Temporal Dispersion Research Articles

A VLC Channel Model for Underground Mining Environments With Scattering and Shadowing

Underground mining is an industry that preserves the miners' safety and efficiency in their work using wireless communication systems as a tool. In addition to communication links characterized by radio frequency signals, optical links in the visible light spectrum are under intense research for underground mining applications due to their high transmission rates and immunity to electromagnetic interference. However, the design of a robust visible-light communication (VLC) system for underground mining is a challenging task due to the harsh propagation conditions encountered in mining tunnels. To assist researchers in the design of such VLC systems, we present in this paper a novel channel model that incorporates important factors that influence the quality of the VLC link in underground mines. Features such as an arbitrary positioning and orientation of the optical transmitter and receiver, tunnels with irregular walls, shadowing by large machinery, and scattering by dust clouds are considered. These factors are integrated into a single modeling framework that lends itself for the derivation of compact mathematical expressions for the overall DC gain, the impulse response, the root mean square delay spread, and the received power of the proposed VLC channel model. Our analytical results are validated by computer simulations. These results show that the rotation and tilt of the transmitter and receiver, as well as the tunnels' irregular walls have a notorious influence on the magnitude and temporal dispersion of the VLC channel's line of sight (LoS) and non-LoS components. Furthermore, results show that shadowing reduces the LoS component's magnitude significantly. Our findings also show that scattering by dust particles contributes slightly to the total VLC channel gain, although it generates a large temporal dispersion of the received optical signal.

Longitudinal Changes in Children's Accelerometer-derived Activity Pattern Metrics.

The objective of this study was to quantify age-related changes in accelerometer-derived day-level physical activity and sedentary behavior pattern metrics (i.e., number, length, and temporal dispersion of bouts and breaks) across 3 yr of middle childhood. Differences by child sex and weekend versus weekday were examined. Children (N = 169, 54% female, 56% Hispanic; 8-12 yr old at enrollment) participated in a longitudinal study with six assessments across 3 yr. Day-level moderate-to-vigorous physical activity (MVPA; i.e., total minutes, number of short (<10 min) bouts, proportion of long (≥20 min) bouts, temporal dispersion) and sedentary behavior (i.e., total minutes, number of breaks, proportion of long (≥60 min) bouts, temporal dispersion) pattern metrics were measured using a waist-worn accelerometer (Actigraph GT3X). Random intercept multilevel linear regression models showed that age-related decreases in the number of short MVPA bouts per were steeper for girls than for boys (b = -1.28; 95% confidence interval (CI), -1.93 to -0.64; P < 0.01) and on weekend days than on weekdays (b = -1.82; 95% CI, -2.36 to -1.29; P < 0.01). The evenness of the temporal dispersion of MVPA across the day increased more on weekend days than on weekdays as children got older (b = -0.02; 95% CI, -0.02 to -0.01; P < 0.01). Girls had steeper age-related decreases in the number of sedentary breaks per day (b = -2.89; 95% CI, -3.97 to -1.73; P < 0.01) and the evenness of the temporal dispersion of sedentary behavior across the day (b ≤ 0.01; 95% CI, <0.01 to 0.01; P < 0.01) than did boys. Changes in sedentary behavior metrics did not differ between weekend days and weekdays. Strategies to protect against declines in short physical activity bouts and promote sedentary breaks, especially among girls and on weekend days, could reduce cardiometabolic risks.

Temporal Dispersion of Atrial Activation Causes Postoperative Atrial Fibrillation.

Spatial dispersion of atrial activation is a cause of postoperative atrial fibrillation (PoAF) after cardiac surgery. This study evaluated whether temporal dispersion of atrial activation causes PoAF after surgery in a clinical setting. Nineteen patients were enrolled. Postoperative atrial activation was evaluated by 24-hour Holter electrocardiography, with atrial pacing wires on the right atrium, for 5 days after cardiac surgery. No patient received antiarrhythmic drugs, including beta-blockers. The cycle length of 15 continuous atrial beats was measured at 4 time points: (i) earlier than 12 hours before PoAF, as a control, (ii) just before PoAF onset, (iii) during PoAF, and (iv) just before cessation of PoAF. Inhomogeneity of atrial activation was quantified by using the variation coefficient for a cycle length of 15 atrial beats during each phase. The median inhomogeneity index of atrial activation (interquartile range) was 0.102 (0.046-0.136) in controls, 0.943 (0.582-1.610) just before PoAF onset (vs. control; p=0.009), 0.966 (0.631-1.117) during PoAF, and 0.471 (0.138-0.645) just before cessation of PoAF. Dispersion of atrial activation significantly increased just before PoAF onset. Temporal dispersion of atrial activation is a precursory variation of PoAF.

