Effects of hip joint centre mislocation on gait kinematics of children with cerebral palsy calculated using patient-specific direct and inverse kinematic models

Joint kinematics can be calculated by Direct Kinematics (DK), which is used in most clinical gait laboratories, or Inverse Kinematics (IK), which is mainly used for musculoskeletal research. In both approaches, joint centre locations are required to compute joint angles. The hip joint centre (HJC) in DK models can be estimated using predictive or functional methods, while in IK models can be obtained by scaling generic models. The aim of the current study was to systematically investigate the impact of HJC location errors on lower limb joint kinematics of a clinical population using DK and IK approaches. Subject-specific kinematic models of eight children with cerebral palsy were built from magnetic resonance images and used as reference models. HJC was then perturbed in 6mm steps within a 60mm cubic grid, and kinematic waveforms were calculated for the reference and perturbed models. HJC perturbations affected only hip and knee joint kinematics in a DK framework, but all joint angles were affected when using IK. In the DK model, joint constraints increased the sensitivity of joint range-of-motion to HJC location errors. Mean joint angle offsets larger than 5° were observed for both approaches (DK and IK), which were larger than previously reported for healthy adults. In the absence of medical images to identify the HJC, predictive or functional methods with small errors in anterior-posterior and medial-lateral directions and scaling procedures minimizing HJC location errors in the anterior-posterior direction should be chosen to minimize the impact on joint kinematics

Role of carbon dioxide and ion transport in the formation of sub-embryonic fluid by the blastoderm of the Japanese quail

1. The explanted blastoderm of the Japanese quail was used to explore the role of ions and carbon dioxide in determining the rate of sub-embryonic fluid (SEF) production between 54 and 72 h of incubation. 2. Amiloride, an inhibitor of Na+/H+ exchange, at concentrations of 10-3 to 10-6 M substantially decreased the rate of SEF production when added to the albumen culture medium. N-ethylmaleimide, an inhibitor of V type H+ ATPase, also decreased this rate but only to a small extent at the highest dose applied, 10-3 M. Both inhibitors had no effect on SEF production when added to the SEF. 3. The inhibitors of cellular bicarbonate and chloride exchange, 4-acetamido-4-'isothiocyano-2, 2-'disulphonic acid (SITS) and 4,4'diisothiocyanostilbene-2,2-'disulphonic acid (DIDS), had no effect upon SEF production. 4. Ouabain, an inhibitor of Na+/K+ ATPase, decreased SEF production substantially at all concentrations added to the SEF (10-3 to 10-6 M). Three sulphonamide inhibitors of carbonic anhydrase, acetazolamide, ethoxzolamide and benzolamide, decreased SEF production when added to the SEF at concentrations of 10-3 to 10-6 M. Benzolamide was by far the most potent. Neither ouabain nor the sulphonamides altered SEF production when added to the albumen culture medium. 5. Using a cobalt precipitation method, carbonic anhydrase activity was localised to the endodermal cells of the area vasculosa. The carbonic anhydrase activity was primarily associated with the lateral plasma membranes, which together with the potent inhibitory effect of benzolamide, suggests the carbonic anhydrase of these cells is the membrane-associated form, CA IV. 6. The changes in SEF composition produced by inhibitors were consistent with the production of SEF by local osmotic gradients. 7. It is concluded that a Na+/K+ ATPase is located on the basolateral membranes of the endodermal cells of the area vasculosa , and that a sodium ion/hydrogen ion exchanger is located on their apical surfaces. Protons for this exchanger would be provided by the hydration of CO2 catalysed by the membrane-associated carbonic anhydrase. Furthermore, it is proposed that the prime function of the endodermal cells of the area vasculosa is the production of SEF

Reliability of four models for clinical gait analysis

Three-dimensional gait analysis (3DGA) has become a common clinical tool for treatment planning in children with cerebral palsy (CP). Many clinical gait laboratories use the conventional gait analysis model (e.g. Plug-in-Gait model), which uses Direct Kinematics (DK) for joint kinematic calculations, whereas, musculoskeletal models, mainly used for research, use Inverse Kinematics (IK). Musculoskeletal IK models have the advantage of enabling additional analyses which might improve the clinical decision-making in children with CP. Before any new model can be used in a clinical setting, its reliability has to be evaluated and compared to a commonly used clinical gait model (e.g. Plug-in-Gait model) which was the purpose of this study. Two testers performed 3DGA in eleven CP and seven typically developing participants on two occasions. Intra- and inter-tester standard deviations (SD) and standard error of measurement (SEM) were used to compare the reliability of two DK models (Plug-in-Gait and a six degrees-of-freedom model solved using Vicon software) and two IK models (two modifications of ‘gait2392′ solved using OpenSim). All models showed good reliability (mean SEM of 3.0° over all analysed models and joint angles). Variations in joint kinetics were less in typically developed than in CP participants. The modified ‘gait2392′ model which included all the joint rotations commonly reported in clinical 3DGA, showed reasonable reliable joint kinematic and kinetic estimates, and allows additional musculoskeletal analysis on surgically adjustable parameters, e.g. muscle-tendon lengths, and, therefore, is a suitable model for clinical gait analysis

Metabolic Flux Analysis of Mammalian Cells

Metabolic flux analysis has become a standard tool for analyzing metabolism and optimizing bioprocesses. Metabolic flux analysis makes use of a metabolic reaction network in combination with extra-cellular measurements and mass balancing to calculate flux distributions in metabolism. It is a useful tool to analyze metabolism of cells and can be used to optimize the bioprocess in terms of medium design and metabolic engineering of the cells. In this chapter first the fundamental aspects of metabolic networks and the mathematical methods are described. Next a metabolic model for mammalian cells is discussed, Finally, applications of metabolic flux balancing are reviewed. Further extension of the metabolic network models, possibly towards genome-scale models, will further increase the value of these model