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The clinical assessment of patients with disorders of consciousness (DoC) relies on the observation of behavioural responses to standardised sensory stimulation. However, several medical comorbidities may directly impair the production of reproducible and appropriate responses, thus reducing the sensitivity of behaviour‐based diagnoses. One such comorbidity is akinetic mutism (AM), a rare neurological syndrome characterised by the inability to initiate volitional motor responses, sometimes associated with clinical presentations that overlap with those of DoC. In this paper, we describe the case of a patient with large bilateral mesial frontal lesions, showing prolonged behavioural unresponsiveness and severe disorganisation of electroencephalographic (EEG) background, compatible with a vegetative state/unresponsive wakefulness syndrome (VS/UWS). By applying an unprecedented multimodal battery of advanced imaging and electrophysiology‐based techniques (AIE) encompassing spontaneous EEG, evoked potentials, event‐related potentials, transcranial magnetic stimulation combined with EEG and structural and functional MRI, we provide the following: (i) a demonstration of the preservation of consciousness despite unresponsiveness in the context of AM, (ii) a plausible neurophysiological explanation for behavioural unresponsiveness and its subsequent recovery during rehabilitation stay and (iii) novel insights into the relationships between DoC, AM and parkinsonism. The present case offers proof‐of‐principle evidence supporting the clinical utility of a multimodal hierarchical workflow that combines AIEs to detect covert signs of consciousness in unresponsive patients. [ABSTRACT FROM AUTHOR]

Prediction of recovery of consciousness after severe brain injury is difficult and limited by a lack of reliable, standardized biomarkers. Multiple approaches for analysis of clinical electroencephalography (EEG) that shed light on prognosis in acute severe brain injury have emerged in recent years. These approaches fall into two major categories: conventional characterization of EEG background and quantitative measurement of resting state or stimulus-induced EEG activity. Additionally, a small number of studies have associated the presence of electrophysiologic sleep features with prognosis in the acute phase of severe brain injury. In this review, we focus on approaches for the analysis of clinical EEG that have prognostic significance and that could be readily implemented with minimal additional equipment in clinical settings, such as intensive care and intensive rehabilitation units, for patients with acute disorders of consciousness. [ABSTRACT FROM AUTHOR]

Can Patients with Encephalitis Lethargica Wake Up from Local Sleep? According to Brigo and colleagues, patients affected by EL in chronic phase were not actually asleep but rather severely slowed down by dopaminergic depletion. A Reply to Brigo et al. "You Are Older, although You Do Not Know That": Time, Consciousness, and Memory in "A Kind of Alaska" by Harold Pinter (1930-2008). [Extracted from the article]

• We provide an overview of EEG-based techniques in the prognostic and diagnostic assessment of DoC. • We highlight bridging principles between conventional and investigational approaches. • We share expert opinions and considerations on the technical and conceptual caveats. The analysis of spontaneous EEG activity and evoked potentials is a cornerstone of the instrumental evaluation of patients with disorders of consciousness (DoC). The past few years have witnessed an unprecedented surge in EEG-related research applied to the prediction and detection of recovery of consciousness after severe brain injury, opening up the prospect that new concepts and tools may be available at the bedside. This paper provides a comprehensive, critical overview of both consolidated and investigational electrophysiological techniques for the prognostic and diagnostic assessment of DoC. We describe conventional clinical EEG approaches, then focus on evoked and event-related potentials, and finally we analyze the potential of novel research findings. In doing so, we (i) draw a distinction between acute, prolonged and chronic phases of DoC, (ii) attempt to relate both clinical and research findings to the underlying neuronal processes and (iii) discuss technical and conceptual caveats. The primary aim of this narrative review is to bridge the gap between standard and emerging electrophysiological measures for the detection and prediction of recovery of consciousness. The ultimate scope is to provide a reference and common ground for academic researchers active in the field of neurophysiology and clinicians engaged in intensive care unit and rehabilitation. [ABSTRACT FROM AUTHOR]

We present a practical, robust, and effective pipeline to compute a high-resolution (HR) image of the corneal endothelium starting from a low-resolution (LR) video sequence obtained with a general purpose slit lamp biomicroscope. An image quality typical of dedicated and more expensive confocal microscopes is achieved via software magnification by exploiting information redundancy in the video sequence. In particular, the HR image is generated from the best LR frames, obtained by identifying the most suitable endothelium video subsequence using a support vector machine-based learning approach, followed by a robust graph-based frame registration. Results on long, real sequences show that the proposed approach is fast and produces better quality images than both classical multiframe super-resolution approaches and commercial state-of-the-art mosaicing software. Only low-cost equipment is required that makes the proposed method a valid diagnostic tool and an affordable resource for medical practice in both developed and developing countries. © 2018 SPIE and IS&T [DOI: 10 .1117/1.JEI.27.4.043029] [ABSTRACT FROM AUTHOR]

This work investigates the use of an advanced long-term vibration-based structural health monitoring tool to automatically detect earthquake-induced damages in heritage structures. Damage produced in a monumental bell-tower at increasing values of the Peak Ground Acceleration (PGA) of the seismic input is predicted by incremental nonlinear dynamic analysis, using a Finite Element model calibrated on the basis of experimentally identified natural modes. Then, predicted damage effects are artificially introduced in the monitoring data to check for their detectability. The results demonstrate that a very small damage, associated to a low intensity and low return period earthquake, is clearly detected by the monitoring system. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) represents the most common form of dementia among older age subjects, and despite decades of studies, the underlying mechanisms remain unresolved. The definition of AD has changed over the past 100 years, and while early-onset AD is commonly related to genetic mutations, late-onset AD ismore likely due to a gradual accumulation of age-related modifications. "Normal brain aging" and AD may represent different pathways of successful or failed capability to adapt brain structures and cerebral functions. Cellular senescence and age-related changes (ARCs) affecting the brain may be considered as biologic manifestations of increasing entropy, a measure of disorder. Late-onset AD may be regarded as the final effect of a reduced energy production, due to exhausted mitochondria, and an increased entropy in the brain. This unique trajectory enables a bioenergetics-centered strategy targeting disease-stage specific profile of brain metabolism for disease prevention and treatment. [ABSTRACT FROM AUTHOR]

