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The aim of the study is to evaluate the economic-financial performance of a sample of 236 Italian companies in relation to their environmental performance, measured in terms of CO2 emissions normalized by company turnover. In addition to the company’s economic management, the analysis also considers the equity structure and company liquidity, over a period of six years (2008-2013). The analysis involves the creation of four maps of positioning, serving to represent the companies of the sample in relation to their different attitudes: i) green efficiency; ii) operational efficiency; iii) company profitability; iv) financial viability; v) company liquidity. The examination of positioning maps also serves in identifying extreme cases, meaning the totally inefficient and the “virtuous” companies, and for conducting sectoral analyses to evaluate potential relations between company performances and the characteristics of their industrial sector

Background: Matrix metalloproteinases (MMPs) are a heterogeneous family of endopeptidases that play a role in many physiological functions, including the immune response. An imbalance between the activity of MMPs and their physiological tissue inhibitors (TIMPs) has been proposed in the pathophysiology of different autoimmune disorders. We aimed to assess the plasmatic levels of MMP-2, MMP-9, and their inhibitors TIMP-1 and -2 in patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Subjects and methods: Twenty patients with CIDP and 20 age- and sex-matched healthy controls were enrolled. Plasma concentrations of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined by the enzyme-linked immunosorbent assay. Results: CIDP subjects had higher MMP-9 concentrations along with TIMP-1 downregulation when compared to controls, with the consequent increase in the MMP-9/TIMP-1 ratio (p

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Background Hepatitis C virus (HCV) elimination by 2030, as targeted by the World Health Organization (WHO), requires that 90% of people with chronic infection be diagnosed and 80% treated. We estimated the cascade of care (CoC) for chronic HCV infection in mainland France in 2011 and 2016, before and after the introduction of direct-acting antivirals (DAAs). Methods The numbers of people (1) with chronic HCV infection, (2) aware of their infection, (3) receiving care for HCV and (4) on antiviral treatment, were estimated for 2011 and 2016. Estimates for 1) and 2) were based on modelling studies for 2011 and on a virological sub-study nested in a national cross-sectional survey among the general population for 2016. Estimates for 3) and 4) were made using the National Health Data System. Results Between 2011 and 2016, the number of people with chronic HCV infection decreased by 31%, from 192,700 (95% Credibility interval: 150,900-246,100) to 133,500 (95% Confidence interval: 56,900-312,600). The proportion of people aware of their infection rose from 57.7 to 80.6%. The number of people receiving care for HCV increased by 22.5% (representing 25.7% of those infected in 2016), while the number of people on treatment increased by 24.6% (representing 12.1% of those infected in 2016). Conclusions This study suggests that DAAs substantially impact CoC. However, access to care and treatment for infected people remained insufficient in 2016. Updating CoC estimates will help to assess the impact of new measures implemented since 2016 as part of the goal to eliminate HCV.

The topic of sustainability of reinforced concrete structures is strictly related with their durability in aggressive environments. In particular, at equal environmental impact, the higher the durability of construction materials, the higher the sustainability. The present review deals with the possible strategies aimed at producing sustainable and durable reinforced concrete structures in different environments. It focuses on the design methodologies as well as the use of unconventional corrosion-resistant reinforcements, alternative binders to Portland cement, and innovative or traditional solutions for reinforced concrete protection and prevention against rebars corrosion such as corrosion inhibitors, coatings, self-healing techniques, and waterproofing aggregates. Analysis of the scientific literature highlights that there is no preferential way for the production of “green” concrete but that the sustainability of the building materials can only be achieved by implementing simultaneous multiple strategies aimed at reducing environmental impact and improving both durability and performances.

