How changing the inversion/eversion foot angle affects the nondriving intersegmental knee moments and the relative activation of the vastii muscles in cycling

Nondriving intersegmental knee moment components (i.e., varus/valgus and internal/external axial moments) are thought to be primarily responsible for the etiology of overuse knee injuries such as patellofermoral pain syndrome in cycling because of their relationship to muscular imbalances. However the relationship between these moments and muscle activity has not been studied. Thus the four primary objectives of this study were to test whether manipulating the inversion/eversion foot angle alters the varus/valgus knee moment (Objective 1) and axial knee moment (Objective 2) and to determine whether activation patterns of the vastus medialis oblique (VMO), vastus lateralis (VL), and tensor fascia latae (TFL) were affected by changes in the varus/valgus (Objective 3) and axial knee moments (Objective 4). To fulfill these objectives, pedal loads and lower limb kinematic data were collected from 15 subjects who pedaled with five randomly assigned inversion/eversion angles: 10 deg and 5 deg everted and inverted and 0 deg (neutral). A previously described mathematical model was used to compute the nondriving intersegmental knee moments throughout the crank cycle. The excitations of the VMO, VL, and TFL muscles were measured with surface electromyography and the muscle activations were computed. On average, the 10-deg everted position decreased the peak varus moment by 55% and decreased the peak internal axial moment by 53% during the power stroke (crank cycle region where the knee moment is extensor). A correlation analysis revealed that the VMO/VL activation ratio increased significantly and the TFL activation decreased significantly as the varus moment decreased. For both the VMO/VL activation ratio and the TFL activation, a path analysis indicated that the varus/valgus moment was highly correlated to the axial moment but that the correlation between muscle activation and the varus moment was due primarily to the varus/valgus knee moment rather than the axial knee moment. The conclusion from these results is that everting the foot may be beneficial towards either preventing or ameliorating patellofemoral pain syndrome in cycling.     

In vitro study of foot kinematics using a dynamic walking cadaver model

There is a dearth of information on navicular, cuboid, cuneiform and metatarsal kinematics during walking and our objective was to study the kinematic contributions these bones might make to foot function. A dynamic cadaver model of walking was used to apply forces to cadaver feet and mobilise them in a manner similar to in vivo. Kinematic data were recorded from 13 cadaver feet. Given limitations to the simulation, the data describe what the cadaver feet were capable of in response to the forces applied, rather than exactly how they performed in vivo. The talonavicular joint was more mobile than the calcaneocuboid joint. The range of motion between cuneiforms and navicular was similar to that between talus and navicular. Metatarsals four and five were more mobile relative to the cuboid than metatarsals one, two and three relative to the cuneiforms. This work has confirmed the complexity of rear, mid and forefoot kinematics. The data demonstrate the potential for often-ignored foot joints to contribute significantly to the overall kinematic function of the foot. Previous emphasis on the ankle and sub talar joints as the principal articulating components of the foot has neglected more distal articulations. The results also demonstrate the extent to which the rigid segment assumptions of previous foot kinematics research have over simplified the foot.     

Error in the description of foot kinematics due to violation of rigid body assumptions

Kinematic data from rigid segment foot models inevitably includes errors because the bones within each segment move relative to each other. This study sought to define error in foot kinematic data due to violation of the rigid segment assumption. The research compared kinematic data from 17 different mid and forefoot rigid segment models to kinematic data of the individual bones comprising these segments. Kinematic data from a previous dynamic cadaver model study was used to derive individual bone as well as foot segment kinematics.Mean and maximum errors due to violation of the rigid body assumption varied greatly between models. The model with least error was the combination of navicular and cuboid (mean errors <=1.3°, average maximum error <=2.4°). Greatest error was seen for the model combining all the ten bones (mean errors <=4.4°, average maximum errors <=6.9°). Based on the errors reported a three segment mid and forefoot model is proposed: (1) Navicular and cuboid, (2) cuneiforms and metatarsals 1, 2 and 3, and (3) metatarsals 4 and 5. However the utility of this model will depend on the precise purpose of the in vivo foot kinematics research study being undertaken.     

