ICARUS at the Fermilab Short-Baseline Neutrino program: initial operation.

The ICARUS collaboration employed the 760-ton T600 detector in a successful 3-year physics run at the underground LNGS laboratory, performing a sensitive search for LSND-like anomalous νe appearance in the CERN Neutrino to Gran Sasso beam, which contributed to the constraints on the allowed neutrino oscillation parameters to a narrow region around 1 eV2. After a significant overhaul at CERN, the T600 detector has been installed at Fermilab. In 2020 the cryogenic commissioning began with detector cool down, liquid argon filling and recirculation. ICARUS then started its operations collecting the first neutrino events from the booster neutrino beam (BNB) and the Neutrinos at the Main Injector (NuMI) beam off-axis, which were used to test the ICARUS event selection, reconstruction and analysis algorithms. ICARUS successfully completed its commissioning phase in June 2022. The first goal of the ICARUS data taking will be a study to either confirm or refute the claim by Neutrino-4 short-baseline reactor experiment. ICARUS will also perform measurement of neutrino cross sections with the NuMI beam and several Beyond Standard Model searches. After the first year of operations, ICARUS will search for evidence of sterile neutrinos jointly with the Short-Baseline Near Detector, within the Short-Baseline Neutrino program. In this paper, the main activities carried out during the overhauling and installation phases are highlighted. Preliminary technical results from the ICARUS commissioning data with the BNB and NuMI beams are presented both in terms of performance of all ICARUS subsystems and of capability to select and reconstruct neutrino events.

Analysis of risk factors for pharyngocutaneous fistula after total laryngectomy with particular focus on nutritional status.

Pharyngocutaneous fistula (PCF) is the most common complication following total laryngectomy and the most difficult to manage. It often causes increased morbidity, delays starting adjuvant therapy, prolongs hospitalisation, increases treatment costs and reduces the quality of life (QoL). The objective of this study is to analyse the predisposing factors and the most important nutritional parameters related to the development of PCF in patients undergoing total laryngectomy and to suggest medical alternatives that might improve results. We performed a retrospective study of 69 patients who underwent either primary or salvage total laryngectomy in our department between January 2008 and January 2012. Risk factors for fistula formation were analysed including tumour characteristics (histology, grading, AJCC stage), treatment (primary or salvage surgery, extent of resection, flap reconstruction, preoperative radiotherapy), comorbidity and nutritional status (preoperative haemoglobin, albumin and prealbumin levels and their changes during hospitalisation). Twenty-four patients developed a PCF (overall incidence 34.8%). Fistula formation was significantly higher in patients with diabetes, preoperative malnutrition (identified from low preoperative albumin and prealbumin levels). After specific nutritional evaluation and support, no patient developed a PCF. Risk factors for PCF formation are extensively treated in the literature but identification of high-risk patients is still controversial. Our study demonstrates that nutritional status of the patient, assessed by preoperative albumin, is also an important risk factor for PCF formation in addition to classical factors. Maintenance of a normal perioperative nutritional status can be helpful to avoid this complication.

Caracterización del perfil epidemiológico de las llamadas alCentro de Información Toxicológica de la Universidad Católica (CITUC), en el año 2010 / Characterization of the epidemiological profile of calls received at the Poison Information Center of the Catholic University (CITUC), in 2010