We present a probabilistic methodology for designing tuned mass dampers for flutter suppression in long-span bridges. The procedure is computationally efficient and computes the probability of flutter occurrence based on a modified first-order method of reliability analysis, a reduced-order representation of the structure and a time domain formulation of aeroelastic loads. Results of a parametric investigation show that the proposed methodology is preferable to a deterministic design procedure, which relies on nominal values of mechanical and aerodynamic parameters and does not guarantee the maximum safety. Furthermore, the reliability-based approach can be effectively used in the design of multiple tuned mass damper configurations by enhancing robustness against frequency mistuning and by reducing costs associated with supplemental damping for a given safety performance level. [ABSTRACT FROM AUTHOR]

Continuously identified natural frequencies of vibration can provide unique information for low-cost automated condition assessment of civil constructions and infrastructures. However, the effects of changes in environmental parameters, such as temperature and humidity, need to be effectively investigated and accurately removed from identified frequency data for an effective performance assessment. This task is particularly challenging in the case of historical constructions that are typically massive and heterogeneous masonry structures characterized by complex variations of materials' properties with varying environmental parameters and by a differential heat conduction process where thermal capacity plays a major role. While there is abundance of documented monitoring data highlighting correlations between environmental parameters and natural frequencies in the case of new structures, such as long-span bridges, similar studies for historical constructions are still missing, with only a few literature works occasionally reporting increments in natural frequencies with increasing temperature of construction materials due to the closure of internal micro-cracks in the mortar layers caused by thermal expansion. In order to gain some knowledge on the effects of changes in temperature and humidity on the natural frequencies of slender masonry buildings, the paper focuses on the case study of an Italian monumental bell tower that has been monitored by the authors for more than nine months. Correlations between natural frequencies and environmental parameters are investigated in detail and the predictive capabilities of linear statistical regressive models based on the use of several environmental continuous monitoring sensors are assessed. At the end, three basic mechanisms governing environmentally-induced changes in the dynamic behavior of the tower are identified and essential information is achieved on the optimal location and minimum number of environmental sensors that are necessary in a structural health monitoring perspective. [ABSTRACT FROM AUTHOR]

Objective: Validating objective, brain-based indices of consciousness in behaviorally unresponsive patients represents a challenge due to the impossibility of obtaining independent evidence through subjective reports. Here we address this problem by first validating a promising metric of consciousness-the Perturbational Complexity Index (PCI)-in a benchmark population who could confirm the presence or absence of consciousness through subjective reports, and then applying the same index to patients with disorders of consciousness (DOCs).Methods: The benchmark population encompassed 150 healthy controls and communicative brain-injured subjects in various states of conscious wakefulness, disconnected consciousness, and unconsciousness. Receiver operating characteristic curve analysis was performed to define an optimal cutoff for discriminating between the conscious and unconscious conditions. This cutoff was then applied to a cohort of noncommunicative DOC patients (38 in a minimally conscious state [MCS] and 43 in a vegetative state [VS]).Results: We found an empirical cutoff that discriminated with 100% sensitivity and specificity between the conscious and the unconscious conditions in the benchmark population. This cutoff resulted in a sensitivity of 94.7% in detecting MCS and allowed the identification of a number of unresponsive VS patients (9 of 43) with high values of PCI, overlapping with the distribution of the benchmark conscious condition.Interpretation: Given its high sensitivity and specificity in the benchmark and MCS population, PCI offers a reliable, independently validated stratification of unresponsive patients that has important physiopathological and therapeutic implications. In particular, the high-PCI subgroup of VS patients may retain a capacity for consciousness that is not expressed in behavior. Ann Neurol 2016;80:718-729. [ABSTRACT FROM AUTHOR]

We recently published in this journal (Caronni and colleagues, Brain Injury, 2021–04-16) the first description of the spread of the SARS-CoV-2 infection in a cohort of brain injured patients with a disorder of consciousness (DOC). Surprisingly enough we showed that, in these patients, the COVID was moderate and did not result in fatalities. The pathogenesis of the COVID is characterized by the profound dysregulation of the immune system. To explain our findings, we speculated that the immunosuppression due to the brain injury could be protective against the development of the COVID in patients with DOC. More recently, a second group of authors (Marino and colleagues, PLoSOne, 2021–06-30) described the course of the COVID in an independent cohort of patients with DOC. Since our results were quite unexpected, we have been very comforted by the data reported by Marino and colleagues. Moreover, these data also offer a unique opportunity to further evaluate our theory regarding the COVID pathogenesis in patients with DOC. In the current Letter to the Editor it is shown that the independent data presented by Marino and colleagues do support our theory. Waiting for larger cohorts to further test it (and in case falsify it), our interpretation seems to remain valid. [ABSTRACT FROM AUTHOR]

Tools based on multivariate statistical analysis are becoming very popular for automatically revealing the existence of damage in structures using vibration data under changing environmental and operational conditions (typically temperature, humidity and traffic intensity). In this paper, methods of multivariate statistical analysis are newly applied for monitoring the structural health state of the main cables of suspension bridges, with the main contribution of removing non-linear aeroelastic correlations between dynamic features and wind speed. Considering natural frequencies as damage-sensitive features, an analytical parametric model of suspension bridge with damage in one main cable and subjected to wind loading is formulated, at first, as an extension of previous work. Model predictions demonstrate that apparent frequency variations caused by changes in incoming wind speed can likely be more significant than those produced by a small damage. A technique based on principal component analysis and novelty detection is adopted to cope with this issue and its application to long-term pseudo-experimental buffeting response data, generated by means of the analytical model, is presented. The results demonstrate the feasibility of permanent monitoring systems to reveal the existence of damages in wind-excited long-span bridges producing relative variations in the most sensitive natural frequency smaller than 0.1%. [ABSTRACT FROM AUTHOR]

Highlights: [•] Initial evaluation of a multi-component (4CMenB) vaccine against meningococcal disease. [•] Assessment of gene sequence presence and variability for five recombinant antigens and PorA. [•] Sequence-matching for vaccine and variants found among Norwegian meningococci. [•] 4CMenB will offer protection in situations with high microbiological diversity. [•] Sequence-match >70% for MenB strains; 4CMenB likely also protective against >50% non-MenB. [Copyright &y& Elsevier]

