Introduction: Enterocutaneous fistulae are a common cause of intestinal failure, and may necessitate parenteral nutrition (PN) and prolonged hospitalisation. Refeeding of fistula losses back into the distal gut is known to be beneficial, however implementation has been limited because devices are not commonly available, and manual recycling is unpleasant and labour-intensive. We present a novel device designed to enable easy and efficient chyme recycling, and report data from a first-in-human feasibility study. Methods: The novel device comprises a compact centrifugal pump that can be placed inside a standard stoma bag. The pump is connected to an intestinal feeding tube which is inserted into the distal fistula limb. The pump is activated across the stoma bag by magnetic coupling to a custom-designed hand-held driver unit, effecting intermittent bolus refeeding while avoiding contact with the stoma effluent. Five speed settings were included to handle different chyme viscosities. Nutritional, medical, psychological and human-use factors were evaluated in an initial feasibility study. Results: Following benchtop validation, the device was tested in 10 patients (1 drop-out due to unrelated obstruction; median 31d; IQR 22-50d). Indications for inclusion were remediation of high-output fistula / stoma losses (n=7), dependency on PN (n=5), and gut rehabilitation prior to restoration of continuity (n=10). A range of chyme viscosities were successfully recycled with increasing efficiency over the course of the trial, due to iterative device improvements. Patients consumed low residue diets. Once established, chyme recycling was well-tolerated in all patients, using regular boluses of up to 200 ml per episode, performed as many times as needed per day. Patients experienced a variety of benefits including reduced net losses (>65% average volumes), PN cessaton (4/5 patients, including all patients employing the final device iteration), liver function improvement, electrolyte normalisation, and improved quality of life. Of 6 patients with continuity restored at the time of reporting, none experienced post-operative ileus. Conclusions: A novel chyme recycling device was developed and feasibility confirmed in an initial study. The device is easy to use and demonstrates multiple potential benefits including weaning of PN, gut rehabilitation, improved surgical outcomes, and reduced costs of care in these complex patients. A larger efficacy trial is currently planned.

We propose a new non-linear poroelastic model that is suited to the analysis of soft tissues. In this paper the model is tailored to the analysis of cartilage and the engineering design of cartilage constructs. The proposed continuum formulation of the governing equations enables the strain of the individual material components within the extracellular matrix (ECM) to be followed over time, as the individual material components are synthesized, assembled and incorporated within the ECM or lost through passive transport or degradation. The material component analysis developed here naturally captures the effect of time-dependent changes of ECM composition on the deformation and internal stress states of the ECM. For example, it is shown that increased synthesis of aggrecan by chondrocytes embedded within a decellularized cartilage matrix initially devoid of aggrecan results in osmotic expansion of the newly synthesized proteoglycan matrix and tension within the structural collagen network. Specifically, we predict that the collagen network experiences a tensile strain, with a maximum of ~2% at the fixed base of the cartilage. The analysis of an example problem demonstrates the temporal and spatial evolution of the stresses and strains in each component of a self-equilibrating composite tissue construct, and the role played by the flux of water through the tissue.

Models of skeletal muscle can be classified as phenomenological or biophysical. Phenomenological models predict the muscle's response to a specified input based on experimental measurements. Prominent phenomenological models are the Hill-type muscle models, which have been incorporated into rigid-body modeling frameworks, and three-dimensional continuum-mechanical models. Biophysically based models attempt to predict the muscle's response as emerging from the underlying physiology of the system. In this contribution, the conventional biophysically based modeling methodology is extended to include several structural and functional characteristics of skeletal muscle. The result is a physiologically based, multi-scale skeletal muscle finite element model that is capable of representing detailed, geometrical descriptions of skeletal muscle fibers and their grouping. Together with a well-established model of motor-unit recruitment, the electro-physiological behavior of single muscle fibers within motor units is computed and linked to a continuum-mechanical constitutive law. The bridging between the cellular level and the organ level has been achieved via a multi-scale constitutive law and homogenization. The effect of homogenization has been investigated by varying the number of embedded skeletal muscle fibers and/or motor units and computing the resulting exerted muscle forces while applying the same excitatory input. All simulations were conducted using an anatomically realistic finite element model of the tibialis anterior muscle. Given the fact that the underlying electro-physiological cellular muscle model is capable of modeling metabolic fatigue effects such as potassium accumulation in the T-tubular space and inorganic phosphate build-up, the proposed framework provides a novel simulation-based way to investigate muscle behavior ranging from motor-unit recruitment to force generation and fatigue.

