example, a patient may have
+              | difficulty activating the soleus without activating the gastrocnemius. Finally, we
+              | calculated muscle activations that did not cause kinematic compensations (i.e., walking
+              | dynamics were unchanged when muscle activations were varied). Other studies have
+              | demonstrated that altered walking kinematics also decrease tibiofemoral loads (Fregly et
+              | al., 2009; Shull et al., 2013, 2011). Permitting walking kinematics to change along with
+              | muscle activations will likely result in greater reductions in tibiofemoral forces than those
+              | reported here.
+blank         | 
+title         | 2.5. Conclusion
+text          |        This study identified muscles that substantially affect tibiofemoral forces during
+              | walking. Interestingly, inactivity or weakness in the muscles crossing the hip and ankle
+              | joints can affect the loads of the knee joint. Increased activation and force in the gluteus
+              | medius, psoas major, iliacus, and soleus muscles may decrease tibiofemoral forces.
+              | Decreased activation of the gastrocnemius and rectus femoris muscles can also decrease
+              | tibiofemoral forces. Training programs targeting knee rehabilitation should include
+              | exercises that strengthen and activate the gluteus medius, psoas, and soleus muscles. It
+              | may be feasible to combine kinematic gait retraining with muscle coordination and
+blank         | 
+              | 
+meta          |                                                                                            21
+text          | strength training to design interventions that substantially decrease tibiofemoral forces
+              | during walking.
+blank         | 
+              | 
+              | 
+              | 
+meta          | 22
+title         | 3. Compressive tibiofemoral forces during crouch gait
+blank         | 
+title         | 3.1. Introduction
+text          |        Crouch gait is a common pathological walking pattern adopted by individuals
+              | with cerebral palsy that is characterized by excessive hip and knee flexion. Walking in a
+              | crouched posture is inefficient (Rose et al., 1989; Waters and Mulroy, 1999) and can lead
+              | to joint pain and compromise an individual’s walking ability (Opheim et al., 2009).
+              | Surgical and therapeutic treatments for crouch gait aim to produce a more upright posture
+              | to improve walking efficiency and prevent joint pain and deterioration.
+              |        Altered loads on the knee can have adverse effects on joint health. Cartilage and
+              | bone growth and maintenance depend on the loads experienced during daily life (Carter
+              | and Wong, 1988; Wong and Carter, 2003), and abnormal loading can lead to joint pain,
+              | cartilage degeneration (Eckstein et al., 2002), and the formation of bone deformities
+              | (Kerr Graham and Selber, 2003). Joint pain can be a significant contributor to walking
+              | deterioration in adults with cerebral palsy. Jahnsen et al. (2004) found that 41% of adults
+              | with diplegic cerebral palsy reported significant knee pain.
+              |        To develop successful treatment strategies for crouch gait, surgeons and therapists
+              | need to understand how joint loads change with increasing knee flexion during crouch
+              | gait and how joint loads may change with altered knee flexion. Treatments are aimed at
+              | reducing the excessive knee flexion associated with crouch gait, but it is unclear if
+              | changes in knee flexion will alter joint loads. Quantifying the relationship between knee
+              | flexion, muscle forces, and the compressive force on the tibia during gait could help
+              | clinicians determine if a more upright posture could reduce the risks caused by altered
+              | joint loading.
+              |        Perry and colleagues examined knee forces in a static crouched posture using a
+              | cadaver model and reported increasing compressive tibiofemoral force with increasing
+              | knee flexion (Perry et al., 1975). In dynamic activities, such as walking, we expect larger
+              | joint forces than in a static posture due to the additional muscle forces required to support
+              | the body weight during movement and propel the body forward (Liu et al., 2008).
+              | Compressive tibiofemoral forces during unimpaired walking have been reported in the
+              | range of 2-3 times body-weight (D’Lima et al., 2006; Kutzner et al., 2010; Mündermann
+blank         | 
+meta          |                                                                                           23
+text          | et al., 2008b; Shelburne et al., 2005). During crouch gait, muscle forces in the stance-
+              | limb are higher than during unimpaired walking (Steele et al., 2010). Since muscle forces
+              | are the primary contributors to joint loading (Inman, 1947; Sasaki and Neptune, 2010),
+              | we expect that compressive tibiofemoral forces are higher during crouch gait, yet the
+              | relationship between crouch gait severity and the compressive tibiofemoral force remains
+              | unknown.
+              |        The purpose of this study was to estimate the magnitude of the compressive
+              | tibiofemoral force during crouch gait and examine how this force changes with crouch
+              | severity. To achieve this goal we estimated the muscles forces and the compressive force
+              | on the tibia in unimpaired children and children with cerebral palsy who walked in
+              | varying degrees of crouch severity. We used a freely-available biomechanics software
+              | package, OpenSim (Delp et al., 2007), to scale a musculoskeletal model to each
+              | individual and estimate muscle joint loads based upon each individual’s gait dynamics.
+blank         | 
+title         | 3.2. Methods
+blank         | 
+title         | 3.2.1. Subjects
+text          |        The subjects for this study were selected from a database of patients treated at
+              | Gillette Children’s Specialty Healthcare (St. Paul, MN; Table 3.1). Nine subjects with
+              | spastic diplegic cerebral palsy were selected to cover a broad range of crouch severity
+              | and were divided evenly into three groups: mild crouch gait (minimum knee flexion
+              | angle of 20-35º), moderate crouch gait (minimum knee flexion angle of 35-50º), and
+              | severe crouch gait (minimum knee flexion angle greater than 50º). All subjects walked
+              | with excess knee and hip flexion and had at least 5º of ankle dorsiflexion during stance.
+              | We excluded subjects that had greater than 30º of femoral or tibial torsion, which can
+              | affect muscle moment arms and the ability of muscles to generate accelerations (Hicks et
+              | al., 2008). Three unimpaired subjects were chosen who were representative of the age
+              | and stature of the subjects with cerebral palsy. Additionally, a subject with an
+              | instrumented total knee replacement (TKR, age: 80 years, weight: 64 kg, walking
+              | speed/height: 0.74 s-1) was included to provide experimental measurements of the
+              | compressive tibiofemoral force for comparison with forces estimated from the
+              | musculoskeletal model. This subject was not included in subsequent comparisons
+meta          | 24
+text          | between unimpaired gait and crouch gait due to differences in age and stature in relation
+              | to the other subjects.
+blank         | 
+              | 
+              | 
+title         | Table 3.1: Subject characteristics
+blank         | 
+text          |                         N Age     Height          Weight     Speed/Height     Minimum
+              |                          (yrs)      (cm)           (kg)           (s-1)       KFA* (deg)
+              |  Unimpaired        3    10.3 ±   145 ± 16         36.3 ±       0.79 ± 0.1      1.7 ± 5.5
+              |                           3.4                       8.8
+              |  Mild Crouch       3     8.8 ±    123 ± 7         24.2 ±       0.67 ± 0.1      19.1 ± 3.8
+              |                           0.8                       3.6
+              |  Moderate          3     9.2 ±   123 ± 15         43.1 ±       0.63 ± 0.1      36.1 ± 4.0
+              |  Crouch                   2.9                       37
+              |  Severe Crouch     3     14.0    158 ± 12         40.1 ±       0.61 ± 0.1      58.6 ± 5.6
+              |                          ±2.3                       6.8
+              | *KFA: knee flexion angle during walking
+blank         | 
+              | 
+title         | 3.2.2. Motion Analysis
+text          |          Motion analysis data was collected at Gillette Children’s Specialty Healthcare (St.
+              | Paul, MN) using a 12-camera system (Vicon Motion Systems, Lake Forest, CA), four
+              | force plates (AMTI, Watertown, MA), and a standard marker protocol (Davis et al.,
+              | 1991). Ground reaction forces and moments were sampled at 1080 Hz and low-pass
+              | filtered at 20 Hz. Electromyography (EMG) was collected for six of the crouch gait
+              | subjects from the quadriceps, hamstrings, and gastrocnemius (Motion Laboratory
+              | Systems, Baton Rouge, LA). The EMG data was sampled at 1080 Hz, band-pass filtered
+              | between 20 and 400 Hz, rectified, and low-pass filtered at 10 Hz. All subjects walked at
+              | their self-selected speed and achieved two consecutive force plate strikes during which
+              | only one foot contacted each force plate. The motion analysis data for the subject with the
+              | instrumented TKR was obtained from www.simtk.org where it is freely available for
+              | researchers (Zhao et al., 2007).
+blank         | 
+title         | 3.2.3. Musculoskeletal Modeling
+text          |          A generic musculoskeletal model based upon adult cadaver data (Delp et al.,
+              | 1990) with 19 degrees of freedom and 92 musculotendon actuators was scaled to each
+              | subject according to anthropometric measurements. This musculoskeletal model has been
+blank         | 
+              | 
+meta          |                                                                                             25
+text          | used for studies involving unimpaired children and children with cerebral palsy (Hicks et
+              | al., 2008; Liu et al., 2008; Reinbolt et al., 2008). The degrees of freedom in the
+              | musculoskeletal model included six degrees of freedom at the pelvis, a ball-and-socket
+              | joint at the third lumbar vertebra between the pelvis and torso, a ball-and-socket joint at
+              | each hip, a planar joint with coupled translations at each knee (Yamaguchi and Zajac,
+              | 1989), and a revolute joint at each ankle. Joint angles during walking were calculated by
+              | minimizing the error between experimental marker trajectories and markers placed on the
+              | model at locations corresponding to the experimental markers.
+              |        Static optimization was used to calculate the muscle forces required to reproduce
+              | the joint moments of each subject throughout the gait cycle. To distribute muscle forces,
+              | static optimization was used to minimize the objective function:
+              |                                               \
+blank         | 
+text          |                                         XYZ         [& '&( $$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$$Equation$3.1
+              |                                               &01
+blank         | 
+text          | where N is the number of muscles in the model, a is the activation level (between zero
+              | and one) of each muscle, and c is an integer weighting constant for each muscle with a
+              | default value of one. The weighting constants were determined by comparing calculated
+              | compressive tibiofemoral force to the experimentally measured force for the subject with
+              | the instrumented TKR, as described below.
+              |        The compressive tibiofemoral force was calculated using the Joint Reaction
+              | analysis in OpenSim. A detailed description of this analysis is provided in the
+              | Supplementary Material. Briefly, the tibiofemoral force was calculated as a point load
+              | acting on the tibial plateau using the Newton-Euler equation:
+blank         | 
+              | 
+text          |           ]^)// = ;     >&_&C '>&_&C   − ]C)^./ +         3a+,-./, + 3bBCc&>U                        Equation 3.2
+blank         | 
+              | 
+text          | In Equation 3.2, ]^)// is the force from the femur on the tibia, [M]tibia is the matrix of
+              | inertial properties of the tibia, '>&_&C is the six dimensional angular and linear acceleration
+              | of the tibia, ]C)^./ is the force from the foot on the tibia, and 3a+,-./, and 3bBCc&>U are the
+              | muscle forces and gravitational forces acting on the tibia. The compressive tibiofemoral
+blank         | 
+              | 
+meta          | 26
+text          | force was calculated as the component of ]^)// parallel to the longitudinal axis of the
+              | tibia and used for all subsequent analyses.
+              |        For the subject with the instrumented TKR, we varied the static optimization
+              | weighting constants for the major muscle groups that cross the knee: the hamstrings,
+              | gastrocnemius, and quadriceps. The hamstrings included independent muscle models for
+              | the semimembranosus, semitendinousus, biceps femoris long head, and biceps femoris
+              | short head. The quadriceps included independent muscle models for the rectus femoris,
+              | the vastus medialis, the vastus intermedius, and the vastus lateralis. The same weighting
+              | constant was applied to all muscles in each group and the results for the muscles within
+              | each group were compared and, if found to be similar, were combined to facilitate
+              | analysis. The weighting constants were given integer values between one and ten. We
+              | performed static optimization for all combinations of integer weighting constants and
+              | calculated the resulting compressive tibiofemoral force. The peak compressive force was
+              | compared to the experimentally measured force, and we selected the combination of
+              | weighting constants that had the minimum average value and resulted in a difference
+              | between the estimated and experimental peak compressive force of less than twenty
+              | percent body-weight. The set of weighting constants that met this criterion was a weight
+              | of three for the hamstrings, seven for the gastrocnemius, and one for the quadriceps. This
+              | combination of weighting constants resulted in a root mean square error of 0.28 times
+              | body-weight and an average error of 0.02 times body-weight over the gait cycle between
+              | the estimated force and the experimental measurements (Figure 3.1). These weighting
+              | constants were then used to perform static optimization for all other subjects. OpenSim’s
+              | Joint Reaction analysis algorithm was used to calculate the compressive tibiofemoral
+              | force for one representative gait cycle for each subject.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                            27
+text          | Figure 3.1: Tibiofemoral contact forces expressed in multiples of body weight (BW) from experimental
+              | forces measured using an instrumented total knee replacement (TKR, gray) and estimated with the
+              | computer model (black). The average ± 1 standard deviation is shown from four trials.
+blank         | 
+              | 
+              | 
+text          |         To evaluate whether muscle activations calculated from static optimization
+              | reflected the subjects’ muscle activity we qualitatively compared the estimated muscle
+              | activations to EMG recordings during stance for the six subjects for whom EMG data
+              | was available (Figure 3.2). EMG and estimated muscle activations indicated that the
+              | quadriceps were active during stance. Hamstring activity decreased during stance in both
+              | the EMG and estimated muscle activations; however, estimated muscle activations
+              | decreased earlier in stance than indicated by EMG for some of the subjects. For these
+              | subjects, increased hamstring activity during stance would have increased estimates of
+              | the compressive tibiofemoral contact force. The gastrocnemius muscle was active during
+              | the majority of stance in both the EMG and estimated muscle activations.
+blank         | 
+              | 
+              | 
+              | 
+meta          | 28
+text          | Figure 3.2: Comparison of
+              | EMG (gray, average ± one
+              | standard deviation over all gait
+              | cycles) and muscle activations
+              | from static optimization (black
+              | line) for the six subjects with
+              | crouch gait for whom EMG
+              | data was available. EMG and
+              | activations were normalized
+              | from zero to one for each
+              | subject based upon the
+              | minimum and maximum values
+              | over the gait cycle. Note that
+              | subject “Severe 1” did not have
+              | EMG data from the
+              | gastrocnemius.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                    29
+title         | 3.3. Results
+text          |        Compressive tibiofemoral force was higher during moderate and severe crouch
+              | gait than during unimpaired gait (Figure 3.3). Subjects with a mild crouch gait had
+              | similar compressive tibiofemoral forces to subjects with unimpaired gait. The maximum
+              | force during mild crouch gait was 3.2 ±0.4 times body-weight compared to 3.0 ±0.5 times
+              | body-weight during unimpaired gait. Maximum force during a moderate crouch gait was
+              | 4.2 ±1.2 times body-weight. During a severe crouch gait maximum force was 6.5 ±0.7
+              | times body-weight.