Abstract: A novel technique for monitoring of submarine groundwater discharge (SGD) in coastal zones based on an in situ underwater gamma-ray spectrometry of radon-decay products is described. Several sites were visited during the IAEA’2002 expedition offshore Donnalucata in the south-eastern Sicily. Continuous monitoring of 222Rn in the beach spring at Donnalucata has shown variable 222Rn activity concentrations in groundwater (from 12 to ), depending inversely on water levels during tide. Spatial variations of SGD have been observed in the Donnalucata boat basin. Average 222Rn activity concentrations in seawater varied from to , showing an inverse relationship with salinity. A continuous monitoring carried out at the site closest to the coast has also revealed an inverse relationship of 222Rn activity concentration on tide and salinity. The 222Rn concentrations in seawater varied from during high tides to during low tides, confirming the tidal influence on SGD. [Copyright &y& Elsevier]

The background characteristics of large volume HPGe detectors installed in IAEA-MEL''s underground counting laboratory situated at a depth of 35 m water equivalent have been investigated. Both single gamma-ray spectra as well as gamma-ray spectra gated by anti-cosmic shielding made of plastic scintillators are presented. The advantages of anti-cosmic shielding for HPGe detectors, especially in underground counting laboratories operating at shallow depths, are discussed. The authors present several examples of analysis of radionuclides in marine samples by single gamma-ray spectrometers with anti-cosmic shielding, an anti-Compton spectrometer and a Ge–Ge telescope designed for the analysis of low energy gamma-emitters. [Copyright &y& Elsevier]

Background: Disorders of consciousness (DoC) refers to a group of clinical conditions of altered consciousness. To improve their diagnosis and prognosis, multimodal assessment can be of great importance. Informal caregivers of people with DoC who are confronted with new technologies as such can benefit from interventions to expand their health literacy, i.e., the ability to use information to make health decisions for oneself and others. Methods: We developed an information brochure on multimodal assessment for DoC in a participatory process, with decisions made by a steering group. The process was based on a methodological framework for the development of patient decision aids that built on the International Patient Decision Aid Standards (IPDAS). Results: On the background of a broad variety of needs, the priority was to focus on the explanation of multimodal testing and provide information about its uncertainty. Its development aimed at enhancing informal caregivers' understanding of implications of results from multimodal assessment and its relevance for prognosis. It should avoid the portrayal of information that could lead to the impression of false hope or suboptimal rehabilitation care. Informal caregivers rated its usability and acceptability highly, though they preferred less technical language. Conclusion: The participatory process was crucial to the project. Future studies should investigate the effectiveness of the brochure in fostering informal caregivers' health literacy. Patient or Public Contribution: Informal caregivers of people with DoC were deliberately included in the steering group and they participated in a field test of the prototype brochure. [ABSTRACT FROM AUTHOR]

Focuses on the contributions of the document, 'Suum Cuique Tribuere,' by Aulis Aarnio and Aleksander Peczenik to the study of the philosophy of law. Explanatory picture of social interaction provided by the study; Significant aspects of the study in relation to the philosophy of law; Deficiencies of the study.

My comments will focus basically on Leader's paper. First, I will make some semantic remarks about the uses of the word “toleration”; second, I will offer some criticisms of Leader's paper; and, finally, I will put forward the outline of a modest proposal. [ABSTRACT FROM AUTHOR]

Guillain–Barré syndrome (GBS) is an acute disorder of the peripheral nervous system, causing flaccid paralysis, areflexia, and variable sensory involvement. Proximal as well distal muscles of the limbs can be involved, and in most severe and advanced cases progresses to respiratory failure and death. GBS is considered an autoimmune disease, and at the basis of the attack at the peripheral nervous system different mechanisms have been recognized, in particular viral infections or other immune stimulations. Cranial nerve involvement in patients with diffuse large B‐cell lymphoma (DLBCL) and primary central nervous system lymphoma are rare conditions that could present with similar clinical features. Here we present a case of a 36‐year‐old man hospitalized for acute polyradiculoneuritis of the cranial nerves and lumbar roots that arose a 14 days after severe acute respiratory syndrome COVID‐19 2 (Sars‐CoV‐2) vaccination. Most of the main criteria for the diagnosis of GBS were met, including clinical and electrophysiological criteria. Albuminocytologic dissociation and high protein level in cerebrospinal fluid were also found. Therefore, the patient was treated with a cycle of intravenous immunoglobulin (IVIG) with notable improvement of symptoms and gradual recovery of motility. A five months later, following SARS‐CoV‐2 infection, the patient presented with worsening of neurological symptoms and was readmitted to the hospital. He underwent instrumental tests again and was treated with repeated cycles of IVIG and then with a cycle of plasmapheresis without any improvement. In the following 10 days he developed very serious conditions; he was transferred to intensive care unit and deceased after 6 days. The cause of the neurological syndrome was determined only after autoptic analysis, which revealed the presence of primary peripheral nervous system (PNS) DLBCL. The reported case highlights that GBS‐like presentation always requires a careful differential diagnosis, and physicians should also consider the possibility of an occult cancer. [ABSTRACT FROM AUTHOR]

The analysis of spontaneous electroencephalogram (EEG) is a cornerstone in the assessment of patients with disorders of consciousness (DoC). Although preserved EEG patterns are highly suggestive of consciousness even in unresponsive patients, moderately or severely abnormal patterns are difficult to interpret. Indeed, growing evidence shows that consciousness can be present despite either large delta or reduced alpha activity in spontaneous EEG. Quantifying the complexity of EEG responses to direct cortical perturbations (perturbational complexity index [PCI]) may complement the observational approach and provide a reliable assessment of consciousness even when spontaneous EEG features are inconclusive. To seek empirical evidence of this hypothesis, we compared PCI with EEG spectral measures in the same population of minimally conscious state (MCS) patients (n = 40) hospitalized in rehabilitation facilities. We found a remarkable variability in spontaneous EEG features across MCS patients as compared with healthy controls: in particular, a pattern of predominant delta and highly reduced alpha power—more often observed in vegetative state/unresponsive wakefulness syndrome (VS/UWS) patients—was found in a non‐negligible number of MCS patients. Conversely, PCI values invariably fell above an externally validated empirical cutoff for consciousness in all MCS patients, consistent with the presence of clearly discernible, albeit fleeting, behavioural signs of awareness. These results confirm that, in some MCS patients, spontaneous EEG rhythms may be inconclusive about the actual capacity for consciousness and suggest that a perturbational approach can effectively compensate for this pitfall with practical implications for the individual patient's stratification and tailored rehabilitation. [ABSTRACT FROM AUTHOR]

