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Heart rate variability (HRV) analysis has quantified the functioning of the autonomic regulation of the heart and heart's ability to respond. However, majority of studies on HRV report several differences between patients with congestive heart failure (CHF) and healthy subjects, such as time-domain, frequency domain and nonlinear HRV measures. In the paper, we mainly presented a new approach to detect congestive heart failure (CHF) based on combination support vector machine (SVM) and three nonstandard heart rate variability (HRV) measures (e.g. SUM_TD, SUM_FD and SUM_IE). The CHF classification model was presented by using SVM classifier with the combination SUM_TD and SUM_FD. In the analysis performed, we found that the CHF classification algorithm could obtain the best performance with the CHF classification accuracy, sensitivity and specificity of 100%, 100%, 100%, respectively. [ABSTRACT FROM AUTHOR]

This paper formulates a support vector machine with quantile hyper-spheres (QHSVM) for pattern classification. The idea of QHSVM is to build two quantile hyper-spheres with the same center for positive or negative training samples. Every quantile hyper-sphere is constructed by using pinball loss instead of hinge loss, which makes the new classification model be insensitive to noise, especially the feature noise around the decision boundary. Moreover, the robustness and generalization of QHSVM are strengthened through maximizing the margin between two quantile hyper-spheres, maximizing the inner-class clustering of samples and optimizing the independent quadratic programming for a target class. Besides that, this paper proposes a novel local center-based density estimation method. Based on it, ρ-QHSVM with surrounding and clustering samples is given. Under the premise of high accuracy, the execution speed of ρ-QHSVM can be adjusted. The experimental results in artificial, benchmark and strip steel surface defects datasets show that the QHSVM model has distinct advantages in accuracy and the ρ-QHSVM model is fit for large-scale datasets. [ABSTRACT FROM AUTHOR]

Background: Toxoplasma gondii is one of the most widespread parasites in humans and can cause severe illness in immunocompromised individuals. However, its role in healthy people is probably under-appreciated. The complex epidemiology of this protozoan recognizes several infection routes but consumption of contaminated food is likely to be the predominant one. Among food, consumption of raw and undercooked meat is a relevant route of transmission, but the role of different meat producing animal species and meats thereof is controversial. Objectives: The aim of the present work is to summarize and analyse literature data reporting prevalence estimates of T. gondii in meat animals/meats. Data Sources: We searched Medline, Web of Science, Science Direct (last update 31/03/2015). Eligibility Criteria: Relevant papers should report data from primary studies dealing with the prevalence of T. gondii in meat from livestock species as obtained through direct detection methods. Meta-analysis and meta-regression were performed. Results: Of 1915 papers screened, 69 papers were included, dealing mainly with cattle, pigs and sheep. Pooled prevalences, based on random-effect models, were 2.6% (CI95 [0.5–5.8]) for cattle, 12.3% (CI95 [7.6–17.8]) for pigs and 14.7% (CI95 [8.9–21.5]) for sheep. Due to the high heterogeneity observed, univariable and multivariable meta-regression models were fitted showing that the geographic area for cattle (p = 0.032), the farming type for pigs (p = 0.0004) and the sample composition for sheep (p = 0.03) had significant effects on the prevalences of Toxoplasma detected/estimated. Moreover, the role of different animal species was dependent on the geographic location of animals’ origin. Limitations: Limitations were due mainly to a possible publication bias. Conclusions and Implications: The present work confirms the role of meat, including beef, as T. gondii sources, and highlights the need for a control system for this parasite to be implemented along the meat production chain. Moreover, consumer knowledge should be strengthened in order to reduce the impact of disease. [ABSTRACT FROM AUTHOR]

Recent advances in the efficacy and tolerability of hepatitis C treatments and the introduction of a universal access scheme for the new Direct Acting Antiviral (DAA) therapies in March 2016, has resulted in a rapid increase in the uptake of hepatitis C treatment in Australia. Despite these positive developments, recent data suggest a plateauing of treatment numbers, indicating that more work may need to be done to identify and address ongoing barriers to hepatitis C treatment access and uptake. This paper aims to contribute to our understanding of the ongoing barriers to DAA therapies, with a focus on people who inject drugs. The paper draws on participant interview data from a qualitative research study based on a participatory research design that included a peer researcher with direct experience of both hepatitis C DAA treatment and injecting drug use at all stages of the research process. The study’s findings show that residual barriers to DAA treatment exist at personal, provider and system levels and include poor venous access, DAA treatments not considered ‘core-business’ by opioid substitution treatment (OST) providers, and patients having to manage multiple health and social priorities that interfere with keeping medical appointments such as childcare and poor access to transport services. Further, efforts to increase access to and uptake of DAA hepatitis C treatment over time will require a focus on reducing stigma and discrimination towards people who inject drugs as this remains as a major barrier to care for many people. [ABSTRACT FROM AUTHOR]

Participation in magnetic resonance imaging (MRI) scanning is associated with increased anxiety, thus possibly impacting baseline recording for functional MRI studies. The goal of the paper is to elucidate the significant hemispheric asymmetry between blood-oxygenation-level-dependent (BOLD) signals from precentral gyrus (PCG) and insula in 23 healthy individuals without any former MRI experience recently published in a PLOSONE paper. In addition to BOLD signals state anxiety and heart rate variability (HRV) were analyzed in two resting state sessions (R1, R2). Phase-locking and time delays from BOLD signals were computed in the frequency band 0.07–0.13 Hz. Positive (pTD) and negative time delays (nTD) were found. The pTD characterize descending neural BOLD oscillations spreading from PCG to insula and nTD characterize ascending vascular BOLD oscillations related to blood flow in the middle cerebral artery. HRV power in two low frequency bands 0.06–0.1 Hz and 0.1–0.14 Hz was computed. Based on the anxiety change from R1 to R2, two groups were separated: one with a strong anxiety decline (large change group) and one with a moderate decline or even anxiety increase (small change group). A significant correlation was found only between the left-hemispheric time delay (pTD, nTD) and anxiety change, with a dominance of nTD in the large change group. The analysis of within-scanner HRV revealed a pronounced increase of low frequency power between both resting states, dominant in the band 0.06–0.1 Hz in the large change group and in the band 0.1–0.14 Hz in the small change group. These results suggest different mechanisms related to anxiety processing in healthy individuals. One mechanism (large anxiety change) could embrace an increase of blood circulation in the territory of the left middle cerebral artery (vascular BOLD) and another (small anxiety change) translates to rhythmic central commands (neural BOLD) in the frequency band 0.1–0.14 Hz. [ABSTRACT FROM AUTHOR]

The human pulmonary valve, one of the key cardiac structures, plays an important role in circulatory system. However, there are few mathematical models to accurately simulate it. In this paper, we establish a geometric model of the normal human pulmonary valve from a mathematical perspective in the fully opening case. Based on the statistical data of the human pulmonary valves, we assume that the motions of the three cusps are symmetrical in the cardiac cycle. Thus, we first propose that each cusp is a part of the cylindrical shell according to its structure and physiological feature. The parameters for the pulmonary valve cusps in three-dimensional space are obtained by the fitting functions. We verify the accuracy of our results by comparing the areas of the pulmonary valve and pulmonary valve flap. [ABSTRACT FROM AUTHOR]

