Magnetoelectric nanoparticles shape modulates their electrical output.

Core-shell magnetoelectric nanoparticles (MENPs) have recently gained popularity thanks to their capability in inducing a local electric polarization upon an applied magnetic field and vice versa. This work estimates the magnetoelectrical behavior, in terms of magnetoelectric coupling coefficient (αME), via finite element analysis of MENPs with different shapes under either static (DC bias) and time-variant (AC bias) external magnetic fields. With this approach, the dependence of the magnetoelectrical performance on the MENPs geometrical features can be directly derived. Results show that MENPs with a more elongated morphology exhibits a superior αME if compared with spherical nanoparticles of similar volume, under both stimulation conditions analyzed. This response is due to the presence of a larger surface area at the interface between the magnetostrictive core and piezoelectric shell, and to the MENP geometrical orientation along the direction of the magnetic field. These findings pave a new way for the design of novel high-aspect ratio magnetic nanostructures with an improved magnetoelectric behaviour.

Computational Evaluation of Combined Cerebellar and Frontal Transcranial Direct Current Stimulation for Treatment-Resistant Depression.

This work aimed to estimate the distribution of the electric field generated by a combined cerebellar and frontal transcranial direct current stimulation (tDCS) for treatment-resistant depression using electromagnetics computational techniques applied to a realistic head human model. Results showed that the stronger electric fields occur mainly in the cerebellum and in DLPFC areas, where the two pairs of electrodes were applied. Furthermore, the study demonstrated that the simultaneous use of the two pairs of electrodes did not imply a lower effectiveness of the tDCS technique, in fact the electric field distributions in the primarily targets of the anatomical regions (i.e., cerebellum and DLPFC) were very similar to when the pairs of electrodes were applied separately.

Gold nanoparticles as enablers of cell membrane permeabilization by time-varying magnetic field: influence of distance and geometry.

This study is based on the quantification of the influence of the presence of gold nanoparticles (Au NPs), of their geometry and their distance from cell membrane during time-varying electromagnetic fields cell membrane permeabilization on the pores opening dynamics. Results showed that the combined use of Au NPs and time-varying magnetic field can improve significantly the permeabilization of cell membrane. The presence of Au NPs allowed to reach transmembrane potential values enabling the cell membrane permeabilization only when placed at very short distance, equal to 20 nm. Both geometry and variability of the positioning in proximity of the cell membrane showed a strong influence on the probability of enabling pores opening. Clinical Relevance- This study provides a better comprehension about the mechanisms, still not completely understood, underlying cell membrane permeabilization by combining Au NPs and time-varying magnetic fields.

Application of Stochastic Dosimetry for assessing the Human RFEMF Exposure in a 5G indoor Scenario.

In recent years the introduction of 5G networks is causing a drastically change of human exposure levels in the radio frequency range. The aim of this paper is on expanding the knowledge on this issue, assessing the exposure levels for a particular case of indoor 5G scenario, where the presence of an Access Point (AP) was simulated. Coupling the traditional deterministic computational method with an innovative stochastic approach, called Polynomial Chaos Kriging, allowed to evaluate the exposure variability of an user considering the 3D beamforming capability of the antenna. The exposure levels, expressed in terms of specific absorption rate (SAR) in specific tissues, showed low values compared to ICNIRP guidelines.

Contactless Cell Permeabilization by Time-Varying Magnetic fields: Modelling Transmembrane Potential and Mechanical Stress in in- vitro Experimental Set-Up.

The feasibility of using time-varying magnetic field as a contactless cells permeabilization method was demonstrated by experimental results, but the underlying mechanism is still poorly understood. In this study a numerical analysis of the transmembrane potential (TMP) at cell membranes during permeabilization by time-varying magnetic fields was proposed, and a first quantification of mechanical stress induced by the magnetic and electric fields and hypothesized to play an important role in the permeabilization mechanism was carried out. TMP values induced by typical in-vitro experimental conditions were far below the values needed for membrane permeabilization, with a strong dependence on distance of the cell from the coil. The preliminary assessment of the mechanical pressure and potential deformation of cells showed that stress values evaluated in conditions in which TMP values were too low to cause membrane permeabilization were comparable to those known to influence the pore opening mechanisms.Clinical Relevance- Results represent a significant step towards a better comprehension of the mechanism underlying cell membrane permeabilization by time-varying magnetic fields.

Cell transmembrane potential in contactless permeabilization by time-varying magnetic fields.

