Search

The paper describes an analytical and experimental framework which investigates performance of electrically-driven ground vehicles powered by battery packs, with the objective of providing simple indications for preliminary sizing of rovers designed for mission on the surface of extraterrestrial bodies. For this class of missions, power is at a premium, and energy-efficient locomotion is clearly a critical issue. An analytical model for the estimate of cruise distance is derived and mobility performance is thus analyzed as a function of cruise speed, relevant vehicle parameters, soil mechanical properties, and atmospheric data. Results are then validated by numerical simulations and an experimental campaign for an Earth-based rover.

Congenital anomalies may have an increased risk of noncommunicable diseases (NCDs) We performed a clinical exome analysis in an infant affected by “Vertebral, Anorectal, Cardiac, Tracheoesophageal, Genitourinary, and Limb” (VACTERL) malformation association to identify potential biomarkers that may be helpful for preventing malignancy risk or other chronic processes. Among the variants, six variants that may be linked with VACTERL were identified in the exome analysis. The variants c.501G>C on OLR1 and c.-8C>G on PSMA6 were previously associated with myocardial infarction. The variants c.1936A>G on AKAP10 and c.575A>G on PON1 are linked to defects in cardiac conduction and artery disease, respectively. Alterations in metabolism were also suggested by the variants c.860G>A on EPHX2 and c.214C>A on GHRL. In addition, three variants associated with colon cancer were discovered. Specifically, the reported variants were c.723G>A on CCND1 and c.91T>A on AURKA proto-oncogenes as well as c.827A>C in the tumor suppressor PTPRJ. A further inspection identified 15 rare variants carried by cancer genes. Specifically, these mutations are located on five tumor suppressors (SDHA, RB1CC1, PTCH1, DMBT1, BCR) and eight proto-oncogenes (MERTK, CSF1R, MYB, ROS1, PCM1, FGFR2, MYH11, BRCC3) and have an allele frequency lower than 0.01 in the Genome Aggregation Database (GnomAD). We observed that the cardiac and metabolic phenotypic traits are linked with the genotype of the patient. In addition, the risk of developing neoplasia cannot be excluded a priori. Long-term surgical issues of patients with VATER syndrome could benefit from the clinical exome sequencing of a personalized risk assessment for the appearance of further disease in pubertal timing and adult age.

Driving a car requires high cognitive demands, from sustained attention to perception and action planning. Recent research investigated the neural processes reflecting the planning of driving actions, aiming to better understand the factors leading to driving errors and to devise methodologies to anticipate and prevent such errors by monitoring the driver’s cognitive state and intention. While such anticipation was shown for discrete driving actions, such as emergency braking, there is no evidence for robust neural signatures of continuous action planning. This study aims to fill this gap by investigating continuous steering actions during a driving task in a car simulator with multimodal recordings of behavioural and electroencephalography (EEG) signals. System identification is used to assess whether robust neurophysiological signatures emerge before steering actions. Linear decoding models are then used to determine whether such cortical signals can predict continuous steering actions with progressively longer anticipation. Results point to significant EEG signatures of continuous action planning. Such neural signals show consistent dynamics across participants for anticipations up to 1 s, while individual-subject neural activity could reliably decode steering actions and predict future actions for anticipations up to 1.8 s. Finally, we use canonical correlation analysis to attempt disentangling brain and non-brain contributors to the EEG-based decoding. Our results suggest that low-frequency cortical dynamics are involved in the planning of steering actions and that EEG is sensitive to that neural activity. As a result, we propose a framework to investigate anticipatory neural activity in realistic continuous motor tasks.

Obstacle avoidance is a major challenge during independent mobility for blind or visually impaired (BVI) people. Typically, BVI people can only perceive obstacles at a short distance (about 1 m, in case they are using the white cane), and some obstacles are hard to detect (e.g . , those elevated from the ground), or should not be hit by the white cane (e.g . , a standing person). A solution to these problems can be found in recent computer-vision techniques that can run on mobile and wearable devices to detect obstacles at a distance. However, in addition to detecting obstacles, it is also necessary to convey information about them in real time. This contribution presents WatchOut , a sonification technique for conveying real-time information about the main properties of an obstacle to a BVI person, who can then use this additional feedback to safely navigate in the environment. WatchOut was designed with a user-centered approach, involving four iterations of online listening tests with BVI participants in order to define, improve and evaluate the sonification technique, eventually obtaining an almost perfect recognition accuracy. WatchOut was also implemented and tested as a module of a mobile app that detects obstacles using state-of-the-art computer vision technology. Results show that the system is considered usable and can guide the users to avoid more than 85% of the obstacles.

Background: To face the health emergency due to the first spread in Italy of COVID- 19, a nationwide lockdown was instituted from 9 March to 3 May 2020. During this period all the hospital outpatient activities were suspended except for urgent cases. Objective: To evaluate the cardiological urgent outpatient examinations done in our hospital during the lockdown in view of the reduced hospitalizations and the increased cardiovascular deaths observed during the COVID-19 outbreak. Methods: The urgent cardiological examinations (requests with priority U and B, i.e., to be done within 3 and 10 days respectively) performed during the 8-week period of lockdown (38 working days) were compared with those performed during the same period in the previous year (37 working days). During the lockdown and the control period, the availability of urgent cardiological visits was the same (2 per day with priority U and 2 per day with priority B). The number of cardiological examinations performed and the main characteristics of the subjects attending the outpatient clinic in the two periods were evaluated, comparing them with the chi-square test and considering as significant p values

Introduction Chest pain and its clinical manifestations are the most common reasons for presentation to the emergency department (ED). Given that the prevalence of chest pain due to acute myocardial infarction (AMI) in the ED is modest, clinicians should use cardiac troponins to safely and rapidly rule out AMI, avoiding the delayed release of low risk patients. The study aims to develop and validate an algorithm to early rule-out of non-ST elevation myocardial infarction (NSTEMI) in subjects admitted to the ED with symptoms of myocardial infarction. Methods High sensitivity cardiac Troponin T (hs-cTnT) serial measurements (baseline, T0; after 1 h, T1; after 3 h, T3) were used to develop and validate the algorithm, respectively, in 6403 and 773 consecutive admissions suggestive of AMI. Results Patients were classified as having or not having NSTEMI according to clinical assessment, diagnostic imaging, and serial measurements ofhs-cTnT; ROC curve analysis allowed to find changes in consecutive hs-cTnT associated with diagnostic sensitivity close to 100%. Only patients with hs-cTnTat T0 lower than 14 ng/L resultedto be eligible for the safe rule-out of NSTEMI. Conclusions Although some points remain to be improved, the results obtained indicate that algorithms for fast NSTEMI rule-out are feasible and safe.