Daphnia laevis ephippia cemetery in the sediment of a permanent tropical lake

Aiming to evaluate the importance of egg banks from a tropical lake for the active Daphnia laevis dynamics, we investigated ephippia down to a 28-cm sediment depth, and used data obtained by traps to compare with the in situ production and hatching rates of fresh ephippia. All the ephippia from the sediment were opened for inspection of the presence of resting eggs, and those found were incubated to verify hatching. Ephippia density degradation rate was tested by putting isolated ephippia immersed in the sediment lake for 75 days, and found to exponentially decrease with increasing sediment depth. Higher densities were recorded in 2017 (maximum of 1.43 ephippia per cm2) than in 2016 (maximum of 0.8 ephippia per cm2). The empty ephippia rates were high in all sediment depths ranging from 83% to 100%. In contrast, the hatching rates in situ of fresh ephippia were high, suggesting that those that sink are mostly unviable or empty, forming an unusual egg bank in the sediment. In the laboratory, ephippia degradation signs were observed as early as the fifteenth day after contact with sediment. We conclude that the egg bank is not able to support an active population since most of the ephippia are empty and also rapidly degrade in sediment. Our results contribute to the current understanding of diapause in tropical cladocerans, demonstrating that the presence of Daphnia ephippia in the sediment of permanent lakes do not always correspond to an egg bank for temporal dispersion.

Point of View: Electrophysiological Endpoints Differ When Comparing the Mode of Action of Highly Successful Anti-arrhythmic Drugs in the CAVB Dog Model With TdP.

In the anaesthetized, chronic atrioventricular block (CAVB) dog, ventricular ectopic beats and Torsade de pointes arrhythmias (TdP) are believed to ensue from an abrupt prolongation of ventricular repolarization and increased temporal dispersion of repolarization, quantified as short-term variability (STV). These TdP stop spontaneously or, when supported by substantial spatial dispersion of repolarization (SDR), degenerate into ventricular fibrillation. However, most studies involving ventricular arrhythmias do not quantify SDR by means of an electrophysiological parameter. Therefore, we reviewed the effects of 4 highly effective anti-arrhythmic drugs (flunarizine, verapamil, SEA-0400, and GS-458967) on the repolarization duration and associated STV. All drugs were tested as anti-arrhythmic strategies against TdP in CAVB dogs, their high anti-arrhythmic efficacy was defined as suppressing drug-induced TdP in 100% of the experiments. This comparison demonstrates that even though the anti-arrhythmic outcome was similar for all drugs, distinct responses of repolarization duration and associated STV were observed. Moreover, the aforementioned and commonly adopted electrophysiological parameters were not always sufficient in predicting TdP susceptibility, and additional quantification of the SDR proved to be of added value in these studies. The variability in electrophysiological responses to the different anti-arrhythmic drugs and their inconsistent adequacy in reflecting TdP susceptibility, can be explained by distinct modes of interference with TdP development. As such, this overview establishes the separate involvement of temporal and spatial dispersion in ventricular arrhythmogenesis in the CAVB dog model and proposes SDR as an additional parameter to be included in future fundamental and/or pharmaceutical studies regarding TdP arrhythmogenesis.