BACKGROUND: Although experimental results proved the feasibility of using time-varying magnetic field as a contactless cells permeabilization method, the underlying mechanism is still poorly understood. In this study a numerical analysis of the time-dependent transmembrane potential (TMP) at cell membranes during permeabilization by time-varying magnetic fields was proposed, and a first quantification of mechanical stress induced by the magnetic and electric fields, hypothesized to play an important role in the permeabilization mechanism, was carried out. METHODS: Starting from the simulation of real in vitro experimental conditions, the analysis was widened quantifying the influence of pulse frequency, cell dimension and distance of the cell from the magnetic field source. The mechanical pressure on cell membrane due to the interaction between free charges and induced electric field and due to the gradient of the magnetic field was quantified in all those conditions in which the TMP values were not high enough to cause membrane permeabilization. RESULTS: TMP values induced by typical in-vitro experimental conditions were far below the values needed for membrane permeabilization, with a strong dependence on pulse frequency and distance of the cell from the coil. CONCLUSION: The preliminary assessment of the mechanical pressure on cell membrane showed that stress values evaluated in conditions in which TMP values were too low to cause membrane permeabilization were comparable to those known to influence the pores opening mechanisms. Results represent a significant step towards a better comprehension of the mechanism underlying cell membrane permeabilization by time-varying magnetic fields.

Computational simulation of electromagnetic fields on human targets for magnetic targeting applications.

In the last few years, the use of nanoparticles for therapeutic applications has attracted the interest of many scientists, who are looking for effective methods to target nanoparticles linked to drugs directly to the diseased organs. Among them, magnetic targeting consists of magnetic systems (magnets or coils) which can impress high gradient magnetic fields and then magnetic forces on the magnetic nanoparticles. Despite some studies have reported an effective improvement in drug delivery by using this technique, there is still a paucity of studies able to quantify and explain the experimental results. In this scenario, "in silico" models allow to analyze and compare different magnetic targeting systems in their ability to generate the required magnetic field gradient for specific human targets.In this paper we then evaluated, by means of computational electromagnetics techniques, the attitude of various ad-hoc designed magnetic systems in targeting the heart tissues of differently aged human anatomical models.

Assessment of Children Exposure Variability to Near-Field Sources using Stochastic Dosimetry.

In this paper, the exposure of a child to a hairdryer model is evaluated. Nowadays, the assessment of children exposure to near-field sources has become in fact a topic of high interest, because it was found that even domestic appliances could be relevant for children exposure level. Therefore, the aim of the present work is to use a method based on stochastic dosimetry to assess the exposure variability due to near-field sources, not limiting it only on some worst-case exposure scenario. In particular, electric field amplitudes induced in specific tissues composing the central nervous system and the peripheral nervous system (following the ICNIRP guidelines) were analyzed. The results highlight a high exposure variability depending on the hairdryer position in respect with the child.

Modelling of the Current Density Distributions during Cortical Electric Stimulation for Neuropathic Pain Treatment.

In the last two decades, motor cortex stimulation has been recognized as a valuable alternative to pharmacological therapy for the treatment of neuropathic pain. Although this technique started to be used in clinical studies, the debate about the optimal settings that enhance its effectiveness without inducing tissue damage is still open. To this purpose, computational approaches applied to realistic human models aimed to assess the current density distribution within the cortex can be a powerful tool to provide a basic understanding of that technique and could help the design of clinical experimental protocols. This study aims to evaluate, by computational techniques, the current density distributions induced in the brain by a realistic electrode array for cortical stimulation. The simulation outcomes, summarized by specific metrics quantifying the efficacy of the stimulation (i.e., the effective volume and the effective depth of penetration) over two cortical targets, were evaluated by varying the interelectrode distance, the stimulus characteristics (amplitude and frequency), and the anatomical human model. The results suggest that all these parameters somehow affect the current density distributions and have to be therefore taken into account during the planning of effective electrical cortical stimulation strategies. In particular, our calculations show that (1) the most effective interelectrode distance equals 2 cm; (2) increasing voltage amplitudes increases the effective volume; (3) increasing frequencies allow enlarging the effective volume; and (4) the effective depth of penetration is strictly linked to both the anatomy of the subject and the electrode placement.

Stochastic Dosimetry for the Assessment of Children Exposure to Uniform 50 Hz Magnetic Field with Uncertain Orientation.

