INFN muon tomography demonstrator: past and recent results with an eye to near-future activities.

A short description of the muon tomography demonstrator at the INFN Laboratori Nazionali di Legnaro near Padua, Italy, is given and the principal achievements owing to the data collected at that experimental facility are presented. In particular, the feasibility studies for several applications based on the muon-tomographic technology, within national and European projects, are discussed. The experimental problems and the procedures used to improve the performance are underlined. In addition, new activities and the related detector optimization are illustrated.This article is part of the Theo Murphy meeting issue 'Cosmic-ray muography'.

AEgIS at ELENA: outlook for physics with a pulsed cold antihydrogen beam.

The efficient production of cold antihydrogen atoms in particle traps at CERN's Antiproton Decelerator has opened up the possibility of performing direct measurements of the Earth's gravitational acceleration on purely antimatter bodies. The goal of the AEgIS collaboration is to measure the value of g for antimatter using a pulsed source of cold antihydrogen and a Moiré deflectometer/Talbot-Lau interferometer. The same antihydrogen beam is also very well suited to measuring precisely the ground-state hyperfine splitting of the anti-atom. The antihydrogen formation mechanism chosen by AEgIS is resonant charge exchange between cold antiprotons and Rydberg positronium. A series of technical developments regarding positrons and positronium (Ps formation in a dedicated room-temperature target, spectroscopy of the n=1-3 and n=3-15 transitions in Ps, Ps formation in a target at 10 K inside the 1 T magnetic field of the experiment) as well as antiprotons (high-efficiency trapping of [Formula: see text], radial compression to sub-millimetre radii of mixed [Formula: see text] plasmas in 1 T field, high-efficiency transfer of [Formula: see text] to the antihydrogen production trap using an in-flight launch and recapture procedure) were successfully implemented. Two further critical steps that are germane mainly to charge exchange formation of antihydrogen-cooling of antiprotons and formation of a beam of antihydrogen-are being addressed in parallel. The coming of ELENA will allow, in the very near future, the number of trappable antiprotons to be increased by more than a factor of 50. For the antihydrogen production scheme chosen by AEgIS, this will be reflected in a corresponding increase of produced antihydrogen atoms, leading to a significant reduction of measurement times and providing a path towards high-precision measurements.This article is part of the Theo Murphy meeting issue 'Antiproton physics in the ELENA era'.

Evaluating the cost implications of integrating SARS-CoV-2 genome sequencing for infection prevention and control investigation of nosocomial transmission within hospitals.

BACKGROUND: The COG-UK hospital-onset COVID-19 infection (HOCI) trial evaluated the impact of SARS-CoV-2 whole-genome sequencing (WGS) on acute infection, prevention, and control (IPC) investigation of nosocomial transmission within hospitals. AIM: To estimate the cost implications of using the information from the sequencing reporting tool (SRT), used to determine likelihood of nosocomial infection in IPC practice. METHODS: A micro-costing approach for SARS-CoV-2 WGS was conducted. Data on IPC management resource use and costs were collected from interviews with IPC teams from 14 participating sites and used to assign cost estimates for IPC activities as collected in the trial. Activities included IPC-specific actions following a suspicion of healthcare-associated infection (HAI) or outbreak, as well as changes to practice following the return of data via SRT. FINDINGS: The mean per-sample costs of SARS-CoV-2 sequencing were estimated at £77.10 for rapid and £66.94 for longer turnaround phases. Over the three-month interventional phases, the total management costs of IPC-defined HAIs and outbreak events across the sites were estimated at £225,070 and £416,447, respectively. The main cost drivers were bed-days lost due to ward closures because of outbreaks, followed by outbreak meetings and bed-days lost due to cohorting contacts. Actioning SRTs, the cost of HAIs increased by £5,178 due to unidentified cases and the cost of outbreaks decreased by £11,246 as SRTs excluded hospital outbreaks. CONCLUSION: Although SARS-CoV-2 WGS adds to the total IPC management cost, additional information provided could balance out the additional cost, depending on identified design improvements and effective deployment.

Experimental determination of in-medium cluster binding energies and Mott points in nuclear matter.

