Biophysics and electrophysiology of pulsed field ablation in normal and infarcted porcine cardiac ventricular tissue.

Pulsed Field Ablation (PFA) is a new ablation method being rapidly adopted for treatment of atrial fibrillation, which shows advantages in safety and efficiency over radiofrequency and cryo-ablation. In this study, we used an in vivo swine model (10 healthy and 5 with chronic myocardial infarct) for ventricular PFA, collecting intracardiac electrograms, electro-anatomical maps, native T1-weighted and late gadolinium enhancement MRI, gross pathology, and histology. We used 1000-1500 V pulses, with 1-16 pulse trains to vary PFA dose.

Arrhythmogenicity of monophasic and biphasic PFA waveforms in a porcine model.

Objective: The potential risk of inducing ventricular arrhythmias was explored by employing pulsed field ablation (PFA) through the administration of both monophasic and biphasic waveform deliveries.

Methods: PFA was applied to specific locations in the right ventricle (RV, n = 5 sites) in swine (n = 2), utilizing identical settings with consistent amplitude, pulse width, and a number of pulses for both monophasic and biphasic waveforms. PFA deliveries were precisely timed in 10-ms intervals across the entire T wave.

Squeezing the quantum noise of a gravitational-wave detector below the standard quantum limit.

The Heisenberg uncertainty principle dictates that the position and momentum of an object cannot be simultaneously measured with arbitrary precision, giving rise to an apparent limitation known as the standard quantum limit (SQL). Gravitational-wave detectors use photons to continuously measure the positions of freely falling mirrors and so are affected by the SQL. We investigated the performance of the Laser Interferometer Gravitational-Wave Observatory (LIGO) after the experimental realization of frequency-dependent squeezing designed to surpass the SQL.

The importance of electrode-tissue proximity in creating pulsed field ablation lesions: insights from a sub-acute preclinical model.

Background: We sought to evaluate the anatomic and functional lesion development over time at different atrial sites immediately following delivery of pulsed field ablation (PFA).

Methods: Using a porcine model, PFA ablations were performed in the superior vena cava (SVC), right atrial lateral wall (RA), left atrial appendage (LAA), and right superior pulmonary vein (RSPV) using four different PFA profiles. Mapping was done sequentially in 5-20-min increments up to 280-min post lesion delivery for low voltage area (LVA) assessment and conduction velocity.

The Effects of Interphase and Interpulse Delays and Pulse Widths on Induced Muscle Contractions, Pain and Therapeutic Efficacy in Electroporation-Based Therapies.

Electroporation is used in medicine for drug and gene delivery, and as a nonthermal ablation method in tumor treatment and cardiac ablation. Electroporation involves delivering high-voltage electric pulses to target tissue; however, this can cause effects beyond the intended target tissue like nerve stimulation, muscle contractions and pain, requiring use of sedatives or anesthetics. It was previously shown that adjusting pulse parameters may mitigate some of these effects, but not how these adjustments would affect electroporation's efficacy.

Determination of lethal electric field threshold for pulsed field ablation in perfused porcine and human hearts.

Introduction: Pulsed field ablation is an emerging modality for catheter-based cardiac ablation. The main mechanism of action is irreversible electroporation (IRE), a threshold-based phenomenon in which cells die after exposure to intense pulsed electric fields. Lethal electric field threshold for IRE is a tissue property that determines treatment feasibility and enables the development of new devices and therapeutic applications, but it is greatly dependent on the number of pulses and their duration.

Characterization of Experimentally Observed Complex Interplay between Pulse Duration, Electrical Field Strength, and Cell Orientation on Electroporation Outcome Using a Time-Dependent Nonlinear Numerical Model.

Electroporation is a biophysical phenomenon involving an increase in cell membrane permeability to molecules after a high-pulsed electric field is applied to the tissue. Currently, electroporation is being developed for non-thermal ablation of cardiac tissue to treat arrhythmias. Cardiomyocytes have been shown to be more affected by electroporation when oriented with their long axis parallel to the applied electric field.

A Multiscale Computational Model of Skeletal Muscle Electroporation Validated Using In Situ Porcine Experiments.

Objective: The goal of our study was to determine the importance of electric field orientation in an anisotropic muscle tissue for the extent of irreversible electroporation damage by means of an experimentally validated mathematical model.

Methods: Electrical pulses were delivered to porcine skeletal muscle in vivo by inserting needle electrodes so that the electric field was applied in direction either parallel or perpendicular to the direction of the muscle fibres. Triphenyl tetrazolium chloride staining was used to determine the shape of the lesions.

Effect of contact force on pulsed field ablation lesions in porcine cardiac tissue.

