Changes in bone structure and metabolism during simulated weightlessness: Endocrine and dietary factors

The role of vitamin D, PTH and corticosterone in the skeletal alterations induced by simulated weightlessness was examined. The first objective was to determine if changes in the serum concentrations of Ca, P sub i, osteocalcin, 25-OH-D, 24,25(OH)2D or 1,25(OH)2D also occur following acute skeletal unloading. Animals were either suspended or pair fed for 2, 5, 7, 10, 12 and 15 days and the serum concentrations of Ca, P sub i, osteocalcin and the vitamin D metabolites measured. Bone histology was examined at day 5 after suspension. Acute skeletal unloading produced a transient hypercalcemia, a significant fall in serum osteocalcin and serum 1,25(OH)2D, a slight rise in serum 24,25(OH)2D, but did not affect the serum concentrations of P sub i or 25-OH-D. At the nadir in serum 1,25(OH)2D serum osteocalcin was reduced by 22%, osteoblast surface by 32% and longitudinal bone growth by 21%

The role of 1,25-dihydroxyvitamin D in the inhibition of bone formation induced by skeletal unloading

Skeletal unloading results in osteopenia. To examine the involvement of vitamin D in this process, the rear limbs of growing rats were unloaded and alterations in bone calcium and bone histology were related to changes in serum calcium (Ca), inorganic phosphorus (P sub i), 25-hydroxyvitamin D (25-OH-D), 24,25-dihydroxyvitamin D (24,25(OH)2D and 1,25-dihydroxyvitamin D (1,25(OH)2D. Acute skeletal unloading induced a transitory inhibition of Ca accumulation in unloaded bones. This was accompanied by a transitory rise in serum Ca, a 21% decrease in longitudinal bone growth (P 0.01), a 32% decrease in bone surface lined with osteoblasts (P .05), no change in bone surface lined with osteoclasts and a decrease in circulating (1,25(OH)2D. No significant changes in the serum concentrations of P sub i, 25-OH-D or 24,25(OH)2D were observed. After 2 weeks of unloading, bone Ca stabilized at approximately 70% of control and serum Ca and 1,25(OH)2D returned to control values. Maintenance of a constant serum 1,25(OH)2D concentration by chronic infusion of 1,25(OH)2D (Alza osmotic minipump) throughout the study period did not prevent the bone changes induced by acute unloading. These results suggest that acute skeletal unloading in the growing rat produces a transitory inhibition of bone formation which in turn produces a transitory hypercalcemia

Exploring Agricultural Production Systems and Their Fundamental Components with System Dynamics Modelling

Agricultural production in the United States is undergoing marked changes due to rapid shifts in consumer demands, input costs, and concerns for food safety and environmental impact. Agricultural production systems are comprised of multidimensional components and drivers that interact in complex ways to influence production sustainability. In a mixed-methods approach, we combine qualitative and quantitative data to develop and simulate a system dynamics model that explores the systemic interaction of these drivers on the economic, environmental and social sustainability of agricultural production. We then use this model to evaluate the role of each driver in determining the differences in sustainability between three distinct production systems: crops only, livestock only, and an integrated crops and livestock system. The result from these modelling efforts found that the greatest potential for sustainability existed with the crops only production system. While this study presents a stand-alone contribution to sector knowledge and practice, it encourages future research in this sector that employs similar systems-based methods to enable more sustainable practices and policies within agricultural production

Adaptive Surrogate Modeling for Efficient Coupling of Musculoskeletal Control and Tissue Deformation Models

Background Finite element (FE) modeling and multibody dynamics have traditionally been applied separately to the domains of tissue mechanics and musculoskeletal movements, respectively. Simultaneous simulation of both domains is needed when interactions between tissue and movement are of interest, but this has remained largely impractical due to high computational cost. Method of Approach Here we present a method for concurrent simulation of tissue and movement, in which state of the art methods are used in each domain, and communication occurs via a surrogate modeling system based on locally weighted regression. The surrogate model only performs FE simulations when regression from previous results is not within a user-specified tolerance. For proof of concept and to illustrate feasibility, the methods were demonstrated on an optimization of jumping movement using a planar musculoskeletal model coupled to a FE model of the foot. To test the relative accuracy of the surrogate model outputs against those of the FE model, a single forward dynamics simulation was performed with FE calls at every integration step and compared with a corresponding simulation with the surrogate model included. Neural excitations obtained from the jump height optimization were used for this purpose and root mean square (RMS) difference between surrogate and FE model outputs (ankle force and moment, peak contact pressure and peak von Mises stress) were calculated. Results Optimization of jump height required 1800 iterations of the movement simulation, each requiring thousands of time steps. The surrogate modeling system only used the FE model in 5% of time steps, i.e. a 95% reduction of computation time. Errors introduced by the surrogate model were less than 1 mm in jump height and RMS errors of less than 2 N in ground reaction force, 0.25 Nm in ankle moment, and 10 kPa in peak tissue stress. Conclusion Adaptive surrogate modeling based on local regression allows efficient concurrent simulations of tissue mechanics and musculoskeletal movement

Concurrent Muscoskeletal Dynamics and Finite Element Analysis Predicts Altered Gait Patterns to Reduce Foot Tissue Loading

Current computational methods for simulating locomotion have primarily used muscle-driven multibody dynamics, in which neuromuscular control is optimized. Such simulations generally represent joints and soft tissue as simple kinematic or elastic elements for computational efficiency. These assumptions limit application in studies such as ligament injury or osteoarthritis, where local tissue loading must be predicted. Conversely, tissue can be simulated using the finite element method with assumed or measured boundary conditions, but this does not represent the effects of whole body dynamics and neuromuscular control. Coupling the two domains would overcome these limitations and allow prediction of movement strategies guided by tissue stresses. Here we demonstrate this concept in a gait simulation where a musculoskeletal model is coupled to a finite element representation of the foot. Predictive simulations incorporated peak plantar tissue deformation into the objective of the movement optimization, as well as terms to track normative gait data and minimize fatigue. Two optimizations were performed, first without the strain minimization term and second with the term. Convergence to realistic gait patterns was achieved with the second optimization realizing a 44% reduction in peak tissue strain energy density. The study demonstrated that it is possible to alter computationally predicted neuromuscular control to minimize tissue strain while including desired kinematic and muscular behavior. Future work should include experimental validation before application of the methodology to patient care