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Large-region acoustic source mapping is important for city-scale noise monitoring. Approaches using a single-position measurement scheme to scan large regions using small arrays cannot provide clean acoustic source maps, while deploying large arrays spanning the entire region of interest is prohibitively expensive. A multiple-position measurement scheme is applied to scan large regions at multiple spatial positions using a movable array of small size. Based on the multiple-position measurement scheme, a sparse-constrained multiple-position vectorized covariance matrix fitting approach is presented. In the proposed approach, the overall sample covariance matrix of the incoherent virtual array is first estimated using the multiple-position array data and then vectorized using the Khatri-Rao (KR) product. A linear model is then constructed for fitting the vectorized covariance matrix and a sparse-constrained reconstruction algorithm is proposed for recovering source powers from the model. The user parameter settings are discussed. The proposed approach is tested on a 30 m × 40 m region and a 60 m × 40 m region using simulated and measured data. Much cleaner acoustic source maps and lower sound pressure level errors are obtained compared to the beamforming approaches and the previous sparse approach [Zhao, Tuna, Nguyen, and Jones, Proc. IEEE Intl. Conf. on Acoustics, Speech and Signal Processing (ICASSP) (2016)].

© 2019 Wiley Periodicals, Inc. Introduction: Catheter-tissue contact force is a determinant of radiofrequency (RF) ablation lesion effectiveness. However, ablation on a beating heart is subject to force variability, making it difficult to optimally deliver consistently durable and transmural lesions. This work evaluates improvements in contact force stability and lesion reproducibility by using a catheter contact-force controller (CFC) during lesion delivery in vitro and in vivo. Methods and Results: Using a sheath and force-sensing catheter, an experienced operator attempted to maintain a constant force of 20 g at targets within the atria and left ventricle of a pig manually and using the CFC; the average force and contact-force variation (CFV) achieved using each approach were compared. Ablation lesions (20 W, 30 seconds, 17 mL/min irrigation) were created in bovine tissue samples mounted on a platform programmed to reproduce clinically relevant motion. CFC-assisted lesions were delivered to stationary and moving tissue with forces of 5 to 35 g. Mimicking manual intervention, lesions were also delivered to moving tissue while the CFC was disabled. Resultant lesion volumes were compared using two-way analysis of variance. When using the CFC, the average force was within 1 g of the set level, with a CFV less than 5 g, during both in vitro and in vivo experiments. Reproducible and statistically identical (P =.82) lesion volumes proportional to the set force were achieved in both stationary and moving tissue when the CFC was used. Conclusions: CFC assistance maintains constant force in vivo and removes effect of motion on lesion volume during RF lesion delivery.

Environmental noise is a risk factor for human physical and mental health, demanding an efficient large-scale noise-monitoring scheme. The current technology, however, involves extensive sound pressure level (SPL) measurements at a dense grid of locations, making it impractical on a city-wide scale. This paper presents an alternative approach using a microphone array mounted on a moving vehicle to generate two-dimensional acoustic tomographic maps that yield the locations and SPLs of the noise-sources sparsely distributed in the neighborhood traveled by the vehicle. The far-field frequency-domain delay-and-sum beamforming output power values computed at multiple locations as the vehicle drives by are used as tomographic measurements. The proposed method is tested with acoustic data collected by driving an electric vehicle with a rooftop-mounted microphone array along a straight road next to a large open field, on which various pre-recorded noise-sources were produced by a loudspeaker at different locations. The accuracy of the tomographic imaging results demonstrates the promise of this approach for rapid, low-cost environmental noise-monitoring.

Intermittent hypoxia (IH) is a major pathophysiological consequence of obstructive sleep apnea. Recently, it has been shown that IH results in changes in body energy balance, leptin secretion and concomitant alterations in arcuate nucleus (ARC). In this study, the role of leptin on these changes was investigated in leptin-deficient rats exposed to IH or normoxic control conditions. Body weights, consumatory and locomotor behaviours, and protein signaling in ARC were assessed immediately after IH exposure. Compared to normoxia, IH altered body weight, food intake, locomotor pattern, and the plasma concentration of leptin and angiotensin II in the wild-type rat. However, these changes were not observed in the leptin-deficient rat. Within ARC of wild-type animals, IH increased phosphorylated signal transducer and activator of transcription 3 and pro-opiomelanocortin protein expression, but not in the leptin-deficient rat. The long-form leptin receptor protein expression was not altered following IH in either rat strain. These data suggest that leptin is involved in mediating the alterations to body energy balance and ARC activity following IH.