+              |        Compressive tibiofemoral force during stance exhibited two peaks in unimpaired
+              | and crouch gait (Figure 3.3B). These two peaks in the tibiofemoral force coincided with
+              | the two characteristic peaks of the ground reaction force. The largest tibiofemoral forces
+              | occurred during early and late stance with smaller forces in mid-stance and swing. During
+              | unimpaired gait, the primary contributors to compressive tibiofemoral force were the
+              | quadriceps in early stance and the gastrocnemius during late stance. During crouch gait,
+              | the quadriceps were the primary contributors to tibiofemoral force throughout stance
+              | (Figure 3.3C).
+              |        There was a quadratic relationship between the average knee flexion angle during
+              | stance and the average compressive tibiofemoral force during stance (r2 = 0.97, Figure
+              | 3.4). The relationship is described by:
+              |                            3^)// = 0.0013d ( − 0.06d + 2.54                   Equation 3.3
+              | where Fknee is the average compressive tibiofemoral force during stance, and Ө is the
+              | average knee flexion angle during stance with values from 15 to 70 degrees of flexion.
+              |        The increase in average compressive tibiofemoral force during stance with
+              | increasing crouch severity was primarily due to an increase in quadriceps force. The
+              | average quadriceps force during stance also increased quadratically with knee flexion
+              | angle (r2=0.99, Figure 3.4) with the relationship:
+              |                              3e+Cf = 0.0011d ( − 0.03d + 0.7                  Equation 3.4
+              |        The average force produced by the hamstrings during stance did not change with
+              | knee flexion; however, the average force of gastrocnemius decreased with crouch
+              | severity. Individuals with crouch gait had smaller ankle plantarflexor moments during
+              | terminal stance.
+meta          | 30
+text          | Figure 3.3: (A) Average knee flexion
+              | angle, (B) average compressive
+              | tibiofemoral force, and (C) average
+              | quadriceps force expressed as
+              | multiples of body-weight (xBW)
+              | during one gait cycle for the
+              | subjects who walked with an
+              | unimpaired gait and mild, moderate,
+              | and severe crouch gait.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                        31
+text          |               5
+              |                                                                         R² = 0.97
+              |               4                        Tibiofemoral Force
+              |                                        Quadriceps Force
+              |                                                                                         R² = 0.99
+              | Force (xBW)
+blank         | 
+              | 
+              | 
+              | 
+text          |               3
+blank         | 
+              | 
+text          |               2
+blank         | 
+text          |                                                                      Hamstrings Force
+              |               1
+              |                                                                      Gastrocnemius Force
+blank         | 
+text          |               0
+              |                   0               20                   40                     60                       80
+              |                          Average Stance Knee Flexion Angle (deg)
+              | Figure 3.4: Correlation of average knee flexion angle during stance with average compressive tibiofemoral
+              | force during stance (black circles), average quadriceps force during stance (dark gray squares), average
+              | hamstrings force during stance (light gray triangles), and average gastrocnemius force during stance
+              | (black outlined diamonds). Tibiofemoral force and average quadriceps force are expressed as multiples of
+              | bodyweight (xBW). A quadratic relationship described the change in both tibiofemoral force and
+              | quadriceps force with increasing crouch.
+blank         | 
+              | 
+title         | 3.2. Discussion
+text          |               Individuals who walk in a moderate or severe crouch gait experience substantially
+              | greater compressive tibiofemoral forces than individuals with an unimpaired gait;
+              | however, individuals who walk in a mild crouch gait have similar compressive
+              | tibiofemoral forces to unimpaired gait. The increase in tibiofemoral force was primarily
+              | due to the increase in quadriceps force required to support the body during crouch gait.
+              | There was a quadratic increase in quadriceps force with increasing knee flexion which is
+              | similar to a reported quadratic increase in EMG magnitude in static, crouch postures (Hsu
+meta          | 32
+text          | et al., 1993). The increase in quadriceps force with crouch severity not only contributes to
+              | increased tibiofemoral load but would also increase patellofemoral load (Dhaher and
+              | Kahn, 2002) and may give rise to knee pain in individuals with cerebral palsy and crouch
+              | gait. To reduce the average compressive tibiofemoral force and quadriceps force during
+              | stance to within one standard deviation of the average during unimpaired gait, individuals
+              | with crouch gait need to achieve an average knee flexion angle less than 25 degrees
+              | during stance.
+              |        Compressive tibiofemoral force during crouch gait reported here are slightly
+              | higher than those estimated by Perry et al. (1975), who used statically loaded cadavers in
+              | a crouch posture. Perry determined the compressive tibiofemoral force at 30 and 45
+              | degrees of knee flexion to be 2.9 and 3.8 times body-weight, respectively, whereas we
+              | found the maximum force during a crouch gait with an average knee flexion angle of 30
+              | and 45 degrees to be 3.3 and 4.1 times body-weight. The static cadaver testing
+              | implemented by Perry did not include contributions from the gastrocnemius or hamstring
+              | muscles to compressive tibiofemoral force. The small difference in compressive
+              | tibiofemoral force between standing and walking demonstrates that, although walking
+              | requires additional muscle force to propel the body forward (Steele et al., 2010), the
+              | increased quadriceps demand arising from a static crouched posture accounts for the
+              | majority of the increased tibiofemoral force. The tibiofemoral contact force of the
+              | unimpaired children included in this analysis were also similar to previously reported
+              | results for adults (D’Lima et al., 2006; Kutzner et al., 2010; Mündermann et al., 2008b;
+              | Shelburne et al., 2005).
+              |        Our calculation of compressive tibiofemoral force depends on the accuracy of
+              | estimated muscle activations. The estimated muscle activations showed patterns similar
+              | to EMG such as increased activity of the quadriceps; however, EMG activity was
+              | available for a limited number of muscles in six of the subjects. When muscle activations
+              | differed from the EMG signals the optimization tended to underestimate muscle activity
+              | compared to EMG signals. This suggests that the optimization functions commonly used
+              | for unimpaired walking may not be appropriate for individuals with cerebral palsy who
+              | have altered motor control and muscle physiology. Muscle over-activity and excess co-
+              | contraction are common in individuals with cerebral palsy. Greater muscle forces due to
+blank         | 
+meta          |                                                                                            33
+text          | co-contraction would increase the estimated tibiofemoral contact forces suggesting that
+              | our calculations of compressive tibiofemoral force may be low estimates.
+              |        We compared our calculated tibiofemoral forces to experimental forces from an
+              | instrumented total knee replacement, but this did not provide a robust evaluation of knee
+              | forces during crouch gait. The total knee replacement data was used to select the static
+              | optimization weighting constants that reduced the error between the estimated and
+              | measured compressive tibiofemoral force. Different weighting constants may be
+              | appropriate for younger patients or patients with gait pathology. In this study, the
+              | weighting constants penalized recruitment of the hamstrings and gastrocnemius, which
+              | resulted in the recruitment of other muscles to actuate the hip and ankle without
+              | increasing the compressive load on the tibia. Although the quadriceps are the major
+              | contributors to compressive tibiofemoral force, increasing the quadriceps’ weighting
+              | constant did not reduce the estimated tibiofemoral force since no other muscles could
+              | replace the quadriceps’ function at the knee.
+              |        To test the sensitivity of our results to the objective function we evaluated how
+              | estimated tibiofemoral contact force changed with altering the weighting constants and
+              | the power of activation. The quadratic relationship between knee flexion angle and
+              | tibiofemoral contact force and quadriceps force was similar in all tested objective
+              | functions (Figure 3.5). Using a linear objective function resulted in an average reduction
+              | in tibiofemoral contact force during stance of 7 percent while an objective function that
+              | minimized activation cubed increased tibiofemoral contact force during stance by 11
+              | percent. Using weighting constants of one for all muscles also increased the estimated
+              | tibiofemoral contact force during stance by an average of 15 percent due primarily to a
+              | ten percent average increase in gastrocnemius force during stance. Future studies that
+              | measure compressive tibiofemoral force from individuals with instrumented total knee
+              | replacements walking in pathologic gait patterns, such as crouch gait, could provide
+              | further points of comparison for model-based estimates of compressive tibiofemoral force
+              | and help to determine the optimal objective functions.
+blank         | 
+              | 
+              | 
+              | 
+meta          | 34
+text          | Figure 3.5: Average (A) tibiofemoral contact force, (B) quadriceps force, (C) hamstring force, and (D)
+              | gastrocnemius force during stance with the objective function shown in Eqn. 1 and weighting constants,
+              | minimizing activation with weighting constants, minimizing activation cubed with weighting constants, and
+              | minimizing activation squared with all weighting constants equal to one.
+blank         | 
+meta          |                                                                                                          35
+title         | 3.2. Conclusion
+text          |        This study has demonstrated that walking in a moderate or severe crouch gait
+              | increases the compressive tibiofemoral force, which could be contributing to joint pain
+              | and cartilage degeneration. Surgeries and therapies that produce a more upright walking
+              | posture will reduce forces at the knee and may help moderate the adverse effects of
+              | excessive joint loading.
+blank         | 
+              | 
+              | 
+              | 
+meta          | 36
+title         | 4. Preparatory co-activation of the ankle muscles may prevent
+              | ankle inversion injuries
+blank         | 
+title         | 4.1. Introduction
+text          |        Ankle sprains are the most common of all acute musculoskeletal injuries that
+              | occur during physical activity (Fong et al., 2009, 2007). Roughly 80% of acute ankle
+              | injuries involve excessive inversion, with 77% resulting in sprains of the lateral ligaments
+              | (Fong et al., 2009). These injuries often occur during landing, especially on irregular or
+              | unexpected surfaces, such as a competitor’s foot (Bahr et al., 1997, 1994). High impact
+              | forces directed medially to the subtalar joint induce rapid inversion of the foot (Fuller,
+              | 1999; Wright et al., 2000a, 2000b). Injury occurs when excessive ankle inversion
+              | stretches the lateral ankle ligaments that cross the talocrural and subtalar joints, causing
+              | plastic strains or ligament rupture (Hertel, 2002). Such injuries result in long, incomplete
+              | recoveries that leave the ankle prone to recurring injuries.
+              |        Load–deflection studies on cadavers have quantified the passive mechanics of the
+              | ankle (Chen et al., 1988; Lapointe et al., 1997; Siegler et al., 1990). Passive ankle
+              | stiffness decreases due to lateral ligament sprains, reducing resistance to excessive ankle
+              | inversion (Lapointe et al., 1997; Siegler et al., 1990). Computer simulations of ankle
+              | inversion scenarios predicted that decreased passive ankle stiffness could increase the
+              | probability of inversion injuries (Wright et al., 2000b). Observations from large cohorts
+              | of athletes corroborate this finding, showing that ankles with previous inversion injuries
+              | are more susceptible to future injury than uninjured ankles (McGuine and Keene, 2006;
+              | Surve et al., 1994). Athletic tape and braces can reinforce and stiffen ankles with
+              | previous injuries and decrease rates of recurring injuries (Kamiya et al., 2009); however,
+              | tape and braces have not been shown to decrease injury rates in uninjured ankles
+              | (Calatayud et al., 2014; Verhagen and Bay, 2010).
+              |        Posture and muscle coordination may also affect ankle stability, but the
+              | relationships between muscle activity, landing pose, and the risk of inversion injury have
+              | not been adequately characterized. Landing with a plantarflexed or inverted ankle
+              | increased the rate of injury in musculoskeletal simulations (Wright et al., 2000a), while
+              | retraining trunk and leg posture has decreased the rate of ankle injuries in volleyball
+blank         | 
+meta          |                                                                                              37
+text          | players (Bahr et al., 1997). Neuromotor interventions, which retrain muscle coordination,
+              | have also been shown to protect the ankle. For example, balance board training, in which
+              | the participant stands with one foot on an unstable surface, has decreased the rates of
+              | recurring ankle injuries in previously injured ankles (Bahr et al., 1997; Verhagen et al.,
+              | 2004). Similarly, interventions combining balance, strength, and plyometric training have
+              | decreased the rates of recurring ankle injuries (Emery and Meeuwisse, 2010). However,
+              | according to multiple reviews (Calatayud et al., 2014; van der Wees et al., 2006;
+              | Verhagen and Bay, 2010), the majority of studies have found no effect of neuromotor
+              | retraining on preventing first-time ankle sprains.
+              |        While studies of neuromotor retraining show promising results, outcomes are
+              | mixed and the underlying mechanisms behind the protective effects are unknown, largely
+              | because the role of the ankle muscles in resisting inversion sprains is an area of
+              | controversy. Some hypothesize that improved ankle proprioception (Arnold et al., 2009a;
+              | Hertel, 2002, 2000; Munn et al., 2010) and increased strength in the ankle evertor
+              | muscles (Arnold et al., 2009b) are responsible. However, experiments exploring the
+              | effects of balance interventions found that neuromuscular retraining neither targets nor
+              | improves ankle proprioception (Gauffin et al., 1988; Kiers et al., 2012). Additionally,
+              | patients with recurring ankle sprains (Hiller et al., 2011) or functional ankle instability
+              | (Munn et al., 2003) do not demonstrate deficits in evertor strength, although patients with
+              | ankle instability or recent ankle sprains may exhibit longer evertor muscle reaction times
+              | (Delahunt, 2007; Konradsen and Ravn, 1990; Löfvenberg et al., 1995). These findings
+              | suggest that changes in muscle coordination may be the primary protective mechanism of
+              | neuromuscular retraining. However, the capacity for the ankle muscles to prevent
+              | inversion injuries under various coordination strategies remains largely unexplored.
+              |        The purpose of this study was to determine whether coordinated activity of the
+              | ankle muscles could prevent excessive ankle inversion during an inversion-inducing
+              | landing scenario. We used musculoskeletal simulations to avoid the risk of injuring
+              | human subjects and to allow for systematic manipulation of muscle coordination. We
+              | used a musculoskeletal model (Delp et al., 1990) to which we added muscle excitation
+              | controllers, a foot–floor contact model, and passive mechanics of the ankle. We tested the
+              | model against experimental data and then used the model to generate muscle-driven
+meta          | 38
+text          | simulations of a single-leg landing under a variety of muscle control strategies. Our first
+              | goal was to quantify how co-activating the ankle evertor and invertor muscles affects
+              | maximum inversion angles for a range of co-activation levels. Our second goal was to
+              | quantify ankle inversion when the evertor and invertor muscles were coordinated with
+              | stretch reflexes. Thus, we were able to compare the efficacy of a planned ankle muscle
+              | co-activation strategy to that of a purely reflexive strategy during an inversion-inducing
+              | landing.
+blank         | 
+              | 
+              | 
+title         | 4.2. Methods
+blank         | 
+title         | 4.2.1. A new musculoskeletal model for simulating ankle inversion injuries
+text          |        We developed a model (Figure 4.1) for simulating single-leg landings in OpenSim
+              | (Delp et al., 2007) by augmenting a well-established full-body musculoskeletal model.
+              | The model used the musculoskeletal geometry of the lower limb defined by Delp et al.
