Supernova neutrino physics with a nuclear emulsion detector

The existence of the coherent neutrino-nucleus scattering reaction requires to evaluate, for any detector devoted to WIMP searches, the irreducible background due to conventional neutrino sources and at same time, it gives a unique chance to reveal supernova neutrinos. We report here a detailed study concerning a new directional detector, based on the nuclear emulsion technology. A Likelihood Ratio test shows that, in the first years of operations and with a detector mass of several tens of tons, the observation of the supernova signal can be achieved. The determination of the distance of the supernova from the neutrinos and the observation of $^8$B neutrinos are also discussed.Comment: 22 pages, 12 figure

"What is hidden behind the mask?" Facial emotion recognition at the time of COVID-19 pandemic in cognitively normal multiple sclerosis patients

Social cognition deficits have been described in people with multiple sclerosis (PwMS), even in absence of a global cognitive impairment, affecting predominantly the ability to adequately process emotions from human faces. The COVID-19 pandemic has forced people to wear face masks that might interfere with facial emotion recognition. Therefore, in the present study, we aimed at investigating the ability of emotion recognition in PwMS from faces wearing masks. We enrolled a total of 42 cognitively normal relapsing-remitting PwMS and a matched group of 20 healthy controls (HCs). Participants underwent a facial emotion recognition task in which they had to recognize from faces wearing or not surgical masks which of the six basic emotions (happiness, anger, fear, sadness, surprise, disgust) was presented. Results showed that face masks negatively affected emotion recognition in all participants (p < 0.001); in particular, PwMS showed a global worse accuracy than HCs (p = 0.005), mainly driven by the "no masked" (p = 0.021) than the "masked" (p = 0.064) condition. Considering individual emotions, PwMS showed a selective impairment in the recognition of fear, compared with HCs, in both the conditions investigated ("masked": p = 0.023; "no masked": p = 0.016). Face masks affected negatively also response times (p < 0.001); in particular, PwMS were globally hastier than HCs (p = 0.024), especially in the "masked" condition (p = 0.013). Furthermore, a detailed characterization of the performance of PwMS and HCs in terms of accuracy and response speed was proposed. Results from the present study showed the effect of face masks on the ability to process facial emotions in PwMS, compared with HCs. Healthcare professionals working with PwMS at the time of the COVID-19 outbreak should take into consideration this effect in their clinical practice. Implications in the everyday life of PwMS are also discussed

A Model Driven Approach to Water Resource Analysis based on Formal Methods and Model Transformation

AbstractSeveral frameworks have been proposed in literature in order to cope with critical infrastructure modelling issues, and almost all rely on simulation techniques. Anyway simulation is not enough for critical systems, where any problem may lead to consistent loss in money and even human lives. Formal methods are widely used in order to enact exhaustive analyses of these systems, but their complexity grows with system dimension and heterogeneity. In addition, experts in application domains could not be familiar with formal modelling techniques. A way to manage complexity of analysis is the use of Model Based Transformation techniques: analysts can express their models in the way they use to do and automatic algorithms translate original models into analysable ones, reducing analysis complexity in a completely transparent way.In this work we describe an automatic transformation algorithm generating hybrid automata for the analysis of a natural water supply system. We use real system located in the South of Italy as case study

A novel prognostic score to assess the risk of progression in relapsing-remitting multiple sclerosis patients

BACKGROUND: At patient-level, the prognostic value of several features that are known to be associated with an increased risk of converting from relapsing remitting (RR) to secondary phase (SP) multiple sclerosis (MS), remain limited.METHODS: Among 262 RRMS patients followed up for ten years, we assessed the probability of developing the SP course based on clinical and conventional and non-conventional magnetic resonance imaging (MRI) parameters at diagnosis and after two years. We used a machine learning method, the Random Survival Forests, to identify, according to their minimal depth (MD), the most predictive factors associated with the risk of SP conversion, which were then combined to compute the Secondary Progressive Risk Score (SP-RiSc).RESULTS: During the observation period, 69 (26%) patients converted to SPMS. The number of cortical lesions (MD=2.47) and age (MD=3.30) at diagnosis, the global cortical thinning (MD = 1.65), the cerebellar cortical volume loss (MD = 2.15) and the cortical lesion load increase (MD=3.15) over the first two years, exerted the greatest predictive effect. Three patients' risk-groups were identified; in the high-risk group, 85% (46 out of 55) of patients entered the SP phase in 7 median years. The SP-RiSc optimal cut-off estimated was 17.7 showing specificity and sensitivity of 87% and 92% respectively, and overall accuracy of 88%.CONCLUSIONS: The SP-RiSc yielded a high performance in identifying MS patients with high probability to develop SPMS, which can help improve management strategies. These findings are the premise of further larger prospective studies to assess its use in clinical settings