Cusp and Nightside Auroral Sources of O+ in the Plasma Sheet

AbstractEnergetic O+ outflow is observed from both the dayside cusp and the nightside aurora, but the relative importance of these regions in populating the plasma sheet and ring current is not known. During a storm on 16 July 2017, the Arase and MMS satellites were located in the near‐earth and midtail plasma sheet boundary layers (PSBL). During the storm main phase, Arase and MMS both observe O+ in the lobe entering the PSBL, followed by a time period with energy‐dispersed bursts of tailward‐streaming O+. The ions at MMS are at higher energies than at Arase. Trajectory modeling shows that the ions coming in from the lobe are cusp origin, while the more energetic bursty ions are from the nightside aurora. The observed and simulated energies and temporal dispersion are consistent with these sources. Thus, both regions directly contribute O+ to the plasma sheet during this storm main phase.

Occurrence of Guillain-Barr\xe9 syndrome and Myasthenia Gravis in an elderly male

IntroductionThe occurrence of both Guillain-Barré syndrome(GBS) and myasthenia gravis (MG) in the same individual is rare. The underlying pathophysiology was assumed to be autoimmune humoral mechanisms and molecular mimicry with a cross-reaction between autoantibodies and myelin sheath of peripheral nerves and acetylcholine receptors of the neuromuscular junction (NMJ).Case descriptionA 68-year-old male known diabetic and hypertensive with good drug compliance presented with acute onset quadriparesis with bulbar involvement for 1 day. On examination, he had mild neck flexion weakness and bulbar weakness. He had flaccid quadriparesis with absent deep tendon reflexes and negative Babinski. The rest of the neurological examination was normal.Discussion and evaluationBlood and electrophysiological studies showed evidence of demyelinating polyradiculoneuropathy with temporal dispersion suggestive of Guillain-Barré syndrome. He was treated with intravenous immunoglobin and complete resolution of symptoms. Two months later, he presented with new-onset asymmetrical ptosis and bulbar symptoms for 3 days. On further evaluation, repetitive nerve stimulation showed postsynaptic neuromuscular disorder pattern typical of myasthenia gravis, which was further confirmed by positive acetylcholinesterase receptor antibodies (AChR). Thymoma was ruled out by imaging. He was treated with anticholinesterases, low dose steroids, and immunosuppressants (azathioprine) following which he had improvement of symptoms.ConclusionOur patient, who was initially diagnosed with Guillain-Barré syndrome and recovered, presented 2 months later with a new-onset illness suggestive of myasthenia gravis. This existence of two different neurological entities in the same individual is a rarity, and early recognition is essential for treatment decision and prognostic strategies.

Elastic full-waveform inversion based on GPU accelerated temporal fourth-order finite-difference approximation

Elastic full-waveform inversion (FWI) estimates the subsurface velocity model by inverting multi-component seismic data. Most of the current elastic FWI solves the elastic wave equation by a temporal second-order finite-difference time-domain (FDTD) method. However, the traditional temporal second-order FDTD introduces large temporal dispersion in the case of a large time-stepping size. To suppress the temporal dispersion, a relatively small time step should be used, which increases the computational cost of FWI. We introduce a temporal fourth-order and spatial arbitrary even-order FDTD method for elastic wave modeling and inversion. The temporal fourth-order scheme can simulate a highly accurate wavefield, even when a large time step is used for temporal extrapolation. Compared with the traditional temporal second-order FDTD scheme, the temporal fourth-order FDTD enables a larger time step for its more relaxed stability condition and smaller dispersion. As a result, FWI with temporal fourth-order FDTD scheme can achieve high accuracy inversion without reducing much computational efficiency. We run our elastic FWI codes on a Graphic Processing Unit (GPU) computing platform, and to accelerate the GPU computing, we propose to use the GPU shared memory to reduce the data access delay. By transferring the data frequently accessed for the FDTD approximations, from the global memory to the shared memory, we realize the FDTD calculation in a more efficient way. Forward modeling and FWI examples are carried out to confirm the effectiveness of our elastic FWI.

