Protocol for constructing subject-specific biomechanical models of knee joint

A robust protocol for building subject-specific biomechanical models of the human knee joint is proposed which uses magnetic resonance imaging, motion analysis and force platform data in conjunction with detailed 3D finite element models. The proposed protocol can be used for determining stress and strain distributions and contact kinetics in different knee elements at different body postures during various physical activities. Several examples are provided to highlight the capabilities and potential applications of the proposed protocol. This includes preliminary results on the role of body weight on the stresses and strains induced in the knee articular cartilages and meniscus during single-leg stance and calculations of the induced stresses and ligament forces during the gait cycle.     

Surface EMG and torsion measurements during snow skiing: laboratory and field tests

The relationship between mean rectified EMG (MREMG) measured with surface electrodes and the longitudinal torsion of the lower extremity was investigated in laboratory and snow skiing experiments. Linear regression of the MREMG from the gluteus medius and the peroneus longus with the torsion measured at the foot in the laboratory tests showed that torsion can be predicted with correlation coefficients greater than 0.95 and with a standard deviation less than 5 Nm over all knee flexions and weight bearing. A similar correspondence between MREMG and torsion during skiing does not exist. MREMG is dominantly correlated to posture and body position control functions in skiing. During falling, during ski binding release, and during possible injury sustaining situations, the MREMG was always relatively large, but it was not distinguishable from that associated with smaller torsion of the lower extremity.     

In vitro analysis of varus-valgus laxity of the knee joint: Comparison of clinical evaluation with measurements using a reference motion analysis system

IntroductionNumerous measurement devices can help clinicians during the knee examination. However, manual evaluation still remains routinely used to assess the knee laxities. The present study evaluated how accurate was a clinician for a varus-valgus stress test. We compared the clinician evaluation to the objective measurement of the knee movements during the same test session.MethodsWe studied six fresh-frozen anatomical lower limbs. The clinician performed a varus-valgus stress test in extension and at 25° flexion. The limbs were equipped with intracortical pins in femur and tibia, and spherical retro-reflecting markers were glued on the pins. Objective knees movements were measured by means of a Motion Analysis^® system (Motion Analysis Corporation, Santa Rosa, CA, USA). Two statistical analyses were performed. A single sample t-test was first used to verify the required 25? flexion. Then, a multivariate anova was performed to analyse the varus-valgus laxity under the fixed factors of measurement method and flexion of the knee.ResultsThe results for varus-valgus and total laxity of the clinician always exhibited a greater variability than objective measurements of the device. Test condition is a factor of grouping differences for Valgus and for global mediolateral laxity. Statistical analysis revealed that the objective measurement was able to show a difference between extension and 25° flexion for global mediolateral laxity, whereas the clinician was not.DiscussionThe clinician was relatively accurate in his manual evaluation. However, we demonstrated that a measurement device could clearly help clinician to exhibit differences in laxity. This can be very useful to compare a knee to itself in two successive conditions, e.g., before and after a surgery.     

Human locomotion on snow: determinants of economy and speed of skiing across the ages

We explore here the evolution of skiing locomotion in the last few thousand years by investigating how humans adapted to move effectively in lands where a cover of snow, for several months every year, prevented them from travelling as on dry ground. Following historical research, we identified the sets of skis corresponding to the 'milestones' of skiing evolution in terms of ingenuity and technology, built replicas of them and measured the metabolic energy associated to their use in a climate-controlled ski tunnel.Six sets of skis were tested, covering a span from 542 AD to date. Our results show that: (i) the history of skiing is associated with a progressive decrease in the metabolic cost of transport, (ii) it is possible today to travel at twice the speed of ancient times using the same amount of metabolic power and (iii) the cost of transport is speed-independent for each ski model, as during running. By combining this finding with the relationship between time of exhaustion and the sustainable fraction of metabolic power, a prediction of the maximum skiing speed according to the distance travelled is provided for all past epochs, including two legendary historical journeys (1206 and 1520 AD) on snow. Our research shows that the performances in races originating from them (Birkebeiner and Vasaloppet) and those of other modern competitions (skating versus classical techniques) are well predicted by the evolution of skiing economy. Mechanical determinants of the measured progression in economy are also discussed in the paper.     