The use of the central vein sign in the diagnosis of multiple sclerosis: a systematic review and meta-analysis

Background: The central vein sign (CVS) is a radiological feature proposed as a multiple sclerosis (MS) imaging biomarker able to accurately differentiate MS from other white matter diseases of the central nervous system. In this work, we evaluated the pooled proportion of the CVS in brain MS lesions and to estimate the diagnostic performance of CVS to perform a diagnosis of MS and propose an optimal cut-off value. Methods: A systematic search was performed on publicly available databases (PUBMED/MEDLINE and Web of Science) up to 24 August 2020. Analysis of the proportion of white matter MS lesions with a central vein was performed using bivariate random-effect models. A meta-regression analysis was performed and the impact of using particular sequences (such as 3D echo-planar imaging) and post-processing techniques (such as FLAIR*) was investigated. Pooled sensibility and specificity were estimated using bivariate models and meta-regression was performed to address heterogeneity. Inclusion and publication bias were assessed using asymmetry tests and a funnel plot. A hierarchical summary receiver operating curve (HSROC) was used to estimate the summary accuracy in diagnostic performance. The Youden index was employed to estimate the optimal cut-off value using individual patient data. Results: The pooled proportion of lesions showing a CVS in the MS population was 73%. The use of the CVS showed a remarkable diagnostic performance in MS cases, providing a pooled specificity of 92% and a sensitivity of 95%. The optimal cut-off value obtained from the individual patient data pooled together was 40% with excellent accuracy calculated by the area under the ROC (0.946). The 3D-EPI sequences showed both a higher pooled proportion compared to other sequences and explained heterogeneity in the meta-regression analysis of diagnostic performances. The 1.5 Tesla (T) scanners showed a lower (58%) proportion of MS lesions with a CVS compared to both 3T (74%) and 7T (82%). Conclusions: The meta-analysis we have performed shows that the use of the CVS in differentiating MS from other mimicking diseases is encouraged; moreover, the use of dedicated sequences such as 3D-EPI and the high MRI field is beneficial

Immune Response after COVID-19 mRNA Vaccination in Multiple Sclerosis Patients Treated with DMTs

The impact of disease-modifying therapies (DMTs) on the immune response to coronavirus disease-2019 (COVID-19) vaccines in persons with multiple sclerosis (pwMS) needs further elucidation. We investigated BNT162b2 mRNA COVID-19 vaccine effects concerning antibody seroconversion, inflammatory mediators' level and immunophenotype assessment in pwMS treated with cladribine (c-pwMS, n = 29), fingolimod (f-pwMS, n = 15) and ocrelizumab (o-pwMS, n = 54). Anti-spike immunoglobulin (Ig)-G detection was performed by an enzyme immunoassay; molecular mediators (GrB, IFN-gamma and TNF-alpha) were quantified using the ELLA platform, and immunophenotype was assessed by flow cytometry. ANCOVA, Student's t-test and Pearson correlation analyses were applied. Only one o-pwMS showed a mild COVID-19 infection despite most o-pwMS lacking seroconversion and showing lower anti-spike IgG titers than c-pwMS and f-pwMS. No significant difference in cytokine production and lymphocyte count was observed in c-pwMS and f-pwMS. In contrast, in o-pwMS, a significant increase in GrB levels was detected after vaccination. Considering non-seroconverted o-pwMS, a significant increase in GrB serum levels and CD4+ T lymphocyte count was found after vaccination, and a negative correlation was observed between anti-spike IgG production and CD4+ T cells count. Differences in inflammatory mediators' production after BNT162b2 vaccination in o-pwMS, specifically in those lacking anti-spike IgG, suggest a protective cellular immune response

Cerebrospinal fluid IgM levels in association with inflammatory pathways in multiple sclerosis patients