Aim To examine the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors compared with other antihyperglycaemic agents (AHAs) in large and unselected populations of the Lombardy and Apulia regions in Italy. Materials and methods An observational cohort study of first-time users of GLP-1RAs, SGLT2 inhibitors or other AHAs was conducted from 2010 to 2018. Death and cardiovascular (CV) events were evaluated using conditional Cox models in propensity-score-matched populations. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for each region and in a meta-analysis for pooled risks. Results After propensity-score matching, the Lombardy cohort included 18 716 and 11 683 patients and the Apulia cohort 9772 and 6046 patients for the GLP-1RA and SGLT2 inhibitor groups, respectively. Use of GLP-1RAs was associated with lower rates of death (HR 0.61, CI 0.56-0.65, Lombardy; HR 0.63, CI 0.55-0.71, Apulia), cerebrovascular disease and ischaemic stroke (HR 0.70, CI 0.63-0.79; HR 0.72, CI 0.60-0.87, Lombardy), peripheral vascular disease (HR 0.72, CI 0.64-0.82, Lombardy; HR 0.80, CI 0.67-0.98, Apulia), and lower limb complications (HR 0.67, CI 0.56-0.81, Lombardy; HR 0.69, CI 0.51-0.93, Apulia). Compared with other AHAs, SGLT2 inhibitor use decreased the risk of death (HR 0.47, CI 0.40-0.54, Lombardy; HR 0.43, CI 0.32-0.57, Apulia), cerebrovascular disease (HR 0.75, CI 0.61-0.91, Lombardy; HR 0.72, CI 0.54-0.96, Apulia), and heart failure (HR 0.56, CI 0.46-0.70, Lombardy; HR 0.57, CI 0.42-0.77, Apulia). In the pooled cohorts, a reduction in heart failure was also observed with GLP-1RAs (HR 0.89, 95% CI 0.82-0.97). Serious adverse events were quite low in frequency. Conclusion Our findings from real-world practice confirm the favourable effect of GLP-1RAs and SGLT2 inhibitors on death and CV outcomes across both regions consistently. Thus, these drug classes should be preferentially considered in a broad type 2 diabetes population beyond those with CV disease.

Purpose The “Spedali Civili”, one of the largest hospitals in the Italian region most affected by SARS-CoV-2 infection, is managing a large number of traumatic injuries. The objective of this article is to share our operational protocols to deliver an appropriate hospital trauma care in the context of the COVID-19 pandemic. Methods We changed our work shifts, in consideration of the high number of patients; colleagues from smaller hospitals in the area joined us to increase the number of surgeons available. Thanks to the collaboration between orthopaedists, anaesthesiologists, and nurses, we created a flow chart and separate routes (in the emergency room, in the wards, and in the operating rooms) to optimize patient management. Our protocols allow us to always provide healthcare professionals with the correct personal protective equipment for the task they are performing. Results Our strategies proved to be practical and feasible. Having a well thought plan helped us to provide for the most robust response possible. We have not yet been able to study the effectiveness of our protocols, and our recommendations may not be applicable to all healthcare facilities. Nonetheless, sharing our early experience can help other institutions conducting and adapting such plans more quickly. Conclusions Having a clear strategy during the COVID-19 pandemic kept our systems resilient and effective and allowed us to provide high-quality trauma care. We offer this approach for other institutions to adopt and adapt to their local setting.

AIM Insulin is the preferred treatment for the control of diabetes in hospital, but it raises the risk of hypoglycaemia, often because oral intake of carbohydrates in hospitalized persons is lower than planned. Our aim was to assess the effect on the incidence of hypoglycaemia of giving prandial insulin immediately after a meal depending on the amount of carbohydrate ingested. METHODS A prospective pre-post intervention study in hospitalized persons with diabetes eating meals with stable doses of carbohydrates present in a few fixed foods. Foods were easily identifiable on the tray and contained fixed doses of carbohydrates that were easily quantifiable by nurses as multiples of 10 g (a 'brick'). Prandial insulin was given immediately after meals in proportion to the amount of carbohydrates eaten. RESULTS In 83 of the first 100 people treated with the 'brick diet', the oral carbohydrate intake was lower than planned on at least one occasion (median: 3 times; Q1-Q3: 2-6 times) over a median of 5 days. Compared with the last 100 people treated with standard procedures, postprandial insulin given on the basis of ingested carbohydrate significantly reduced the incidence of hypoglycaemic events per day, from 0.11 ± 0.03 to 0.04 ± 0.02 (P