Objective: To implement a University Faculty mentorship program in the Division of Emergency Medicine. Methods: A program based on a unique Schulich faculty mentorship policy was implemented with the help of a Provider Value Officer. The process involved creating a training program which defined the roles of the mentors and mentees and established the principles of an effective mentor-mentee relationship. Faculty received training on how to participate effectively in a Schulich faculty mentorship committee. Each committee consisted of a mentee, and two mentors at the associate professor level (one internal and one external) . Thirteen distinct external divisions were represented. They were instructed to meet twice per year, as arranged by the mentee. The mentee created mentor minutes using a template, and then submitted the minutes to the members of the mentorship committee and the Chair/Chief of Emergency medicine. The Chair/Chief used the minutes during the annual Continuing Professional Development meeting.Results: In less than a year, the division has successfully transformed its mentorship program. Using the above-mentioned process, 31 of 34 (91%) eligible assistant professors have functioning mentorship committees. Collaboration and participation between the different faculties has increased. Follow-up meetings with the Chair/Chief and the Provider Value Officer revealed the theme that, universally, participants have perceived Schulich Faculty Mentorship committees as beneficial and are happy with the "fit" of their mentorship committees. Conclusion: Through careful planning and training, a successful Faculty Mentorship program can be initiated in an academic division in less than a year with the help of a local champion given protected time.

Background The Collaboration of Practitioners and Researchers Seminar Series is student-led program comprised of seminars delivered jointly by medical and graduate students on a topic in medicine of mutual interest to an audience of both medical and graduate students. Methods Following its inaugural year in 2016–2017, we evaluated changes in attendees’ perceived understanding of translational research through an electronic survey and semi-structured interviews with attendees. Results Study participants rated their understanding of translational research and comfort with interacting with students from the other program higher following attending seminars. Participants believed that the seminars helped in breaking barriers between medical and graduate students. Conclusions We conclude that this seminar series positively impacted attendees’ understanding of translational research and attitudes towards collaboration between medical and graduate students. We believe that similar initiatives may be of value in fostering new opportunities for collaboration between medical and graduate students at other institutions.

Noise-mapping is an effective sound visualization tool for the identification of urban noise hotspots, which is crucial to taking targeted measures to tackle environmental noise pollution. This paper develops a high-resolution wideband acoustic source mapping methodology using a portable microphone array, where the joint localization and power spectrum estimation of individual sources sparsely distributed over a large region are achieved by tomographic imaging with the multi-frequency delay-and-sum beamforming power outputs from multiple array positions. Exploiting the fact that a wideband source has a common spatial signal-support across the frequency spectrum, two-dimensional tomographic maps are produced by applying compressive sensing techniques including group least absolute shrinkage selection operator formulation and sparse Bayesian learning to promote group sparsity over multiple frequency bands. The high-resolution mapping is demonstrated with experimental data recorded with a microphone array mounted atop an electric vehicle driven along a road while playing audio clips from a loudspeaker positioned within the adjacent open field.

The Schulich School of MedicineDentistry in London, Ontario, has a mentorship program for all full-time faculty. The school would like to expand its outreach to physician faculty located in distributed medical education sites. The purpose of this study was to determine what, if any, mentorship distributed physician faculty currently have, to gauge their interest in expanding the mentorship program to distributed physician faculty and to determine their vision of the most appropriate design of a mentorship program that would address their needs.We conducted a mixed-methods study. The quantitative phase consisted of surveys sent to all distributed faculty members that elicited information on basic demographic characteristics and mentorship experiences/needs. The qualitative phase consisted of 4 focus groups of distributed faculty administered in 2 large and 2 small centres in both regions of the school's distributed education network: Sarnia, Leamington, Stratford and Hanover. Interviews were 90 minutes long and involved standardized semistructured questions.Of the 678 surveys sent, 210 (31.0%) were returned. Most respondents (136 [64.8%]) were men, and almost half (96 [45.7%]) were family physicians. Most respondents (197 [93.8%]) were not formal mentors to Schulich faculty, and 178 (84.8%) were not currently being formally mentored. Qualitative analysis suggested that many respondents were involved in informal mentoring. In addition, about half of the respondents (96 [45.7%]) wished to be formally mentored in the future, but they may be inhibited owing to time constraints and geographical isolation. Consistently, respondents wished to have mentoring by a colleague in a similar practice, with the most practical being one-on-one mentoring.Our analysis suggests that the school's current formal mentoring program may not be applicable and will require modification to address the needs of distributed faculty.L’École de médecine et de dentisterie Schulich, à London en Ontario, offre un programme de mentorat à tout le personnel enseignant à temps plein. L’École aimerait étendre son programme aux médecins enseignants des établissements de formation médicale décentralisée. Le but de cette étude était de déterminer à quel mentorat, le cas échéant, ces médecins ont accès actuellement et d’établir leur intérêt pour le programme de mentorat de l’École et leur vision du programme le plus approprié pour répondre à leurs besoins.Nous avons mené une étude en méthodologie mixte. Lors de la phase quantitative, nous avons envoyé des questionnaires à tous les médecins des établissements de formation médicale décentralisée afin d’obtenir des renseignements sur les caractéristiques démographiques de base ainsi que les expériences et besoins de mentorat. La phase qualitative comprenait quatre groupes de discussion composés de médecins enseignants décentralisés dans deux grands et deux petits centres des deux régions du réseau de formation décentralisée de l’École, soit Sarnia, Leamington, Stratford et Hanover. Les entrevues étaient d’une durée de 90 minutes et se composaient de questions semi-structurées normalisées.Sur les 678 questionnaires distribués, 210 (31 %) ont été retournés. La plupart des répondants (136 [64,8 %]) étaient des hommes et presque la moitié (96 [45,7 %]) étaient des médecins de famille. La plupart des répondants (197 [93,8 %]) n’agissaient pas comme mentors officiels auprès du personnel enseignant de l’École de médecine et de dentisterie Schulich et 178 (84,8 %) ne recevaient pas de mentorat officiel actuellement. L’analyse qualitative suggère que plusieurs répondants participaient à une forme quelconque de mentorat informel. De plus, environ la moitié des répondants (96 [45,7 %]) souhaitaient recevoir un mentorat officiel à l’avenir, mais avaient possiblement des contraintes liées au manque de temps et à l’isolement géographique. Les répondants ont systématiquement exprimé le désir d’obtenir un mentorat d’un collègue dans une pratique similaire et un mentorat individualisé, de façon pratique.Notre analyse suggère que le programme actuel de mentorat de l’École n’est peut-être pas applicable et nécessitera des modifications pour répondre aux besoins du personnel enseignant décentralisé.

