A match coefficient approach for damage imaging in structural components by ultrasonic synthetic aperture focus

Ultrasonic Synthetic Aperture Focus (SAF) techniques are commonly used to image structural defects. In this paper, a variation of SAF based on ideas borrowed from Matched Field Processing (MFP) is evaluated to reduce artifacts and sidelobes of the resulting images. In particular, instead of considering the full RF ultrasonic waveforms for the SAF time backpropagation, only selected features from the waveforms are utilized to form a “data vector” and a “replica” (expected) vector of MFP. These vectors are adaptive for the pair of transmitter-receiver and the focus point. The image is created as a matched filter between these two vectors. Experimental results are shown for an isotropic and homogenous metallic plate with simulated defects, probed by six piezoelectric patches used as receivers or transmitters

Methods for preclinical validation of software as a medical device

Software as a medical device is subject to dedicated regulatory requirements before it can be used on human beings. The certification process in Europe requires that sufficient data on clinical benefits are available before the device is CE marked. This position paper describes our proposal of a risk-based approach to technical and preclinical validation of software as medical devices. This approach ensures that all technical solutions for safety are implemented in the software and that all information for safe use is consistent before the software can be made available to patients. This approach is compliant to the main international standards ISO 13485 on quality systems and ISO 14971 on risk management and therefore ensures regulatory compliance as well as patient protection. This integrated approach allows the designers of the software to integrate regulatory and safety testing in the technical testing of the candidate release version of the device. This approach ensures patient safety and regulatory compliance at the same time as technical functionality

A novel method for validating multi-classifiers. A case study for ICF-based health status classification

In this paper, we propose a novel method for the validation of a multi-classification model according to the intended use and aim of a device for health status classification and the clinical needs of the practitioners involved

Usability assessment of an intraoperative planning software

Usability is a crucial aspect of medical device safety. The brand-new European Regulation requires the manufacturer to assess the usability of the new medical devices. In this study, we evaluate the usability of a new medical device intended to assist the intraoperative planning with the visualization of 3d patient-specific organ models. The usability study started from the early stage of the device design and iterated through an early formative, completed with desk-based activities, late formative, completed with a focus group, and summative phase, that comprised a user test, and questionnaire filling. The identified usability issues are mitigated, the safety of the device user interface is confirmed and the training contents are defined and confirmed. Additional information regarding the user experience is collected and analyzed to identify further improvements of the device

Microbial regulation of the L cell transcriptome.

L cells are an important class of enteroendocrine cells secreting hormones such as glucagon like peptide-1 and peptide YY that have several metabolic and physiological effects. The gut is home to trillions of bacteria affecting host physiology, but there has been limited understanding about how the microbiota affects gene expression in L cells. Thus, we rederived the reporter mouse strain, GLU-Venus expressing yellow fluorescent protein under the control of the proglucagon gene, as germ-free (GF). Lpos cells from ileum and colon of GF and conventionally raised (CONV-R) GLU-Venus mice were isolated and subjected to transcriptomic profiling. We observed that the microbiota exerted major effects on ileal L cells. Gene Ontology enrichment analysis revealed that microbiota suppressed biological processes related to vesicle localization and synaptic vesicle cycling in Lpos cells from ileum. This finding was corroborated by electron microscopy of Lpos cells showing reduced numbers of vesicles as well as by demonstrating decreased intracellular GLP-1 content in primary cultures from ileum of CONV-R compared with GF GLU-Venus mice. By analysing Lpos cells following colonization of GF mice we observed that the greatest transcriptional regulation was evident within 1 day of colonization. Thus, the microbiota has a rapid and pronounced effect on the L cell transcriptome, predominantly in the ileum

A public early intervention approach to first-episode psychosis: Treated incidence over 7 years in the Emilia-Romagna region

