A Comparative Study of Early Afterdepolarization-Mediated Fibrillation in Two Mathematical Models for Human Ventricular Cells

Early afterdepolarizations (EADs), which are abnormal oscillations of the membrane potential at the plateau phase of an action potential, are implicated in the development of cardiac arrhythmias like Torsade de Pointes. We carry out extensive numerical simulations of the TP06 and ORd mathematical models for human ventricular cells with EADs. We investigate the different regimes in both these models, namely, the parameter regimes where they exhibit (1) a normal action potential (AP) with no EADs, (2) an AP with EADs, and (3) an AP with EADs that does not go back to the resting potential. We also study the dependence of EADs on the rate of at which we pace a cell, with the specific goal of elucidating EADs that are induced by slow or fast rate pacing. In our simulations in two-and three-dimensional domains, in the presence of EADs, we find the following wave types: (A) waves driven by the fast sodium current and the L-type calcium current (Na-Ca-mediated waves); (B) waves driven only by the L-type calcium current (Ca-mediated waves); (C) phase waves, which are pseudo-travelling waves. Furthermore, we compare the wave patterns of the various wave-types (Na-Ca-mediated, Ca-mediated, and phase waves) in both these models. We find that the two models produce qualitatively similar results in terms of exhibiting Na-Ca-mediated wave patterns that are more chaotic than those for the Ca-mediated and phase waves. However, there are quantitative differences in the wave patterns of each wave type. The Na-Ca-mediated waves in the ORd model show short-lived spirals but the TP06 model does not. The TP06 model supports more Ca-mediated spirals than those in the ORd model, and the TP06 model exhibits more phase-wave patterns than does the ORd model.

A Computational Study of the Factors Influencing the PVC-Triggering Ability of a Cluster of Early Afterdepolarization-Capable Myocytes

Premature ventricular complexes (PVCs), which are abnormal impulse propagations in cardiac tissue, can develop because of various reasons including early afterdepolarizations (EADs). We show how a cluster of EAD-generating cells (EAD clump) can lead to PVCs in a model of cardiac tissue, and also investigate the factors that assist such clumps in triggering PVCs. In particular, we study, through computer simulations, the effects of the following factors on the PVC-triggering ability of an EAD clump: (1) the repolarization reserve (RR) of the EAD cells; (2) the size of the EAD clump; (3) the coupling strength between the EAD cells in the clump; and (4) the presence of fibroblasts in the EAD clump. We find that, although a low value of RR is necessary to generate EADs and hence PVCs, a very low value of RR leads to low-amplitude EAD oscillations that decay with time and do not lead to PVCs. We demonstrate that a certain threshold size of the EAD clump, or a reduction in the coupling strength between the EAD cells, in the clump, is required to trigger PVCs. We illustrate how randomly distributed inexcitable obstacles, which we use to model collagen deposits, affect PVC-triggering by an EAD clump. We show that the gap-junctional coupling of fibroblasts with myocytes can either assist or impede the PVC-triggering ability of an EAD clump, depending on the resting membrane potential of the fibroblasts and the coupling strength between the myocyte and fibroblasts. We also find that the triggering of PVCs by an EAD clump depends sensitively on factors like the pacing cycle length and the distribution pattern of the fibroblasts.

UK guidance on the initial evaluation of an infant or an adolescent with a suspected disorder of sex development

It is paramount that any child or adolescent with a suspected disorder of sex development (DSD) is assessed by an experienced clinician with adequate knowledge about the range of conditions associated with DSD. If there is any doubt, the case should be discussed with the regional team. In most cases, particularly in the case of the newborn, the paediatric endocrinologist within the regional DSD team acts as the first point of contact. The underlying pathophysiology of DSD and the strengths and weaknesses of the tests that can be performed should be discussed with the parents and affected young person and tests undertaken in a timely fashion. This clinician should be part of a multidisciplinary team experienced in management of DSD and should ensure that the affected person and parents are as fully informed as possible and have access to specialist psychological support. Finally, in the field of rare conditions, it is imperative that the clinician shares the experience with others through national and international clinical and research collaboration. © 2011 Blackwell Publishing Ltd.

A possible alchemist apparatus from the early islamic period excavated at Ramla, Israel

Abstract: During extensive salvage excavations carried out during the years 2004-2008 in a large Early Islamic industrial area at the vicinities of Ramla, in Central Israel, an unparalleled industrial device was unearthed. The star-shaped, soil embedded installation, whose lower part was preserved, consisted of a central pottery jar surrounded by five minor jars, linked by ceramic pipes. Evidence of heat was observed mainly around the central vessel, and metal hollow cones perforated in the tip were found inside the surrounding jars. Although the manufacturing procedures and operation techniques of the installation are not completely clear, it is proposed that the installation is part of an industrial workshop or an alchemy laboratory. Both industry and alchemy were well-developed during the Early Islamic period and very often closely related, to the point that sometimes it is difficult to distinguish between them. The identification proposed is based on comparisons with tools described in literary sources, and somewhat later drawings and etchings. Circumstantial ceramic evidence was found, as well as the proximity of a bathhouse whose guests could have been the consumers of perfumes and unguents seem to reinforce this possibility. Due to the poor state of preservation of the device and the lack of available comparisons, the identification proposed here is tentative, and future research coupled with eventual new discoveries is needed in order to clarify this matter.

Local exchange in the southern levant during the early bronze age: a political economy viewpoint

Trade and relations between the southern Levant and other regions of the Near East (mainly Egypt) during the Early Bronze Age (ca. 3,600–2,300 BC) have been the subject of many studies. Research concerning the exchange of local commodities was almost ignored or was discussed in parochial studies, focusing on specific archaeological finds. It is the intention of this paper to present the results of recent research of the exchange of commodities provided by archaeological data from excavations in the Southern Levant with regard to economic theories on the exchange-value of goods and exchange networks. Conclusions regarding the type of society and the forms of government in the Southern Levant during the Early Bronze Age are also presented.

Vortex motion in the early stages of unsteady flow around a circular cylinder

In this paper, processes in the early stages of vortex motion and the development of flow structure behind an impulsively-started circular cylinder at high Reynolds number are investigated by combining the discrete vortex model with boundary layer theory, considering the separation of incoming flow boundary layer and rear shear layer in the recirculating flow region. The development of flow structure and vortex motion, particularly the formation and development of secondary vortex and a pair of secondary vortices and their effect on the flow field are calculated. The results clearly show that the flow structure and vortices motion went through a series of complicated processes before the symmetric main vortices change into asymmetric: development of main vortices induces secondary vortices; growth of the secondary vortices causes the main vortex sheets to break off and causes the symmetric main vortices to become “free” vortices, while a pair of secondary vortices is formed; then the vortex sheets, after breaking off, gradually extend downstream and the structure of a pair of secondary vortices becomes relaxed. These features of vortex motion look very much like the observed features in some available flow field visualizations. The action of the secondary vortices causes the main vortex sheets to break off and converts the main vortices into free vortices. This should be the immediate cause leading to the instability of the motion of the symmetric main vortices. The flow field structure such as the separation position of boundary layer and rear shear layer, the unsteady pressure distributions and the drag coefficient are calculated. Comparison with other results or experiments is also made.