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Atrial Fibrillation (AF) is the most common cardiac arrhythmia. Signal-processing approaches are widely used for the analysis of intracardiac electrograms (iEGMs), which are collected during catheter ablation from patients with AF. In order to identify possible targets for ablation therapy, dominant frequency (DF) is widely used and incorporated in electroanatomical mapping systems. Recently, a more robust measure, multiscale frequency (MSF), for iEGM data analysis was adopted and validated. However, before completing any iEGM analysis, a suitable bandpass (BP) filter must be applied to remove noise. Currently, no clear guidelines for BP filter characteristics exist. The lower bound of the BP filter is usually set to 3–5 Hz, while the upper bound (BP¯th) of the BP filter varies from 15 Hz to 50 Hz according to many researchers. This large range of BP¯th subsequently affects the efficiency of further analysis. In this paper, we aimed to develop a data-driven preprocessing framework for iEGM analysis, and validate it based on DF and MSF techniques. To achieve this goal, we optimized the BP¯th  using a data-driven approach (DBSCAN clustering) and demonstrated the effects of different BP¯th on subsequent DF and MSF analysis of clinically recorded iEGMs from patients with AF. Our results demonstrated that our preprocessing framework with BP¯th = 15 Hz has the best performance in terms of the highest Dunn index. We further demonstrated that the removal of noisy and contact-loss leads is necessary for performing correct data iEGMs data analysis.

Paroxysmal atrial fibrillation (Paro. AF) is challenging to identify at the right moment. This disease is often undiagnosed using currently existing methods. Nonlinear analysis is gaining importance due to its capability to provide more insight into complex heart dynamics. The aim of this study is to use several recently developed nonlinear techniques to discriminate persistent AF (Pers. AF) from normal sinus rhythm (NSR), and more importantly, Paro. AF from NSR, using short-term single-lead electrocardiogram (ECG) signals. Specifically, we adapted and modified the time-delayed embedding method to minimize incorrect embedding parameter selection and further support to reconstruct proper phase plots of NSR and AF heart dynamics, from MIT-BIH databases. We also examine information-based methods, such as multiscale entropy (MSE) and kurtosis (Kt) for the same purposes. Our results demonstrate that embedding parameter time delay ( τ ), as well as MSE and Kt values can be successfully used to discriminate between Pers. AF and NSR. Moreover, we demonstrate that τ and Kt can successfully discriminate Paro. AF from NSR. Our results suggest that nonlinear time-delayed embedding method and information-based methods provide robust discriminating features to distinguish both Pers. AF and Paro. AF from NSR, thus offering effective treatment before suffering chaotic Pers. AF.

Background Intrinsic atrioventricular (AV) conduction is used to optimize AV intervals with cardiac resynchronization therapy (CRT) in most device algorithms. Atrial pacing and heart rate affect conduction times, but little is known regarding differeces among chronotropic incompetent(CI) and competent(CC) patients to guide programming. Methods RAVE was a multicenter prospective trial of CRT patients. Heart rate was increased with incremental atrial pacing and with submaximal exercise. According to the maximal heart rate achieved during exercise, patients were classified as either CI or CC. For CI patients, an additional symptom-limited exercise with rate-adaptive pacing activated was performed. Intracardiac intervals were measured from the implantable lead electrograms in multiple postures. Results There were 12 subjects with CI and 24 with CC. With atrial pacing, AV interval immediately increased and gradually increased with incremental atrial pacing in all patients. However, the changes in the atrial to right ventricular (ARV) and atrial to left ventricular (ALV) intervals with increasing atrial pacing rates were about threefold greater in CI patients compared to CC patients (24.3 ± 28.9 vs. 7.2 ± 5.5 ms/10 bpm for ARV and 22.7 ± 25.6 vs. 7.1 ± 5.7 ms/10 bpm for ALV in the standing position, p  < 0.05). In CI pacing with rate-adaptive pacing during exercise, AV interval changes with paced heart rate were variable. Conclusions The AV response to overdrive atrial pacing at rest may provide a simple means of identifying chronotropic competence in CRT patients. For patients with CI, who often require rate-adaptive atrial pacing, rate-adaptive AV algorithms should be adjusted individually.