Prediction of total knee motion using a three-dimensional computer-graphics model

Twenty-three knees were sectioned, digitized, and standardized to determine the 'average' three-dimensional bony geometry and ligamentous attachments. Data on normal knee motion were obtained from a cadaveric study. An algorithm was written to simulate three-dimensional patella motion. Verification of the knee model was achieved by determining femoro-tibial and patello-femoral contact locations, as well as ligament length patterns, and comparing the results with published data. The criterion for maximum predicted knee motion with a prosthesis in place was the length of the posterior cruciate ligament. Three total knee replacement surfaces were mathematically generated: flat, laxity and conforming. A greater flexion angle was obtained with a flat tibial surface than for the laxity or conforming. Posterior tibial component displacement increased the range of motion, but only slightly. For all tibial surfaces, increased range of motion was achieved with a 10 degrees posterior tilt of the tibial tray. Anterior femoral component displacement increased motion due to reduction in posterior cruciate tension during flexion. The results are applicable to the design and surgical technique of total knee replacement.     

Ligament-bone interaction in a three-dimensional model of the knee

In mathematical knee-joint models, the ligaments are usually represented by straight-line elements, connecting the insertions of the femur and tibia. Such a model may not be valid if a ligament is bent in its course over bony-surfaces, particularly not if the resulting redirection of the ligament force has a considerable effect on the laxity or motion characteristics of the knee-joint model. In the present study, a model for wrapping of a ligament around bone was incorporated in a three-dimensional mathematical model of the human knee. The bony edge was described by a curved line on which the contact point of the line element representing a ligament bundle was located. Frictionless contact between the ligament bundle and the bone was assumed. This model was applied to the medial collateral ligament (MCL) interacting with the bony edge of the tibia. It was found that, in comparison with the original model without bony interactions, the bony edge redirected the ligament force of the MCL in such a way that it counterbalanced valgus moments on the tibia more effectively. The effect of the bony interaction with the MCL on the internal-external rotation laxity, however, was negligible.     

The effect of simplifying assumptions in the bidomain model of cardiac tissue: application to ST segment shifts during partial ischaemia

In this study various electrical conductivity approximations used in bidomain models of cardiac tissue are considered. Comparisons are based on epicardial surface potential distributions arising from regions of subendocardial ischaemia situated within the cardiac tissue. Approximations studied are a single conductivity bidomain model, an isotropic bidomain model and equal and reciprocal anisotropy ratios both with and without fibre rotation. It is demonstrated both analytically and numerically that the approximations involving a single conductivity bidomain, an isotropic bidomain or equal anisotropy ratios (ignoring fibre rotation) results in identical epicardial potential distributions for all degrees of subendocardial ischaemia. This result is contrary to experimental observations. It is further shown that by assuming reciprocal anisotropy ratios, epicardial potential distributions vary with the degree of subendocardial ischaemia. However, it is concluded that unequal anisotropy ratios must be used to obtain the true character of experimental observations.     

Comparison of kinematics in the healthy and ACL injured knee using MRI

Magnetic Resonance Imaging (MRI) was used to examine the characteristics of abnormal motion in the injured knee by mapping tibiofemoral contact. Eleven healthy subjects and 20 subjects with a unilateral ACL injury performed a leg-press against resistance. MRI scans of both knees at 15 degrees intervals from 0 degrees to 90 degrees of flexion were used to record the tibiofemoral contact pattern. The tibiofemoral contact pattern of the injured knees was more posterior on the tibial plateau than the healthy knees, particularly in the lateral compartment. The tibiofemoral contact pattern of the loaded knees did not differ from the unloaded knees. The difference in the tibiofemoral contact pattern in the ACL injured knee was associated with more severe knee symptoms, irrespective of the passive anterior laxity of the knee.     

