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Brugada Syndrome (BrS) is a primary electrical epicardial disease characterized by ST-segment elevation followed by a negative T-wave in the right precordial leads on the surface electrocardiogram (ECG), also known as the ‘type 1’ ECG pattern. The risk stratification of asymptomatic individuals with spontaneous type 1 ECG pattern remains challenging. Clinical and electrocardiographic prognostic markers are known. As none of these predictors alone is highly reliable in terms of arrhythmic prognosis, several multi-factor risk scores have been proposed for this purpose. This article presents a new workflow for processing endocardial signals acquired with high-density RV electro-anatomical mapping (HDEAM) from BrS patients. The workflow, which relies solely on Matlab software, calculates various electrical parameters and creates multi-parametric maps of the right ventricle. The workflow, but it has already been employed in several research studies involving patients carried out by our group, showing its potential positive impact in clinical studies. Here, we will provide a technical description of its functionalities, along with the results obtained on a BrS patient who underwent an endocardial HDEAM.

Cockayne syndrome (CS) is a rare hereditary autosomal recessive disorder primarily caused by mutations in Cockayne syndrome protein A (CSA) or B (CSB). While many of the functions of CSB have been at least partially elucidated, little is known about the actual developmental dysregulation in this devasting disorder. Of particular interest is the regulation of cerebral development as the most debilitating symptoms are of neurological nature. We generated neurospheres and cerebral organoids utilizing Cockayne syndrome B protein (CSB)-deficient induced pluripotent stem cells derived from two patients with distinct severity levels of CS and healthy controls. The transcriptome of both developmental timepoints was explored using RNA-Seq and bioinformatic analysis to identify dysregulated biological processes common to both patients with CS in comparison to the control. CSB-deficient neurospheres displayed upregulation of the VEGFA-VEGFR2 signalling pathway, vesicle-mediated transport and head development. CSB-deficient cerebral organoids exhibited downregulation of brain development, neuron projection development and synaptic signalling. We further identified the upregulation of steroid biosynthesis as common to both timepoints, in particular the upregulation of the cholesterol biosynthesis branch. Our results provide insights into the neurodevelopmental dysregulation in patients with CS and strengthen the theory that CS is not only a neurodegenerative but also a neurodevelopmental disorder.

Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score ˂ 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59–0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.

Traders and investors are interested in accurately predicting cryptocurrency prices to increase returns and minimize risk. However, due to their uncertainty, volatility, and dynamism, forecasting crypto prices is a challenging time series analysis task. Researchers have proposed predictors based on statistical, machine learning (ML), and deep learning (DL) approaches, but the literature is limited. Indeed, it is narrow because it focuses on predicting only the prices of the few most famous cryptos. In addition, it is scattered because it compares different models on different cryptos inconsistently, and it lacks generality because solutions are overly complex and hard to reproduce in practice. The main goal of this paper is to provide a comparison framework that overcomes these limitations. We use this framework to run extensive experiments where we compare the performances of widely used statistical, ML, and DL approaches in the literature for predicting the price of five popular cryptocurrencies, i.e., XRP, Bitcoin (BTC), Litecoin (LTC), Ethereum (ETH), and Monero (XMR). To the best of our knowledge, we are also the first to propose using the temporal fusion transformer (TFT) on this task. Moreover, we extend our investigation to hybrid models and ensembles to assess whether combining single models boosts prediction accuracy. Our evaluation shows that DL approaches are the best predictors, particularly the LSTM, and this is consistently true across all the cryptos examined. LSTM reaches an average RMSE of 0.0222 and MAE of 0.0173, respectively, 2.7% and 1.7% better than the second-best model. To ensure reproducibility and stimulate future research contribution, we share the dataset and the code of the experiments.

As there is currently no consensus on managing deep neck infections in pediatric populations, we report a case series from a large pediatric hospital. Clinical data of patients discharged from Istituto Gaslini-Children’s Hospital from January 2014 to June 2020 with peritonsillar, parapharyngeal, or retropharyngeal abscess diagnoses were collected. A total of 59 patients were identified. Patients underwent surgical drainage in 47% of cases. Streptococcus mitis/oralis was the most isolated pathogen. Surgically treated patients did have larger abscesses compared to others, but there were no differences in the duration of hospitalization. Children who received NSAIDs at home had significant delays in diagnosis (median 4 vs. 1.5 days, p = 0.008). In our experience, clinical presentation of DNIs is often evocative, but evaluation should include imaging with CT/MRI. Surgery is effective in larger abscesses, allowing for etiological diagnosis with consequent antibiotic adjusting. From an anamnestic point of view, home medications such as NSAIDs could delay diagnosis.