Background: Neurological immune-related adverse events (nirAEs) are rare toxicities of immune-checkpoint inhibitors (ICI). With the increase of ICI oncological indications, their incidence is growing. Their recognition and management remain nevertheless challenging. Methods: A national, web-based database was built to collect cases of neurological symptoms in patients receiving ICI and not attributable to other causes after an adequate workup. Results: We identified 27 patients who developed nirAEs (20 males, median age 69years). Patients received anti-PD1/PDL1 (78%), anti-CTLA4 (4%), or both (19%). Most common cancers were melanoma (30%) and non-small cell lung cancer (26%). Peripheral nervous system was mostly affected (78%). Median time to onset was 43.5days and was shorter for peripheral versus central nervous system toxicities (36 versus 144.5days, p = 0.045). Common manifestations were myositis (33%), inflammatory polyradiculoneuropathies (33%), and myasthenia gravis (19%), alone or in combination, but the spectrum of diagnoses was broad. Most patients received first-line glucocorticoids (85%) or IVIg (15%). Seven patients (26%) needed second-line treatments. At last follow-up, four (15%) patients were deceased (encephalitis, 1; myositis/myasthenia with concomitant myocarditis, 2; acute polyradiculoneuropathy, 1), while seven (26%) had a complete remission, eight (30%) partial improvement, and six (22%) stable/progressing symptoms. ICI treatment was discontinued in most patients (78%). Conclusions: Neurological irAEs are rare but potentially fatal. They primarily affect neuromuscular structures but encompass a broad range of presentations. A prompt recognition is mandatory to timely withheld immunotherapy and administrate glucocorticoids. In corticoresistant or severely affected patients, second-line treatments with IVIg or plasmapheresis may result in additional benefit.

Autoimmune encephalitis associated with antibodies against neuronal surface targets (NSAE) are rare but still underrecognized conditions that affect adult and pediatric patients. Clinical guidelines have recently been published with the aim of providing diagnostic clues regardless of antibody status. These syndromes are potentially treatable but the choice of treatment and its timing, as well as differential diagnoses, long-term management, and clinical and paraclinical follow-up, remain major challenges. In the absence of evidence-based guidelines, management of these conditions is commonly based on single-center expertise. Taking into account different published expert recommendations in addition to the multicenter experience of the Italian Working Group on Autoimmune Encephalitis, both widely accepted and critical aspects of diagnosis, management and particularly of immunotherapy for NSAE have been reviewed and are discussed. Finally, we provide consensus-based practical advice for managing hospitalization and follow-up of patients with NSAE.

Objectives Autoimmune encephalitis due to antibodies against neuronal surface antigens (NSA-Ab) frequently presents with cognitive impairment, often as the first and prevalent manifestation, but few studies have systematically assessed the frequency of NSA-Ab in consecutive patients with established neurodegenerative disorders. Methods We studied sera of 93 patients (41F, 52 M), aged 69.2 ± 9.4 years, with neurodegenerative conditions, and of 50 population controls aged over 60 years. Specific NSA-Abs were investigated by antigen-specific cell-based assays (CBAs). After testing, we evaluated the association between the NSA-Abs and clinical, CSF and radiological features. Results The patients included 13/93 (13.8%) who had specific antibodies to neuronal surface antigens: 6 GlyR, 3 GABAAR (1 also positive for AMPAR), 2 LGI1, 1 CASPR2 and 1 GABABR. One of the 50 controls (2%) was positive for NMDAR antibody and the others were negative on all tests (P = 0.020). No difference was observed in antibody frequency between patients presenting with parkinsonism and those presenting with dementia (P = 0.55); however, NSA-Ab were more frequent in those with unclassified forms of dementia (5/13, 38.5%) than in those with unclassified parkinsonism (2/9, 22.2%) or with classified forms of dementia (4/43, 9.3%) or parkinsonism (2/28, 7.1%) (P = 0.03). A logistic regression analysis demonstrated that an unclassified diagnosis (P = 0.02) and an irregular progression (P = 0.024) were predictors of seropositive status. Conclusions NSA-Abs are relatively frequent in patients with neurodegenerative disorders, particularly in those with an irregular disease progression of atypical clinical features, inconsistent with a recognized diagnosis. The significance of these antibodies and their possible primary or secondary roles need to be investigated in prospective studies.