+              | (1990) with an articulating patella and quadriceps (DeMers et al., 2014). The model
+              | incorporated a lumped torso–head segment connected to the pelvis by a ball-and-socket
+              | joint. The arms connected to the torso with ball-and-socket shoulder joints (Hamner et al.,
+              | 2010). Forty-nine muscle–tendon units (muscles) actuated the legs and the lumbar joint
+              | (21 degrees of freedom in total). All muscles incorporated force–length, force–velocity,
+              | and activation dynamics behavior described by Thelen (2003) and implemented in
+              | OpenSim by Millard et al. (2013). The ankle evertor muscles included the three peronei
+              | and extensor digitorum muscles. The ankle invertor muscles included the tibialis anterior,
+              | tibialis posterior, flexor digitorum, flexor hallucis, and extensor hallucis. Excitations of
+              | the model’s muscles were determined either by feedforward controllers or by stretch
+              | feedback controllers, as described below.
+              |        To represent the landing surface, the simulation included a contact plane, fixed to
+              | a configurable platform, which could be set at any desired height and orientation below
+              | the musculoskeletal model. This contact plane interacted with the feet, which were
+              | defined by a three dimensional mesh digitized from computed tomography of a cadaver
+              | foot (Erdemir et al., 2009). An elastic foundation contact model between the contact
+              | plane and the foot mesh generated reaction forces between the foot and floor. Stiffness
+blank         | 
+meta          |                                                                                                39
+text          | (50 MPa/m), coefficient of friction (0.9), and dissipation (5 s/m) parameters were
+              | selected to represent rubber contacting rubber (Sherman et al., 2011), with a shoe sole
+              | thickness of approximately 2 centimeters.
+blank         | 
+              | 
+              | 
+              | 
+text          | Figure 4.1: Musculoskeletal model used to simulate single-leg landings. 49 muscles (red) actuated the
+              | model’s 21 degrees of freedom in the right leg, the pelvis, and a lumped torso/head segment. The left leg
+              | was locked in the flexed pose shown. The arms were fixed in a posture anterior to the chest by locking the
+              | shoulder and elbow joints. Forces between the feet and floor were modeled as elastic foundation forces
+              | between a mesh fixed to the foot (green) and the plane of the floor (blue). We simulated landing from a 0.3
+              | meter fall onto the floor, which was tilted at 30 degrees in the coronal plane to induce rapid ankle
+              | inversion.
+blank         | 
+              | 
+              | 
+text          |          The passive mechanics of the ankle have been measured in cadavers (Chen et al.,
+              | 1988; Lapointe et al., 1997; Siegler et al., 1990) and were represented in the model as a
+              | three-dimensional torsional bushing. The bushing acted like a set of three uncoupled,
+              | nonlinear torsional springs between the distal tibia and the calcaneus, crossing the
+              | talocrural and subtalar joints. We represented the nonlinear torque–deflection behavior
+meta          | 40
+text          | about the x, y, and z axes as uncoupled functions defined by cubic polynomials (Figure
+              | 4.2). We determined the polynomial coefficients by minimizing the root-mean-squared
+              | error between the cubic polynomials and the passive torque–angle behavior measured in
+              | cadavers (Chen et al., 1988). The bushing captured the passive response of all ligaments
+              | and soft structures that cross the ankle, excluding musculature. The root-mean-squared
+              | errors between the bushing moments and the measured moments were 0.2 N-m about the
+              | x-axis, 0.6 N-m about the y-axis, and 0.2 N-m about the z-axis.
+blank         | 
+              | 
+              | 
+              | 
+text          | Figure 4.2: Load–deflection mechanics of passive ankle structures in the model compared to soft tissue
+              | mechanics measured in cadavers (Chen et al., 1988). The model lumped all ligament and other soft tissue
+              | loads—excluding the muscles—into a three-directional torsional bushing crossing the talocrural and
+              | subtalar joints. Load–deflection profiles about the x, y, and z axes were modeled with uncoupled, cubic
+              | polynomials and were fit to the average experimental data using least-squares error minimization.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                                           41
+title         | 4.2.2. Generating nominal simulations of landing
+text          |         We generated a nominal simulation of single-leg landing on level ground based
+              | on experimental measurements (Shultz et al., 2015). We used the three-dimensional
+              | kinematics and ground reaction force data of a single subject (19 year old female, 68 kg
+              | mass, 1.8 m height) performing five landing trials onto her right leg. Each trial began
+              | with the subject standing on a block 0.4 meters above the ground, followed by a
+              | voluntary drop onto a flat, level surface after which she landed and balanced solely on her
+              | right foot.
+              |         We generated simulations of single-leg landing using the Forward Dynamics Tool
+              | in OpenSim (Delp et al., 2007). Simulations began at the time of first foot-floor contact.
+              | Initial conditions for the joint angles and velocities were determined from the average
+              | values of the five experimental trials measured at the time of first foot–floor contact.
+              | Excitations of the torso, hip, knee, ankle plantarflexor, and ankle dorsiflexor muscles
+              | were modeled with muscle stretch feedback controllers. The stretch feedback controllers
+              | excited the leg muscles prior to and during landing. Each muscle’s stretch feedback
+              | controller computed the instantaneous muscle excitation, xm, according to Equation 4.1.
+blank         | 
+              | 
+text          |                                              f
+              |                          ha i = jk la (i) − la      m
+              |                                                         + jc la (i)              Equation 4.1
+              |                                                                       m
+blank         | 
+text          |         The stretch feedback controllers behave like a proportional-derivative controller
+              | on the muscle’s length, where kp is the gain on normalized muscle stretch length and kv is
+              | the gain on normalized muscle stretch velocity. Normalized muscle stretch was computed
+              | as the difference between the current normalized muscle fiber length, la , and the desired
+              |                                  f
+              | normalized muscle fiber length, la . Both were normalized by the optimal muscle fiber
+blank         | 
+text          | length. Normalized muscle stretch velocity, la , was computed as the ratio of current
+              | muscle fiber lengthening velocity, la , to the maximum contractile velocity of the muscle,
+              |  aCA
+              | la   . Only positive muscle stretch and velocity were considered, as indicated by the
+              | parentheses, ( )+, in Eqn. 1. Each muscle was assigned to one of five functional groups in
+              |                                           f
+              | which all controller parameters (kp, kv, la ) were the same (Table 4.1). These five groups
+              | were the torso, hip, knee, ankle plantarflexor, and ankle dorsiflexor muscles.
+              | Multiarticular muscles were assigned to the functional group corresponding to the largest
+meta          | 42
+text          | average moment arm for any joints they crossed. Excitations of the ankle evertor and
+              | invertor muscles were constrained to be zero during the nominal simulation. We chose
+              | stretch feedback controller parameters with an optimization that minimized the integral of
+              | error between the simulated and experimentally measured kinematics. The stretch
+              | feedback controller produced muscle activations that allowed the leg to flex under the
+              | influence of gravity and muscles, and reproduced the experimentally measured landing
+              | kinematics (Figure 4.3, average error 1.1 degrees).
+blank         | 
+              | 
+text          |                                                                  Desired
+              |                                                                                    Length          Velocity
+              |                                                                 Normalized
+              |  Muscle Group                        Muscles                                        Gain            Gain
+              |                                                                  Length
+              |                                                                                      kp               kv
+              |                                                                       npo
+              |                          Erector Spinae, Internal Oblique,
+              |   Trunk Muscles                                                      1.00            1.21            0.91
+              |                                  External Oblique
+              |                         Gluteus Maximus, Gluteus Medius,
+              |                          Gluteus Minimus, Tensor Fasciae
+              |                        Latae, Iliacus, Psoas Major, Adductor
+              |                         Brevis, Adductor Longus, Adductor
+              |         Hip                                                          1.14            0.74            0.98
+              |                            Magnus, Sartorius, Gracilis,
+              |                          Pectineus, Piriformis, Quadratus
+              |                                  Femoris, Gemellus
+blank         | 
+text          |                          Rectus Femoris, Vastus Lateralis,
+              |                        Vastus Intermedius, Vastus Medialis,
+              |        Knee             Biceps Femoris Long Head, Biceps             0.73            1.29            0.37
+              |                                Femoris Short Head,
+              |                         Semimebranosus, Semitendinosus
+              |       Ankle               Medial Gastrocnemius, Lateral
+              |                                                                      0.56            1.37            0.00
+              |   Plantarflexors              Gastrocnemius, Soleus
+              |       Ankle
+              |                                  Tibialis Anterior                   0.57            0.60            1.40
+              |    Dorsiflexors
+blank         | 
+              | 
+text          | Table 4.1: Parameters of the muscle stretch feedback controllers that coordinated the trunk, hip, knee, and
+              | ankle plantar/dorsiflexor muscles. Muscles were assigned to one of 5 stretch length controllers
+              | corresponding to functional groups (trunk muscles, hip muscles, knee muscles, ankle plantarflexors, and
+              | ankle dorsiflexors). All muscles in each group shared the same stretch length controller parameters
+              | (desired normalized fiber length, normalized stretch length gain, and normalized stretch velocity gain).
+              | Since the stretch controller is a function of unitless muscle fiber states, all three controller parameters are
+              | unitless quantities.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                                               43
+text          |                                                          Figure 4.3: Simulated hip, knee, and
+              |                                                          ankle plantar flexion kinematics
+              |                                                          after initial ground contact for a
+              |                                                          0.3-meter landing onto level ground
+              |                                                          compared to kinematics measured
+              |                                                          from a subject executing the same
+              |                                                          landing. Kinematics of the model
+              |                                                          (black line) evolved due to simple
+              |                                                          stretch reflexes in the torso, hip,
+              |                                                          knee, plantarflexor, and dorsiflexor
+              |                                                          muscles of the right leg. Similarity
+              |                                                          to the range of kinematics measured
+              |                                                          during five landing trials (gray
+              |                                                          lines) indicates that simulated
+              |                                                          coordination strategy at the hip,
+              |                                                          knee, and triceps surae muscles
+              |                                                          mimics the behavior of the subject
+              |                                                          during a nominal, level landing task.
+blank         | 
+              | 
+              | 
+title         | 4.2.3. Inducing ankle inversion in simulated landings
+text          |        Quantifying the protective effects of muscle coordination strategies required a
+              | landing condition that induced inversion injuries. Having generated a nominal simulation
+              | of a safe landing on level ground, we perturbed the landing conditions to induce rapid
+              | ankle inversion upon impact. Firstly, the subtalar joint angle and velocity at landing were
+              | set to 0 degrees and 0 degrees/second. Secondly, we inclined the floor to 30 degrees in
+blank         | 
+meta          | 44
+text          | the coronal plane such that the medial aspect of the landing foot impacted first, inducing
+              | a moment about the subtalar joint that rapidly inverted the ankle. This simulation scenario
+              | served as the basis for exploring coordination of the ankle evertor and invertor muscles.
+blank         | 
+title         | 4.2.4. Quantifying the effect of planned co-activation
+text          |        We quantified the effect of planned co-activation by varying the level of muscular
+              | co-activation of muscles that cross the subtalar joint during the 30-degree incline landing
+              | scenario. Co-activation was modeled as constant, feedforward activation of the opposing
+              | ankle evertor and invertor muscles groups, which generated zero net subtalar moment at
+              | initial ground contact (subtalar angle equal to zero). For a given co-activation level, all
+              | evertor muscles received the same activation. All invertor muscles received 93% of the
+              | evertor activations due to their larger moment-generating capacity. We generated eleven
+              | independent simulations varying the level of constant, planned co-activation from 0% (no
+              | active contraction) to 100% (maximal evertor contraction and 93% invertor contraction)
+              | in 10% increments. All other parameters and inputs were held constant. The simulation
+              | began when the foot impacted the inclined ground and proceeded for 150 milliseconds.
+              | To quantify the effects of co-activation level on ankle inversion, we observed whether the
+              | subtalar joint angle exceeded a predetermined injury threshold of 30 degrees, which was
+              | chosen based on a cadaver study (Aydogan et al., 2006) which found that repaired lateral
+              | ligaments of the ankle failed at inversion angles of 35±6 degrees (Figure 4.4, gray area).
+blank         | 
+title         | 4.2.5. Quantifying the effect of ankle stretch reflexes
+text          |        We quantified the effect of stretch reflexes by varying the intensities of ankle
+              | evertor and invertor muscular responses to stretch during the 30 degree incline landing
+              | scenario. Evertor and invertor muscle stretch reflexes were modeled as muscle velocity
+              | controllers with a response delay. The constant response delay captured the latency due to
+              | neural transmission delay between muscle stretch and muscle excitation, which has been
+              | measured experimentally as 60–120 milliseconds in the human peroneal muscles
+              | (Beckman and Buchanan, 1995; Karlsson and Andreasson, 1992; Konradsen and Bohsen
+              | Ravn, 1991; Vaes et al., 2002). We chose a constant response delay of 60 milliseconds to
+              | test whether the fastest feasible human evertor reflex could prevent injurious ankle
+blank         | 
+              | 
+              | 
+meta          |                                                                                               45
+text          | inversion angles in our simulation scenario. Each muscle’s stretch reflex controller
+              | computed the instantaneous muscle excitation according to Equation 2.
+blank         | 
+              | 
+text          |                              ha = jc la i − 0.060                                Equation 4.2
+              |                                                          m
+blank         | 
+text          | The stretch reflex controller behaves like a delayed derivative controller on a muscle’s
+blank         | 
+text          | normalized stretch velocity, la , in which kv is the gain on stretch velocity 60 milliseconds
+              | in the past. To determine the effect of reflex intensity on ankle inversion, we generated
+              | six independent simulations of landing on a 30 degree incline, varying only the gain, kv.
+              | For the six simulations, kv was set to 0.0, 0.1, 0.5, 1, 5, and 10; results corresponding to kv
+              | > 10 are not reported since simulations with kv = 10 and kv = 100 generated the same
+              | kinematics. To quantify the effects of reflex intensity on ankle inversion, we observed
+              | whether the subtalar angle exceeded the injury threshold of 30 degrees based on the range
+              | failure angles reported by Aydogan et al. (2006)(Figure 4.5, gray region).
+blank         | 
+title         | 4.3. Results
+text          |        Strong co-activation of the ankle evertors and invertors prior to landing prevented
+              | ankle inversion angles from exceeding the injury threshold (Figure 4.4). Increasing co-
+              | activation level from 0% (blue) to 100% (red) decreased peak inversion angle from 49
+              | degrees to 17 degrees. Increasing co-activation also decreased peak inversion velocity
+              | from 950 degrees/second to 550 degrees/second. Increasing simulated co-activation up to
+              | 60% increased the time to exceeding the injury threshold (gray area) from 62 to 120
+              | milliseconds. Co-activation levels of 62% and above prevented ankle inversion from
+              | exceeding the injury threshold altogether.
+              |        Stretch reflexes of the evertors in response to landing failed to prevent excessive
+              | ankle inversion (Figure 4.5). For all values of the reflex gain, kv, ranging from 0 (blue) to
+              | 10 (red), ankle inversion angles exceeded the injury threshold (grey area). Also for all
+              | values of kv, ankle inversion angle exceeded the injury threshold quickly, within 62
+              | milliseconds of impact. Prior to 60 milliseconds, the ankle inversion trajectories under all
+              | conditions were identical, due to the 60 millisecond reflex delay, and exhibited a peak
+              | inversion velocity of 950 degrees/second.
+blank         | 
+meta          | 46
+text          | Figure 4.4: Ankle inversion trajectories
+              | immediately after impact for various levels
+              | of evertor and invertor muscle co-
+              | activation. Each contour represents
+              | excursion of the subtalar joint during a
+              | single simulation in which the evertor and
+              | invertor muscles generated force due to
+              | constant activation. Co-activation level
+              | was varied from 0% (blue) to 100% (red).