Purpose: Recently, altered visual cortical processes i.e., lack of habituation to visual evoked potentials (VEP), has been highlighted in both photosensitive epilepsy and in a specific i.e., analytic mode of processing visual inputs. In this study we aimed at evaluating the relationship between photosensitivity (PS) and analytic style of processing visual information, in a sample of 30 patients with Idiopathic Generalized Epilepsy (IGE) and matched healthy controls. Methods: At our Epilepsy unit of the Sapienza University of Rome, we consecutively enrolled 15 patients with IGE with PSand matched them with 15 patients with IGE without PS and 15 Healthy Volunteers. All patients underwent EEG recording in basal conditions during hyperventilation (3 Min), and intermittent light stimulation. The most effective frequencies comprised from 12 to 16 Hz. The instruments used to gather psychological cognitive behavioral data, consisted of participation in two tests: the Sternberg-Wagner Self-Assessment Inventory and the Mariani Learning Style Questionnaire. Results: Compared to controls, both IGE groups show significantly higher scores for the analytic style (One-way ANOVA, F(2,44) = 110.3, p < 0.0001). Epilepsy groups thereby showed very distinctive cognitive styles as measured with the Sternberg test. In the visual style, scores of the photosensitive Individuals with IGE were significantly higher than the non-photosensitive individuals with IGE (p < 0.0001, Tukey's post hoc test). Conclusions: An association between analytic style of processing visual information and PS in IGE has been shown. The common neurophysiological features between these two factors, suggest the possibility to evaluate this cognitive behavior as a potential target for nonpharmacological therapeutic strategies in photosensitive epilepsy.

Objective: To create the first structured surgical report form for NBL with international consensus, to permit standardized documentation of all NBL-related surgical procedures and their outcomes. Summary of Background Data: NBL, the most common extracranial solid malignant tumor in children, covers a wide spectrum of tumors with significant differences in anatomical localization, organ or vessel involvement, and tumor biology. Complete surgical resection of the primary tumor is an important part of NBL treatment, but maybe hazardous, prone to complications and its role in high-risk disease remains debated. Various surgical guidelines exist within the protocols of the different cooperative groups, although there is no standardized operative report form to document the surgical treatment of NBL. Methods: After analyzing the treatment protocols of the SIOP Europe International Neuroblastoma Study Group, Children's Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie – German Association of Pediatric Oncology and Haematology pediatric cooperative groups, important variables were defined to completely describe surgical biopsy and resection of NBL and their outcomes. All variables were discussed within the Surgical Committees of SIOP Europe International Neuroblastoma Study Group, Children's Oncology Group, and Gesellschaft fuer Paediatrische Onkologie und Haematologie – German Association of Pediatric Oncology and Haematology. Thereafter, joint meetings were organized to obtain intercontinental consensus. Results: The “International Neuroblastoma Surgical Report Form” provides a structured reporting tool for all NBL surgery, in every anatomical region, documenting all Image Defined Risk Factors and structures involved, with obligatory reporting of intraoperative and 30 day-postoperative complications. Conclusion: The International Neuroblastoma Surgical Report Form is the first universal form for the structured and uniform reporting of NBL-related surgical procedures and their outcomes, aiming to facilitate the postoperative communication, treatment planning and analysis of surgical treatment of NBL.

Ensuring proper dosage of treatment and repetition over time is a major challenge in neurorehabilitation. However, a requirement of physical distancing to date compromises their achievement. While mostly associated to COVID-19, physical distancing is not only required in a pandemic scenario, but also advised for several clinical conditions (e.g. immunocompromised individuals) or forced for specific social contexts (e.g. people living in remote areas worldwide). All these contexts advocate for the implementation of alternative healthcare models. The objective of this perspective is to highlight the benefits of remote administration of rehabilitative treatment, namely telerehabilitation, in counteracting physical distancing barriers in neurorehabilitation. Sustaining boosters of treatment outcome, such as compliance, sustainability, as well as motivation, telerehabilitation may adapt to multiple neurological conditions, with the further advantage of a high potential for individualization to patient’s or pathology’s specificities. The effectiveness of telerehabilitation can be potentiated by several technologies available to date: virtual reality can recreate realistic environments in which patients may bodily operate, wearable sensors allow to quantitatively monitor the patient’s performance, and signal processing may contribute to the prediction of long-term dynamics of patient recovery. Telerehabilitation might spark its advantages far beyond the mere limitation of physical distancing effects, mitigating criticalities of daily neurorehabilitative practice, and thus paving the way to the envision of mixed models of care, where hospital-based procedures are complementarily integrated with telerehabilitative ones. Supplementary Information The online version contains supplementary material available at 10.1007/s00415-021-10397-w.

BACKGROUND AND OBJECTIVEAction observation can sustain motor skill improvement. At the neurophysiological level, action observation affects the excitability of the motor cortices, as measured by transcranial magnetic stimulation. However, whether the cortical modulations induced by action observation may explain the amount of motor improvement driven by action observation training (AOT) remains to be addressed.METHODSWe conducted a two-phase study involving 40 volunteers. First, we assessed the effect of action observation on corticospinal excitability (amplitude of motor evoked potentials), short-interval intracortical inhibition, and transcallosal inhibition (ipsilateral silent period). Subsequently, a randomized-controlled design was applied, with AOT participants asked to observe and then execute, as quickly as possible, a right-hand dexterity task six consecutive times, whereas controls had to observe a no-action video before performing the same task.RESULTSAOT participants showed greater performance improvement relative to controls. The amount of improvement in the AOT group was predicted by the amplitude of corticospinal modulation during action observation and even more by the amount of intracortical inhibition induced by action observation. Importantly, these relations were found specifically for the AOT group and not for the controls.CONCLUSIONSIn this study, we identified the neurophysiological signatures associated with, and potentially sustaining, the outcome of AOT. Intracortical inhibition driven by action observation plays a major role. These findings elucidate the cortical mechanisms underlying AOT efficacy and open to predictive assessments for the identification of potential responders to AOT, informing the rehabilitative treatment individualization.