Audio classification techniques often depend on the availability of a large labeled training dataset for successful performance. However, in many application domains of audio classification (e.g., wildlife monitoring), obtaining labeled data is still a costly and laborious process. Motivated by this observation, a technique is proposed to efficiently learn a clean template from a few labeled, but likely corrupted (by noise and interferences), data samples. This learning can be done efficiently via tensorial dynamic time warping on the articulation index-based time-frequency representations of audio data. The learned template can then be used in audio classification following the standard template-based approach. Experimental results show that the proposed approach outperforms both (1) the recurrent neural network approach and (2) the state-of-the-art in the template-based approach on a wildlife detection application with few training samples.

Previous studies in our laboratory have shown that muscarinic receptors become uncoupled from G-proteins in brains of patients with Alzheimer’s disease (AD). Interestingly, this process began prior...

Background Remote catheter navigation systems protect interventionalists from scattered ionizing radiation. However, these systems typically require specialized catheters and extensive operator training. Methods A new compact and sterilizable telerobotic system is described, which allows remote navigation of conventional tip-steerable catheters, with three degrees of freedom, using an interface that takes advantage of the interventionalist's existing dexterity skills. The performance of the system is evaluated ex vivo and in vivo for remote catheter navigation and ablation delivery. Results The system has absolute errors of 0.1 ± 0.1 mm and 7 ± 6° over 100 mm of axial motion and 360° of catheter rotation, respectively. In vivo experiments proved the safety of the proposed telerobotic system and demonstrated the feasibility of remote navigation and delivery of ablation. Conclusion The proposed telerobotic system allows the interventionalist to use conventional steerable catheters; while maintaining a safe distance from the radiation source, he/she can remotely navigate the catheter and deliver ablation lesions. Copyright © 2015 John Wiley & Sons, Ltd.

This paper presents an Immersive Telepresence system for Entertainment and Meetings (ITEM). The system aims to provide a radically new video communication experience by seamlessly merging participants into the same virtual space to allow a natural interaction among them and shared collaborative contents. With the goal to make a scalable, flexible system for various business solutions as well as easily accessible by massive consumers, we address the challenges in the whole pipeline of media processing, communication, and displaying in our design and realization of such a system. Particularly, in this paper we focus on the system aspects that maximize the end-user experience, optimize the system and network resources, and enable various teleimmersive application scenarios. In addition, we also present a few key technologies, i.e. fast object-based video coding for real world data and spatialized audio capture and 3D sound localization for group teleconferencing. Our effort is to investigate and optimize the key system components and provide an efficient end-to-end optimization and integration by considering user needs and preferences. Extensive experiments show the developed system runs reliably and comfortably in real time with a minimal setup requirement (e.g. a webcam and/or a depth camera, an optional microphone array, a laptop/desktop connected to the public Internet) for teleimmersive communication. With such a really minimal deployment requirement, we present a variety of interesting applications and user experiences created by ITEM.

Atrial fibrillation is a side effect of ibrutinib, an irreversible inhibitor of Bruton tyrosine kinase used for treatment of B-cell lymphoproliferative disorders. We determined if single (2 or 10 mg/kg), or chronic (14 days) oral ibrutinib followed by 24-hour washout conferred susceptibility to electrically induced arrhythmias in 1-month-old male C57BL/6 mice. A single higher dose of ibrutinib increased arrhythmia inducibility. There was no inducibility difference after chronic dosing with washout. This suggests that high serum drug levels might be responsible for the proarrhythmic effect of ibrutinib and that an altered dosing strategy might mitigate the side effects.