Each heartbeat is controlled by an electrical wave of excitation that propagates through the heart and initiates cardiac contraction. The normal heartbeat is initiated by pacemaker cells in the sinus node located in the right atrium, propagate throughout the atria, and then enters the ventricles via the atrioventricular junction and finally ends in the Purkinje fibers. The rate and regularity of these cardiac rhythms are determined by the intrinsic firing rate (automaticity) of the pacemaker cells and the influence of extrinsic factors, including various ionic mechanisms and drugs. Abnormal regimes of wave initiation and propagation result in cardiac arrhythmias. Various mechanisms, including local ectopic activity, focal triggers, wave breaks, and functional reentry, drive the arrhythmic activity in the heart. The spatiotemporal complexity of each of these underlying mechanisms is different, with more complexity seen in tachyarrhythmias and less complexity for bradyarrhythmias. Understanding the spatiotemporal complexity of the different arrhythmias is of great interest to electrophysiologists.In recent years, catheter ablation therapy (non-pharmacological approach) has had an increasingly important role in curing many arrhythmias. The underlying spatiotemporal complexity of each arrhythmia plays an important role in deciding the target sites for ablation in this therapy. Currently, existing signal analysis techniques are not robust for all types of arrhythmias. Therefore it is essential to develop new approaches that can fully capture the intrinsic dynamics and the spatiotemporal complexity of both atrial and ventricular arrhythmias using intracardiac electrogram signals.Some novel approaches, namely multiscale frequency, multiscale entropy, kurtosis, and Shannon entropy, were developed using the ex-vivo optical mapping of rabbit hearts. But, the nature of signals obtained during optical mapping is very different from the intracardiac electrograms obtained during the catheter ablation procedure. Also, the clinical recordings suffer from limitations such as sparse spatial data availability and sequential mapping. Therefore it is essential to enhance the above techniques to work on the intracardiac electrograms and also identify the spatial sites in the heart that maintain these arrhythmic activities.For my study, the intracardiac analysis was performed under two different types of cardiac arrhythmic rhythms, namely Atrial Fibrillation (AF) and Ventricular Fibrillation (VF). Atrial Fibrillation (AF) is an arrhythmia in the upper two chambers (atria) of the heart. AF is responsible for significant impairment in quality of life and contributes to substantial morbidity and health care expenditure. AF is the most common arrhythmia in humans and, as such, is heterogeneous in its mechanism, presentation, and clinical course and therefore requires individualized treatment. Ventricular fibrillation (VF) is a type of lethal heart rhythm. During ventricular fibrillation, disorganized heart signals cause the lower heart chambers (ventricles) to quiver, and the heart does not pump blood to the rest of the body. Ventricular fibrillation is an emergency that requires immediate medical attention. It's the most frequent cause of sudden cardiac death.Although both these rhythms originate at different locations of the heart and have different types of rhythms and morphology, the underlying spatiotemporal organizations and intracardiac electrogram analysis approaches are similar. Therefore, my thesis consists of the following three objectives:1. Clinical implementation and validation of novel approaches using intracardiac electrograms to characterize the spatiotemporal dynamics of the AF arrhythmic activities. 2. Development of a similarity score using a combination of various iEGMs analysis techniques to more accurately identify the spatial location of active sites in AF patients. 3. Development of an analytical approach to characterize the organization (organized or disorganized) of VF electrical activities using clinical intracardiac electrograms.

Bionic-engineered tissues have been proposed for testing the performance of cardiovascular medical devices and predicting clinical outcomes ex vivo. Progress has been made in the development of compliant electronics that are capable of monitoring treatment parameters and being coupled to engineered tissues; however, the scale of most engineered tissues is too small to accommodate the size of clinical-grade medical devices. Here, we show substantial progress toward bionic tissues for evaluating cardiac ablation tools by generating a centimeter-scale human cardiac disk and coupling it to a hydrogel-based soft-pressure sensor. The cardiac tissue with contiguous electromechanical function was made possible by our recently established method to 3D bioprint human pluripotent stem cells in an extracellular matrix-based bioink that allows for in situ cell expansion prior to cardiac differentiation. The pressure sensor described here utilized electrical impedance tomography to enable the real-time spatiotemporal mapping of pressure distribution. A cryoablation tip catheter was applied to the composite bionic tissues with varied pressure. We found a close correlation between the cell response to ablation and the applied pressure. Under some conditions, cardiomyocytes could survive in the ablated region with more rounded morphology compared to the unablated controls, and connectivity was disrupted. This is the first known functional characterization of living human cardiomyocytes following an ablation procedure that suggests several mechanisms by which arrhythmia might redevelop following an ablation. Thus, bionic-engineered testbeds of this type can be indicators of tissue health and function and provide unique insight into human cell responses to ablative interventions.