The Extreme-Energy Events (EEE) Experiment is a cosmic ray observatory based on a network of detecting stations distributed over the Italian territory and at CERN. A station of the network, called “telescope”, consists of three superimposed Multi-gap Resistive Plate Chambers (MRPCs), each one covering a surface of about 1.5 $m^2$, used with the same technology as the time-of-flight detector of the ALICE experiment at CERN-LHC. Data are collected and sent in real time to the INFN-CNAF computer center for reconstruction and analysis. The large area covered by the network, ranging from Southern Italy up to the CERN laboratories, was achieved with the decision to install the detectors inside high schools, involving students and teachers in a modern experiment within a unique program. This very coexistence of scientific activity and outreach represents the uniqueness of the EEE Project. % The outreach programme is articulated in several initiatives, each encoding the different aspects of the research activity normally expected in a high-energy physics experiment. Students are involved in detector construction at CERN, installation in school, and in the commissioning of the station when data taking starts. Once the detector reaches a steady working regime, students are requested to monitor on a daily basis the performance of the telescope and report any failure. In parallel to the hardware-related operations, students learn how to perform the analysis of EEE data under the supervision of their teachers and of the EEE researchers, supporting the scientific output of the experiment. Every month students report progress and issues in a dedicated online meeting open to all schools and to the EEE researchers. Beside this monthly appointment, in the pre-COVID era an in-person meeting was taking place twice per year, hosted by the \textit{Ettore Majorana Foundation and Centre for Scientific Culture} in Erice or by a school or institution involved in the project. During a three-day, students attend masterclasses and take part in measurement campaigns, disseminating their results by submitting contributions to important outreach-oriented journals (such as the Italian \textit{Giornale di Fisica}).

Spacecraft attitude stabilization based on active magnetic actuators represents a challenging problem, since the available control torque is constrained on a plane orthogonal to the direction of the local geomagnetic field, making the system instantaneously underactuated. A novel magnetic controller is proposed, driving a satellite flying on a Low-Earth-Orbit to three-axis stabilization on a prescribed attitude in the Nadir-pointing orbit frame. A proof of stability is provided for an idealized configuration (axisymmetric spacecraft with no disturbances). Robustness of the control technique against environmental disturbances, parameter uncertainties, corrupted measurements, and other control implementation issues is then demonstrated by numerical simulations, where the effect of magnetic residual dipoles is mitigated by online estimation.

Due to their efficiency, tracking capabilities and long-term operational conditions, Multigap Resistive Plate Chambers (MRPC) may be used in a stable location in coincidence with additional detectors fixed to other parts of a civil building, to detect relative displacements of different parts of the building due to long term deformations of the structure. In this contribution we report the results of two different measurements carried out in the Department of Physics and Astronomy of the University of Catania (with three floors above the ground and an underground basement), using one of the MRPC telescopes of the Extreme Energy Events project, in coincidence with two scintillator-based muon telescopes located in various positions inside the building. Experimental results obtained by these measurements campaigns over a period of about three months are reported, together with a discussion about the performance of the technique. The sensitivity of the method is also discussed by means of Monte Carlo simulations.

Purpose To clarify the role of primary tumor resection in stage 4S neuroblastoma. Methods We investigated a cohort of 172 infants diagnosed with stage 4S neuroblastoma between 1994 and 2013. Of 160 evaluable patients, 62 underwent upfront resection of the primary tumor and 98 did not. Results Five-year progression-free and overall survival were significantly better in those who had undergone upfront surgery (83.6% vs 64.2% and 96.8% vs 85.7%, respectively). One post-operative death and four non-fatal complications occurred in the resection group. Three patients who had not undergone resection died of chemotherapy-related toxicity. Thirteen patients underwent late surgery to remove a residual tumor, without complications: all but one alive. Outcomes were better in patients diagnosed from 2000 onwards. Conclusion Infants diagnosed with stage 4S neuroblastoma who underwent upfront tumor resection had a better outcome. However, this result cannot be definitely attributed to surgery, since these patients were selected on the basis of their favorable presenting features. Although the question of whether to operate or not at disease onset is still unsolved, this study confirms the importance of obtaining enough adequate tumor tissue to enable histological and biological studies to properly address treatment, to achieve the best possible outcome.

We present a novel methodology for the automated resource analysis of non-deterministic, probabilistic imperative programs, which gives rise to a modular approach . Program fragments are analysed in full independence. Moreover, the established results allow us to incorporate sampling from dynamic distributions , making our analysis applicable to a wider class of examples, for example the Coupon Collector’s problem . We have implemented our contributions in the tool , exploiting a constraint-solver over iterative refineable cost functions facilitated by off-the-shelf SMT solvers. We provide ample experimental evidence of the prototype’s algorithmic power. Our experiments show that our tool runs typically at least one order of magnitude faster than comparable tools. On more involved examples, it may even be the case that execution times of seconds become milliseconds. At the same time we retain the precision of existing tools. The extensions in applicability and the greater efficiency of our prototype, yield scalability of sorts. This effects into a wider class of examples, whose expected cost analysis can be thus be performed fully automatically.

Deidentifying MRIs constitutes an imperative challenge, as it aims at precluding the possibility of re‐identification of a research subject or patient, but at the same time it should preserve as much geometrical information as possible, in order to maximize data reusability and to facilitate interoperability. Although several deidentification methods exist, no comprehensive and comparative evaluation of deidentification performance has been carried out across them. Moreover, the possible ways these methods can compromise subsequent analysis has not been exhaustively tested. To tackle these issues, we developed AnonyMI, a novel MRI deidentification method, implemented as a user‐friendly 3D Slicer plugin‐in, which aims at providing a balance between identity protection and geometrical preservation. To test these features, we performed two series of analyses on which we compared AnonyMI to other two state‐of‐the‐art methods, to evaluate, at the same time, how efficient they are at deidentifying MRIs and how much they affect subsequent analyses, with particular emphasis on source localization procedures. Our results show that all three methods significantly reduce the re‐identification risk but AnonyMI provides the best geometrical conservation. Notably, it also offers several technical advantages such as a user‐friendly interface, multiple input–output capabilities, the possibility of being tailored to specific needs, batch processing and efficient visualization for quality assurance., In this article we present a novel MRI de‐identification method and perform a comparison of its performance with respect to other two state‐of‐the‐art methods. We show that our method performs similarly in terms of de‐identification but better preserves the geometrical properties of the images. It is open‐source and also includes an easy to use graphical user interface.