Objective Progressive multifocal leukoencephalopathy (PML) is still burdened by high mortality in a subset of patients, such as those affected by hematological malignancies. The aim of this study was to analyze the safety and carry out preliminary evaluation of the efficacy of polyomavirus JC (JCPyV)-specific T cell therapy in a cohort of hematological patients with PML. Methods Between 2014 and 2019, 9 patients with a diagnosis of "definite PML" according to the 2013 consensus who were showing progressive clinical deterioration received JCPyV-specific T cells. Cell lines were expanded from autologous or allogenic peripheral blood mononuclear cells by stimulation with JCPyV antigen-derived peptides. Results None of the patients experienced treatment-related adverse events. In the evaluable patients, an increase in the frequency of circulating JCPyV-specific lymphocytes was observed, with a decrease or clearance of JCPyV viral load in cerebrospinal fluid. In responsive patients, transient appearance of punctate areas of contrast enhancement within, or close to, PML lesions was observed, which was interpreted as a sign of immune control and which regressed spontaneously without the need for steroid treatment. Six of 9 patients achieved PML control, with 5 alive and in good clinical condition at their last follow-up. Interpretation Among other novel treatments, T cell therapy is emerging as a viable treatment option in patients with PML, particularly for those not amenable to restoration of specific immunity. Neurologists should be encouraged to refer PML patients to specialized centers to allow access to this treatment strategy. ANN NEUROL 2021;89:769-779.

ObjectiveTo assess the prevalence and isotypes of anti-nodal/paranodal antibodies to nodal/paranodal proteins in a large chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cohort, compare clinical features in seronegative vs seropositive patients, and gather evidence of their isotype-specific pathogenic role.MethodsAntibodies to neurofascin-155 (Nfasc155), neurofascin-140/186 (Nfasc140/186), contactin-1 (CNTN1), and contactin-associated protein 1 (Caspr1) were detected with ELISA and/or cell-based assay. Antibody pathogenicity was tested by immunohistochemistry on skin biopsy, intraneural injection, and cell aggregation assay.ResultsOf 342 patients with CIDP, 19 (5.5%) had antibodies against Nfasc155 (n = 9), Nfasc140/186 and Nfasc155 (n = 1), CNTN1 (n = 3), and Caspr1 (n = 6). Antibodies were absent from healthy and disease controls, including neuropathies of different causes, and were mostly detected in patients with European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) definite CIDP (n = 18). Predominant antibody isotypes were immunoglobulin G (IgG)4 (n = 13), IgG3 (n = 2), IgG1 (n = 2), or undetectable (n = 2). IgG4 antibody-associated phenotypes included onset before 30 years, severe neuropathy, subacute onset, tremor, sensory ataxia, and poor response to intravenous immunoglobulin (IVIG). Immunosuppressive treatments, including rituximab, cyclophosphamide, and methotrexate, proved effective if started early in IVIG-resistant IgG4-seropositive cases. Five patients with an IgG1, IgG3, or undetectable isotype showed clinical features indistinguishable from seronegative patients, including good response to IVIG. IgG4 autoantibodies were associated with morphological changes at paranodes in patients' skin biopsies. We also provided preliminary evidence from a single patient about the pathogenicity of anti-Caspr1 IgG4, showing their ability to penetrate paranodal regions and disrupt the integrity of the Nfasc155/CNTN1/Caspr1 complex.ConclusionsOur findings confirm previous data on the tight clinico-serological correlation between antibodies to nodal/paranodal proteins and CIDP. Despite the low prevalence, testing for their presence and isotype could ultimately be part of the diagnostic workup in suspected inflammatory demyelinating neuropathy to improve diagnostic accuracy and guide treatment.Classification of evidenceThis study provides Class III evidence that antibodies to nodal/paranodal proteins identify patients with CIDP (sensitivity 6%, specificity 100%).

