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Register a new userInvestigating the spatial resolution of EMG and MMG based on a systemic multi-scale model
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While electromyography (EMG) and magnetomyography (MMG) are both methods to measure the electrical activity of skeletal muscles, no systematic comparison between both signals exists. Within this work, we propose a systemic in silico model for EMG and MMG and test the hypothesis that MMG surpasses EMG in terms of spatial selectivity. The results show that MMG provides a slightly better spatial selectivity than EMG when recorded directly on the muscle surface. However, there is a remarkable difference in spatial selectivity for non-invasive surface measurements. The spatial selectivity of the MMG components aligned with the muscle fibres and normal to the body surface outperforms the spatial selectivity of surface EMG. Particularly, for the MMGs normal-to-the-surface component the influence of subcutaneous fat is minimal. Further, for the first time, we analyse the contribution of different structural components, i.e., muscle fibres from different motor units and the extracellular space, to the measurable biomagnetic field. Notably, the simulations show that the normal-to-the-surface MMG component, the contribution from volume currents in the extracellular space and in surrounding inactive tissues is negligible. Further, our model predicts a surprisingly high contribution of the passive muscle fibres to the observable magnetic field.
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Contemporary realistic mathematical models of single-cell cardiac electrical excitation are immensely detailed. Model complexity leads to parameter uncertainty, high computational cost and barriers to mechanistic understanding. There is a need for reduced models that are conceptually and mathematically simple but physiologically accurate. To this end, we consider an archetypal model of single-cell cardiac excitation that replicates the phase-space geometry of detailed cardiac models, but at the same time has a simple piecewise-linear form and a relatively low-dimensional configuration space. In order to make this archetypal model practically applicable, we develop and report a robust method for estimation of its parameter values from the morphology of single-stimulus action potentials derived from detailed ionic current models and from experimental myocyte measurements. The procedure is applied to five significant test cases and an excellent agreement with target biomarkers is achieved. Action potential duration restitution curves are also computed and compared to those of the target test models and data, demonstrating conservation of dynamical pacing behaviour by the fine-tuned archetypal model. An archetypal model that accurately reproduces a variety of wet-lab and synthetic electrophysiology data offers a number of specific advantages such as computational efficiency, as also demonstrated in the study. Open-source numerical code of the models and methods used is provided.
The epidemiology of lumbar degenerative spondylolisthesis (DS) remains controversial. We performed a systemic review with the aim to have a better understanding of DSs prevalence in general population. The results showed the prevalence of DS is very gender specific and age specific. Both women and men have few DS before 50 years old, after 50 years old both women and men start to develop DS, with women having a faster developing rate than men. For elderly Chinese (>=65 yrs, mean age: 72.5 yrs), large population based studies (MsOS(Hong Kong) and MrOS (Hong Kong), females n=2000 and males n=2000) showed DS prevalence was for 25.0% for women and 19.1% for men, and the prevalence F:M (women:men) ratio was 1.3:1. The published data (MsOS(USA) and MrOS(USA) studies) seem to show elderly Caucasian American has a higher DS prevalence, being approximately 60-70% higher than elderly Chinese; however the prevalence F:M ratio was similar to elderly Chinese population. Patient data showed female patients more often received treatment than men; and preliminary data show the ratio of numbers of female patients received treatment compared with men did not differ between Northeast Asians (Chinese, Japanese, and Korean) and European and American Caucasians, being around 2:1 in elderly population. The existing data also suggest that menopause may be a contributing factor for the accelerated DS development in post-menopausal
In this paper we consider chemotherapy in a spatial model of tumor growth. The model, which is of reaction-diffusion type, takes into account the complex interactions between the tumor and surrounding stromal cells by including densities of endothelial cells and the extra-cellular matrix. When no treatment is applied the model reproduces the typical dynamics of early tumor growth. The initially avascular tumor reaches a diffusion limited size of the order of millimeters and initiates angiogenesis through the release of vascular endothelial growth factor (VEGF) secreted by hypoxic cells in the core of the tumor. This stimulates endothelial cells to migrate towards the tumor and establishes a nutrient supply sufficient for sustained invasion. To this model we apply cytostatic treatment in the form of a VEGF-inhibitor, which reduces the proliferation and chemotaxis of endothelial cells. This treatment has the capability to reduce tumor mass, but more importantly, we were able to determine that inhibition of endothelial cell proliferation is the more important of the two cellular functions targeted by the drug. Further, we considered the application of a cytotoxic drug that targets proliferating tumor cells. The drug was treated as a diffusible substance entering the tissue from the blood vessels. Our results show that depending on the characteristics of the drug it can either reduce the tumor mass significantly or in fact accelerate the growth rate of the tumor. This result seems to be due to complicated interplay between the stromal and tumor cell types and highlights the importance of considering chemotherapy in a spatial context.
We propose the Hawkes flocking model that assesses systemic risk in high-frequency processes at the two perspectives -- endogeneity and interactivity. We examine the futures markets of WTI crude oil and gasoline for the past decade, and perform a comparative analysis with conditional value-at-risk as a benchmark measure. In terms of high-frequency structure, we derive the empirical findings. The endogenous systemic risk in WTI was significantly higher than that in gasoline, and the level at which gasoline affects WTI was constantly higher than in the opposite case. Moreover, although the relative influences degree was asymmetric, its difference has gradually reduced.
Exploring the genetic basis of heritable traits remains one of the central challenges in biomedical research. In simple cases, single polymorphic loci explain a significant fraction of the phenotype variability. However, many traits of interest appear to be subject to multifactorial control by groups of genetic loci instead. Accurate detection of such multivariate associations is nontrivial and often hindered by limited power. At the same time, confounding influences such as population structure cause spurious association signals that result in false positive findings if they are not accounted for in the model. Here, we propose LMM-Lasso, a mixed model that allows for both, multi-locus mapping and correction for confounding effects. Our approach is simple and free of tuning parameters, effectively controls for population structure and scales to genome-wide datasets. We show practical use in genome-wide association studies and linkage mapping through retrospective analyses. In data from Arabidopsis thaliana and mouse, our method is able to find a genetic cause for significantly greater fractions of phenotype variation in 91% of the phenotypes considered. At the same time, our model dissects this variability into components that result from individual SNP effects and population structure. In addition to this increase of genetic heritability, enrichment of known candidate genes suggests that the associations retrieved by LMM-Lasso are more likely to be genuine.
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