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Primary lateral sclerosis (PLS) is a slowly progressing disorder, which is characterized primarily by the degeneration of upper motor neurons (UMNs) in the primary motor area (M1). It is not yet clear how the function of sensorimotor networks beyond M1 are affected by PLS. The aim of this study was to use cortico-muscular coherence (CMC) to characterize the oscillatory drives between cortical regions and muscles during a motor task in PLS and to examine the relationship between CMC and the level of clinical impairment. We recorded EEG and EMG from hand muscles in 16 participants with PLS and 18 controls during a pincer-grip task. In PLS, higher CMC was observed over contralateral-M1 (α- and γ-band) and ipsilateral-M1 (β-band) compared with controls. Significant correlations between clinically assessed UMN scores and CMC measures showed that higher clinical impairment was associated with lower CMC over contralateral-M1/frontal areas, higher CMC over parietal area, and both higher and lower CMC (in different bands) over ipsilateral-M1. The results suggest an atypical engagement of both contralateral and ipsilateral M1 during motor activity in PLS, indicating the presence of pathogenic and/or adaptive/compensatory alterations in neural activity. The findings demonstrate the potential of CMC for identifying dysfunction within the sensorimotor networks in PLS.

Factor analysis proposes an alternative approach to standard portfolio theory: the latter is optimisation based, while the former is estimation based. Also, in standard portfolio theory, returns are only explained by the portfolio volatility factor, while factor analysis proposes a multiplicity of factors, which the managers can choose from to tilt their portfolios. In attempting to reconcile these alternative worlds, we propose a penalised utility function, incorporating both the Markowitzian risk-return trade-off and the manager’s preferences towards factors, and discriminating among losses and gains relative to a reference asset. The penalisation affects the optimisation process, favouring the selection of portfolios with less variance and more tilted towards the chosen risk factors. Penalty levels set by the manager generalise the traditional notion of risk aversion. We test our model by building an investment portfolio based on a combination of asset classes and selected investing factors, focussed on the eurozone. To identify the optimal portfolio, we adopt a set of three metaheuristic optimisation algorithms: the fitness function stochastic maximization using genetic algorithms, differential evolution algorithm for global optimisation, and the particle swarm optimisation, and dynamically choose the best solution. In this way, we can improve the Markowitzian optimisation by tilting the asset allocation with managers’ expectations and desired exposures towards designated factors.

Amyotrophic lateral sclerosis is a devastating disease characterized primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. Amyotrophic lateral sclerosis is both clinically and biologically heterogeneous. Subgrouping is currently undertaken using clinical parameters, such as site of symptom onset (bulbar or spinal), burden of disease (based on the modified El Escorial Research Criteria) and genomics in those with familial disease. However, with the exception of genomics, these subcategories do not take into account underlying disease pathobiology, and are not fully predictive of disease course or prognosis. Recently, we have shown that resting-state EEG can reliably and quantitatively capture abnormal patterns of motor and cognitive network disruption in amyotrophic lateral sclerosis. These network disruptions have been identified across multiple frequency bands, and using measures of neural activity (spectral power) and connectivity (comodulation of activity by amplitude envelope correlation and synchrony by imaginary coherence) on source-localized brain oscillations from high-density EEG. Using data-driven methods (similarity network fusion and spectral clustering), we have now undertaken a clustering analysis to identify disease subphenotypes and to determine whether different patterns of disruption are predictive of disease outcome. We show that amyotrophic lateral sclerosis patients (n = 95) can be subgrouped into four phenotypes with distinct neurophysiological profiles. These clusters are characterized by varying degrees of disruption in the somatomotor (α-band synchrony), frontotemporal (β-band neural activity and γl-band synchrony) and frontoparietal (γl-band comodulation) networks, which reliably correlate with distinct clinical profiles and different disease trajectories. Using an in-depth stability analysis, we show that these clusters are statistically reproducible and robust, remain stable after reassessment using a follow-up EEG session, and continue to predict the clinical trajectory and disease outcome. Our data demonstrate that novel phenotyping using neuroelectric signal analysis can distinguish disease subtypes based exclusively on different patterns of network disturbances. These patterns may reflect underlying disease neurobiology. The identification of amyotrophic lateral sclerosis subtypes based on profiles of differential impairment in neuronal networks has clear potential in future stratification for clinical trials. Advanced network profiling in amyotrophic lateral sclerosis can also underpin new therapeutic strategies that are based on principles of neurobiology and designed to modulate network disruption.