The catastrophic misinterpretation model of panic disorder (PD) predicts that the catastrophic misinterpretation of bodily sensations is a distinctive characteristic of PD. Existing research on this prediction has produced mixed findings. This paper presents a systematic review and meta-analysis of studies comparing the strength of catastrophic misinterpretation of bodily sensations and external events in patients with PD, patients with other anxiety disorders, and healthy controls. Following a systematic screening, seven studies were included in the meta-analysis. For the catastrophic misinterpretation of bodily sensations, analyses showed medium to large effects between patients with PD and healthy controls and between patients with PD and patients with other anxiety disorders. For the catastrophic misinterpretation of external events, analyses showed medium to large effects between patients with PD and healthy controls and a small negative effect between patients with PD and patients with other anxiety disorders. The findings support the assumption that the catastrophic misinterpretation of bodily sensations is a distinctive characteristic of panic disorder and thus lend support to the catastrophic misinterpretation model of PD. [ABSTRACT FROM AUTHOR]

The variability of the heart rate (HRV) is widely studied as it contains information about the activity of the autonomic nervous system (ANS). However, HRV is influenced by breathing, independently of ANS activity. It is therefore important to include respiratory information in HRV analyses in order to correctly interpret the results. In this paper, we propose to record respiratory activity and use this information to separate the tachogram in two components: one which is related to breathing and one which contains all heart rate variations that are unrelated to respiration. Several algorithms to achieve this have been suggested in the literature, but no comparison between the methods has been performed yet. In this paper, we conduct two studies to evaluate the methods' performances to accurately decompose the tachogram in two components and to assess the robustness of the algorithms. The results show that orthogonal subspace projection and an ARMAX model yield the best performances over the two comparison studies. In addition, a real-life example of stress classification is presented to demonstrate that this approach to separate respiratory information in HRV studies can reveal changes in the heart rate variations that are otherwise masked by differing respiratory patterns. [ABSTRACT FROM AUTHOR]

As a common ocular complication for diabetic patients, diabetic retinopathy has become an important public health problem in the world. Early diagnosis and early treatment with the help of fundus imaging technology is an effective control method. In this paper, a robust inverse diffusion equation combining a self-similarity filtering is presented to detect and evaluate diabetic retinopathy using retinal image enhancement. A flux corrected transport technique is used to control diffusion flux adaptively, which eliminates overshoots inherent in the Laplacian operation. Feature preserving denoising by the self-similarity filtering ensures a robust enhancement of noisy and blurry retinal images. Experimental results demonstrate that this algorithm can enhance important details of retinal image data effectively, affording an opportunity for better medical interpretation and subsequent processing. [ABSTRACT FROM AUTHOR]

Air-breathing fish risk losing aerially sourced oxygen to ambient hypoxic water since oxygenated blood from the air-breathing organ returns through the heart to the branchial basket before distribution. This loss is thought to help drive the evolutionary reduction in gill size with the advent of air-breathing. In many teleost fish, gill size is known to be highly plastic by modulation of their anatomic diffusion factor (ADF) with inter-lamellar cell mass (ILCM). In the anoxia-tolerant crucian carp, ILCM recedes with hypoxia but regrows in anoxia. The air-breathing teleost Chitala ornata has been shown to increase gill ADF from normoxic to mildly hypoxic water by reducing ILCM. Here, we test the hypothesis that ADF is modulated to minimize oxygen loss in severe aquatic hypoxia by measuring ADF, gas-exchange, and by using computed tomography scans to reveal possible trans-branchial shunt vessels. Contrary to our hypothesis, ADF does not modulate to prevent oxygen loss and despite no evident trans-branchial shunting, C. ornata loses only 3% of its aerially sourced O2 while still excreting 79% of its CO2 production to the severely hypoxic water. We propose this is achieved by ventilatory control and by compensating the minor oxygen loss by extra aerial O2 uptake. [ABSTRACT FROM AUTHOR]

The maturation of photon-counting detector (PCD) technology promises to enhance routine CT imaging applications with high-fidelity spectral information. In this paper, we demonstrate the power of this synergy and our complementary reconstruction techniques, performing 4D, cardiac PCD-CT data acquisition and reconstruction in a mouse model of atherosclerosis, including calcified plaque. Specifically, in vivo cardiac micro-CT scans were performed in four ApoE knockout mice, following their development of calcified plaques. The scans were performed with a prototype PCD (DECTRIS, Ltd.) with 4 energy thresholds. Projections were sampled every 10 ms with a 10 ms exposure, allowing the reconstruction of 10 cardiac phases at each of 4 energies (40 total 3D volumes per mouse scan). Reconstruction was performed iteratively using the split Bregman method with constraints on spectral rank and spatio-temporal gradient sparsity. The reconstructed images represent the first in vivo, 4D PCD-CT data in a mouse model of atherosclerosis. Robust regularization during iterative reconstruction yields high-fidelity results: an 8-fold reduction in noise standard deviation for the highest energy threshold (relative to unregularized algebraic reconstruction), while absolute spectral bias measurements remain below 13 Hounsfield units across all energy thresholds and scans. Qualitatively, image domain material decomposition results show clear separation of iodinated contrast and soft tissue from calcified plaque in the in vivo data. Quantitatively, spatial, spectral, and temporal fidelity are verified through a water phantom scan and a realistic MOBY phantom simulation experiment: spatial resolution is robustly preserved by iterative reconstruction (10% MTF: 2.8–3.0 lp/mm), left-ventricle, cardiac functional metrics can be measured from iodine map segmentations with ~1% error, and small calcifications (615 μm) can be detected during slow moving phases of the cardiac cycle. Given these preliminary results, we believe that PCD technology will enhance dynamic CT imaging applications with high-fidelity spectral and material information. [ABSTRACT FROM AUTHOR]

We developed a whole-circulation computational model by integrating a transmission line (TL) model describing vascular wave transmission into the established CircAdapt platform of whole-heart mechanics. In the present paper, we verify the numerical framework of our TL model by benchmark comparison to a previously validated pulse wave propagation (PWP) model. Additionally, we showcase the integrated CircAdapt–TL model, which now includes the heart as well as extensive arterial and venous trees with terminal impedances. We present CircAdapt–TL haemodynamics simulations of: 1) a systemic normotensive situation and 2) a systemic hypertensive situation. In the TL–PWP benchmark comparison we found good agreement regarding pressure and flow waveforms (relative errors ≤ 2.9% for pressure, and ≤ 5.6% for flow). CircAdapt–TL simulations reproduced the typically observed haemodynamic changes with hypertension, expressed by increases in mean and pulsatile blood pressures, and increased arterial pulse wave velocity. We observed a change in the timing of pressure augmentation (defined as a late-systolic boost in aortic pressure) from occurring after time of peak systolic pressure in the normotensive situation, to occurring prior to time of peak pressure in the hypertensive situation. The pressure augmentation could not be observed when the systemic circulation was lumped into a (non-linear) three-element windkessel model, instead of using our TL model. Wave intensity analysis at the carotid artery indicated earlier arrival of reflected waves with hypertension as compared to normotension, in good qualitative agreement with findings in patients. In conclusion, we successfully embedded a TL model as a vascular module into the CircAdapt platform. The integrated CircAdapt–TL model allows detailed studies on mechanistic studies on heart-vessel interaction. [ABSTRACT FROM AUTHOR]