In-medium binding energies and Mott points for d, t, 3He and α clusters in low-density nuclear matter have been determined at specific combinations of temperature and density in low-density nuclear matter produced in collisions of 47A MeV 40Ar and 64Zn projectiles with 112Sn and 124Sn target nuclei. The experimentally derived values of the in-medium modified binding energies are in good agreement with recent theoretical predictions based upon the implementation of Pauli blocking effects in a quantum statistical approach.

Laboratory tests of low density astrophysical nuclear equations of state.

Clustering in low density nuclear matter has been investigated using the NIMROD multidetector at Texas A&M University. Thermal coalescence modes were employed to extract densities, ρ, and temperatures, T, for evolving systems formed in collisions of 47A MeV (40)Ar+(112)Sn, (124)Sn and (64)Zn+(112)Sn, (124)Sn. The yields of d, t, (3)He, and (4)He have been determined at ρ=0.002 to 0.03 nucleons/fm(3) and T=5 to 11 MeV. The experimentally derived equilibrium constants for α particle production are compared with those predicted by a number of astrophysical equations of state. The data provide important new constraints on the model calculations.

[Nephrotic syndrome after treatment with d-penicillamine in a pediatric patient with Wilson's disease]. / Sindrome nefrosica da penicillamina in un caso pediatrico di Morbo di Wilson.

We describe a case of nephrotic syndrome (NS) after a 7 months treatment with D-penicillamine in a 14 years old girl with Wilson's disease, with a prompt regression at the discontinuation of the drug. Kidney function, proteinuria in particular, must be always monitored during the chelating therapy, and the drug must be discontinued as soon as signs of renal injury are detected.

Nosocomial acquisition of influenza is associated with significant morbidity and mortality: Results of a prospective observational study.

BACKGROUND: Nosocomial acquisition of influenza is known to occur but the risk after exposure to a known case and the outcomes after acquisition are poorly defined. METHODS: Prospective observational study of patients exposed to influenza from another patient in a multi-site healthcare organisation, with follow-up of 7 days or until discharge, and PCR-confirmation of symptomatic disease. Multivariable analysis was used to investigate association of influenza acquisition with high dependency unit/intensive care unit (HDU/ITU) admission and in-hospital mortality. RESULTS: 23/298 (7.7%) contacts of 11 cases were subsequently symptomatic and tested influenza-positive during follow-up. HDU/ITU admission was significantly higher in these secondary cases (6/23, 26%) compared to flu-negative contacts (20/275, 7.2%; p = 0.002). In-hospital mortality was significantly higher in secondary cases (5/23, 21.7%) compared to flu-negative contacts (11/275, 4%; p < 0.001). In multivariable analysis, age (OR 1.25 95% CI: 1.01-1.54, p = 0.02) and being a secondary case (OR 4.77, 95% CI: 1.63-13.9, p = 0.008) were significantly associated with HDU/ITU admission in contacts. Age (OR 1.00, 95% CI: 0.93-1.00, p = 0.02), being a secondary case after exposure to influenza (OR 3.81, 95% CI 1.09-13.3, p = 0.049) and co-morbidity (OR 1.29 per unit increment in the Charlson score, 95% CI 1.02-1.61, p = 0.03) were significantly associated with in-hospital mortality in contacts. CONCLUSIONS: Nosocomial acquisition of influenza was significantly associated with increased risk of HDU/ITU admission and in-hospital mortality.

[Pediatric steatohepatitis: is it only obesity?]. / Steatoepatite in un bambino obeso: solo questione di peso?

We describe the case of an 11-year-old obese child with nonalcoholic steatohepatitis and Wilson's disease. Nonalcoholic steatohepatitis, although frequently found in patients with obesity, can also be caused by other etiologies, including Wilson's disease, which must therefore always be ruled out in the obese child.

Diagnostic Approach to Acute Liver Failure in Children: A Position Paper by the SIGENP Liver Disease Working Group.