Simultaneous control of hand displacements and rotations in orientation-matching experiments.

In reach-to-grasp movements, the interaction between the hand changes in position and those in orientation is poorly understood. A theoretical approach previously proposed (Torres EB and Zipser D. J Neurophysiol 88: 1-13, 2002) assumes that motion strategies are resolved in space independently from the temporal dynamics of the motion and predicts the coarticulation of the hand transport and rotation along the path. The model implies that this simultaneous control is independent of variations in speed and initial posture and required matching orientation. This paper presents experimental data from human subjects that confirm the model's predictions in the context of realistic, unconstrained, orientation-matching motions. Speed independence is quantified in the similarity of the postural and endpoint position-orientation paths obtained under three different speeds. Significant differences in hand and joint kinematics are shown in response to changes in initial posture and target orientation. The robustness of coarticulation under all three experimental conditions supports the idea of an intermediate stage that resolves the geometry of the motion independent of its temporal dynamics.     

Memory for events and their spatial context: models and experiments

The computational role of the hippocampus in memory has been characterized as: (i) an index to disparate neocortical storage sites; (ii) a time-limited store supporting neocortical long-term memory; and (iii) a content-addressable associative memory. These ideas are reviewed and related to several general aspects of episodic memory, including the differences between episodic, recognition and semantic memory, and whether hippocampal lesions differentially affect recent or remote memories. Some outstanding questions remain, such as: what characterizes episodic retrieval as opposed to other forms of read-out from memory; what triggers the storage of an event memory; and what are the neural mechanisms involved? To address these questions a neural-level model of the medial temporal and parietal roles in retrieval of the spatial context of an event is presented. This model combines the idea that retrieval of the rich context of real-life events is a central characteristic of episodic memory, and the idea that medial temporal allocentric representations are used in long-term storage while parietal egocentric representations are used to imagine, manipulate and re-experience the products of retrieval. The model is consistent with the known neural representation of spatial information in the brain, and provides an explanation for the involvement of Papez''s circuit in both the representation of heading direction and in the recollection of episodic information. Two experiments relating to the model are briefly described. A functional neuroimaging study of memory for the spatial context of life-like events in virtual reality provides support for the model''s functional localization. A neuropsychological experiment suggests that the hippocampus does store an allocentric representation of spatial locations.     

Uncertainty of knee joint muscle activity during knee joint torque exertion: the significance of controlling adjacent joint torque.

In the single-joint torque exertion task, which has been widely used to control muscle activity, only the relevant joint torque is specified. However, the neglect of the neighboring joint could make the procedure unreliable, considering our previous result that even monoarticular muscle activity level is indefinite without specifying the adjacent joint torque. Here we examined the amount of hip joint torque generated with knee joint torque and its influence on the activity of the knee joint muscles. Twelve healthy subjects were requested to exert various levels of isometric knee joint torque. The knee and hip joint torques were obtained by using a custom-made device. Because no information about hip joint torque was provided to the subjects, the hip joint torque measured here was a secondary one associated with the task. The amount of hip joint torque varied among subjects, indicating that they adopted various strategies to achieve the task. In some subjects, there was a considerable internal variability in the hip joint torque. Such variability was not negligible, because the knee joint muscle activity level with respect to the knee joint torque, as quantified by surface electromyography (EMG), changed significantly when the subjects were requested to change the strategy. This change occurred in a very systematic manner: in the case of the knee extension, as the hip flexion torque was larger, the activity of mono- and biarticular knee extensors decreased and increased, respectively. These results indicate that the conventional single knee joint torque exertion has the drawback that the intersubject and/or intertrial variability is inevitable in the relative contribution among mono- and biarticular muscles because of the uncertainty of the hip joint torque. We discuss that the viewpoint that both joint torques need to be considered will bring insights into various controversial problems such as the shape of the EMG-force relationship, neural factors that help determine the effect of muscle strength training, and so on.     