Indoleamine 2,3-dioxygenase 2 (IDO2) is a tryptophan-catabolizing enzyme and a homolog of IDO1 with a distinct expression pattern compared with IDO1. In dendritic cells (DCs), IDO activity and the resulting changes in tryptophan level regulate T-cell differentiation and promote immune tolerance. Recent studies indicate that IDO2 exerts an additional, non-enzymatic function and pro-inflammatory activity, which may play an important role in diseases such as autoimmunity and cancer. Here, we investigated the impact of aryl hydrocarbon receptor (AhR) activation by endogenous compounds and environmental pollutants on the expression of IDO2. Treatment with AhR ligands induced IDO2 in MCF-7 wildtype cells but not in CRISPR-cas9 AhR-knockout MCF-7 cells. Promoter analysis with IDO2 reporter constructs revealed that the AhR-dependent induction of IDO2 involves a short-tandem repeat containing four core sequences of a xenobiotic response element (XRE) upstream of the start site of the human ido2 gene. The analysis of breast cancer datasets revealed that IDO2 expression increased in breast cancer compared with normal samples. Our findings suggest that the AhR-mediated expression of IDO2 in breast cancer could contribute to a pro-tumorigenic microenvironment in breast cancer.

Active and passive vibration control systems are of paramount importance in many engineering applications. If an external load excites a structure’s resonance and the damping is too low, detrimental events, such as crack initiation, growth and, in the worst case, fatigue failure, can be entailed. Damping systems can be commonly found in applications such as industrial machines, vehicles, buildings, turbomachinery blades, and so forth. Active control systems usually achieve higher damping effectiveness than passive ones, but they need a sensor to detect the working conditions that require damping system activation. Recently, the development of such systems in rotating structures has received considerable interest among designers. As a result, the development of vibration monitoring equipment in rotating structures is also a topic of particular interest. In this respect, a reliable, inexpensive and wireless monitoring system is of utmost importance. Typically, optical systems are used to measure vibrations, but they are expensive and require rather complex processing algorithms. In this paper, a wireless system based on a commercial MEMS accelerometer is developed for rotating blade vibration monitoring. The proposed system measurement accuracy was assessed by means of comparison with a reference wired measurement setup based on a mini integrated circuit piezoelectric (ICP) accelerometer adapted for data acquisition in a rotating frame. Both the accelerometers were mounted on the tip of the blade and, in order to test the structure under different conditions, the first four blade resonances were excited by means of piezoelectric actuators, embedded in a novel experimental setup. The frequency and amplitude of acceleration, simultaneously measured by the reference and MEMS sensors, were compared with each other in order to investigate the viability and accuracy of the proposed wireless monitoring system. The rotor angular speed was varied from 0 to 300 rpm, and the data acquisitions were repeated six times for each considered condition. The outcomes reveal that the wireless measurement system may be successfully used for vibration monitoring in rotating blades.

Cr(VI) is highly soluble and mobile in water solution and extremely toxic. In order to obtain a specific material with adsorption properties towards Cr(VI), and that can be used in environmental remediation of water contaminated with Cr(VI), one-step sol-gel technique, at low temperature (50 °C), has been optimized to prepare transparent silica-based xerogel monolith by using tetraethyl orthosilicate as precursor. The obtained xerogel, with disk shape, was fully characterized by Raman, BET, FE-SEM and XRD analysis. The results indicated that the material showed silica amorphous phase and high porosity. The study of the adsorption properties towards different concentrations of Cr(VI), in the form of HCrO4− in acidic condition, showed prominent results. The absorption kinetics were evaluated by studying different models, the final result showing that the absorption of Cr(VI) occurred through intra-particle diffusion process, following two steps, and that the absorption equilibrium is regulated by Freundlich isotherm model. The material can be restored by reducing the hazardous Cr(VI) to Cr(III), a less toxic form of chromium, by 1,5-diphenylcarbazide, and with successive treatment in acidic water.

We provide a study comparison between two-dimensional measurement and volumetric (3D) segmentation of the lateral ventricles and brain structures in fetuses with isolated and non-isolated ventriculomegaly with 3D virtual organ computer-aided analysis (VOCAL) ultrasonography vs. magnetic resonance imaging (MRI) analyzed with 3D-Slicer software. In this cross-sectional study, 40 fetuses between 20 and 38 gestational weeks with various degrees of ventriculomegaly were included. A total of 71 ventricles were measured with ultrasound (US) and with MRI. A total of 64 sonographic ventricular volumes, 80 ventricular and 40 fetal brain MR volumes were segmented and analyzed using both imaging modalities by three observers. Sizes and volumes of the ventricles and brain parenchyma were independently analyzed by two radiologists, and interobserver correlation of the results with 3D fetal ultrasound data was performed. The semiautomated rotational multiplanar 3D VOCAL technique was performed for ultrasound volumetric measurements. Results were compared to manually extracted ventricular and total brain volumes in 3D-Slicer. Segmentation of fetal brain structures (cerebral and cerebellar hemispheres, brainstem, ventricles) performed independently by two radiologists showed high interobserver agreement. An excellent agreement between VOCAL and MRI volumetric and two-dimensional measurements was established, taking into account the intraclass correlation coefficients (ICC), and a Bland–Altman plot was established. US and MRI are valuable tools for performing fetal brain and ventricular volumetry for clinical prognosis and patient counseling. Our datasets could provide the backbone for further construction of quantitative normative trajectories of fetal intracranial structures and support earlier detection of abnormal brain development and ventriculomegaly, its timing and progression during gestation.