Acute liver failure (ALF) is a clinical condition characterized by the abrupt onset of coagulopathy and biochemical evidence of hepatocellular injury, leading to rapid deterioration of liver cell function. In children, ALF has been characterized by raised transaminases, coagulopathy, and no known evidence of pre-existing chronic liver disease; unlike in adults, the presence of hepatic encephalopathy is not required to establish the diagnosis. Although rare, ALF has a high mortality rate without liver transplantation (LT). Etiology of ALF varies with age and geographical location, although it may remain indeterminate in a significant proportion of cases. However, identifying its etiology is crucial to undertake disease-specific management and evaluate indication to LT. In this position statement, the Liver Disease Working Group of the Italian Society of Gastroenterology, Hepatology and Nutrition (SIGENP) reviewed the most relevant studies on pediatric ALF to provide recommendations on etiology, clinical features and diagnostic work-up of neonates, infants and children presenting with ALF. Recommendations on medical management and transplant candidacy will be discussed in a following consensus conference.

Real-world deployment of lateral flow SARS-CoV-2 antigen detection in the emergency department to provide rapid, accurate and safe diagnosis of COVID-19.

BACKGROUND: Point-of-care (POC) SARS-CoV-2 lateral-flow antigen detection (LFD) testing in the emergency department (ED) could inform rapid infection control decisions but requirements for safe deployment have not been fully defined. METHODS: Review of LFD test results, laboratory and POC-RT-PCR results and ED-performance metrics during a two-week high SARS-CoV-2 prevalence period followed by several months of falling prevalence. AIM: Determine whether LFD testing can be safely deployed in ED to provide an effective universal SARS-CoV-2 testing capability. FINDINGS: 93% (345/371) of COVID-19 patients left ED with a virological diagnosis during the 2-week universal LFD evaluation period compared to 77% with targeted POC-RT-PCR deployment alone, on background of approximately one-third having an NHS Track and Trace RT-PCR test-result at presentation. LFD sensitivity and specificity was 70.7% and 99.1% respectively providing a PPV of 97.7% and NPV of 86.4% with disease prevalence of 34.7%. ED discharge-delays (breaches) attributable to COVID-19 fell to 33/3532 (0.94%) compared with the preceding POC-RT-PCR period (107/4114 (2.6%); p=<0.0001). Importantly, LFD testing identified 1 or 2 clinically-unsuspected COVID-19 patients/day. Three clinically-confirmed LFD false positive patients were appropriately triaged based on LFD action-card flowchart, and only 5 of 95 false-negative LFD results were inappropriately admitted to non-COVID-19 areas where no onward-transmission was identified. LFD testing was restricted to asymptomatic patients when disease prevalence fell below 5% and detected 1-3 cases/week. CONCLUSION: Universal SARS-CoV-2 LFD testing can be safely and effectively deployed in ED alongside POC-RT-PCR testing during periods of high and low disease prevalence.

Functional impairment of cytomegalovirus specific CD8 T cells predicts high-level replication after renal transplantation.

Human cytomegalovirus (HCMV) remains an important cause of morbidity after allotransplantation, causing a range of direct effects including hepatitis, pneumonitis, enteritis and retinitis. A dominant risk factor for HCMV disease is high level viral replication in blood but it remains unexplained why only a subset of patients develop such diseases. In this detailed study of 25 renal transplant recipients, we show that functional impairment of HCMV specific CD8 T cells in the production of interferon gamma was associated with a 14-fold increased risk of progression to high level replication. The CD8 T-cell impairment persisted during the period of high level replication and was more prominent in patients above 40 years of age (odds ratio = 1.37, p = 0.01) and was also evident in dialysis patients. Threshold levels of functional impairment were associated with an increased risk of future HCMV replication and there was a direct relationship between the functional capacity of HCMV ppUL83 CD8 T cells and HCMV load (R(2)= 0.83). These results help to explain why a subset of seropositive individuals develop HCMV replication and are at risk of end-organ disease and may facilitate the early identification of individuals who would benefit from targeted anti-HCMV therapy after renal transplantation.

Polyfunctional cytomegalovirus-specific CD4+ and pp65 CD8+ T cells protect against high-level replication after liver transplantation.