Beta-blockers are the standard of care for the treatment of long QT syndrome (LQTS), and have been shown to reduce recurrent syncope and mortality in patients with type 1 LQTS (LQT1). Although beta-blockers have minimal effect on the resting corrected QT interval, their effect on the dynamics of the non-corrected QT interval is unknown, and may provide insight into their protective effects.Twenty-three patients from eight families with genetically distinct mutations for LQT1 performed exercise stress testing before and after beta-blockade. One hundred and fifty-two QT, QTc, and Tpeak-Tend intervals were measured before starting beta-blockers and compared with those at matched identical cycle lengths following beta-blockade. Beta-blockers demonstrated heart-rate-dependent effects on the QT and QTc intervals. In the slowest heart rate tertile (90 b.p.m.), beta-blockade increased the QT and QTc intervals (QT: 405 vs. 409 ms; P = 0.06; QTc: 459 vs. 464 ms; P = 0.06). In the fastest heart rate tertile (100 b.p.m.), the use of beta-blocker was associated with a reduction in both the QT and QTc intervals (QT: 367 vs. 358 ms; P0.0001; QTc: 500 vs. 486 ms; P0.0001). The Tpeak-Tend interval showed minimal change at slower heart rates (90 b.p.m.) (93 vs. 87 ms; P = 0.09) and at faster heart rates (100 b.p.m.) (87 vs. 84 ms; P = NS) following beta-blockade.Beta-blockers have heart-rate-dependent effects on the QT and QTc intervals in LQTS. They appear to increase the QT and QTc intervals at slower heart rates and shorten them at faster heart rates during exercise.

In many species of chorusing frogs, callers can rapidly adjust their call timing with reference to neighboring callers so as to maintain call rate while minimizing acoustic interference. The rules governing the interactions, in particular, who is listening to whom are largely unknown, presumably influenced by distance between callers, caller density, and intensities of interfering calls. We report vocal interactions in a unison bout caller, the green tree frog (Hyla cinerea). Using a microphone array, we monitored bouts from a local group of six callers embedded in a larger chorus. Data were analyzed in a 21-min segment at the peak of the chorus. Callers within this group were localized and their voices were separated for analysis of spatio-temporal interactions. We show that callers in this group: (1) synchronize with one another, (2) prefer to time their calls antiphonally, almost exactly at one-third and two-thirds of the call intervals of their neighbors, (3) tolerate call collision when antiphonal calling is not possible, and (4) perform discrete phase-hopping between three preferred phases when tracking other callers. Further, call collision increases and phase-locking decreases, with increasing inter-caller spacing. We conclude that the precise phase-positioning, phase-tracking, and phase-hopping minimizes acoustic jamming while maintaining chorus synchrony.

Direction-of-arrival (DoA) estimation of incoming electromagnetic signals can play a critical role in surveillance, sensing, and cognitive radio applications. Typical DoA antenna arrays use an aperture measuring several wavelengths across to ensure reliable measurement of phase information. For a UHF application, such an array would need to be a few meters across-too large for a portable array. This work demonstrates a practical DoA array composed of antennas with diverse radiation patterns which is combined with an algorithm which relies primarily on amplitude information rather than phase information. This approach yields a much smaller array with similar direction-finding capabilities to larger ones. A calibration procedure captures the antenna responses, including the parasitic effects of the closely spaced antennas. The calibrated array and direction-finding algorithm then achieves measured accuracy with resolution of six degrees with no front-to-back or quadrant ambiguities.

Equipping everyday objects with sensing and computational capabilities creates the potential to achieve context and situational awareness through the detection of natural events. A major challenge in energy-constrained devices is that the detection of natural events generally demands sophisticated signal modeling and processing, along with continuous sensing. In this paper, we propose to use a cascade architecture to control signal-model complexity; this approach allows the device to sense continuously and trigger a more accurate signal model only when an event of interest is likely to be occurring. The sensitivity of the triggering affects detection performance and device energy consumption, so we formulate and solve the problem of optimal threshold allocation to control this sensitivity. We prove that for controlling signal-model complexity, triggering as often as possible maximizes detection performance; this seemingly intuitive result does not hold in other popular cascading techniques, most notably in low-power wakeup mechanisms. Our analysis leads to a simple threshold-tracking algorithm that can adjust to time-varying environmental conditions and energy supply. Combining a low-power MCU with controllable supply-voltage scaling, we present an acoustic wildlife monitoring system that exhibits 12× energy scalability from cascading detectors, and an additional 2× from synergistic hardware scaling on commercially available components. In practical scenarios, we demonstrate energy savings ranging from 3× to 20× with minimal loss in performance, compared to the conventional approach.

Detection systems in the emerging Internet of Things (IoT) paradigm, unlike existing stovepipe ones, are envisioned to be a platform for multiple applications. As a result, the design for IoT systems often places strong emphasis on modularity, where components can be composed to form various applications. This modular constraint creates new challenges in finding the optimal trade-off between resource consumption and performance of detection systems. This work focuses on the problem of optimizing modular detection systems whose modules are cascade. The solution results in a dynamic-programming-based algorithm that can optimize cascade detection systems with an arbitrary number of modules. Simulation results on both synthetic and real data confirm the superiority of an optimized system against unoptimized ones.