Grinding is a finishing process for high precision, high surface quality parts, and hard materials, including tool fabrication and sharpening. The recycling of grinding scraps, which often contain rare and costly materials such as tungsten carbide (WC-Co), has been established for decades. However, there is a growing need for more energy-efficient and environmentally friendly recycling processes. Currently, grinding sludges, which are a mixture of abrasives, lubricants, and hard metal chips, are only treated through chemical recycling. Direct recycling (“reuse” of chips as raw material) is the most effective but not yet viable process due to the presence of contaminants. This paper presents an oil-free dry grinding process that produces high-quality chips (i.e., oil-free and with few contaminants, smaller than 60 mesh particle size) that can be directly recycled, as opposed to the oil-based wet grinding that generates sludges, which require indirect recycling. The proposed alternative recycling method is validated experimentally using WC-Co chips from a leading hard metals’ processing specialized company. The contaminant level (oxygen 0.8 wt.%, others < 0.4 wt.%), granulometry (chip D50 = 10.4 µm with grain size < 3 µm) and morphology of the recycled chips’ powder is comparable to commercial powders proving the research and industrial potential of direct recycling. The comparison of sintered products using recycled and commercial powder provided equivalent characteristics for hardness (HRA of 90.7, HV30 of 1430), porosity grade (A02-04) and grain size (

Vibration mitigation is a prominent matter in several engineering fields. Several adverse phenomena are related to vibrations, such as fatigue, noise, etc. The availability of smart materials increases the solutions for both vibration damping and energy harvesting applications. Piezoelectric materials seem to be the most promising for these applications. However, their positioning significantly affects their efficiency. Several studies were performed on the positioning of piezoelectric actuators to dampen a target resonance in cantilever beams with constant cross-sections. Here, an analytical model for the optimal voltage distribution on an array of piezoceramic (PZT) actuator pairs is proposed in the case of tapered beams. The effect of tapering on the optimal voltage distribution was investigated for several eigenmode excitations and tapering ratios. The model outcomes were corroborated via FEM simulations and a fair agreement was found for each considered case.

In recent decades, many studies have been conducted on the use of smart materials in order to dampen and control vibrations. Lead zirconate titanate piezoceramics (PZT) are very attractive for such applications due to their ability of delivering high energy strain in the structure. A pair of piezoelectric actuators can actively dampen the resonances of the structure, but the damping effectiveness strongly relies on its location. Damping effectiveness can be substantially increased if the structure is fully covered with PZT actuator pairs and the voltage distribution on each pair is optimized. In this way, each actuator pair contributes to the vibration attenuation and only the driving voltage’s sign, distributed on each actuator pair, needs to be identified for each resonance. This approach is here applied to the case of Euler–Bernoulli beams with constant cross-section and the optimal voltage distribution is investigated for several boundary conditions. The theoretical model results were corroborated with finite element simulations, which were carried out considering beams covered by ten PZT actuator pairs. The numerical results agree remarkably well with the theoretical predictions for each examined case (i.e., free-free, pinned-pinned, and fixed-fixed).

In the management of drinking water networks, operational costs generally play second fiddle to capital investment costs, because their optimization strategies are often distinct. However, under the pressure of an aged network infrastructure with limited available budgets, a solution that targets the optimization of capital expenditure (CAPEX) and operational expenditure (OPEX) is desirable for reducing water losses and achieving lower non-revenue water (NRW). As part of a strategy to minimize pipe bursts and physical losses, Suez and Optimatics, a Suez software company, have partnered to develop an integrated approach. The result is a framework that allows Suez operators to identify strategies for pipe renewal and pressure management that minimize OPEX and CAPEX and exploit positive interactions between them, without degrading water network performance.

Despite their key role in the low-carbon transition, cities depend on methods with pressing data availability and quality issues for carbon monitoring. Origins.earth and partners have leveraged cutting-edge data and scientific knowledge to deploy an operational digital solution delivering high-quality climate data in under a month. The solution relies on networks of innovative CO2 monitoring stations, big data, and expert knowledge, and delivers historical and current emissions and associated indicators. We demonstrate the robustness of the technology and its applicability for informing policy decisions in Paris and explore its expansion into other mature markets, with a particular focus on Italy.