This study focused on the evaluation of the exposure of children aging from five to fourteen years to 50 Hz homogenous magnetic field uncertain orientation using stochastic dosimetry. Surrogate models allowed assessing how the variation of the orientation of the magnetic field influenced the induced electric field in each tissue of the central nervous system (CNS) and in the peripheral nervous system (PNS) of children. Results showed that the electric field induced in CNS and PNS tissues of children were within the ICNIRP basic restrictions for general public and that no significant difference was found in the level of exposure of children of different ages when considering 10000 possible orientations of the magnetic field. A "mean stochastic model," useful to estimate the level of exposure in each tissue of a representative child in the range of age from five to fourteen years, was developed. In conclusion, this study was useful to deepen knowledge about the ELF-MF exposure, including the evaluation of variable and uncertain conditions, thus representing a step towards a more realistic characterization of the exposure to EMF.

Transcranial Direct Current Stimulation: Personalizing the neuromodulation.

The beneficial effects of transcranial direct current stimulation (tDCS) has been demonstrated, but the neuroscientific community is working to increase its efficiency. A promising line of advancement may be reducing the inter-individual variability of the response through the personalization of the stimulation, adapted to fit the structural and functional features of individual subjects. In this paper, we approach the personalization of stimulation parameters using modeling, a powerful tool to test montages enabling the optimization of brain's targeting.

A retrospective evaluation of doxorubicin-based chemotherapy for dogs with right atrial masses and pericardial effusion.

OBJECTIVE: To report the outcome of doxorubicin-based chemotherapy as the sole treatment for dogs with echocardiographically identified right atrial masses and pericardial effusion. METHODS: A retrospective study of case records of dogs with right atrial masses treated with doxorubicin. Dogs were excluded from the study if they had any type of surgery performed such as pericardiectomy or right atrial mass resection, or if their chemotherapy protocol did not include doxorubicin. The data collected included signalment, history, physical examination findings, diagnostic test results and long-term survival. RESULTS: Dogs with right atrial masses and pericardial effusion that received doxorubicin-based chemotherapy alone had a median survival of 139 · 5 days (range 2 to 302 days). Chemotherapy side effects were frequent but mild. CLINICAL SIGNIFICANCE: Doxorubicin-based chemotherapy alone appears to be a viable treatment option for dogs with echocardiographically identified right atrial masses and pericardial effusion.

Polynomial Chaos decomposition applied to stochastic dosimetry: study of the influence of the magnetic field orientation on the pregnant woman exposure at 50 Hz.

Polynomial Chaos (PC) is a decomposition method used to build a meta-model, which approximates the unknown response of a model. In this paper the PC method is applied to the stochastic dosimetry to assess the variability of human exposure due to the change of the orientation of the B-field vector respect to the human body. In detail, the analysis of the pregnant woman exposure at 7 months of gestational age is carried out, to build-up a statistical meta-model of the induced electric field for each fetal tissue and in the fetal whole-body by means of the PC expansion as a function of the B-field orientation, considering a uniform exposure at 50 Hz.

Modelling of deep transcranial magnetic stimulation: different coil configurations.

This paper provides a characterization of the induced electric field distributions in the brain of a realistic human model due to 16 different coil configurations. We used the scalar potential finite element method to calculate the induced electric field distributions differentiating the brain structures, e.g. cortex, white matter, cerebellum, thalamus, hypothalamus, hippocampus, pons and midbrain. We found that, despite the presence of a depth-focality tradeoff, some configurations are able to reach subcortical white matter tracts at effective electric field level.

Computational model of cerebellar transcranial direct current stimulation.

This work aimed to estimate the distribution of the electric field and current density generated by cerebellar tDCS using electromagnetics computational techniques applied to a realistic human models of different ages and gender. Results show that the stronger electric field and current density occur mainly in the cerebellar cortex, with a spread toward the occipital region of the cortex, while the current spread to other structures is negligible. Moreover, changes of about 1 cm in the position of the scalp electrode delivering tDCS did not influence the E and J distribution in the cerebellum.

Estimate of the fetal temperature increase due to UHF RFID exposure.

Exposure from electromagnetic (EM) devices has increased during the last decades due to the rapid development of new technologies. Among them, radiofrequency identification (RFID) applications are used in almost every aspect of everyday life, which could expose people unselectively. This scenario could pose potential risks for certain groups of general population, such as pregnant women, who are more sensitive to thermal effects produced by EM exposure. In this paper, the temperature rise at the steady state in two pregnant women models exposed to UHF RFID has been assessed. Results show that heating of tissues is far from the threshold of biological effects indicated by radiation protection guidelines.

