Modification of the in vivo four-point loading model for studying mechanically induced bone adaptation

We modified the noninvasive, in vivo technique for strain application in the tibiae of rats (Turner et al,, Bone 12:73-79, 1991), The original model applies four-point bending to right tibiae via an open-loop, stepper-motor-driven spring linkage, Depending on the magnitude of applied load, the model produces new bone formation at periosteal (Ps) or endocortical surfaces (Ec.S). Due to the spring linkage, however, the range of frequencies at which loads can be applied is limited. The modified system replaces this design with an electromagnetic vibrator. A load transducer in series with the loading points allows calibration, the loaders' position to be adjusted, and cyclic loading completed under load central as a closed servo-loop. Two experiments were conducted to validate the modified system: (1) a strain gauge was applied to the lateral surface of the right tibia of 5 adult female rats and strains measured at applied loads from 10 to 60 N; and (2) the bone formation response was determined in 28 adult female Sprague-Dawley rats. Loading was applied as a haversine wave with a frequency of 2 Hz for 18 sec, every second day for 10 days. Peak bending loads mere applied at 33, 40, 52, and 64 N, and a sham-loading group tr as included at 64 N, Strains in the tibiae were linear between 10 and 60 N, and the average peak strain at the Ps.S at 60 N was 2664 +/- 250 microstrain, consistent with the results of Turner's group. Lamellar bone formation was stimulated at the Ec.S by applied bending, but not by sham loading. Bending strains above a loading threshold of 40 N increased Ec Lamellar hone formation rate, bone forming surface, and mineral apposition rate with a dose response similar to that reported by Turner et al, (J Bone Miner Res 9:87-97, 1994). We conclude that the modified loading system offers precision for applied loads of between 0 and 70 N, versatility in the selection of loading rates up to 20 Hz, and a reproducible bone formation response in the rat tibia, Adjustment of the loader also enables study of mechanical usage in murine tibia, an advantage with respect to the increasing variety of transgenic strains available in bone and mineral research. (Bone 23:307-310; 1998) (C) 1998 by Elsevier Science Inc. All rights reserved.

Are transitions in human gait determined by mechanical, kinetic or energetic factors?

It is currently unclear whether it is the need to maintain metabolic efficiency, the need to keep skeletal loading below critical force levels, or simple mechanical factors that drive the walk-to-run (W R) and run-to-walk (R-W) transitions in human gait. Eighteen adults (9 males and 9 females) locomoted on an instrumented treadmill using their preferred gait. Each completed 2 ascending (W-R) and 2 descending (R-W) series of trials under three levels of loading (0%, 15% and 30% body weight). For each trial, participants locomoted for 60 s at each of 9 different speeds -4 speeds both above and below their preferred transition speed (PTS) plus their PTS. Evidence was sought for critical levels of key kinetic (maximum vertical force, impulse, first peak force, time to first peak force and maximum loading rate), energetic (oxygen consumption, transport cost) and mechanical variables (limb lengths, strength) predictive of the gait transition. Analyses suggested the kinetic variables of time to first peak force and loading rate as the most likely determinants of the W-R and R-W transitions. (C) 2003 Elsevier Science B.V. All rights reserved.

Maximum Likelihood Estimation of Mixture Densities for Binned and Truncated Multivariate Data

Binning and truncation of data are common in data analysis and machine learning. This paper addresses the problem of fitting mixture densities to multivariate binned and truncated data. The EM approach proposed by McLachlan and Jones (Biometrics, 44: 2, 571-578, 1988) for the univariate case is generalized to multivariate measurements. The multivariate solution requires the evaluation of multidimensional integrals over each bin at each iteration of the EM procedure. Naive implementation of the procedure can lead to computationally inefficient results. To reduce the computational cost a number of straightforward numerical techniques are proposed. Results on simulated data indicate that the proposed methods can achieve significant computational gains with no loss in the accuracy of the final parameter estimates. Furthermore, experimental results suggest that with a sufficient number of bins and data points it is possible to estimate the true underlying density almost as well as if the data were not binned. The paper concludes with a brief description of an application of this approach to diagnosis of iron deficiency anemia, in the context of binned and truncated bivariate measurements of volume and hemoglobin concentration from an individual's red blood cells.