We present a colorimetric sensor based on functionalized silver nanoparticles for the detection of metal ions in aqueous solutions. The interaction between the target metal ion and the functionalizing agent triggers the aggregation of these nanoparticles, and the consequent change in optical properties allows the detection/quantification of the analyte. In detail, this work describes the synthesis of AgNPs by a chemical reduction method, and the production of mercaptoundecanoic acid functionalized NPs with different surface densities (multi-, full-, and two partial layers). UV-Vis spectroscopy was used to monitor the functionalization processes, and to investigate the aggregation behavior of each AgNPs@11MUA sensor upon titration with the metal ions of interest, namely Ni2+, Zn2+, Co2+, Cd2+, Mn2+, and Cu2+. The resulting UV-Vis raw data obtained for each layer density were submitted to principal component analysis to dissect the role of the metal ions in NP aggregation and in establishing the sensitivity and selectivity of the AgNPs@11MUA sensor. Interestingly, we observed an increase in sensor sensitivity and selectivity at a lower density of the functionalizing agent on the AgNPs’ surface, which results in characteristic colors of the NP suspension upon titration with each metal ion.

This work pertains to the design of a cantilever-based piezoelectric MEMS device that is capable of generating arbitrary paths of its tip. The conceived device consists of a pair of rigidly coupled piezoelectric bimorph cantilevers, and a theoretical model is developed for the analytical evaluation of the proper voltage distribution to be supplied to the inner and outer electrodes of each piezoelectric actuator, in order to drive the tip along any desired trajectory. Such a device could be appealing in some microsurgical operations, i.e., the unclogging of arteries, endoluminal treatment of obstructive lesions, but also as a 2D micropositioning stage, etc. Theoretical predictions of voltage versus time that allow several pathways such as circles, ellipses, spirals, etc., to be accomplished have been verified with multiphysics FEM simulations and the numerical outcomes seem to corroborate the proposed model.

Due to the ubiquity of environmental micro- and nanoplastics (MNPs), inhalation and ingestion by humans is very likely, but human health effects remain largely unknown. The NLRP3 inflammasome is a key player of the innate immune system and is involved in responses towards foreign particulate matter and the development of chronic intestinal and respiratory inflammatory diseases. We established NLRP3-proficient and -deficient THP-1 cells as an alternative in vitro screening tool to assess the potential of MNPs to activate the NLRP3 inflammasome. By investigating cytokine release (IL-1β and IL-8) and cytotoxicity after treatment with engineered nanomaterials, this in vitro approach was compared to earlier published ex vivo murine bone marrow-derived macrophages and in vivo data. This approach showed a strong correlation with previously published data, verifying that THP-1 cells are a suitable model to investigate NLRP3 inflammasome activation. We then investigated the proinflammatory potential of eight MNPs of different size, shape, and chemical composition. Only amine-modified polystyrene (PS-NH2) acted as a direct NLRP3 activator. However, polyethylene terephthalate (PET), polyacrylonitrile (PAN), and nylon (PA6) induced a significant increase in IL-8 release in NLRP3−/− cells. Our results suggest that most MNPs are not direct activators of the NLRP3 inflammasome, but specific MNP types might still possess pro-inflammatory potential via other pathways.

This work offers a new alternative tool for atherectomy operations, with the purpose of minimizing the risks for the patients and maximizing the number of clinical cases for which the system can be used, thanks to the possibility of scaling its size down to lumen reduced to a few tenths of mm. The development of this microsystem has presented a certain theoretical work during the kinematic synthesis and the design stages. In the first stage a new multi-loop mechanism with a Stephenson’s kinematic chain (KC) was found and then adopted as the so-called pseudo-rigid body mechanism (PRBM). Analytical modeling was necessary to verify the synthesis requirements. In the second stage, the joint replacement method was applied to the PRBM to obtain a corresponding and equivalent compliant mechanism with lumped compliance. The latter presents two loops and six elastic joints and so the evaluation of the microsystem mechanical advantage (MA) had to be calculated by taking into account the accumulation of elastic energy in the elastic joints. Hence, a new closed form expression of the microsystem MA was found with a method that presents some new aspects in the approach. The results obtained with Finite Element Analysis (FEA) were compared to those obtained with the analytical model. Finally, it is worth noting that a microsystem prototype can be fabricated by using MEMS Technology classical methods, while the microsystem packaging could be a further development for the present investigation.