Direct cardiac compression (DCC) holds enormous potential as a safe and effective means to treat heart failure patients who require long-term, or even permanent, biventricular support. However, devices developed to date are not tuned to meet the individual compression requirements of the left and right ventricles, which can differ substantially. In this paper, a systematic study examining the relationship, range, and effect of independent pressures on the left and right epicardial surfaces of a passive human heart model was performed as a means to optimize cardiac output via DCC support. Hemodynamic and tissue deformation effects produced by varying epicardial compressions were examined using finite element analysis. Results indicate that 1) designing a direct cardiac compression pump that applies separate pressures to the left and right ventricles is critical to maintain equivalent stroke volume for both ventricles, and 2) left and right ventricular epicardial pressures of 340 mmHg and 44 mmHg, respectively, are required to induce normal ejection fractions in a passive heart. This pilot study provides fundamental insights and guidance towards the design of improved direct cardiac compression devices for long-term circulatory support. [ABSTRACT FROM AUTHOR]

The primary mode of visualization during transcatheter procedures for structrural heart disease is fluoroscopy, which suffers from low contrast and lacks any depth perception, thus limiting the ability of an interventionalist to position a catheter accurately. This paper describes a new image guidance system by utilizing augmented reality to provide a 3D visual environment and quantitative feedback of the catheter’s position within the heart of the patient. The real-time 3D position of the catheter is acquired via two fluoroscopic images taken at different angles, and a patient-specific 3D heart rendering is produced pre-operatively from a CT scan. The spine acts as a fiduciary land marker, allowing the position and orientation of the catheter within the heart to be fully registered. The automated registration method is based on Fourier transformation, and has a high success rate (100%), low registration error (0.42 mm), and clinically acceptable computational cost (1.22 second). The 3D renderings are displayed and updated on the augmented reality device (i.e., Microsoft HoloLens), which can provide pre-set views of various angles of the heart using voice-command. This new image-guidance system with augmented reality provides a better visualization to interventionalists and potentially assists them in understanding of complicated cases. Furthermore, this system coupled with the developed 3D printed models can serve as a training tool for the next generation of cardiac interventionalists. [ABSTRACT FROM AUTHOR]

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatation of the coronary arteries. However, a direct measurement of the coronaries’ lumen diameter in IUGR has not been reported before. The aim of this paper is to perform, for the first time, a quantitative analysis of the effects of IUGR in cardiac geometry and coronary vessel size in a well-known rabbit model of IUGR using synchrotron-based X-ray Phase Contrast Tomography Imaging (X-PCI). Eight rabbit fetal hearts were imaged non-destructively with X-PCI. 3D reconstructions of the coronary arterial tree were obtained after semi-automatic image segmentation. Different morphometric features including vessel lumen diameter of the three main coronaries were automatically quantified. IUGR fetuses had more globular hearts and dilated coronary arteries as compared to controls. We have quantitatively shown that IUGR leads to structural coronary vascular tree remodelling and enlargement as an adaptation mechanism in response to an adverse environment of restricted oxygen and nutrients and increased perfusion pressure. [ABSTRACT FROM AUTHOR]

The advent of smartphones has advanced the use of embedded sensors to acquire various physiological information. For example, smartphone camera sensors and accelerometers can provide heart rhythm signals to the subjects, while microphones can give respiratory signals. However, the acquired smartphone-based physiological signals are more vulnerable to motion and noise artifacts (MNAs) compared to using medical devices, since subjects need to hold the smartphone with proper contact to the smartphone camera and lens stably and tightly for a duration of time without any movement in the hand or finger. This results in more MNA than traditional methods, such as placing a finger inside a tightly enclosed pulse oximeter to get PPG signals, which provides stable contact between the sensor and the subject’s finger. Moreover, a smartphone lens does not block ambient light in an effective way, while pulse oximeters are designed to block the ambient light effectively. In this paper, we propose a novel diversity method for smartphone signals that reduces the effect of MNAs during heart rhythm signal detection by 1) acquiring two heterogeneous signals from a color intensity signal and a fingertip movement signal, and 2) selecting the less MNA-corrupted signal of the two signals. The proposed method has advantages in that 1) diversity gain can be obtained from the two heterogeneous signals when one signal is clean while the other signal is corrupted, and 2) acquisition of the two heterogeneous signals does not double the acquisition procedure but maintains a single acquisition procedure, since two heterogeneous signals can be obtained from a single smartphone camera recording. In our diversity method, we propose to choose the better signal based on the signal quality indices (SQIs), i.e., standard deviation of instantaneous heart rate (STD–HR), root mean square of the successive differences of peak-to-peak time intervals (RMSSD–T), and standard deviation of peak values (STD–PV). As a performance metric evaluating the proposed diversity method, the ratio of usable period is considered. Experimental results show that our diversity method increases the usable period 19.53% and 6.25% compared to the color intensity or the fingertip movement signals only, respectively. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy is a complication of diabetes that produces changes in the blood vessel structure in the retina, which can cause severe vision problems and even blindness. In this paper, we demonstrate that by identifying topological features in very high resolution retinal images, we can construct a classifier that discriminates between healthy patients and those with diabetic retinopathy using summary statistics of these features. Topological data analysis identifies the features as connected components and holes in the images and describes the extent to which they persist across the image. These features are encoded in persistence diagrams, summaries of which can be used to discrimate between diabetic and healthy patients. The method has the potential to be an effective automated screening tool, with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Background and aim: The development and use of experimental models using lymphatic cannulation techniques have been hampered by the lack of high-quality colour imaging of lymphatic vessels in situ. Most descriptions of lymphatic anatomy in sheep have historically depended on schematic diagrams due to limitations in the ability to publish colour images of the lymphatic vessels with decent resolution. The aim of this work was to encourage more widespread use of the ovine cannulation model by providing clear photographic images identifying the location and anatomical layout of some major lymphatic ducts and their in situ relationship to surrounding tissues. Methods: The cadavers of the sheep were collected after they had been euthanized at the end of animal trials not associated with this study. The lymphatics were dissected and exposed to show their appearance in the surrounding tissues and their relationship to other organs. Patent Blue was used to locate lymphatic vessels in exploratory preparations. However, in order to present the natural appearance of the vessels, we used minimal dissection and dye was not used for the photographed examples. Instead, we have indicated the course of the vessels with lines where their position is less clear. Results and conclusion: In this paper, we have used sheep specimens as examples to show characteristic images of lymphatic vessels. The images of in situ lymphatics and lymph nodes combined with schematic summaries provide a concise illustration of the lymphatic drainage scheme in sheep. [ABSTRACT FROM AUTHOR]

In this paper, we demonstrate a comprehensive method for segmenting the retinal vasculature in camera images of the fundus. This is of interest in the area of diagnostics for eye diseases that affect the blood vessels in the eye. In a departure from other state-of-the-art methods, vessels are first pre-grouped together with graph partitioning, using a spectral clustering technique based on morphological features. Local curvature is estimated over the whole image using eigenvalues of Hessian matrix in order to enhance the vessels, which appear as ridges in images of the retina. The result is combined with a binarized image, obtained using a threshold that maximizes entropy, to extract the retinal vessels from the background. Speckle type noise is reduced by applying a connectivity constraint on the extracted curvature based enhanced image. This constraint is varied over the image according to each region's predominant blood vessel size. The resultant image exhibits the central light reflex of retinal arteries and veins, which prevents the segmentation of whole vessels. To address this, the earlier entropy-based binarization technique is repeated on the original image, but crucially, with a different threshold to incorporate the central reflex vessels. The final segmentation is achieved by combining the segmented vessels with and without central light reflex. We carry out our approach on DRIVE and REVIEW, two publicly available collections of retinal images for research purposes. The obtained results are compared with state-of-the-art methods in the literature using metrics such as sensitivity (true positive rate), selectivity (false positive rate) and accuracy rates for the DRIVE images and measured vessel widths for the REVIEW images. Our approach out-performs the methods in the literature. [ABSTRACT FROM AUTHOR]

