Altered knee kinematics after posterior cruciate ligament single-bundle reconstruction-a comprehensive prospective biomechanical in vivo analysis.

Purpose: Passive tibiofemoral anterior-posterior (AP) laxity has been extensively investigated after posterior cruciate ligament (PCL) single-bundle reconstruction. However, the PCL also plays an important role in providing rotational stability in the knee. Little is known in relation to the effects of PCL single-bundle reconstruction on passive tibiofemoral rotational laxity. Gait biomechanics after PCL reconstruction are even less understood. The aim of this study was a comprehensive prospective biomechanical in vivo analysis of the effect of PCL single-bundle reconstruction on passive tibiofemoral rotational laxity, passive anterior-posterior laxity, and gait pattern. Methods: Eight patients undergoing PCL single-bundle reconstruction (seven male, one female, mean age 35.6 ± 6.6 years, BMI 28.0 ± 3.6 kg/m2) were analyzed preoperatively and 6 months postoperatively. Three of the eight patients received additional posterolateral corner (PLC) reconstruction. Conventional stress radiography was used to evaluate passive translational tibiofemoral laxity. A previously established rotometer device with a C-arm fluoroscope was used to assess passive tibiofemoral rotational laxity. Functional gait analysis was used to examine knee kinematics during level walking. Results: The mean side-to-side difference (SSD) in passive posterior translation was significantly reduced postoperatively (12.1 ± 4.4 mm vs. 4.3 ± 1.8 mm; p < 0.01). A significant reduction in passive tibiofemoral rotational laxity at 90° knee flexion was observed postoperatively (27.8° ± 7.0° vs. 19.9° ± 7.5°; p = 0.02). The range of AP tibiofemoral motion during level walking was significantly reduced in the reconstructed knees when compared to the contralateral knees at 6-month follow-up (16.6 ± 2.4 mm vs. 13.5 ± 1.6 mm; p < 0.01). Conclusion: PCL single-bundle reconstruction with optional PLC reconstruction reduces increased passive tibiofemoral translational and rotational laxity in PCL insufficient knees. However, increased passive tibiofemoral translational laxity could not be fully restored and patients showed altered knee kinematics with a significantly reduced range of tibiofemoral AP translation during level walking at 6-month follow-up. The findings of this study indicate a remaining lack of restoration of biomechanics after PCL single-bundle reconstruction in the active and passive state, which could be a possible cause for joint degeneration after PCL single-bundle reconstruction.

Model-based exploration of hypokalemia in dairy cows.

Hypokalemia in dairy cows, which is characterized by too low serum potassium levels, is a severe mineral disorder that can be life threatening. In this paper, we explore different originating conditions of hypokalemia-reduced potassium intake, increased excretion, acid-base disturbances, and increased insulin-by using a dynamic mathematical model for potassium balance in non-lactating and lactating cows. The simulations confirm observations described in literature. They illustrate, for example, that changes in dietary intake or excretion highly effect intracellular potassium levels, whereas extracellular levels vary only slightly. Simulations also show that the higher the potassium content in the diet, the more potassium is excreted with urine. Application of the mathematical model assists in experimental planning and therefore contributes to the 3R strategy: reduction, refinement and replacement of animal experiments.

PCL insufficient patients with increased translational and rotational passive knee joint laxity have no increased range of anterior-posterior and rotational tibiofemoral motion during level walking.