Praying mantids (class Insecta, order Mantodea) are a group of predatory insects comprising approximately 2500 described species, that occur across all continents except Antarctica, with the greatest species diversity in tropical and subtropical regions. Mantids predominantly prey on other invertebrates but are known to feed on small vertebrates. During April and May 2021, we observed mantid feeding events in Manujan County, Kerman Province in southern Iran. Two distinct feeding events were observed where female European Mantids (

In our paper, we study the impact of active investment strategies and factors of their success in the Russian market of collective investment — self-confidence of managers, commissions of management companies (MC) — on return rates of mutual funds. For the first time, not only equity mutual funds, but also bond mutual funds are considered as an object of study; the time period is since 2012. Our study is based on data on the structure of mutual fund portfolios provided by Investfunds. We propose a number of original indicators of an active management style and consider the profitability of mutual funds relative to various benchmarks. Based on testing of multivariate regression models, it has been revealed that the return rate of equity mutual funds is negatively affected by a share of stocks in the fund portfolio which are not included in the market index. When managers take into account their previous negative investment experience, it contributes to the growth of mutual fund return rates. Active investment strategies correlate with increased commissions (up to 4.5% of NAV), but they do not allow an investor to receive higher return rates than index investments. An increase in the share of corporate bonds allows the fund manager to outperform benchmarks for bond funds. For the first time, a nonlinear relationship between the size of mutual funds and the value of commissions has been revealed for the Russian market.

In recent times electrophysiologists started considering the possibility of performing Radiofrequency (RF) ablation for the treatment of atrial fibrillation by delivering shorter pulses of larger power (e.g. 60W, 6s applications). Such a technique is known as High Power Short Duratio (HPSD) Ablation [1-5].

Objective: To identify cortical regions engaged during the sustained attention to response task (SART) and characterize changes in their activity associated with the neurodegenerative condition amyotrophic lateral sclerosis (ALS). Methods: High-density electroencephalography (EEG) was recorded from 33 controls and 23 ALS patients during a SART paradigm. Differences in associated event-related potential peaks were measured for Go and NoGo trials. Sources active during these peaks were localized, and ALS-associated differences were quantified. Results: Go and NoGo N2 and P3 peak sources were localized to the left primary motor cortex, bilateral dorsolateral prefrontal cortex (DLPFC), and lateral posterior parietal cortex (PPC). NoGo trials evoked greater bilateral medial PPC activity during N2 and lesser left insular, PPC and DLPFC activity during P3. Widespread cortical hyperactivity was identified in ALS during P3. Changes in the inferior parietal lobule and insular activity provided very good discrimination (AUROC > 0.75) between patients and controls. Activation of the right precuneus during P3 related to greater executive function in ALS, indicative of a compensatory role. Interpretation: The SART engages numerous frontal and parietal cortical structures. SART–EEG measures correlate with specific cognitive impairments that can be localized to specific structures, aiding in differential diagnosis.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease primarily affecting motor function, with additional evidence of extensive nonmotor involvement. Despite increasing recognition of the disease as a multisystem network disorder characterised by impaired connectivity, the precise neuroelectric characteristics of impaired cortical communication remain to be fully elucidated. Here, we characterise changes in functional connectivity using beamformer source analysis on resting‐state electroencephalography recordings from 74 ALS patients and 47 age‐matched healthy controls. Spatiospectral characteristics of network changes in the ALS patient group were quantified by spectral power, amplitude envelope correlation (co‐modulation) and imaginary coherence (synchrony). We show patterns of decreased spectral power in the occipital and temporal (δ‐ to β‐band), lateral/orbitofrontal (δ‐ to θ‐band) and sensorimotor (β‐band) regions of the brain in patients with ALS. Furthermore, we show increased co‐modulation of neural oscillations in the central and posterior (δ‐, θ‐ and γl‐band) and frontal (δ‐ and γl‐band) regions, as well as decreased synchrony in the temporal and frontal (δ‐ to β‐band) and sensorimotor (β‐band) regions. Factorisation of these complex connectivity patterns reveals a distinct disruption of both motor and nonmotor networks. The observed changes in connectivity correlated with structural MRI changes, functional motor scores and cognitive scores. Characteristic patterned changes of cortical function in ALS signify widespread disease‐associated network disruption, pointing to extensive dysfunction of both motor and cognitive networks. These statistically robust findings, that correlate with clinical scores, provide a strong rationale for further development as biomarkers of network disruption for future clinical trials.

