The need for novel, efficacious, antiseizure therapies is widely acknowledged. This study investigates in humans the feasibility, safety, and efficacy of high-frequency electrical stimulation (HFES; 100-500 Hz) triggered by automated seizure detections. Eight patients were enrolled in this study, which consisted of a control and an experimental phase. HFES was delivered directly to the epileptogenic zone (local closed-loop) in four patients and indirectly, through anterior thalami (remote closed-loop), to the other four patients for every other automated seizure detection made by a validated algorithm. Interphase (control vs experimental phase) and intraphase (stimulated vs nonstimulated) comparisons of clinical seizure rate and relative severity (clinical and electrographic) were performed, and differences were assessed using effect size. Patients were deemed "responders" if seizure rate was reduced by at least 50%; the remaining patients were deemed "nonresponders." All patients completed the study; rescue medications were not required. There were 1,491 HFESs (0.2% triggered after-discharges). Mean change in seizure rate in the local closed-loop group was -55.5% (-100 to +36.8%); three of four responders had a mean change of -86% (-100 to -58.8%). In the remote closed-loop, the mean change of seizure rate was -40.8% (-72.9 to +1.4%); two of four responders had a mean change of -74.3% (-75.6 to -72.9%). Mean effect size was zero in the local closed-loop (responders: beneficial and medium to large in magnitude) and negligible in the remote closed-loop group (responders: beneficial and medium to large). HFES effects on epileptogenic tissue were immediate and also outlasted the stimulation period. This study demonstrates the feasibility and short-term safety of automated HFES for seizure blockage, and also raises the possibility that it may be beneficial in pharmaco-resistant epilepsies.

We used the finite element method to study the effect of radio-frequency (RF) catheter ablation on tissue heating and lesion formation at different intracardiac sites exposed to different regional blood velocities. We examined the effect of application of RF current in temperature- and power-controlled mode above and beneath the mitral valve annulus where the regional blood velocities are high and low respectively. We found that for temperature-controlled ablation, more power was delivered to maintain the preset tip temperature at sites of high local blood velocity than at sites of low local blood velocity. This induced more tissue heating and larger lesion volumes than ablations at low velocity regions. In contrast, for power-controlled ablation, tissue heating was less at sites of high compared with low local blood velocity for the same RF power setting. This resulted in smaller lesion volumes at sites of low local velocity. Our numerical analyzes showed that during temperature-controlled ablation at 60 degrees C, the lesion volumes at sites above and underneath the mitral valve were comparable when the duration of RF current application was 10 s. When the duration of RF application was extended to 60 s and 120 s, lesion volumes were 33.3% and 49.4% larger above the mitral valve than underneath the mitral valve. Also, with temperature-controlled ablation, tip temperature settings of 70 degrees C or greater were associated with a risk of tissue overheating during long ablations at high local blood velocity sites. In power-controlled ablation (20 W), the lesion volume formed underneath the mitral valve was 165.7% larger than the lesion volume above the mitral valve after 10 s of ablation. We summarized the guidelines for energy application at low and high flow regions.

Automated seizure blockage is a top research priority of the American Epilepsy Society. This delivery modality (referred to herein as contingent or closed loop) requires for implementation a seizure detection algorithm for control of delivery of therapy via a suitable device. The authors address the many potential advantages of this modality over conventional alternatives (periodic or continuous), and the challenges it poses in the design and analysis of trials to assess efficacy and safety-in the particular context of direct delivery of electrical stimulation to brain tissue. The experimental designs of closed-loop therapies are currently limited by ethical, technical, medical, and practical considerations. One type of design that has been used successfully in an in-hospital "closed-loop" trial using subjects undergoing epilepsy surgery evaluation as their own controls is discussed in detail. This design performs a two-way comparison of seizure intensity, duration, and extent of spread between the control (surgery evaluation) versus the experimental phase, and, within the experimental phase, between treated versus untreated seizures. The proposed statistical analysis is based on a linear model that accounts for possible circadian effects, changes in treatment protocols, and other important factors such as change in seizure probability. The analysis is illustrated using seizure intensity as one of several possible end points from one of the subjects who participated in this trial. In-hospital ultra-short-term trials to assess safety and efficacy of closed-loop delivery of electrical stimulation for seizure blockage are both feasible and valuable.

Values of the spectral dependence of the optical absorption and reduced scattering coefficients, and thermal conductivity and diffusivity of cartilage were measured. The invasive and noninvasive diffusivity measurements were consistent and concluded that the infrared imaging radiometric technique has an advantage to determine thermal properties, because damage to the cartilage sample may be avoided. The measured values of absorption and reduced scattering coefficients can be used for predicting the optical fluence distribution in cartilage and determining optical source wavelengths for the laser-assisted cartilage reshaping studies. The thermal conductivity and diffusivity values can play role in understanding thermal-dependent phenomenon in cartilage during laser irradiation and determining laser dosimetry for the laser-assisted cartilage reshaping studies.

Input from continuous glucose monitors (CGMs) is a critical component of artificial pancreas (AP) systems, but CGM performance issues continue to limit progress in AP research. While G4 PLATINUM has been integrated into AP systems around the world and used in many successful AP controller feasibility studies, this system was designed to address the needs of ambulatory CGM users as an adjunctive use system. Dexcom and the University of Padova have developed an advanced CGM, called G4AP, to specifically address the heightened performance requirements for future AP studies. The G4AP employs the same sensor and transmitter as the G4 PLATINUM but contains updated denoising and calibration algorithms for improved accuracy and reliability. These algorithms were applied to raw data from an existing G4 PLATINUM clinical study using a simulated prospective procedure. The results show that mean absolute relative difference (MARD) compared with venous plasma glucose was improved from 13.2% with the G4 PLATINUM to 11.7% with the G4AP. Accuracy improvements were seen over all days of sensor wear and across the plasma glucose range (40-400 mg/dl). The greatest improvements occurred in the low glucose range (40-80 mg/dl), in euglycemia (80-120 mg/dl), and on the first day of sensor use. The percentage of sensors with a MARD <15% increased from 69% to 80%. Metrics proposed by the AP research community for addressing specific AP requirements were also computed. The G4AP consistently exhibited improved sensor performance compared with the G4 PLATINUM. These improvements are expected to enable further advances in AP research.