The inflammatory response plays a central role in the complications of congenital pulmonary airway malformations (CPAM) and severe coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the transcriptional changes induced by SARS-CoV-2 exposure in pediatric MSCs derived from pediatric lung (MSCs-lung) and CPAM tissues (MSCs-CPAM) in order to elucidate potential pathways involved in SARS-CoV-2 infection in a condition of exacerbated inflammatory response. MSCs-lung and MSCs-CPAM do not express angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TRMPSS2). SARS-CoV-2 appears to be unable to replicate in MSCs-CPAM and MSCs-lung. MSCs-lung and MSCs-CPAM maintained the expression of stemness markers MSCs-lung show an inflammatory response (IL6, IL1B, CXCL8, and CXCL10), and the activation of Notch3 non-canonical pathway, this route appears silent in MSCs-CPAM, and cytokine genes expression is reduced. Decreased value of p21 in MSCs-lung suggested no cell cycle block, and cells did not undergo apoptosis. MSCs-lung appears to increase genes associated with immunomodulatory function but could contribute to inflammation, while MSCs-CPAM keeps stable or reduce the immunomodulatory receptors expression, but they also reduce their cytokines expression. These data indicated that, independently from their perilesional or cystic origin, the MSCs populations already present in a patient affected with CPAM are not permissive for SARS-CoV-2 entry, and they will not spread the disease in case of infection. Moreover, these MSCs will not undergo apoptosis when they come in contact with SARS-CoV-2, on the contrary, they maintain their staminality profile.

This paper presents a novel approach to support rehabilitation employing Action Observation Therapy (AOT), mixed reality (MR) and wearable technologies to foster common rehabilitative methods in restoring motor function. Here, the platform was specifically designed to support the standard physical treatments in post-stroke patients during upper limb rehabilitation. The proposed platform integrates 3D stereo view of egocentric AOT stimuli, multi-level exergaming in MR and motion tracking. This solution represents a practical method for both in/outpatients and at-home rehabilitation programs. A feasibility study on sub-acute post-stroke patients was performed and preliminary findings suggested the effectiveness of this integrated approach.

Background Mesenchymal stromal cell (MSC)-mediated therapeutic effects have been observed in the treatment of lung diseases. For the first time, this treatment was used as rescue therapy in a pediatric patient with a life-threatening respiratory syndrome associated with the filamin A (FLNA) gene mutation. Methods A child with a new pathogenic variant of the FLNA gene c.7391_7403del (p.Val2464AlafsTer5), at the age of 18 months, due to serious and irreversible chronic respiratory failure, was treated with repeated intravenous infusions of allogeneic bone marrow (BM)-MSCs. The child's respiratory condition was monitored. Immunologic studies before each MSC treatment were performed. Results No acute adverse events related to the MSC infusions were observed. After the second infusion, the child's respiratory condition progressively improved, with reduced necessity for mechanical ventilation support. A thorax computed tomography (CT) scan showed bilateral recovery of the basal parenchyma, anatomical-functional alignment and aerial penetration improvement. After the first MSC administration, an increase in Th17 and FoxP3+ T percentages in the peripheral blood was observed. After the second MSC infusion, a significant rise in the Treg/Th17 ratio was noted, as well as an increased percentage of CD20+ /CD19+ B lymphocytes and augmented PHA-induced proliferation. Discussion MSC infusions are a promising therapeutic modality for patients in respiratory failure, as observed in this pediatric patient with an FLNA mutation. MSCs may have an immunomodulatory effect and thus mitigate lung injury; although in this case, MSC antimicrobial effects may have synergistically impacted the clinical improvements. Further investigations are planned to establish the safety and efficacy of this treatment option for interstitial lung diseases in children.

The authors describe a newborn diagnosed with localized neuroblastoma that evolved to stage 4s at the age of 5 months. Peculiar features of the case included a bilateral adrenal primary, the skin as the only metastatic site, and the development of a muscular lesion late in the clinical course. The patient underwent left adrenalectomy and all other lesions regressed without further therapy. The case prompted a search for similar cases both in the Italian Neuroblastoma Registry and in the literature. All patients identified, although variously treated, survived with the exception of the 2 with MYCN gene amplification. We conclude that infants with neuroblastoma who undergo a transition from a localized to stage 4s disease could be less rare than expected. In the absence of unfavorable biology, a wait-and-see policy with strict follow-up could be adopted for these patients, avoiding potentially damaging systemic therapy.

Electrical source imaging (ESI) aims at reconstructing the electrical brain activity from measurements of the electric field on the scalp. Even though the localization of single focal sources should be relatively straightforward, different methods provide diverse solutions due to the different underlying assumptions. Furthermore, their input parameter(s) further affects the solution provided by each method, making localization even more challenging. In addition, validations and comparisons are typically performed either on synthetic data or through post-operative outcomes, in both cases with considerable limitations.We use an in-vivo high-density EEG dataset recorded during intracranial single pulse electrical stimulation, in which the true sources are substantially dipolar and their locations are known. We compare ten different ESI methods under multiple choices of input parameters, to assess the accuracy of the best reconstruction, as well as the impact of the parameters on the localization performance.Best reconstructions often fall within 1 cm from the true source, with more accurate methods outperforming less accurate ones by 1 cm, on average. Expectedly, dipolar methods tend to outperform distributed methods. Sensitivity to input parameters varies widely between methods. Depth weighting played no role for three out of six methods implementing it. In terms of regularization parameters, for several distributed methods SNR=1 unexpectedly turned out to be the best choice among the tested ones.Our data show similar levels of accuracy of ESI techniques when applied to “conventional” (32 channels) and dense (64, 128, 256 channels) EEG recordings.Overall findings reinforce the importance that ESI may have in the clinical context, especially when applied to identify the surgical target in potential candidates for epilepsy surgery.