The decrease in apparent relative viscosity that occurs when blood is made to flow through a tube whose diameter is less than about 0.3 mm is a well-known and documented phenomenon in physiology, known as the Fåhræus-Lindqvist effect. However, since the historical work of Fåhræus and Lindqvist (Amer. J. Physiol. 96(3): pp. 562–568, 1931), the underlying physical mechanism has remained enigmatic. A widely accepted qualitative explanation was provided by Haynes (Amer. J. Physiol. 198, pp. 1193–1200, 1960) according to which blood flows in microvessels with a core-annulus structure, where the erythrocytes concentrate within a central core surrounded by a plasma layer. Although sustained by observations, this conjecture lacks a rigorous deduction from the basic principles of continuum dynamics. Moreover, relations aimed to reproduce the blood apparent relative viscosity, extensively used in micro-circulation, are all empirical and not derived from the analysis of the fluid mechanical phenomena involved. In this paper, we apply the recent results illustrated in Guadagni and Farina (Int. J. Nonlinear Mech. 126, p. 103587, 2020), with the purpose of showing that Haynes’ conjecture, slightly corrected to make it more realistic, can be proved and can be used to reach a sound explanation of the Fåhræus-Lindqvist effect based on continuum mechanics. We propose a theoretical model for the blood apparent relative viscosity which is validated by matching not only the original experimental data reported by Fåhræus and Lindqvist (Amer. J. Physiol. 96(3), pp. 562–568, 1931), but also those provided by several subsequent authors.

Objective To compare the incidence and clinical features of individuals presenting in emergency rooms (ER) with facial palsy during the Italian COVID‐19 outbreak and in the same period of 2019. Methods We retrospectively reviewed the medical records for all accesses to the six ER in the province of Reggio Emilia, Italy, during the first phase of the COVID‐19 pandemic (27 February‐3 May 2020) to identify all cases of diagnosed facial palsy. Clinical information was retrieved for each patient and compared with that of facial palsy cases presenting in 2019. Result Between 27 February and 3 May 2020, 38 patients presented to provincial ERs for facial palsy; in 2019, there were 22 cases, for an incidence rate ratio of 1.73 (95% CI 1.02–2.92) for the 2020 cohort. Of the 2020 cohort, eight patients (21%) presented with active or recent symptoms consistent with COVID‐19 infection, compared with 2 (9%) in 2019 (p = .299); one was tested and resulted positive for SARS‐CoV‐2. Moreover, patients were younger (−11 years, p = .037) than those of the previous year and manifested a longer lag (+1.1 days, p = .001) between symptoms onset and ER presentation. Conclusion We observed a higher occurrence of facial palsy during the COVID‐19 outbreak compared to the same period of the previous year; 21% of patients presenting with facial palsy had active or recent symptoms consistent with SARS‐CoV‐2 infection, suggesting an excess risk of facial palsy during or after COVID‐19. These patients searched for medical attention later, probably because of the fear of contracting COVID‐19 during assistance., The objective of this study is to describe the clinical features of individuals presenting with facial palsy during the Italian COVID‐19 outbreak. We retrospectively reviewed the medical records for all accesses to the emergency departments in the province of Reggio Emilia, Italy, during the first phase of the COVID‐19 pandemic (27 February‐3 May 2020) to identify all cases of diagnosed facial palsy. We observed a higher occurrence of facial palsy during the COVID‐19 outbreak compared to the same period of the previous year; 21% of patients presenting with facial palsy had active or recent symptoms consistent with SARS‐CoV‐2 infection, suggesting a potential correlation.

This work considers the propagation of a tumor from the stage of a small avascular sphere in a host tissue and the progressive onset of a tumor neovasculature stimulated by a pro-angiogenic factor secreted by hypoxic cells. The way new vessels are formed involves cell sprouting from pre-existing vessels and following a trail via a chemotactic mechanism (CM). Namely, it is first proposed a detailed general family of models of the CM, based on a statistical mechanics approach. The key hypothesis is that the CM is composed by two components: i) the well–known bias induced by the angiogenic factor gradient; ii) the presence of stochastic changes of the velocity direction, thus giving rise to a diffusive component. Then, some further assumptions and simplifications are applied in order to derive a specific model to be used in the simulations. The tumor progression is favored by its acidic aggression towards the healthy cells. The model includes the evolution of many biological and chemical species. Numerical simulations show the onset of a traveling wave eventually replacing the host tissue with a fully vascularized tumor. The results of simulations agree with experimental measures of the vasculature density in tumors, even in the case of particularly hypoxic tumors. © 2020 Elsevier Ltd. All rights reserved., With funding from the Spanish government through the Severo Ochoa Centre of Excellence accreditation SEV-2017-0709.