Objetivo: Describir y caracterizar el perfil epidemiológico de las llamadas recibidas en el año 2010 correspondiente a exposiciones, por el Centro de Información Toxicológica de la Pontificia Universidad Católica de Chile. Método: Se realizó un estudio retrospectivo y descriptivo de las llamadas registradas por el CITUC durante el año 2010. Se analizaron los siguientes datos: número total de llamadas, lugar de la llamada, circunstancia de la exposición, tipo y número de los agentes involucrados, vías de exposición, tiempo desde la exposición, género y edad de los pacientes. Resultados: Se registraron 29.592 llamadas. 45,2 por ciento de las consultas provenían del hogar y 53,2 por ciento de instalaciones médicas. 69,3 por ciento fueron exposiciones accidentales y 27,6 por ciento intencionales. Los medicamentos se presentaron como agente causal de una exposición en 58,4 por ciento de las llamadas, seguidos por los productos de uso doméstico (18,7 por ciento) y plaguicidas (5,8 por ciento). La ingestión fue la vía de exposición que predominó en un 79,3 por ciento del total de casos. 41,0 por ciento del total de las llamadas, se realizaron dentro de la primera hora post-exposición. Las exposiciones en niños menores de 14 años correspondieron a 51,6 por ciento de las llamadas. Conclusiones: Los medicamentos constituyen el principal agente involucrado en intoxicaciones. La principal vía de exposición es la ingesta y el principal grupo de población afectado son los niños menores de 14 años,. Estos indicadores muestran la necesidad imperante de desarrollar campañas de prevención e información avaladas por el Ministerio de Salud, respecto al correcto uso de los medicamentos, como también la introducción del envase resistente ala manipulación de los niños y la educación de la población.

Objective: To describe and to characterize the epidemiologoc profile of the entering pone calls in 2010 belonging to exposures by the Centro de Información Toxicológica de la Pontificia Universidad Católica de Chile. Method: A retrospective and descriptive study of pone calls registered by the CITUC has been made during 2010. The following has been analyzed: total pone calls number, place of the call, exposure circumstances, kind and number ofagents involved, exposure way, time from exposure, gender and age of the patients. Outcomes: 29.592 phone calls were registered. 45,2 percent of the questions came from home and 53,2 percent from medical institutions. 69,3 percent were non intented exposures and 27,6 percent were intented. The drugs were the causal agent of exposures in 58,4 percent of the phone calls, followed by cleaning use products (18,7 percent) and insecticides (5,8 percent). Swallowing was the predominant exposure way with 79,3 percent of the total. 41 percent of total of phone calls, were made in the first hour after exposure. The children under 14 years exposure cases, were were 51,6 percent of total phone calls. Conclusions: Medical drugs are the principal involved agent in intoxications. The main way of exposition is swallowing and the major population group involved is children under 14 years. These indicators shows the need of developing prevention and information campaigns supported by Secretary of Health, oriented to right use of drugs, as well as the use of safety drug boxes for children and population education.

Regional spread pattern predicts survival in patients with sporadic amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Sporadic amyotrophic lateral sclerosis (sALS) is a disease with a focal clinical onset and contiguous spread. We examined patterns of disease spread following symptoms onset in sALS and whether the pattern of spread predicted survival. METHODS: Review of medical records (2003-2009) at London Ontario and Buenos Aires clinic cohorts retrieved 318 patients with sporadic sALS. According to patient self-report, we determined eight spread patterns: rostro-caudal, caudo-rostral, crossed, circular, superior interposed, middle interposed, inferior interposed and isolated. The variables studied were as follows: age, gender, sALS phenotypes, time from onset to diagnosis and time and direction of the spreading to the first region. Survival from symptoms onset was analysed by Kaplan-Meier, Tarone-Ware and Cox proportional hazards methods. RESULTS: The direction of first spread was horizontal in 33%, rostral to caudal in 32% and caudal to rostral in 21%, whereas spread to remote regions was observed in 14% of patients. Survival curves and 3- and 5-year survival rates favoured patients with an isolated and caudo-rostral pattern of spread compared to patients progressing to distant regions without involvement in the intervening region, or 'superior and inferior interposed patterns' (Tarone-Ware P = 0.001, χ(2) = 0.002 and χ(2) = 0.006, respectively). Factors affecting survival were gender, time to diagnosis, flail arm phenotype and age at diagnosis. CONCLUSIONS: We have provided evidence that not all spread in ALS is contiguous and that the nature of symptom progression influences survival. Patients with sALS with 'interposed patterns' had a worse prognosis, whereas patients with caudo-rostral pattern fared better than the rest.

Acute induction of human IL-8 production by intestinal epithelium triggers neutrophil infiltration without mucosal injury.