1. Auckland Bioengineering Institute, The University of Auckland, New Zealand 2. Dept of Surgery, The University of Auckland, New Zealand 3. CSIRO Materials Science and Engineering, NSW, Australia 4. Academic Surgical Unit (GI Physiology Unit), Queen Mary University London, Barts and The London School of Medicine and Dentistry, UK 5. Dept of Engineering Science, The University of Auckland, New Zealand 6. Riddet Institute, Centre of Research Excellence hosted by Massy University, New Zealand. 7. School of Medicine, St. George Hospital, University of New South Wales, Australia

BackgroundColonic propagating sequences (PS) are important for the movement of colonic content and defecation, and aberrant PS patterning has been associated with slow transit constipation. However, because these motor patterns are typically recorded over long periods (24 h +), the visualization of PS spatiotemporal patterning is difficult. Here, we develop a novel method for displaying pan-colonic motility patterns.MethodsA 3D mesh representing the geometry of the human colon was created as follows: (i) Human colon images from the Visible Human Dataset were digitized to create a 3D data cloud, and (ii) A surface mesh was fitted to the cloud using a least-squares minimization technique. Colonic manometry catheters were placed in the ascending colon of healthy controls and patients with slow transit constipation (STC), with the aid of a colonoscope. The colonic manometry data were interpolated and mapped to the model according to the following anatomical landmarks: cecum, hepatic flexure, splenic flexure, sigmoid-descending junction, and anus.Key ResultsThese 3D images clearly and intuitively communicate characteristics of normal and abnormal colonic motility. Specifically we have shown the reduced amplitude of the antegrade propagating pressure waves (PPW) throughout the colon and reduced frequency of PPWs at the mid-colon in patients with STC.Conclusions and InferencesA novel method for the 3D visualization of PS is presented, providing an intuitive method for representing a large volume of physiological data. These techniques can be used to display frequency, amplitude or velocity data, and will help to convey regions of abnormally in patient populations.

The AIGO project is the proposed southern hemisphere advanced large scale gravitational wave detector. With this southern hemisphere detector, the global array of ground based gravitational wave detectors will be substantially improved. Here we summarize the current plans for the AIGO detector.

This paper describes the proposed AIGO detector for the worldwide array of interferometric gravitational wave detectors.The first part of the paper summarizes the benefits that AIGO provides to the worldwide array of detectors.The second part gives a technical description of the detector, which will follow closely the Advanced LIGO design.Possible technical variations in the design are discussed.

Normal gastrointestinal (GI) motility results from the coordinated interplay of multiple cooperating mechanisms, both intrinsic and extrinsic to the GI tract. A fundamental component of this activity is an omnipresent electrical activity termed slow waves, which is generated and propagated by the interstitial cells of Cajal (ICCs). The role of ICC loss and network degradation in GI motility disorders is a significant area of ongoing research. This review examines recent progress in the multiscale modeling framework for effectively integrating a vast range of experimental data in GI electrophysiology, and outlines the prospect of how modeling can provide new insights into GI function in health and disease. The review begins with an overview of the GI tract and its electrophysiology, and then focuses on recent work on modeling GI electrical activity, spanning from cell to body biophysical scales. Mathematical cell models of the ICCs and smooth muscle cell are presented. The continuum framework of monodomain and bidomain models for tissue and organ models are then considered, and the forward techniques used to model the resultant body surface potential and magnetic field are discussed. The review then outlines recent progress in experimental support and validation of modeling, and concludes with a discussion on potential future research directions in this field.

This paper introduces a framework for skeletal muscles that couples outputs from a detailed biophysically based electrophysiological cell model to a three-dimensional continuum-based finite element model of muscle mechanics. Due to the unique manner in which a skeletal muscle is activated, specifically the fact that neighboring fibers are electrically isolated and can act independently of each other, a completely new and novel coupling framework has been created. Within this framework, the electrical activity within a fiber is modeled with a biophysically based cell model, which is itself an amalgamation of several existing cell models. From this amalgamated cell model, specific output parameters that describe the level of crossbridge activity are computed and stored within a lookup table. This lookup table is then used to map the appropriate level of activity to all fibers within the muscle. To link the level of activity to a three-dimensional finite flement model of a skeletal muscle, which is based on principles of continuum mechanics, an upscaling method is introduced to compensate for the fact that the finite element mesh does not attempt to separately represent each individual fiber. This upscaling method allows the stress equilibrium equations to be computed at each Gauss point based on different values of the cell model outputs in all the neighboring cells. Since adjacent fibers can operate independently, the cell model outputs used in the finite element solution of the finite elasticity equations are discontinuous. The behavior and performance of the entire coupling framework is carefully analyzed in some simple test cases analyzing the reduction of the discretization error with respect to a sequence of uniformly refined meshes and different activation patterns. The results show that the error-reduction factors obtained from the electromechanical framework using triquadratic Lagrange and tricubic Hermite basis functions in solving the Galerkin finite element stress equilibrium equations are very similar to those obtained from a mechanics-only continuum-based model. Following this, an example of this process applied to the lateral pterygoid muscle is presented. The proposed framework can be used, for example, to investigate the mechanical effects with respect to cellular changes or to analyze the effects of different neuromuscular activation patterns on the tissue response.