The effects of viscous loading of the human forearm flexors on the stability of coordination

This experiment investigated whether the stability of rhythmic unimanual movements is primarily a function of perceptual/spatial orientation or neuro-mechanical in nature. Eight participants performed rhythmic flexion and extension movements of the left wrist for 30 s at a frequency of 2.25 Hz paced by an auditory metronome. Each participant performed 8 flex-on-the-beat trials and 8 extend-on-the-beat trials in one of two load conditions, loaded and unload. In the loaded condition, a servo-controlled torque motor was used to apply a small viscous load that resisted the flexion phase of the movement only. Both the amplitude and frequency of the movement generated in the loaded and unloaded conditions were statistically equivalent. However, in the loaded condition movements in which participants were required to flex-on-the-beat became less stable (more variable) while extend-on-the-beat movements remained unchanged compared with the unload condition. The small alteration in required muscle force was sufficient to result in reliable changes in movement stability even a situation where the movement kinematics were identical. These findings support the notion that muscular constraints, independent of spatial dependencies, can be sufficiently strong to reliably influence coordination in a simple unimanual task.

Analysis of small signal stability margins using genetic optimization

Power system small signal stability analysis aims to explore different small signal stability conditions and controls, namely: (1) exploring the power system security domains and boundaries in the space of power system parameters of interest, including load flow feasibility, saddle node and Hopf bifurcation ones; (2) finding the maximum and minimum damping conditions; and (3) determining control actions to provide and increase small signal stability. These problems are presented in this paper as different modifications of a general optimization to a minimum/maximum, depending on the initial guesses of variables and numerical methods used. In the considered problems, all the extreme points are of interest. Additionally, there are difficulties with finding the derivatives of the objective functions with respect to parameters. Numerical computations of derivatives in traditional optimization procedures are time consuming. In this paper, we propose a new black-box genetic optimization technique for comprehensive small signal stability analysis, which can effectively cope with highly nonlinear objective functions with multiple minima and maxima, and derivatives that can not be expressed analytically. The optimization result can then be used to provide such important information such as system optimal control decision making, assessment of the maximum network's transmission capacity, etc. (C) 1998 Elsevier Science S.A. All rights reserved.

Rheological behaviour of the mushy zone and its effect on the formation of casting defects during solidification

A new conceptual framework has been developed which explains the formation of shear-related casting defects such as porosity, segregation and tears. The theory relates defect formation to the mechanical behaviour of the partially solidified microstructure when shear stresses are developed during the filling of a casting and by the subsequent feeding processes during solidification. Two transition points, the dendrite coherency point and the maximum packing solid fraction, divide the mushy zone into three regions of different mechanical and feeding behaviours. The response of the mush to shear is related to the presence of these zones during solidification of a casting. The resulting defects are rationalized by considering the governing local shear stress and shear rate, local strength and time available for fluid flow. The design of the casting, the casting process used and the alloy composition all influence the relative importance of shearing on defect formation. (C) 1998 Acta Metallurgica Inc. Published by Elsevier Science Ltd. All rights reserved.

The crack tip strain field of AISI 4340 - Part I - Measurement technique

This is the first paper in a study on the influence of the environment on the crack tip strain field for AISI 4340. A stressing stage for the environmental scanning electron microscope (ESEM) was constructed which was capable of applying loads up to 60 kN to fracture-mechanics samples. The measurement of the crack tip strain field required preparation (by electron lithography or chemical etching) of a system of reference points spaced at similar to 5 mu m intervals on the sample surface, loading the sample inside an electron microscope, image processing procedures to measure the displacement at each reference point and calculation of the strain field. Two algorithms to calculate strain were evaluated. Possible sources of errors were calculation errors due to the algorithm, errors inherent in the image processing procedure and errors due to the limited precision of the displacement measurements. Estimation of the contribution of each source of error was performed. The technique allows measurement of the crack tip strain field over an area of 50 x 40 mu m with a strain precision better than +/- 0.02 at distances larger than 5 mu m from the crack tip. (C) 1999 Kluwer Academic Publishers.