Background and aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. Conclusions To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

Objective Poliomyelitis results in changes to the anterior horn cell. The full extent of cortical network changes in the motor physiology of polio survivors has not been established. Our aim was to investigate how focal degeneration of the lower motor neurons (LMN) in infancy/childhood affects motor network connectivity in adult survivors of polio. Methods Surface electroencephalography (EEG) and electromyography (EMG) were recorded during an isometric pincer grip task in 25 patients and 11 healthy controls. Spectral signal analysis of cortico-muscular (EEG-EMG) coherence (CMC) was used to identify the cortical regions that are functionally synchronous and connected to the periphery during the pincer grip task. Results A pattern of CMC was noted in polio survivors that was not present in healthy individuals. Significant CMC in low gamma frequency bands (30–47 Hz) was observed in frontal and parietal regions. Conclusion These findings imply a differential engagement of cortical networks in polio survivors that extends beyond the motor cortex and suggest a disease-related functional reorganisation of the cortical motor network. Significance This research has implications for other similar LMN conditions, including spinal muscular atrophy (SMA). CMC has potential in future clinical trials as a biomarker of altered function in motor networks in post-polio syndrome, SMA, and other related conditions.

Highlights • COVID-19 infection could led to a pro-inflammatory and pro-thrombotic state. • Cerebrovascular involvement may occur in COVID-19 infection even in young patients. • Physicians should be aware that stroke may be the first COVID-19 manifestation.

In this paper, the constrained thrust allocation problem is studied and solved for the class of over-actuated Remotely Operated Vehicles. In detail, we find the solution of the thrust allocation when the thrusters are affected by possible faults and, simultaneously, taking into account the thrusters’ saturation limits. The proposed thrust allocation algorithm is tested both numerically, with randomly generated input samples, and applied in simulation for the trajectory tracking of a Remotely Operated Vehicle, with real parameters and in combination with different control laws. The algorithm is compared with two commonly used approaches, that are the saturated pseudo-inverse method and the Matlab Quadratic Programming solver; both accuracy and computation time are considered in the analysis of the performances. The simulations show that the proposed algorithm performs better, in terms of computation time, w.r.t. the Matlab Quadratic Programming solver, while still retaining the optimality of the solution despite the saturation constraints; moreover, there is also an improvement in the tracking error regardless of the adopted control law.

An active failure and fault tolerant control scheme for an underwater remotely operated vehicle is proposed in this work. The proposed solution is based on a fault tolerant allocation, which takes into account an estimate of the faults on the vehicle’s thrusters for an accurate redistribution of the control effort. The diagnosis is based on a sliding mode observer, which generates three residuals and allows to evaluate the health condition of each actuator of the vehicle. The scheme can be adapted to any control law for the vehicle dynamics, and has been tested in simulation using a backstepping controller for the dynamics and with real world parameters, demonstrating the effectiveness of the proposed active fault tolerant control scheme.

The aim of this study is to evaluate the association between changes in routinely prescribed laboratory tests and tracheostomy-free survival in amyotrophic lateral sclerosis (ALS). Two hundred seventy-five ALS patients were retrospectively studied. BMI, forced vital capacity, hemoglobin, hematocrit, lymphocytes, cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, proteins, albumin, creatine-phosphokinase, iron, ferritin, transferrin, glucose, urea, uric acid, and creatinine were measured every 6 months from baseline to 24 months, death or study end, together with the probability of death or tracheostomy. Missing data were handled using multiple imputation chained equations. Hemoglobin (OR = 1.71, 95%CI 1.24-2.36 for IQR increase), hematocrit (OR = 1.87, 95%CI 1.34-2.63 for IQR increase), urea (OR = 1.51, 95%CI 1.21-1.89 for IQR increase), and uric acid (OR = 1.98, 95%CI 1.23-3.20 for IQR increase) were directly associated, while triglycerides (OR = 0.69, 0.51 to 0.93 for IQR increase) were inversely associated with the odds of death or tracheostomy. In our cohort, an increase of hemoglobin, hematocrit, urea, and uric acid was directly associated, and an increase of triglycerides was inversely associated with the odds of death or tracheostomy. Should these findings be replicated in an external cohort, they might help to discriminate ALS progression and patients' decisions about procedures and end of life.