This paper presents a lightweight synthesis algorithm, named adaptive region segmentation based piecewise linear (ARSPL) algorithm, for reconstructing standard 12-lead electrocardiogram (ECG) signals from a 3-lead subset (I, II and V2). Such a lightweight algorithm is particularly suitable for healthcare mobile devices with limited resources for computing, communication and data storage. After detection of R-peaks, the ECGs are segmented by cardiac cycles. Each cycle is further divided into four regions according to different cardiac electrical activity stages. A personalized linear regression algorithm is then applied to these regions respectively for improved ECG synthesis. The proposed ARSPL method has been tested on 39 subjects randomly selected from the PTB diagnostic ECG database and achieved accurate synthesis of remaining leads with an average correlation coefficient of 0.947, an average root-mean-square error of 55.4μV, and an average runtime performance of 114ms. Overall, these results are significantly better than those of the common linear regression method, the back propagation (BP) neural network and the BP optimized using the genetic algorithm. We have also used the reconstructed ECG signals to evaluate the denivelation of ST segment, which is a potential symptom of intrinsic myocardial disease. After ARSPL, only 10.71% of the synthesized ECG cycles are with a ST-level synthesis error larger than 0.1mV, which is also better than those of the three above-mentioned methods. [ABSTRACT FROM AUTHOR]

The minimally invasive transcatheter aortic valve implantation (TAVI) is the most prevalent method to treat aortic valve stenosis. For pre-operative surgical planning, contrast-enhanced coronary CT angiography (CCTA) is used as the imaging technique to acquire 3-D measurements of the valve. Accurate localization of the eight aortic valve landmarks in CT images plays a vital role in the TAVI workflow because a small error risks blocking the coronary circulation. In order to examine the valve and mark the landmarks, physicians prefer a view parallel to the hinge plane, instead of using the conventional axial, coronal or sagittal view. However, customizing the view is a difficult and time-consuming task because of unclear aorta pose and different artifacts of CCTA. Therefore, automatic localization of landmarks can serve as a useful guide to the physicians customizing the viewpoint. In this paper, we present an automatic method to localize the aortic valve landmarks using colonial walk, a regression tree-based machine-learning algorithm. For efficient learning from the training set, we propose a two-phase optimized search space learning model in which a representative point inside the valvular area is first learned from the whole CT volume. All eight landmarks are then learned from a smaller area around that point. Experiment with preprocedural CCTA images of TAVI undergoing patients showed that our method is robust under high stenotic variation and notably efficient, as it requires only 12 milliseconds to localize all eight landmarks, as tested on a 3.60 GHz single-core CPU. [ABSTRACT FROM AUTHOR]

One-compartment models are widely used to quantify hemodynamic parameters such as perfusion, blood volume and mean transit time. These parameters are routinely used for clinical diagnosis and monitoring of disease development and are thus of high relevance. However, it is known that common estimation techniques are discretization dependent and values can be erroneous. In this paper we present a new model that enables systematic quantification of discretization errors. Specifically, we introduce a continuous flow model for tracer propagation within the capillary tissue, used to evaluate state-of-the-art one-compartment models. We demonstrate that one-compartment models are capable of recovering perfusion accurately when applied to only one compartment, i.e. the whole region of interest. However, substantial overestimation of perfusion occurs when applied to fractions of a compartment. We further provide values of the estimated overestimation for various discretization levels, and also show that overestimation can be observed in real-life applications. Common practice of using compartment models for fractions of tissue violates model assumptions and careful interpretation is needed when using the computed values for diagnosis and treatment planning. [ABSTRACT FROM AUTHOR]

The biological pacemaker approach is an alternative to cardiac electronic pacemakers. Its main objective is to create pacemaking activity from added or modified distribution of spontaneous cells in the myocardium. This paper aims to assess how automaticity strength of pacemaker cells (i.e. their ability to maintain robust spontaneous activity with fast rate and to drive neighboring quiescent cells) and structural linear anisotropy, combined with density and spatial distribution of pacemaker cells, may affect the macroscopic behavior of the biological pacemaker. A stochastic algorithm was used to randomly distribute pacemaker cells, with various densities and spatial distributions, in a semi-continuous mathematical model. Simulations of the model showed that stronger automaticity allows onset of spontaneous activity for lower densities and more homogeneous spatial distributions, displayed more central foci, less variability in cycle lengths and synchronization of electrical activation for similar spatial patterns, but more variability in those same variables for dissimilar spatial patterns. Compared their isotropic counterparts, in silico anisotropic monolayers had less central foci and displayed more variability in cycle lengths and synchronization of electrical activation for both similar and dissimilar spatial patterns. The present study established a link between microscopic structure and macroscopic behavior of the biological pacemaker, and may provide crucial information for optimized biological pacemaker therapies. [ABSTRACT FROM AUTHOR]

Engaged scholarship, a movement that has been growing steadily since 1995, offers a new way of bridging gaps between the university and civil society. Numerous papers and reports have been published since Boyer’s foundational discourse in 1996. Yet, beyond a growing interest in orienting universities’ missions, we observed a lack a formal definition and conceptualization of this movement. Based on a scoping review of the literature over the past 20 years, the objective of this article is to propose a conceptualization of engaged scholarship. More specifically, we define its values, principles, and processes. We conclude with a discussion of the implications of this new posture for faculty and students, as well as for the university as an institution. [ABSTRACT FROM AUTHOR]

The structure and appearance of the blood vessel network in retinal fundus images is an essential part of diagnosing various problems associated with the eyes, such as diabetes and hypertension. In this paper, an automatic retinal vessel segmentation method utilizing matched filter techniques coupled with an AdaBoost classifier is proposed. The fundus image is enhanced using morphological operations, the contrast is increased using contrast limited adaptive histogram equalization (CLAHE) method and the inhomogeneity is corrected using Retinex approach. Then, the blood vessels are enhanced using a combination of B-COSFIRE and Frangi matched filters. From this preprocessed image, different statistical features are computed on a pixel-wise basis and used in an AdaBoost classifier to extract the blood vessel network inside the image. Finally, the segmented images are postprocessed to remove the misclassified pixels and regions. The proposed method was validated using publicly accessible Digital Retinal Images for Vessel Extraction (DRIVE), Structured Analysis of the Retina (STARE) and Child Heart and Health Study in England (CHASE_DB1) datasets commonly used for determining the accuracy of retinal vessel segmentation methods. The accuracy of the proposed segmentation method was comparable to other state of the art methods while being very close to the manual segmentation provided by the second human observer with an average accuracy of 0.972, 0.951 and 0.948 in DRIVE, STARE and CHASE_DB1 datasets, respectively. [ABSTRACT FROM AUTHOR]

