INFN What Next: Ultra-relativistic Heavy-Ion Collisions

This document was prepared by the community that is active in Italy, within INFN (Istituto Nazionale di Fisica Nucleare), in the field of ultra-relativistic heavy-ion collisions. The experimental study of the phase diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP) deconfined state will proceed, in the next 10-15 years, along two directions: the high-energy regime at RHIC and at the LHC, and the low-energy regime at FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the present and future programme of the ALICE experiment, the upgrade of which will open, in the 2020s, a new phase of high-precision characterisation of the QGP properties at the LHC. As a complement of this main activity, there is a growing interest in a possible future experiment at the SPS, which would target the search for the onset of deconfinement using dimuon measurements. On a longer timescale, the community looks with interest at the ongoing studies and discussions on a possible fixed-target programme using the LHC ion beams and on the Future Circular Collider.Comment: 99 pages, 56 figure

The future of Cybersecurity in Italy: Strategic focus area

This volume has been created as a continuation of the previous one, with the aim of outlining a set of focus areas and actions that the Italian Nation research community considers essential. The book touches many aspects of cyber security, ranging from the definition of the infrastructure and controls needed to organize cyberdefence to the actions and technologies to be developed to be better protected, from the identification of the main technologies to be defended to the proposal of a set of horizontal actions for training, awareness raising, and risk management

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

Introduction: Stroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and Methods: We retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. Results: The underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4–34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. Conclusions: SLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

IntroductionStroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (>= 500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and MethodsWe retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. ResultsThe underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (+/- 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (+/- 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. ConclusionsSLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

Influenza at the animal-human interface: A review of the literature for virological evidence of human infection with swine or avian influenza viruses other than A(H5N1)

Factors that trigger human infection with animal influenza virus progressing into a pandemic are poorly understood. Within a project developing an evidence-based risk assessment framework for influenza viruses in animals, we conducted a review of the literature for evidence of human infection with animal influenza viruses by diagnostic methods used. The review covering Medline, Embase, SciSearch and CabAbstracts yielded 6,955 articles, of which we retained 89; for influenza A(H5N1) and A(H7N9), the official case counts of the World Health Organization were used. An additional 30 studies were included by scanning the reference lists. Here, we present the findings for confirmed infections with virological evidence. We found reports of 1,419 naturally infected human cases, of which 648 were associated with avian influenza virus (AIV) A(H5N1), 375 with other AIV subtypes, and 396 with swine influenza virus (SIV). Human cases naturally infected with AIV spanned haemagglutinin subtypes H5, H6, H7, H9 and H10. SIV cases were associated with endemic SIV of H1 and H3 subtype d

Rabies and canine distemper virus epidemics in the red fox population of Northern Italy (2006–2010)

Since 2006 the red fox (Vulpes vulpes) population in north-eastern Italy has experienced an epidemic of canine distemper virus (CDV). Additionally, in 2008, after a thirteen-year absence from Italy, fox rabies was re-introduced in the Udine province at the national border with Slovenia. Disease intervention strategies are being developed and implemented to control rabies in this area and minimise risk to human health. Here we present empirical data and the epidemiological picture relating to these epidemics in the period 2006-2010. Of important significance for epidemiological studies of wild animals, basic mathematical models are developed to exploit information collected from the surveillance program on dead and/or living animals in order to assess the incidence of infection. These models are also used to estimate the rate of transmission of both diseases and the rate of vaccination, while correcting for a bias in early collection of CDV samples. We found that the rate of rabies transmission was roughly twice that of CDV, with an estimated effective contact between infected and susceptible fox leading to a new infection occurring once every 3 days for rabies, and once a week for CDV. We also inferred that during the early stage of the CDV epidemic, a bias in the monitoring protocol resulted in a positive sample being almost 10 times more likely to be collected than a negative sample. We estimated the rate of intake of oral vaccine at 0.006 per day, allowing us to estimate that roughly 68% of the foxes would be immunised. This was confirmed by field observations. Finally we discuss the implications for the eco-epidemiological dynamics of both epidemics in relation to control measures