Hirschsprung disease (HSCR) is a congenital anomaly of the enteric nervous system. Abnormal microbiome composition was reported in HSCR patients. In this study, we addressed and analyzed microbiome modifications with relation tosurgery and HSCR associated enterocolitis (HAEC). The faecal microbiome of 31 HSCR patients (overall 64 samples) was analyzed. HAEC was diagnosed and classified according to a combination of Pastor’s and Elhalabi’s criteria. Stool samples were analyzed by 16S sequencing (7 out of 9 polymorphic regions). Compositional and relative abundance profiles, as well as the functional potentials of the microbial community, were analyzed with the marker gene sequencing profiles using PICRUSt. The relative abundance of Bacteroidetes showed a severe decrease with slow recovery after surgery. Conversely, Proteobacteria transiently increased their abundance. Noteworthy, a strong linkage has been found between Proteobacteria descendants and HAEC occurrences. The inferred functional analysis indicated that virulence factors and fimbriae or pili might be associated with HAEC. Our study, addressing microbiome dynamics, demonstrated relevant changes after surgical manipulation. Alpha-diversity analyses indicated that surgery deeply affects microbiome composition. Proteobacteria and Enterobacteriaceae seem to play a pivotal role in HAEC occurrences. Several virulence factors, such as fimbriae or pili, might explain the HAEC-predisposing potential of selected microbiomes. These results suggest some innovative therapeutic approaches that deserve to be tested in appropriate clinical trials.

The explanation for cancer recurrence still remains to be fully elucidated. Moreover, tumor dormancy, which is a process whereby cells enter reversible G0 cell cycle arrest, appears to be a critical step in this phenomenon. We evaluated the cell cycle proliferation pattern in pediatric tumor-derived mesenchymal stromal cells (MSCs), in order to provide a better understanding of the complex mechanisms underlying cancer dormancy. Specimens were obtained from 14 pediatric patients diagnosed with solid tumors and submitted to surgery. Morphology, phenotype, differentiation, immunological capacity, and proliferative growth of tumor MSCs were studied. Flow cytometric analysis was performed to evaluate the cell percentage of each cell cycle phase. Healthy donor bone marrow-derived mesenchymal stromal cells (BM-MSCs) were employed as controls. It was noted that the DNA profile of proliferating BM-MSC was different from that of tumor MSCs. All BM-MSCs expressed the typical DNA profile of proliferating cells, while in all tumor MSC samples, ≥70% of the cells were detected in the G0/G1 phase. In particular, seven tumor MSC samples displayed intermediate cell cycle behavior, and the other seven tumor MSC samples exhibited a slow cell cycle. The increased number of tumor MSCs in the G0–G1 phase compared with BM-MSCs supports a role for quiescent MSCs in tumor dormancy regulation. Understanding the mechanisms that promote dormant cell cycle arrest is essential in identifying predictive markers of recurrence and to promote a dedicated surgical planning.

The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR4.0) and 17% (MR4.5) of patients at 2 years; 58% of the enrolled patients achieved a MR4.0 at least once, with a sustained MR4.0 in 52% of them. With a median observation of 29 months (range 24–37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391).

Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, accounting for approximately 15% of all cancer-related deaths in the pediatric population. The overall survival of children with high-risk disease is around 40–50% despite the aggressive treatment protocols. In accordance with the most recent guidelines, a complete classification of the primary tumor, including its histopathological and molecular analysis, is necessary. In this regard, the biopsy of the primary tumor is an important diagnostic procedure adopted not only to confirm the diagnosis but also for staging and risk stratification of the disease. In this study, the authors describe their unicentric experience with four different approaches adopted for sampling NB tumors: (i) the open incisional biopsy, (ii) the minimally invasive thoracoscopic/laparoscopic incisional biopsy, (iii) the ultrasound-guided core needle biopsy, (iv) the laparoscopic-assisted core needle biopsy. The benefits of each technique are analyzed along with their contraindications.

In the last few decades, obesity has increased dramatically in pediatric patients. Obesity is a chronic disease correlated with systemic inflammation, characterized by the presence of CD4 and CD8 T cell infiltration and modified immune response, which contributes to the development of obesity related diseases and metabolic disorders, including impaired glucose metabolism. In particular, Treg and Th17 cells are dynamically balanced under healthy conditions, but imbalance occurs in inflammatory and pathological states, such as obesity. Some studies demonstrated that peripheral Treg and Th17 cells exhibit increased imbalance with worsening of glucose metabolic dysfunction, already in children with obesity. In this review, we considered the role of adipose tissue immunomodulation and the potential role played by Treg/T17 imbalance on the impaired glucose metabolism in pediatric obesity. In the patient care, immune monitoring could play an important role to define preventive strategies of pediatric metabolic disease treatments.

The purpose of this paper is the design and the performance analysis of a control technique that allows simultaneous attitude control and angular momentum management for a Low Earth Orbit satellite equipped with a set of three magnetic actuators and three reaction wheels. A Proof of global asymptotic stability is derived for a control law driving a rigid spacecraft towards a prescribed, yet generic attitude fixed in the orbit frame. An analytical technique allowing for control gain selection is also proposed, which provides optimal convergence performance for the proposed controller, as demonstrated by means of Monte Carlo simulations. Robustness to external disturbances is finally evaluated within a realistic implementation scenario.

This paper introduces a new methodology for the complexity analysis of higher-order functional programs, which is based on three ingredients: a powerful type system for size analysis and a sound type inference procedure for it, a ticking monadic transformation and constraint solving. Noticeably, the presented methodology can be fully automated, and is able to analyse a series of examples which cannot be handled by most competitor methodologies. This is possible due to various key ingredients, and in particular an abstract index language and index polymorphism at higher ranks. A prototype implementation is available.