High-throughput gene expression data are often obtained from pure or complex (heterogeneous) biological samples. In the latter case, data obtained are a mixture of different cell types and the heterogeneity imposes some difficulties in the analysis of such data. In order to make conclusions on gene expresssion data obtained from heterogeneous samples, methods such as microdissection and flow cytometry have been employed to physically separate the constituting cell types. However, these manual approaches are time consuming when measuring the responses of multiple cell types simultaneously. In addition, exposed samples, on many occasions, end up being contaminated with external perturbations and this may result in an altered yield of molecular content. In this paper, we model the heterogeneous gene expression data using a Bayesian framework, treating the cell type proportions and the cell-type specific expressions as the parameters of the model. Specifically, we present a novel sequential Monte Carlo (SMC) sampler for estimating the model parameters by approximating their posterior distributions with a set of weighted samples. The SMC framework is a robust and efficient approach where we construct a sequence of artificial target (posterior) distributions on spaces of increasing dimensions which admit the distributions of interest as marginals. The proposed algorithm is evaluated on simulated datasets and publicly available real datasets, including Affymetrix oligonucleotide arrays and national center for biotechnology information (NCBI) gene expression omnibus (GEO), with varying number of cell types. The results obtained on all datasets show a superior performance with an improved accuracy in the estimation of cell type proportions and the cell-type specific expressions, and in addition, more accurate identification of differentially expressed genes when compared to other widely known methods for blind decomposition of heterogeneous gene expression data such as Dsection and the nonnegative matrix factorization (NMF) algorithms. MATLAB implementation of the proposed SMC algorithm is available to download at . [ABSTRACT FROM AUTHOR]

The mitral valve, which lies between the left atrium and the left ventricle, plays an important role in controlling the uniflux of blood from the left atrium to the left ventricle as one of the four human heart valves. A precise description of the shape of human mitral valve has vital significance in studying its physiological structure and periodic movement. Unsatisfyingly, there is almost no unified mathematical description of the same shape of human mitral valve in literature. In this paper, we present a geometric model for human mitral valve, as an elastic shell with a special shape. Parametric equations for the shape of human mitral valve are provided, including the anterior and the posterior parts, which can be thought as portions of two interfacing semi-elliptic cylindrical shells. The minor axis of one ellipse is equal to the major axis of the other. All the parameters are determined from the statistical data. Comparison of fitting results with existing examples validates the accuracy of our geometric model. Based on the fitting shape, one can further simulate the physiological function of the mitral valve using a suitable dynamic physical equation. [ABSTRACT FROM AUTHOR]

Patients with a Ventricular Assist Device (VAD) are hemodynamically stable but show an impaired exercise capacity. Aim of this work is to identify and to describe the limiting factors of exercise physiology with a VAD. We searched for data concerning exercise in heart failure condition and after VAD implantation from the literature. Data were analyzed by using a cardiorespiratory simulator that worked as a collector of inputs coming from different papers. As a preliminary step the simulator was used to reproduce the evolution of hemodynamics from rest to peak exercise (ergometer cycling) in heart failure condition. Results evidence an increase of cardiac output of +2.8 l/min and a heart rate increase to 67% of the expected value. Then, we simulated the effect of a continuous-flow VAD at both rest and exercise. Total cardiac output increases of +3.0 l/min (+0.9 l/min due to the VAD and +2.1 l/min to the native ventricle). Since the left ventricle works in a non-linear portion of the diastolic stiffness line, we observed a consistent increase of pulmonary capillary wedge pressure (from 14 to 20 mmHg) for a relatively small increase of end-diastolic volume (from 182 to 189 cm3). We finally increased VAD speed during exercise to the maximum possible value and we observed a reduction of wedge pressure (-4.5 mmHg), a slight improvement of cardiac output (8.0 l/min) and a complete unloading of the native ventricle. The VAD can assure a proper hemodynamics at rest, but provides an insufficient unloading of the left ventricle and does not prevent wedge pressure from rising during exercise. Neither the VAD provides major benefits during exercise in terms of total cardiac output, which increases to a similar extend to an unassisted heart failure condition. VAD speed modulation can contribute to better unload the ventricle but the maximal flow reachable with the current devices is below the cardiac output observed in a healthy heart. [ABSTRACT FROM AUTHOR]

Blood oxygenation mapping by the means of optical oximetry is of significant importance in clinical trials. This paper uses hyperspectral imaging technology to obtain in vivo images for blood oxygenation detection. The experiment involves dorsal skin fold window chamber preparation which was built on adult (8–10 weeks of age) female BALB/c nu/nu mice and in vivo image acquisition which was performed by hyperspectral imaging system. To get the accurate spatial and spectral information of targets, an automatic registration scheme is proposed. An adaptive feature detection method which combines the local threshold method and the level-set filter is presented to extract target vessels. A reliable feature matching algorithm with the correlative information inherent in hyperspectral images is used to kick out the outliers. Then, the registration images are used for blood oxygenation mapping. Registration evaluation results show that most of the false matches are removed and the smooth and concentrated spectra are obtained. This intensity invariant feature detection with outliers-removing feature matching proves to be effective in hyperspectral vessel image registration. Therefore, in vivo hyperspectral imaging system by the assistance of the proposed registration scheme provides a technique for blood oxygenation research. [ABSTRACT FROM AUTHOR]

Objective: Thrombin-activatable fibrinolysis inhibitor (TAFI) reduces the breakdown of fibrin clots through its action as an indirect inhibitor of plasmin. Studies in TAFI-deficient mice have implicated a potential role for TAFI in Abdominal Aortic Aneurysm (AAA) disease. The role of TAFI inhibition on AAA formation in adult ApoE-/- mice is unknown. The aim of this paper was to investigate the effects of TAFI inhibition on AAA development and progression. Methods: Using the Angiotensin II model of AAA, male ApoE-/- mice were infused with Angiotensin II 750ng/kg/min with or without a monoclonal antibody inhibitor of plasmin-mediated activation of TAFI, MA-TCK26D6, or a competitive small molecule inhibitor of TAFI, UK-396082. Results: Inhibition of TAFI in the Angiotensin II model resulted in a decrease in the mortality associated with AAA rupture (from 40.0% to 16.6% with MA-TCK26D6 (log-rank Mantel Cox test p = 0.16), and 8.3% with UK-396082 (log-rank Mantel Cox test p = 0.05)). Inhibition of plasmin-mediated TAFI activation reduced the incidence of AAA from 52.4% to 30.0%. However, late treatment with MA-TCK26D6 once AAA were already established had no effect on the progression of AAA in this model. Conclusions: The formation of intra-mural thrombus is responsible for the dissection and early rupture in the angiotensin II model of AAA, and this process can be prevented through inhibition of TAFI. Late treatment with a TAFI inhibitor does not prevent AAA progression. These data may indicate a role for inhibition of plasmin-mediated TAFI activation in the early stages of AAA development, but not in its progression. [ABSTRACT FROM AUTHOR]

The BeatBox simulation environment combines flexible script language user interface with the robust computational tools, in order to setup cardiac electrophysiology in-silico experiments without re-coding at low-level, so that cell excitation, tissue/anatomy models, stimulation protocols may be included into a BeatBox script, and simulation run either sequentially or in parallel (MPI) without re-compilation. BeatBox is a free software written in C language to be run on a Unix-based platform. It provides the whole spectrum of multi scale tissue modelling from 0-dimensional individual cell simulation, 1-dimensional fibre, 2-dimensional sheet and 3-dimensional slab of tissue, up to anatomically realistic whole heart simulations, with run time measurements including cardiac re-entry tip/filament tracing, ECG, local/global samples of any variables, etc. BeatBox solvers, cell, and tissue/anatomy models repositories are extended via robust and flexible interfaces, thus providing an open framework for new developments in the field. In this paper we give an overview of the BeatBox current state, together with a description of the main computational methods and MPI parallelisation approaches. [ABSTRACT FROM AUTHOR]