Passive translational tibiofemoral laxity has been extensively examined in posterior cruciate ligament (PCL) insufficient patients and belongs to the standard clinical assessment. However, objective measurements of passive rotational knee laxity, as well as range of tibiofemoral motion during active movements, are both not well understood. None of these are currently quantified in clinical evaluations of patients with PCL insufficiency. The objective of this study was to quantify passive translational and rotational knee laxity as well as range of anterior-posterior and rotational tibiofemoral motion during level walking in a PCL insufficient patient cohort as a basis for any later clinical evaluation and therapy. The laxity of 9 patient knees with isolated PCL insufficiency or additionally posterolateral corner (PLC) insufficiency (8 males, 1 female, age 36.78 ± 7.46 years) were analysed and compared to the contralateral (CL) knees. A rotometer device with a C-arm fluoroscope was used to assess the passive tibiofemoral rotational laxity while stress radiography was used to evaluate passive translational tibiofemoral laxity. Functional gait analysis was used to examine the range of anterior-posterior and rotational tibiofemoral motion during level walking. Passive translational laxity was significantly increased in PCL insufficient knees in comparison to the CL sides (15.5 ± 5.9 mm vs. 3.7 ± 1.9 mm, p < 0.01). Also, passive rotational laxity was significantly higher compared to the CL knees (26.1 ± 8.2° vs. 20.6 ± 5.6° at 90° knee flexion, p < 0.01; 19.0 ± 6.9° vs. 15.5 ± 5.9° at 60° knee flexion, p = 0.04). No significant differences were observed for the rotational (16.3 ± 3.7° vs. 15.2 ± 3.6°, p = 0.43) and translational (17.0 ± 5.4 mm vs. 16.1 ± 2.8 mm, p = 0.55) range of anterior-posterior and rotational tibiofemoral motion during level walking conditions for PCL insufficient knees compared to CL knees respectively. The present study illustrates that patients with PCL insufficiency show a substantial increased passive tibiofemoral laxity, not only in tibiofemoral translation but also in tibiofemoral rotation. Our data indicate that this increased passive multiplanar knee joint laxity can be widely compensated during level walking. Further studies should investigate progressive changes in knee joint laxity and kinematics post PCL injury and reconstruction to judge the individual need for therapy and effects of physiotherapy such as quadriceps force training on gait patterns in PCL insufficient patients.

Mathematical Modeling and Simulation Provides Evidence for New Strategies of Ovarian Stimulation.

New approaches to ovarian stimulation protocols, such as luteal start, random start or double stimulation, allow for flexibility in ovarian stimulation at different phases of the menstrual cycle. It has been proposed that the success of these methods is based on the continuous growth of multiple cohorts ("waves") of follicles throughout the menstrual cycle which leads to the availability of ovarian follicles for ovarian controlled stimulation at several time points. Though several preliminary studies have been published, their scientific evidence has not been considered as being strong enough to integrate these results into routine clinical practice. This work aims at adding further scientific evidence about the efficiency of variable-start protocols and underpinning the theory of follicular waves by using mathematical modeling and numerical simulations. For this purpose, we have modified and coupled two previously published models, one describing the time course of hormones and one describing competitive follicular growth in a normal menstrual cycle. The coupled model is used to test ovarian stimulation protocols in silico. Simulation results show the occurrence of follicles in a wave-like manner during a normal menstrual cycle and qualitatively predict the outcome of ovarian stimulation initiated at different time points of the menstrual cycle.

Quantification of morning stiffness to assess disease activity and treatment effects in rheumatoid arthritis.

OBJECTIVES: The clinical parameter of morning stiffness is widely used to assess the status of RA, but its accurate quantitative assessment in a clinical setting has not yet been successful. This lack of individual quantification limits both personalized medication and efficacy evaluation in the treatment of RA. METHODS: We developed a novel technology to assess passive resistance of the MCP III joint (stiffness) and its passive range of motion (PRoM). Within this pilot study, 19 female postmenopausal RA patients and 9 healthy controls were examined in the evening as well as the morning of the following day. To verify the specificity of the biomechanical quantification, 11 patients with RA were assessed both prior to and ∼3 h after glucocorticoid therapy. RESULTS: While the healthy controls showed only minor changes between afternoon and morning, in RA patients the mean PRoM decreased significantly by 18% (s.d. 22) and stiffness increased significantly by 20% (s.d. 18) in the morning compared with the previous afternoon. We found a significant positive correlation between RA activity and biomechanical measures. Glucocorticoids significantly increased the mean PRoM by 16% (s.d. 11) and reduced the mean stiffness by 23% (s.d. 22). CONCLUSION: This technology allowed mechanical stiffness to be quantified in MCP joints and demonstrated high sensitivity with respect to disease status as well as medication effect in RA patients. Such non-invasive, low-risk and rapid assessment of biomechanical joint stiffness opens a novel avenue for judging therapy efficacy in patients with RA and potentially also in other non-RA inflammatory joint diseases.

Quantifying Asymmetry in Gait: The Weighted Universal Symmetry Index to Evaluate 3D Ground Reaction Forces.