Introduction The association between congenital pulmonary airway malformations (CPAM) and malignancy is reported in the literature. Interactions between the tumor, immune, and mesenchymal stromal/stem cells (MSCs) have been recognized as crucial for understanding tumorigenesis. We characterized MSCs isolated from CPAM lesions in order to define potential malignancy risks. Methods CPAM II pulmonary tissue was used for MSC expansion; a “healthy” lung section from the same child was used as a comparator. Morphology, immunophenotype, differentiation and immunological capacity, proliferative growth, gene signature telomerase activity, and in vivo tumorigenicity in nude mice were evaluated. Results MSCs were successfully isolated and propagated from CPAM tissue. CPAM-MSCs presented the typical MSC morphology and phenotype, while exhibiting high proliferative capacity, reaching confluence at a median time of 5 days as well as differentiation capabilities. CPAM-MSCs at early passages were not neoplastic and chromosomally normal, even though unbalanced chromosomal rearrangements were noted by molecular karyotype. Conclusions CPAM-MSCs exhibited specific features similar to tumor derived MSCs. Whilst there was no evidence of malignant transformation in the cystic tissue, our results provide evidence that this abnormal tissue has malignant potential. MSCs are considered important players in the tumor microenvironment and they have been closely linked to regulation of tumor survival, growth, and progression. Thus, early lesion resection also in asymptomatic patients might be indicated to exclude that the microenvironment may be potentially permissive to cancer development.

Due to their penetration capability, cosmic muons may provide a way to monitor the alignment and possible long term deformations of large structures, such as historical or other civil buildings. The basic idea behind this possibility is to look for any misalignment between position-sensitive detectors, fixed to different parts of the structure, relative to the original alignment condition. In this paper we discuss the possibility of employing Multigap Resistive Plate Chambers (MRPC) as tracking devices, operating them in coincidence with additional detectors without tracking capability. One of the MRPC telescopes (size 158× 82 cm2) of the Extreme Energy Events (EEE) project, installed in the underground floor at the Department of Physics and Astronomy in Catania, was used together with a 40× 60 cm2 scintillator-based detector, located at about 16 m vertical distance, on the third floor of the same building. Coincidence measurements were carried out over a period of about two months by shifting the position of the smaller detector, to mimic the movement of the structure. Plans for future studies with different detectors and under different geometrical configurations are also discussed.

The Extreme Energy Events (EEE) Project employs Multi-gap Resistive Plate Chamber (MRPC) for studying the secondary cosmic ray muons in Extensive Air Showers. The array consists of about 60 tracking detectors, sparse on Italian territory and at CERN. The MRPCs are flowed with a gas mixture based on $C_2H_2F_4$ and $SF_6$, both of which are fluorinated greenhouse gases with a high environmental impact on the atmosphere. Due to the restrictions imposed by the European Union, these gases are being phased out of production and their cost is largely increasing. The EEE Collaboration started a campaign to reduce the gas emission from its array with the aim of containing costs and decreasing the experiment global warming impact. One method is to reduce the gas rate in each EEE detector. Another is to develop a gas recirculation system, whose a first prototype has been installed at one of the EEE stations located at CERN. Jointly a parallel strategy is focused on searching for environmental friendly gas mixtures which are able to substitute the standard mixture without affecting the MRPC performance. An overview and first results are presented here., Comment: 11 pages, 9 figures

The Extreme Energy Events (EEE) Project is mainly devoted to the study of the secondary cosmic ray radiation by using muon tracker telescopes made of three Multigap Resistive Plate Chambers (MRPC) each. The experiment consists of a telescope network mainly distributed across Italy, hosted in different building structures pertaining to high schools, universities and research centers. Therefore, the possibility to take into account the effects of these structures on collected data is important for the large physics programme of the project. A simulation tool, based on GEANT4 and using GEMC framework, has been implemented to take into account the muon interaction with EEE telescopes and to estimate the effects on data of the structures surrounding the experimental apparata.A dedicated event generator producing realistic muon distributions, detailed geometry and microscopic behavior of MRPCs have been included to produce experimental-like data. The comparison between simulated and experimental data, and the estimation of detector resolutions is here presented and discussed.

The Extreme Energy Events (EEE) Project is an experiment aimed at the detection of secondary cosmic ray muons. It consists of a sparse array of about 60 telescopes, based on Multigap Resistive Plate Chambers (MRPCs), mostly distributed throughout the Italian territory, mainly in high schools locations, and at CERN. The telescopes are now operational and taking data since more than ten years with a high duty cycle and detection efficiency. The analysis activity is currently in progress and focused on several items, including the detailed study of the muon ux under dfferent conditions, its connection with atmospheric and solar events, the detection of extensive air showers and the search for long distance correlations between different extensive air showers. In this paper an overall description of the experiment will be given, together with its educational fallout. The operation of the whole array is also discussed by showing the most recent results obtained from the analysis of the collected data.

Background: Vagal nerve stimulation (VNS) is an effective palliative therapy in drug-resistant epileptic patients and is also approved as a therapy for treatment-resistant depression. Depression is a frequent comorbidity in epilepsy and it affects the quality of life of patients more than the seizure frequency itself. The aim of this systematic review is to analyze the available literature about the VNS effect on depressive symptoms in epileptic patients. Material and methods: A comprehensive search of PubMed, Medline, Scopus, and Google Scholar was performed, and results were included up to January 2020. All studies concerning depressive symptom assessment in epileptic patients treated with VNS were included. Results: Nine studies were included because they fulfilled inclusion criteria. Six out of nine papers reported a positive effect of VNS on depressive symptoms. Eight out of nine studies did not find any correlation between seizure reduction and depressive symptom amelioration, as induced by VNS. Clinical scales for depression, drug regimens, and age of patients were broadly different among the examined studies. Conclusions: Reviewed studies strongly suggest that VNS ameliorates depressive symptoms in drug-resistant epileptic patients and that the VNS effect on depression is uncorrelated to seizure response. However, more rigorous studies addressing this issue are encouraged.