Application of perfectly matched layers in 3D transient controlled-source electromagnetic modeling by the rapid expansion method

I have developed an extension of the rapid expansion method (REM) for 3D time-domain controlled-source electromagnetic modeling that includes perfectly matched layers (PMLs) as the absorbing boundary. The REM solves the time-domain electric field by a weighted summation of the Chebyshev polynomials. The results are free of temporal dispersion and accurate to the Nyquist frequency, yet the domain of Chebyshev polynomials lacks an accurate absorbing boundary. I find that by introducing a fictitious magnetic field in the Chebyshev domain, the recursion of the Chebyshev polynomials obeys a discrete coupled wave equation, which shares a similarity with the propagation of EM waves in a lossless medium. The time and frequency components in the Chebyshev domain are derived based on the eigenvalues of the propagation matrix, and the PML theory designed for EM waves can be extended to the Chebyshev domain in a straightforward way. Numerical tests against analytical solution and spectral methods show an excellent agreement after PML solves the boundary problem in the Chebyshev domain, which demonstrates the accuracy of the REM algorithm and the usefulness of the PML absorbing boundary.

Signal Modeling and Simulation of Temporal Dispersion and Conduction Block in Motor Nerves.

Electroneurography is a well-established diagnostic test for supporting the diagnosis of disorders of myelinated peripheral nerves. Neurophysiological quantities are automatically calculated and are used to determine the pathology of the nerve (axonal damage) or its sheath (myelin damage). Specific differential diagnostic criteria are derived from time-domain normative data, which result primarily from a computer simulation in the early 1990s based on animal data, namely rats. However, the rat signals studied differ significantly from those of humans because of anatomical differences. We present a model-based simulation of nerve conduction in healthy and pathological motor nerves. In contrast to earlier simulations, the present model is based on motor unit action potentials extracted from real human measurements facilitating the generation of realistic signals, starting from a conduction velocity distribution. In addition to the modeling of healthy nerves, we model a hereditary peripheral nerve disease as well as an acute and a chronic inflammatory demyelinating condition. Quantitative signal differences based on standard variables in the time-domain are presented. The findings for the demyelinating conditions demonstrate amplitude reductions of 71% and 65% between the distal and proximal responses, which result from an increase in the variance of the nerve fiber conduction velocities. The simulation results closely match those of empirical measurements, indicating that the signal model captures relevant pathological mechanisms. An amplitude reduction of more than 50% in demyelinating conditions is in accordance with routine measurements and shows that temporal dispersion is quite well-modeled compared to previous simulation models. The simulation outcomes can serve as the basis for an improved pathophysiological understanding of peripheral nerve disorders and should aid neurophysiologists to refine their diagnostic armamentarium resulting in a more precise differential diagnosis.

Ultrashort pulse propagation through depressed-cladding channel waveguides in YAG crystal: Spatio-temporal characterization

Inscription of optical waveguides by direct femtosecond laser irradiation has become a very versatile tool for the development of integrated photonic devices, such as waveguide lasers, frequency converters or photonic lanterns, among many others. The potential application of such devices for the control and manipulation of ultrashort pulses requires the precise knowledge of the temporal distortions that may be induced in the pulse propagation. Currently, research in this topic is scarce, and to our knowledge there is no previous experimental study on the spatio-temporal characterization at the output of waveguides inscribed inside crystals. Here, we have firstly fabricated depressed-cladding waveguides with different modal behavior in YAG crystal by direct femtosecond laser irradiation. Then, we implemented an experimental method based on the fiber coupler assisted spectral interferometry technique, that allows obtaining: (1) the temporal dispersion of a pulse at the output of an inscribed waveguide and, (2) full spatio-spectral and spatio-temporal characterization of the output of single-mode and multi-mode waveguides. Our results suggest that the main contribution to the pulse dispersion is due to the material dispersion. Moreover, we found that multimodal waveguides may induce an appreciable inhomogeneity in the temporal features of the pulses that needs to be taken into account in the design of complex devices.