+              | Impact occurs at zero milliseconds (ms).
+              | An approximate injury threshold of 30 to
+              | 40 degrees inversion (Aydogan et al.,
+              | 2006) is shown for reference (gray area).
+blank         | 
+              | 
+              | 
+              | 
+text          | Figure 4.5: Ankle inversion trajectories
+              | immediately after impact with ankle
+              | evertor and invertor stretch reflexes of
+              | various intensities. Reflexes were modeled
+              | as feedback from the muscle lengthening
+              | speed to muscle excitations, with reflex
+              | intensity modulated using a feedback gain.
+              | Each contour represents ankle inversion
+              | angle during a single simulation in which
+              | the evertor and invertor muscles generated
+              | force with a constant reflex gain. Reflex
+              | gains were varied from 0.0 (blue) to 10
+              | (red). Impact occurs at zero milliseconds
+              | (ms). An approximate injury threshold of
+              | 30 to 40 degrees inversion (Aydogan et al.,
+              | 2006) is shown for reference (gray area).
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                             47
+text          | Figure 4.6: Examples of the contributions of muscles and ligaments to the protective eversion moment
+              | when adopting planned co-activation or strong stretch reflexes in the ankle evertor and invertor muscles.
+              | Co-activating the evertors and invertors at the level of 70% (panel A) generated large eversion moments
+              | (dark gray region, max. 29 Newton-meters) compared to all other muscles (dashed gray line) and the ankle
+              | ligaments (light gray region), resulting in a net eversion moment (solid black line) throughout the landing
+              | simulation. Conversely, strong reflexes in the ankle evertors and invertors (panel B, stretch velocity gain of
+              | 10, delay 60 ms) failed to generate a net eversion moment until 38 ms after landing and produced less than
+              | 10 N-m of eversion moment at the time of injury.
+blank         | 
+              | 
+              | 
+text          |          Co-activating the ankle evertors and invertors resulted in higher net eversion
+              | moments (Figure 4.6A) compared to the moments resulting from stretch reflexes in the
+              | same muscles (Figure 4.6B) during the first 150 milliseconds of landing. For both cases,
+              | the soleus and gastrocnemius muscles, plantarflexors which also cross the subtalar joint,
+              | generated a net inversion moment immediately after initial ground contact (Figure 4.6A
+blank         | 
+meta          | 48
+text          | and 4.6B, dashed gray lines). Co-activating the evertors and invertors at levels that
+              | protected the ankle generated large eversion moments. For example, co-activation of 70%
+              | resulted in a maximum moment of 29 Newton-meters (Figure 4.6A, dark gray region).
+              | Passive forces from the ankle ligaments generated small eversion moments compared to
+              | the muscle-generated moments (Figure 4.6A, light grey region). The superposition of
+              | muscle and ligament loads resulted in net eversion moments throughout the landing
+              | simulations for the co-activation case. Conversely, for the case of strong stretch reflexes
+              | in the ankle evertors and invertors (Figure 4.6B), the superposition of all muscles and
+              | ligaments generated net inversion moments until 38 milliseconds after initial ground
+              | contact. Regardless of the gain of the stretch reflex controllers, the ankle evertors and
+              | invertors produced less than 10 Newton-meter of eversion moment (Figure 4.6B, dark
+              | grey area) before the time of injury.
+blank         | 
+              | 
+              | 
+title         | 4.4. Discussion
+text          |        Our simulations suggest that coordinated activity of the ankle muscles can prevent
+              | excessive ankle inversion during an inversion-inducing landing scenario. Co-activating
+              | the evertor and invertor muscles prevented ankle inversion angles from exceeding the
+              | threshold for ankle inversion sprains. Conversely, stretch reflexes of the evertor and
+              | invertor muscles failed to prevent excessive ankle inversion angles because the injury
+              | occurs within 62 milliseconds in our simulated landing scenario, before reflexes generate
+              | stabilizing forces. This result suggests that interventions aimed at retraining muscle
+              | coordination should target feedforward co-activation to prevent lateral ankle sprains.
+              |        Planned, feedforward co-activation of the ankle evertor and invertor muscles
+              | rapidly and effectively protects the ankle from unanticipated inversion insults in our
+              | simulated landing. With planned coordination of the evertors and invertors, the muscles
+              | are active and generating force to stiffen the ankle in preparation for the large inversion
+              | moment induced at landing. As the ankle inverts, the actively lengthening evertors and
+              | shortening invertors generate a net eversion moment that immediately resists inversion.
+              | This occurs because of the force–length–velocity property of muscle, which has a
+              | stabilizing influence (John et al., 2013), and has been called a ‘preflex’ to refer to the pre-
+blank         | 
+              | 
+meta          |                                                                                               49
+text          | reflex response of intrinsic muscle properties to disturbances (Loeb et al., 1999). When
+              | the net active muscle moment is large enough, the passive moment due to the lateral
+              | ankle ligaments is negligible. Experimental electromyography recordings show that
+              | individuals co-activate the ankle muscles in midair during landing and jumping tasks
+              | (Caulfield et al., 2004; Grüneberg et al., 2003), suggesting that it may be possible to
+              | increase co-activation through training. Higher co-activation generated higher joint
+              | stiffness and reduced the maximum inversion angles during our landing simulations.
+              | Wright et al. (2000a) found that increased ankle stiffness due to passive structures, such
+              | as ankle orthoses and tape, reduced the incidence of simulated inversion injuries. Our
+              | simulations support the protective effect of ankle stiffening and demonstrate that the
+              | evertor and invertor muscles can achieve this stiffness without assistance from orthoses
+              | or tape.
+              |            Stretch reflexes, regardless of their intensity, show little capacity to protect the
+              | ankle from unanticipated inversion insults upon landing, especially when the injuries
+              | occur within approximately 60 milliseconds, as they did in our simulations. Our
+              | simulations demonstrate that the fastest stretch reflexes consistently recorded in healthy
+              | human evertor muscles (Calatayud et al., 2014; Vaes et al., 2002) are too slow to prevent
+              | the inversion injury posed in this study. This finding contradicts research that suggests
+              | improving peroneal reflex latency may prevent inversion injuries (Akhbari et al., 2007;
+              | Clark and Burden, 2005; Delahunt, 2007; Osborne et al., 2001; Sheth et al., 1997). Fong
+              | et al., (2013, 2012) demonstrated that a device with fast injury detection and external
+              | electrical stimulation could provide artificially fast peroneal contractions in under 10
+              | milliseconds. However, our findings show that, lacking advanced feedback control
+              | devices such as Fong’s, interventions to reduce evertor latency are unlikely to prevent
+              | rapid (< 60 milliseconds) inversion injuries.
+              |            Our simulation approach for exploring ankle inversion injuries is subject to
+              | limitations. First, we defined an injury threshold of 30 degrees supination about the
+              | subtalar joint based on an experiment on repaired lateral ligaments (Aydogan et al.,
+              | 2006). We chose a conservative injury threshold of 30 degrees such that a simulated
+              | injury represents the limit at which injury would likely occur in the highest-risk
+              | individuals. The injury threshold could vary in non-injured ankles and between
+meta          | 50
+text          | individuals. Second, we lumped all 47 muscles of the landing leg and torso into only five
+              | groups of stretch feedback controllers (torso, hip, knee, plantarflexor, and dorsiflexor
+              | muscles). These groups did not separate hip flexors from hip extensors or knee flexors
+              | from knee extensors. Supplementary to this study, we developed landing models using up
+              | to nine functional groups coordinating the landing leg. Adding this complexity did not
+              | affect our findings, thus we present the simplest model here. Additionally, by using the
+              | same muscle controllers at the torso, hip, knee, and plantarflexion degrees of freedom in
+              | all simulation conditions, we assumed that the landing model could not alter whole-body
+              | coordination. This assumption corresponds to rapid injury scenarios, in which the
+              | individual would not have sufficient time to change her landing posture or leg stiffness.
+              | However, altering landing posture and leg stiffness may help mitigate ankle inversion
+              | injuries and could be explored in future studies. Finally, while ankle inversion injuries
+              | occur during landing, running, change of direction, and collision, we only simulated
+              | injuries during landing on a surface inclined at 30 degrees. Other scenarios, which allow
+              | more time to adjust, may allow for reflexes to make a significant contribution to
+              | protecting the joint. It should be noted, however, that the mechanisms allowing co-
+              | activated evertors to resist inversion moments more rapidly than evertor reflexes would
+              | apply to any ankle inversion scenario, regardless of what causes the injurious inversion
+              | moment.
+blank         | 
+title         | 4.5. Conclusion
+text          |        Through development of a contact-based landing model and implementation of
+              | novel muscle controllers, this study provides a rich platform for investigating ankle
+              | injuries and strategies for mitigating them. All models, software, and data for this study
+              | are publicly available online (http://simtk.org/home/ankle-sprains) along with tutorials on
+              | their use. We encourage others to use these tools to explore other injury scenarios and
+              | protective mechanisms.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                              51
+title         | 5. Conclusion
+text          |        This dissertation presents three studies conducted to advance the understanding of
+              | human motor coordination and its effects on knee and ankle function. The first study
+              | described a modeling and optimization framework we developed for varying muscle
+              | activations and tibiofemoral forces during walking. Increased tibiofemoral forces during
+              | walking have been linked to osteoarthritis and pain in the knee. Our analyses revealed
+              | that activating the gluteus medius, psoas major, iliacus, and soleus muscles decreased the
+              | tibiofemoral force, while activating the gastrocnemius and rectus femoris muscles
+              | increased in tibiofemoral force. The second study employed a similar modeling and
+              | optimization framework to estimate the tibiofemoral forces during walking in crouch gait
+              | and quantify the variation in tibiofemoral forces due to varying severity of crouch. Our
+              | results demonstrate that compressive tibiofemoral force increases quadratically with
+              | crouch severity, which may explain why knee pain is common among individuals who
+              | walk in crouch. The final study described a human landing simulator with novel muscle
+              | stretch controllers for exploring muscle coordinations that may prevent lateral ankle
+              | sprains. By varying the intensity to two strategies for coordinating the ankle evertors and
+              | invertors at landing, we discovered that preparatory co-activation may prevent rapid
+              | ankle inversion sprains while fast stretch reflexes likely would not. When regarded as a
+              | body of work, these three studies make significant contributions in the form of impactful
+              | scientific findings and freely available technology for the research community.
+blank         | 
+title         | 5.1. Contributions
+blank         | 
+title         | 5.1.1. Scientific Findings
+text          |        Activating the prime hip and ankle muscles, which are uniarticular and do not
+              | cross the knee, decreases tibiofemoral force, while activating the gastrocnemius and
+              | rectus femoris increases tibiofemoral force during walking. Our findings provide new
+              | insight about how specific muscle activations might cause compensatory changes in other
+              | muscles to decrease or increase tibiofemoral forces during walking. Prior to this
+              | dissertation, the mathematical redundancy caused by having many more muscles than
+              | joints was considered a technological challenge. Often named “the muscle redundancy
+blank         | 
+meta          | 52
+text          | problem”, this was typically “solved” using optimizations to pick one possible
+              | distribution of muscle forces by expressing an objective function, such as minimizing
+              | muscle force, muscle effort, or metabolic cost. Researchers studying the knee joint would
+              | then use these specific distributions of muscle forces as the “solutions” and analyze
+              | which muscles directly loaded the tibiofemoral joint. Conversely, we chose to use muscle
+              | redundancy as a feature, leveraging it to vary the distribution of muscle forces and
+              | resulting tibiofemoral forces during the same walking motion. As a result, we discovered
+              | that activating muscles at the hip and ankle caused compensatory changes in activations
+              | of muscles crossing the knee and altered the compressive tibiofemoral force. We
+              | identified that the gluteus medius, psoas major, iliacus, and soleus, (uniarticular hip and
+              | ankle muscles) had the greatest capacity to decrease tibiofemoral force during walking,
+              | making them prime targets for interventions against knee OA and pain.
+              |        Compressive tibiofemoral forces increase quadratically with knee flexion during
+              | the stance phase of walking in a crouch gait. Knee pain and even early onset
+              | osteoarthritis are common among individuals who walk with a crouch gait. Our findings
+              | show that walking in severe crouch gait generates tibiofemoral forces at least three-times
+              | larger than those generated in unimpaired gait. This result suggests that the crouched
+              | posture and elevated tibiofemoral forces could contribute to early cartilage degeneration
+              | and knee pain, but also suggest that correcting crouch gait could help slow this
+              | degradation or alleviate pain. However, since our results show that walking in mild
+              | crouch could feasibly generate tibiofemoral forces as low as unimpaired walking,
+              | interventions to correct crouch and achieve unimpaired kinematics may have diminishing
+              | returns with regard to joint loading.
+              |        Preparatory co-activation of the ankle evertors and invertor muscles during
+              | landing can provide strong and rapid resistance to ankle sprains, while stretch reflexes
+              | are too slow. Our findings reveal that a co-activated, stiff ankle can generate moments in
+              | equilibrium when the ankle is neutral, then rapidly generate protective moments as soon
+              | as any perturbation inverts the ankle toward a sprain. Unlike reflexes which incur a
+              | neuromotor delay of up to 150 milliseconds, the co-activated ankle muscles are already
+              | generating force and provide a purely mechanical “preflex” response that acts instantly.
+              | Prior to this dissertation, neuromotor retraining interventions to prevent ankle sprains
+blank         | 
+meta          |                                                                                            53
+text          | largely focused on exercising the ankle evertor reflexes in order to decrease their delay.
+              | However, even after those interventions, evertors reflexes still incur delays of 60
+              | milliseconds or more. Our findings demonstrate that even the fastest reflexes with 60
+              | millisecond delays are too slow to protect the ankle from sprains during common
+              | scenarios. Therefore, our findings highlight that studies proposing ankle sprain
+              | interventions should focus on methods for training co-activation “preflexes” at landing
+              | instead of improving evertors reaction times.
+blank         | 
+title         | 5.1.2. Technological Contributions to the Research Community
+text          |        Open source optimization software for simultaneously minimizing joint loads and
+              | muscle activations during a motion. In Chapter 2, we used an optimization with a
+              | customizable objective function (Equation 2.1) to specify different muscle coordination
+              | strategies and vary muscle activations. This optimization, which allowed us to penalize
+              | combinations of muscle activity and joint forces in the model, is versatile and applicable
+              | to many regimes of biomechanical research. Therefore, we ensured that this optimization
+              | was flexible, reusable, and available to the research community. We designed the
+              | optimization software as a plugin to OpenSim (Delp et al., 2007) so that others could
+              | easily download and use it within the OpenSim GUI or command line tools. The open
+              | source implementation in C++ is available and documented online such that any
+              | researcher may download, modify, and use the software without restriction
+              | (https://simtk.org/home/jointloadopt).