This paper presents an eigenvector clustering approach for estimating the direction of arrival (DOA) of multiple speech signals using a microphone array. Existing clustering approaches usually only use low frequencies to avoid spatial aliasing. In this study, we propose a probabilistic eigenvector clustering approach to use all frequencies. In our work, time-frequency (TF) bins dominated by only one source are first detected using a combination of noise-floor tracking, onset detection and coherence test. For each selected TF bin, the largest eigenvector of its spatial covariance matrix is extracted for clustering. A mixture density model is introduced to model the distribution of the eigenvectors, where each component distribution corresponds to one source and is parameterized by the source DOA. To use eigenvectors of all frequencies, the steering vectors of all frequencies of the sources are used in the distribution function. The DOAs of the sources can be estimated by maximizing the likelihood of the eigenvectors using an expectation-maximization (EM) algorithm. Simulation and experimental results show that the proposed approach significantly improves the root-mean-square error (RMSE) for DOA estimation of multiple speech sources compared to the MUSIC algorithm implemented on the single-source dominated TF bins and our previous clustering approach.

This paper presents a generalized multiple-point sparse constrained deconvolution approach for mapping acoustic noise sources in large regions using a movable array. Extended from our previous MPSC-DAMAS approach, we first derive a generalized inverse problem relating to the source powers and the array manifold using a generic beamformer and an explicit measurement noise model. We then propose a generalized MPSC-DAMAS (GMPSC-DAMAS) approach for resolving the inverse problem. A new parameter setting method based on a multiple-point minimum-variance-distortionless-response (MVDR) beamformer is also presented. The realizations of the GMPSC-DAMAS approach using the delay- and-sum (DAS) beamformer and the MVDR beamformer are evaluated. Simulation results show the proposed GMPSC-DAMAS approach achieves much lower absolute power estimation errors and processing time than the MPSC-DAMAS approach in terms of number of sources and robustness to measurement noise.

The rat vibrissal (whisker) system is one of the oldest and most important models for the study of active tactile sensing and sensorimotor integration. It is well established that primary sensory neurons in the trigeminal ganglion respond to deflections of one and only one whisker, and that these neurons are strongly tuned for both the speed and direction of individual whisker deflections. During active whisking behavior, however, multiple whiskers will be deflected simultaneously. Very little is known about how neurons at central levels of the trigeminal pathway integrate direction and speed information across multiple whiskers. In the present work, we investigated speed and direction coding in the trigeminal brainstem nuclei, the first stage of neural processing that exhibits multi-whisker receptive fields. Specifically, we recorded both single-unit spikes and local field potentials from fifteen sites in spinal trigeminal nucleus interpolaris and oralis while systematically varying the speed and direction of coherent whisker deflections delivered across the whisker array. For 12/15 neurons, spike rate was higher when the whisker array was stimulated from caudal to rostral rather than rostral to caudal. In addition, 10/15 neurons exhibited higher firing rates for slower stimulus speeds. Interestingly, using a simple decoding strategy for the local field potentials and spike trains, classification of speed and direction was higher for field potentials than for single unit spike trains, suggesting that the field potential is a robust reflection of population activity. Taken together, these results point to the idea that population responses in these brainstem regions in the awake animal will be strongest during behaviors that stimulate a population of whiskers with a directionally coherent motion.

Transcatheter aortic valve implantation is a minimally invasive alternative to open-heart surgery for aortic stenosis in which a stent-based bioprosthetic valve is delivered into the heart on a catheter. Limited visualization during this procedure can lead to severe complications. Improved visualization can be provided by live registration of transesophageal echo (TEE) and fluoroscopy images intraoperatively. Since the TEE probe is always visible in the fluoroscopy image, it is possible to track it using fiducial-based single-perspective pose estimation. In this study, inherent probe tracking performance was assessed, and TEE to fluoroscopy registration accuracy and robustness were evaluated. Results demonstrated probe tracking errors of below 0.6 mm and 0.2°, a 2-D RMS registration error of 1.5 mm, and a tracking failure rate of below 1%. In addition to providing live registration and better accuracy and robustness compared to existing TEE probe tracking methods, this system is designed to be suitable for clinical use. It is fully automatic, requires no additional operating room hardware, does not require intraoperative calibration, maintains existing procedure and imaging workflow without modification, and can be implemented in all cardiac centers at extremely low cost.

Tele-Operated Catheter Ablation, In Vivo. Introduction: The close proximity between the interventionalist and patient during catheter-based interventions for cardiac arrhythmia exposes the interventionalist to harmful radiation. A prototype remote catheter navigation system (RCNS) has been developed to reduce occupational dose. The safety, feasibility of this RCNS and a comparison of remote and conventional navigation techniques is investigated in vivo. Methods: Seven anatomical locations in the right side of the heart in porcine models were chosen as navigation targets. Using fluoroscopy and electrogram analysis, an experienced electrophysiology interventionalist manipulated a radiofrequency (RF) ablation catheter to each target using the RCNS and conventional navigation. Success rate, navigation time, exposure, exposure time and procedure time was recorded for all anatomical targets. Time to integrate the RCNS with the procedure suite was also measured. Results: All targets were successfully reached with the RCNS and conventional navigation. No erratic catheter motion was observed with the RCNS whereas 1 operation failure occurred. The anatomical targets were found to have the largest effect on navigation time (P < 0.05), exposure (P < 0.05), and exposure time (P < 0.01), although the navigation method had little to no effect on the metrics. These results suggest that remote navigation procedures can be performed with navigation times comparable to conventional bedside navigation. Conclusion: Remote navigation with the RCNS may present a safe method of reducing occupational dose, while providing comparable navigation time with conventional bedside navigation. (J Cardiovasc Electrophysiol, Vol. 23, pp. 81-87, January 2012)