Planning and executing missions in terms of trajectory generation are challenging problems in the operational phase of unmanned aerial vehicles (UAVs) lifecycle. The growing adoption of UAVs in several civil applications requires the definition of precise procedures and tools to safely manage UAV missions that may involve flight over populated areas. The paper aims at providing a contribution toward the definition of a reliable environment, called FLIP (flight planner) for route planning and risk evaluation in the framework of mini- and micro-UAV missions over populated areas. The environment represents a decision support system (DSS) for UAV operators and other decision makers, like airports authorities and aviation agencies. A new ICT tool integrating an innovative procedure for evaluating the risk related to the use of UAV over populated areas is proposed.

Significance In several clinical conditions, especially those related to orthopedic trauma or specific injuries of the peripheral nervous system, patients may experience a period of limb nonuse that has detrimental cascade effects on corticomotor organization and ultimately, on motor performance. During limb nonuse, treatments based on action observation may be suitable for stimulating the motor system via the mirror mechanism. Using short-term immobilization in healthy volunteers, our study showed that administering action observation during immobilization limits the movement alterations induced by limb nonuse. Given action observation’s protective role against the decline of motor performance, it represents a valid tool for early interventions during limb nonuse, thus reducing the burden of further motor rehabilitation., There is rich clinical evidence that observing normally executed actions promotes the recovery of the corresponding action execution in patients with motor deficits. In this study, we assessed the ability of action observation to prevent the decay of healthy individuals’ motor abilities following upper-limb immobilization. To this end, upper-limb kinematics was recorded in healthy participants while they performed three reach-to-grasp movements before immobilization and the same movements after 16 h of immobilization. The participants were subdivided into two groups; the experimental group observed, during the immobilization, the same reach-to-grasp movements they had performed before immobilization, whereas the control group observed natural scenarios. After bandage removal, motor impairment in performing reach-to-grasp movements was milder in the experimental group. These findings support the hypothesis that action observation, via the mirror mechanism, plays a protective role against the decline of motor performance induced by limb nonuse. From this perspective, action observation therapy is a promising tool for anticipating rehabilitation onset in clinical conditions involving limb nonuse, thus reducing the burden of further rehabilitation.

Pediatric thoracic tumors are a heterogeneous group of neoplasms, accounting for 15–20% of all malignant tumors in childhood. Primary and metastatic thoracic tumors are classified according to where they originate, i.e., the lung parenchyma, the airways, the mediastinum, and the chest wall. The vast majority of pediatric thoracic tumors arise from the mediastinum, either posterior or anterior compartments. The imaging evaluation of these children is initially directed by clinical presentation and usually begins with a chest radiograph. Further imaging with CT, MRI, or rarely ultrasonography may be performed to better detect, localize, or characterize the lesion(s). These diseases require a complex approach in which a combination of chemotherapy, radiotherapy, and surgery play a fundamental role. Treatment efforts are directed toward improving quality of life through reduced surgery-related morbidity. A minimally invasive approach offers, whenever possible, proved advantages leading to an earlier transition to postoperative adjuvant therapy. A thorough patient-specific discussion evaluating pros and cons should address the most appropriate surgical strategy and approach. The complexity of a multidisciplinary approach requires specialized centers, where all the professional figures needed are trained and experienced to guarantee the best possible treatment for these little patients.

Hirschsprung’s disease (HSCR), anorectal malformations (ARM), and inflammatory bowel diseases (IBD) are the main paediatric colorectal diseases treated with minimally invasive surgery (MIS). The authors describe their experience and track the historical evolution of MIS in these entities. A non-systematic review is performed to determine the incidence and type of complications reported to date. The literature research was performed using PubMed database. The personal series included all patients with HSCR, ARM, or IBD who underwent MIS from 2006 to 2018. Demographic data, type of surgical procedure, complications and long-term outcomes were analysed. The literature research showed an increasing use of MIS for HSCR over the years, with less post-operative pain, shorter hospital stay, and improved cosmesis compared to open surgery; without differences in complication rates and outcomes. Only high ARMs are considered for managment by MIS; with laparoscopy, however being a risk factor for the development of a remnant of the original fistula (ROOF) and rectal mucosal prolapse. MIS procedures have shown excellent results in adults affected by IBD, whereas only a few studies have been published on paediatric patients. We have performed 269 laparoscopic colorectal procedures; half of them for HSCR with 3 major complications (2.3%). Twenty-one laparoscopic procedures for ARM were associated with 1 anastomotic stricture and 1 ROOF. One hundred and fourteen laparoscopic procedures were performed for IBD, with 13.1% complication. Minimally invasive surgery provides similar results when compared to total trans-anal approach and open surgery in HSCR. Similarly, its use in ARM and IBD seems to be safe and beneficial, provided that selected cases are performed by highly experienced surgeons.

Recent developments in sensor technologies allowed the definition of new human-computer interaction channels, useful for people with very limiting motor disabilities such as quadriplegia. Some of these sensors are available pre-packaged on the mass market, complete with computer interaction softwares, while others are easily achievable at low costs through DIY approaches. In this article we present Resin, an Accessible Digital Musical Instrument dedicated to people with quadriplegic disability. Resin exploits two interaction channels, head movements and the shape of the vocal tract, detected through the corresponding acoustic resonances, to control musical performance parameters. The structure of the instrument is discussed, from both the hardware and software points of view. Feature extraction algorithms for both channels are explained, particularly focusing on the vocal tract resonances interaction paradigm.