Introducing a novel test with unanticipated medial/lateral diagonal hops that reliably captures hip and knee kinematics in healthy women

Despite a vast literature on one-leg hops and cutting maneuvers assessing knee control pre/post-injury of the anterior cruciate ligament (ACL), comprehensive and reliable tests performed under unpredictable conditions are lacking. This study aimed to: (1) assess the feasibility of an innovative, knee-challenging, one-leg double-hop test consisting of a forward hop followed by a diagonal hop (45°) performed medially (UMDH) or laterally (ULDH) in an unanticipated manner; and (2) determine within- and between-session reliability for 3-dimensional hip and knee kinematics and kinetics of these tests. Twenty-two healthy women (22.3 ± 3.3 years) performed three successful UMDH and ULDH, twice 1–4 weeks apart. Hop success rate was 69–84%. Peak hip and knee angles demonstrated moderate to excellent within-session reliability (intraclass correlation coefficient [ICC] 95% confidence interval [CI]: 0.67–0.99, standard error of measurement [SEM] ≤  3°) and poor to excellent between-session reliability (ICC CI: 0.22–0.94, SEM ≤ 3°) for UMDH and ULDH. The smallest real difference (SRD) was low (≤ 5°) for nearly all peak angles. Peak hip and knee moments demonstrated poor to excellent reliability (ICC CI: 0–0.97) and, in general, moments were more reliable within-session (SEM ≤ 0.14 N.m/kg.m, both directions) than between-session (SRD ≤ 0.43 N.m/kg.m). Our novel test was feasible and, in most but not all cases, provided reliable angle estimates (within-session > between-session, both directions) albeit less reliable moments (within-session > between-session, both directions). The relatively large hip and knee movements in the frontal and transverse planes during the unanticipated hops suggest substantial challenge of dynamic knee control. Thus, the test seems appropriate for evaluating knee function during ACL injury rehabilitation.     

Approximation of the functional kinematics of posterior stabilised total knee replacements using a two-dimensional sagittal plane patello-femoral model: comparing model approximation to in vivo measurement

Previous in vivo studies have observed that current designs of posterior stabilised (PS) total knee replacements (TKRs) may be ineffective in restoring normal kinematics in Late flexion. Computer-based models can prove a useful tool in improving PS knee replacement designs. This study investigates the accuracy of a two-dimensional (2D) sagittal plane model capable of predicting the functional sagittal plane kinematics of PS TKR implanted knees against direct in vivo measurement. Implant constraints are often used as determinants of anterior–posterior tibio-femoral positioning. This allowed the use of a patello-femoral modelling approach to determine the effect of implant constraints. The model was executed using motion simulation software which uses the constraint force algorithm to achieve a solution. A group of 10 patients implanted with Scorpio PS implants were recruited and underwent fluoroscopic imaging of their knees. The fluoroscopic images were used to determine relative implant orientation using a three-dimensional reconstruction method. The determined relative tibio-femoral orientations were then input to the model. The model calculated the patella tendon angles (PTAs) which were then compared with those measured from the in vivo fluoroscopic images. There were no significant differences between the measured and calculated PTAs. The average root mean square error between measured and modelled ranged from 1.17° to 2.10° over the flexion range. A sagittal plane patello-femoral model could conceivably be used to predict the functional 2D kinematics of an implanted knee joint. This may prove particularly useful in optimising PS designs.     

A computational model for the prediction of total knee replacement kinematics in the sagittal plane

A computational model has been developed using a current generation computer-aided engineering (CAE) package to predict total knee replacement (TKR) kinematic in the sagittal plane. The model includes friction and soft tissue restraint varying according to the flexion angle. The model was validated by comparing the outcomes of anterior-posterior (A-P) laxity tests of two contemporary knee replacements against data obtained from a knee simulating machine. It was also validated against predictions from a computer model reported in the literature. Results show good agreement in terms of A-P displacements. Further tests were performed to determined the influence of the soft tissue restraints varying with flexion angle. This work represents the first attempt to use a sophisticated commercial CAE package to predict TKR motions and the advantages of the modelling procedure chosen are discussed.     