Spinal Cord Stimulation Modulates Vagal Atrial Influences. Introduction: Experimental evidence suggests that spinal cord stimulation (SCS) can cause augmentation of parasympathetic influences on the heart via enhanced vagus nerve (VgN) activity. Herein, we investigated whether this might lead to enhanced inducibility of vagally mediated atrial tachyarrhythmias (AT) and whether such actions depend on intact autonomic neural connections with central neurons. Method and Results: Epidural SCS electrodes were implanted at T1-T4 in anesthetized canines. Sinus cycle length prolongation, atrial repolarization changes (191 epicardial electrode sites), and AT inducibility in response to right VgN stimuli applied at the cervical level were determined before and during SCS. VgN-induced sinus cycle length prolongation was potentiated during SCS among the animals with intact neural connections or bilateral vagotomy proximal to the stimulation site, whereas such prolongation was unaffected by SCS among animals with bilateral decentralization of stellate ganglia. Likewise, the atrial surface area in which VgN-induced repolarization wave form changes were identified was significantly augmented during SCS among the former but not among the latter. AT facilitation occurred during SCS in the majority of animals with intact neural connections, particularly among those displaying relatively greater potentiation of vagally mediated sinus cycle length prolongation. Conclusion: The data indicate that SCS may cause potentiation of parasympathetic influences on the atria in response to cervical VgN stimulation. Such SCS effects appear to be mediated via decreased tonic inhibitory sympathetic influences in the presence of intact stellate ganglion connections to central neurons. (J Cardiovasc Electrophysiol, Vol. 22, pp. 440-447)

In this paper, the stochastic networked computation (SNC) paradigm for designing robust and energy-efficient systems-on-a-chip in nanoscale process technologies, where robust computation is treated as a statistical estimation problem is presented. The benefits of SNC are demonstrated by employing it to design an energy-efficient and robust pseudonoise-code acquisition system for the wireless CDMA2000 standard (http://www.3gpp2.org). Simulations in IBM's 130-nm CMOS process show that the SNC-based architecture enhances the average probability of detection (PDet) in the presence of process variations by two to three orders of magnitude, reduces power by 31%-39%, and reduces the variation in PDet by one to two orders of magnitude at a typical false-alarm rate of 5% over a conventional architecture. SNC performance in the presence of voltage overscaling and across technology nodes (90, 65, 45, and 32 nm) is also studied.

This paper discusses the use of ground-penetrating radar (GPR) to assess railroad track substructure conditions. An ultra-wide band (UWB) GPR system, having a centre frequency at or higher than 2 GHz, can be used to detect the scattering pattern and to predict air void volume in railroad ballast. A time–frequency technique was implemented to characterise the signal in time and frequency domains simultaneously. Because electromagnetic energy attenuation is highly frequency dependent, the frequency sub-bands of the reflected UWB GPR signal can be analysed separately to quantify the fouling material and quantify moisture content. Additionally, to validate the GPR system capability, a ground truth field survey was conducted. Using ballast samples collected from the field for validation, this paper shows that a time–frequency analysis may provide a new method to measure the thickness of clean ballast, detect the trapped water and assess the ballast fouling and moisture content along the track.

Traditional integrated circuit design achieves error-free operation by designing with margins (clock frequency and supply voltage) and/or including hardware replication and recomputation, which may counter the full energy and area benefits of aggressive technology scaling. It is thus desirable that modern systems-on-chip (SoCs) permit hardware errors while maintaining robust system-level performance. Treating hardware errors as computational noise and extending traditional estimation theory to include practical SoC design constraints yields a novel and general design optimization framework. This work demonstrates the breadth of applicability of the estimation-theoretic framework for system design by showcasing two different application classes that demonstrate 36% to 50% power reduction.