The limits of the standard, behaviour‐based clinical assessment of patients with disorders of consciousness (DoC) prompted the employment of functional neuroimaging, neurometabolic, neurophysiological and neurostimulation techniques, to detect brain‐based covert markers of awareness. However, uni‐modal approaches, consisting in employing just one of those techniques, are usually not sufficient to provide an exhaustive exploration of the neural underpinnings of residual awareness. This systematic review aimed at collecting the evidence from studies employing a multimodal approach, that is, combining more instruments to complement DoC diagnosis, prognosis and better investigating their neural correlates. Following the PRISMA guidelines, records from PubMed, EMBASE and Scopus were screened to select peer‐review original articles in which a multi‐modal approach was used for the assessment of adult patients with a diagnosis of DoC. Ninety‐two observational studies and 32 case reports or case series met the inclusion criteria. Results highlighted a diagnostic and prognostic advantage of multi‐modal approaches that involve electroencephalography‐based (EEG‐based) measurements together with neuroimaging or neurometabolic data or with neurostimulation. Multimodal assessment deepened the knowledge on the neural networks underlying consciousness, by showing correlations between the integrity of the default mode network and the different clinical diagnosis of DoC. However, except for studies using transcranial magnetic stimulation combined with electroencephalography, the integration of more than one technique in most of the cases occurs without an a priori‐designed multi‐modal diagnostic approach. Our review supports the feasibility and underlines the advantages of a multimodal approach for the diagnosis, prognosis and for the investigation of neural correlates of DoCs. [ABSTRACT FROM AUTHOR]

We have previously demonstrated lacking of facilitation on repetitive nerve stimulation (RNS) due to structural blockage by botulinum toxin. In the current study we aimed to assess timing of the neurophysiological findings induced by botulinum toxin A. After inoculation of 15 U botulin toxin type A in extensor brevis digitorum (EDB), 10 healthy volunteers were evaluated by weekly EMG, SFEMG, and 3 and 20 Hz RNS examinations, for 12 consecutive weeks. All subjects showed reduced cMAP by one week after inoculation, with subsequent normalization within 12 weeks. No decrement at 3 Hz and no facilitation at 20 Hz RNS were observed. Abnormal jitter and blocking were mostly recorded between the 5th and 8th week, always associated with denervation/reinnervation EMG findings. Low cMAP is an early finding in iatrogenic botulism with no evidence of facilitation. Jitter abnormalities are concomitant with denervation/reinnervation findings. We speculate that the increase in jitter and blocking induced by botulinum toxin could be due to nerve terminal sprouting in addition to the formation of new neuromuscular junctions. [ABSTRACT FROM AUTHOR]

The assessment of the Attention Deficit/Hyperactivity Disorder (ADHD) in adults is often challenging, particularly due to the absence of specific diagnostic criteria. We applied a non-motor triplet protocol in a ADHD population to study the anticipatory attention as reflected by the slow cortical potential named Stimulus Preceding Negativity(SPN). We recorded 26 ADHD patients and 26 control subjects who did not receive any task instructions. We delivered trains of three stimuli belonging to the acoustic or the electric modality. In the first session(Triplet Same) the three stimuli belong to the same modality. In the second session(Triplet Different) the third stimulus belongs to the alternative modality. Grand-average waveforms were analyzed to evaluate the presence of the SPN in the interval time preceding the 1st, 2nd and 3rd stimulus. The ADHD group showed a significant N1 amplitude reduction in response to S1 and also a significant attenuation of the SPN before electric stimuli. We hypothesized that an abnormal attention processing combined with a dysfunction in emotional awareness may impair the anticipatory expectancy to the upcoming salient stimuli. We think that our findings may reflect an atypical attentional processing in the ADHD group, providing an additional level of analysis to the clinical psychiatric evaluation. [ABSTRACT FROM AUTHOR]

Short-term habituation (STH) represents a “bottom-up” filter for salient stimuli and a prerequisite for a subsequent “top-down” processing. Our aim was to ascertain if STH is preserved in patients with different levels of disorder of consciousness (DOC). We recorded 35 DOC patients assessed with Coma Recovery Scale-Revised. We delivered trains of stimuli (S1–S2–S3): S1 and S2 always belongs to the same sensory modality (auditory/somatosensory) whereas S3 can belong either to the same modality, (triplet“same”) or to the other modality (triplet “different”). S1/S2/S3-related N1–P2 amplitudes were compared in order to detect any significant STH. STH was detected in each emerging and MCS patient, whereas it was found absent only in VS patients (10 out of 19): until now, none of these 10 patients has regained consciousness. Among the 9 VS patients showing STH, 4 have subsequently become MCS. STH could represent a new potential diagnostic/prognostic neurophysiological indicator in DOC. We have found STH in every patient with a preserved level of consciousness. It remains to be determined whether the presence/absence of STH in an early DOC stage could have a prognostic value and whether the absence of STH in chronic VS could assume significance of a diagnostic confirmation. [Copyright &y& Elsevier]

Transcranial magnetic stimulation (TMS) of the primary motor cortex (M1) can excite both cortico-cortical and cortico-spinal axons resulting in TMS-evoked potentials (TEPs) and motor-evoked potentials (MEPs), respectively. Despite this remarkable difference with other cortical areas, the influence of motor output and its amplitude on TEPs is largely unknown. Here we studied TEPs resulting from M1 stimulation and assessed whether their waveform and spectral features depend on the MEP amplitude. To this aim, we performed two separate experiments. In experiment 1, single-pulse TMS was applied at the same supra-threshold intensity on primary motor, prefrontal, premotor and parietal cortices and the corresponding TEPs were compared by means of local mean field power and time-frequency spectral analysis. In experiment 2 we stimulated M1 at resting motor threshold in order to elicit MEPs characterized by a wide range of amplitudes. TEPs computed from high-MEP and low-MEP trials were then compared using the same methods applied in experiment 1. In line with previous studies, TMS of M1 produced larger TEPs compared to other cortical stimulations. Notably, we found that only TEPs produced by M1 stimulation were accompanied by a late event-related desynchronization (ERD—peaking at ~300 ms after TMS), whose magnitude was strongly dependent on the amplitude of MEPs. Overall, these results suggest that M1 produces peculiar responses to TMS possibly reflecting specific anatomo-functional properties, such as the re-entry of proprioceptive feedback associated with target muscle activation. [ABSTRACT FROM AUTHOR]