This paper develops a means of more easily and less invasively estimating ventricular dead space volume (Vd), an important, but difficult to measure physiological parameter. Vd represents a subject and condition dependent portion of measured ventricular volume that is not actively participating in ventricular function. It is employed in models based on the time varying elastance concept, which see widespread use in haemodynamic studies, and may have direct diagnostic use. The proposed method involves linear extrapolation of a Frank-Starling curve (stroke volume vs end-diastolic volume) and its end-systolic equivalent (stroke volume vs end-systolic volume), developed across normal clinical procedures such as recruitment manoeuvres, to their point of intersection with the y-axis (where stroke volume is 0) to determine Vd. To demonstrate the broad applicability of the method, it was validated across a cohort of six sedated and anaesthetised male Pietrain pigs, encompassing a variety of cardiac states from healthy baseline behaviour to circulatory failure due to septic shock induced by endotoxin infusion. Linear extrapolation of the curves was supported by strong linear correlation coefficients of R = 0.78 and R = 0.80 average for pre- and post- endotoxin infusion respectively, as well as good agreement between the two linearly extrapolated y-intercepts (Vd) for each subject (no more than 7.8% variation). Method validity was further supported by the physiologically reasonable Vd values produced, equivalent to 44.3–53.1% and 49.3–82.6% of baseline end-systolic volume before and after endotoxin infusion respectively. This method has the potential to allow Vd to be estimated without a particularly demanding, specialised protocol in an experimental environment. Further, due to the common use of both mechanical ventilation and recruitment manoeuvres in intensive care, this method, subject to the availability of multi-beat echocardiography, has the potential to allow for estimation of Vd in a clinical environment. [ABSTRACT FROM AUTHOR]

Cardiovascular disease is one of the leading causes of death worldwide, in particular myocardial dysfunction, which may lead to heart failure eventually. Understanding the electro-mechanics of the heart will help in developing more effective clinical treatments. In this paper, we present a multi-scale electro-mechanics model of the left ventricle (LV). The Holzapfel-Ogden constitutive law was used to describe the passive myocardial response in tissue level, a modified Grandi-Pasqualini-Bers model was adopted to model calcium dynamics in individual myocytes, and the active tension was described using the Niederer-Hunter-Smith myofilament model. We first studied the electro-mechanics coupling in a single myocyte in the healthy and diseased left ventricle, and then the single cell model was embedded in a dynamic LV model to investigate the compensation mechanism of LV pump function due to myocardial dysfunction caused by abnormality in cellular calcium dynamics. The multi-scale LV model was solved using an in-house developed hybrid immersed boundary method with finite element extension. The predictions of the healthy LV model agreed well with the clinical measurements and other studies, and likewise, the results in the failing states were also consistent with clinical observations. In particular, we found that a low level of intracellular Ca2+ transient in myocytes can result in LV pump function failure even with increased myocardial contractility, decreased systolic blood pressure, and increased diastolic filling pressure, even though they will increase LV stroke volume. Our work suggested that treatments targeted at increased contractility and lowering the systolic blood pressure alone are not sufficient in preventing LV pump dysfunction, restoring a balanced physiological Ca2+ handling mechanism is necessary. [ABSTRACT FROM AUTHOR]

This paper presents the concept of perfect matrices of Lagrange differences which are used to analyze relationships between RR and JT intervals during the bicycle ergometry exercise. The concept of the perfect matrix of Lagrange differences, its parameters, the construction of the load function and the corresponding optimization problem, the introduction of internal and external smoothing, embedding of the scalar parameter time series into the phase plane—all these computational techniques allow visualization of complex dynamical processes taking place in the cardiovascular system during the load and the recovery processes. Detailed analysis is performed with one person’s RR and JT records only—but the presented techniques open new possibilities for novel interpretation of the dynamics of the cardiovascular system. [ABSTRACT FROM AUTHOR]

Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group. [ABSTRACT FROM AUTHOR]

Abdominal aortic aneurysm (AAA) is a localized enlargement of the abdominal aorta, such that the diameter exceeds 3 cm. The natural history of AAA is progressive growth leading to rupture, an event that carries up to 90% risk of mortality. Hence there is a need to predict the growth of the diameter of the aorta based on the diameter of a patient’s aneurysm at initial screening and aided by non-invasive biomarkers. IL-6 is overexpressed in AAA and was suggested as a prognostic marker for the risk in AAA. The present paper develops a mathematical model which relates the growth of the abdominal aorta to the serum concentration of IL-6. Given the initial diameter of the aorta and the serum concentration of IL-6, the model predicts the growth of the diameter at subsequent times. Such a prediction can provide guidance to how closely the patient’s abdominal aorta should be monitored. The mathematical model is represented by a system of partial differential equations taking place in the aortic wall, where the media is assumed to have the constituency of an hyperelastic material. [ABSTRACT FROM AUTHOR]

Spiral waves are observed in the chemical, physical and biological systems, and the emergence of spiral waves in cardiac tissue is linked to some diseases such as heart ventricular fibrillation and epilepsy; thus it has importance in theoretical studies and potential medical applications. Noise is inevitable in neuronal systems and can change the electrical activities of neuron in different ways. Many previous theoretical studies about the impacts of noise on spiral waves focus an unbounded Gaussian noise and even colored noise. In this paper, the impacts of bounded noise and rewiring of network on the formation and instability of spiral waves are discussed in small-world (SW) network of Hodgkin-Huxley (HH) neurons through numerical simulations, and possible statistical analysis will be carried out. Firstly, we present SW network of HH neurons subjected to bounded noise. Then, it is numerically demonstrated that bounded noise with proper intensity σ, amplitude A, or frequency f can facilitate the formation of spiral waves when rewiring probability p is below certain thresholds. In other words, bounded noise-induced resonant behavior can occur in the SW network of neurons. In addition, rewiring probability p always impairs spiral waves, while spiral waves are confirmed to be robust for small p, thus shortcut-induced phase transition of spiral wave with the increase of p is induced. Furthermore, statistical factors of synchronization are calculated to discern the phase transition of spatial pattern, and it is confirmed that larger factor of synchronization is approached with increasing of rewiring probability p, and the stability of spiral wave is destroyed. [ABSTRACT FROM AUTHOR]

R-/S-2-(2-Hydroxypropanamido) benzoic acid (R-/S-HPABA), a marine-derived anti-inflammatory drug, however, the antiplatelet and antithrombotic effects have not been investigated. In this paper, the in vitro antiplatelet activities and in vivo antithrombotic effects of R-/S-HPABA were investigated, for the first time. The effects of R-/S-HPABA on platelet aggregation induced by adenosine diphosphate (ADP), collagen (COLL) and arachidonic acid (AA) were evaluated. In addition, the in vivo bleeding time, clotting time, collagen-epinephrine induced pulmonary thrombosis and common carotid artery thrombosis were also investigated in rats. R-/S-HPABA significantly inhibited ADP, COLL and AA induced platelet aggregation in rabbit platelet rich plasma in vitro compared with control group, to a degree similar to that of aspirin. Besides, R-/S-HPABA prolonged bleeding time and clotting time as well as increased the recovery rate obviously in pulmonary thrombosis. Moreover, the level of thromboxane B2 (TXB2) was decreased while the production of 6-keto-prostaglandin F1α (6-keto-PGF1α) was increased markedly by R-/S-HPABA. Furthermore, R-/S-HPABA reduced carotid artery thrombosis weight. These results illustrated that R-/S-HPABA could be a potent antiplatelet aggregation and antithrombotic agent. [ABSTRACT FROM AUTHOR]