Atrial fibrillation (AF) is the most common arrhythmia seen in general practice. Muscarinic ACh receptors (M2R, M3R) are involved in vagally induced AF. M2R and M3R activate the heterotrimeric G proteins, Gi and Gq, respectively, by promoting GTP binding, and these in turn activate distinct K+ channels. Signaling is terminated by GTP hydrolysis, a process accelerated by regulator of G protein signaling (RGS) proteins. RGS2 is selective for Gq and thus may regulate atrial M3R signaling. We hypothesized that knockout of RGS2 (RGS2−/−) would render the atria more susceptible to electrically induced AF. One-month-old male RGS2−/− and C57BL/6 wild-type (WT) mice were instrumented for intracardiac electrophysiology. Atrial effective refractory periods (AERPs) were also determined in the absence and presence of carbachol, atropine, and/or the selective M3R antagonist darifenacin. Susceptibility to electrically induced AF used burst pacing and programmed electrical stimulation with one extrastimulus. Real-time RT-PCR measured atrial and ventricular content of RGS2, RGS4, M2R, M3R, and M4R mRNA. AERP was lower in RGS2−/− compared with WT mice in both the high right atrium (HRA) (30 ± 1 vs. 34 ± 1 ms, P < 0.05) and mid right atrium (MRA) (21 ± 1 vs. 24 ± 1 ms, P < 0.05). Darifenacin eliminated this difference (HRA: 37 ± 2 vs. 39 ± 2 ms, and MRA: 30 ± 2 vs. 30 ± 1, P > 0.4). RGS2−/− were more susceptible than WT mice to atrial tachycardia/fibrillation (AT/F) induction (11/22 vs. 1/25, respectively, P < 0.05). Muscarinic receptor expression did not differ between strains, whereas M2R expression was 70-fold higher than M3R ( P < 0.01). These results suggest that RGS2 is an important cholinergic regulator in the atrium and that RGS2−/− mice have enhanced susceptibility to AT/F via enhanced M3 muscarinic receptor activity.

Background— Neuronal nitric oxide synthase (nNOS) is expressed in cardiomyocytes and plays a role in regulating cardiac function and Ca 2+ homeostasis. However, the role of nNOS in cardiac electrophysiology after myocardial infarction (MI) is unclear. We hypothesized that nNOS deficiency increases ventricular arrhythmia and mortality after MI. Methods and Results— MI was induced in wild-type (WT) or nNOS −/− mice by ligation of the left coronary artery. Thirty-day mortality was significantly higher in nNOS −/− compared with WT mice. Additionally, nNOS −/− mice had impaired cardiac function 2 days after MI. Telemetric ECG monitoring showed that compared with WT, nNOS −/− mice had significantly more ventricular arrhythmias and were more likely to develop ventricular fibrillation after MI. Treatment with the L-type Ca 2+ channel blocker verapamil reduced the incidence of arrhythmia and ventricular fibrillation in nNOS −/− mice after MI. To assess the role of nNOS in Ca 2+ handling, patch-clamp and Ca 2+ fluorescence techniques were used. Ca 2+ transients and L-type Ca 2+ currents were higher in nNOS −/− compared with WT cardiomyocytes. Additionally, nNOS −/− cardiomyocytes exhibited significantly higher systolic and diastolic Ca 2+ over a range of pacing frequencies. Treatment with the NO donor S -nitroso N -acetyl-penicillamine decreased Ca 2+ transients and L-type Ca 2+ current in both nNOS −/− and WT cardiomyocytes. Furthermore, S -nitrosylation of Ca 2+ handling proteins was significantly decreased in nNOS −/− myocardium after MI. Conclusions— Deficiency in nNOS increases ventricular arrhythmia and mortality after MI in mice. The antiarrhythmic effect of nNOS involves inhibition of L-type Ca 2+ channel activity and regulation of Ca 2+ handling proteins via S -nitrosylation.

Objective To test an alternative to catheter and open-heart techniques, by documenting the feasibility of implanting an unmodified mechanical aortic valve (AoV) in the off pump, beating heart using the universal cardiac introducer (UCI) attached to the left ventricular (LV) apex. Methods In six pigs, the LV apex was exposed by a median sternotomy. The UCI was attached to the apex. A 12-mm punching tool (punch), introduced through the UCI, was used to create a cylindrical opening through the apex. Then, the AoV, secured to a holder, was introduced into the LV, using transesophageal echocardiographic, guided through the apical LV opening, navigated into the LV outflow tract, and positioned within the aortic annulus. Trans-esophageal echocardiographic guidance was useful for navigation and positioning by superimposing the aortic annulus and prosthetic ring while Doppler imaging verified preserved prosthetic function and absence of perivalvular leaks. The valve function and hemodynamics were observed before termination for macroscopic evaluation. Results The punch produced a clean opening without fragmentation or myocardial embolization. During advancement of the mechanical AoV, there were no arrhythmias, mitral valve dysfunctions, evidence of myocardial ischemia, or hemodynamic instability. The AoVs were well seated over the annulus, without obstructing the coronaries or contact with the conduction system. The ring of AoVs was well circumscribed by the aortic annulus. Conclusions This study documented the feasibility of positioning a mechanical AoV on the closed, beating heart. These results should encourage the development of adjunct technologies to deliver current tissue or mechanical AoV with minimal side effects.