Though gait asymmetry is used as a metric of functional recovery in clinical rehabilitation, there is no consensus on an ideal method for its evaluation. Various methods have been proposed to analyze single bilateral signals but are limited in scope, as they can often use only positive signals or discrete values extracted from time-scale data as input. By defining five symmetry axioms, a framework for benchmarking existing methods was established and a new method was described here for the first time: the weighted universal symmetry index (wUSI), which overcomes limitations of other methods. Both existing methods and the wUSI were mathematically compared to each other and in respect to their ability to fulfill the proposed symmetry axioms. Eligible methods that fulfilled these axioms were then applied using both discrete and continuous approaches to ground reaction force (GRF) data collected from healthy gait, both with and without artificially induced asymmetry using a single instrumented elbow crutch. The wUSI with a continuous approach was the only symmetry method capable of identifying GRF asymmetry differences in different walking conditions in all three planes of motion. When used with a continuous approach, the wUSI method was able to detect asymmetries while avoiding artificial inflation, a common problem reported in other methods. In conclusion, the wUSI is proposed as a universal method to quantify three-dimensional GRF asymmetries, which may also be expanded to other biomechanical signals.

Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation.

Understanding the pathophysiological processes of cartilage degradation requires adequate model systems to develop therapeutic strategies towards osteoarthritis (OA). Although different in vitro or in vivo models have been described, further comprehensive approaches are needed to study specific disease aspects. This study aimed to combine in vitro and in silico modeling based on a tissue-engineering approach using mesenchymal condensation to mimic cytokine-induced cellular and matrix-related changes during cartilage degradation. Thus, scaffold-free cartilage-like constructs (SFCCs) were produced based on self-organization of mesenchymal stromal cells (mesenchymal condensation) and (i) characterized regarding their cellular and matrix composition or secondly (ii) treated with interleukin-1ß (IL-1ß) and tumor necrosis factor α (TNFα) for 3 weeks to simulate OA-related matrix degradation. In addition, an existing mathematical model based on partial differential equations was optimized and transferred to the underlying settings to simulate the distribution of IL-1ß, type II collagen degradation and cell number reduction. By combining in vitro and in silico methods, we aimed to develop a valid, efficient alternative approach to examine and predict disease progression and effects of new therapeutics.

Negative affect is unrelated to fluctuations in hormone levels across the menstrual cycle: Evidence from a multisite observational study across two successive cycles.

BACKGROUND: Female sex hormones may play a crucial role in the occurrence of cycle-related mood disorders. However, the literature is inconsistent and methodologically stringent observational studies on the relationship between sex hormones and negative affect are lacking. METHODS: In this longitudinal multisite study from Hannover, Germany, and Zurich, Switzerland, we examined oestrogen, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone serum levels in association with negative affect as measured with the Positive and Negative Affect Schedule (PANAS). Negative affect and hormone assays were collected at four consecutive time points comprising menstrual, pre-ovulatory, mid-luteal and premenstrual phase across two cycles (n=87 and n=67 for the first and second cycles). The Beck Depression Inventory (BDI) was assessed once prior to the first cycle and included as a secondary measure. RESULTS: Mean negative affect scores did not significantly fluctuate across both cycles and there was in particular no symptom increase premenstrually. No sex hormone consistently related to repeated measures of negative affect across two consecutive cycles. The BDI sum-score assessed at baseline was not related to hormone levels across the first cycle. CONCLUSIONS: This is the first multisite longitudinal study on the association between negative affect and sex hormone levels encompassing two consecutive menstrual cycles. Negative affect did not fluctuate across the cycle and there was no direct and uniform association between sex hormones and self-reported negative affect. These findings suggest that moderators such as personality traits and epigenetics should be considered in future research.

Parameter identification in a tuberculosis model for Cameroon.

A deterministic model of tuberculosis in Cameroon is designed and analyzed with respect to its transmission dynamics. The model includes lack of access to treatment and weak diagnosis capacity as well as both frequency- and density-dependent transmissions. It is shown that the model is mathematically well-posed and epidemiologically reasonable. Solutions are non-negative and bounded whenever the initial values are non-negative. A sensitivity analysis of model parameters is performed and the most sensitive ones are identified by means of a state-of-the-art Gauss-Newton method. In particular, parameters representing the proportion of individuals having access to medical facilities are seen to have a large impact on the dynamics of the disease. The model predicts that a gradual increase of these parameters could significantly reduce the disease burden on the population within the next 15 years.

Anterior cruciate ligament-deficient patients with passive knee joint laxity have a decreased range of anterior-posterior motion during active movements.