AIM: Neutrophil migration in the intestine depends on chemotaxis of neutrophils to CXC chemokines produced by epithelial cells. The goal of this project was to determine if acute induction of a CXC chemokine gradient originating from intestinal epithelial cells is sufficient to induce neutrophil influx into intact intestinal tissue. METHODS AND RESULTS: The authors developed a double transgenic mouse model with doxycycline induced human IL-8 expression restricted to intestinal epithelial cells. Doxycycline treatment of double transgenic mice for three days resulted in a 50-fold increase in the caecal IL-8 concentration and influx of neutrophils into the lamina propria. Although neutrophils entered the paracellular space between epithelial cells, complete transepithelial migration was not observed. Doxycycline treatment also increased the water content of the caecal and colonic stool, indicating dysfunctional water transport. However, the transmural electrical resistance was not decreased. Neutrophils recruited to the intestinal epithelium did not show evidence of degranulation and the epithelium remained intact as judged by histology. CONCLUSIONS: This conditional transgenic model of chemokine expression provides evidence that acute induction of IL-8 in the intestinal epithelium is sufficient to trigger neutrophil recruitment to the lamina propria, but additional activation signals are needed for full activation and degranulation of neutrophils, mucosal injury, and complete transepithelial migration.

Oxygen radical-mediated reduction in basal and agonist-evoked NO release in isolated rat heart.

Oxygen free radicals (OFR) play a primary role in ischemia-reperfusion-mediated vascular dysfunction and this is paralleled by a loss of endothelial nitric oxide synthase (eNOS) activity. The authors tested whether a direct exposure to OFR may affect vascular relaxation by altering nitric oxide (NO) release. Effects of electrolysis(EL)-generated OFR on basal and agonist-evoked NO release were monitored in isolated rat hearts by oxyhemoglobin assay. Electrolysis-induced changes were compared with those obtained after 30 min perfusion with NOS and cyclooxygenase (COX) inhibitors NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and indomethacin (INDO, 1 m M). Electrolysis-generated hydroxyl radical (.OH) formed by.O2-and H2O2 via the Fenton reaction as revealed by Electron Paramagnetic Resonance (EPR). After EL, basal NO release declined by 60% and coronary perfusion pressure (CPP) increased by approximately 70%. L-NAME/INDO perfusion similarly lowered NO release (-63%) but increased CPP less than EL (56+/-3%P<0.03 v post-EL). In presence of excess substrates and cofactors eNOS activity was not affected by EL. Both acetylcholine (ACh; 1 microM) and bradykinin (BK; 10 n M) had minimal effect in reversing EL-induced vasoconstriction, whereas both partially reversed L -NAME/INDO-mediated constriction. Sodium nitroprusside (SNP, 1 microM) completely reversed L-NAME/INDO constriction and partly countered that after EL (-38+/-2.5, P<0.001). Acetylcholine-evoked NO release was nearly abolished by both treatments whereas BK still elicited partial NO release after eNOS/cyclooxygenase inhibition (P<0.001) but not after EL. In conclusion, OFR severely impair NO-mediated coronary vasorelaxation affecting both basal and agonist-evoked NO release but not eNOS activity. However, EL also significantly blunts NOS/COX-independent vasodilation suggesting alteration of other vasodilatative pathways.

Detection of Chlamydophila pneumoniae DNA in peripheral blood mononuclear cells of blood donors in the north-east of Italy.

Recent studies have implicated Chlamydia pneumoniae (now Chlamydophila pneumoniae) in the pathogenesis of atherosclerosis and demonstrated its presence within human peripheral blood mononuclear cells (PBMCs). In this study the presence of C. pneumoniae DNA was assessed, using nested PCR, in PBMCs from 169 active blood donors as a function of age, of specific antibodies and C-reactive protein. The results obtained demonstrated a high degree of global positivity (46.15%), which was higher in females (52%) than in males (43.7%). Seroepidemiological studies showed a high percentage of positivity both in subjects positive by PCR (65.91%) and negative by PCR (71.74%). The clinical implication of such finding are under study.

Endothelin-1 and NO2/NO3 circulating levels after short-term (1h) oxygen supplementation in patients with chronic respiratory failure during long-term oxygen treatment (LTOT).

