Quantifying the effect of uncertainty in input parameters in a simplified bidomain model of partial thickness ischaemia

Reduced blood flow in the coronary arteries can lead to damaged heart tissue (myocardial ischaemia). Although one method for detecting myocardial ischaemia involves changes in the ST segment of the electrocardiogram, the relationship between these changes and subendocardial ischaemia is not fully understood. In this study, we modelled ST-segment epicardial potentials in a slab model of cardiac ventricular tissue, with a central ischaemic region, using the bidomain model, which considers conduction longitudinal, transverse and normal to the cardiac fibres. We systematically quantified the effect of uncertainty on the input parameters, fibre rotation angle, ischaemic depth, blood conductivity and six bidomain conductivities, on outputs that characterise the epicardial potential distribution. We found that three typical types of epicardial potential distributions (one minimum over the central ischaemic region, a tripole of minima, and two minima flanking a central maximum) could all occur for a wide range of ischaemic depths. In addition, the positions of the minima were affected by both the fibre rotation angle and the ischaemic depth, but not by changes in the conductivity values. We also showed that the magnitude of ST depression is affected only by changes in the longitudinal and normal conductivities, but not by the transverse conductivities

Burst-Time-Dependent Plasticity Robustly Guides ON/OFF Segregation in the Lateral Geniculate Nucleus

Spontaneous retinal activity (known as “waves”) remodels synaptic connectivity to the lateral geniculate nucleus (LGN) during development. Analysis of retinal waves recorded with multielectrode arrays in mouse suggested that a cue for the segregation of functionally distinct (ON and OFF) retinal ganglion cells (RGCs) in the LGN may be a desynchronization in their firing, where ON cells precede OFF cells by one second. Using the recorded retinal waves as input, with two different modeling approaches we explore timing-based plasticity rules for the evolution of synaptic weights to identify key features underlying ON/OFF segregation. First, we analytically derive a linear model for the evolution of ON and OFF weights, to understand how synaptic plasticity rules extract input firing properties to guide segregation. Second, we simulate postsynaptic activity with a nonlinear integrate-and-fire model to compare findings with the linear model. We find that spike-time-dependent plasticity, which modifies synaptic weights based on millisecond-long timing and order of pre- and postsynaptic spikes, fails to segregate ON and OFF retinal inputs in the absence of normalization. Implementing homeostatic mechanisms results in segregation, but only with carefully-tuned parameters. Furthermore, extending spike integration timescales to match the second-long input correlation timescales always leads to ON segregation because ON cells fire before OFF cells. We show that burst-time-dependent plasticity can robustly guide ON/OFF segregation in the LGN without normalization, by integrating pre- and postsynaptic bursts irrespective of their firing order and over second-long timescales. We predict that an LGN neuron will become ON- or OFF-responsive based on a local competition of the firing patterns of neighboring RGCs connecting to it. Finally, we demonstrate consistency with ON/OFF segregation in ferret, despite differences in the firing properties of retinal waves. Our model suggests that diverse input statistics of retinal waves can be robustly interpreted by a burst-based rule, which underlies retinogeniculate plasticity across different species

Entanglements of faith: Discourses, practices of care and homeless people in an Italian City of Saints

This is the author accepted manuscript. The final version is available from SAGE via http://dx.doi.org/10.1177/0042098013514620This paper investigates how Catholic-inspired services for homeless people are delivered in Turin, Italy. The purpose is to critically interrogate particular faith-based organisations’ moral discourses on homelessness, and to show how they are enacted through practices of care directed at the homeless subject. The paper contributes to the geographical literature on faith-based organisations addressing its shortcomings – namely the lack of critical and contextual focus on faith-based organisations’ ‘love for the poor’. To address this point, the paper takes a vitalist perspective on the urban and introduces the notion of the ‘entanglements of faith’, which allows an integrated and grounded perspective on faith-based organisations’ interventions. The outcomes of the work suggest that these faith-based organisations propose standardised services that, producing particular assemblages and affective atmospheres, have deep emotional and relational effects on their recipients. Further lines of research are sketched in the conclusions

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Quantitative comparison of myocardial fiber structure between mice, rabbit, and sheep using diffusion tensor cardiovascular magnetic resonance

<p>Abstract</p> <p>Background</p> <p>Accurate interpretations of cardiac functions require precise structural models of the myocardium, but the latter is not available always and for all species. Although scaling or substitution of myocardial fiber information from alternate species has been used in cardiac functional modeling, the validity of such practice has not been tested.</p> <p>Methods</p> <p>Fixed mouse (n = 10), rabbit (n = 6), and sheep (n = 5) hearts underwent diffusion tensor imaging (DTI). The myocardial structures in terms of the left ventricular fiber orientation helix angle index were quantitatively compared between the mouse rabbit and sheep hearts.</p> <p>Results</p> <p>The results show that significant fiber structural differences exist between any two of the three species. Specifically, the subepicardial fiber orientation, and the transmural range and linearity of fiber helix angles are significantly different between the mouse and either rabbit or sheep. Additionally, a significant difference was found between the transmural helix angle range between the rabbit and sheep. Across different circumferential regions of the heart, the fiber orientation was not found to be significantly different.</p> <p>Conclusions</p> <p>The current study indicates that myocardial structural differences exist between different size hearts. An immediate implication of the present findings for myocardial structural or functional modeling studies is that caution must be exercised when extrapolating myocardial structures from one species to another.</p