With the development of hybrid imaging scanners, micro-CT is widely used in locating abnormalities, studying drug metabolism, and providing structural priors to aid image reconstruction in functional imaging. Due to the low contrast of soft tissues, segmentation of soft tissue organs from mouse micro-CT images is a challenging problem. In this paper, we propose a mouse segmentation scheme based on dynamic contrast enhanced micro-CT images. With a homemade fast scanning micro-CT scanner, dynamic contrast enhanced images were acquired before and after injection of non-ionic iodinated contrast agents (iohexol). Then the feature vector of each voxel was extracted from the signal intensities at different time points. Based on these features, the heart, liver, spleen, lung, and kidney could be classified into different categories and extracted from separate categories by morphological processing. The bone structure was segmented using a thresholding method. Our method was validated on seven BALB/c mice using two different classifiers: a support vector machine classifier with a radial basis function kernel and a random forest classifier. The results were compared to manual segmentation, and the performance was assessed using the Dice similarity coefficient, false positive ratio, and false negative ratio. The results showed high accuracy with the Dice similarity coefficient ranging from 0.709 ± 0.078 for the spleen to 0.929 ± 0.006 for the kidney. [ABSTRACT FROM AUTHOR]

This paper aims to study the thrombolytic effect of low-frequency ultrasound combined with targeted urokinase-containing microbubble contrast agents on treatment of thrombosis in rabbit femoral artery; and to determine the optimal combination of parameters for achieving thrombolysis in this model. A biotinylated-avidin method was used to prepare microbubble contrast agents carrying urokinase and Arg-Gly-Asp-Ser (RGDS) peptides. Following femoral artery thrombosis in New Zealand white rabbits, microbubble contrast agents were injected intravenously, and ultrasonic exposure was applied. A 3 × 2 × 2 factorial table was applied to categorize the experimental animals based on different levels of combination of ultrasonic frequencies (Factor A: 1.6 MHz, 2.2 MHz, 2.8 MHz), doses of urokinase (Factor B: 90,000 IU/Kg, 180,000 IU/Kg) and ultrasound exposure time (Factor C: 30 min, 60 min). A total of 72 experimental animals were randomly divided into 12 groups (n = 6/group). Doppler techniques were used to assess blood flow in the distal end of the thrombotic femoral artery during the 120 minutes thrombolysis experiment. The rate of recanalization following thrombolysis was calculated, and thrombolytic efficacy was evaluated and compared. The thrombolytic recanalization rate for all experimental subjects after thrombolytic therapy was 68.1%. The optimal parameters for thrombolysis were determined to be 1) an ultrasound frequency of 2.2 MHz and 2) a 90,000 IU/kg dose of urokinase. Ultrasound exposure time (30 min vs. 60 min) had no significant effect on the thrombolytic effects. The combination of local low-frequency ultrasound radiation, targeted microbubbles, and thrombolytic urokinase induced thrombolysis of femoral artery thrombosis in a rabbit model. The ultrasonic frequency of 2.2 MHz and urokinase dose of 90,000 IU/kg induced optimal thrombolytic effects, while the application of either 30 min or 60 min of ultrasound exposure had similar effects. [ABSTRACT FROM AUTHOR]

Current paper is focused on transient modeling of blood flow through a tapered stenosed arteries surrounded a by solenoid under the presence of heat transfer. The oxygenated and deoxygenated blood are considered here by the Newtonian and Non-Newtonian fluid (power law and Carreau-Yasuda) models. The governing equations of bio magnetic fluid flow for an incompressible, laminar, homogeneous, non-Newtonian are solved by finite volume method with SIMPLE algorithm for structured grid. Both magnetization and electric current source terms are well thought-out in momentum and energy equations. The effects of fluid viscosity model, Hartmann number, and magnetic number on wall shear stress, shearing stress at the stenosis throat and maximum temperature of the system are investigated and are optimized. The current study results are in agreement with some of the existing findings in the literature and are useful in thermal and mechanical design of spatially varying magnets to control the drug delivery and biomagnetic fluid flows through tapered arteries. [ABSTRACT FROM AUTHOR]

Ex vivo lung perfusion (EVLP) is a promising procedure for evaluation, reconditioning, and treatment of marginal lungs before transplantation. Small animal models can contribute to improve clinical development of this technique and represent a substantial platform for bio-molecular investigations. However, to accomplish this purpose, EVLP models must sustain a prolonged reperfusion without pharmacological interventions. Currently available protocols only partly satisfy this need. The aim of the present research was accomplishment and optimization of a reproducible model for a protracted rat EVLP in the absence of anti-inflammatory treatment. A 180 min, uninjured and untreated perfusion was achieved through a stepwise implementation of the protocol. Flow rate, temperature, and tidal volume were gradually increased during the initial reperfusion phase to reduce hemodynamic and oxidative stress. Low flow rate combined with open atrium and protective ventilation strategy were applied to prevent lung damage. The videos enclosed show management of the most critical technical steps. The stability and reproducibility of the present procedure were confirmed by lung function evaluation and edema assessment. The meticulous description of the protocol provided in this paper can enable other laboratories to reproduce it effortlessly, supporting research in the EVLP field. [ABSTRACT FROM AUTHOR]

Huang Qin (root of Scutellaria baicalensis) is a widely used herb in different countries for adjuvant therapy of inflammation, diabetes, hypertension, different kinds of cancer and virus related diseases. Baicalin is the main flavonoid in this herb and has been extensively studied for 30 years. The angiogenic effect of herb Huang Qin extract and baicalin was found 13 years ago, however, the results were controversial with pro-angiogenic effect in some studies and anti-angiogenic effect in others. In this paper, the angiogenic effect of baicalin, its aglycone form baicalein and aqueous extract of Huang Qin was studied in chick embryo chorioallantoic membrane (CAM) model. Dose dependent dual effect was found in both aqueous extract and baicalin, but not in baicalein, in which only inhibitory effect was observed. In order to reveal the cellular and molecular mechanism of how baicalin and baicalein affect angiogenesis, cell proliferation and programmed cell death assays were performed in treated CAM. In addition, quantitative PCR array including 84 angiogenesis related genes was used to detect high and low dosage of baicalin and baicalein responsive genes. Low dose baicalin increased cell proliferation in developing blood vessels through upregulation of multiple angiogenic genes expression, but high dose baicalin induced cell death, performing inhibitory effect on angiogenesis. Both high and low dose of baicalein down regulated the expression of multiple angiogenic genes, decreased cell proliferation, and leads to inhibitory effects on angiogenesis. [ABSTRACT FROM AUTHOR]

The slowly inactivating or late Na+ current, INa-L, can contribute to the initiation of both atrial and ventricular rhythm disturbances in the human heart. However, the cellular and molecular mechanisms that underlie these pro-arrhythmic influences are not fully understood. At present, the major working hypothesis is that the Na+ influx corresponding to INa-L significantly increases intracellular Na+, [Na+]i; and the resulting reduction in the electrochemical driving force for Na+ reduces and (may reverse) Na+/Ca2+ exchange. These changes increase intracellular Ca2+, [Ca2+]i; which may further enhance INa-L due to calmodulin-dependent phosphorylation of the Na+ channels. This paper is based on mathematical simulations using the O’Hara et al (2011) model of baseline or healthy human ventricular action potential waveforms(s) and its [Ca2+]i homeostasis mechanisms. Somewhat surprisingly, our results reveal only very small changes (≤ 1.5 mM) in [Na+]i even when INa-L is increased 5-fold and steady-state stimulation rate is approximately 2 times the normal human heart rate (i.e. 2 Hz). Previous work done using well-established models of the rabbit and human ventricular action potential in heart failure settings also reported little or no change in [Na+]i when INa-L was increased. Based on our simulations, the major short-term effect of markedly augmenting INa-L is a significant prolongation of the action potential and an associated increase in the likelihood of reactivation of the L-type Ca2+ current, ICa-L. Furthermore, this action potential prolongation does not contribute to [Na+]i increase. [ABSTRACT FROM AUTHOR]