+              |        Open source musculoskeletal model for estimating tibiofemoral and
+              | patellofemoral loads during full-body, muscle-driven motion. Accurate estimates of
+              | tibiofemoral forces require a knee mechanism that captures the tibiofemoral,
+              | patellofemoral, and quadriceps mechanisms and the loads transferred between them. Prior
+              | to this dissertation, full body models in OpenSim were designed for and excelled at
+              | modeling quadriceps moment arms and tensions, but could not resolve the tibiofemoral
+              | and patellofemoral contact loads. We developed (Chapter 2 and 3) a knee mechanism
+              | within a full-body model which could resolve the resultant knee contact forces using a
+              | coupled tibiofemoral and patellofemoral mechanism actuated by the quadriceps muscles.
+              | This knee mechanism has been used in numerous scientific publications (DeMers et al.,
+blank         | 
+meta          | 54
+text          | 2014; Lerner et al., 2014; Steele et al., 2012; Wagner et al., 2013) and has served as a
+              | launching point for further augmented models that resolve mediolateral distributions of
+              | tibiofemoral forces (Lerner et al., 2015).
+              |        Open source library for muscle stretch feedback control in OpenSim. In Chapter
+              | 4, we generated simulations of single-leg landing using muscle stretch feedback
+              | controllers. These stretch controllers, which allowed us to define the conditions and
+              | intensity of spring-like stiffness control of individual muscles, are versatile and
+              | applicable to many regimes of biomechanical research. Therefore, we ensured that these
+              | controllers were flexible, reusable, and available to the research community. We designed
+              | the controller software as a plugin to OpenSim (Delp et al., 2007) so that others could
+              | easily download and use them within the OpenSim GUI or command line tools. The open
+              | source implementation in C++ is available and documented online such that any
+              | researcher may download, modify, and use the software without restriction
+              | (https://github.com/msdemers/opensim-reflex-controllers).
+              |        Library of single-leg landing models and simulations under various coordination
+              | conditions. To test the effectiveness of varied ankle muscle coordination in preventing
+              | sprains, we created a detailed landing model and generated landing simulations under
+              | multiple control conditions. The model incorporates contact interactions between the feet
+              | and the floor, nonlinear and passive ankle structures based on experiments, and muscle
+              | controllers trained to land like a human. The model is a valuable tool for further research
+              | on landing, ankle mechanics, full-body control. The simulations themselves are a
+              | valuable launching point for further study of muscle control and injury in single-leg
+              | landing. The models, simulations, and data used to generate them are freely available
+              | online (https://simtk.org/home/ankle-sprains) such that other researchers to download,
+              | modify, and extend them.
+blank         | 
+title         | 5.2. Future work
+blank         | 
+title         | 5.2.1. Immediate Next Steps
+text          |        Coordination strategies to decrease the independent medial and lateral
+              | components of tibiofemoral force. In this dissertation, tibiofemoral forces were modeled
+              | as single point-forces acting at the tibiofemoral joint center. The true human knee
+blank         | 
+meta          |                                                                                            55
+text          | mechanism generates separate medial and lateral contact loads between each of two
+              | femoral condyles and the tibial plateau. OA typically develops more frequently and more
+              | severely in the medial compartment of the knee (Felson et al., 2008). When studying
+              | medial compartment OA, researchers often use the externally applied knee adduction
+              | moment as a surrogate measure of the medial knee contact force (Baliunas, 2002; Shull et
+              | al., 2013; Zhao et al., 2007) because it is easy to estimate from human motion capture
+              | measurements. However, the external knee adduction moment can not capture the effects
+              | of muscles tensions crossing the knee and how they change the distribution of medial and
+              | lateral tibiofemoral contact forces. We, in collaboration with Lerner and colleagues, have
+              | augmented the knee mechanism described in this dissertation to include coupled medial
+              | and lateral tibiofemoral joints which can resolve separate medial and lateral tibiofemoral
+              | contact forces in a full-body human model (Lerner et al., 2015). An exciting opportunity
+              | exists to combine the new human model with the optimization tools presented in this
+              | dissertation and explore the effects of varied muscle coordination on the medial and
+              | lateral distribution of knee forces. Thus, future research of walking in healthy and
+              | pathologic populations should aim to quantify the changes in medial and lateral
+              | tibiofemoral forces due to changes in muscle activity (similar to Chapter 2) and changes
+              | in walking kinematics (similar to Chapter 3). Quantifying these relationships will one day
+              | enable better interventions for reducing medial knee pain or slowing medial knee
+              | cartilage degradation associated with walking.
+              |        Coordination strategies to change joint contact forces during various activities
+              | of daily living. When quantifying the effects of varying muscle coordination on
+              | tibiofemoral forces, this dissertation only considers walking motions. Furthermore, we
+              | analyzed walking performed post surgery by individuals with total knee replacements.
+              | However, the modeling and optimization tools presented in Chapters 2 and 3 could easily
+              | be applied to many activities of daily living in both diseased and healthy populations.
+              | Activities of daily living that significantly affect quality of life for individuals with knee
+              | OA and pain include ascending and descending stairs, sit-to-stand transitions, and stand-
+              | to-sit transitions because they generate large knee forces (Kutzner et al., 2010). While
+              | researchers have measured tibiofemoral forces during these motions using instrumented
+              | total knee replacements (D’Lima et al., 2006; Mündermann et al., 2008b), the potential to
+meta          | 56
+text          | vary these tibiofemoral forces by altering muscle coordination remains unclear. Unique
+              | data sets (Fregly et al., 2012) publicly distribute motion capture measurements of high-
+              | flexion activities similar to sit-stand transitions and stair climbing. Therefore, these
+              | unique measurements combined with the open-source optimization framework presented
+              | in this dissertation could quantify the variation in tibiofemoral forces due to variation of
+              | muscle coordination during activities of daily living.
+              |        Quantify the effects of landing limb pose and stiffness on the mechanics of
+              | lateral ankle sprains. While quantifying the effects of ankle muscle coordination on
+              | ankle injuries, we assumed that the coordination of the remaining leg muscles and the
+              | landing pose did not change. Analyses of ankle injury mechanics typically focus on the
+              | ankle itself and prohibit changes in full-body coordination. For example, Wright et al.
+              | analyzed ankle injuries during side-stepping maneuvers, but specifically varied only the
+              | passive ankle stiffness (Wright et al., 2000b) and the ankle pose (Wright et al., 2000a) at
+              | landing while specifying identical limb pose, trunk pose, and muscle activations in a feed
+              | forward manner. Studies testing coaching interventions to reduce the incidence of ankle
+              | sprains in sports indicate that altering landing leg pose and torso pose at landing might
+              | affect the likelihood of injury (Bahr et al., 1997). However, the effects of landing pose,
+              | leg stiffness, or other full-body coordination elements have not been explored in a
+              | systematic or mechanistic way. The open-source landing model and muscle stretch
+              | controllers we developed could be used to systematically vary torso posture, limb pose,
+              | and muscle coordination of the hip, knee, and ankle during landing to quantify the effect
+              | on the ankle excursion and moments. Such work could yield valuable mechanical insight
+              | about ankle sprains and uncover targets for coaching interventions to prevent these ankle
+              | sprains.
+              |        Quantify the effects of landing coordination strategies on incidence of lateral
+              | ankle sprains in a diverse population of injury scenarios. The primary limitation of our
+              | ankle sprain analyses is that we only considered one sprain inducing scenario. We only
+              | considered lateral ankle sprains occurring during vertical landing on one foot, a common
+              | injury mode in sports like basketball, volleyball, tennis, and hiking. However, ankle
+              | injuries also occur during other movements, including horizontal maneuvers such as
+              | running or run-to-cut, and a small proportion of ankle sprains involve injuries of the
+blank         | 
+meta          |                                                                                              57
+text          | medial ligaments or the ankle syndesmosis (Doherty et al., 2014; Waterman et al., 2010).
+              | Reducing the epidemic incidence of ankle injuries requires making humans more resilient
+              | to many injury modes. Therefore, an appropriate next step is to quantify the effects of
+              | kinematic and muscle coordination in a wide population of injury scenarios. Monte carlo
+              | simulation methods would be well suited to this task, allowing researches to
+              | stochastically generate many injury scenarios from a few key motions and defined
+              | expectations of how the scenario conditions and injury perturbations might vary.
+              | Researchers could then systematically vary and test different coordination strategies, or
+              | even assistive devices, against this population of injury conditions to simulate the effect
+              | on incidence of injury.
+blank         | 
+title         | 5.2.1. New Lines of Research
+text          |        Simultaneous optimization of kinematic strategy, muscle coordination strategy,
+              | and joint loads to predict novel walking patterns. Research into the effects of muscle
+              | coordination and kinematics on internal joint forces has largely fallen into two motifs:
+              | first to alter muscle coordination without controlling for walking kinematics (Brandon et
+              | al., 2014; DeMers et al., 2014), and second to alter walking kinematics without
+              | controlling for muscle coordination (Fregly et al., 2009; Mündermann et al., 2008a; Shull
+              | et al., 2011). Our work on varying muscle coordination during walking indicates that
+              | changes in muscle activity can substantially decrease tibiofemoral forces during the
+              | second half the stance phase. Conversely, studies to retrain and modify walking
+              | kinematics show significant decreases in tibiofemoral forces during the first half of stance
+              | phase. Combined, these findings indicate that coupling muscle activity and kinematics
+              | corrections could dramatically decrease tibiofemoral forces throughout the entire walking
+              | gait cycle. A grand research opportunity exists to systematically explore and co-optimize
+              | the muscle coordination and kinematics of walking to decrease joint contact forces in
+              | simulations.
+              |        A new and powerful motif in musculoskeletal simulation, sometimes called
+              | predictive simulation (Dorn et al., 2015), may be well suited to exploring coordination
+              | and kinematics for decreasing joint contact forces. In predictive simulation, we embed
+              | biologically-inspired controllers within a 3-D humanoid model to autonomously generate
+blank         | 
+meta          | 58
+text          | motions in simulations. We then define heuristics, such as penalizing metabolic energy
+              | expenditure, falling, or stubbing the toe, in optimizations that learn and tune appropriate
+              | parameters for the biologically-inspired controllers. This process has resulted in
+              | autonomous locomotion controllers that predict realistic human walking and running
+              | motions by simply specifying slow or fast over-ground speeds and without relying on
+              | motion capture data (Wang et al., 2012). Furthermore, these autonomous locomotion
+              | controllers have been retrained under new conditions, such as loaded or inclined walking,
+              | which predicted humanlike compensations in their walking strategies (Dorn et al., 2015).
+              |         The predictive simulation approach enables an exciting new line of research to
+              | predict novel changes in muscle activity and kinematics that decrease joint contact forces
+              | during walking. Instead of posing movement heuristics that minimize metabolic
+              | expenditure, future work could focus on heuristics that minimize joint contact forces or
+              | other estimates of joint pain. By combining and balancing metabolic expenditure and
+              | joint loading heuristics, future predictive simulations could be “pain-aware”. Perhaps
+              | such simulations could generate and predict walking gait compensations that individuals
+              | with knee pain typically exhibit, such as quadriceps avoidance gaits or limping. Once
+              | optimized, humanlike walking controllers have been trained, further research could
+              | propose specific variations in the control of individual muscles, muscle groups, or
+              | antagonist muscle pairs to predict the downstream effect on the walking motion and joint
+              | contact forces. This could serve as a platform for systematically proposing and testing
+              | future interventions to decrease joint contact forces and mitigate joint degradation and
+              | pain.
+              |         Design and testing of novel retraining interventions to mitigate chronic knee
+              | pain or prevent acute ankle sprains. We used models to explore variations in muscle
+              | coordination that could protect the knee or ankle, but it remains unclear whether living
+              | humans could exercise the same variations to produce similar effects. Our models treated
+              | all individual muscle activations as independent, meaning the muscle coordination
+              | strategies could exercise up to 98 degrees of freedom to both meet the motion task
+              | (walking or landing) and optimize the function of the knee or ankle. In living humans,
+              | individual muscle activations are coupled by mechanism and limitations of the nervous
+              | system. For example, principle component analysis of muscle activations during walking
+blank         | 
+meta          |                                                                                            59
+text          | indicate that muscles activate together in synergies, and that fewer than 6 synergies are
+              | required to reproduce human walking (Chvatal and Ting, 2013; Walter et al., 2014). We
+              | aren’t aware of any studies that similarly analyzed the complexity of muscle activations
+              | during landing, but it is possible that even fewer degrees of freedom are required or used.
+              | This suggests that healthy individuals may not be capable of the same flexibility in
+              | muscle activity that our models exhibit, meaning the most optimal muscle coordination
+              | patterns could be infeasible. Individuals with gait pathologies like crouch gait exhibit
+              | even fewer synergies (Steele et al., 2015), indicating that retraining muscle coordination
+              | could be an even greater challenge in those populations. Therefore, future research must
+              | propose interventions to promote the lower limb muscle coordination strategies found in
+              | this dissertation and test their feasibility in experiments with living subjects.
+              |        The major challenge to proving the feasibility of such interventions is in
+              | demonstrating that individuals can learn to increase or decrease activations of individual
+              | muscles during walking or landing. Retraining interventions have successfully employed
+              | real-time feedback to modify kinematics of walking and reduce knee loads in living
+              | subjects (Shull et al., 2013, 2011). Conceivably, similar real-time feedback on muscle
+              | coordination to increase gluteus medius and soleus activity while decreasing
+              | gastrocnemius and rectus femoris activity may be possible, but remains largely
+              | unexplored. Similarly, the capacity of individuals to modulate the level of invertor and
+              | evertor co-activity during landing is unknown. Systems for real-time detection and
+              | feedback of muscle electromyography (EMG) do exist for the upper extremity, and have
+              | been used used with visual (Young et al., 2011) and tactile (Bloom et al., 2010; Casellato
+              | et al., 2013) feedback to modify muscle activity during reaching tasks. EMG
+              | measurements of the gluteus medius, soleus, gastrocnemius, and rectus femoris are
+              | commonly collected during experiments of walking and other motions of the lower body.
+              | In ankle injury research, EMG of the superficial ankle invertors and evertors are
+              | commonly measured as well. Therefore, a real-time feedback system for measuring EMG
+              | and suggesting changes in lower limb muscle activity is feasible, but the capacity of
+              | subjects heed the suggestion and change muscle activity during walking or landing
+              | remains unknown. This leaves a rich opportunity for human subject research aimed at
+blank         | 
+              | 
+meta          | 60
+text          | proposing coordination strategies to improve knee or ankle function, then testing the
+              | propensity of individuals to adopt and retain these strategies after interventions.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                         61
+title         | List of References
+ref           | Akhbari, B., Takamjani, I.E., Salavati, M., Sanjari, M.A., 2007. A 4-week biodex
+              |     stability exercise program improved ankle musculature onset, peak latency and
+              |     balance measures in functionally unstable ankles. Phys. Ther. Sport 8, 117–129.
+              |     doi:10.1016/j.ptsp.2007.03.004
+              | Anderson, F.C., Pandy, M.G., 2001. Dynamic Optimization of Human Walking. J.
+              |     Biomech. Eng. 123, 381. doi:10.1115/1.1392310
+              | Arnold, A.S., Salinas, S., Asakawa, D.J., Delp, S.L., 2000. Accuracy of muscle moment
+              |     arms estimated from MRI-based musculoskeletal models of the lower extremity.