BACKGROUND: Although instability of the knee joint is known to modify gait patterns, the amount that patients compensate for joint laxity during active movements remains unknown. PURPOSE: By developing a novel technique to allow the assessment of tibiofemoral kinematics, this study aimed to elucidate the role of passive joint laxity on active tibiofemoral kinematics during walking. STUDY DESIGN: Controlled laboratory study. METHODS: Using motion capture, together with combinations of advanced techniques for assessing skeletal kinematics (including the symmetrical axis of rotation approach [SARA], symmetrical center of rotation estimation [SCoRE], and optimal common shape technique [OCST]), a novel noninvasive approach to evaluate dynamic tibiofemoral motion was demonstrated as both reproducible and repeatable. Passive and active anterior-posterior translations of the tibiofemoral joint were then examined in 13 patients with anterior cruciate ligament (ACL) ruptures that were confirmed by magnetic resonance imaging and compared with those in their healthy contralateral limbs. RESULTS: Passive tibial anterior translation was significantly greater in the ACL-ruptured knees than in the contralateral healthy controls. However, the femora of the ACL-ruptured knees generally remained more posterior (~3 mm) relative to the tibia within a gait cycle of walking compared with the healthy limbs. Surprisingly, the mean range of tibiofemoral anterior-posterior translation over an entire gait cycle was significantly lower in ACL-ruptured knees than in the healthy joints (P = .026). A positive correlation was detected between passive laxity and active joint mobility, but with a consistent reduction in the range of tibiofemoral anterior-posterior translation of approximately 3 mm in the ACL-deficient knees. CONCLUSION: It seems that either active stabilization of tibiofemoral kinematics or anterior subluxation of the tibia reduces joint translation in lax knees. This implies that either a muscular overcompensation mechanism or a physical limitation due to secondary passive stabilizers occurs within the joint and thus produces a situation that has a reduced range of active motion compared with knees with physiological stability. CLINICAL RELEVANCE: The reduced range of active tibiofemoral translation suggests overloading of the passive structures in passively lax knees, either through excessive muscular action or joint subluxation, and could provide a plausible mechanism for explaining posttraumatic degeneration of cartilage in the joint.

The weighted optimal common shape technique improves identification of the hip joint center of rotation in vivo.

Functional methods present a promising approach for the identification of skeletal kinematics, but their accuracy is limited by soft tissue artifacts (STAs). We hypothesized that consideration of the nonuniform distribution of STAs across the segment can lead to a significant improvement in the determination of the center of rotation at the hip. Twenty-four total hip arthroplasty (THA) patients performed repetitions of a star-arc movement. The location of the hip centers of rotation (CoRs) were estimated from the motion data using the Symmetrical Center of Rotation Estimation (SCoRE), both with and without procedures to minimize the effect of STAs. The precision of the CoR estimations was evaluated using the SCoRE residual, a measure of joint precision. Application of the newly developed weighted Optimal Common Shape Technique (wOCST) achieved the best CoR estimations with a precision of better than 3 mm, while the precision using raw data alone was up to seven times worse. Furthermore, consideration of the nonuniform distribution of STA across the surface of the skin using the wOCST produced an improvement of ∼24% over kinematics data processed using the standard OCST. Functional determination of the CoR at the hip using the newly developed wOCST can now identify the joint CoR with a precision of millimeters. Such approaches therefore offer improved precision in the assessment of skeletal kinematics and may aid in evaluating clinical treatment success and differentiating between therapy outcomes.

The SCoRE residual: a quality index to assess the accuracy of joint estimations.

The determination of an accurate centre of rotation (CoR) from skin markers is essential for the assessment of abnormal gait patterns in clinical gait analysis. Despite the many functional approaches to estimate CoRs, no non-invasive analytical determination of the error in the reconstructed joint location is currently available. The purpose of this study was therefore to verify the residual of the symmetrical centre of rotation estimation (SCoRE) as a reliable indirect measure of the error of the computed joint centre. To evaluate the SCoRE residual, numerical simulations were performed to evaluate CoR estimations at different ranges of joint motion. A statistical model was developed and used to determine the theoretical relationships among the SCoRE residual, the magnitude of the skin marker artefact, the corrections to the marker positions, and the error of the CoR estimations to the known centre of rotation. We found that the equation err=0.5r(s) provides a reliable relationship among the CoR error, err, and the scaled SCoRE residual, r(s), providing that any skin marker artefact is first minimised using the optimal common shape technique (OCST). Measurements on six healthy volunteers showed a reduction of SCoRE residual from 11 to below 6mm and therefore demonstrated consistency of the theoretical considerations and numerical simulations with the in vivo data. This study also demonstrates the significant benefit of the OCST for reducing skin marker artefact and thus for predicting the accuracy of determining joint centre positions in functional gait analysis. For the first time, this understanding of the SCoRE residual allows a measure of error in the non-invasive assessment of joint centres. This measure now enables a rapid assessment of the accuracy of the CoR as well as an estimation of the reproducibility and repeatability of skeletal motion patterns.