Introduction: Contact force has been used to titrate lesion formation for radiofrequency ablation. Pulsed field ablation (PFA) is a field-based ablation technology for which limited evidence on the impact of contact force on lesion size is available.

Methods: Porcine hearts (n = 6) were perfused using a modified Langendorff set-up.

Reversible and Irreversible Effects of Electroporation on Contractility and Calcium Homeostasis in Isolated Cardiac Ventricular Myocytes.

Background: Irreversible electroporation is an energy form utilizing high-voltage pulsed electric field, leading to cellular homeostasis disruption and cell death. Recently, irreversible electroporation has shown promising results for the treatment of cardiac arrhythmias. However, reversible and irreversible effects of pulsed electric field on cardiac myocytes remain poorly understood.

Effects of Electrode-Tissue Proximity on Cardiac Lesion Formation Using Pulsed Field Ablation.

Background: Pulsed field ablation (PFA) is a novel energy modality for treatment of cardiac arrhythmias. The impact of electrode-tissue proximity on lesion formation by PFA has not been conclusively assessed. The objective of this investigation was to evaluate the effects of electrode-tissue proximity on cardiac lesion formation with a biphasic, bipolar PFA system.

Characterization of Phrenic Nerve Response to Pulsed Field Ablation.

Background: Phrenic nerve palsy is a well-known complication of cardiac ablation, resulting from the application of direct thermal energy. Emerging pulsed field ablation (PFA) may reduce the risk of phrenic nerve injury but has not been well characterized.

Methods: Accelerometers and continuous pacing were used during PFA deliveries in a porcine model.

Point Absorber Limits to Future Gravitational-Wave Detectors.

High-quality optical resonant cavities require low optical loss, typically on the scale of parts per million. However, unintended micron-scale contaminants on the resonator mirrors that absorb the light circulating in the cavity can deform the surface thermoelastically and thus increase losses by scattering light out of the resonant mode. The point absorber effect is a limiting factor in some high-power cavity experiments, for example, the Advanced LIGO gravitational-wave detector.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection.

Approaching the motional ground state of a 10-kg object.

The motion of a mechanical object, even a human-sized object, should be governed by the rules of quantum mechanics. Coaxing them into a quantum state is, however, difficult because the thermal environment masks any quantum signature of the object's motion. The thermal environment also masks the effects of proposed modifications of quantum mechanics at large mass scales.

Point absorbers in Advanced LIGO.

Small, highly absorbing points are randomly present on the surfaces of the main interferometer optics in Advanced LIGO. The resulting nanometer scale thermo-elastic deformations and substrate lenses from these micron-scale absorbers significantly reduce the sensitivity of the interferometer directly though a reduction in the power-recycling gain and indirect interactions with the feedback control system. We review the expected surface deformation from point absorbers and provide a pedagogical description of the impact on power buildup in second generation gravitational wave detectors (dual-recycled Fabry-Perot Michelson interferometers).

Group decisions based on confidence weighted majority voting.

Background: It has repeatedly been reported that, when making decisions under uncertainty, groups outperform individuals. Real groups are often replaced by simulated groups: Instead of performing an actual group discussion, individual responses are aggregated by a numerical computation. While studies have typically used unweighted majority voting (MV) for this aggregation, the theoretically optimal method is confidence weighted majority voting (CWMV)-if independent and accurate confidence ratings from the individual group members are available.

Particle-based Ising model.

We characterize equilibrium properties and relaxation dynamics of a two-dimensional lattice containing, at each site, two particles connected by a double-well potential (dumbbell). Dumbbells are oriented in the orthogonal direction with respect to the lattice plane and interact with each other through a Lennard-Jones potential truncated at the nearest neighbor distance. We show that the system's equilibrium properties are accurately described by a two-dimensional Ising model with an appropriate coupling constant.

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA.

We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is binary neutron star, neutron star-black hole, and binary black hole systems.

Microcanonical coarse-graining of the kinetic Ising model.

We propose a scheme for coarse-graining the dynamics of the 2-D kinetic Ising model onto the microcanonical ensemble. At subcritical temperatures, 2-D and higher-dimensional Ising lattices possess two basins of attraction separated by a free energy barrier. Projecting onto the microcanonical ensemble has the advantage that the dependence of the crossing rate constant on environmental conditions can be obtained from a single Monte Carlo trajectory.

Quantum-Enhanced Advanced LIGO Detectors in the Era of Gravitational-Wave Astronomy.

The Laser Interferometer Gravitational Wave Observatory (LIGO) has been directly detecting gravitational waves from compact binary mergers since 2015. We report on the first use of squeezed vacuum states in the direct measurement of gravitational waves with the Advanced LIGO H1 and L1 detectors. This achievement is the culmination of decades of research to implement squeezed states in gravitational-wave detectors.