+              |     Comput. Aided Surg. 5, 108–19. doi:10.1002/1097-0150(2000)5:2<108::AID-
+              |     IGS5>3.0.CO;2-2
+              | Arnold, B.L., de la Motte, S., Linens, S., Ross, S.E., 2009a. Ankle instability is
+              |     associated with balance impairments: A meta-analysis. Med. Sci. Sports Exerc. 41,
+              |     1048–1062. doi:10.1249/MSS.0b013e318192d044
+              | Arnold, B.L., Linens, S.W., de la Motte, S.J., Ross, S.E., 2009b. Concentric evertor
+              |     strength differences and functional ankle instability: A meta-analysis. J. Athl. Train.
+              |     44, 653–662. doi:10.4085/1062-6050-44.6.653
+              | Arnold, E.M., Ward, S.R., Lieber, R.L., Delp, S.L., 2010. A model of the lower limb for
+              |     analysis of human movement. Ann. Biomed. Eng. 38, 269–79. doi:10.1007/s10439-
+              |     009-9852-5
+              | Aydogan, U., Glisson, R.R., Nunley, J.A., 2006. Extensor Retinaculum Augmentation
+              |     Reinforces Anterior Talofibular Ligament Repair. Clin. Orthop. Relat. Res. 442,
+              |     210–215. doi:10.1097/01.blo.0000183737.43245.26
+              | Bahr, R., Karlsen, R., Lian, Ø., Øvrebø, R.V., 1994. Incidence and Mechanisms of Acute
+              |     Ankle Inversion Injuries in Volleyball: A Retrospective Cohort Study. Am. J. Sports
+              |     Med. 22, 595–600. doi:10.1177/036354659402200505
+              | Bahr, R., Lian, Ø., Bahr, I.A., 1997. A twofold reduction in the incidence of acute ankle
+              |     sprains in volleyball after the introduction of an injury prevention program: a
+              |     prospective cohort study. Scand. J. Med. Sci. Sports 7, 172–177.
+              | Baliunas, a, 2002. Increased knee joint loads during walking are present in subjects with
+              |      knee osteoarthritis. Osteoarthr. Cartil. 10, 573–579. doi:10.1053/joca.2002.0797
+              | Beckman, S.M., Buchanan, T.S., 1995. Ankle inversion injury and hypermobility: Effect
+              |     on hip and ankle muscle electromyography onset latency. Arch. Phys. Med. Rehabil.
+              |     76, 1138–1143. doi:10.1016/S0003-9993(95)80123-5
+meta          | 62
+ref           | Bloom, R., Przekop, A., Sanger, T.D., 2010. Prolonged electromyogram biofeedback
+              |     improves upper extremity function in children with cerebral palsy. J. Child Neurol.
+              |     25, 1480–1484. doi:10.1177/0883073810369704
+              | Bolanos, A.A., Colizza, W.A., McCann, P.D., Gotlin, R.S., Wootten, M.E., Kahn, B.A.,
+              |     Insall, J.N., 1998. A comparison of isokinetic strength testing and gait analysis in
+              |     patients with posterior cruciate-retaining and substituting knee arthroplasties. J.
+              |     Arthroplasty 13, 906–915. doi:10.1016/S0883-5403(98)90198-X
+              | Brandon, S.C.E., Miller, R.H., Thelen, D.G., Deluzio, K.J., 2014. Selective lateral muscle
+              |     activation in moderate medial knee osteoarthritis subjects does not unload medial
+              |     knee condyle. J. Biomech. 47, 1409–1415. doi:10.1016/j.jbiomech.2014.01.038
+              | Calatayud, J., Borreani, S., Colado, J.C., Flandez, J., Page, P., Andersen, L.L., 2014.
+              |      Exercise and ankle sprain injuries: a comprehensive review. Phys. Sportsmed. 42,
+              |      88–93. doi:10.3810/psm.2014.02.2051
+              | Carter, D.R., Wong, M., 1988. The role of mechanical loading histories in the
+              |      development of diarthrodial joints. J. Orthop. Res. 6, 804–16.
+              |      doi:10.1002/jor.1100060604
+              | Casellato, C., Pedrocchi, A., Zorzi, G., Vernisse, L., Ferrigno, G., Nardocci, N., 2013.
+              |     EMG-based visual-haptic biofeedback: A tool to improve motor control in children
+              |     with primary dystonia. IEEE Trans. Neural Syst. Rehabil. Eng. 21, 474–480.
+              |     doi:10.1109/TNSRE.2012.2222445
+              | Caulfield, B., Crammond, T., O’Sullivan, A., Reynolds, S., Ward, T., 2004. Altered
+              |     ankle-muscle activation during jump landing in participants with functional
+              |     instability of the ankle joint. J. Sport Rehabil. 13, 189–200.
+              | Chan, Y.-Y., Fong, D.T.-P., Yung, P.S.-H., Fung, K.-Y., Chan, K.-M., 2008. A
+              |     mechanical supination sprain simulator for studying ankle supination sprain
+              |     kinematics. J. Biomech. 41, 2571–4. doi:10.1016/j.jbiomech.2008.05.034
+              | Chang, A., Hurwitz, D., Dunlop, D., Song, J., Cahue, S., Hayes, K., Sharma, L., 2007.
+              |     The relationship between toe-out angle during gait and progression of medial
+              |     tibiofemoral osteoarthritis. Ann. Rheum. Dis. 66, 1271–5.
+              |     doi:10.1136/ard.2006.062927
+              | Chen, J., Siegler, S., Schneck, C.D., 1988. The three-dimensional kinematics and
+              |     flexibility characteristics of the human ankle and subtalar joint—Part II: Flexibility
+              |     characteristics. J. Biomech. Eng. 110, 374–385.
+              | Chvatal, S. a, Ting, L.H., 2013. Common muscle synergies for balance and walking.
+              |     Front. Comput. Neurosci. 7, 48. doi:10.3389/fncom.2013.00048
+meta          |                                                                                           63
+ref           | Clark, V.M., Burden, A.M., 2005. A 4-week wobble board exercise programme improved
+              |      muscle onset latency and perceived stability in individuals with a functionally
+              |      unstable ankle. Phys. Ther. Sport 6, 181–187. doi:10.1016/j.ptsp.2005.08.003
+              | D’Lima, D.D., Patil, S., Steklov, N., Slamin, J.E., Colwell, C.W., 2006. Tibial Forces
+              |     Measured In Vivo After Total Knee Arthroplasty. J. Arthroplasty 21, 255–262.
+              |     doi:10.1016/j.arth.2005.07.011
+              | D’Lima, D.D., Townsend, C.P., Arms, S.W., Morris, B. a, Colwell, C.W., 2005. An
+              |     implantable telemetry device to measure intra-articular tibial forces. J. Biomech. 38,
+              |     299–304. doi:10.1016/j.jbiomech.2004.02.011
+              | Davis, R.B., Ounpuu, S., Tyburski, D., Gage, J.R., 1991. A gait analysis data collection
+              |     and reduction technique. Hum. Mov. Sci. 10, 575–587. doi:10.1016/0167-
+              |     9457(91)90046-Z
+              | Delahunt, E., 2007. Peroneal reflex contribution to the development of functional
+              |     instability of the ankle joint. Phys. Ther. Sport 8, 98–104.
+              |     doi:10.1016/j.ptsp.2007.01.001
+              | Delp, S.L., Anderson, F.C., Arnold, A.S., Loan, P., Habib, A., John, C.T., Guendelman,
+              |     E., Thelen, D.G., 2007. OpenSim: open-source software to create and analyze
+              |     dynamic simulations of movement. IEEE Trans. Biomed. Eng. 54, 1940–1950.
+              |     doi:10.1109/TBME.2007.901024
+              | Delp, S.L., Loan, J.P., Hoy, M.G., Zajac, F.E., Topp, E.L., Rosen, J.M., 1990. An
+              |     interactive graphics-based model of the lower extremity to study orthopaedic
+              |     surgical procedures. IEEE Trans. Biomed. Eng. 37, 757–767.
+              |     doi:10.1109/10.102791
+              | DeMers, M.S., Pal, S., Delp, S.L., 2014. Changes in tibiofemoral forces due to variations
+              |    in muscle activity during walking. J. Orthop. Res. 32, 769–76.
+              |    doi:10.1002/jor.22601
+              | Dhaher, Y.Y., Kahn, L.E., 2002. The effect of vastus medialis forces on patello-femoral
+              |     contact: a model-based study. J Biomech Eng 124, 758–767. doi:10.1115/1.1516196
+              | Doherty, C., Delahunt, E., Caulfield, B., Hertel, J., Ryan, J., Bleakley, C., 2014. The
+              |     incidence and prevalence of ankle sprain injury: A systematic review and meta-
+              |     analysis of prospective epidemiological studies. Sport. Med. 44, 123–140.
+              |     doi:10.1007/s40279-013-0102-5
+              | Dorn, T.W., Wang, J.M., Hicks, J.L., Delp, S.L., 2015. Predictive Simulation Generates
+              |     Human Adaptations during Loaded and Inclined Walking. PLoS One 10, e0121407.
+blank         | 
+meta          | 64
+ref           |      doi:10.1371/journal.pone.0121407
+              | Eckstein, F., Faber, S., Mühlbauer, R., Hohe, J., Englmeier, K.-H., Reiser, M., Putz, R.,
+              |     2002. Functional adaptation of human joints to mechanical stimuli. Osteoarthr.
+              |     Cartil. 10, 44–50. doi:10.1053/joca.2001.0480
+              | Emery, C.A., Meeuwisse, W.H., 2010. The effectiveness of a neuromuscular prevention
+              |     strategy to reduce injuries in youth soccer: a cluster-randomised controlled trial. Br.
+              |     J. Sports Med. 44, 555–562. doi:10.1136/bjsm.2010.074377
+              | Erdemir, A., Sirimamilla, P.A., Halloran, J.P., van den Bogert, A.J., 2009. An elaborate
+              |     data set characterizing the mechanical response of the foot. J. Biomech. Eng. 131,
+              |     094502. doi:10.1115/1.3148474
+              | Felson, D.T., Nevitt, M.C., Yang, M., Clancy, M., Niu, J., Torner, J.C., Lewis, C.E.,
+              |      Aliabadi, P., Sack, B., McCulloch, C., Zhang, Y., 2008. A new approach yields high
+              |      rates of radiographic progression in knee osteoarthritis. J. Rheumatol. 35, 2047–
+              |      2054. doi:08/13/0920 [pii]
+              | Fong, D.T.-P., Chan, Y.-Y., Mok, K.-M., Yung, P.S., Chan, K.-M., 2009. Understanding
+              |     acute ankle ligamentous sprain injury in sports. Sports Med. Arthrosc. Rehabil.
+              |     Ther. Technol. 1, 14. doi:10.1186/1758-2555-1-14
+              | Fong, D.T.-P., Chu, V.W.-S., Chan, K.-M., 2012. Myoelectric stimulation on peroneal
+              |     muscles resists simulated ankle sprain motion. J. Biomech. 45, 2055–2057.
+              |     doi:10.1016/j.jbiomech.2012.04.025
+              | Fong, D.T.-P., Hong, Y., Chan, L.-K., Yung, P.S.-H., Chan, K.-M., 2007. A systematic
+              |     review on ankle injury and ankle sprain in sports. Sports Med. 37, 73–94.
+              | Fong, D.T.-P., Wang, D., Chu, V.W.-S., Chan, K.-M., 2013. Myoelectric stimulation on
+              |     peroneal muscles with electrodes of the muscle belly size attached to the upper
+              |     shank gives the best effect in resisting simulated ankle sprain motion. J. Biomech.
+              |     46, 1088–1091. doi:10.1016/j.jbiomech.2013.01.019
+              | Fregly, B.J., Besier, T.F., Lloyd, D.G., Delp, S.L., Banks, S. a, Pandy, M.G., D’Lima,
+              |      D.D., 2012. Grand challenge competition to predict in vivo knee loads. J. Orthop.
+              |      Res. 30, 503–13. doi:10.1002/jor.22023
+              | Fregly, B.J., D’Lima, D.D., Colwell, C.W., 2009. Effective gait patterns for offloading
+              |      the medial compartment of the knee. J. Orthop. Res. 27, 1016–21.
+              |      doi:10.1002/jor.20843
+              | Fukashiro, S., Komi, P. V., Jarvinen, M., Miyashita, M., 1993. Comparison between the
+              |     directly measured achilles tendon force and the tendon force calculated from the
+blank         | 
+meta          |                                                                                           65
+ref           |      ankle joint moment during vertical jumps. Clin. Biomech. 8, 25–30.
+              |      doi:10.1016/S0268-0033(05)80006-3
+              | Fuller, E. a, 1999. Center of pressure and its theoretical relationship to foot pathology. J.
+              |      Am. Podiatr. Med. Assoc. 89, 278–291.
+              | Gauffin, H., Tropp, H., Odenrick, P., 1988. Effect of ankle disk training on postural
+              |     control in patients with functional instability of the ankle joint. Int. J. Sports Med. 9,
+              |     141–144. doi:10.1055/s-2007-1024996
+              | Glitsch, U., Baumann, W., 1997. The three-dimensional determination of internal loads in
+              |      the lower extremity. J. Biomech. 30, 1123–31.
+              | Graichen, F., Arnold, R., Rohlmann, A., Bergmann, G., 2007. Implantable 9-channel
+              |      telemetry system for in vivo load measurements with orthopedic implants. IEEE
+              |      Trans. Biomed. Eng. 54, 253–61. doi:10.1109/TBME.2006.886857
+              | Gregor, R.J., Komi, P. V, Browning, R.C., Järvinen, M., 1991. A comparison of the
+              |     triceps surae and residual muscle moments at the ankle during cycling. J. Biomech.
+              |     24, 287–297. doi:10.1016/0021-9290(91)90347-P
+              | Grood, E.S., Suntay, W.J., Noyes, F.R., Butler, D.L., 1984. Biomechanics of the Knee-
+              |     Extension Exercise. J. Bone Jt. Surg. 66, 725–734.
+              | Grüneberg, C., Nieuwenhuijzen, P.H.J.A., Duysens, J., 2003. Reflex responses in the
+              |     lower leg following landing impact on an inverting and non-inverting platform. J.
+              |     Physiol. 550, 985–993. doi:10.1113/jphysiol.2002.036244
+              | Guo, M., Axe, M.J., Manal, K., 2007. The influence of foot progression angle on the knee
+              |     adduction moment during walking and stair climbing in pain free individuals with
+              |     knee osteoarthritis. Gait Posture 26, 436–41. doi:10.1016/j.gaitpost.2006.10.008
+              | Gutierrez, G.M., Knight, C. a., Swanik, C.B., Royer, T., Manal, K., Caulfield, B.,
+              |      Kaminski, T.W., 2012. Examining Neuromuscular Control During Landings on a
+              |      Supinating Platform in Persons With and Without Ankle Instability. Am. J. Sports
+              |      Med. 40, 193–201. doi:10.1177/0363546511422323
+              | Hamner, S.R., Seth, A., Delp, S.L., 2010. Muscle contributions to propulsion and support
+              |    during running. J. Biomech. 43, 2709–2716. doi:10.1016/j.jbiomech.2010.06.025
+              | Handsfield, G.G., Meyer, C.H., Hart, J.M., Abel, M.F., Blemker, S.S., 2014.