To determine whether polyfunctional CD4+ T-cell responses coupled with CD8+ T-cell responses against human cytomegalovirus (HCMV) are key to the control of HCMV replication we prospectively analyzed 29 liver transplant recipients for CD4+ T-cell responses against soluble HCMV antigen, pp65 and IE1 proteins, CD8+ T-cell responses against pp65 and IE1 proteins and a range of T helper (Th) 1 and Th2 cytokines. Eleven patients (38%) developed HCMV DNAemia at a median of 21 days post-liver transplantation (range 17-31 days). There was a significantly lower frequency and absolute number of total HCMV CD4+ T cells producing IFNgamma, IFNgamma+IL2 and IL2 and pp65-CD8+ T cells producing IFNgamma in patients with DNAemia. The quantities of Th1 and Th2 cytokines present during the first 20 days posttransplant were not predictive of DNAemia. Cut-off levels during the first 20 days posttransplant of 0.1% of lysate stimulated CD4+ T cells producing IL2, and pp65-CD8+ T cells producing IFNgamma above 0.4% had positive and negative predictive values for DNAemia of 54% and 100% and 50% and 92%, respectively. Measuring polyfunctional CD4+ T cells against HCMV early posttransplant may allow targeted intervention to minimize the occurrence and acute and long-term consequences of HCMV replication.

Measurement of 14MeV neutron-induced prompt gamma-ray spectra from 15 elements found in cargo containers.

Within the EURopean Illicit TRAfficking Countermeasures Kit (EURITRACK) project, the gamma-ray spectra produced in a series of materials by 14-MeV tagged-neutron beams have been collected in the inspection portal equipped with large volume NaI(Tl) detectors, in order to build a database of signatures for various elements: C, N, O, Na, Al, Si, Cl, K, Ca, Cr, Fe, Ni, Cu, Zn, Pb. The measured spectra have been compared with prediction from Monte Carlo simulations to verify the consistency of the relevant nuclear data inputs. This library of measured 14-MeV neutron-induced gamma-ray spectra is currently used in a data processing algorithm to unfold the energy spectra of the transported goods into elementary contributions, thus allowing material identification.

[Hepatitis type A with atypical course]. / Epatite A ad evoluzione atipica.

Hepatitis A virus infection is usually asymptomatic in children. Classic symptomatic forms and atypical clinical manifestations are known. We report a paediatric case of hepatitis A with marked cholestasis, treated with steroids, and with an unusual prolonged course.

[Acute acalculous cholecystitis as a complication of hepatitis A: report of 2 pediatric cases]. / Colecistite acuta acalcolotica in corso di epatite A: 2 casi pediatrici.

Acute acalculous cholecystitis (CAA) is very rare in children and it is usually related to infectious agents. We report 2 paediatric cases of CAA complicating hepatitis type A, with a favourable evolution with conservative treatment.

Monte Carlo analysis of tagged neutron beams for cargo container inspection.

Fast neutrons produced via D+T reactions and tagged by the associated particle technique have been recently proposed to inspect cargo containers. The general characteristics of this technique are studied with Monte Carlo simulations by determining the properties of the tagged neutron beams as a function of the relevant design parameters (energy and size of the deuteron beam, geometry of the charged particle detector). Results from simulations, validated by experiments, show that the broadening of the correlation between the alpha-particle and the neutron, induced by kinematical as well as geometrical (beam and detector size) effects, is important and limits the dimension of the minimum voxel to be inspected. Moreover, the effect of the container filling is explored. The material filling produces a sizeable loss of correlation between alpha-particles and neutrons due to scattering and absorption. Conditions in inspecting cargo containers are discussed.

The detection of landmines by neutron backscattering: exploring the limits of the technique.

Neutron backscattering (NB) sensors have been proposed for Humanitarian De-mining applications. Recently, a prototype hand-held system integrating a NB sensor in a metal detector has been developed within the EU-funded DIAMINE Project. The results obtained in terms of performance of the NB systems and limitations in its use are presented in this work. It is found that the performance of NB sensors is strongly limited by the presence of the soil moisture and by its small-scale variations. The use of the neutron hit distribution to reduce false alarms is explored.