A dynamic model of a Conjugate-Surface Flexure Hinge (CSFH) has been proposed as a component for MEMS/NEMS Technology-based devices with lumped compliance. However, impacts between the conjugate surfaces have not been studied yet and, therefore, this paper attempts to fill this gap by proposing a detailed multibody system (MBS) model that includes not only rigid-body dynamics but also elastic forces, friction, and impacts. Two models based on the Lankarani-Nikravesh constitutive law are first recalled and a new model based on the contact of cylinders is proposed. All three models are complemented by the friction model proposed by Ambrosìo. Then, the non-smooth Moreau time-stepping scheme with Coulomb friction is described. The four models are compared in different scenarios and the results confirm that the proposed model outcomes comply with the most reliable models.

The demand for building materials has been constantly increasing, which leads to excessive energy consumption for their provision. The looming environmental consequences have triggered the search for sustainable alternatives. Mycelium, as a rapidly renewable, low-carbon natural material that can withstand compressive forces and has inherent acoustic and fire-resistance properties, could be a potential solution to this problem. However, due to its low tensile, flexural and shear strength, mycelium is not currently widely used commercially in the construction industry. Therefore, this research focuses on improving the structural performance of mycelium composites for interior use through custom robotic additive manufacturing processes that integrate continuous wood fibers into the mycelial matrix as reinforcement. This creates a novel, 100% bio-based, wood-veneer-reinforced mycelium composite. As base materials, Ganoderma lucidum and hemp hurds for mycelium growth and maple veneer for reinforcement were pre-selected for this study. Compression, pull-out, and three-point bending tests comparing the unreinforced samples to the veneer-reinforced samples were performed, revealing improvements on the bending resistance of the reinforced samples. Additionally, the tensile strength of the reinforcement joints was examined and proved to be stronger than the material itself. The paper presents preliminary experiment results showing the effect of veneer reinforcements on increasing bending resistance, discusses the potential benefits of combining wood veneer and mycelium’s distinct material properties, and highlights methods for the design and production of architectural components.

The role of MR Arterial-Spin-Labeling Cerebral Blood Flow maps (ASL-CBF) in the assessment of pediatric focal epilepsy is still debated. We aim to compare the Seizure Onset Zone (SOZ) detection rate of three methods of evaluation of ASL-CBF: 1) qualitative visual (qCBF), 2) z-score voxel-based quantitative analysis of index of asymmetry (AI-CBF), and 3) z-score voxel-based cluster analysis of the quantitative difference of patient’s CBF from the normative data of an age-matched healthy population (cCBF). Interictal ASL-CBF were acquired in 65 pediatric patients with focal epilepsy: 26 with focal brain lesions and 39 with a normal MRI. All hypoperfusion areas visible in at least 3 contiguous images of qCBF analysis were identified. In the quantitative evaluations, clusters with a significant z-score AI-CBF ≤ −1.64 and areas with a z-score cCBF ≤ −1.64 were considered potentially related to the SOZ. These areas were compared with the SOZ defined by the anatomo-electro-clinical data. In patients with a positive MRI, SOZ was correctly identified in 27% of patients using qCBF, 73% using AI-CBF, and 77% using cCBF. In negative MRI patients, SOZ was identified in 18% of patients using qCBF, in 46% using AI-CBF, and in 64% using cCBF (p < 0.001). Quantitative analyses of ASL-CBF maps increase the detection rate of SOZ compared to the qualitative method, principally in negative MRI patients.

Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive genetic disorder caused by mutations within nibrin (NBN), a DNA damage repair protein. Hallmarks of NBS include chromosomal instability and clinical manifestations such as growth retardation, immunodeficiency, and progressive microcephaly. We employed induced pluripotent stem cell-derived cerebral organoids from two NBS patients to study the etiology of microcephaly. We show that NBS organoids carrying the homozygous 657del5 NBN mutation are significantly smaller with disrupted cyto-architecture. The organoids exhibit premature differentiation, and Neuronatin (NNAT) over-expression. Furthermore, pathways related to DNA damage response and cell cycle are differentially regulated compared to controls. After exposure to bleomycin, NBS organoids undergo delayed p53-mediated DNA damage response and aberrant trans-synaptic signaling, which ultimately leads to neuronal apoptosis. Our data provide insights into how mutations within NBN alters neurogenesis in NBS patients, thus providing a proof of concept that cerebral organoids are a valuable tool for studying DNA damage-related disorders.

Downscaling has been a focal task of Electronics and Electromechanics in the last few decades, and a great engine for technological progress as well. Nevertheless, a scaling operation affects device physics, functioning and performance. The present paper investigates about the impact of scaling on a test case compliant electrostatic micro or nano actuator that is under development with two preferred micro fabrication methods, namely, thick SOI and thin amorphous silicon. A series of numerical trials on materials strength, electro-mechanical characteristics, sensitivity and overall actuation performance have been carried out at different grades of down-scaling and of aspect ratio. This gave rise to new design charts that we propose here as a predictive and friendly guide to select the most appropriate micro fabrication method.