Ventricular fibrillation (VF) is a lethal cardiac arrhythmia that is a significant cause of sudden cardiac death. Comprehensive studies of spatiotemporal characteristics of VF in situ are difficult to perform with current mapping systems and catheter technology. The goal of this study was to develop a computational approach to characterize VF using a commercially available technology in a large animal model. Prior data suggests that characterization of spatiotemporal organization of electrical activity during VF can be used to provide better mechanistic understanding and potential ablation targets to modify VF and its substrate. We therefore evaluated intracardiac electrograms during biventricular mapping of the endocardium (ENDO) and epicardium (EPI) in acute canine studies. To develop thresholds for organized and disorganized activity, a linear discriminant analysis (LDA)-based approach was performed to the known organized and disorganized activities recorded in ex vivo Langendorff-perfused rat and rabbit hearts using optical mapping experiments. Several frequency- and time-domain approaches were used as individual and paired features to identify the optimal thresholds for the LDA approach. Subsequently, VF was sequentially mapped in 4 canine hearts, using the CARTO mapping system with a multipolar mapping catheter in the ENDO left and right ventricles and EPI to capture the progression of VF at 3 discrete post-induction time intervals: VF period 1 (just after induction of VF to 15 min), VF period 2 (15 to 30 min), and VF period 3 (30 to 45 min). The developed LDA model, cycle lengths (CL), and regularity indices (RI) were applied to all recorded intracardiac electrograms to quantify the spatiotemporal organization of VF in canine hearts. We demonstrated the presence of organized activity in the EPI as VF progresses, in contrary to the ENDO, where the activity stays disorganized. The shortest CL always occurred in the ENDO, especially the RV, indicating a faster VF activity. The highest RI was found in the EPI in all hearts for all VF stages, indicating spatiotemporal consistency of RR intervals. We identified electrical organization and spatiotemporal differences throughout VF in canine hearts from induction to asystole. Notably, the RV ENDO is characterized by a high level of disorganization and faster VF frequency. In contrast, EPI has a high spatiotemporal organization of VF and consistently long RR intervals.

Staphylococcus aureus is a major pathogen in India causing community and nosocomial infections, but little is known about its molecular epidemiology and mechanisms of resistance in hospital settings. Here, we use whole-genome sequencing (WGS) to characterize 478 S . aureus clinical isolates (393 methicillin-resistant Staphylococcus aureus (MRSA) and 85 methicilin-sensitive Staphylococcus aureus (MSSA) collected from 17 sentinel sites across India between 2014 and 2019. Sequencing results confirmed that sequence type 22 (ST22) (142 isolates, 29.7%), ST239 (74 isolates, 15.48%), and ST772 (67 isolates, 14%) were the most common clones. An in-depth analysis of 175 clonal complex (CC) 22 Indian isolates identified two novel ST22 MRSA lineages, both Panton-Valentine leukocidin+, both resistant to fluoroquinolones and aminoglycosides, and one harboring the the gene for toxic shock syndrome toxin 1 (tst) . A temporal analysis of 1797 CC22 global isolates from 14 different studies showed that the two Indian ST22 lineages shared a common ancestor in 1984 (95% highest posterior density [HPD]: 1982–1986), as well as evidence of transmission to other parts of the world. Moreover, the study also gives a comprehensive view of ST2371, a sublineage of CC22, as a new emerging lineage in India and describes it in relationship with the other Indian ST22 isolates. In addition, the retrospective identification of a putative outbreak of multidrug-resistant (MDR) ST239 from a single hospital in Bangalore that persisted over a period of 3 years highlights the need for the implementation of routine surveillance and simple infection prevention and control measures to reduce these outbreaks. To our knowledge, this is the first WGS study that characterized CC22 in India and showed that the Indian clones are distinct from the EMRSA-15 clone. Thus, with the improved resolution afforded by WGS, this study substantially contributed to our understanding of the global population of MRSA. The study conducted in India between 2014 and 2019 presents novel insights into the prevalence of MRSA in the region. Previous studies have characterized two dominant clones of MRSA in India, ST772 and ST239, using whole-genome sequencing. However, this study is the first to describe the third dominant clone, ST22, using the same approach. The ST22 Indian isolates were analyzed in-depth, leading to the discovery of two new sublineages of hospital-acquired Staphylococcus aureus in India, both carrying antimicrobial resistance genes and mutations, which limit treatment options for patients. One of the newly characterized sublineages, second Indian cluster, carries the tsst-1 virulence gene, increasing the risk of severe infections. The geographic spread of the two novel lineages, both within India and internationally, could pose a global public health threat. The study also sheds light on ST2371 in India, a single-locus variant of ST22. The identification of a putative outbreak of MDR ST239 in a single hospital in Bangalore emphasizes the need for routine surveillance and simple infection prevention and control measures to reduce these outbreaks. Overall, this study significantly contributes to our understanding of the global population of MRSA, thanks to the improved resolution afforded by WGS.