Facilitating arrhythmia simulation: the method of quantitative cellular automata modeling and parallel running

BACKGROUND: Many arrhythmias are triggered by abnormal electrical activity at the ionic channel and cell level, and then evolve spatio-temporally within the heart. To understand arrhythmias better and to diagnose them more precisely by their ECG waveforms, a whole-heart model is required to explore the association between the massively parallel activities at the channel/cell level and the integrative electrophysiological phenomena at organ level. METHODS: We have developed a method to build large-scale electrophysiological models by using extended cellular automata, and to run such models on a cluster of shared memory machines. We describe here the method, including the extension of a language-based cellular automaton to implement quantitative computing, the building of a whole-heart model with Visible Human Project data, the parallelization of the model on a cluster of shared memory computers with OpenMP and MPI hybrid programming, and a simulation algorithm that links cellular activity with the ECG. RESULTS: We demonstrate that electrical activities at channel, cell, and organ levels can be traced and captured conveniently in our extended cellular automaton system. Examples of some ECG waveforms simulated with a 2-D slice are given to support the ECG simulation algorithm. A performance evaluation of the 3-D model on a four-node cluster is also given. CONCLUSIONS: Quantitative multicellular modeling with extended cellular automata is a highly efficient and widely applicable method to weave experimental data at different levels into computational models. This process can be used to investigate complex and collective biological activities that can be described neither by their governing differentiation equations nor by discrete parallel computation. Transparent cluster computing is a convenient and effective method to make time-consuming simulation feasible. Arrhythmias, as a typical case, can be effectively simulated with the methods described

Utilizing associational resistance for biocontrol: impacted by temperature, supported by indirect defence

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Comparison of diffusion tensor imaging by cardiovascular magnetic resonance and gadolinium enhanced 3D image intensity approaches to investigation of structural anisotropy in explanted rat hearts

Background: Cardiovascular magnetic resonance (CMR) can through the two methods 3D FLASH and diffusion tensor imaging (DTI) give complementary information on the local orientations of cardiomyocytes and their laminar arrays. Methods: Eight explanted rat hearts were perfused with Gd-DTPA contrast agent and fixative and imaged in a 9.4T magnet by two types of acquisition: 3D fast low angle shot (FLASH) imaging, voxels 50 × 50 × 50 μm, and 3D spin echo DTI with monopolar diffusion gradients of 3.6 ms duration at 11.5 ms separation, voxels 200 × 200 × 200 μm. The sensitivity of each approach to imaging parameters was explored. Results:The FLASH data showed laminar alignments of voxels with high signal, in keeping with the presumed predominance of contrast in the interstices between sheetlets. It was analysed, using structure-tensor (ST) analysis, to determine the most (v 1 ST ), intermediate (v 2 ST ) and least (v 3 ST ) extended orthogonal directions of signal continuity. The DTI data was analysed to determine the most (e 1 DTI ), intermediate (e 2 DTI ) and least (e 3 DTI ) orthogonal eigenvectors of extent of diffusion. The correspondence between the FLASH and DTI methods was measured and appraised. The most extended direction of FLASH signal (v 1 ST ) agreed well with that of diffusion (e 1 DTI ) throughout the left ventricle (representative discrepancy in the septum of 13.3 ± 6.7°: median ± absolute deviation) and both were in keeping with the expected local orientations of the long-axis of cardiomyocytes. However, the orientation of the least directions of FLASH signal continuity (v 3 ST ) and diffusion (e 3 ST ) showed greater discrepancies of up to 27.9 ± 17.4°. Both FLASH (v 3 ST ) and DTI (e 3 DTI ) where compared to directly measured laminar arrays in the FLASH images. For FLASH the discrepancy between the structure-tensor calculated v 3 ST and the directly measured FLASH laminar array normal was of 9 ± 7° for the lateral wall and 7 ± 9° for the septum (median ± inter quartile range), and for DTI the discrepancy between the calculated v 3 DTI and the directly measured FLASH laminar array normal was 22 ± 14° and 61 ± 53.4°. DTI was relatively insensitive to the number of diffusion directions and to time up to 72 hours post fixation, but was moderately affected by b-value (which was scaled by modifying diffusion gradient pulse strength with fixed gradient pulse separation). Optimal DTI parameters were b = 1000 mm/s2 and 12 diffusion directions. FLASH acquisitions were relatively insensitive to the image processing parameters explored. Conclusions: We show that ST analysis of FLASH is a useful and accurate tool in the measurement of cardiac microstructure. While both FLASH and the DTI approaches appear promising for mapping of the alignments of myocytes throughout myocardium, marked discrepancies between the cross myocyte anisotropies deduced from each method call for consideration of their respective limitations