Minimal Flavour Violation and Neutrino Masses without R-parity

We study the extension of the Minimal Flavour Violation (MFV) hypothesis to the MSSM without R-parity. The novelty of our approach lies in the observation that supersymmetry enhances the global symmetry of the kinetic term and in the fact that we consider as irreducible sources of the flavour symmetry breaking all the couplings of the superpotential including the R-parity violating ones. If R-parity violation is responsible for neutrino masses, our setup can be seen as an extension of MFV to the lepton sector. We analyze two patterns based on the non-abelian flavour symmetries SU(3)^4 \otimes SU(4) and SU(3)^5. In the former case the total lepton number and the lepton flavour number are broken together, while in the latter the lepton number can be broken independently by an abelian spurion, so that visible effects and peculiar correlations can be envisaged in flavour changing charged lepton decays like \ell_i \rightarrow \ell_j \gamma.Comment: 23 pages, 3 figures. References added. Minor changes, to appear in JHE

Trends in chronic hepatitis B virus infection in Italy over a 10-year period: Clues from the nationwide PITER and MASTER cohorts toward elimination

Objectives: The study measures trends in the profile of patients with chronic hepatitis B virus linked to care in Italy. Methods: A cross-sectional, multicenter, observational cohort (PITER cohort) of consecutive patients with hepatitis B surface antigen (HBsAg) over the period 2019-2021 from 46 centers was evaluated. The reference was the MASTER cohort collected over the years 2012-2015. Standard statistical methods were used. Results: The PITER cohort enrolled 4583 patients, of whom 21.8% were non-Italian natives. Compared with those in MASTER, the patients were older and more often female. The prevalence of hepatitis B e antigen (HBeAg) declined (7.2% vs 12.3; P <0.0001) and that of anti-hepatitis D virus (HDV) remained stable (9.3% vs 8.3%). In both cohorts, about 25% of the patients had cirrhosis, and those in the PITER cohort were older. HBeAg-positive was 5.0% vs 12.6% (P <0.0001) and anti-HDV positive 24.8% vs 17.5% (P <0.0017). In the logistic model, the variables associated with cirrhosis were anti-HDV-positive (odds ratio = 10.08; confidence interval 7.63-13.43), age, sex, and body mass index; the likelihood of cirrhosis was reduced by 40% in the PITER cohort. Among non-Italians, 12.3% were HBeAg-positive (vs 23.4% in the MASTER cohort; P <0.0001), and 12.3% were anti-HDV-positive (vs 11.1%). Overall, the adherence to the European Association for the Study of the Liver recommendations for antiviral treatment increased over time. Conclusion: Chronic hepatitis B virus infection appears to be in the process of becoming under control in Italy; however, HDV infection is still a health concern in patients with cirrhosis and in migrants

Intra-operative gallbladder scoring predicts conversion of laparoscopic to open cholecystectomy: a WSES prospective collaborative study

Abstract Introduction Laparoscopic cholecystectomy, the gold-standard approach for cholecystectomy, has surprisingly variable outcomes and conversion rates. Only recently has operative grading been reported to define disease severity and few have been validated. This multicentre, multinational study assessed an operative scoring system to assess its ability to predict the need for conversion from laparoscopic to open cholecystectomy. Methods A prospective, web-based, ethically approved study was established by WSES with a 10-point gallbladder operative scoring system; enrolling patients undergoing elective or emergency laparoscopic cholecystectomy between January 2016 and December 2017. Gallbladder surgery was considered easy if the G10 score < 2, moderate (2 ≦ 4), difficult (5 ≦ 7) and extreme (8 ≦ 10). Demographics about the patients, surgeons and operative procedures, use of cholangiography and conversion rates were recorded. Results Five hundred four patients, mean age 53.5 (range 18–89), were enrolled by 55 surgeons in 16 countries. Surgery was performed by consultants in 70% and was elective in (56%) with a mean operative time of 78.7 min (range 15-400). The mean G10 score was 3.21, with 22% deemed to have difficult or extreme surgical gallbladders, and 71/504 patients were converted. The G10 score was 2.98 in those completed laparoscopically and 4.65 in the 71/504 (14%) converted. (p <  0.0001; AUC 0.772 (CI 0.719–0.825). The optimal cut-off point of 0.067 (score of 3) was identified in G10 vs conversion to open cholecystectomy. Conversion occurred in 33% of patients with G10 scores of ≥ 5. The four variables statistically predictive of conversion were GB appearance—completely buried GB, impacted stone, bile or pus outside GB and fistula. Conclusion The G10 operative scores provide simple grading of operative cholecystectomy and are predictive of the need to convert to open cholecystectomy. Broader adaptation and validation may provide a benchmark to understand and improve care and afford more standardisation in global comparisons of care for cholecystectomy