This paper presents the development of a new microgripper actuated by means of rotary-comb drives equipped with two cooperating fingers arrays. The microsystem presents eight CSFH flexures (Conjugate Surface Flexure Hinge) that allow the designer to assign a prescribed motion to the gripping tips. In fact, the adoption of multiple CSFHs gives rise to the possibility of embedding quite a complex mechanical structure and, therefore, increasing the number of design parameters. For the case under study, a double four-bar linkage in a mirroring configuration was adopted. The presented microgripper has been fabricated by using a hard metal mask on a Silicon-on-Insulator (SOI) wafer, subject to DRIE (Deep Reactive Ion Etching) process, with a vapor releasing final stage. Some prototypes have been obtained and then tested in a lab. Finally, the experimental results have been used in order to assess simulation tools that can be used to minimize the amount of expensive equipment in operational environments.

An outbreak was described among the guests of a Long-Term Care Facility in the North of Italy. Among 23 guests, 20 of whom were fully vaccinated with BNT162b2 vaccine, the outbreak led to a final count of 11 positive guests, 9 of whom were vaccinated, and 4 positive healthcare workers, of whom only 1 was vaccinated. Eight of the positive guests (six vaccinated and two unvaccinated) had symptoms that in five cases (three vaccinated and two unvaccinated) led to death. The risk of infection and the risk of death appeared not to be correlated with the health status neither with the serological titer, but only with age.

Molecular autopsy is the process of investigating sudden death through genetic analysis. It is particularly useful in cases where traditional autopsy is negative or only shows non-diagnostic features, i.e., in sudden unexplained deaths (SUDs), which are often due to an underlying inherited arrhythmogenic cardiac disease. The final goal of molecular autopsy in SUD cases is to aid medico-legal inquiries and to guide cascade genetic screening of the victim’s relatives. Early attempts of molecular autopsy relied on Sanger sequencing, which, despite being accurate and easy to use, has a low throughput and can only be employed to analyse a small panel of genes. Conversely, the recent adoption of next-generation sequencing (NGS) technologies has allowed exome/genome wide examination, providing an increase in detection of pathogenic variants and the discovery of newer genotype-phenotype associations. NGS has nonetheless brought new challenges to molecular autopsy, especially regarding the clinical interpretation of the large number of variants of unknown significance detected in each individual.

Silver nanoparticles (AgNPs) can be used as a surface plasmon resonance (SPR) colorimetric sensor; the correlation between the SPR phenomenon and the aggregation state of nanoparticle allows the real-time detection of a target molecule. Surface functionalization of NPs with proper molecular baits is often performed to establish the selectivity of the sensor. This work reports on the synthesis of AgNPs under reducing conditions and on the functionalization thereof with mercaptoundecanoic acid (11-MUA). UV-VIS Spectroscopy confirmed the formation of AgNPs, eliciting a surface plasmon absorption band (SPAB) at 393 nm that shifted to 417 nm upon surface coating. Dynamic light scattering was used to investigate the surface coatings; moreover, pelleted AgNPs@11MUA nanoparticles were characterized by scanning electron microscopy (SEM), energy dispersive X-ray analyzers (EDX), and infrared spectroscopy to corroborate the presence of 11MUA on the surface. Most interestingly, the resulting AgNPs@11MUA selectively detected micromolar levels of Ni2+, also in the presence of other cations such as Mn2+, Co2+, Cd2+, Cu2+, Zn2+, Fe2+, Hg2+, Pb2+, and Cr3+.

The obligatory path towards a lean manufacturing organization requires assessment and monitoring. However, a lean assessment framework is not yet available for the engineer to order (ETO) scenario. This work explored ten lean ETO maturity principles—identified from the literature—that take insight from three formally defined sets (Toyota Way, lean construction, and lean product development principles). A practical assessment model was proposed based on the evaluation of ten lean ETO objective criteria (four with mathematical formulation) and was validated on a real industrial case. A problem-solving tool, including a new lean tool, called the Problem Focus Matrix (PFM), was also presented; this tool was aimed toward development of an integrated framework that would include the organization mission, management, and continuous improvement.

Chemical composition in seawater of marine sediments, as well as the physical properties and chemical composition of soils, influence the phase behavior of natural gas hydrate by disturbing the hydrogen bond network in the water-rich phase before hydrate formation. In this article, some marine sediments samples, collected in National Antarctic Museum in Trieste, were analyzed and properties such as pH, conductivity, salinity, and concentration of main elements of water present in the sediments are reported. The results, obtained by inductively coupled plasma-mass spectrometry (ICP-MS) and ion chromatography (IC) analysis, show that the more abundant cation is sodium and, present in smaller quantities, but not negligible, are calcium, potassium, and magnesium, while the more abundant anion is chloride and sulfate is also appreciable. These results were successively used to determine the thermodynamic parameters and the effect on salinity of water on hydrates’ formation. Then, hydrate formation was experimentally tested using a small-scale apparatus, in the presence of two different porous media: a pure silica sand and a silica-based natural sand, coming from the Mediterranean seafloor. The results proved how the presence of further compounds, rather than silicon, as well as the heterogeneous grainsize and porosity, made this sand a weak thermodynamic and a strong kinetic inhibitor for the hydrate formation process.

