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This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this record. ; The double membrane cell envelope of Gram negative bacteria is a sophisticated barrier that facilitates the uptake of nutrients and protects the organism from toxic compounds. An antibiotic molecule must find its way through the negatively charged lipopolysaccharide layer on the outer surface, pass through either a porin or the hydrophobic layer of the outer membrane, then traverse the hydrophilic peptidoglycan layer only to find another hydrophobic lipid bilayer before it finally enters the cytoplasm, where it typically finds its target. This complex uptake pathway with very different physico-chemical properties is one reason that Gram-negatives are intrinsically protected against multiple classes of antibiotic-like molecules, and is likely the main reason that in vitro target based screening programmes have failed to deliver novel antibiotics for these organisms. Due to the lack of general methods available for quantifying the flux of drugs into the cell, little is known about permeation rates, transport pathways and accumulation at the target sites for particular molecules. Here we summarise the current tools available for measuring antibiotic uptake across the different compartments of Gram-negative bacteria. ; Biotechnology and Biological Sciences Research Council (BBSRC) ; European Research Council (ERC) ; Warwick University ; Cross Council AMR ; Innovative Medicines Initiatives ; European Union ; EFPIA companies

The rat is one of the most widely used laboratory animal species. Therefore development of mathematical models aimed to analyze electromechanical coupling in the rat myocardium is a matter of top interest. We have developed a novel model of excitation-contraction coupling in the rat cardiomyocyte. This model combines equations from the Pandit electrophysiological model and Hinch model of calcium handling with equations describing myofilament mechanical activity from the 'Ekaterinburg-Oxford' mathematical model. The model reproduces both fast and slow responses to mechanical interventions in rat myocardium. © 2018 Creative Commons Attribution. ; Russian Foundation for Basic Research, RFBR: 18-01-00059 ; The work is performed in the frameworks of IIP UrB RAS projects (Nos. AAAA-A18-118020590031-8, АААА-А18-118020590134-6), and supported by RFBR (No. 18-01-00059), by Act 211 Government of the Russian Federation, contract No. 02.A03.21.0006.

This book establishes a dialog between experimental psychology and electrophysiology in the study of infant language development. On the one hand, traditional methods of investigation into language development have reached a high level of refinement despite being confined to observing infants' overt behavioral responses. On the other hand, more recent methods such as neuroimaging and, in particular, event-related potentials provide access to implicit responses from the infant brain while often relying on rather gross experimental contrasts. The aims of this book are both to provide neuroscient.

Medical devices have been targets of hacking for over a decade, and this cybersecurity issue has affected many types of medical devices. Lately, the potential for hacking of cardiac devices (pacemakers and defibrillators) claimed the attention of the media, patients, and health care providers. This is a burgeoning problem that our newly electronically connected world faces. In this paper from the Electrophysiology Section Council, we briefly discuss various aspects of this relatively new threat in light of recent incidents involving the potential for hacking of cardiac devices. We explore the possible risks for the patients and the effect of device reconfiguration in an attempt to thwart cybersecurity threats. We provide an outline of what can be done to improve cybersecurity from the standpoint of the manufacturer, government, professional societies, physician, and patient.

AbstractThis study explored the electrophysiology underlying intonational phrase processing at different stages of syntax acquisition. Developmental studies suggest that children's syntactic skills advance significantly between 2 and 3 years of age. Here, children of three age groups were tested on phrase‐level prosodic processing before and after this developmental phase, while their brain activity was recorded. The Closure Positive Shift (CPS), which indexes the perception of intonational phrasing in adults, served as dependent variable. The event‐related brain potentials of 3‐ and 6‐year‐olds, but not of 21‐month‐olds, showed a CPS. These results suggest that prosodic phrase processing, as indicated by the CPS, is established only later during children's development, pointing to a close interaction of prosody and syntax acquisition.