Maximum packings of K-v-K-u with triples

We construct, for all positive integers u, and v with u less than or equal to v, a decomposition of K-v - K-u (the complete graph on v vertices with a. hole of size u) into the maximum possible number of edge disjoint triangles.

A two-dimensional analytical solution of groundwater responses to tidal loading in an estuary and ocean

Previous studies on tidal dynamics of coastal aquifers have focussed on the inland propagation of oceanic tides in the cross-shore direction, a configuration that is essentially one-dimensional. Aquifers at natural coasts can also be influenced by tidal waves in nearby estuaries, resulting in a more complex behaviour of head fluctuations in the aquifers. We present an analytical solution to the two-dimensional depth-averaged groundwater flow equation for a semi-infinite aquifer subject to oscillating head conditions at the boundaries. The solution describes the tidal dynamics of a coastal aquifer that is adjacent to a cross-shore estuary. Both the effects of oceanic and estuarine tides on the aquifer are included in the solution. The analytical prediction of the head fluctuations is verified by comparison with numerical solutions computed using a standard finite-difference method. An essential feature of the present analytical solution is the interaction between the cross- and along-shore tidal waves in the aquifer area near the estuary's entry. As the distance from the estuary or coastline increases, the wave interaction is weakened and the aquifer response is reduced, respectively, to the one-dimensional solution for oceanic tides or the solution of Sun (Sun H. A two-dimensional analytical solution of groundwater response to tidal loading in an estuary, Water Resour Res 1997;33:1429-35) for two-dimensional non-interacting tidal waves. (C) 2000 Elsevier Science Ltd. All rights reserved.

Improving maximum walking distance in early peripheral arterial disease: Randomised controlled trial

The purpose of this study was to determine the impact of increased physical activity and cessation of smoking on the natural history of early peripheral arterial disease, We conducted a randomised controlled trial in Perth, Western Australia, involving 882 men with early peripheral arterial disease identified via population-based screening using the Edinburgh Claudication Questionnaire and the ankle:brachial index. Members of the control group (n = 441) received usual care from their general practitioner while members of the intervention group (n = 441) were allocated to a stop smoking and keep walking regime - a combined community-based intervention of cessation of smoking (where applicable) and increased physical activity. Postal follow-up occurred at two and 12 months post-entry into the trial. The main outcome of interest was maximum walking distance. There were no statistically significant differences in the characteristics of the intervention and usual care groups at recruitment. Follow-up information at two and 12 months was available for 85% and 84% of participants, respectively. At 12 months, more men allocated to the intervention group had improved their maximum walking distance (23% vs 15%; chi(2) = 9.74, df = 2, p = 0.008). In addition, more men in the intervention group reported walking more than three times per week for recreation (34% vs 25%, p = 0.01). Although not statistically significant, more men in the intervention group who were smokers when enrolled in the trial had stopped smoking (12% vs 8%, p = 0.43). It is concluded that referral of older patients with intermittent claudication to established physiotherapy programs in the community can increase levels of physical activity and reduce disability related to peripheral arterial disease. A combination of simple and safe interventions that are readily available in the community through physiotherapists and general practitioners has the potential to improve early peripheral arterial disease.

Event-related FMRI analysis with maximum correlation modelling

Functional magnetic resonance imaging (FMRI) analysis methods can be quite generally divided into hypothesis-driven and data-driven approaches. The former are utilised in the majority of FMRI studies, where a specific haemodynamic response is modelled utilising knowledge of event timing during the scan, and is tested against the data using a t test or a correlation analysis. These approaches often lack the flexibility to account for variability in haemodynamic response across subjects and brain regions which is of specific interest in high-temporal resolution event-related studies. Current data-driven approaches attempt to identify components of interest in the data, but currently do not utilise any physiological information for the discrimination of these components. Here we present a hypothesis-driven approach that is an extension of Friman's maximum correlation modelling method (Neurolmage 16, 454-464, 2002) specifically focused on discriminating the temporal characteristics of event-related haemodynamic activity. Test analyses, on both simulated and real event-related FMRI data, will be presented.