AimTo estimate the treated incidence of individuals with first-episode psychosis (FEP) who contacted the Emilia-Romagna public mental healthcare system (Italy); to examine the variability of incidence and user characteristics across centres and years. MethodsWe computed the raw treated incidence in 2013-2019, based on FEP users aged 18-35, seen within or outside the regional program for FEP. We modelled FEP incidence across 10 catchment areas and 7 years using Bayesian Poisson and Negative Binomial Generalized Linear Models of varying complexity. We explored associations between user characteristics, study centre and year comparing variables and socioclinical clusters of subjects. ResultsThousand three hundred and eighteen individuals were treated for FEP (raw incidence: 25.3 / 100.000 inhabitant year, IQR: 15.3). A Negative Binomial location-scale model with area, population density and year as predictors found that incidence and its variability changed across centres (Bologna: 36.55; 95% CrI: 30.39-43.86; Imola: 3.07; 95% CrI: 1.61-4.99) but did not follow linear temporal trends or density. Centers were associated with different user age, gender, migrant status, occupation, living conditions and cluster distribution. Year was associated negatively with HoNOS score (R = -0.09, p < .001), duration of untreated psychosis (R = -0.12, p < .001) and referral type. ConclusionsThe Emilia-Romagna region presents a relatively high but variable incidence of FEP across areas, but not in time. More granular information on social, ethnic and cultural factors may increase the level of explanation and prediction of FEP incidence and characteristics, shedding light on social and healthcare factors influencing FEP

In Vivo Delta Opioid Receptor Internalization Controls Behavioral Effects of Agonists

GPCRs regulate a remarkable diversity of biological functions, and are thus often targeted for drug therapies. Stimulation of a GPCR by an extracellular ligand triggers receptor signaling via G proteins, and this process is highly regulated. Receptor activation is typically accompanied by desensitization of receptor signaling, a complex feedback regulatory process of which receptor internalization is postulated as a key event. The in vivo significance of GPCR internalization is poorly understood. In fact, the majority of studies have been performed in transfected cell systems, which do not adequately model physiological environments and the complexity of integrated responses observed in the whole animal.In this study, we used knock-in mice expressing functional fluorescent delta opioid receptors (DOR-eGFP) in place of the native receptor to correlate receptor localization in neurons with behavioral responses. We analyzed the pain-relieving effects of two delta receptor agonists with similar signaling potencies and efficacies, but distinct internalizing properties. An initial treatment with the high (SNC80) or low (AR-M100390) internalizing agonist equally reduced CFA-induced inflammatory pain. However, subsequent drug treatment produced highly distinct responses. Animals initially treated with SNC80 showed no analgesic response to a second dose of either delta receptor agonist. Concomitant receptor internalization and G-protein uncoupling were observed throughout the nervous system. This loss of function was temporary, since full DOR-eGFP receptor responses were restored 24 hours after SNC80 administration. In contrast, treatment with AR-M100390 resulted in retained analgesic response to a subsequent agonist injection, and ex vivo analysis showed that DOR-eGFP receptor remained G protein-coupled on the cell surface. Finally SNC80 but not AR-M100390 produced DOR-eGFP phosphorylation, suggesting that the two agonists produce distinct active receptor conformations in vivo which likely lead to differential receptor trafficking.Together our data show that delta agonists retain full analgesic efficacy when receptors remain on the cell surface. In contrast, delta agonist-induced analgesia is abolished following receptor internalization, and complete behavioral desensitization is observed. Overall these results establish that, in the context of pain control, receptor localization fully controls receptor function in vivo. This finding has both fundamental and therapeutic implications for slow-recycling GPCRs

Current drive at plasma densities required for thermonuclear reactors

Progress in thermonuclear fusion energy research based on deuterium plasmas magnetically confined in toroidal tokamak devices requires the development of efficient current drive methods. Previous experiments have shown that plasma current can be driven effectively by externally launched radio frequency power coupled to lower hybrid plasma waves. However, at the high plasma densities required for fusion power plants, the coupled radio frequency power does not penetrate into the plasma core, possibly because of strong wave interactions with the plasma edge. Here we show experiments performed on FTU (Frascati Tokamak Upgrade) based on theoretical predictions that nonlinear interactions diminish when the peripheral plasma electron temperature is high, allowing significant wave penetration at high density. The results show that the coupled radio frequency power can penetrate into high-density plasmas due to weaker plasma edge effects, thus extending the effective range of lower hybrid current drive towards the domain relevant for fusion reactors