This article newly proposes the application of the stretching method, that is used in geophysics for detecting variations in the velocity with which waves propagate in the earth's crust from seismic noise recordings, in the context of vibration-based Structural Health Monitoring (SHM) of civil structures. The result is a computationally efficient long-term vibration-based SHM tool, that follows the current trend of using a very limited number of sensors permanently installed on site to measure operational structural responses for the purpose of damage detection. In the SHM setting, the proposed method aims at a direct identification of small permanent shifts in the natural frequencies of the structure in a changing environment, which is achieved by maximizing the correlation coefficient between a reference waveform, computed in a training reference period in which the structure is assumed to be undamaged, and a stretched version of the same waveform evaluated at the current time. The comparison is performed in the frequency domain and the waveform of interest is obtained from cross-correlations of the ambient vibration measurements. More specifically, in the case of multiple sensors, the waveform can be either the cross-power spectral density of the signals recorded by a pair of sensors, or the largest singular value of the spectral matrix of the measurements. It follows that the method can be regarded as an extension of the classic Frequency Domain Decomposition (FDD). A key feature of the proposed stretching method is mitigating the effects of environmental fluctuations by time domain averaging of cross-correlations over a proper period of time, before taking their Fourier transform to estimate the spectral densities. Such a time domain averaging is carried out in a relatively long period of time for estimating the reference waveform, whereas it is carried out in a shorter time for estimating the current waveform. The main features of the proposed methodology are its very low sensitivity to environmental fluctuations, resulting in a quite short training period length, and its low computational cost, which could be compatible with a direct integration within smart sensors with embedded electronics. The performance of the method is illustrated in the case study of an Italian historical monumental bell tower that has been monitored by the authors for more than 1 year. [ABSTRACT FROM AUTHOR]

Complexity analysis of electroencephalogram (EEG) signals has emerged as a valuable tool for characterizing Parkinson's disease (PD). Fractal dimension (FD) is a widely employed method for measuring the complexity of shapes with many applications in neurodegenerative disorders. Nevertheless, very little is known on the fractal characteristics of EEG in PD measured by FD. In this study we performed a spatio-temporal analysis of EEG in PD using FD in four dimensions (4DFD). We analyzed 42 resting-state EEG recordings comprising two groups: 27 PD patients without dementia and 15 healthy control subjects (HC). From the original resting-state EEG we derived the cortical activations defined by a source reconstruction at each time sample, generating point clouds in three dimensions. Then, a sliding window of one second (the fourth dimension) was used to compute the value of 4DFD by means of the box-counting algorithm. Our results showed a significantly higher value of 4DFD in the PD group (p < 0.001). Moreover, as a diagnostic classifier of PD, 4DFD obtained an area under curve value of 0.97 for a receiver operating characteristic curve analysis. These results suggest that 4DFD could be a promising method for characterizing the specific changes in the brain dynamics associated with PD. [ABSTRACT FROM AUTHOR]

Early reemergence of consciousness predicts long-term functional recovery for patients with severe brain injury. However, tools to reliably detect consciousness in the intensive care unit are lacking. Transcranial magnetic stimulation electroencephalography has the potential to detect consciousness in the intensive care unit, predict recovery, and prevent premature withdrawal of life-sustaining therapy. [ABSTRACT FROM AUTHOR]

How can an intentional movement be distinguished from the same movement done nonintentionally? How can this distinction be drawn without asking the subject, or in patients who are unable to communicate? Here we address these questions, by focusing on blinking. This is one of the most frequent spontaneous actions in our daily life, but it can also be done intentionally. Furthermore, blinking is often spared in patients with severe brain injuries, and for some, it is the only way to report complex meanings. Using kinematic and EEG-based measures, we found that intentional and spontaneous blinking are preceded by different brain activities, even when they are indistinguishable. Unlike spontaneous ones, intentional blinks are characterized by a slow negative EEG drift, resembling the classic readiness potential. We investigated the theoretical implication of this finding in stochastic decision models as well as the practical significance of using brain-based signals to improve the discrimination between intentional and nonintentional actions. As proof of principle, we considered three brain-injured patients with rare neurological syndromes characterized by motor and communicative impairments. Although further research is needed, our results indicate that brain-based signals can offer a feasible way to infer intentionality even in absence of overt communication. [ABSTRACT FROM AUTHOR]

Background: Disorders of consciousness (DoC) are severe neurological conditions in which consciousness is impaired to various degrees. They are caused by injury or malfunction of neural systems regulating arousal and awareness. Over the last decades, major efforts in improving and individualizing diagnostic and prognostic accuracy for patients affected by DoC have been made, mainly focusing on introducing multimodal assessments to complement behavioral examination. The present EU-funded multicentric research project "PerBrain" is aimed at developing an individualized diagnostic hierarchical pathway guided by both behavior and multimodal neurodiagnostics for DoC patients. Methods: In this project, each enrolled patient undergoes repetitive behavioral, clinical, and neurodiagnostic assessments according to a patient-tailored multi-layer workflow. Multimodal diagnostic acquisitions using state-of-the-art techniques at different stages of the patients' clinical evolution are performed. The techniques applied comprise well-established behavioral scales, innovative neurophysiological techniques (such as quantitative electroencephalography and transcranial magnetic stimulation combined with electroencephalography), structural and resting-state functional magnetic resonance imaging, and measurements of physiological activity (i.e. nasal airflow respiration). In addition, the well-being and treatment decision attitudes of patients' informal caregivers (primarily family members) are investigated. Patient and caregiver assessments are performed at multiple time points within one year after acquired brain injury, starting at the acute disease phase. Discussion: Accurate classification and outcome prediction of DoC are of crucial importance for affected patients as well as their caregivers, as individual rehabilitation strategies and treatment decisions are critically dependent on the latter. The PerBrain project aims at optimizing individual DoC diagnosis and accuracy of outcome prediction by integrating data from the suggested multimodal examination methods into a personalized hierarchical diagnosis and prognosis procedure. Using the parallel tracking of both patients' neurological status and their caregivers' mental situation, well-being, and treatment decision attitudes from the acute to the chronic phase of the disease and across different countries, this project aims at significantly contributing to the current clinical routine of DoC patients and their family members. Trial registration: ClinicalTrials.gov, NCT04798456. Registered 15 March 2021 – Retrospectively registered. [ABSTRACT FROM AUTHOR]