A differential is a gear train that transmits an engine's torque to the wheels. During a turn, the outer and inner wheels of the vehicle are forced to travel along paths of different radii. A differential allows the outer driving wheel to rotate at a faster speed when compared to the inner driving wheel during a turn. It is designed such that, increase in speed of one wheel is balanced by a decrease in speed of the other. This ensures that the vehicle can negotiate a turning without slipping. The gears in the differential are supported by a cage which results in its bulky appearance and heavy form. This causes a number of disadvantages such as difference in length of the driveshafts and offset center of mass of the system due to asymmetrical design. Such a cage also adds additional weight to the vehicle and increases fuel consumption as a consequence. Its elimination results in a more compact and lightweight configuration. This paper focuses on the complete methodology of designing and analyzing a cageless differential. Various materials were considered for the assembly and one with adequate properties of strength, wear resistance and other core parameters was selected. Gear ratios were obtained through theoretical calculation and the values were used as input for designing using Solidworks software. Finite element analysis of the gear train was carried out using ANSYS Workbench to test the structural integrity and durability of the system through various types of analysis such as linear static structural, fatigue and explicit dynamic analysis. The results proved that the design meets the desired functionality and is an improvement to the conventional type of differential gearbox.

Questions are raised in effective utilization of farmer's wisdom by communities in their farming. Planners support to livelihood emphasize mostly of inputs from outside and not setting up sustainable goals. Formal institutions and planners of program are finding constraints and sceptical in wider dissemination of indigenous knowledge research system (IKRS). This is in spite of evidence that considerable number of farmer's in livestock sector depends on IKRS. In this context, it is pertinent to showcase dissemination potential of these knowledge system(s) in larger geographical areas. The review illustrates different challenges encountered while control of livestock ailments like ectoparasite infestation through IKRS. Several times, it was opinioned to provide or share IKRS to thwart ailments in a specific region. This is interesting as it was narrated how formal system is unable to recognize farmer's problem and challenges in integrating these sustainable practices. It has to be noted that disseminating activities seldom takes into account the experimental potential of farmers. This review paper articulates various evidences generated in enhancing diffusion thereby dissemination of IKRS. The nature of support extended by IKRS in entrepreneurial activity of smallholder farming units did not get adequate recognition. There needs to be minimum standard protocol in deriving benefit from such low-cost alternative technologies. This will enrich incremental innovation activities as per location specific need and provide scope for wider dissemination.

We report the persistent circulation of third-generation cephalosporin resistant Salmonella Typhi in Mumbai, linked to the acquisition and maintenance of a previously characterized IncX3 plasmid carrying the ESBL gene blaSHV-12 and the fluoroquinolone resistance gene qnrB7 in the genetic context of a triple mutant also associated with fluoroquinolone resistance. Competing Interest Statement The authors have declared no competing interest.