Personalised cardiac models were built from the computed tomography imaging data for two patients with implanted cardiac resynchronisation therapy devices. The cardiac models comprised a biventricular model of myocardial electrophysiology coupled with a model of the torso to simulate the body surface potential map. The models were verified against electrocardiogams (ECG) recorded in the patients from 240 leads on the body surface under left ventricular pacing. The simulated ECG demonstrated a significant sensitivity to the myocardial anisotropy and location of the pacing electrode tip in the models. An apicobasal cellular heterogeneity was shown to be less significant for the ECG pattern at the paced-ventricle activation than that showed earlier by Keller and co-authors (2012) for the normal activation sequence. © 2017 IEEE Computer Society. All rights reserved. ; This study was supported by the RAS Presidium Programme I.33Π, and Government of the Russian Federation (agreement 02.A03.21.0006). We used the computational clusters of Ural Federal University and "URAN" of Institute of Mathematics and Mechanics (Ekaterinburg).

This study was aimed to assess electrophysiological brain activity in newborns of various gestational ages using electroencephalography (EEG). We summarized the data on the main EEG characteristics of premature infants and their dynamics and described the most common pathological EEG changes that can be identified at this age. We also discussed prognostic value of various neonatal EEG patterns (including their proportion and location), which allow verification of functional brain disorders at early stages. © 2019 ABV-Press Publishing House. All rights reserved. ; Russian Science Foundation, RSF ; Финансирование. Работа выполнена при финансовой поддержке гранта №16-18-10371 Российского научного фонда. Исследование прово-дится в рамках программы, поддержанной постановлением №211 Правительства Российской Федерации, соглашение №02.A03.21.0006. Financing. The study was funded by the grant No. 16-18-10 371 from the Russian Science Foundation. The study conducts within a program, supported by the resolution of the Russian Government No. 211, agreement No. 02.A03.21.0006.

AbstractSymbolic numeracy first emerges as children learn the meanings of number words and how to use them to precisely count sets of objects. This development starts before children enter school and forms a foundation for lifelong mathematics achievement. Despite its importance, exactly how children acquire this basic knowledge is unclear. Here we test competing theories of early number learning by measuring event‐related brain potentials during a novel number word‐quantity comparison task in 3–4‐year‐old preschool children (N = 128). We find several qualitative differences in neural processing of number by conceptual stage of development. Specifically, we find differences in early attention‐related parietal electrophysiology (N1), suggesting that less conceptually advanced children process arrays as individual objects and more advanced children distribute attention over the entire set. Subsequently, we find that only more conceptually advanced children show later‐going frontal (N2) sensitivity to the numerical‐distance relationship between the number word and visual quantity. The nature of this response suggested that exact rather than approximate numerical meanings were being associated with number words over frontal sites. No evidence of numerical distance effects was observed over posterior scalp sites. Together these results suggest that children may engage parallel individuation of objects to learn the meanings of the first few number words, but, ultimately, create new exact cardinal value representations for number words that cannot be defined in terms of core, nonverbal number systems. More broadly, these results document an interaction between attentional and general cognitive mechanisms in cognitive development.Research Highlights
Conceptual development in numeracy is associated with a shift in attention from objects to sets.
Children acquire meanings of the first few number words through associations with parallel attentional individuation of objects.
Understanding of cardinality is associated with attentional processing of sets rather than individuals.
Brain signatures suggest children attribute exact rather than approximate numerical meanings to the first few number words.
Number‐quantity relationship processing for the first few number words is evident in frontal but not parietal scalp electrophysiology of young children.

