Piezoelectric Transformer-Based High-Voltage Pulse Generator Using Wide-Bandgap Semiconductors for Medical Electroporation Therapy.

In this paper, a new application of Piezoelectric Transformer (PT)-based power converters to generate high-voltage (HV) bipolar pulses for medical electroporation therapy is proposed. In particular, PT-based power conversion is investigated as an alternative to magnetics-based approaches of generating HV from a relatively low-voltage (LV) input source for application in electroporation therapy. The detailed PT-based system design and selection of wide bandgap semiconductor switches such as GaN FETs, high-voltage SiC diodes and SiC MOSFETs, as well as simulation results to demonstrate proof-of-concept using LTSpice are presented. Preliminary experimental results of the PT-based capacitor charger are shown, and work is ongoing to develop a complete hardware prototype of the proposed HV pulse generator.

Comparative Double Auction Approach for Peer-to-Peer Energy Trading on Multiple microgrids.

Peer-to-peer (P2P) energy trading is one of the most effective methods to increase the usage of Renewable Energy (RE) resources in the distribution network and reduce losses by eliminating long transmission and distribution lines. This research aims to enhance the efficiency of P2P energy trading by examining the suitability of four distinct double auction mechanisms: Average, McAfee, Trade Reduction and Vickrey-Clarke-Groves (VCG). We conducted a systematic evaluation of these mechanisms across various microgrid (MG) types. The study algorithm integrates user preferences, bidding strategies and time-of-use tariffs, allowing participants to indicate their willingness to pay for different energy qualities and specific time periods. Notably, both the Average and VCG mechanisms emerged as the most effective across a majority of MG setups. Specifically, the average mechanism was found to be optimal for a consumer-centric MG, while the VCG mechanism was predominantly advantageous during non-peak hours trading. However, it was observed that P2P energy trading from MG to MG was inefficient due to the lesser number of peers. In conclusion, this work offers a comprehensive solution that adeptly identifies and recommends the most fitting auction mechanisms for diverse MG configurations and usage timings, paving the way for more efficient P2P energy trading.

SDI-118, a novel procognitive SV2A modulator: First-in-human randomized controlled trial including PET/fMRI assessment of target engagement.

Background: Current treatments for progressive neurodegenerative disorders characterized by cognitive impairment either have limited efficacy or are lacking altogether. SDI-118 is a small molecule which modulates the activity of synaptic vesicle glycoprotein 2A (SV2A) in the brain and shows cognitive enhancing effects in a range of animal models of cognitive deficit. Methods: This first-in-human study evaluated safety, tolerability, and pharmacokinetics/pharmacodynamics of SDI-118 in single ascending oral doses up to 80 mg administered to 32 healthy male subjects. Brain target occupancy was measured in eight subjects using positron emission tomography with PET-ligand [11C]-UCB-J. Food effect was assessed in seven subjects. Mood state was regularly evaluated using standardized questionnaires, and resting state fMRI data were analyzed as exploratory objectives. Key Results: At all doses tested, SDI-118 was well tolerated and appeared safe. Adverse events were mainly dizziness, hypersomnia, and somnolence. All were mild in intensity and increased in frequency with increasing administered dose. No dose-limiting adverse reactions were observed at any dose. SDI-118 displayed a linear pharmacokinetic profile with no significant food effect. Brain penetration and target engagement were demonstrated by a dose-proportional SV2A occupancy. Conclusion: Single oral doses of SDI-118 up to 80 mg were very well tolerated in healthy male subjects. Dose-proportional SV2A occupancy in the brain was demonstrated with brain imaging. Adverse effects in humans mainly occurred in higher dose ranges, with high occupancy levels, and were all mild and self-limiting. These data support further clinical exploration of the compound in patients with cognitive disorders. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT05486195.

OpenTCC: An open source low-cost temperature-control chamber.

Microbial electrochemical technologies (MET) are emerging systems for environmental applications such as renewable energy production or pollution remediation. MET research often requires stable temperatures and low levels of electromagnetic interference. Due to the presence of electrical wires and sensors, heating MET using water jacket recirculation can raise safety issues, whereas heating coils may affect the results of electrochemical analyses. The proposed open-source temperature-control chamber (OpenTCC) aims to provide a low-cost solution for controlling temperature (in the range 20-55 °C) while simultaneously reducing the electromagnetic interferences caused by switching mode power supplies. OpenTCC consists of a light and cheap structure, incorporating eight heating pads and two Peltier-cooling modules powered by open-source electronic circuits. Its hardware is controlled by an Arduino microcontroller and a Python interface which provides data-logging and serve as a basis for programable temperature cycles. The system has a modular design to allow stacking several independent modules. OpenTCC provides a reliable and tunable temperature control at lower costs than currently available commercial temperature controllers and provides a platform for field-specific upgrades. Though optimized for MET, Open-TCC can be adapted to other laboratory applications due to its flexible design.

