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Objective: Brain-body interfaces (BBIs) have emerged as a very promising solution for restoring voluntary hand control in people with upper-limb paralysis. The BBI module decoding motor commands from brain signals should provide the user with intuitive, accurate, and stable control. Here, we present a preliminary investigation in a monkey of a brain decoding strategy based on the direct coupling between the activity of intrinsic neural ensembles and output variables, aiming at achieving ease of learning and long-term robustness. Results: We identified an intrinsic low-dimensional space (called manifold) capturing the co-variation patterns of the monkey's neural activity associated to reach-to-grasp movements. We then tested the animal's ability to directly control a computer cursor using cortical activation along the manifold axes. By daily recalibrating only scaling factors, we achieved rapid learning and stable high performance in simple, incremental 2D tasks over more than 12 weeks of experiments. Finally, we showed that this brain decoding strategy can be effectively coupled to peripheral nerve stimulation to trigger voluntary hand movements. Conclusions: These results represent a proof of concept of manifold-based direct control for BBI applications.

Hand neuroprostheses restore voluntary movement in people with paralysis through neuromodulation protocols. There are a variety of strategies to control hand neuroprostheses, which can be based on residual body movements or brain activity. There is no universally superior solution, rather the best approach may vary from patient to patient. Here, we propose a protocol based on an immersive virtual reality (VR) environment that simulates the use of a hand neuroprosthesis to allow patients to experience and familiarize themselves with various control schemes in clinically relevant tasks and choose the preferred one. We used our VR environment to compare two alternative control strategies over 5 days of training in four patients with C6 spinal cord injury: (a) control via the ipsilateral wrist, (b) control via the contralateral shoulder. We did not find a one-fits-all solution but rather a subject-specific preference that could not be predicted based only on a general clinical assessment. The main results were that the VR simulation allowed participants to experience the pros and cons of the proposed strategies and make an educated choice, and that there was a longitudinal improvement. This shows that our VR-based protocol is a useful tool for personalization and training of the control strategy of hand neuroprostheses, which could help to promote user comfort and thus acceptance.

Spinal cord injury (SCI) causes severe motor and sensory deficits, and there are currently no approved treatments for recovery. Nearly 70% of patients with SCI experience pathological muscle cocontraction and spasticity, accompanied by clinical signs such as patellar hyperreflexia and ankle clonus. The integration of epidural electrical stimulation (EES) of the spinal cord with rehabilitation has substantial potential to improve recovery of motor functions; however, abnormal muscle cocontraction and spasticity may limit the benefit of these interventions and hinder the effectiveness of EES in promoting functional movements. High-frequency excitation block introduced in peripheral nerve stimulation could reduce abnormal activity and lead to more physiological activation patterns. Here, we evaluated the application of high-frequency EES (HF-EES) in alleviating undesired muscular cocontraction and spasticity in two patients with motor incomplete SCI implanted with a commercial 32-channel EES paddle commonly used for pain therapy. To design custom HF-EES protocols, we first mapped the muscles targeted by different EES configurations. Our results showed that HF-EES substantially reduced patellar reflex in one participant and eliminated both patellar reflex and ankle clonus in the other participant. By combining HF-EES and low-frequency EES (LF-EES) to enhance functional movements with intensive rehabilitation, we observed notable improvements in lower limb kinematics, muscle strength, and clinical lower limb motor assessments over the trial period. This study suggests that HF-EES could be an important supplementary tool in SCI treatment, emphasizing the importance of personalized rehabilitation approaches and advanced tools to optimize EES treatments and offering hope for individuals with SCI-related motor deficits. Editor's summary: Spinal cord injury (SCI) leads to severe motor impairments that can greatly limit a patient's quality of life. Residual neural signals to impaired limbs can cause undesirable movements such as simultaneous contraction of opposing muscles or spasticity, which can hinder functional movement and rehabilitation. Here, Romeni et al. tested the use of high-frequency epidural electrical stimulation (HF-EES) of the injured spinal cord as part of a broader physical rehabilitation program to attempt to mitigate these pathological movements. In two patients with motor incomplete SCI, the authors show that HF-EES reduced spasticity and pathologic muscle cocontraction. HF-EES was paired with low-frequency (LF)–EES, which enhances activation of the desired muscles for walking and other tasks. Both patients demonstrated improvements in motor ability over the course of rehabilitation, supporting the rationale for further examination of HF-EES as an adjuvant electrical stimulation protocol for patients recovering from SCI. —Molly Ogle [ABSTRACT FROM AUTHOR]