Background Intrathecal immunoglobulin M (IgM) synthesis has been demonstrated in the early disease stages of multiple sclerosis (MS) as a predictor factor of a worsening disease course. Similarly, increased cerebrospinal fluid (CSF) molecules related to B-cell intrathecal activity have been associated with a more severe MS progression. However, whether CSF levels of IgM are linked to specific inflammatory and clinical profile in MS patients at the time of diagnosis remains to be elucidated. Methods Using customized Bio-Plex assay, the protein levels of IgG, IgA, IgM, and of 34 other inflammatory molecules, related to B-cell, T-cell, and monocyte/macrophage activity, were analyzed in the CSF of 103 newly diagnosed relapsing-remitting MS patients and 36 patients with other neurological disorders. CSF IgM levels were also correlated with clinical and neuroradiological measures [advanced 3-T magnetic resonance imaging (MRI) parameters], at diagnosis and after 2 years of follow-up. Results A 45.6% increase in CSF IgM levels was found in MS patients compared to controls (p = 0.013). CSF IgM levels correlated with higher CSF levels of CXCL13 (p = 0.039), CCL21 (p = 0.023), interleukin 10 (IL-10) (p = 0.025), IL-12p70 (p = 0.020), CX3CL1 (p = 0.036), and CHI3L1 (p = 0.048) and were associated with earlier age of patients at diagnosis (p = 0.008), white matter lesion (WML) number (p = 0.039) and disease activity (p = 0.033) after 2 years of follow-up. Conclusion IgMs are the immunoglobulins mostly expressed in the CSF of naive MS patients compared to other neurological conditions at the time of diagnosis. The association between increased CSF IgM levels and molecules related to both B-cell immunity (IL-10) and recruitment (CXCL13 and CCL21) and to macrophage/microglia activity (IL-12p70, CX3CL1, and CHI3L1) suggests possible correlation between humoral and innate intrathecal immunity in early disease stage. Furthermore, the association of IgM levels with WMLs and MS clinical and MRI activity after 2 years supports the idea of key role of IgM in the disease course

CSF levels of CXCL12 and osteopontin as early markers of primary progressive multiple sclerosis

Background and objectives: To evaluate the extent of intrathecal inflammation in patients with primary progressive MS (PPMS) at the time of diagnosis and to define markers and a specific inflammatory profile capable of distinguishing progressive from relapsing-remitting multiple sclerosis (RRMS). Methods: Levels of 34 pro- and anti-inflammatory cytokines and chemokines in the CSF were evaluated at the diagnosis in 16 patients with PPMS and 80 with RRMS. All patients underwent clinical evaluation, including Expanded Disability Status Scale assessment and a 3T brain MRI to detect white matter and cortical lesion number and volume and global and regional cortical thickness. Results: Higher levels of CXCL12 (odds ratio [OR] = 3.97, 95% CI [1.34-11.7]) and the monocyte-related osteopontin (OR = 2.24, 95% CI [1.01-4.99]) were detected in patients with PPMS, whereas levels of interleukin-10 (IL10) (OR = 0.28, 95% CI [0.09-0.96]) were significantly increased in those with RRMS. High CXCL12 levels were detected in patients with increased gray matter lesion number and volume (p = 0.001, r = 0.832 and r = 0.821, respectively). Pathway analysis confirmed the chronic inflammatory processes occurring in PPMS. Conclusions: At the time of diagnosis, a specific CSF protein profile can recognize the presence of early intrathecal inflammatory processes, possibly stratifying PPMS with respect to RRMS. Elevated CSF levels of CXCL12 and osteopontin suggested a key role of brain innate immunity and glia activity in MS. These molecules could represent useful candidate markers of MS progression, with implications for the pathogenesis and treatment of progressive MS. Classification of evidence: This study provides Class III evidence that CXCL12 and monocyte-related osteopontin may be correlated with PPMS, and IL-10 may be related to RRMS. It is may be correlated due to Bonferroni correction negating the statistical correlations found in the study

Chapter The offshore environmental impact by Sarno river in Naples bay (South-West Italy)

The goal of this work has been to establish the influence of the Sarno river on the present sedimentation in the Naples bay continental shelf by evaluating organic matter contribution and pollution. Sediments samples were collected, by van Veen grab, in 71 stations located offshore the Sarno river between Vesuvian and Sorrento Peninsula coasts. The characteristics of the surface sediments were analysed to highlight spatial trends in the (i) granulometry (grain-size); (ii) total nitrogen, organic carbon and total phosphorus; (iii) metal content (Hg, Cd, Pb, As, Cr, Cu, Ni, Zn, Fe and Mn)