+              |     Relationships of 35 lower limb muscles to height and body mass quantified using
+              |     MRI. J. Biomech. 47, 631–638. doi:10.1016/j.jbiomech.2013.12.002
+              | Hertel, J., 2002. Functional Anatomy, Pathomechanics, and Pathophysiology of Lateral
+blank         | 
+meta          | 66
+ref           |      Ankle Instability. J. Athl. Train. 37, 364–375.
+              | Hertel, J., 2000. Functional Instability Following Lateral Ankle Sprain. Sport. Med. 29,
+              |      361–371.
+              | Hicks, J.L., Schwartz, M.H., Arnold, A.S., Delp, S.L., 2008. Crouched postures reduce
+              |     the capacity of muscles to extend the hip and knee during the single-limb stance
+              |     phase of gait. J. Biomech. 41, 960–967. doi:10.1016/j.jbiomech.2008.01.002
+              | Hiller, C.E., Nightingale, E.J., Lin, C.-W.C., Coughlan, G.F., Caulfield, B., Delahunt, E.,
+              |      2011. Characteristics of people with recurrent ankle sprains: a systematic review
+              |      with meta-analysis. Br. J. Sports Med. 45, 660–672. doi:10.1136/bjsm.2010.077404
+              | Hsu, A.-T., Perry, J., Gronley, J.K., Hislop, H.J., 1993. Quadriceps force and myoeletric
+              |      activity during flexed knee stance. Clin. Orthop. Relat. Res. doi:10.1097/00003086-
+              |      199303000-00032
+              | Inman, V.T., 1947. Functional aspects of the abductor muscles of the hip. J. Bone Joint
+              |     Surg. Am. 29, 607–19.
+              | Isman, R., Inman, V., 1969. Anthropometric Studies of the Human Foot and Ankle. Foot
+              |     Ankle 11, 97–129.
+              | Jahnsen, R., Villien, L., Aamodt, G., Stanghelle, J.K., Holm, I., 2004. Musculoskeletal
+              |     pain in adults with cerebral palsy compared with the general population. J. Rehabil.
+              |     Med. 36, 78–84. doi:10.1080/16501970310018305
+              | John, C.T., Anderson, F.C., Higginson, J.S., Delp, S.L., 2013. Stabilisation of walking by
+              |     intrinsic muscle properties revealed in a three-dimensional muscle-driven
+              |     simulation. Comput. Methods Biomech. Biomed. Engin. 16, 451–462.
+              |     doi:10.1080/10255842.2011.627560
+              | Kamiya, T., Kura, H., Suzuki, D., Uchiyama, E., Fujimiya, M., Yamashita, T., 2009.
+              |    Mechanical stability of the subtalar joint after lateral ligament sectioning and ankle
+              |    brace application: a biomechanical experimental study. Am. J. Sports Med. 37,
+              |    2451–2458. doi:10.1177/0363546509339578
+              | Karlsson, J., Andreasson, G.O., 1992. The effect of external ankle support in chronic
+              |      lateral ankle joint instability. An electromyographic study. Am. J. Sports Med. 20,
+              |      257–261.
+              | Kerr Graham, H., Selber, P., 2003. Musculoskeletal aspects of cerebral palsy. J. Bone Jt.
+              |      Surg. 85, 157–166. doi:10.1302/0301-620X.85B2.14066
+              | Kiers, H., Brumagne, S., van Dieën, J., van der Wees, P., Vanhees, L., 2012. Ankle
+              |      proprioception is not targeted by exercises on an unstable surface. Eur. J. Appl.
+blank         | 
+meta          |                                                                                            67
+ref           |      Physiol. 112, 1577–1585. doi:10.1007/s00421-011-2124-8
+              | Kim, H.J., Fernandez, J.W., Akbarshahi, M., Walter, J.P., Fregly, B.J., Pandy, M.G.,
+              |     2009. Evaluation of predicted knee-joint muscle forces during gait using an
+              |     instrumented knee implant. J. Orthop. Res. 27, 1326–31. doi:10.1002/jor.20876
+              | Kirking, B., Krevolin, J., Townsend, C., Colwell, C.W., D’Lima, D.D., 2006. A
+              |      multiaxial force-sensing implantable tibial prosthesis. J. Biomech. 39, 1744–51.
+              |      doi:10.1016/j.jbiomech.2005.05.023
+              | Klein Horsman, M.D., Koopman, H.F.J.M., van der Helm, F.C.T., Prosé, L.P., Veeger,
+              |      H.E.J., 2007. Morphological muscle and joint parameters for musculoskeletal
+              |      modelling of the lower extremity. Clin. Biomech. 22, 239–247.
+              |      doi:10.1016/j.clinbiomech.2006.10.003
+              | Konradsen, L., Bohsen Ravn, J., 1991. Prolonged Peroneal Reaction Time in Ankle
+              |     Instability. Int. J. Sports Med. 12, 290–292. doi:10.1055/s-2007-1024683
+              | Konradsen, L., Ravn, J., 1990. Ankle instability caused by prolonged peroneal reaction
+              |     time. Acta Orthop. 61, 388–390.
+              | Kutzner, I., Heinlein, B., Graichen, F., Bender, a, Rohlmann, a, Halder, a, Beier, a,
+              |     Bergmann, G., 2010. Loading of the knee joint during activities of daily living
+              |     measured in vivo in five subjects. J. Biomech. 43, 2164–2173.
+              |     doi:10.1016/j.jbiomech.2010.03.046
+              | Lapointe, S.J., Siegler, S., Hillstrom, H., Nobilini, R.R., Mlodzienski, A., Techner, L.,
+              |     1997. Changes in the flexibility characteristics of the ankle complex due to damage
+              |     to the lateral collateral ligaments: Anin vitro andin vivo study. J. Orthop. Res. 15,
+              |     331–341. doi:10.1002/jor.1100150304
+              | Lerner, Z.F., DeMers, M.S., Delp, S.L., Browning, R.C., 2015. How tibiofemoral
+              |     alignment and contact locations affect predictions of medial and lateral tibiofemoral
+              |     contact forces. J. Biomech. 48, 644–650. doi:10.1016/j.jbiomech.2014.12.049
+              | Lerner, Z.F., Haight, D.J., DeMers, M.S., Board, W.J., Browning, R.C., 2014. The effects
+              |     of walking speed on tibiofemoral loading estimated via musculoskeletal modeling. J.
+              |     Appl. Biomech. 30, 197–205. doi:10.1123/jab.2012-0206
+              | Liu, M.Q., Anderson, F.C., Schwartz, M.H., Delp, S.L., 2008. Muscle contributions to
+              |      support and progression over a range of walking speeds. J. Biomech. 41, 3243–52.
+              |      doi:10.1016/j.jbiomech.2008.07.031
+              | Loeb, G.E., Brown, I.E., Cheng, E.J., 1999. A hierarchical foundation for models of
+              |     sensorimotor control. Exp. Brain Res. 126, 1–18. doi:10.1007/s002210050712
+meta          | 68
+ref           | Löfvenberg, R., Karrholm, J., Sundelin, G., 1995. Reaction Time in Patients with Chronic
+              |     Lateral Instability of the Ankle Prolonged. Am J Sport. Med. 23, 414–417.
+              | Losina, E., Weinstein, A.M., Reichmann, W.M., Burbine, S. a., Solomon, D.H., Daigle,
+              |     M.E., Rome, B.N., Chen, S.P., Hunter, D.J., Suter, L.G., Jordan, J.M., Katz, J.N.,
+              |     2013. Lifetime risk and age at diagnosis of symptomatic knee osteoarthritis in the
+              |     US. Arthritis Care Res. 65, 703–711. doi:10.1002/acr.21898
+              | McClelland, J. a, Webster, K.E., Feller, J. a, Menz, H.B., 2010. Knee kinetics during
+              |    walking at different speeds in people who have undergone total knee replacement.
+              |    Gait Posture 32, 205–10. doi:10.1016/j.gaitpost.2010.04.009
+              | McGuine, T.A., Keene, J.S., 2006. The effect of a balance training program on the risk of
+              |    ankle sprains in high school athletes. Am. J. Sports Med. 34, 1103–1111.
+              |    doi:10.1177/0363546505284191
+              | Millard, M., Uchida, T., Seth, A., Delp, S.L., 2013. Flexing computational muscle:
+              |      modeling and simulation of musculotendon dynamics. J. Biomech. Eng. 135,
+              |      021005. doi:10.1115/1.4023390
+              | Modenese, L., Phillips, a T.M., Bull, a M.J., 2011. An open source lower limb model:
+              |    Hip joint validation. J. Biomech. 44, 2185–93. doi:10.1016/j.jbiomech.2011.06.019
+              | Mündermann, A., Asay, J.L., Mündermann, L., Andriacchi, T.P., 2008a. Implications of
+              |    increased medio-lateral trunk sway for ambulatory mechanics. J. Biomech. 41, 165–
+              |    70. doi:10.1016/j.jbiomech.2007.07.001
+              | Mündermann, A., Dyrby, C.O., D’Lima, D.D., Colwell, C.W., Andriacchi, T.P., 2008b.
+              |    In vivo knee loading characteristics during activities of daily living as measured by
+              |    an instrumented total knee replacement. J. Orthop. Res. 26, 1167–72.
+              |    doi:10.1002/jor.20655
+              | Munn, J., Beard, D.J., Refshauge, K.M., Lee, R.Y.W., 2003. Eccentric muscle strength in
+              |    functional ankle instability. Med. Sci. Sports Exerc. 35, 245–250.
+              |    doi:10.1249/01.MSS.0000048724.74659.9F
+              | Munn, J., Sullivan, S.J., Schneiders, A.G., 2010. Evidence of sensorimotor deficits in
+              |    functional ankle instability: A systematic review with meta-analysis. J. Sci. Med.
+              |    Sport 13, 2–12. doi:10.1016/j.jsams.2009.03.004
+              | Opheim, A., Jahnsen, R., Olsson, E., Stanghelle, J.K., 2009. Walking function, pain, and
+              |     fatigue in adults with cerebral palsy: a 7-year follow-up study. Dev. Med. Child
+              |     Neurol. 51, 381–388. doi:10.1111/j.1469-8749.2008.03250.x
+              | Osborne, M.D., Chou, L.S., Laskowski, E.R., Smith, J., Kaufman, K.R., 2001. The effect
+blank         | 
+meta          |                                                                                          69
+ref           |      of ankle disk training on muscle reaction time in subjects with a history of ankle
+              |      sprain. Am. J. Sports Med. 29, 627–632.
+              | Pandy, M.G., Lin, Y.-C., Kim, H.J., 2010. Muscle coordination of mediolateral balance
+              |     in normal walking. J. Biomech. 43, 2055–64. doi:10.1016/j.jbiomech.2010.04.010
+              | Perry, J., Antonelli, D., Ford, W., 1975. Analysis of knee-joint forces during flexed-knee
+              |      stance. J. Bone Joint Surg. Am. 57, 961–967.
+              | Reinbolt, J. a, Fox, M.D., Arnold, A.S., Ounpuu, S., Delp, S.L., 2008. Importance of
+              |     preswing rectus femoris activity in stiff-knee gait. J. Biomech. 41, 2362–9.
+              |     doi:10.1016/j.jbiomech.2008.05.030
+              | Rose, J., Gamble, J.G., Medeiros, J., Burgos, A., Haskell, W.L., 1989. Energy cost of
+              |     walking in normal children and in those with cerebral palsy: Comparison of Heart
+              |     Rate and Oxygen Uptake. J. Pediatr. Orthop. 9, 276–279.
+              | Sasaki, K., Neptune, R.R., 2010. Individual muscle contributions to the axial knee joint
+              |     contact force during normal walking. J. Biomech. 43, 2780–4.
+              |     doi:10.1016/j.jbiomech.2010.06.011
+              | Schnitzer, T.J., Popovich, J.M., Andersson, G.B., Andriacchi, T.P., 1993. Effect of
+              |     piroxicam on gait in patients with osteoarthritis of the knee. Arthritis Rheum. 36,
+              |     1207–13.
+              | Sharma, L., Hurwitz, D.E., Thonar, E.J., Sum, J. a, Lenz, M.E., Dunlop, D.D., Schnitzer,
+              |     T.J., Kirwan-Mellis, G., Andriacchi, T.P., 1998. Knee adduction moment, serum
+              |     hyaluronan level, and disease severity in medial tibiofemoral osteoarthritis. Arthritis
+              |     Rheum. 41, 1233–40. doi:10.1002/1529-0131(199807)41:7<1233::AID-
+              |     ART14>3.0.CO;2-L
+              | Shelburne, K.B., Torry, M.R., Pandy, M.G., 2006. Contributions of muscles, ligaments,
+              |     and the ground-reaction force to tibiofemoral joint loading during normal gait. J.
+              |     Orthop. Res. 24, 1983–90. doi:10.1002/jor.20255
+              | Shelburne, K.B., Torry, M.R., Pandy, M.G., 2005. Muscle, Ligament, and Joint-Contact
+              |     Forces at the Knee during Walking. Med. Sci. Sport. Exerc. 37, 1948–1956.
+              |     doi:10.1249/01.mss.0000180404.86078.ff
+              | Sherman, M.A., Seth, A., Delp, S.L., 2011. Simbody: multibody dynamics for biomedical
+              |     research. Procedia IUTAM 2, 241–261. doi:10.1016/j.piutam.2011.04.023
+              | Sheth, P., Bing Yu, Laskowski, E.R., An, K.-N., 1997. Ankle Disk Training Influences
+              |     Reaction Times of Selected Muscles in a Simulated Ankle Sprain. Am. J. Sports
+              |     Med. 25, 538–543. doi:10.1177/036354659702500418
+meta          | 70
+ref           | Shull, P.B., Lurie, K.L., Cutkosky, M.R., Besier, T.F., 2011. Training multi-parameter
+              |      gaits to reduce the knee adduction moment with data-driven models and haptic
+              |      feedback. J. Biomech. 44, 1605–9. doi:10.1016/j.jbiomech.2011.03.016
+              | Shull, P.B., Silder, A., Shultz, R., Dragoo, J.L., Besier, T.F., Delp, S.L., Cutkosky, M.R.,
+              |      2013. Six-Week Gait Retraining Program Reduces Knee Adduction Moment,
+              |      Reduces Pain, and Improves Function for Individuals with Medial Compartment
+              |      Knee Osteoarthritis. J. Orthop. Res. 1–6. doi:10.1002/jor.22340
+              | Shultz, R., Silder, A., Malone, M., Braun, H.J., Dragoo, J.L., 2015. Unstable Surface
+              |      Improves Quadriceps:Hamstring Co-contraction for Anterior Cruciate Ligament
+              |      Injury Prevention Strategies. Sport. Heal. A Multidiscip. Approach 7, 166–171.
+              |      doi:10.1177/1941738114565088
+              | Siegler, S., Chen, J., Schneck, C.D., 1990. The effect of damage to the lateral collateral
+              |      ligaments on the mechanical characteristics of the ankle joint--an in-vitro study. J.
+              |      Biomech. Eng. 112, 129–137.