Measurement of strength and loading variables on the knee during Alpine skiing

The study focusses on the prevention of knee injuries during snow skiing. In order to develop a technology of knee injury prevention, both the strength and loading on the knee during skiing activity must be known. This paper reports measurements of variables influencing both knee strength and loading of the joint. The strength variables measured included the degree of activity in six muscles crossing the knee, the knee flexion angle, and the axial load (i.e. weight bearing) transmitted to the knee. Transducers included surface electrodes to monitor electromyogram signals indicating the degree of muscle activity and a goniometer to measure both hip and knee flexion angles. The complete loading on the knee was derived from a dynamometer which measured the six load components at the boot-dynamometer interface. The transducer data were acquired and stored by a compact, battery powered digital data acquisition-controller system. Three male subjects of similar physical size (nominal was 1.8 m and 75 kg) and skiing ability (advanced intermediate to expert) were tested under similar conditions. Each subject skied a total of four slalom runs--one snowplow and three parallel. The total time of each test was 21 s. Example data plots from different types of runs are presented and discussed. Based on observations from the data, necessary performance features for ski bindings offering improved protection from knee ligamentous injuries are defined.     

Morphomechanics: goals, basic experiments and models

Morphomechanics is a branch of developmental biology, studying the generation, space-time patterns and morphogenetic role of mechanical stresses (MS) which reside in embryonic tissues. All the morphogenetically active embryonic tissues studied in this respect have been shown to bear substantial mechanical stresses of tension or pressure. MS are indispensable for organized cell movements, expression of a number of developmentally important genes and the very viability of cells. Even a temporary relaxation of MS leads to an increase in the morphological variability and asymmetry of embryonic rudiments. Moreover, MS may be among the decisive links of morphogenetic feedback required for driving forth embryonic development and providing its regular space-time patterns. We hypothesize that one such feedback is based upon the tendency of cells and tissues to hyperrestore (restore with an overshoot) their MS values after any deviations, either artificial or produced by neighboring morphogenetically active tissues. This idea is supported by a number of observations and experiments performed on the tissue and individual cell levels. We describe also the models demonstrating that a number of biologically realistic stationary shapes and propagating waves can be generated by varying the parameters of the hyperrestoration feedback loop. Morphomechanics is an important and rapidly developing branch of developmental and cell biology, being complementary to other approaches.     

Effect of knee joint flexion and femur rotation on retropatellar contact of the human knee joint]

The aim of the present study was to evaluate retropatellar contact characteristics at different angles of flexion of the knee joint. To this end, 6 cadaveric legs were examined using pressure sensitive film (Fuji Prescale type "super low") at angles of flexion of 45 degrees, 60 degrees, 90 degrees and 120 degrees both in neutral rotation and 10 degrees internal and external rotation of the femur in the same knee joints. A force of 140 N was applied to both the vastus medialis and lateralis, and a comparison made with a medially and a laterally dominating muscle force. The contact areas decreased with increasing angles of flexion. The medially dominating muscle traction increased the contact area. Comparison between internal and external rotation revealed a decrease in contact area on internal rotation. The pressure measurements were comparable in all loading situations. Comparison between neutral and medial traction revealed significant differences in contact area, pressure and force. The influence of femoral rotation showed no significant difference. A comparison of the different angles of flexion revealed only few significant differences. To prevent the development of retropatellar arthrosis, maximum contact areas are necessary. The study has shown an advantage for medially dominating muscle traction, and external rotation of the femur.     

Pigmentation pattern formation in butterflies: experiments and models

Butterfly pigmentation patterns are one of the most spectacular and vivid examples of pattern formation in biology. They have attracted much attention from experimentalists and theoreticians, who have tried to understand the underlying genetic, chemical and physical processes that lead to patterning. In this paper, we present a brief review of this field by first considering the generation of the localised, eyespot, patterns and then the formation of more globally controlled patterns. We present some new results applied to pattern formation on the wing of the mimetic butterfly Papilio dardanus.     