Background and purpose : Autoimmune encephalitides (AE) include a spectrum of neurological disorders whose diagnosis revolves around the detection of neuronal antibodies (Abs). Consensus-based diagnostic criteria (AE-DC) allow clinic-serological subgrouping of AE, with unclear prognostic implications. The impact of AE-DC on patients’ management was studied, focusing on the subgroupofAb-negative-AE. Methods: This was a retrospective multicenter study on patients fulfilling AE-DC. All patients underwent Ab testing with commercial cell-based assays (CBAs) and, when available, in-house assays (immunohistochemistry, live/fixed CBAs, neuronal cultures) that contributed to defining final categories. Patients were classified as Ab-positive-AE [N-methyl-d-aspartate-receptor encephalitis (NMDAR-E), Ab-positive limbic encephalitis (LE), definite-AE] or Ab-negative-AE (Ab-negative-LE, probable-AE, possible-AE). Results: Commercial CBAs detected neuronal Abs in 70/118 (59.3%) patients. Testing 37/48 Ab-negative cases, in-house assays identified Abs in 11 patients (29.7%). A hundred and eighteen patients fulfilled the AE-DC, 81 (68.6%) with Ab-positive-AE (Ab-positive-LE, 40; NMDAR-E, 32; definite-AE, nine) and 37 (31.4%) with Ab-negative-AE (Ab-negative-LE, 17; probable/possible-AE, 20). Clinical phenotypes were similar in Ab-positive-LE versus Ab-negative-LE. Twenty-four/118 (20.3%) patients had tumors, and 19/118 (16.1%) relapsed, regardless of being Ab-positive or Ab-negative. Ab-positive-AE patients were treated earlier than Ab-negative-AE patients (P=0.045), responded more frequently to treatments (92.3% vs. 65.6%, P&nbsp

This document presents the guidelines for the cerebrospinal fluid (CSF) analysis and the determination of oligoclonal bands (OCBs) as pivotal tests in neuroin flammatory pathologies of the central nervous system. The guidelines have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on the pathologies in which the CSF analysis is indicated, and, particularly, on those characterized by the presence of OCBs in the intrathecal compartment, indications and limits of CSF analysis and OCB determination, instructions for result interpretation, and agreed laboratory protocols (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

This document presents the guidelines for onconeural antibody testing that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on paraneoplastic neurological syndromes, indications and limits of onconeural antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

The use of neural networks to predict airport passenger activity choices inside the terminal is presented in this paper. Three network architectures are proposed: Feedforward Neural Networks (FNN), Long Short-Term Memory (LSTM) networks, and a combination of the two. Inputs to these models are both static (passenger and trip characteristics) and dynamic (real-time passenger tracking). A real-world case study exemplifies the application of these models, using anonymous WiFi traces collected at Bologna Airport to train the networks. The performance of the models were evaluated according to the misclassification rate of passenger activity choices. In the LSTM approach, two different multi-step forecasting strategies are tested. According to our findings, the direct LSTM approach provides better results than the FNN, especially when the prediction horizon is relatively short (20 minutes or less)., Post-print of paper presented at the 2019 6th International Conference on Models and Technologies for Intelligent Transportation Systems (MT-ITS)