Tibio-femoral movement in the living knee. A study of weight bearing and non-weight bearing knee kinematics using 'interventional' MRI

The aim of this study was to image tibio-femoral movement during flexion in the living knee. Ten loaded male Caucasian knees were initially studied using MRI, and the relative tibio-femoral motions, through the full flexion arc in neutral tibial rotation, were measured. On knee flexion from hyperextension to 120 degrees , the lateral femoral condyle moved posteriorly 22 mm. From 120 degrees to full squatting there was another 10 mm of posterior translation, with the lateral femoral condyle appearing almost to sublux posteriorly. The medial femoral condyle demonstrated minimal posterior translation until 120 degrees . Thereafter, it moved 9 mm posteriorly to lie on the superior surface of the medial meniscal posterior horn. Thus, during flexion of the knee to 120 degrees , the femur rotated externally through an angle of 20 degrees . However, on flexion beyond 120 degrees , both femoral condyles moved posteriorly to a similar degree. The second part of this study investigated the effect of gender, side, load and longitudinal rotation. The pattern of relative tibio-femoral movement during knee flexion appears to be independent of gender and side. Femoral external rotation (or tibial internal rotation) occurs with knee flexion under loaded and unloaded conditions, but the magnitude of rotation is greater and occurs earlier on weight bearing. With flexion plus tibial internal rotation, the pattern of movement follows that in neutral. With flexion in tibial external rotation, the lateral femoral condyle adopts a more anterior position relative to the tibia and, particularly in the non-weight bearing knee, much of the femoral external rotation that occurs with flexion is reversed.     

Optimal control analysis of a malaria disease transmission model that includes treatment and vaccination with waning immunity

We derive and analyse a deterministic model for the transmission of malaria disease with mass action form of infection. Firstly, we calculate the basic reproduction number, R(0), and investigate the existence and stability of equilibria. The system is found to exhibit backward bifurcation. The implication of this occurrence is that the classical epidemiological requirement for effective eradication of malaria, R(0)<1, is no longer sufficient, even though necessary. Secondly, by using optimal control theory we derive the conditions under which it is optimal to eradicate the disease and examine the impact of a possible combined vaccination and treatment strategy on the disease transmission. When eradication is impossible, we derive the necessary conditions for optimal control of the disease using Pontryagin's Maximum Principle. The results obtained from the numerical simulations of the model show that a possible vaccination combined with effective treatment regime would reduce the spread of the disease appreciably.     

Variability of a three-dimensional finite element model constructed using magnetic resonance images of a knee for joint contact stress analysis

Magnetic resonance (MR) imaging has been widely used to evaluate the thickness and volume of articular cartilage both in vivo and in vitro. While morphological information on the cartilage can be obtained using MR images, image processing for extracting geometric boundaries of the cartilage may introduce variations in the thickness of the cartilage. To evaluate the variability of using MR images to construct finite element (FE) knee cartilage models, five investigators independently digitized the same set of MR images of a human knee. The topology of cartilage thickness was determined using a minimal distance algorithm. Less than 8 percent variation in cartilage thickness was observed from the digitized data. The effect of changes in cartilage thickness on contact stress analysis was then investigated using five FE models of the knee. One FE model (average FE model) was constructed using the mean values of the digitized contours of the cartilage, and the other four were constructed by varying the thickness of the average FE model by +/- 5 percent and +/- 10 percent, respectively. The results demonstrated that under axial tibial compressive loading (up to 1,400 N), variations of cartilage thickness caused by digitization of MR images may result in a difference of approximately 10 percent in peak contact stresses (surface pressure, von Mises stress, and hydrostatic pressure) in the cartilage. A reduction of cartilage thickness caused increases of contact stresses, while an increase of cartilage thickness reduced contact stresses. Furthermore, the effect of variation of material properties of the cartilage on contact stress analysis was investigated. The peak contact stress increased almost linearly with the Young's modulus of the cartilage. The peak von Mises stress was dramatically reduced when the Poisson,s ratio was increased from 0.05 to 0.49 under an axial compressive load of 1,400 N, while peak hydrostatic pressure was dramatically increased. Peak surface pressure was also increased with the Poisson's ratio, but with a lower magnitude compared to von Mises stress and hydrostatic pressure. In conclusion, the imaging process may cause 10 percent variations in peak contact stress, and the predicted stress distribution is sensitive to the accuracy of the material properties of the cartilage model, especially to the variation of Poisson's ratio.     