Surface electrical stimulation of denervated skeletal muscles has been used as a method to induce muscle contraction. However, questions still remain as to how to achieve a desired contraction or how to selectively activate parts of a given skeletal muscle. To begin to address these issues, a detailed biophysically based model, incorporating full fibre architecture, of the human anterior tibialis muscle was developed. Using a recently published skeletal muscle cell model, action potentials of each fibre were simulated using different electrode configurations. The size of the activated region as a function of electrode size and inter-electrode distance were

The ability for muscle to repeatedly generate force is limited by fatigue. The cellular mechanisms behind muscle fatigue are complex and potentially include breakdown at many points along the excitation–contraction pathway. In this paper we construct a mathematical model of the skeletal muscle excitation–contraction pathway based on the cellular biochemical events that link excitation to contraction. The model includes descriptions of membrane voltage, calcium cycling and crossbridge dynamics and was parameterised and validated using the response characteristics of mouse skeletal muscle to a range of electrical stimuli. This model was used to uncover the complexities of skeletal muscle fatigue. We also parameterised our model to describe force kinetics in fast and slow twitch fibre types, which have a number of biochemical and biophysical differences. How these differences interact to generate different force/fatigue responses in fast- and slow- twitch fibres is not well understood and we used our modelling approach to bring new insights to this relationship.

A mathematical model of the cellular responses of skeletal muscles has been integrated within a three‐dimensional biomechanical Finite Element (FEM) model. The FEM model is based on a tri‐cubic Hermite Finite Element discretisation of the governing equations of finite elasticity theory and a transversely isotropic constitutive law. To incorporate the cellular information, homogenised values of key physiological parameters, e.g. the pre‐ and post‐power stroke concentration of crossbridge attachments, are computed at the Gauss points of the FEMintegration scheme. These values are then used to modify the stress tensor in such a way that it resembles the contractile response. The advantages of such an improved three‐dimensional FEM model are far reaching. These models can be used, for example, to investigate and study local muscle contraction, muscle recruitment patterns, force generation, or fatigue response of skeletal muscles. As an illustrative example, one twitch of the tibialis anterior, in which 25% of the muscle fibres are excited by a nerve stimulus, is simulated. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)

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BACKGROUND:Functional Electrical Stimulation (FES) is a technique that aims to rehabilitate or restore functionality of skeletal muscles using external electrical stimulation. Despite the success achieved within the field of FES, there are still a number of questions that remain unanswered. One way of providing input to the answers is through the use of computational models.METHODS:This paper describes the development of an anatomically based computer model of the motor neurons in the lower limb of the human leg and shows how it can be used to simulate electrical signal propagation from the beginning of the sciatic nerve to a skeletal muscle. One-dimensional cubic Hermite finite elements were used to represent the major portions of the lower limb nerves. These elements were fit to data that had been digitised using images from the Visible Man project. Nerves smaller than approximately 1 mm could not be seen in the images, and thus a tree-branching algorithm was used to connect the ends of the fitted nerve model to the respective skeletal muscle. To simulate electrical propagation, a previously published mammalian nerve model was implemented and solved on the anatomically based nerve mesh using a finite difference method. The grid points for the finite difference method were derived from the fitted finite element mesh. By adjusting the tree-branching algorithm, it is possible to represent different levels of motor-unit recruitment.RESULTS:To illustrate the process of a propagating nerve stimulus to a muscle in detail, the above method was applied to the nerve tree that connects to the human semitendinosus muscle. A conduction velocity of 89.8 m/s was obtained for a 15 mum diameter nerve fibre. This signal was successfully propagated down the motor neurons to a selected group of motor units in the muscle.CONCLUSION:An anatomically and physiologically based model of the posterior motor neurons in the human lower limb was developed. This model can be used to examine the effect of external stimulation on nerve and muscle activity, as may occur, for example, in the field of FES.