The effect of acute oxygen administration on endothelin-1 (ET-1) and nitrates (NO.2/NO.3), the latter as stable end products of nitric oxide (NO), were evaluated in arterial and venous blood of chronic respiratory failure (CRF) patients underwent to a continuous long-term oxygen therapy (LTOT). After one hour of oxygen supplementation, ET-1 showed a marked and significant decrease more pronounced in venous blood whereas no statistical change in NO.2/NO.3 concentrations were observed in both arterial and venous blood. There are evidences for increased expression of ET-1 in several pulmonary diseases and for ET-1 plasma reduction in Adult Respiratory Distress Syndrome (ARDS) in patients which recovered. ET-1 is a potent human pulmonary vessel constrictor and may have other effects including plasma exudation, increased mucus secretion and a increased fibrinogenesis. Our data suggest that the improvement in air function, evaluated in part by the decreased release of inflammatory mediators and mainly by reduction in the pulmonary arterial resistance, may be a consequence of the decrease in ET-1 content in the lungs of CRF patients treated with LTOT.

Immunopathological mechanisms underlying the time-course of Trichinella spiralis cardiomyopathy in rats.

The present study shows that isolated, perfused hearts from rats orally infected with Trichinella spiralis have a reduced left ventricular developed pressure (LVDP), heart rate (HR) and coronary flow (CF). This reduction is considerably enhanced by a single bolus (100 pM) of PAF (platelet activating factor, an eosinophil activator), especially at 21 days post-infection (d.p.i.), which is the time of the maximum increase in blood and tissue eosinophilia. Helminthic DNA analysis shows that, from 21 d.p.i. onwards, the morphological and functional changes in the myocardium cannot be ascribed to the parasite's presence, whereas its antigens and the attendant immunopathological reactions might have a role in the induction of myocardial damage and dysfunction. Some perivascular inflammatory cells (eosinophils and mast cells) appear to undergo degranulation. All these data suggest a complex sequence of events, from acute myocarditis (21 d.p.i.) which may lead in time (48 d.p.i. onwards) to a dilating cardiomyopathy.

Emergency medical services in mass gatherings: the experience of the Formula 1 Grand Prix 'San Marino' in Imola.

Mass gatherings are special situations for which mass medical care must be preplanned. Acute emergencies occur at public gatherings and medical coverage on site has proven benefit. Responsibility of general plan, management of specific problems, transport planning, communications system, guidelines and protocols, special situations management, ancillary supports, sources of extra help for unforeseen needs are the most important items to consider. In mass gatherings the whole emergency medical service (EMS) planning and management has to depend on the emergency department direction, with its authority on all aspects of patient care in the EMS system. This report concerns the planning of EMS and of medical care in a situation at risk for mass casualties at the Formula I Grand Prix-Championship Racing 'San Marino' of Imola.

Removal of platelet-activating factor in experimental continuous arteriovenous hemofiltration.

OBJECTIVE: There is a positive correlation between the amount of ultrafiltration and the improved survival rate of patients with ischemia or sepsis-induced acute renal failure. Continuous arteriovenous hemofiltration (CAVH) removes vasoactive substances with a molecular weight of < 1000 daltons. This study evaluated the removal of platelet-activating factor, a lipid mediator of endotoxic shock, by CAVH with respect to kinetics, adsorption, and ultrafiltration. DESIGN: Prospective laboratory study. SUBJECTS: Normal human subjects. INTERVENTIONS: Radioactive [3H] or biologically active platelet-activating factor was added to whole blood or washed blood resuspended in Tris-buffered (pH 7.2) physiologic saline with 4% human serum albumin or plasma. Whole or washed blood cells or plasma were recirculated at 100 mL/min through polysulfone hemofilters for 120 mins with ultrafiltration (condition A), without ultrafiltration (condition B), or in a static condition (condition C). Concentrations of albumin, total protein, and radioactive or biologically active platelet-activating factor in samples obtained from the blood and ultrafiltrate compartment were determined. MEASUREMENTS: Biologically active platelet-activating factor was quantified on washed rabbit platelets and results were expressed in ng/mL over a calibration curve obtained with synthetic platelet-activating factor. MAIN RESULTS: [3H]-platelet-activating factor added to recirculated whole blood was ultrafiltered (percent of ultrafiltered platelet-activating factor/min: 0.48 +/- 0.02 [SD]; total platelet-activating factor removed in 120 mins: 15.52%; condition A) at significantly (p < .001) higher amounts than when added to washed blood cells (percent of ultrafiltered platelet-activating factor removed/min: 0.195 +/- 0.06; total platelet-activating factor removed in 120 mins: 7.46%). The highest amounts of [3H]-platelet-activating factor were bound to polysulfone membranes after recirculation with whole blood (44.5 +/- 12.2%) than with washed blood (1.1 +/- 0.3%) or plasma (11.9 +/- 0.7%). Biologically active platelet-activating factor concentrations significantly decreased in both conditions A and B (maximal decrease at 120 mins: 63% and 59%, respectively). No significant reduction could be observed in condition C. CONCLUSIONS: These studies provide experimental evidence for the prompt, efficient removal of platelet-activating factor in CAVH and provide a possible rationale for the beneficial effect of this therapy in the development of multiple organ failure in sepsis.