Neurotoxic chemicals including several pesticides have been suggested to play a role in the etiology of amyotrophic lateral sclerosis (ALS). We investigated the relation between organochlorine pesticides and their metabolites (OCPs), polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in the etiology of sporadic ALS, determining for the first time their levels in cerebrospinal fluid as indicator of antecedent exposure. We recruited 38 ALS patients and 38 controls referred to an Italian clinical center for ALS care, who underwent a lumbar puncture for diagnostic purposes between 1994-2013, and had 1mL of cerebrospinal fluid available for the determination of OCPs, PCBs and PAHs. Many chemicals were undetectable in both case and control CSF samples, and we found little evidence of any increased disease risk according to higher levels of exposure. Among males >60 years, we found a slight but statistically very unstable increased ALS risk with higher levels of the congener PCB 28 and the OCP metabolite p,p'-DDE. Overall, these results do not suggest an involvement of the neurotoxic chemicals investigated in this study in disease etiology, although small numbers limited the precision of our results.

The Fahraeus-Lindqvist effect is usually explained from a physical point of view with the so-called Haynes’ marginal zone theory, i.e., migration of red blood cells (RBCs) to a core layer surrounded by an annular RBCs-free plasma layer. In this paper we show that the marginal layer, though causing a substantial reduction in flow resistance and increasing discharge, does not reduce the rate of energy dissipation. This fact is not surprising if one considers the electric analog of the flow in a vessel: a resistance reduction increases both the current intensity (i.e., the discharge) and the energy dissipation. This result is obtained by considering six rheological models that relate the blood viscosity to hematocrit (volume fraction occupied by erythrocytes). Some physiological implications are discussed.

We investigated whether the C9orf72 repeat expansion is associated with specific clinical features, comorbidities, and prognosis in patients with amyotrophic lateral sclerosis (ALS). A cohort of 1417 ALS patients, diagnosed between January 1, 2009 and December 31, 2013 by 13 Italian ALS Referral Centers, was screened for the C9orf72 repeat expansion, and the analyses were performed comparing patients carrying this expansion (ALS-C9Pos) to those negative for this and other explored ALS-related mutations (ALS without genetic mutations, ALSwoGM). Compared to the ALSwoGM group, ALS-C9Pos patients (n = 84) were younger at disease onset, at the first clinical observation and at diagnosis (p < 0.001). After correcting for these differences, we found that ALS-C9Pos patients had higher odds of bulbar onset, diagnosis of frontotemporal dementia (FTD) and family history of ALS, FTD, and Alzheimer's disease and had lower odds of spinal onset, non-invasive ventilation, hypertension and psychiatric diseases than ALSwoGM patients. Among these variables, those related to shorter survival time were: bulbar onset, presence of FTD, hypertension, psychiatric disease, and family history of ALS (p < 0.05). Cox proportional hazards regression multivariate analysis suggested that carrying the C9orf72 repeat expansion was an independent factor negatively impacting on survival time in men (HR 1.58, 95% CI 1.07–2.33, p = 0.021), but not in women (p > 0.05) as well as in the whole sample (p > 0.05). When compared to ALSwoGM, ALS-C9Pos showed an earlier disease onset, no significant diagnostic delay and a higher odds of bulbar onset, FTD and family history of ALS and dementia. Moreover, male sex drove the negative effect of expanded variant on survival, confirming the hypothesis that sex is likely to be a crucial factor in the biology of C9orf72-related disease.

Objective Exercise may be physically and psychologically important for people with ALS, especially in the earlier stages of the disease, and, as a consequence, current ALS clinical management includes individualized rehabilitation as part of multidisciplinary care because. However, while recent studies focused on which type of exercise is more indicated to ALS patients, there is no evidence at which frequency training sessions should be performed. Methods We performed an assessor blinded randomized clinical trial to investigate the superiority of two different frequencies of exercise on rate of progression in ALS. We enrolled 65 patients in two groups: intensive exercise regimen (IER, five sessions/week) versus usual exercise regimen (UER, two sessions/week). The primary aim was to assess if IER decreased disease progression, measured through Amyotrophic Lateral Sclerosis Functional Rating Scale‐Revised, with respect to UER. Secondary aims included assessment of adverse events, tracheostomy‐free survival, motor and respiratory functions, fatigue, quality of life and caregiver burden. Treatment regimen consisted for both groups of the same kind of exercise including aerobic training, endurance training, stretching or assisted active mobilization, differing for frequency of intervention. Results No significant changes in disease progression were found in patients under IER versus UER. At the end of the study, there were no significant differences between the two groups in survival, respiratory function, time to supporting procedures, and quality of life. Adverse events, fatigue, and caregiver burden were not different between the two treatment regimens. Conclusions Despite some limitations, our trial demonstrated that high‐frequency physical exercise was not superior to UER on ALSFRS‐R scores, motor and respiratory functions, survival, fatigue, and quality of life of ALS patients.

