Computational Modelling of Cardiac Trabecula Mechanics

Cardiac trabeculae are thin strips of muscle within the ventricles that can be readily excised and used to investigate contractile mechanics of cardiac muscle. Recently, the Auckland Bioengineering Institute has developed a novel cardiac myometer that simultaneously measures force, length and shape of actively contracting isolated cardiac trabeculae. Here we have developed a muscle-specific computational model based on optical coherence tomography geometric surface data that replicates passive mechanics of trabecula. We hypothesised that the muscle's surface geometry data, in addition to force-length data, would improve the fit between the model simulated mechanics and the experimental data. The trabecula model was optimised using two different objective functions (muscle length or shape) driven by a pressure boundary condition. For both objective functions, there was a region of optimal parameters the optimiser tended towards but, due to the coupling between parameters, the ability to find the true optimal parameters was hindered. Due to the limitations of the data, we found that the addition of surface data did not improve parameter estimation and that using only the force-length data provided sufficient information to produce an optimal fit. References A. Anderson. The Cardiac Myometer: Measuring Matters of the Heart. PhD thesis, University of Auckland, 2016. K. F. Augenstein, Brett R. Cowan, Ian J. LeGrice, Poul M. F. Nielsen, and Alistair A. Young. Method and apparatus for soft tissue material parameter estimation using tissue tagged Magnetic Resonance Imaging. Journal of Biomechanical Engineering, 127(1):148–157, February 2005. C. Bradley, Andy Bowery, Randall Britten, Vincent Budelmann, Oscar Camara, Richard Christie, Andrew Cookson, Alejandro F. Frangi, Thiranja Babarenda Gamage, Thomas Heidlauf, Sebastian Krittian, David Ladd, Caton Little, Kumar Mithraratne, Martyn Nash, David Nickerson, Poul Nielsen, Oyvind Nordbo, Stig Omholt, Ali Pashaei, David Paterson, Vijayaraghavan Rajagopal, Adam Reeve, Oliver Rohrle, Soroush Safaei, Rafael Sebastian, Martin Steghofer, Tim Wu, Ting Yu, Heye Zhang, and Peter Hunter. OpenCMISS: A multi-physics and multi-scale computational infrastructure for the VPH/Physiome project. Progress in Biophysics and Molecular Biology, 107(1):32–47, October 2011. doi:http://dx.doi.org/10.1016/j.pbiomolbio.2011.06.015 M. L. Cheuk, A. J. Anderson, J. C. Han, N. Lippok, F. Vanholsbeeck, B. P. Ruddy, D. S. Loiselle, P. M. F. Nielsen, and A. J. Taberner. Four-Dimensional Imaging of Cardiac Trabeculae Contracting In Vitro Using Gated OCT. IEEE Transactions on Biomedical Engineering, 64(1):218–224, January 2017. doi:http://dx.doi.org/10.1109/TBME.2016.2553154 M. L. Cheuk, N. Lippok, A. W. Dixon, B. P. Ruddy, F. Vanholsbeeck, P. M. F. Nielsen, and A. J. Taberner. Optical coherence tomography imaging of cardiac trabeculae. In 2014 36th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, pages 182–185, August 2014. doi:http://dx.doi.org/10.1109/EMBC.2014.6943559 J. M Guccione, Andrew D McCulloch, and LK Waldman. Passive material properties of intact ventricular myocardium determined from a cylindrical model. J Biomech Eng, 113(1):42–55, 1991. J. C. Han, Andrew J. Taberner, Robert S. Kirton, Poul M. Nielsen, Nicholas P. Smith, and Denis S. Loiselle. A unique micromechanocalorimeter for simultaneous measurement of heat rate and force production of cardiac trabeculae carneae. Journal of Applied Physiology, 107(3):946–951, September 2009. doi:http://dx.doi.org/10.1152/japplphysiol.00549.2009 M. P. Nash and P. J. Hunter. Regional mechanics of the beating heart. In Cardiac Perfusion and Pumping Engineering, volume Volume 1 of Clinically-Oriented Biomedical Engineering, pages 83–127. WORLD SCIENTIFIC, July 2007. doi:http://dx.doi.org/10.1142/9789812775597_0004 J. H. Omens, D. A. MacKenna, and A. D. McCulloch. Measurement of strain and analysis of stress in resting rat left ventricular myocardium. Journal of Biomechanics, 26(6):665–676, June 1993. doi:http://dx.doi.org/10.1016/0021-9290(93)90030-I V. Y. Wang, H. I. Lam, Daniel B. Ennis, Brett R. Cowan, Alistair A. Young, and Martyn P. Nash. Modelling passive diastolic mechanics with quantitative MRI of cardiac structure and function. Medical Image Analysis, 13(5):773–784, October 2009. doi:http://dx.doi.org/10.1016/j.media.2009.07.00

Effect of Global Cardiac Ischemia on Human Ventricular Fibrillation: Insights from a Multi-scale Mechanistic Model of the Human Heart