The current trend in full-scale applications of active mass drivers for mitigating buildings׳ vibrations is to rely on the use of electric servomotors and low friction transmission devices. While similar full-scale applications have been recently documented, there is still the need for deepening the understanding of the behavior of such active mass drivers, especially as it concerns their reliability in the case of extreme loading events. This paper presents some considerations arisen in the physical implementation of a prototype active mass driver system, fabricated by coupling an electric torsional servomotor with a ball screw transmission device, using state-of-the-art electronics and a high speed digital communication protocol between controller and servomotor drive. The prototype actuator is mounted on top of a scaled-down five-story frame structure, subjected to base excitation provided by a sliding table actuated by an electrodynamic shaker. The equations of motion are rigorously derived, at first, by considering the torque of the servomotor as the control input, in agreement with other literature work. Then, they are extended to the case where the servomotor operates under kinematic control, that is, by commanding its angular velocity instead of its torque, including control-structure-interaction effects. Experiments are carried out by employing an inherently stable collocated skyhook control algorithm, proving, on the one hand, the control effectiveness of the device but also revealing, on the other hand, the possibility of closed-loop system instability at high gains. Theoretical interpretation of the results clarifies that the dynamic behavior of the actuator plays a central role in determining its control effectiveness and is responsible for the observed stability issues, operating similarly to time delay effects. Numerical extension to the case of earthquake excitation confirms the control effectiveness of the device and highlights that different controllers essentially provide similar performances in the mitigation of the structural response. [ABSTRACT FROM AUTHOR]

Abstract: Neisseria meningitidis (Nm) serogroups B, C and Y are the major causes of meningococcal diseases in the United States. NmB accounts for ∼1/3 of the disease but no licensed vaccine is yet available. Two candidate vaccines are being developed specifically to target NmB, but may also provide protection against other serogroups. To assess the potential impact of these vaccines on NmB and other serogroups causing disease in the US, we determined the prevalence, genetic diversity and epidemiological characteristics of three candidate antigen genes in Nm isolates collected through Active Bacterial Core surveillance (ABCs), a population-based active surveillance program. fHbp was detected in all NmB, NmY and NmW135 isolates. Eleven NmC isolates contain fHbp with a single base-pair deletion creating a frame shift in the C-terminal region. Among NmB, 59% were FHbp subfamily/variant B/v1 and 41% A/v2-3. Among NmC and NmY, 39% and 3% were B/v1, respectively. nadA was detected in 39% of NmB, 61% of NmC and 4% of NmY. Among isolates tested, nhbA was present in all NmB and 96% of non-B. For the subset of strains sequenced for NadA and NhbA, pairwise identity was greater than 93% and 78%, respectively. The proportion of FHbp subfamily/variant was different between ABCs site and year, but no linear temporal trend was observed. Although assessment of the vaccine coverage also requires understanding of the antigen expression and the ability to induce bactericidal activity, our finding that all isolates contain one or more antigen genes suggests these candidate vaccines may protect against multiple Nm serogroups. [Copyright &y& Elsevier]

Meningitis and sepsis caused by serogroup B meningococcus are two severe diseases that still cause significant mortality. To date there is no universal vaccine that prevents these diseases. In this work, five antigens discovered by reverse vaccinology were expressed in a form suitable for large-scale manufacturing and formulated with adjuvants suitable for human use. The vaccine adjuvanted by aluminum hydroxide induced bactericidal antibodies in mice against 78% of a panel of 85 meningococcal strains representative of the global population diversity. The strain coverage could be increased to 90% and above by the addition of CpG oligonucleotides or by using MF59 as adjuvant. The vaccine has the potential to conquer one of the most devastating diseases of childhood. [ABSTRACT FROM AUTHOR]

Artery of Percheron (AOP) stroke is a rare event. We describe an AOP stroke involving both thalami and the midbrain, resulting in a multifunctional clinical impairment. Intensive inpatient multidisciplinary rehabilitation favored the recovery of motor deficits, together with the improvement of cognitive dysfunctions. MRI assessment in the chronic post-stroke phase showed structural and functional reorganization in response to the extended thalamic tissue damage and absence of revascularization. Thalamo-cortical networks involving frontal and prefrontal regions, as well as parietal areas were disrupted, whereas increased functional thalamo-occipital connectivity was found. This report sheds light on brain reorganization following AOP stroke after rehabilitation.. [ABSTRACT FROM AUTHOR]

Background and purpose: Stroke-associated pneumonia (SAP) affects 10 to 38% of patients in the acute phase of stroke. Stroke patients diagnosed with dysphagia have an 11-fold higher risk of developing SAP. Thus, identifying dysphagic patients through a highly accurate screening tool might be crucial in reducing the incidence of SAP. We present a case–control study designed to evaluate efficacy in reducing the risk of SAP between two swallowing screening tools, the classic water swallow test (WST) and a recently validated tool such as the GLOBE-3S (the Sapienza GLObal Bedside Evaluation of Swallowing after Stroke), which is a highly sensitive swallowing screening tool particularly accurate in detecting silent aspiration as well. Methods: We analyzed the occurrence of dysphagia in 100 acute stroke patients distributed in two groups: half were screened with WST and the other half with GLOBE-3S. Results: Dysphagia was diagnosed in 28 patients. The main result is that, among patients who passed the dysphagia screenings, none of those screened with the GLOBE-3S method developed pneumonia compared to 31.82% in the WST group. Discriminant function analysis (DFA) showed that NIH Stroke Scale (NIHSS) score and the dysphagia screening method (i.e., GLOBE-3S vs. WST) were the two main factors in the SAP's predicting model and the only significant ones per se. Conclusions: The new GLOBE-3S screening test can reduce the risk of SAP compared to WST. [ABSTRACT FROM AUTHOR]