Objective. To characterize the cortical oscillations associated with performance of the sustained attention to response task (SART) and their disruptions in the neurodegenerative condition amyotrophic lateral sclerosis (ALS). Approach. A randomised SART was undertaken by 24 ALS patients and 33 healthy controls during 128-channel electroencephalography (EEG). Complex Morlet wavelet transform was used to quantify non-phase-locked oscillatory activity in event-related spectral perturbations associated with performing the SART. We investigated the relationships between these perturbations and task performance, and associated motor and cognitive changes in ALS. Main results. SART induced theta-band event-related synchronization (ERS) and alpha- and beta-band event-related desynchronization (ERD), followed by rebound beta ERS, in both Go and NoGo trials across the frontoparietal axis, with NoGo trials eliciting greater theta ERS and lesser beta ERS. Controls with greater Go trial beta ERS performed with greater speed and less accuracy. ALS patients exhibited increased anticipation compared to controls but similar reaction times and accuracy. Prefrontal (area under the receiver operating characteristic curve (AUROC) = 0.8, Cohen’s d = 0.97) and parietal (AUROC = 0.82, Cohen’s d = 1.12) beta-band ERD was significantly reduced in ALS but did not relate to performance, while patients with higher Edinburgh Cognitive and Behavioural ALS Screen (ECAS) ALS-specific scores demonstrated greater ERS in beta (rho = 0.72) upon successful withholding. Significance. EEG measurement of task-related oscillation changes reveals variation in cortical network engagement in relation to speed versus accuracy strategies. Such measures can also capture cognitive and motor network pathophysiology in the absence of task performance decline, which may facilitate development of more sensitive early neurodegenerative disease biomarkers.

We study the flow of a viscous fluid through a slender tapered tube whose radius may reduce to zero. The vessel is closed at the end, so that the flow is made possible owing to the fact that a portion of the tube wall is permeable. The smallness of the tube aspect ratio is exploited using an upscaling technique leading to a degenerate differential equation for pressure. Solutions are found either in explicit form or as power series expansions. This class of flows may represent, though in a largely approximated way, the blood flow though a coronary artery.

The role of cancer stem cells (CSC) in tumour growth has received increasing attention in the recent literature. Here we stem from an integro-differential system describing the evolution of a population of CSC and of ordinary (non-stem) tumour cells formulated and studied in a previous paper, and we investigate an approximation in which the system reduces to a pair of nonlinear coupled parabolic equation. We prove that the new system is well posed and we examine some general properties. Numerical simulations show more on the qualitative behaviour of the solutions, concerning in particular the so-called tumour paradox, according to which an increase of the mortality rate of ordinary (non-stem) tumour cells results asymptotically in a faster growth.

Objective: To identify cortical regions engaged during the sustained attention to response task (SART) and characterize changes in their activity associated with the neurodegenerative condition amyotrophic lateral sclerosis (ALS). Methods: High-density electroencephalography (EEG) was recorded from 33 controls and 23 ALS patients during a SART paradigm. Differences in associated event-related potential peaks were measured for Go and NoGo trials. Sources active during these peaks were localized, and ALS-associated differences were quantified. Results: Go and NoGo N2 and P3 peak sources were localized to the left primary motor cortex, bilateral dorsolateral prefrontal cortex (DLPFC), and lateral posterior parietal cortex (PPC). NoGo trials evoked greater bilateral medial PPC activity during N2 and lesser left insular, PPC and DLPFC activity during P3. Widespread cortical hyperactivity was identified in ALS during P3. Changes in the inferior parietal lobule and insular activity provided very good discrimination (AUROC > 0.75) between patients and controls. Activation of the right precuneus during P3 related to greater executive function in ALS, indicative of a compensatory role. Interpretation: The SART engages numerous frontal and parietal cortical structures. SART–EEG measures correlate with specific cognitive impairments that can be localized to specific structures, aiding in differential diagnosis.

