Uncertainty that arises from measurement error and parameter estimation can significantly impact the interpretation of musculoskeletal simulations; however these effects are hardly ever tackled. bounds (5-95%) and level of sensitivity of outputs to model input parameters were determined throughout the gait cycle. The combined effect of uncertainty resulted in mean bounds that ranged from 2.7�� to 6.4�� in joint kinematics 2.7 to 8.1 N m in joint moments and 35.8 to 130.8 N in muscle mass forces. The effect of movement artifact was 1.8 times larger than some other propagated resource. Sensitivity to specific body segment guidelines and muscle guidelines were linked to where in the gait cycle they were determined. We anticipate that through the increased use of probabilistic tools experts will better understand the advantages and limitations of their musculoskeletal simulations and more effectively use simulations to evaluate hypotheses and inform medical decisions. and = 0.2-0.4) moderately sensitive (= 0.4-0.6) or highly sensitive (= 0.6-1.0). The slope of each relationship was determined and multiplied by the standard deviation of the input parameter from Table 2. This additional scaling locations the slope in the context of the potential variance of the input FR 180204 parameter. To assess if calculating sensitivity at the maximum value of the output is a consistent representation of level of sensitivity throughout the gait cycle a Pearson Product-Moment Correlation was determined for the input parameter and the generated range of outputs at each individual time point. Results 5 Confidence Bounds The effect of marker placement error and movement artifact on joint kinematics can be observed by the size of the 5-95 confidence bounds for each joint angle output (Fig. 3 Stage 1). The knee flex/ext IRF5 joint angle exhibited the smallest bounds (2.7 �� 0.3��) but the largest motion during the gait cycle. The relative bound sizes for hip angle in add/abd (3.0 �� 0.3��) and int/ext (5.1 �� 1.0��) were large considering the smaller motions in these examples of freedom. Number 3 5 confidence bounds for each simulation stage output following inverse kinematics (Stage 1) inverse dynamics (Stage 2) and static optimization (Stage 3). Ideals for the determined mean 5-95 confidence bounds are displayed. Kinematic … When considering the combined effects of marker error (marker placement and movement artifact) and body section parameter uncertainty bounds for hip flex/ext (8.0 �� 2.8 N m) and add/abd (7.4 �� 2.8 N m) moments were substantially larger than some other degree of freedom (ankle: 2.7 �� 1.8 N m; knee: 4.4 �� 1.4 N m; hip int/ext: 1.8 �� 1.0 N m) (Fig. 3 Stage 2). Joint instant bound sizes during the swing period were 81.7% smaller in the ankle and 16.5% smaller in the knee compared to the stance period; however bound sizes in hip examples of freedom were 42.9% larger normally in the swing period compared to the stance period. The combined effect of all sources of uncertainty had the greatest impact on medial gastrocnemius (142.3 �� 110.8 N) and the gluteus medius (130.8 �� 89.2 N) which proven the largest bounds for muscle force output (Fig. 3 Stage 3). Gastrocnemius and gluteus medius also generated the largest peak forces during the gait cycle (gastrocnemius: 663.1 �� 105.5 N; gluteus medius: 1025.4 �� 62.9 N). The FR 180204 average muscle force bound size for those eight muscle tissue was 83.1 �� 39.6 N. Variability was present in peak muscle push timing for each of the eight muscle tissue that was normally 104 �� 112 ms and as high as 402 ms for the gluteus medius. By comparing 5-95% bounds with all uncertainty sources regarded as vs. the individual sources FR 180204 relative contributions of each resource can be evaluated (Fig. 4). For Stage 1 the effect of movement artifact was 1.8 times larger than marker placement on joint kinematics for those examples of freedom with the greatest difference occurring in the ankle (5.9 �� 0.8�� vs. 2.2 �� 0.1��). When this uncertainty was propagated to joint instant calculation in Stage 2 the relative effect of movement artifact compared to marker placement increased to 2.3-4.0 times with higher effect in swing period than in the stance period for hip add/abd and hip int/ext. BSPs had a relatively small impact on joint moments compared to the effect of marker error. The exception was hip flex/ext during the swing period where BSP uncertainty has the largest effect and was 2.1 FR 180204 instances greater during the stance period compared to the swing period. FR 180204