Background: Current guidelines on diastolic function (DF) by the American Society of Echocardiography and the European Association of Cardiovascular Imaging (ASE/EACVI) have been disputed and two alternative algorithms have been proposed by Johansen et al. and Oh et al. We sought (a) to assess the concordance of ASE/EACVI guidelines on DF using these proposed alternative approaches and (b) to evaluate the prevalence of indeterminate diastolic dysfunction (DD) by each method, exploring means for reducing their number. Methods: We retrospectively analyzed the echocardiographic reports of 1158 outpatients including subjects at risk of heart failure without (n = 644) or with (n = 241) structural heart disease, and 273 healthy individuals. Concordance was calculated using the k coefficient and overall proportion of DD reclassification rate. The effectiveness of pulmonary vein flow (PVF), Valsalva maneuver, and left atrial volume index/late diastolic a’-ratio (LAVi/a’) over indeterminate grading was assessed. Results: The DD reclassification rate was 30.1% (k = 0.35) for ASE/EACVI and OH, 36.5% (k = 0.27) for ASE/EACVI and JOHANSEN and 31.1% (k = 0.37) for OH and JOHANSEN (p < 0.0001 for all comparisons). DF could not be graded only by ASE/EACVI and OH in 9% and 11% patients, respectively. The majority of patients could be reclassified using PVF or Valsalva maneuver or LAVi/a’, with the latter being the single most effective parameter. Conclusion: Inconsistencies between updated guidelines and independent approaches to assess and grade DF impede their interchangeable clinical use. The inconclusive diagnoses can be reconciled by conventional echocardiography in most patients, and LAVi/a’ emerges as a simple and effective approach to this aim.

Background: This systematic review summarizes the current knowledge on the superimposition of three-dimensional (3D) diagnostic records to realize an orthodontic virtual patient. The aim of this study is to analyze the accuracy of the state-of-the-art digital workflow. Methods: The research was carried out by an electronic and manual query effectuated from ISS (Istituto Superiore di Sanità in Rome) on three different databases (MEDLINE, Cochrane Library and ISI WEB OF SCIENCE) up to 31st January 2020. The search focused on studies that superimposed at least two different 3D records to build up a 3D virtual patient—information about the devices used to acquire 3D data, the software used to match data and the superimposition method applied have been summarized. Results: 1374 titles were retrieved from the electronic search. After title-abstract screening, 65 studies were selected. After full-text analysis, 21 studies were included in the review. Different 3D datasets were used: facial skeleton (FS), extraoral soft tissues (ST) and dentition (DENT). The information provided by the 3D data was superimposed in four different combinations: FS + DENT (13 papers), FS + ST (5 papers), ST + DENT (2 papers) and all the types (FS + ST + DENT) (1 paper). Conclusions: The surface-based method was most frequently used for 3D objects superimposition (11 papers), followed by the point-based method (6 papers), with or without fiducial markers, and the voxel-based method (1 paper). Most of the papers analyzed the accuracy of the superimposition procedure (15 papers), while the remaining were proof-of-principles (10 papers) or compared different methods (3 papers). Further studies should focus on the definition of a gold standard. The patient is going to have a huge advantage from complete digital planning when more information about the spatial relationship of anatomical structures are needed: ectopic, impacted and supernumerary teeth, root resorption and angulations, cleft lip and palate (CL/P), alveolar boundary conditions, periodontally compromised patients, temporary anchorage devices (TADs), maxillary transverse deficiency, airway analyses, obstructive sleep apnea (OSAS), TMJ disorders and orthognathic and cranio-facial surgery.

There remains great interest in understanding the relationship between visual impairment (VI) and autism spectrum disorder (ASD) due to the extraordinarily high prevalence of ASD in blind and visually impaired children. The broad variability across individuals and assessment methodologies have made it difficult to understand whether autistic-like symptoms shown by some children with VI might reflect the influence of the visual deficit, or represent a primary neurodevelopmental condition that occurs independently of the VI itself. In the absence of a valid methodology adapted for the visually impaired population, diagnosis of ASD in children with VI is often based on non-objective clinical impression, with inconclusive prevalence data. In this review, we discuss the current state of knowledge and suggest directions for future research.