A Study of Diffuse Scattering in Massive MIMO Channels at Terahertz Frequencies

The use of massive multiple-input multiple-output (MIMO) systems is becoming progressively feasible, as well as progressively important, as the carrier frequency increases. Terahertz (THz) frequencies lead to smaller-sized RF components including antennas, so that even antenna arrays with a large number of antennas have a reasonable form factor while providing large beamforming gain and multi-user MIMO (MU-MIMO) capability. However, the THz propagation mechanisms differ in various ways from previously explored channels. In fact, reflections by a rough surface and diffuse scattering mechanisms are the most critical features contributing to spatial and temporal dispersion at THz frequencies. For this article, first, we develop a hybrid modeling approach of 3-D ray-tracing simulations in a realistic office room at 300 and 350 GHz to obtain estimates of the impact of surface roughness on the channel capacity which depends on generic channel characteristics. Then, the indoor multipath propagation and its impact on massive MIMO channels considering smooth and rough surfaces are investigated by employing the Beckmann-Kirchhoff (B-K) model. Finally, channel capacities of indoor THz massive MIMO channels with different surface roughnesses for both line-of-sight (LoS) and non-LoS (NLoS) scenarios are calculated. Though based on modeling results, the scattering properties of materials can favorably be exploited to maximize spatial multiplexing gains, especially in LoS scenarios.

Atypical course of Charcot-Marie-Tooth disease: what shall we be thinking of?

Charcot-Marie-Tooth disease (CMT) is an inherited polyneuropathy with a gradually progressive course. Atypical features such as acute or subacute deterioration and unusual electrophysiological findings should be alarming. A 54 year-old woman with medical history of hypothyroidism, was referred to our department for weakness of her 4 limbs with a subacute onset and rapid worsening. The family history was marked by feet deformities. The pedigree was suggestive of autosomal dominant inheritance. On examination the proband had steppage gait, with distal muscle weakness in four limbs, absent tendon reflexes, hummer toes and hollow feet. Nerve conduction studies showed homogeneous demyelination but with temporal dispersion in motor nerves. We noted slight increase in protein level in cerebrospinal fluid (CSF). The patient was diagnosed with autosomal dominant CMT type I based on family history, neurological examination of the proband and her relatives, and electrophysiological findings, associated with chronic inflammatory demyelinating polyneuropathy. The patient was treated with high-dose steroids and than moderately improved. Further reported features suggesting a co-existent hereditary and inflammatory process are: conduction blocks in motor nerve conduction studies, high protein levels in CSF, evidence of inflammatory process in nerve biopsy and nerve root enhancement in spinal imaging. Atypical course and unusaul biological, electrical and imaging features in CMT disease should be alarming about the co-existence of inflammatory neuropathy. Immunomodulatory treatment may substancially improve the outcome.

Regimes of two-color light bullet formation in a gradient waveguide

In this paper we concentrate on the remarkable role of a gradient waveguide in two-color light bullet formation. We study generation of the second harmonic in such an inhomogeneous nonlinear medium, taking into account diffraction and relatively weak temporal dispersion. Using the averaged Lagrangian method we consider all possible combinations of the range of group velocities (normal or anomalous dispersion) and waveguide geometry (focusing or defocusing waveguide). Stability conditions for a propagating two-color light bullet are derived analytically. We demonstrate the formation of a stable two-component light bullet in a parabolic planar quadratically nonlinear waveguide either at anomalous or at normal group velocity dispersion. We discuss also the results of numerical simulation confirming our analytical findings. Besides that, simulation allows us to expand the scope of the study and to show light bullet propagation at a certain phase mismatching and the formation of a stable coupled localized structure from a signal at the fundamental frequency as well.

Biphoton shaping with cascaded entangled-photon sources

Quantum entanglement is an integral part of quantum optics and has been exploited in areas such as computation, cryptography and metrology. The entanglement between photons can be present in various degrees of freedom (DOFs), and even the simplest bi-partite systems can occupy a large Hilbert space. Therefore, it is desirable to exploit this multi-dimensional space for various quantum applications by fully controlling the properties of the entangled photons in multiple DOFs. While current entangled-photon sources are capable of generating entanglement in one or more DOFs, there is currently a lack of practical techniques that can shape and control the entanglement properties in multiple DOFs. Here we show that cascading two or more entangled-photon sources with tunable linear media in between allows us to generate photon-pairs whose entanglement properties can be tailored and shaped in the frequency and polarisation domains. We first develop a quantum mechanical model to study the quantum state generated from the cascade structure with special considerations paid to the effects of pump temporal coherence, linear dispersion, and in-structure polarisation transformation applied between the entangled-photon sources. We then experimentally generate photon-pairs with tunable entanglement properties by manipulating the dispersion and birefringence properties of the linear medium placed in between two entangled-photon sources. This is done in an all-fibre, phase stable, and alignment-free configuration. Our results show that the cascade structure offers a great deal of flexibility in tuning the properties of entangled photons in multiple DOFs, opening up a new avenue in engineering quantum light sources.