© 2018 Elsevier Inc., To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

Purpose. The paper analyses the impact of active management styles on portfolios’ risk-return profiles, in a country specific — the BRIC market area — and in the integrated context. Our aim is to see how and if the local and global results differ and if we can outline a BRIC specific consistent behaviour. Methodology. First, we identify formally the notion of active management as an investment policy focusing on specific assets/styles; therefore we measure this concentration a) in terms of the portfolio distance from a diversified index and b) with respect to the (opposite notion of) portfolio style breadth . Given these assumptions, to test empirically how the active policies affect the fund performances we propose to use the R-square as a diversification reverse proxy . The rationale behind is that the more the fund’s tracking error the more the fund wealth is focused on a given industry or sector, and therefore on few assets, deviating from a passive portfolio strategy replicating the benchmark. Thereafter we propose to reimplement Grinold’s qualitative notion of breadth. To approximate the breadth of the fund strategies, we consider the number of factors in a predictive model to which the funds are exposed. In particular, with a factor model we investigate whether being exposed to multiple factors simultaneously is important for improving performance. Finally we assess the impact of the local risk factors, by ranking local/global portfolios through the Spearman correlation of both symmetric (Sharpe ratio) and asymmetric (Sortino-Satchel ratio, Farinelli-Tibiletti ratio) risk measures. Results. The main finding of the paper is that, contrary to similar works, not related to BRIC markets, we do not find a sound relationship between concentration and performance. This is true whether we measure the concentration in terms of higher tracking error levels or we consider portfolio concentration in terms of breadth of strategies. Based on these findings, investors called for picking for best-performing funds should take into account that the Fundamental Law of Active Management is not always true in BRIC context. As for the impact of local risk factors the rank correlation analysis between the local risk benchmark and global risk index, shows that there are some specific local factor effects coupled to the change of ratios’ benchmark. We also find that Farinelli-Tibiletti ratio, among our RAP measures, is the one exhibiting more consistent behaviour for the cross-country ranking analysis. The theoretical contribution. Some original, while grounded in the literature, approaches are introduced with respect to the study of active investment policies. Results are presented contrasting the BRIC regions with the global context, which might add new evidence to the literature of domestic CAPM and helps identifying BRIC pricing behaviours. Practical implications Traders and portfolio managers committed to active investment strategies can find new evidences concerning the implications and formal effects of these policies, particularly with respect to BRIC or BRIC focused funds. Keywords: BRIC Markets, Active Investment, Performance, Alpha, Risk. Paper type : Research paper.

This paper presents a preliminary set of results on the design of a virtual thruster-based failure tolerant control scheme for underwater vehicles. The proposed control scheme is based on the use of a suitable thruster allocation algorithm, which consists on a modified version of the Moore-Penrose pseudo inverse. When a thruster experencies a failure, the “virtual” thruster concept is introduced, as an ideal faultless thruster that operates in places of the real failed one. Thus, the resulting thrust force, which should be allocated to the failed actuator (i.e., virtual thrust), is instead reallocated to the still functional thrusters. A bank of controllers is built so that each controller is designed to control the considered underwater vehicle under a specific actuator failure scenario.

Background and purpose Only a few studies have considered the role of comorbidities in the prognosis of amyotrophic lateral sclerosis (ALS) and have provided conflicting results. Methods Our multicentre, retrospective study included patients diagnosed from 1 January 2009 to 31 December 2013 in 13 referral centres for ALS located in 10 Italian regions. Neurologists at these centres collected a detailed phenotypic profile and follow-up data until death in an electronic database. Comorbidities at diagnosis were recorded by main categories and single medical diagnosis, with the aim of investigating their role in ALS prognosis. Results A total of 2354 incident cases were collected, with a median survival time from onset to death/tracheostomy of 43 months. According to univariate analysis, together with well-known clinical prognostic factors (age at onset, diagnostic delay, site of onset, phenotype, Revised El Escorial Criteria and body mass index at diagnosis), the presence of dementia, hypertension, heart disease, chronic obstructive pulmonary disease, haematological and psychiatric diseases was associated with worse survival. In multivariate analysis, age at onset, diagnostic delay, phenotypes, body mass index at diagnosis, Revised El Escorial Criteria, dementia, hypertension, heart diseases (atrial fibrillation and heart failure) and haematological diseases (disorders of thrombosis and haemostasis) were independent prognostic factors of survival in ALS. Conclusions Our large, multicentre study demonstrated that, together with the known clinical factors that are known to be prognostic for ALS survival, hypertension and heart diseases (i.e. atrial fibrillation and heart failure) as well as haematological diseases are independently associated with a shorter survival. Our findings suggest some mechanisms that are possibly involved in disease progression, giving new interesting clues that may be of value for clinical practice and ALS comorbidity management.