Abstract Despite the sparseness of the currently available data, there is accumulating evidence of information processing impairment in post-traumatic stress disorder (PTSD). Studies of event-related potentials (ERPs) are the main tool in real time examination of information processing. In this paper, we sought to critically review the ERP evidence of information processing abnormalities in patients with PTSD. We also examined the evidence supporting the existence of a relationship between ERP abnormalities and symptom profiles or severity in PTSD patients. An extensive Medline search was performed. Keywords included PTSD or post-traumatic stress disorder, electrophysiology or EEG, electrophysiology, P50, P100, N100, P2, P200, P3, P300, sensory gating, CNV (contingent negative variation) and MMN (mismatch negativity). We limited the review to ERP adult human studies with control groups which were reported in the English language. After applying our inclusion-exclusion review criteria, 36 studies were included. Subjects exposed to wide ranges of military and civilian traumas were studied in these reports. Presented stimuli were both auditory and visual. The most widely studied components included P300, P50 gating, N100 and P200. Most of the studies reported increased P300 response to trauma-related stimuli in PTSD patients. A smaller group of studies reported dampening of responses or no change in responses to trauma-related and/or unrelated stimuli. P50 studies were strongly suggestive of impaired gating in patients with PTSD. In conclusion, the majority of reports support evidence of information processing abnormalities in patients with PTSD diagnosis. The predominance of evidence suggests presence of mid-latency and late ERP components differences in PTSD patients in comparison to healthy controls. Heterogeneity of assessment methods used contributes to difficulties in reaching firm conclusions regarding the nature of these differences. We suggest that future ERP-PTSD studies utilize standardized assessment scales that provide detailed information regarding the symptom clusters and the degree of symptom severity. This would allow assessment of electrophysiological indices-clinical symptoms relationships. Based on the available data, we suggest that ERP abnormalities in PTSD are possibly affected by the level of illness severity. If supported by future research, ERP studies may be used for both initial assessment and treatment follow-up.

In this work, a computer simulation of the reentrant ventricular tachycardia (VT) was used to investigate the peculiar properties of phase maps based on transmembrane potentials (TP) and extracellular potentials (EP). The simulation approach included the bidomain model with full myocardium-torso coupling, a realistic ionic model of the human cardiomyocytes and a personalized geometry of the heart and torso. The phase mapping pipeline includes a signal detrending and the Hilbert transform. It was demonstrated that TP-based phase maps correlated well with the propagation of cardiac excitation. In contrast, EP-based phase mapping provides some aberrations which can complicate electrophysiological interpretation of the phase maps in terms of cardiac activation sequence. It was also shown that a modification of the phase computation algorithm, including the sign inversion of signals and a special transformation of the phase plot, can partially eliminate these aberrations and make EP-based phase maps resemble TP-based maps. © 2018 Creative Commons Attribution. ; Russian Foundation for Basic Research, RFBR: 18-31-00401 ; The reported study was funded by RFBR according to the research project No. 18-31-00401. Development of computer model with personalized geometry was funded by IIP UrB RAS theme No AAAA-A18-118020590031-8, RF Government Act #211 of March 16, 2013 (agreement 02.A03.21.0006), Program of the Presidium RAS #27 (project AAAA-A18-118020590030-1).

Objective To determine the natural history of the morphology of the median nerve after carpal tunnel decompression.
Methods Between October and December 2014, patients with suspected carpal tunnel were prospectively enrolled and underwent pre- and postoperative (3 and 6 months) high-definition ultrasonography, electrophysiology, and clinical testing.
Results A total of 81 patients were enrolled in the study; 75 (93%) could be reached for the 6-month follow-up, and 100% were clinically better at the 6-month follow-up. The mean cross-sectional area decreased from 14.3 ± 4.4 mm2 to 9.6 ± 2.3 mm2 (mean ± standard deviation [SD]). The mean distal motor latency decreased from 6.5 ± 2.2 msec to 4.4 ± 0.8 msec (mean ± SD). Distal motor latency improved statistically significantly after surgical decompression as well, but sooner.
Conclusion We present the second largest series of patients with sonographic follow-up after surgical decompression of the carpal tunnel.