Trapping of two-component light bullets in a gradient waveguide with normal group dispersion.

In this paper we consider the process of the second harmonic generation in a gradient waveguide, taking into account diffraction and relatively weak temporal dispersion. Using the slowly varying envelope approximation and neglecting the dispersion of the nonlinear part of the response of the medium we obtain the system of parabolic equations for the envelopes of both harmonics. We also derive integrals of motion of this system. To solve it numerically we construct a nonlinear finite-difference scheme based on the Crank-Nicolson method preserving the integrals. Primarily, we focus our investigations on the processes of a two-component light bullets generation. We demonstrate that the generation of a coupled pair is possible in a planar waveguide even at normal group velocity dispersion.

Arrhythmic Risk in Elderly Patients Candidates to Transcatheter Aortic Valve Replacement: Predictive Role of Repolarization Temporal Dispersion.

Background/AimDegenerative aortic valve stenosis (AS) is associated to ventricular arrhythmias and sudden cardiac death, as well as mental stress in specific patients. In such a context, substrate, autonomic imbalance as well as repolarization dispersion abnormalities play an undoubted role. Aim of the study was to evaluate the increase of premature ventricular contractions (PVC) and complex ventricular arrhythmias during mental stress in elderly patients candidate to the transcatheter aortic valve replacement (TAVR).MethodsIn eighty-one elderly patients with AS we calculated several short-period RR- and QT-derived variables at rest, during controlled breathing and during mild mental stress, the latter being represented by a mini-mental state evaluation (MMSE).ResultsAll the myocardial repolarization dispersion markers worsened during mental stress (p < 0.05). Furthermore, during MMSE, low frequency component of the RR variability increased significantly both as absolute power (LFRR) and normalized units (LFRRNU) (p < 0.05) as well as the low-high frequency ratio (LFRR/HFRR) (p < 0.05). Eventually, twenty-four (30%) and twelve (15%) patients increased significantly PVC and, respectively, complex ventricular arrhythmias during the MMSE administration. At multivariate logistic regression analysis, the standard deviation of QTend (QTesd), obtained at rest, was predictive of increased PVC (odd ratio: 1.54, 95% CI 1.14–2.08; p = 0.005) and complex ventricular arrhythmias (odd ratio: 2.31, 95% CI 1.40–3.83; p = 0.001) during MMSE. The QTesd showed the widest sensitive-specificity area under the curve for the increase of PVC (AUC: 0.699, 95% CI: 0.576–0.822, p < 0.05) and complex ventricular arrhythmias (AUC: 0.801, 95% CI: 0.648–0.954, p < 0.05).ConclusionIn elderly with AS ventricular arrhythmias worsened during a simple cognitive assessment, this events being a possible further burden on the outcome of TAVR. QTesd might be useful to identify those patients with the highest risk of ventricular arrhythmias. Whether the TAVR could led to a QTesd reduction and, hence, to a reduction of the arrhythmic burden in this setting of patients is worthy to be investigated.

Clay Figurines from Sirkeli Höyük

Sirkeli Höyük is a settlement mound in the cilician plain near Adana, Turkey. It was first excavated in the 1930s by John Garstang. Work there was resumed in the 1990s by Barthel Hrouda and Horst Ehringhaus, and then again from 2006 until the present day; initially by the Universities of Tübingen and Çanakkale and subsequently (2011 onwards) by the Universities of Bern and Çanakkale. My Master’s thesis focused on the terracotta figurines unearthed during the excavations from 1992 onwards. Its aim was to construct a classification for the material from Sirkeli Höyük, which I documented, classified and catalogued according to their shape. I did not create a completely new classification, but rather tried to build on work form A. Pruss and H. Goldmann, who’s approaches I adapted to suit the material from Sirkeli Höyük. The terracotta figurines found to date span the following epochs: the Hellenistic period, the Iron Age, the Late Bronze Age, and the Middle Bronze Age. The first aim of my PhD is to construct a working typology for these terracotta figurines by clearly defining the criteria of each of the different types. In a second phase I intend to elaborate my existing comparison of the material from Sirkeli Höyük and figurines from other excavations in the cicilian plain, to document their geographical distribution and diversity. The final phase will be an evaluation of the temporal dispersion of differing styles with a view to determining the extent of any extra-regional influences.