I comment on a paper just appeared on JAFIB, aimed at providing an index quantifying the convenience of monitoring esophageal temperature during catheter ablation. The authors base their calculation on the data from four papers. I point out that the data from the two papers strongly against monitoring should be interpreted differently and I suggest how to retrieve more data for a more reliable determination of the said index. In addition, I briefly discuss the so-called antenna effect, sometimes put forward to discourage temperature monitoring.

The paper by Knecht et al . 1 has the merit of addressing an important issue concerning monitoring of the luminal oesophageal temperature (LET) during radiofrequency ablation procedures for the treatment of atrial fibrillation. The authors point out that LET value measured by an oesophageal thermal probe not necessarily corresponds to the actual maximum oesophageal temperature, since the lumen width offers the possibility that a flexible probe takes a path avoiding …

Background Cryoablation procedures for pulmonary veins isolation have proved to be a successful treatment of atrial fibrillation, but exposure of surrounding organs to excessively low temperatures is potentially dangerous. Hence the importance of monitoring esophageal temperature and at the same time predicting the thermal field induced by the procedure, so to provide clinicians with a valuable tool to take critical decisions. Methods and results We formulate a mathematical model for computing the temperature in the relevant region and we use numerical simulations to interpret recorded clinical data. The temperature at the outer esophageal surface can be much lower than the luminal one. Observing the esophageal lumen cooling rate at the early stage of the procedure it is possible to forecast whether temperature is bound to reach dangerous values; the same quantity has a correlation with the steepness of the transesophageal thermal gradient. Conclusion Monitoring the time evolution of luminal esophageal temperature is of fundamental importance not only to realize but also to predict well in advance critical developments of the procedure.

To assess the association, at diagnosis, between amyotrophic lateral sclerosis (ALS) and dementia in a large cohort of well-characterized Italian patients. We investigated the phenotypic profile of 1638 incident patients with definite, probable or laboratory-supported probable ALS, diagnosed from January 2009 to December 2013 in 13 Italian Referral Centers, located in 10 Italian Regions, and classified in two independent subsamples accounting for presence or not of dementia. The collected ALS features, including survival and other follow-up data, were compared between the two subgroups using a one-way analysis of variance and Chi-square test, as appropriate, logistic regression models and Kaplan–Meier survival analysis. Between-subgroup comparisons showed an older age at clinical observation (p = .006), at onset and at diagnosis (p = .002) in demented versus non demented ALS patients. After adjustment for these variables, diagnosis of dementia was significantly associated with higher odds of family history of ALS (p = .001) and frontotemporal dementia (p = .003) and of bulbar onset (p = .004), and lower odds of flail leg phenotype (p = .019) and spinal onset (p = .008). The median survival time was shorter in demented versus non-demented patients, especially in case of classical, bulbar and flail limb phenotypes and both bulbar and spinal onset. Our multicenter study emphasized the importance of an early diagnosis of comorbid dementia in ALS patients, which may have clinical impact and prognostic relevance. Moreover, our results may give further inputs to validation of ALS-specific tools for the screening of cognitive impairment in clinical practice.

We present and discuss an integro-differential equation that models economic dynamics in a closed population. An “economic inequality index” is introduced and some examples are provided showing how changes in social mobility can produce increasing (or decreasing) social equity.

In this paper the state estimation problem for linear discrete-time systems with non-Gaussian state and output noises is treated. In order to obtain a state optimal quadratic estimate with a lower computational effort and without loosing the stability, only the observable part of the second-order power system will be considered. The novelty of the proposed algorithm is to provide a method to compute, in a closed form, the rank of the observability matrix for the quadratic system. Considering a new augmented state-space built as the aggregate of the actual state vector and the observable components of the system squared state, and defining a new observation sequence composed of the original output measurements together with their square values, we will be in a condition to use Kalman filtering that, in this case, produces a suboptimal quadratic stable state estimate for the original system. The solution is given in closed form by a recursive algorithm.

We study the laminar flow of binary liquid mixture, whose components are a Newtonian fluid (solvent) and a solute, in a hollow fiber. The fiber walls are porous, but the pores size is small enough preventing the solute molecules to be transported across the membrane. This produces an osmotic pressure that offers resistance (in many cases non negligible) to the fluid cross flow. We model the phenomenon by means of a two scale procedure, introducing a small parameter e ≪ 1 (the ratio between the radius and the length of the fiber) and expanding all relevant quantities in powers of e . Thus, considering just the e 0 order approximation, we obtain a set of two equations governing both the solute concentration and the pressure along the fibers. Performing some numerical simulations we point out the critical importance of the osmosis in order to make the device working properly.