Influence of tinnitus sound therapy signals on the intelligibility of speech.

OBJECTIVE: To assess the influence on speech intelligibility of various signals used in tinnitus sound therapy. MATERIALS AND METHODS: We measured, in normal hearing subjects, the intelligibility of speech in the presence of three different sound therapy signals: wide-band noise, a recording of moving water, and a combination of tones. RESULTS: For a given level of stimulation, speech intelligibility was worst in the presence of wide-band noise, compared with the other sound therapy signals. When the stimulation level of the three different signals was increased, speech intelligibility deteriorated more rapidly with wide-band noise, compared with the other two signals. The combination of tones had the least influence on speech intelligibility. CONCLUSION: The use of different tinnitus sound therapy signals can lead to significantly different effects on the intelligibility of speech. The use of natural sound recordings or combinations of tones may provide the patient with more flexibility to change the stimulation level during treatment.

An open-label, dose-escalating phase I study of elsamitrucin (SPI 28090) in treatment of malignant solid tumors in dogs.

BACKGROUND: Elsamitrucin, the most potent topoisomerase II inhibitor available, is unique in that it does not cause neutropenia or cardiotoxicosis. It has antitumor activity in human patients with relapsed or refractory non-Hodgkin's lymphoma. OBJECTIVES: To determine the maximum tolerated dose (MTD), safety, and toxicity of elsamitrucin when administered to tumor-bearing dogs and to evaluate the incidence and severity of adverse events. ANIMALS: Twenty client-owned dogs with spontaneous malignant solid tumors or lymphoma that were refractory to, or for which the owner declined, conventional therapy were enrolled. METHODS: Prospective, open-label, single-agent study. Escalating doses of elsamitrucin were administered once weekly i.v. for up to 16 weeks in a modified 3 + 3 Phase I design. The starting dose was 0.06 mg/kg with escalation to 0.08 and 0.09 mg/kg. Dogs that remained on the study were monitored for evidence of toxicoses for at least 4 weeks and for survival every 2 months. RESULTS: Serious adverse events (SAEs) possibly attributable to elsamitrucin include: 1 dog developed heart failure and another developed hepatotoxicosis manifested by increased alanine aminotransferase, alkaline phosphatase, and total bilirubin (0.06 mg/kg dose); 1 dog developed severe anorexia and diarrhea, another developed severe diarrhea alone, and a 3rd dog went into cardiac arrest (0.09 mg/kg dose). A dose of 0.08 mg/kg was well tolerated with no SAEs. CONCLUSIONS AND CLINICAL IMPORTANCE: The MTD and recommended dose for Phase II trials of elsamitrucin is 0.08 mg/kg i.v. weekly. Elsamitrucin might be considered for combination protocols with myelosuppressive chemotherapy agents.

Diabetic patients management exploiting case-based reasoning techniques.

In this paper we propose a case-based decision support tool, designed to help physicians in 1st type diabetes therapy revision through the intelligent retrieval of data related to past situations (or 'cases') similar to the current one. A case is defined as a set of variable values (or features) collected during a visit. We defined taxonomy of prototypical patients' conditions, or classes, to which each case should belong. For each input case, the system allows the physician to find similar past cases, both from the same patient and from different ones. We have implemented a two-steps procedure; (1) it finds the classes to which the input case could belong; (2) it lists the most similar cases from these classes, through a nearest neighbor technique, and provides some statistics useful for decision taking. The performance of the system has been tested on a data-base of 147 real cases, collected at the Policlinico S. Matteo Hospital of Pavia. The tool is fully integrated in the web-based architecture of the EU funded Telematic management of Insulin Dependent Diabetes Mellitus (T-IDDM) project.

Protocol-based reasoning in diabetic patient management.

We propose a system for teleconsultation in Insulin Dependent Diabetes Mellitus (IDDM) management, accessible through the use of the net. The system is able to collect monitoring data, to analyze them through a set of tools, and to suggest a therapy adjustment in order to tackle the identified metabolic problems and to fit the patient's needs. The therapy revision has been implemented through the Episodic Skeletal Planning Methodi, it generates an advice and employs it to modify the current therapeutic protocol, presenting to the physician a set of feasible solutions, among which she can choose the new one.