Chlamydia trachomatis pgp3 DNA immunized (no. 300) and non-immunized (no. 300) C3H/HeN mice were infected by vaginal inoculation with infectious C. trachomatis serotype D elementary bodies (EBs) and the spread of infection to the salpinges was assessed by cell culture isolation from tissue homogenates 7, 14, 21, 28, 35 and 42 days post-infection (p.i.). Overall, the pgp3-DNA immunization prevented salpinx infection in 94 (56%) mice, if compared with the 168 positive animals found among the non-immunized animals (P<0.001).A group of negative control animals (i.e. mice immunized with plasmid DNA containing an irrelevant insert) was not protected, whereas all the mice of a positive immune control group (mice that had resolved a primary genital C. trachomatis infection) were resistant to re-infection. Pgp3 DNA immunization induced both humoral and mucosal anti-pgp3 antibodies. [Copyright &y& Elsevier]

Purpose: SARS-CoV-2 infection can cause the coronavirus disease (COVID), ranging from flu-like symptoms to interstitial pneumonia. Mortality is high in COVID pneumonia and it is the highest among the frailest. COVID could be particularly serious in patients with severe acquired brain injury (SABI), such as those with a disorder of consciousness. We here describe a cohort of patients with a disorder of consciousness exposed to SARS-CoV-2 early after their SABI. Materials and methods: The full cohort of 11 patients with SABI hospitalized in March 2020 in the IRCCS Fondazione Don Gnocchi rehabilitation (Milan, Italy) was recruited. Participants received SARS-CoV-2 testing and different clinical and laboratory data were collected. Results: Six patients contracted SARS-CoV-2 and four of them developed the COVID. Of these, one patient had ground-glass opacities on the chest CT scan, while the remaining three developed consolidations. No patient died and the overall respiratory involvement was mild, requiring in the worst cases low-flow oxygen. Conclusions: Here we report the clinical course of a cohort of patients with SABI exposed to SARS-CoV-2. The infection spread among patients and caused COVID in some of them. Unexpectedly, COVID was moderate, caused at most mild respiratory distress and did not result in fatalities. [ABSTRACT FROM AUTHOR]

• 4CMenB antigens are present and conserved in non-MenB meningococcal strains. • The antigens vary across strains in their presence, sequence relatedness and expression level. • 4CMenB sera raised in infants are able to kill 109 genetically diverse isolates belonging to serogroups C, W and Y. • Infant vaccination with 4CMenB may provide high coverage of non-MenB strains. • 4CMenB may induce cross-protection against non-MenB strains. The multicomponent meningococcal serogroup B vaccine (4CMenB) is currently indicated for active immunization against invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB). However, genes encoding the 4CMenB antigens are also variably present and expressed in strains belonging to other meningococcal serogroups. In this study, we evaluated the ability of antibodies raised by 4CMenB immunisation to induce complement-mediated bactericidal killing of non-MenB strains. A total of 227 invasive non-MenB disease isolates were collected between 1 July 2007 and 30 June 2008 from England and Wales, France, and Germany; 41 isolates were collected during 2012 from Brazil. The isolates were subjected to genotypic analyses. A subset of 147 isolates (MenC, MenW and MenY) representative of the meningococcal genetic diversity of the total sample were tested in the human complement serum bactericidal antibody assay (hSBA) using sera from infants immunised with 4CMenB. Serogroup and clonal complex repertoires of non-MenB isolates were different for each country. For the European panel, MenC, MenW and MenY isolates belonged mainly to ST-11, ST-22 and ST-23 complexes, respectively. For the Brazilian panel, most MenC and MenW isolates belonged to the ST-103 and ST-11 complexes, respectively, and most MenY isolates were not assigned to clonal complexes. Of the 147 non-MenB isolates, 109 were killed in hSBA, resulting in an overall coverage of 74%. This is the first study in which 147 non-MenB serogroup isolates have been analysed in hSBA to evaluate the potential of a MenB vaccine to cover strains belonging to other serogroups. These data demonstrate that antibodies raised by 4CMenB are able to induce bactericidal killing of 109 non-MenB isolates, representative of non-MenB genetic and geographic diversity. These findings support previous evidence that 4CMenB immunisation can provide cross-protection against non-MenB strains in infants, which represents an added benefit of 4CMenB vaccination. [ABSTRACT FROM AUTHOR]

Abstract Background The Meningococcal Antigen Typing System (MATS) was developed to identify meningococcus group B strains with a high likelihood of being covered by the 4CMenB vaccine, but is limited by the requirement for viable isolates from culture-confirmed cases. We examined if antigen genotyping could complement MATS in predicting strain coverage by the 4CMenB vaccine. Methods From a panel of 3912 MATS-typed invasive meningococcal disease isolates collected in England and Wales in 2007–2008, 2014–2015 and 2015–2016, and in 16 other countries in 2000–2015, 3481 isolates were also characterized by antigen genotyping. Individual associations between antigen genotypes and MATS coverage for each 4CMenB component were used to define a genetic MATS (gMATS). gMATS estimates were compared with England and Wales human complement serum bactericidal assay (hSBA) data and vaccine effectiveness (VE) data from England. Results Overall, 81% of the strain panel had genetically predictable MATS coverage, with 92% accuracy and highly concordant results across national panels (Lin's accuracy coefficient, 0.98; root-mean-square deviation, 6%). England and Wales strain coverage estimates were 72–73% by genotyping (66–73% by MATS), underestimating hSBA values after four vaccine doses (88%) and VE after two doses (83%). The gMATS predicted strain coverage in other countries was 58–88%. Conclusions gMATS can replace MATS in predicting 4CMenB strain coverage in four out of five cases, without requiring a cultivable isolate, and is open to further improvement. Both methods underestimated VE in England. Strain coverage predictions in other countries matched or exceeded England and Wales estimates. [ABSTRACT FROM AUTHOR]