Purpose: Radiological hallmark of autoimmune limbic encephalitis (LE) is a hyperintense signal in MRI T2-weighted images of mesial temporal structures. We aimed to identify conventional magnetic resonance imaging (MRI) features that can help distinguish LE from temporal glioma. Methods: Brain MRIs of 25 patients affected by antibody-positive autoimmune LE, 24 patients affected by temporal glioma (tumor group), and 5 negative controls were retrospectively blindly evaluated in random order. Results: Ten brain MRIs from the LE group were correctly recognized; one additional patient with mesial temporal hyperintensity with anti-AK5 abs LE was wrongly diagnosed as having a tumor. The brain MRIs of the remaining 14 of the 25 patients with LE were judged negative or, in three cases, showed features not typical for LE. In the tumor group, all MRIs showed pathological alterations diagnosed as tumors in 22/24 cases and as LE in two (2/22, 9%). Unilateral lesions were more common in tumors than in neuroradiologically abnormal LE (96% vs. 18%, p < 0.001). T2/FLAIR hyperintensity of the parahippocampal gyrus was associated more with tumor than with LE (71% vs. 18%) (p = 0,009), as T2/FLAIR hyperintensity of extralimbic structures (p = 0.015), edema (p = 0.041), and mass effect (p = 0.015). Maintenance of gray/white matter distinction was strongly associated with LE (91% vs. 17%, p < 0.001). Conclusion: Conventional brain MRI is a fundamental tool in the differential diagnosis between LE and glioma. Bilateral involvement and maintenance of gray/white matter distinction at the cortical/subcortical interface are highly suggestive of LE.

Paraneoplastic neurological syndromes are very rare and often associated to breast, ovarian and small cells lung cancers. Paraneoplastic motor neuron diseases (MNDs) are even rarer, and frequently described in patients with breast cancer. We presented the first case of patient affected by HER2-positive breast tumor and possible paraneoplastic lower motor neuron disease. In literature, few cases are reported but no one highlights the tumor receptors' profile. Instead, HER2-positive breast cancers are prone to be related to anti-Yo-associated paraneoplastic cerebellar disorders. Anti-onconeural antibodies positivity can be rarely found, confirming that paraneoplastic MND have no specific biomarkers. The presence of CSF oligoclonal bands (OBs) suggests the presence of immune-mediated mechanism, in absence of other possible OBs causes.

This document presents the guidelines for testing antibodies against neuronal surface antigens that have been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on autoimmune encephalitis associated with antibodies against neuronal surface antigens, indications and limits of testing for such antibodies, instructions for result interpretation, and an agreed laboratory protocol (Appendix A) are reported for the communicative community of neurologists and clinical pathologists.

This document presents the guidelines for anti-aquaporin-4 (AQP4) antibody testing that has been developed following a consensus process built on questionnaire-based surveys, internet contacts, and discussions at workshops of the sponsoring Italian Association of Neuroimmunology (AINI) congresses. Essential clinical information on neuromyelitis optica spectrum disorders, indications and limits of anti-AQP4 antibody testing, instructions for result interpretation, and an agreed laboratory protocol (Appendix) are reported for the communicative community of neurologists and clinical pathologists.

Tumoral neoangiogenesis characterizes high grade gliomas. Relative Cerebral Blood Volume (rCBV), calculated with Dynamic Susceptibility Contrast (DSC) Perfusion-Weighted Imaging (PWI), allows for the estimation of vascular density over the tumor bed. The aim of the study was to characterize putative tumoral neoangiogenesis via the study of maximal rCBV with a Region of Interest (ROI) approach in three tumor areas—the contrast-enhancing area, the nonenhancing tumor, and the high perfusion area on CBV map—in patients affected by contrast-enhancing glioma (grades III and IV). Twenty-one patients were included: 15 were affected by grade IV and 6 by grade III glioma. Maximal rCBV values for each patient were averaged according to glioma grade. Although rCBV from contrast-enhancement and from nonenhancing tumor areas was higher in grade IV glioma than in grade III (5.58 and 2.68; 3.01 and 2.2, resp.), the differences were not significant. Instead, rCBV recorded in the high perfusion area on CBV map, independently of tumor compartment, was significantly higher in grade IV glioma than in grade III (7.51 versus 3.78,P=0.036). In conclusion, neoangiogenesis encompasses different tumor compartments and CBV maps appear capable of best characterizing the degree of neovascularization. Facing contrast-enhancing brain tumors, areas of high perfusion on CBV maps should be considered as the reference areas to be targeted for glioma grading.