The medial-lateral force distribution in the ovine stifle joint during walking.

Knowledge of the load distribution in the knee is essential for understanding the interaction between mechanics and biology in both the healthy and diseased joint. While the sheep stifle joint is a predominant model for better understanding regeneration after injury, little is known about the compartmental force distribution between the medial and lateral condyles. By including sheep specific anatomy and gait analyses, we used computational musculoskeletal analyses to estimate the medial-lateral joint contact force distribution in ovine stifle joints during walking by simplifying the system of equations into a 2D problem that was solved directly. Gait analysis was conducted using bone markers in three female Merino-mix sheep. Joint contact forces were computed with respect to the specific anatomy of the ovine tibia, resulting in low (<0.13 bodyweight) mean anteroposterior shear forces throughout the gait cycle, with mean peak contact forces perpendicular to the tibial plateau of 2.2 times bodyweight. The medial-lateral compartmental load distribution across the tibial condyles was determined and revealed loading predominantly on the medial condyle, bearing approximately 75% of the total load during phases of peak loading. By considering the anatomical characteristics of the ovine stifle joint, together with the dynamic forces during gait, this study provides evidence for predominantly medial loading in sheep, somewhat similar to the distribution reported in man. However, the exact conditions under which the loading in the ovine stifle joint is representative of the human situation will need to be elucidated in further studies.

Frontal plane alignment: an imageless method to predict the mechanical femoral-tibial angle (mFTA) based on functional determination of joint centres and axes.

Lower limb alignment is important for the internal loading conditions in the knee. In this study, we aimed to evaluate a new imageless, non-invasive method for quantifying frontal plane alignment by direct comparison against CT. To determine the mechanical femoral-tibial angle (mFTA), functional posture analysis was performed in 15 limbs (13 individuals) using previously published methods for the minimisation of skin marker artefact together with the functional identification of joints, and compared against a published regression method. Whilst the average Functional-mFTA (1.3 + or - 2.3) was not significantly different (p > 0.25) from the CT-mFTA (1.5 + or - 2.1), the Regression-mFTA (4.7 + or - 5.6) showed a significant error (p < 0.01). The Functional-mFTA correlated significantly (R = 0.91; p < 0.0001), with a small bias (0.3 degrees) and agreed better with the CT-mFTA than the Regression-mFTA (R = 0.76; p < 0.001), which had a bias of 3.4 degrees. The results demonstrate that the mFTA can be quantified accurately using an imageless, non-invasive functional approach, which also offers greater accuracy over regression methods.These new techniques could provide an accurate, non-invasive approach for quantifying frontal plane alignment, particularly in cases where X-rays may not be available.

A survey of formal methods for determining functional joint axes.

Axes of rotation e.g. at the knee, are often generated from clinical gait analysis data to be used in the assessment of kinematic abnormalities, the diagnosis of disease, or the ongoing monitoring of a patient's condition. They are additionally used in musculoskeletal models to aid in the description of joint and segment kinematics for patient specific analyses. Currently available methods to describe joint axes from segment marker positions share the problem that when one segment is transformed into the coordinate system of another, artefacts associated with motion of the markers relative to the bone can become magnified. In an attempt to address this problem, a symmetrical axis of rotation approach (SARA) is presented here to determine a unique axis of rotation that can consider the movement of two dynamic body segments simultaneously, and then compared its performance in a survey against a number of previously proposed techniques. Using a generated virtual joint, with superimposed marker error conditions to represent skin movement artefacts, fitting methods (geometric axis fit, cylinder axis fit, algebraic axis fit) and transformation techniques (axis transformation technique, mean helical axis, Schwartz approach) were classified and compared with the SARA. Nearly all approaches were able to estimate the axis of rotation to within an RMS error of 0.1cm at large ranges of motion (90 degrees ). Although the geometric axis fit produced the least RMS error of approximately 1.2 cm at lower ranges of motion (5 degrees ) with a stationary axis, the SARA and Axis Transformation Technique outperformed all other approaches under the most demanding marker artefact conditions for all ranges of motion. The cylinder and algebraic axis fit approaches were unable to compute competitive AoR estimates. Whilst these initial results using the SARA are promising and are fast enough to be determined "on-line", the technique must now be proven in a clinical environment.