Erythropoietin (EPO) is a potent cardioprotective agent in models of myocardial ischemia and reperfusion (I/R). It has been suggested recently that EPO may also reduce ventricular arrhythmia after I/R. The present study investigated the role of neuronal nitric oxide synthase (nNOS) on the antiarrhythmic effects of EPO. EPO treatment increased nNOS expression in isolated neonatal mouse ventricular myocytes. Cotreatment with the phosphatidylinositol 3 (PI3)-kinase inhibitor, LY294002 [2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride], or treatment of cardiomyocytes infected with a dominant negative adenovirus targeted to Akt1 (ADV-dnAkt1) blocked the effects of EPO on nNOS expression, suggesting that EPO regulates nNOS expression via PI3-kinase and Akt. To examine the in vivo antiarrhythmic effects of EPO, wild-type (WT) and nNOS(-/-) mice were anesthetized and, after a baseline measurement, subjected to myocardial I/R to provoke ventricular arrhythmias. Pretreatment with EPO 24 h before ischemia increased nNOS expression and significantly reduced the number of premature ventricular contractions (PVCs) and the incidence of ventricular tachycardia (VT) in WT mice. In contrast, treatment with EPO had no effect on PVCs or the incidence of VT in nNOS(-/-) mice. Furthermore, EPO treatment after ischemia significantly reduced the threshold dose of cesium chloride (CsCl) to induce VT. We conclude that EPO via nNOS protects the heart from spontaneous and CsCl-induced ventricular arrhythmia during myocardial I/R.

Our project is the reintroduction of off-pump intracardiac surgery using the Universal Cardiac Introducer (UCI) for safe intracardiac access. The purpose of this study was to evaluate multimodality visualization using three ultrasound modalities and ultrasound augmented with virtual reality. Image guidance was tested on implanting a mitral valve prosthesis via the UCI in 12 pigs. Initially, two-dimensional (2-D) transesophageal echocardiography (TEE) ultrasound, intravascular ultrasound (intracardiac echocardiography [ICE]), and three-dimensional (3-D) epicardial ultrasound were utilized. Ultrasound augmented with virtual reality was used in the last three experiments. A 2-D TEE assisted navigating the prosthesis into the orifice. Positioning was not intuitive and required trial and error method. A 3-D epicardial ultrasound allowed positioning of the valve into the orifice. Positioning of the clip was difficult because of artifacts with multiple reflections and shadowing. Augmented reality displayed the entire prosthesis and the tools without artifacts; provided intuitive information on navigation, positioning, and orientation of tools; and improved significantly image guidance and surgical skill. Augmented virtual reality, with tracked 2-D or 3-D ultrasound imaging, provides guidance that can effectively substitute for direct vision during beating heart intracardiac surgery.

Connexin 43, the major connexin isoform in gap junctions of cardiac ventricular myocytes, undergoes changes in distribution and expression in cardiac diseases. The Na(+)-H(+) exchanger (NHE-1), a key mediator of hypertrophy and heart failure, has been shown to be localized in the cardiomyocyte gap junctional regions; however, whether NHE-1 regulates gap junction proteins in the hypertrophied cardiomyocyte is not known. To address this question, neonatal rat ventricular myocytes were treated with phenylephrine (PE) for 24 h to induce hypertrophy. Increased Cx43 expression observed with PE treatment (132.4 +/- 6.3% compared to control; P < 0.05) was further significantly augmented by the specific NHE-1 inhibitor EMD87580 [N-[2-methyl-4,5-bis(methylsulfonyl)-benzoyl]-guanidine hydrochloride] (173.2 +/- 8.7% increase compared to control; P < 0.05 versus PE), an effect that was mimicked by another NHE-1 inhibitor cariporide [4-isopropyl-3-(methylsulfonyl)benzoyl-guanidine methanesulfonate]. PE-induced hypertrophy was associated with mitogen-activated protein kinase c-Jun NH(2)-terminal kinase (JNK) 1/2 activation, whereas inhibition of JNK1/2 with either SP600125 [anthra(1,9-cd)pyrazol-6(2H)-one 1,9-pyrazoloanthrone] or small interfering RNA significantly increased PE-induced up-regulation of Cx43 protein levels. Inhibition of reverse mode Na(+)-Ca(2+) exchange (NCX) with KB-R7943 [2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea mesylate] partially reversed JNK1/2 activation (195.2 +/- 21.4 versus 143.7 +/- 14.4% with KB-R7943; P < 0.05) and augmented up-regulation of Cx43 protein (121.1 +/- 8.3 versus 215.9 +/- 25.6% with KB-R7943; P < 0.05) in the presence of PE. Our results demonstrate that NHE-1 negatively regulates Cx43 protein expression in PE-induced cardiomyocyte hypertrophy via a JNK1/2-dependent pathway, which is probably activated by reverse mode NCX activity.

In the censoring approach to decentralized detection, sensors transmit real-valued functions of their observations when "informative" and save energy by not transmitting otherwise. We address several practical issues in the design of censoring sensor networks including the joint dependence of sensor decision rules, randomization of decision strategies, and partially known distributions. In canonical decentralized detection problems involving quantization of sensor observations, joint optimization of the sensor quantizers is necessary. We show that under a send/no-send constraint on each sensor and when the fusion center has its own observations, the sensor decision rules can be determined independently. In terms of design, and particularly for adaptive systems, the independence of sensor decision rules implies that minimal communication is required. We address the uncertainty in the distribution of the observations typically encountered in practice by determining the optimal sensor decision rules and fusion rule for three formulations: a robust formulation, generalized likelihood ratio tests, and a locally optimum formulation. Examples are provided to illustrate the independence of sensor decision rules, and to evaluate the partially known formulations.