Microbial electrochemical technologies: Electronic circuitry and characterization tools.

Microbial electrochemistry merges microbiology, electrochemistry and electronics to provide a set of technologies for environmental engineering applications. Understanding the electronic concepts is crucial for effectively adopting these systems, but the importance of electronic circuitry is often overlooked by microbial electrochemistry researchers. This review provides the background on the electronics and electrochemical concepts involved in the study of microorganisms interacting with electricity, and their applications in microbial electrochemical technology (MET). The potentiostat circuitry is described along with its working principles. Electrochemical analyses are presented together with the rational and parameters employed to study MET devices and electroactive microorganisms. Finally, future directions are delineated towards the adoption of MET, and the related electronics, in environmental engineering applications.

Head-to-nerve analysis of electromechanical impairments of diffuse axonal injury.

The aim was to investigate mechanical and functional failure of diffuse axonal injury (DAI) in nerve bundles following frontal head impacts, by finite element simulations. Anatomical changes following traumatic brain injury are simulated at the macroscale by using a 3D head model. Frontal head impacts at speeds of 2.5-7.5 m/s induce mild-to-moderate DAI in the white matter of the brain. Investigation of the changes in induced electromechanical responses at the cellular level is carried out in two scaled nerve bundle models, one with myelinated nerve fibres, the other with unmyelinated nerve fibres. DAI occurrence is simulated by using a real-time fully coupled electromechanical framework, which combines a modulated threshold for spiking activation and independent alteration of the electrical properties for each three-layer fibre in the nerve bundle models. The magnitudes of simulated strains in the white matter of the brain model are used to determine the displacement boundary conditions in elongation simulations using the 3D nerve bundle models. At high impact speed, mechanical failure occurs at lower strain values in large unmyelinated bundles than in myelinated bundles or small unmyelinated bundles; signal propagation continues in large myelinated bundles during and after loading, although there is a large shift in baseline voltage during loading; a linear relationship is observed between the generated plastic strain in the nerve bundle models and the impact speed and nominal strains of the head model. The myelin layer protects the fibre from mechanical damage, preserving its functionalities.

Effects of nerve bundle geometry on neurotrauma evaluation.

OBJECTIVE: We confirm that alteration of a neuron structure can induce abnormalities in signal propagation for nervous systems, as observed in brain damage. Here, we investigate the effects of geometrical changes and damage of a neuron structure in 2 scaled nerve bundle models, made of myelinated nerve fibers or unmyelinated nerve fibers. METHODS: We propose a 3D finite element model of nerve bundles, combining a real-time full electromechanical coupling, a modulated threshold for spiking activation, and independent alteration of the electrical properties for each fiber. With the inclusion of plasticity, we then simulate mechanical compression and tension to induce damage at the membrane of a nerve bundle made of 4 fibers. We examine the resulting changes in strain and neural activity by considering in turn the cases of intact and traumatized nerve membranes. RESULTS: Our results show lower strain and lower electrophysiological impairments in unmyelinated fibers than in myelinated fibers, higher deformation levels in larger bundles, and higher electrophysiological impairments in smaller bundles. CONCLUSION: We conclude that the insulation sheath of myelin constricts the membrane deformation and scatters plastic strains within the bundle, that larger bundles deform more than small bundles, and that small fibers tolerate a higher level of elongation before mechanical failure.

Electrothermal Equivalent Three-Dimensional Finite-Element Model of a Single Neuron.

OBJECTIVE: We propose a novel approach for modelling the interdependence of electrical and mechanical phenomena in nervous cells, by using electrothermal equivalences in finite element (FE) analysis so that existing thermomechanical tools can be applied. METHODS: First, the equivalence between electrical and thermal properties of the nerve materials is established, and results of a pure heat conduction analysis performed in Abaqus CAE Software 6.13-3 are validated with analytical solutions for a range of steady and transient conditions. This validation includes the definition of equivalent active membrane properties that enable prediction of the action potential. Then, as a step toward fully coupled models, electromechanical coupling is implemented through the definition of equivalent piezoelectric properties of the nerve membrane using the thermal expansion coefficient, enabling prediction of the mechanical response of the nerve to the action potential. RESULTS: Results of the coupled electromechanical model are validated with previously published experimental results of deformation for squid giant axon, crab nerve fibre, and garfish olfactory nerve fibre. CONCLUSION: A simplified coupled electromechanical modelling approach is established through an electrothermal equivalent FE model of a nervous cell for biomedical applications. SIGNIFICANCE: One of the key findings is the mechanical characterization of the neural activity in a coupled electromechanical domain, which provides insights into the electromechanical behaviour of nervous cells, such as thinning of the membrane. This is a first step toward modelling three-dimensional electromechanical alteration induced by trauma at nerve bundle, tissue, and organ levels.