This study aimed to assess the environmental footprint of dairy farms rearing a dual-purpose breed, and to evaluate, through alternative scenario analyses, the fattening of calves and the cultivation of hemp as strategies for reducing the environmental impact of these farms. Eleven farms were evaluated for global warming (GWP), acidification (AC) and eutrophication (EUP) potential. The Life Cycle Assessment method with three scenarios, REAL, based on real data, BEEF, where calves were fattened in farm, and HEMP, where hemp was cultivated in farms, were considered. If referred to 1 m2 of utilizable agricultural land, the GWP, AC and EUP were 1.6 kgCO2eq, 21.7 gSO2eq and 7.1 gPO43−eq, respectively. If referring to 1 kg of fat and protein corrected milk, the emissions were 1.1−1.4 kgCO2eq, 14.8−19.0 gSO2eq, and 5.0−6.4 gPO43−eq, depending on the allocation method adopted. The emissions were associated positively with culling rate and negatively with production intensity. In BEEF and HEMP scenarios, the emissions were reduced by 8−11% and by 1−5%, respectively. Fattening the calves, evaluating the cultivation of alternative plants and improving the productive and reproductive efficiency of animals could be effective strategies for reducing the environmental footprint of the farm.

The quantitative assessment of antimicrobial use (AMU) in food-producing animals contributes to the provision of essential information for developing relevant and effective policies to reduce use and to control antimicrobial resistance. Information on AMU is available mainly for intensive dairy farming systems and specialized high-yielding breeds. The aim of this study is to investigate AMU in different dairy farming systems by comparing the treatment incidence in mountain farms with specialized high-yield dairy breeds or with dual-purpose breeds raised for milk production to the treatment incidence in lowland farms with specialized high-yield dairy breeds or with dual-purpose breeds raised for milk production. Significant differences were found only between the overall treatment incidence, as well as the treatment incidence of highest-priority critically important antimicrobials for human medicine, in lowland farms with high-yielding breeds and mountain farms with dual-purpose breeds. Mountain farms have a generally lower milk production and smaller herd size than lowland farms, provide cows with access to pasture, and limit concentrates in the diet. These management practices and the use of local/dual-purpose breeds could reduce the risk of production diseases and the consequent need for AMU.

The opportunity to know the status of a soft tissue (ST) in situ can be very useful for microsurgery or early diagnosis. Since normal and diseased tissues have different mechanical characteristics, many systems have been developed to carry out such measurements locally. Among them, MEMS tweezers are very relevant for their efficiency and relative simplicity compared to the other systems. In this paper a novel piezoelectric MEMS tweezer for soft materials analysis and characterization is presented. A theoretical approach has developed in order to carry out the values of the stiffness, the equivalent Young’s modulus, and the viscous damping coefficients of the analyzed samples. The method has been validated by using both Finite Element Analysis and data from the literature.

Magnetorheological (MR) fluids are capable of manifesting a rheological behaviour change by means of a magnetic field application and can be employed in many complex systems in many technical fields. One successful example is their use in the development of dampers: magnetorheological dampers (MRDs) are widespread in vibration control systems, as well as civil engineering applications (i.e., earthquake or seismic protection), impact absorption and vibration isolation technology in industrial engineering, and advanced prosthetics in biomedical fields. In the past, many studies have been conducted on MRDs modeling and characterization, but they have usually been focused more on the theoretical models than on the experimental issues. In this work, an overview of both of them is proposed. In particular, after an introduction to the physics of the magnetorheological effect, a short review of the main mathematical models of MRDs is proposed. Finally, in the second part of this study an overview of the main issues that occur in MRDs experimental characterization is reported and discussed.

Vibration damping is prominent in engineering; in fact, vibrations are related to many phenomena (e.g., the fatigue of structural elements). The advent of smart materials has significantly increased the number of available solutions in this field. Among smart materials, piezoelectric materials are most promising. However, their efficiency depends on their placement. There are many studies on their optimal placement for damping a particular mode, but few account for multimodal vibrations damping. In a previous work, an analytical method was proposed to find the optimal placement of piezoelectric plates to control the multimode vibrations of a cantilever beam. In this study, the efficiency of the above method has been improved, considering all plates active simultaneously, regardless of the eigenmodes that are excited, and changing, instead of the plates, the potential distribution. The method results indicate the optimal potential distribution for different excited eigenmodes. The results have been compared with those obtained by experimental tests and numerical simulations, exhibiting very good agreement.

GRB 130427A was the most luminous gamma-ray burst detected in the last 30 years. With an isotropic energy output of 8.5 × 10 53 erg and redshift of 0.34, it combined very high energetics with a relative proximity to Earth in an unprecedented way. Sensitive X-ray observatories such as XMM-Newton and Chandra have detected the afterglow of this event for a record-breaking baseline longer than 80 million seconds. The light curve displays a simple power-law over more than three decades in time. In this presentation, we explore the consequences of this result for a few models put forward so far to interpret GRB 130427A, and more in general the implication of this outcome in the context of the standard forward shock model.