Tibio-femoral joint contact forces in sheep.

Although the sheep has become a standard model for understanding the mechanical conditions that occur after injury and investigating surgical treatments such as osteochondral defect healing and ligament reconstruction, no study has yet evaluated the contact forces that occur in the sheep tibio-femoral joint in vivo. In this study, bone pins, together with reflective markers, were used to measure the 3D kinematics of three sheep hind limbs, simultaneously with the ground reaction forces during repetitions of gait trials. Joint contact forces were then calculated using inverse dynamics and optimisation techniques. Whilst average peak axial tibio-femoral contact forces of 2.1 body weight (BW) were calculated across the 3 sheep, only small medio-lateral and antero-posterior shear forces, averaging 0.7 BW, were determined. Average knee flexion angles ranging from 49 degrees to 70 degrees were observed. From the forces determined in this study, we have provided a better understanding of the mechanical loading environment that occurs in sheep. This has important implications for the interpretation of knee studies in quadrupeds and their relevance to the clinical situation.

A survey of formal methods for determining the centre of rotation of ball joints.

The determination of an accurate centre of rotation (CoR) from segment marker positions is of interest across a wide range of applications, but particularly for clinical gait analysis and for estimating the hip joint centre during surgical intervention of the knee, for limb alignment purposes. For the first time in this survey of formal methods, we classify, analyse and compare different methods (geometric, algebraic, bias compensated algebraic, and Pratt sphere fit methods, as well as the centre transformation technique, the Holzreiter approach, the helical pivot technique, the Schwartz transformation techniques, the minimal amplitude point method and the Stoddart approach) for the determination of spherical joint centres from marker position data. In addition, we propose a new method, the symmetrical CoR estimation or SCoRE, in which the coordinates of the joint centre must only remain constant relative to each segment, thus not requiring the assumption that one segment should remain at rest. For each method, 1000 CoR estimations were analysed with the application of isotropic, independent and identically distributed Gaussian noise (standard deviation 0.1cm) to each of the marker positions, to all markers on the segment simultaneously and the two in combination. For the test conditions used here, most techniques were capable of determining the CoR to within 0.3 cm, as long as the spherical range of motion (RoM) of the joint was 45 degrees or more. Under the most stringent conditions tested, however, the SCoRE was capable of best determining the CoR, to within approximately 1.2mm with a RoM of 20 degrees . The correct selection and application of these methodologies should help improve the accuracy of surgical navigation and clinical kinematic measurement.

On the influence of soft tissue coverage in the determination of bone kinematics using skin markers.

Accurate measurement of underlying bone positions is important for the understanding of normal movement and function, as well as for addressing clinical musculoskeletal or post-injury problems. Non-invasive measurement techniques are limited by the analysis technique and movement of peripheral soft tissues that can introduce significant measurement errors in reproducing the kinematics of the underlying bones when using external skin markers. Reflective markers, skeletally mounted to the right hind limb of three Merino-mix sheep were measured simultaneously with markers attached to the skin of each segment, during repetitions of gait trials. The movement of the skin markers relative to the underlying bone positions was then assessed using the Point Cluster Technique (PCT), raw averaging and the Optimal Common Shape Technique (OCST), a new approach presented in this manuscript. Errors in the position of the proximal joint centre, predicted from the corresponding skin markers, were shown to be phasic and strongly associated with the amount soft tissue coverage, averaging 8.5 mm for the femur, 2.8 for the tibia and 2.0 for the metatarsus. Although the results show a better prediction of bone kinematics associated with the Optimal Common Shape Technique, these errors were large for all three assessment techniques and much greater than the differences between the various techniques. Whilst individual markers moved up to 4 mm from the optimal marker set configuration, average peak errors of up to 16, 5 and 3 mm (hip, knee and tibio-metatarsal joints respectively) were observed, suggesting that a large amount of kinematic noise is produced from the synchronous shifting of marker sets, potentially as a result of underlying muscle firing and the inertial effects of heel impact. Current techniques are therefore limited in their ability to determine the kinematics of underlying bones based on skin markers, particularly in segments with more pronounced soft tissue coverage.