Subretinal Glial Membranes in Eyes With Geographic Atrophy.

Purpose: Müller cells create the external limiting membrane (ELM) by forming junctions with photoreceptor cells. This study evaluated the relationship between focal photoreceptors and RPE loss in geographic atrophy (GA) and Müller cell extension into the subretinal space. Methods: Human donor eyes with no retinal disease or geographic atrophy (GA) were fixed and the eye cups imaged. The retinal posterior pole was stained for glial fibrillary acidic protein (GFAP; astrocytes and activated Müller cells) and vimentin (Müller cells) while the submacular choroids were labeled with Ulex Europaeus Agglutinin lectin (blood vessels). Choroids and retinas were imaged using a Zeiss 710 confocal microscope. Additional eyes were cryopreserved or processed for transmission electron microscopy (TEM) to better visualize the Müller cells. Results: Vimentin staining of aged control retinas (n = 4) revealed a panretinal cobblestone-like ELM. While this pattern was also observed in the GA retinas (n = 7), each also had a distinct area in which vimentin+ and vimentin+/GFAP+ processes created a subretinal membrane. Subretinal glial membranes closely matched areas of RPE atrophy in the gross photos. Choroidal vascular loss was also evident in these atrophic areas. Smaller glial projections were noted, which correlated with drusen in gross photos. The presence of glia in the subretinal space was confirmed by TEM and cross cross-section immunohistochemistry. Conclusions: In eyes with GA, subretinal Müller cell membranes present in areas of RPE atrophy may be a Müller cell attempt to replace the ELM. These membranes could interfere with treatments such as stem cell therapy.

A randomized, double-blind, vehicle-controlled crossover study to determine the anti-pruritic efficacy, safety and local dermal tolerability of a topical formulation (srd174 cream) of the long-acting opiod antagonist nalmefene in subjects with atopic dermatitis.

OBJECTIVE: To investigate the efficacy, safety and tolerability of topical nalmefene (SRD174), a long acting opioid antagonist for the management of pruritus associated with atopic dermatitis (AD). DESIGN: Double-blind, vehicle-controlled, randomized, cross-over trial. SETTING: Eleven dermatology outpatient clinics in the U.S. PATIENTS: Sixty-two out of 136 screened adult subjects with confirmed AD affecting is less than or equal to 20% of body surface area and with moderate-to-severe pruritus. INTERVENTIONS: SRD174 cream or matching vehicle cream applied as required during two 7-day periods separated by a wash-out period. MAIN OUTCOME MEASURE(S): The primary efficacy variable was the period mean of the sum of pruritus intensity difference (SPID) from 0 to 4 hours (SPID0-4) where pruritus was measured on a 0-100 scale Visual Analog Scale (VAS) at seven pre-specified time-points following study drug application. A range of secondary efficacy, safety and tolerance endpoints were included. RESULTS: The LS means for the SPID0-4 (± SD) for SRD174 cream and Vehicle were 210.7 (20.4) and 212.1 (20.2), respectively (Difference = -1.3 (95% CI: -25.9, 23.3). None of the secondary efficacy endpoints tested demonstrated a statistically significant or clinically important difference between the test product and the vehicle. Overall, the SRD174 cream was well tolerated although there was a higher incidence of AEs when subjects took SRD174 cream (22, 36.7 percent of subjects) compared with when they were taking vehicle (14, 23.3 percent of subjects). CONCLUSIONS: SRD174 cream did not demonstrate efficacy in the treatment of pruritus associated with atopic dermatitis raising questions on the role of peripheral opioid receptors as a target for the treatment of pruritus in this population.

Effect of a magnetic core in the receiver coil of a biomedical inductive power system.

The design of an inductive power system is investigated in order to determine the relative benefits provided by the inclusion of a magnetic core in the receiver coil. Both transmitter and receiver coils are chosen to have dimensions similar to those used in many biomedical devices. It is found that while a magnetic core provides enhanced coupling, the operating frequency is limited by losses in the magnetic material. Consequently, the performance of air-core coils is shown to match that of coils with magnetic cores when operated at a higher frequency. Work is ongoing to consider the effects of other limitations imposed by biomedical environments.