Rotational flexibility of the human knee due to varus/valgus and axial moments in vivo

Knee ligamentous injuries persist in the sport of Alpine skiing. To better understand the load mechanisms which lead to injury, pure varus/valgus and pure axial moments were applied both singly and in combination to the right knees of six human test subjects. The corresponding relative knee rotations in three degrees of freedom were measured. Knee flexion angles for each test subject were 15 and 60 degrees for the individual moments and 60 degrees for the combination moments. For both knee flexion angles the hip flexion angle was 0 degrees. Leg muscles were quiescent and axial force was minimal during all tests. Tables of data include sample statistics for each of four flexibility parameters in each loading direction. Data were analyzed statistically to test for significant differences in flexibility parameters between the test conditions. In flexing the knee from 15 to 60 degrees, the resulting knee rotations under single moments depended upon flexion angle with varus, valgus, and internal rotations increasing significantly. Also, rotations were different depending on load direction; varus rotation was significantly different and greater than valgus rotation at both flexion angles. Also external rotation was significantly different and greater than internal at 15 degrees flexion, but not at 60 degrees flexion. Coupled rotations under single moments were also observed. Applying pure varus/valgus moments resulted in coupled external/internal rotations which were inconsistent and hence not significant. Applying pure axial moments resulted in consistent and hence significant varus/valgus rotations; an external axial moment induced varus rotation and an internal axial moment induced valgus rotation. For combination moments, varus/valgus rotations decreased significantly from those rotations at similar load levels in the single moment studies. Also, a varus moment significantly increased external rotation and a valgus moment significantly decreased internal rotation. These differences indicate significant interaction between corresponding load combinations. These results suggest that load interaction is a potentially important phenomenon in knee injury mechanics.     

Acetylcholine and bradykinin trigger preconditioning in the heart through a pathway that includes Akt and NOS

In the rabbit heart, bradykinin and ACh trigger preconditioning by a mechanism involving ATP-sensitive potassium channel-dependent production of reactive oxygen species (ROS). Recent evidence indicates that the pathway by which bradykinin causes ROS generation includes nitric oxide synthase (NOS) and protein kinase G (PKG). On the other hand, Akt was shown to be essential for ACh to generate ROS. This study determines whether these two G-coupled receptor agonists indeed have similar signaling targets, i.e., whether Akt is involved in bradykinin's pathway and whether NOS is involved in ACh's pathway. Isolated adult rabbit cardiomyocytes were incubated for 15 min in reduced MitoTracker red, which becomes fluorescent only after exposure to ROS. Bradykinin (400 nM) and ACh (250 microM) caused a 51.4 +/- 14.8% and 39.8 +/- 11.7% increase, respectively, in ROS production (P <0.005). Coincubation of either agonist with Akt inhibitor (20 microM) or infection of cells with an adenovirus containing dominant negative Akt abolished this increase. The NO donor S-nitroso-N-acetyl penicillamine (SNAP, 1 microM) also increased the ROS signal by 40.8 +/- 15.7%, but this increase was unaffected by Akt inhibitor (39.0 +/- 6.4%), implying that Akt is upstream of NOS. ACh-induced ROS production could be abolished by either of the NOS inhibitors Nomega-monomethyl-L-arginine monoacetate (100 microM) and L-N5-(1-iminoethyl)ornithine hydrochloride (L-NIO, 5 microM). L-NIO also blocked the anti-infarct effect of ACh (550 microM) in isolated rabbit hearts exposed to 30 min of regional ischemia. We conclude that both bradykinin and ACh trigger ROS generation by sequentially activating Akt and NOS.     