Speciation by natural and sexual selection: models and experiments

A large number of mathematical models have been developed that show how natural and sexual selection can cause prezygotic isolation to evolve. This article attempts to unify this literature by identifying five major elements that determine the outcome of speciation caused by selection: a form of disruptive selection, a form of isolating mechanism (assortment or a mating preference), a way to transmit the force of disruptive selection to the isolating mechanism (direct selection or indirect selection), a genetic basis for increased isolation (a one- or two-allele mechanism), and an initial condition (high or low initial divergence). We show that the geographical context of speciation (allopatry vs. sympatry) can be viewed as a form of assortative mating. These five elements appear to operate largely independently of each other and can be used to make generalizations about when speciation is most likely to happen. This provides a framework for interpreting results from laboratory experiments, which are found to agree generally with theoretical predictions about conditions that are favorable to the evolution of prezygotic isolation.     

Assembly and mechanosensory function of focal adhesions: experiments and models

Initial integrin-mediated cell-matrix adhesions (focal complexes) appear underneath the lamellipodia, in the regions of the "fast" centripetal flow driven by actin polymerization. Once formed, these adhesions convert the flow behind them into a "slow", myosin II-driven mode. Some focal complexes then turn into elongated focal adhesions (FAs) associated with contractile actomyosin bundles (stress fibers). Myosin II inhibition does not suppress formation of focal complexes but blocks their conversion into mature FAs and further FA growth. Application of external pulling force promotes FA growth even under conditions when myosin II activity is blocked. Thus, individual FAs behave as mechanosensors responding to the application of force by directional assembly. We proposed a thermodynamic model for the mechanosensitivity of FAs, taking into account that an elastic molecular aggregate subject to pulling forces tends to grow in the direction of force application by incorporating additional subunits. This simple model can explain a variety of processes typical of FA behavior. Assembly of FAs is triggered by the small G-protein Rho via activation of two major targets, Rho-associated kinase (ROCK) and the formin homology protein, Dia1. ROCK controls creation of myosin II-driven forces, while Dia1 is involved in the response of FAs to these forces. Expression of the active form of Dia1, allows the external force-induced assembly of mature FAs, even in conditions when Rho is inhibited. Conversely, downregulation of Dia1 by siRNA prevents FA maturation even if Rho is activated. Dia1 and other formins cap barbed (fast growing) ends of actin filaments, allowing insertion of the new actin monomers. We suggested a novel mechanism of such "leaky" capping based on an assumption of elasticity of the formin/barbed end complex. Our model predicts that formin-mediated actin polymerization should be greatly enhanced by application of external pulling force. Thus, the formin-actin complex might represent an elementary mechanosensing device responding to force by enhancement of actin assembly. In addition to its role in actin polymerization, Dia1 seems to be involved in formation of links between actin filaments and microtubules affecting microtubule dynamics. Alpha-tubulin deacetylase HDAC6 cooperates with Dia1 in formation of such links. Since microtubules are known to promote FA disassembly, the Dia1-mediated effect on microtubule dynamics may possibly play a role in the negative feedback loop controlling size and turnover of FAs.     

Linear models for joint association and linkage QTL mapping

Background

Populational linkage disequilibrium and within-family linkage are commonly used for QTL mapping and marker assisted selection. The combination of both results in more robust and accurate locations of the QTL, but models proposed so far have been either single marker, complex in practice or well fit to a particular family structure.

Results

We herein present linear model theory to come up with additive effects of the QTL alleles in any member of a general pedigree, conditional to observed markers and pedigree, accounting for possible linkage disequilibrium among QTLs and markers. The model is based on association analysis in the founders; further, the additive effect of the QTLs transmitted to the descendants is a weighted (by the probabilities of transmission) average of the substitution effects of founders'' haplotypes. The model allows for non-complete linkage disequilibrium QTL-markers in the founders. Two submodels are presented: a simple and easy to implement Haley-Knott type regression for half-sib families, and a general mixed (variance component) model for general pedigrees. The model can use information from all markers. The performance of the regression method is compared by simulation with a more complex IBD method by Meuwissen and Goddard. Numerical examples are provided.

Conclusion

The linear model theory provides a useful framework for QTL mapping with dense marker maps. Results show similar accuracies but a bias of the IBD method towards the center of the region. Computations for the linear regression model are extremely simple, in contrast with IBD methods. Extensions of the model to genomic selection and multi-QTL mapping are straightforward.