Abstract Many essential oils (EOs) are screened as potential sources of antimicrobial compounds. EOs from the genus Satureja have recognized biological properties, including analgesic, anti-inflammatory, immunomodulatory, anticancer, and antimicrobial activity. This study aimed to obtain a metabolite profile of commercial essential oil of S. montana L. (SEO) and to evaluate its antimicrobial properties, both alone and combined with gentamicin towards Gram-negative and Gram-positive bacterial strains. Untargeted analyses based on direct infusion Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS) and on GC-MS have provided a high metabolome coverage, allowing to identify carvacrol, cymene and thymol as the major components of commercial SEO. SEO exerted an antimicrobial activity and induced a synergistic interaction with gentamicin against both reference and clinical bacterial strains. A significant reduction of Escherichia coli , Staphylococcus aureus and Listeria monocytogenes biofilm formation was induced by SEO. As a result of SEO treatment, clear morphological bacterial alterations were visualized by scanning electron microscopy: L. monocytogenes and S. aureus showed malformed cell surface or broken cells with pores formation, whereas E. coli displayed collapsed cell surface. These results encourage further studies about bactericidal and antibiotic synergistic effect of SEO for combined therapy in clinical setting as well as in agricultural systems. Graphical abstract Image 1 Highlights • Carvacrol, cymene and thymol are major components of Satureja montana essential oil. • S. montana essential oil shows antimicrobial activity. • S. montana essential oil exerts synergistic interaction with gentamicin against bacterial strains. • Reduction of bacterial biofilm formation was induced by S. montana essential oil. [ABSTRACT FROM AUTHOR]

Objectives Patients with chronic disorders of consciousness (DOC) may show alterations of autonomic function; however, in this clinical population, no data are available on the specific effects of nociceptive stimuli on cardiac autonomic control. Thus, we aimed at investigating the effects of a noxious stimulation on heart rate variability (HRV) in a population of patients with chronic DOC, taking into account different states of consciousness (vegetative state/unresponsive wakefulness syndrome, VS/UWS and minimally conscious state, MCS). Methods We enrolled twenty-four DOC patients (VS/UWS, n  = 12 and MCS, n  = 12). ECG and respiration were recorded during baseline, immediately after the nociceptive stimulus and, finally, during the recovery period. Linear and nonlinear HRV measures were used to evaluate the cardiac autonomic control. Results In DOC patients, nonlinear HRV analysis showed that nociceptive stimuli are able to elicit a change of autonomic function characterized by an increased sympathetic and a reduced vagal modulation. A significant reduction of autonomic complexity has also been detected. More interestingly, VS/UWS patients showed a less complex dynamics compared to MCS patients. Conclusions Cardiac autonomic responses are able to significantly differentiate the autonomic function between VS/UWS and MCS patients. Significance Nonlinear HRV analysis may represent a useful tool to characterize the cardiac autonomic responses to nociceptive stimuli in a chronic DOC population. [ABSTRACT FROM AUTHOR]

The response of the San Pietro monumental bell-tower located in Perugia, Italy, to the 2016 Central Italy seismic sequence is investigated, taking advantage of the availability of field data recorded by a vibration-based SHM system installed in December 2014 to detect earthquake-induced damages. The tower is located about 85 km in the NW direction from the epicenter of the first major shock of the sequence, the Accumoli Mw6.0 earthquake of August 24th, resulting in a small local PGA of about 30 cm/s, whereby near-field PGA was measured as 915.97 cm/s (E-W component) and 445.59 cm/s (N-S component). Similar PGA values also characterized the two other major shocks of the sequence (Ussita Mw5.9 and Norcia Mw6.5 earthquakes of October 26th and 30th, respectively). Despite the relatively low intensity of such earthquakes in Perugia, the analysis of long-term monitoring data clearly highlights that small permanent changes in the structural behavior of the bell-tower have occurred after the earthquakes, with decreases in all identified natural frequencies. Such natural frequency decays are fully consistent with what predicted by non-linear finite element simulations and, in particular, with the development of microcracks at the base of the columns of the belfry. Microcracks in these regions, and in the rest of tower, are however hardly distinguishable from pre-existing ones and from the physiological cracking of a masonry structure, what validates the effectiveness of the SHM system in detecting earthquake-induced damage at a stage where this is not yet detectable by visual inspections. [ABSTRACT FROM AUTHOR]

Background: A novel meningococcal multicomponent vaccine, 4CMenB (Bexsero®), has been approved in Europe, Canada, Australia and US. The potential impact of 4CMenB on strain coverage is being estimated by using Meningococcal Antigen Typing System (MATS), an ELISA assay which measures vaccine antigen expression and diversity in each strain. Here we show the genetic characterization and the 4CMenB potential coverage of Spanish invasive strains (collected during one epidemiological year) compared to other European countries and discuss the potential reasons for the lower estimate of coverage in Spain. Material and Methods: A panel of 300 strains, a representative sample of all serogroup B Neisseria meningitidis notified cases in Spain from 2009 to 2010, was characterized by multilocus sequence typing (MLST) and FetA variable region determination. 4CMenB vaccine antigens, PorA, factor H binding protein (fHbp), Neisseria Heparin Binding Antigen (NHBA) and Neisserial adhesin A (NadA) were molecularly typed by sequencing. PorA coverage was assigned to strain with VR2 = 4. The levels of expression and cross-reactivity of fHbp, NHBA and NadA were analyzed using MATS ELISA. Findings: Global estimated strain coverage by MATS was 68.67% (95% CI: 47.77–84.59%), with 51.33%, 15.33% and 2% of strains covered by one, two and three vaccine antigens, respectively. The predicted strain coverage by individual antigens was: 42% NHBA, 36.33% fHbp, 8.33% PorA and 1.33% NadA. Coverage within the most prevalent clonal complexes (cc) was 70.37% for cc 269, 30.19% for cc 213 and 95.83% for cc 32. Conclusions: Clonal complexes (cc) distribution accounts for variations in strain coverage, so that country-by-country investigations of strain coverage and cc prevalence are important. Because the cc distribution could also vary over time, which in turn could lead to changes in strain coverage, continuous detailed surveillance and monitoring of vaccine antigens expression is needed in those countries where the multicomponent vaccine is introduced. This is really important in countries like Spain where most of the strains are predicted to be covered by only one vaccine antigen and the chance for escape mutants to emerge with vaccine use is higher. Based on the observed data, cc213 should receive special attention as it is associated with low predicted strain coverage, and has recently emerged in Spain. [ABSTRACT FROM AUTHOR]