Clinical and electrophysiological profiles in early recognition of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes syndrome.

Background:The detection of polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome at early stage is challenging for neurologists. Since polyneuropathy could be the first manifestation, it could be misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP). The present study aimed to determine the clinical and electrophysiological features of POEMS syndrome to distinguish from CIDP.Methods:The data of a group of patients with POEMS (n = 17) and patients with CIDP (n = 17) in Zhongshan Hospital Fudan University from January 2015 to September 2017 were analyzed in this retrospective study. The clinical features, neurological symptoms, and electrophysiological findings were compared between the two groups.Results:Clinically, patients with POEMS demonstrated significantly more neuropathic pain in the lower extremities than patients with CIDP (58.8% vs. 11.8%, P = 0.01). Multisystem features like edema, skin change, organomegaly, and thrombocytosis were also pointed towards the diagnosis of POEMS syndrome. Electrophysiologically, terminal latency index (TLI) was significantly higher in patients with POEMS than that in patients with CIDP (median nerve: 0.39 [0.17–0.52] vs. 0.30 (0.07–0.69), Z = –2.413, P = 0.016; ulnar nerve: 0.55 [0.23–0.78] vs. 0.42 [0.12–0.70], Z = –2.034, P = 0.042). Patients with POEMS demonstrated a higher frequency of absent compound muscle action potential of the tibial nerve (52.9% vs. 17.6%, P = 0.031), less conduction block (ulnar nerve: 0 vs. 35.3%, P = 0.018), and less temporal dispersion (median nerve: 17.6% vs. 58.8%, P = 0.032) than CIDP group. The combination of positive serum monoclonal protein and high TLI (if either one or both were present) discriminated POEMS from CIDP with a sensitivity of 94.1% and 47.1% and specificity of 76.5% and 100.0%, respectively.Conclusions:POEMS syndrome could be distinguished from CIDP through typical clinical and electrophysiological characteristics in practice. The combination of serum monoclonal protein and high TLI might raise the sensitivity of detecting POEMS syndrome.

Insights Into the Pathogenesis of Catecholaminergic Polymorphic Ventricular Tachycardia From Engineered Human Heart Tissue.

Modeling of human arrhythmias with induced pluripotent stem cell-derived cardiomyocytes has focused on single-cell phenotypes. However, arrhythmias are the emergent properties of cells assembled into tissues, and the impact of inherited arrhythmia mutations on tissue-level properties of human heart tissue has not been reported. Here, we report an optogenetically based, human engineered tissue model of catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmia caused by mutation of the cardiac ryanodine channel and triggered by exercise. We developed a human induced pluripotent stem cell-derived cardiomyocyte-based platform to study the tissue-level properties of engineered human myocardium. We investigated pathogenic mechanisms in CPVT by combining this novel platform with genome editing. In our model, CPVT tissues were vulnerable to developing reentrant rhythms when stimulated by rapid pacing and catecholamine, recapitulating hallmark features of the disease. These conditions elevated diastolic Ca2+ levels and increased temporal and spatial dispersion of Ca2+ wave speed, creating a vulnerable arrhythmia substrate. Using Cas9 genome editing, we pinpointed a single catecholamine-driven phosphorylation event, ryanodine receptor-serine 2814 phosphorylation by Ca2+/calmodulin-dependent protein kinase II, that is required to unmask the arrhythmic potential of CPVT tissues. Our study illuminates the molecular and cellular pathogenesis of CPVT and reveals a critical role of calmodulin-dependent protein kinase II-dependent reentry in the tissue-scale mechanism of this disease. We anticipate that this approach will be useful for modeling other inherited and acquired cardiac arrhythmias.