Mechanical loading modulates glutamate receptor subunit expression in bone

The cellular mechanisms coupling mechanical loading with bone remodeling remain unclear. In the CNS, the excitatory amino acid glutamate (Glu) serves as a potent neurotransmitter exerting its effects via various membrane Glu receptors (GluR). Nerves containing Glu exist close to bone cells expressing functional GluRs. Demonstration of a mechanically sensitive glutamate/aspartate transporter protein and the ability of glutamate to stimulate bone resorption in vitro suggest a role for glutamate linking mechanical load and bone remodeling. We used immunohistochemical techniques to identify the expression of N-methyl-D-aspartate acid (NMDA) and non-NMDA (AMPA or kainate) ionotropic GluR subunits on bone cells in vivo. In bone sections from young adult rats, osteoclasts expressed numerous GluR subunits including AMPA (GluR2/3 and GluR4), kainic acid (GluR567) and NMDA (NMDAR2A, NMDAR2B and NMDAR2C) receptor subtypes. Bone lining cells demonstrated immunoexpression for NMDAR2A, NMDAR2B, NMDAR2C, GluR567, GluR23, GuR2 and GluR4 subunits. Immunoexpression was not evident on osteocytes, chondrocytes or vascular channels. To investigate the effects of mechanical loading on GluR expression, we used a Materials Testing System (MTS) to apply 10 N sinusoidal axial compressive loads percutaneously to the right limbs (radius/ulna, tibia/fibula) of rats. Each limb underwent 300-load cycles/day (cycle rate, 1 Hz) for 4 consecutive days. Contralateral, non-loaded limbs served as controls. Mechanically loaded limbs revealed a load-induced loss of immunoexpression for GluR2/3, GluR4, GluR567 and NMDAR2A on osteoclasts and NMDAR2A, NMDAR2B, GluR2/3 and GluR4 on bone lining cells. Both neonatal rabbit and rat osteoclasts were cultured on bone slices to investigate the effect of the NMDA receptor antagonist, MK801, and the AMPA/kainic acid receptor antagonist, NBQX, on osteoclast resorptive activity in vitro. The inhibition of resorptive function seen suggested that both NMDAR and kainic acid receptor function are required for normal osteoclast function. While the exact role of ionotropic GluRs in skeletal tissue remains unclear, the modulation of GluR subunit expression by mechanical loading lends further support for participation of Glu as a mechanical loading effector. These ionotropic receptors appear to be functionally relevant to normal osteoclast resorptive activity. (C) 2005 Elsevier Inc. All rights reserved.

Altered loading patterns and femoral bone mineral density in children with unilateral Legg-Calve-Perthes disease

Maximization of bone accrual during the growing years is thought to be an important factor in minimizing fracture risk in old age. Mechanical loading through physical activity has been recommended as a modality for the conservation of bone mineral in adults; however, few studies have evaluated the impact of different loading regimes in growing children. The purpose of this study was to compare bone mineral density (BMD) in weight-bearing and non-weight-bearing limbs in 17 children with unilateral Legg Calve Perthes Disease (LCPD). Children with this condition have an altered weight-bearing pattern whereby there is increased mechanical loading on the noninvolved normal hip and reduced loading on the involved painful hip. Thus, these children provide a unique opportunity to study the impact of differential mechanical loading on BMD during the growing years while controlling for genetic disposition. BMD at four regions of the proximal femur (trochanter, intertrochanter, femoral neck, total of the regions) was measured using dual energy x-ray absorptiometry (DXA), and the values were compared between the involved and noninvolved sides of the children with LCPD. The BMD of both sides also were compared with normative values based on both chronological and skeletal age data. A significantly higher BMD was found on the noninvolved side over the involved side for all regions (P