In internally post‐tensioned (PT) prestressed concrete (PC) structures, the prestressing system is usually made of high‐strength steel tendons embedded within concrete through either metallic or plastic ducts filled with cement grout or grease. Construction defects or degradation phenomena may lead to insufficient covering, exposing the prestressing steel to a harmful environment, potentially compromising the durability and load‐bearing capacity of the structure. Based on experimental tests on six 1:5 scaled PT specimens, this study presents accurate numerical simulations of four‐point bending tests on girders with unbonded and partially bonded tendons having different levels of initial prestress. Nonlinear finite element analyses (FEAs) were developed to reflect the friction‐type interaction mechanism between unbonded tendons and external ducts under increasing external load up to failure. Both global and local response parameters of the girders were studied validating numerical results against experimental findings. The numerical simulations provide insights on the stress pattern of unbonded and partially bonded strands, shedding light on the lower bearing capacity of defective girders compared to those with bonded tendons. Such findings contribute to a multi‐scale assessment and decision‐making framework for existing PT girders with defective grouting and low residual prestress levels, enhancing the understanding of their structural behavior and informing maintenance or retrofitting decisions. [ABSTRACT FROM AUTHOR]

La cultura digitale ha una valenza che risente della globalizzazione in atto e ne determina lo sviluppo. Il presente contributo pone l’accento sulla possibilità di considerare un esercizio della libertà religiosa nella società digitale, ovvero verifica come le libertà e i diritti, che, come corollari, discendono dalla libertà religiosa, possano coniugarsi con un esercizio “on line” del culto. Il digitale è diventato il mezzo che abbatte più di tutti le barriere di spazio e tempo: la stessa essenziale assemblea di fedeli che diventa una assemblea, aperta, ma nello stesso tempo non virtuale, quanto piuttosto caratterizzata dalla nuova forma di partecipazione. Partendo dall’analisi dell’assegnazione dei nomi di dominio di primo livello, sarà poi evidenziata la centralità di attuare una efficace Internet governance, finalizzata a garantire fra gli altri, integrazione globale, difesa dei diritti delle persone, e in generale opportunità culturali, economiche, sociali per ognuno nel rispetto dell’effettiva tutela del diritto di ciascuno alla privacy e alla protezione dei dati personali.

The ability of structural health monitoring (SHM) systems to detect defects and damage in existing structures is currently a key issue in the life-cycle management of civil infrastructure. In this respect, the use of dynamic identification to detect the loss of prestress load, grouting defects, cracking, and corrosion in post-tensioned concrete (PC) bridges is receiving special interest as an attractive tool that may drive predictive maintenance for disaster risk mitigation, motivating widespread implementation of SHM systems in engineering practice. In this study, an experimental program on reduced-scale PC beams representative of typical girder bridge decks, at the Department of Structures for Engineering and Architecture, University of Naples Federico II, is presented. The specimens were characterized by different prestressing load levels, grout injection conditions of post-tensioning ducts, and strand rupture during testing. Operational modal analysis (OMA) was carried out at multiple steps of each test, which were associated with different damage states of the specimens. OMA results show that both natural frequencies and mode shapes of PC girders are not significantly influenced by slight cracking corresponding to service load levels, while indicating some frequency variations in the case of local strand failure. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) are currently the standard of care for metastatic urothelial cancer (mUC) after the failure of previous platinum-based chemotherapy. The choice of further therapy after ICI progression is a new challenge, and scarce data support it. We aimed to examine the outcomes of mUC patients after progression to ICI, especially when receiving chemotherapy. Methods: Data were retrospectively collected from clinical records of mUC patients whose disease progressed to anti-programmed death 1 (PD-1)or programmed death ligand 1 (PD-L1) therapy at 14 Italian centers. Patients were grouped according to ICI therapy setting into SALVAGE (ie, ICI delivered ⩾ second-line therapy after platinum-based chemotherapy) and NAÏVE (ie, first-line therapy) groups. Progression-free survival (PFS) and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared among subgroups. Cox regression assessed the effect of treatments after progression to ICI on OS. Objective response rate (ORR) was calculated as the sum of partial and complete radiologic responses. Results: The study population consisted of 201 mUC patients who progressed after ICI: 59 in the NAÏVE cohort and 142 in the SALVAGE cohort. Overall, 52 patients received chemotherapy after ICI progression (25.9%), 20 (9.9%) received ICI beyond progression, 115 (57.2%) received best supportive care only, and 14 (7.0%) received investigational drugs. Objective response rate to chemotherapy in the post-ICI setting was 23.1% (28.0% in the NAÏVE group and 18.5% in the SALVAGE group). Median PFS and OS to chemotherapy after ICI-PD was 5 months (95% confidence interval [CI]: 3-11) and 13 months (95% CI: 7-NA) for the NAÏVE group; 3 months (95% CI: 2-NA) and 9 months (95% CI: 6-NA) for the SALVAGE group, respectively. Overall survival from ICI initiation was 17 months for patients receiving chemotherapy (hazard ratio [HR] = 0.09, p < 0.001), versus 8 months for patients receiving ICI beyond progression (HR = 0.13, p < 0.001), and 2 months for patients who did not receive further active treatment ( p < 0.001). Conclusions: Chemotherapy administered after ICI progression for mUC patients is advisable irrespective of the treatment line.