Interferon treatment in children with chronic hepatitis C: long-lasting remission in responders, and risk for disease progression in non-responders.

BACKGROUND AND AIM: Large interferon-based therapeutic trials are still lacking in children with hepatitis C and the long-term safety and efficacy of interferon is unknown. This study describes the outcome of hepatitis C in 43 children enrolled in an open-label interferon trial, and were followed up to 66 months after stopping treatment. PATIENTS AND METHODS: All patients received interferon alfa2a (5MU/m(2)) thrice weekly for 6 months; children with genotype 1b received 3MU/m(2) thrice weekly for 6 additional months. RESULTS: Nine children discontinued interferon for adverse events and three were not compliant to treatment. Eight (19%, intention to treat analysis), including 2/20 (10%) with genotype 1b and 6/12 (50%) with genotypes 2 or 3, were sustained responders 12 months after stopping therapy. During further follow-up (mean+/-S.D.: 44.7+/-14.6 months), response was maintained; two non-responders cleared viremia, while a young boy progressed to cirrhosis. CONCLUSIONS: Small sample size and therapy withdrawal are the major limitations in the interpretation of our results. Nevertheless, our data, suggesting that response to interferon in children with hepatitis C is genotype-related and stable, agree with the results of large studies in adults. The outcome in non-responders was variable, including persistence of viremia and mild-moderate cytolysis (most cases), progression to cirrhosis, or eventual sustained viremia clearance.

Factors influencing malnutrition in children waiting for liver transplants.

Nutrition deficiencies are common in children with chronic liver disease. To determine whether age, hepatic dysfunction, or energy intake influences this malnutrition, we evaluated the nutritional status of 49 children aged 2.5 mo to 13 y (mean: 35 mo; median: 12 mo). The children were divided into two groups according to age: group 1-29 patients aged < or = 1 y (mean: 7 mo; median: 7 mo); and group 2-20 patients > 1 y (mean: 75 mo; median: 59 mo). Hepatic dysfunction was defined according to the Malatack criteria. Seventy-two-hour dietary intakes were recorded by a nutritionist. Nutritional status was assessed by anthropometric measures when the patients were enrolled on the waiting list for liver transplants. We evaluated the following indexes: weight, height, fat body mass, and lean body mass on the basis of height-age (age at which height reached 50th Italian height percentile). Mean height Z scores were low in both groups, but the difference was not significant. Mean weight Z scores and mean percentages of fat body mass were significantly lower (P < 0.001) in group 1 than in group 2 patients. In group 2, lean body mass and fat body mass were significantly lower (P < 0.05) in patients with moderate-to-severe hepatic failure than in patients with mild hepatic dysfunction. The mean energy intake was in the range of the recommended daily allowances for age but was insufficient for both groups of patients. The evidence of significant acute and chronic malnutrition confirmed the need for nutritional support, especially for younger and older children with moderate-to-severe hepatic dysfunction. We emphasize the necessity of accurate assessment of nutritional status by simple anthropometric measurements to be sure of the effects and adequacy of the nutritional intervention.

Hepatitis C in childhood: epidemiological and clinical aspects.

Hepatitis C virus (HCV) is responsible for most cases of chronic non-A, non-B hepatitis in multi-transfused children, but has been also implicated in at least one third of cases without history of parenteral exposure. We have recently evaluated the natural history of chronic hepatitis C in 37 children without underlying systemic diseases. None of the patients had a history of acute hepatitis and only 22 were symptomatic at presentation. Liver histology was consistent with active liver disease of mild to moderate activity in 42% of cases (one child had cirrhosis) and with persistent or lobular hepatitis in the remaining cases. During a mean follow-up period of 3.4 +/- 3.2 years symptoms were rarely observed and none of the patients developed liver failure, but 97% maintained abnormal alanine-aminotransferase levels. These results suggest that chronic hepatitis C in children, at least in its early stage, is a mild disease infrequently associated with severe liver lesions; however the persistence of liver damage over the years raises questions about the long-term outcome of the illness and about the rationale of antiviral therapy.