During pregnancy, oxygen diffuses from maternal to fetal blood through villous trees in the placenta. In this paper, we simulate blood flow and oxygen transfer in feto-placental capillaries by converting three-dimensional representations of villous and capillary surfaces, reconstructed from confocal laser scanning microscopy, to finite-element meshes, and calculating values of vascular flow resistance and total oxygen transfer. The relationship between the total oxygen transfer rate and the pressure drop through the capillary is shown to be captured across a wide range of pressure drops by physical scaling laws and an upper bound on the oxygen transfer rate. A regression equation is introduced that can be used to estimate the oxygen transfer in a capillary using the vascular resistance. Two techniques for quantifying the effects of statistical variability, experimental uncertainty and pathological placental structure on the calculated properties are then introduced. First, scaling arguments are used to quantify the sensitivity of the model to uncertainties in the geometry and the parameters. Second, the effects of localized dilations in fetal capillaries are investigated using an idealized axisymmetric model, to quantify the possible effect of pathological placental structure on oxygen transfer. The model predicts how, for a fixed pressure drop through a capillary, oxygen transfer is maximized by an optimal width of the dilation. The results could explain the prevalence of fetal hypoxia in cases of delayed villous maturation, a pathology characterized by a lack of the vasculo-syncytial membranes often seen in conjunction with localized capillary dilations. [ABSTRACT FROM AUTHOR]

In this paper, we develop a spatio-temporal modeling approach to describe blood and drug flow, as well as drug uptake and elimination, on an approximation of the liver. Extending on previously developed computational approaches, we generate an approximation of a liver, which consists of a portal and hepatic vein vasculature structure, embedded in the surrounding liver tissue. The vasculature is generated via constrained constructive optimization, and then converted to a spatial grid of a selected grid size. Estimates for surrounding upscaled lobule tissue properties are then presented appropriate to the same grid size. Simulation of fluid flow and drug metabolism (hepatic clearance) are completed using discretized forms of the relevant convective-diffusive-reactive partial differential equations for these processes. This results in a single stage, uniformly consistent method to simulate equations for blood and drug flow, as well as drug metabolism, on a 3D structure representative of a liver. [ABSTRACT FROM AUTHOR]

Congenital heart defects (CHDs) affect 2%–3% of newborns and remain challenging clinically. There is an ongoing project to elucidate the causes of CHDs, focusing primarily on genetics as dictated by the epidemiology. In a paper published in this issue, Santos and colleagues describe studies of Cornelia de Lange syndrome-associated secundum atrial septal defects (ASDs) caused by NIPBL mutations, undertaken with a targeted trapping allele in mice. They show that Nipbl haploinsufficiency in either of two cell populations was sufficient to engender ASDs but that expression solely in either one of those populations was sufficient to rescue them. This work provides novel insights into incomplete penetrance and oligogenic effects underlying CHDs. [ABSTRACT FROM AUTHOR]

Background: The restitution of the action potential duration (APDR) and conduction velocity (CVR) are mechanisms whereby cardiac excitation and repolarization adapt to changes in heart rate. They modulate the vulnerability to dangerous arrhythmia, but the mechanistic link between restitution and arrhythmogenesis remains only partially understood. Methods: This paper provides an experimental and theoretical study of repolarization and excitation restitution properties and their interactions in the intact human epicardium. The interdependence between excitation and repolarization dynamic is studied in 8 patients (14 restitution protocols, 1722 restitution curves) undergoing global epicardial mapping with multi-electrode socks before open heart surgery. A mathematical description of the contribution of both repolarization and conduction dynamics to the steepness of the APDR slope is proposed. Results: This study demonstrates that the APDR slope is a function of both activation and repolarization dynamics. At short cycle length, conduction delay significantly increases the APDR slope by interacting with the diastolic interval. As predicted by the proposed mathematical formulation, the APDR slope was more sensitive to activation time prolongation than to the simultaneous shortening of repolarization time. A steep APDR slope was frequently identified, with 61% of all cardiac sites exhibiting an APDR slope > 1, suggesting that a slope > 1 may not necessarily promote electrical instability in the human epicardium. APDR slope did not change for different activation or repolarization times, and it was not a function of local baseline APD. However, it was affected by the spatial organization of electrical excitation, suggesting that in tissue APDR is not a unique function of local electrophysiological properties. Spatial heterogeneity in both activation and repolarization restitution contributed to the increase in the modulated dispersion of repolarization, which for short cycle length was as high as 250 ms. Heterogeneity in conduction velocity restitution can translate into both activation and repolarization dispersion and increase cardiac instability. The proposed mathematical formulation shows an excellent agreement with the experimental data (correlation coefficient r = 0.94) and provides a useful tool for the understanding of the complex interactions between activation and repolarization restitution properties as well as between their measurements. [ABSTRACT FROM AUTHOR]

Retinal microaneurysms (MAs) are the earliest clinically observable lesions of diabetic retinopathy. Reliable automated MAs detection is thus critical for early diagnosis of diabetic retinopathy. This paper proposes a novel method for the automated MAs detection in color fundus images based on gradient vector analysis and class imbalance classification, which is composed of two stages, i.e. candidate MAs extraction and classification. In the first stage, a candidate MAs extraction algorithm is devised by analyzing the gradient field of the image, in which a multi-scale log condition number map is computed based on the gradient vectors for vessel removal, and then the candidate MAs are localized according to the second order directional derivatives computed in different directions. Due to the complexity of fundus image, besides a small number of true MAs, there are also a large amount of non-MAs in the extracted candidates. Classifying the true MAs and the non-MAs is an extremely class imbalanced classification problem. Therefore, in the second stage, several types of features including geometry, contrast, intensity, edge, texture, region descriptors and other features are extracted from the candidate MAs and a class imbalance classifier, i.e., RUSBoost, is trained for the MAs classification. With the Retinopathy Online Challenge (ROC) criterion, the proposed method achieves an average sensitivity of 0.433 at 1/8, 1/4, 1/2, 1, 2, 4 and 8 false positives per image on the ROC database, which is comparable with the state-of-the-art approaches, and 0.321 on the DiaRetDB1 V2.1 database, which outperforms the state-of-the-art approaches. [ABSTRACT FROM AUTHOR]

When blood vessels undergo remodeling because of the buildup of atherosclerotic plaque, it is thought that they first undergo compensatory or outward remodeling, followed by inward remodeling: the lumen area stays roughly constant or increases slightly and then decreases rapidly. The second phase of remodeling is supposed to start after the plaque burden exceeds about 40%. These changes in the vessel were first observed by S. Glagov who examined cross-sections of coronary arteries at different stages of the disease. In this paper, we use a mathematical model based on growth and elasticity theory to verify the main aspects of Glagov’s result. However, both our model and curve-fitting to the data suggest that the critical stenosis is around 20% rather than 40%. Our model and data from the PROSPECT trial also show that Glagov remodeling is qualitatively different depending on whether measurements are taken ex-vivo or in-vivo. Our results suggest that the first outward phase of “Glagov remodeling” is largely absent for in-vivo measurements: that is, the lumen area always decreases as plaque builds up. We advocate that care must be taken when infering how in-vivo vessels remodel from ex-vivo data. [ABSTRACT FROM AUTHOR]