A range of complex probabilistic models for RNA secondary structure prediction that includes the nearest-neighbor model and more

The standard approach for single-sequence RNA secondary structure prediction uses a nearest-neighbor thermodynamic model with several thousand experimentally determined energy parameters. An attractive alternative is to use statistical approaches with parameters estimated from growing databases of structural RNAs. Good results have been reported for discriminative statistical methods using complex nearest-neighbor models, including CONTRAfold, Simfold, and ContextFold. Little work has been reported on generative probabilistic models (stochastic context-free grammars [SCFGs]) of comparable complexity, although probabilistic models are generally easier to train and to use. To explore a range of probabilistic models of increasing complexity, and to directly compare probabilistic, thermodynamic, and discriminative approaches, we created TORNADO, a computational tool that can parse a wide spectrum of RNA grammar architectures (including the standard nearest-neighbor model and more) using a generalized super-grammar that can be parameterized with probabilities, energies, or arbitrary scores. By using TORNADO, we find that probabilistic nearest-neighbor models perform comparably to (but not significantly better than) discriminative methods. We find that complex statistical models are prone to overfitting RNA structure and that evaluations should use structurally nonhomologous training and test data sets. Overfitting has affected at least one published method (ContextFold). The most important barrier to improving statistical approaches for RNA secondary structure prediction is the lack of diversity of well-curated single-sequence RNA secondary structures in current RNA databases.     

How the stiffness of meniscal attachments and meniscal material properties affect tibio-femoral contact pressure computed using a validated finite element model of the human knee joint

In an effort to prevent degeneration of articular cartilage associated with meniscectomies, both meniscal allografts and synthetic replacements are subjects of current interest and investigation. The objectives of the current study were to (1) determine whether a transversely isotropic, linearly elastic, homogeneous material model of the meniscal tissue is necessary to achieve a normal contact pressure distribution on the tibial plateau, (2) determine which material and boundary condition (attachments) parameters affect the contact pressure distribution most strongly, and (3) set tolerances on these parameters to restore the contact pressure distribution to within a specified error. To satisfy these objectives, a finite element model of the tibio-femoral joint of a human cadaveric knee (including both menisci) was used to study the contact pressure distribution on the tibial plateau. To validate the model, the contact pressure distribution on the tibial plateau was measured experimentally in the same knee used to create the model. Within physiologically reasonable bounds on five material parameters and four attachment parameters associated with a meniscal replacement, an optimization was performed under 1200 N of compressive load on the set of nine parameters to minimize the difference between the experimental and model results. The error between the experimental and model contact variables was minimized to 5.4%. The contact pressure distribution of the tibial plateau was sensitive to the circumferential modulus, axial/radial modulus, and horn stiffness, but relatively insensitive to the remaining six parameters. Consequently, both the circumferential and axial/radial moduli are important determinants of the contact pressure distribution, and hence should be matched in the design and/or selection of meniscal replacements. In addition, during surgical implantation of a meniscal replacement, the horns should be attached with high stiffness bone plugs, and the attachments of the transverse ligament and deep medial collateral ligament should be restored to minimize changes in the contact pressure distribution, and thereby possibly prevent the degradation of articular cartilage.     

Optimisation of solute transport in dialysers using a three-dimensional finite volume model

Dialyser manufacturers only provide limited information about mass removal under well-defined flow and solute conditions in commercially available dialysers for hemodialysis. This computational study aimed at assessing the solute transport efficiency in a dialyser for different geometries (fiber lengths and diameters). A three-dimensional finite volume model of a single fiber in a high flux polysulphone dialyser (Fresenius F60) was developed. Different equations describe blood and dialysate flow (Navier-Stokes), radial filtration flow (Darcy) and solute transport (convection-diffusion). Fluid and membrane properties were derived from in vitro and in vivo tests as well as from literature data. Urea (MW60) was used as marker to simulate small molecule removal, while middle molecule transport was modelled using vitamin B12 (MW1355) and inulin (MW5200). Keeping the fluid velocity in a single fiber constant, fiber diameter and length were changed in a wide range for evaluation of solute removal efficiency. Clearances were found enhanced by 13% (urea), 50% (vitamin B12) and 89% (inulin) for a fiber twice as long as a standard one and by 5.5% (vitamin B12) and 21% (inulin) for a fiber diameter of 150 mum instead of 200 mum. The impact of fiber dimensions was more pronounced for the middle molecules compared to urea.