Organic electrochemical transistors (OECTs) have been widely used as transducers in electrophysiology and other biosensing applications. Their identifying characteristic is a transconductance that increases with channel thickness, and this provides a facile mechanism to achieve high signal amplification. However, little is known about their noise behavior. Here, we investigate noise and extract metrics for the signal-to-noise ratio and limit of detection in OECTs with different channel thicknesses. These metrics are shown to improve as the channel thickness increases, demonstrating that OECTs can be easily optimized to show not only high amplification, but also low noise. ; This work was funded by the European Union's Horizon 2020 research and innovation programme under Grant Agreement No. 732032 (BrainCom) the King Abdullah University of Science and Technology (KAUST) Office of sponsored Research (OSR) under Award No. OSR-2016-CRG5-3003. Authors also acknowledge funding from the 2DTecBio (FIS2017-85787-R) funded by the Spanish Ministry of Science, Innovation and Universities, the State Research Agency (AEI), and the European Regional Development Fund. ; Peer reviewed

The study is aimed to develop a new human cardiomyocyte model, which describes electromechanical coupling and mechano-electric feedbacks. The combined electromechanical model (TP+M) links the TP06 electrophysiological model of the human cardiomyocyte with our earlier developed model of the myocardium mechanical activity and its calcium regulation. In the TP+M model, we tried to maintain principal features of calcium transients and action potentials during the twitches typical for the human cardiomyocytes. The developed TP+M model allows simulating several basic classic phenomena such as load-dependent relaxation and length-dependence of isometric twitches and respective changes in action potential duration. We have also simulated some age-dependent changes in the electrical and mechanical activity in the human cardiomyocytes. © 2018 Creative Commons Attribution. ; The work was carried out within the framework of the IIP UrB RAS themes (Nos. AAAA-A18-118020590031-8, АААА-А18-118020590134-6) and was supported by Act 211 Government of the Russian Federation, contract № 02.A03.21.0006, and by RFBR (18-01-00059 - single cell modeling; 18-015-00368 – ageing simulation).

In scientific work, sonification (i.e., the use of nonspeech audio to convey information) is primarily thought of as a novel way to communicate post hoc research findings to lay audiences but only rarely, if ever, as a component of the research itself. This article argues that, rather than any inherent epistemological limitations of sound as a medium of scientific reasoning, this framing reflects a sociohistorical tendency to "silence" experimental techniques as they become widely adopted—both in terms of the literal silencing of noisy instrumentation and the elision of the role of sound (along with other nonvisual sensory media) in received discovery accounts. This tendency is well-illustrated by the history of electrophysiology research, particularly the case of the electrical penetration graph (EPG), an instrument used by entomologists to study how insects feed on plants. Combining participant observation, interviews, and analysis of EPG technical literature, this article recovers the unacknowledged role of sound in EPG's exploratory stages and gradual emergence as a standard laboratory technique as well as its gradual silencing as a consequence of this standardizing process.

Проведен анализ оказания высокотехнологичной медицинской помощи больным с аритмиями сердца в военно-медицинских лечебных учреждениях (ВМЛУ). Имеющиеся силы и средства ВМЛУ позволяют осуществлять весь спектр высокотехнологичной помощи больным с аритмиями сердца. Для повышения эффективности и доступности этого вида помощи необходимо оснастить аритмологические отделения современным оборудованием и создать при окружных (флотских) госпиталях кабинеты электрокардиостимуляции, где проводить имплантации временных и постоянных водителей ритма сердца. Поднят вопрос о необходимости создания программы подготовки (первичной специализации) и повышения квалификации врачей по клинической электрофизиологии сердца, интервенционной и хирургической аритмологии в Минобороны России. ; Analysis of provision of high-tech medical aid to patients with cardiac arrhythmia based at military medical facilities showed that the available means and workforce are sufficient for the purpose. In order to facilitate access to high-tech medical aid it is necessary to equip arrhythmologic departments with up-to-date-instruments and set up cabinets of electrocardiostimulation in regional (naval) hospitals for implantation of temporary and permanent pacemakers. A program is pending for education (primary specialization) and advanced training of specialists in clinical cardiac electrophysiology, interventional and surgical arrhythmology.