+              | Siegler, S., Chen, J., Schneck, C.D., 1988. The three-dimensional kinematics and
+              |      flexibility characteristics of the human ankle and subtalar joints—Part I: Kinematics.
+              |      J. Biomech. Eng. 110, 364–373.
+              | Sritharan, P., Lin, Y.-C., Pandy, M.G., 2012. Muscles that do not cross the knee
+              |      contribute to the knee adduction moment and tibiofemoral compartment loading
+              |      during gait. J. Orthop. Res. 30, 1586–95. doi:10.1002/jor.22082
+              | Steele, K.M., DeMers, M.S., Schwartz, M.H., Delp, S.L., 2012. Compressive
+              |      tibiofemoral force during crouch gait. Gait Posture 35, 556–60.
+              |      doi:10.1016/j.gaitpost.2011.11.023
+              | Steele, K.M., Rozumalski, A., Schwartz, M.H., 2015. Muscle synergies and complexity
+              |      of neuromuscular control during gait in cerebral palsy. Dev. Med. Child Neurol.
+              |      n/a–n/a. doi:10.1111/dmcn.12826
+              | Steele, K.M., Seth, A., Hicks, J.L., Schwartz, M.S., Delp, S.L., 2010. Muscle
+              |      contributions to support and progression during single-limb stance in crouch gait. J.
+              |      Biomech. 43, 2099–105. doi:10.1016/j.jbiomech.2010.04.003
+              | Surve, I., Schwellnus, M.P., Noakes, T., Lombard, C., 1994. A Fivefold Reduction in the
+              |     Incidence of Recurrent Ankle Sprains in Soccer Players Using the Sport-Stirrup
+              |     Orthosis. Am. J. Sports Med. 22, 601–606. doi:10.1177/036354659402200506
+              | Thelen, D.G., 2003. Adjustment of muscle mechanics model parameters to simulate
+              |     dynamic contractions in older adults., Journal of biomechanical engineering.
+              |     doi:10.1115/1.1531112
+meta          |                                                                                              71
+ref           | Thelen, D.G., Anderson, F.C., Delp, S.L., 2003. Generating dynamic simulations of
+              |     movement using computed muscle control. J. Biomech. 36, 321–328.
+              |     doi:10.1016/S0021-9290(02)00432-3
+              | Vaes, P., Duquet, W., Van Gheluwe, B., 2002. Peroneal Reaction Times and Eversion
+              |     Motor Response in Healthy and Unstable Ankles. J. Athl. Train. 37, 475–480.
+              | van der Wees, P.J., Lenssen, A.F., Hendriks, E.J.M., Stomp, D.J., Dekker, J., de Bie, R. a,
+              |      2006. Effectiveness of exercise therapy and manual mobilisation in ankle sprain and
+              |      functional instability: a systematic review. Aust. J. Physiother. 52, 27–37.
+              |      doi:10.1016/S0004-9514(06)70059-9
+              | Verhagen, E., van der Beek, A., Twisk, J., Bouter, L., Bahr, R., van Mechelen, W., 2004.
+              |     The effect of a proprioceptive balance board training program for the prevention of
+              |     ankle sprains: a prospective controlled trial. Am. J. Sports Med. 32, 1385–1393.
+              |     doi:10.1177/0363546503262177
+              | Verhagen, E.A.L.M., Bay, K., 2010. Optimising ankle sprain prevention: a critical review
+              |     and practical appraisal of the literature. Br. J. Sports Med. 44, 1082–88.
+              |     doi:10.1136/bjsm.2010.076406
+              | Wagner, D.W., Stepanyan, V., Shippen, J.M., Demers, M.S., Gibbons, R.S., Andrews,
+              |    B.J., Creasey, G.H., Beaupre, G.S., 2013. Consistency among musculoskeletal
+              |    models: caveat utilitor. Ann. Biomed. Eng. 41, 1787–99. doi:10.1007/s10439-013-
+              |    0843-1
+              | Walker, P.S., Rovick, J.S., Robertson, D.D., 1988. The effects of knee brace hinge design
+              |     and placement on joint mechanics. J. Biomech. 21, 965–74.
+              | Walter, J.P., Kinney, A.L., Banks, S.A., D’Lima, D.D., Besier, T.F., Lloyd, D.G., Fregly,
+              |     B.J., 2014. Muscle Synergies May Improve Optimization Prediction of Knee
+              |     Contact Forces During Walking. J. Biomech. Eng. 136, 021031.
+              |     doi:10.1115/1.4026428
+              | Wang, J.M., Hamner, S.R., Delp, S.L., Koltun, V., 2012. Optimizing locomotion
+              |    controllers using biologically-based actuators and objectives. ACM Trans. Graph.
+              |    31, 1–11. doi:10.1145/2185520.2335376
+              | Ward, S.R., Eng, C.M., Smallwood, L.H., Lieber, R.L., 2009. Are Current Measurements
+              |     of Lower Extremity Muscle Architecture Accurate? Clin. Orthop. Relat. Res. 467,
+              |     1074–1082. doi:10.1007/s11999-008-0594-8
+              | Waterman, B.R., Belmont, P.J., Cameron, K.L., Deberardino, T.M., Owens, B.D., 2010.
+              |     Epidemiology of ankle sprain at the United States Military Academy. Am. J. Sports
+blank         | 
+meta          | 72
+ref           |     Med. 38, 797–803. doi:10.1177/0363546509350757
+              | Waters, R.L., Mulroy, S., 1999. The energy expenditure of normal and pathologic gait.
+              |     Gait Posture 9, 207–231. doi:10.1016/S0966-6362(99)00009-0
+              | Wei, F., Braman, J.E., Weaver, B.T., Haut, R.C., 2011a. Determination of dynamic ankle
+              |     ligament strains from a computational model driven by motion analysis based
+              |     kinematic data. J. Biomech. 44, 2636–41. doi:10.1016/j.jbiomech.2011.08.010
+              | Wei, F., Hunley, S.C., Powell, J.W., Haut, R.C., 2011b. Development and validation of a
+              |     computational model to study the effect of foot constraint on ankle injury due to
+              |     external rotation. Ann. Biomed. Eng. 39, 756–65. doi:10.1007/s10439-010-0234-9
+              | Winby, C.R., Lloyd, D.G., Besier, T.F., Kirk, T.B., 2009. Muscle and external load
+              |     contribution to knee joint contact loads during normal gait. J. Biomech. 42, 2294–
+              |     300. doi:10.1016/j.jbiomech.2009.06.019
+              | Wong, M., Carter, D.., 2003. Articular cartilage functional histomorphology and
+              |    mechanobiology: a research perspective. Bone 33, 1–13. doi:10.1016/S8756-
+              |    3282(03)00083-8
+              | Wright, I.C., Neptune, R.R., Van Den Bogert, A.J., Nigg, B.M., 2000a. The influence of
+              |     foot positioning on ankle sprains. J. Biomech. 33, 513–519. doi:10.1016/S0021-
+              |     9290(99)00218-3
+              | Wright, I.C., Neptune, R.R., van den Bogert, A.J., Nigg, B.M., 2000b. The effects of
+              |     ankle compliance and flexibility on ankle sprains. Med. Sci. Sports Exerc. 32, 260–
+              |     265. doi:10.1097/00005768-200002000-00002
+              | Yamaguchi, G.T., Zajac, F.E., 1989. A planar model of the knee joint to characterize the
+              |    knee extensor mechanism. J. Biomech. 22, 1–10.
+              | Young, S.J., van Doornik, J., Sanger, T.D., 2011. Visual feedback reduces co-contraction
+              |     in children with dystonia. J. Child Neurol. 26, 37–43.
+              |     doi:10.1177/0883073810371828
+              | Zhao, D., Banks, S.A., Mitchell, K.H., Lima, D.D.D., Jr, C.W.C., Fregly, B.J., 2007.
+              |     Correlation between the Knee Adduction Torque and Medial Contact Force for a
+              |     Variety of Gait Patterns. J. Orthop. Res. 789–797. doi:10.1002/jor
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                          73
+title         | Appendix A: Open source resources from this dissertation
+text          | Resource           Description                                Studies         Content Information
+blank         | 
+text          | Joint Reaction     Calculates internal joint reaction loads   Chapters        Software library
+              | Analysis           transferred between any two                2 and 3         Documentation
+              |                    contacting bodies in OpenSim. Joint                        Examples
+              |                    reaction loads represent the resultant                     Test cases
+              |                    of all forces and moments crossing the
+              |                    joint, including muscles.
+blank         | 
+text          |                    Distributed with OpenSim at http://opensim.stanford.edu/
+blank         | 
+text          | Joint Load         A free and open source plugin to           Chapters        Source code
+              | Optimization       minimize muscle activity and joint         2 and 3         Documentation
+              |                    reaction loads simultaneously in                           Examples
+              |                    OpenSim. Includes example models                           Test cases
+              |                    and analyses for learning researchers.
+blank         | 
+text          |                    Hosted as a SimTK project: https://simtk.org/home/jointloadopt
+blank         | 
+text          | Stretch and        A free and open source plugin to add       Chapter 4       Source code
+              | Reflex             muscle stretch feedback controllers                        Documentation
+              | Controllers        and delayed stretch feedback                               Examples
+              |                    controllers to OpenSim. Includes
+              |                    example models and analyses for
+              |                    learning researchers.
+blank         | 
+text          |                    Hosted on GitHub: https://github.com/msdemers/opensim-reflex-controllers
+blank         | 
+text          | Simulations of     A library of human landing models          Chapter 4       Documentation
+              | landing injuries   and simulations of ankle injuries.                         Data
+              |                    Includes a generic human model with                        Models
+              |                    foot-floor contact and stretch-based                       Simulation results
+              |                    feedback controllers, motion capture
+              |                    data and scaled models of measured
+              |                    human landings, and a battery of
+              |                    landing simulations under different
+              |                    muscle coordination strategies.
+blank         | 
+text          |                    Hosted as a SimTK project: https://simtk.org/home/ankle-sprains
+blank         | 
+              | 
+              | 
+              | 
+meta          | 74
+title         | Appendix B: Calculating joint contact forces in OpenSim
+text          |          In order to calculate tibiofemoral contact forces during walking (Chapters 2 and
+              | 3), we developed a general method to calculate joint loads transferred between any two
+              | contacting bodies in OpenSim. This method, called the Joint Reaction Analysis,
+              | computes the resultant forces and moments that represent the internal loads carried by the
+              | joint structure. For example, Chapters 2 and 3 report joint forces representing the sum of
+              | contact forces between the tibial and femoral cartilage and all ligament forces crossing
+              | the tibiofemoral joint
+blank         | 
+              | 
+              | 
+text          |         (A)                                               (B)                      %"
+blank         | 
+text          |                                 Si-1                       (⃑0123/)
+blank         | 
+text          |                                                                                             !" #⃑"
+              |                                                                     !" g
+blank         | 
+              | 
+text          |                         Si
+blank         | 
+text          |                                            Si+1
+blank         | 
+              | 
+text          |                                        (⃑)*+),-./                           %"&'
+blank         | 
+              | 
+text          | (A) Example kinematic chain of body segments that can be represented in OpenSim. The joint between body
+              | segments Si and Si-1 is described by splines that represent an elliptical surface and thus need not be an
+              | idealized pin joint. (B) Single-body system used to calculate ]& , the reaction load at the proximal joint of Si.
+              | The calculation is in terms of Si’s inertial forces, muscle forces (black arrows), other external forces, and
+              | the previously calculated reaction force at the distal joint.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                                               75
+text          |        OpenSim uses multibody dynamics and simulation methods from Simbody
+              | (https://simtk.org/home/simbody), a free and open source library for representing rigid
+              | body dynamics. Simbody constructs models as tree structures in which rigid bodies
+              | connect in kinematic chains that can branch with joints or reconnect with constraints. The
+              | equations of motion of the system are represented in terms of the generalized coordinates
+              | and generalized forces of the model. Solving these generalized equations of motion does
+              | not require calculating internal forces, such as the joint contact forces. Therefore, the
+              | Joint Reaction Analysis in OpenSim incorporates a post-processing procedure that uses
+              | the muscle forces and joint kinematics to calculate resultant joint loads.
+              |        Figure B.1.A shows an example model consisting of segments linked in a
+              | kinematic chain. Joints between these segments do not need to have classical engineering
+              | definitions, such as a revolute joint or spherical joint, but instead can have more
+              | physiologic descriptions. For example, the motion between body segments q& and q&r1
+              | may be described by splines that couple the rotations and translations of the knee. For
+              | each time point in an analysis, a recursive operation begins with the most distal bodies
+              | and progresses proximally to calculate the joint loads. The force at each joint is
+              | calculated by performing a force balance on the body distal to the joint.
+              |        A single step in this recursive procedure is analogous to constructing a free body
+              | diagram for each rigid body and resolving the point load that must be applied to the joint
+              | to balance the forces and motions of the body. To calculate ]& , the resultant forces and
+              | moments at joint i, the body distal to joint i, q& , is treated as an independent body with
+              | known kinematics in a global reference frame. In the example system (Figure B.1.B), '&
+              | represents the six dimensional vector of known angular and linear accelerations of q& .
+              | Since these accelerations are reconstructed from Simbody’s generalized equations of
+              | motion, they capture any kinematic complexity in the joint description. 3/A>/B)C. and
+              | 3a+,-./ represent the previously calculated forces and moments applied by external loads
+              | and musculotendon actuators respectively. ]&m1 $represents the joint reaction load applied
+              | at the distal joint. ]&m1 $is known since it was calculated in the previous recursive step.
+              | Using the known generalized coordinates (F) and generalized speeds (s) of the body
+blank         | 
+              | 
+              | 
+meta          | 76
+text          | segment and all other applied forces, the desired resultant force is calculated as the vector
+              | sum:
+              |            t=
+              |  ]= = $         = E& F '& + 3-=),>BC&)> − ( 3/A>/B)C. +            3a+,-./, + ]&m1 ) Equation B.1
+              |            3=
+              |           The sum requires that all terms be described in a common reference frame located
+              | at the body origin, thus ]= is the joint force and moment expressed at the body origin.
+              | E& F $is the six-by-six mass matrix for body segment i. 3-=),>BC&)> $represents constraint
+              | forces applied to the body, if applicable. Since the all terms other than ]= result from
+              | generalized coordinates and forces previously solved by Simbody, we can calculate the
+              | moment and force at the body origin, t= and 3= , that are required to balance the equation.
+              | Finally, ]= expressed at the body origin is shifted to an equivalent moment and force, t&
+              | and 3& , at the joint center:
+              |                                          t&        t=       v×3=
+              |                                 ]& = $        ∶=        −                           Equation B.2
+              |                                          3&        3=        0
+              | where v is the vector pointing from the body origin to the joint location.
+              |           The Joint Reaction analysis algorithm is distributed as part of OpenSim versions
+              | 1.9 and later. The value of this algorithm is that it leverages the generalized coordinate
+              | representation and rich set of joint definitions provided by Simbody and OpenSim and
+              | provides a free tool for researchers to use to calculate joint loads for any musculoskeletal
+              | structure.
+blank         | 
+              | 
+              | 
+              | 
+meta          |                                                                                               77
+blank         |