Acute regional ischemia in the heart can lead to cardiac arrhythmias such as ventricular fibrillation (VF), which in turn compromise cardiac output and result in secondary global cardiac ischemia. The secondary ischemia may influence the underlying arrhythmia mechanism. A recent clinical study documents the effect of global cardiac ischaemia on the mechanisms of VF. During 150 seconds of global ischemia the dominant frequency of activation decreased, while after reperfusion it increased rapidly. At the same time the complexity of epicardial excitation, measured as the number of epicardical phase singularity points, remained approximately constant during ischemia. Here we perform numerical studies based on these clinical data and propose explanations for the observed dynamics of the period and complexity of activation patterns. In particular, we study the effects on ischemia in pseudo-1D and 2D cardiac tissue models as well as in an anatomically accurate model of human heart ventricles. We demonstrate that the fall of dominant frequency in VF during secondary ischemia can be explained by an increase in extracellular potassium, while the increase during reperfusion is consistent with washout of potassium and continued activation of the ATP-dependent potassium channels. We also suggest that memory effects are responsible for the observed complexity dynamics. In addition, we present unpublished clinical results of individual patient recordings and propose a way of estimating extracellular potassium and activation of ATP-dependent potassium channels from these measurements

The Role of the Frank–Starling Law in the Transduction of Cellular Work to Whole Organ Pump Function: A Computational Modeling Analysis

We have developed a multi-scale biophysical electromechanics model of the rat left ventricle at room temperature. This model has been applied to investigate the relative roles of cellular scale length dependent regulators of tension generation on the transduction of work from the cell to whole organ pump function. Specifically, the role of the length dependent Ca2+ sensitivity of tension (Ca50), filament overlap tension dependence, velocity dependence of tension, and tension dependent binding of Ca2+ to Troponin C on metrics of efficient transduction of work and stress and strain homogeneity were predicted by performing simulations in the absence of each of these feedback mechanisms. The length dependent Ca50 and the filament overlap, which make up the Frank-Starling Law, were found to be the two dominant regulators of the efficient transduction of work. Analyzing the fiber velocity field in the absence of the Frank-Starling mechanisms showed that the decreased efficiency in the transduction of work in the absence of filament overlap effects was caused by increased post systolic shortening, whereas the decreased efficiency in the absence of length dependent Ca50 was caused by an inversion in the regional distribution of strain

Challenges of operational river forecasting

Skillful and timely streamflow forecasts are critically important to water managers and emergency protection services. To provide these forecasts, hydrologists must predict the behavior of complex coupled human–natural systems using incomplete and uncertain information and imperfect models. Moreover, operational predictions often integrate anecdotal information and unmodeled factors. Forecasting agencies face four key challenges: 1) making the most of available data, 2) making accurate predictions using models, 3) turning hydrometeorological forecasts into effective warnings, and 4) administering an operational service. Each challenge presents a variety of research opportunities, including the development of automated quality-control algorithms for the myriad of data used in operational streamflow forecasts, data assimilation, and ensemble forecasting techniques that allow for forecaster input, methods for using human-generated weather forecasts quantitatively, and quantification of human interference in the hydrologic cycle. Furthermore, much can be done to improve the communication of probabilistic forecasts and to design a forecasting paradigm that effectively combines increasingly sophisticated forecasting technology with subjective forecaster expertise. These areas are described in detail to share a real-world perspective and focus for ongoing research endeavors

The P2X1 receptor and platelet function

Extracellular nucleotides are ubiquitous signalling molecules, acting via the P2 class of surface receptors. Platelets express three P2 receptor subtypes, ADP-dependent P2Y1 and P2Y12 G-protein-coupled receptors and the ATP-gated P2X1 non-selective cation channel. Platelet P2X1 receptors can generate significant increases in intracellular Ca2+, leading to shape change, movement of secretory granules and low levels of αIIbβ3 integrin activation. P2X1 can also synergise with several other receptors to amplify signalling and functional events in the platelet. In particular, activation of P2X1 receptors by ATP released from dense granules amplifies the aggregation responses to low levels of the major agonists, collagen and thrombin. In vivo studies using transgenic murine models show that P2X1 receptors amplify localised thrombosis following damage of small arteries and arterioles and also contribute to thromboembolism induced by intravenous co-injection of collagen and adrenaline. In vitro, under flow conditions, P2X1 receptors contribute more to aggregate formation on collagen-coated surfaces as the shear rate is increased, which may explain their greater contribution to localised thrombosis in arterioles compared to venules within in vivo models. Since shear increases substantially near sites of stenosis, anti-P2X1 therapy represents a potential means of reducing thrombotic events at atherosclerotic plaques

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Juxtaposing BTE and ATE – on the role of the European insurance industry in funding civil litigation

One of the ways in which legal services are financed, and indeed shaped, is through private insurance arrangement. Two contrasting types of legal expenses insurance contracts (LEI) seem to dominate in Europe: before the event (BTE) and after the event (ATE) legal expenses insurance. Notwithstanding institutional differences between different legal systems, BTE and ATE insurance arrangements may be instrumental if government policy is geared towards strengthening a market-oriented system of financing access to justice for individuals and business. At the same time, emphasizing the role of a private industry as a keeper of the gates to justice raises issues of accountability and transparency, not readily reconcilable with demands of competition. Moreover, multiple actors (clients, lawyers, courts, insurers) are involved, causing behavioural dynamics which are not easily predicted or influenced. Against this background, this paper looks into BTE and ATE arrangements by analysing the particularities of BTE and ATE arrangements currently available in some European jurisdictions and by painting a picture of their respective markets and legal contexts. This allows for some reflection on the performance of BTE and ATE providers as both financiers and keepers. Two issues emerge from the analysis that are worthy of some further reflection. Firstly, there is the problematic long-term sustainability of some ATE products. Secondly, the challenges faced by policymakers that would like to nudge consumers into voluntarily taking out BTE LEI

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good