Prevalence of anti-HCV and risk factors for hepatitis C virus infection in healthy pregnant women.

The prevalence of anti-HCV antibodies and the risk factors for HCV infection were assessed in 5,672 pregnant women living in North Italy. All reactive sera were confirmed by RIBA-2 test. Anti-HCV positive pregnant women together with an anti-HCV negative control group, were interviewed by standardised questionnaire to identify "known" or "potential" risk factors for HCV infection. The anti-HCV prevalence was 0.7% (40/5,672), higher than that observed among blood donors in the same geographical area (0.2%). The RIBA-2 assay was positive in 60% (24/40) of cases, indeterminate in 10% (4/40) and negative in 30% (12/40). As for "known" risk factors, considering RIBA-2 positivity, intravenous drug use was by far the main risk factor for HCV infection, resulting in a significantly higher risk than in the control group (50% versus 5.9% [O. R. 15.8, CI 5.4-45.5]). The ten RIBA-2 positive women without histories of transfusion or IV drug use had a significantly higher frequency of "sexual contacts with IV drug users" compared to controls (50% vs 4.9% [O. R. 19.0, CI 3.6-94.0]). In conclusion, our study provides evidence that in our geographical area the anti-HCV antibody prevalence is higher in pregnant women than in blood donors and that IV drug use and sexual contacts with IV drug users represent the most important risk factors for HCV infection among young women in North Italy.

Technical and clinical evaluation of a new asymmetric polysulfone membrane (Biosulfane).

First generation asymmetric polysulfone membranes had high hydraulic permeability (kf = 40 ml/h/mmHg/sqm) but a low diffusive permeability due to the hydrophobic nature and wall thickness of 75-100 microns. We have tested a new polysulfone membrane with a wall thickness of 40 microns in a series of in vitro and in vivo dialysis session experiments. The new "Biosulfane" membrane presented a Kf of 45.8 with constant performance up to 240 mins. The koA was 760 and the clearance value at 350 ml/min of Qb in hemodiafiltration was 255 ml/min for urea, 210 for creatinine, 225 for phosphate, 76 for inulin. In high flux dialysis the clearances were similar except for inulin which was 32% lower due to the lower convection amount. Beta-2 microglobulin clearance was 22 ml/min in high flux dialysis and 37 in hemodiafiltration. Solute sieving coefficients were close to 1 for the majority of the studied solutes in a wide range of molecular weights and slight variations were observed for charged solutes due to Donnan's effect. The sieving for Inulin was 0.96 while that for Beta-2 microglobulin was not measurable due to a large molecule adsorption on the inner structure of the fibres. The good performances of this membrane are probably due to reduced wall thickness and a consequent improvement in diffusive permeability to small size solutes.

A new scintigraphic method to characterize ultrafiltration in hollow fiber dialyzers.

Ultrafiltration and pressure profiles in hollow fiber dialyzers with different hydraulic permeabilities have been investigated with a new scintigraphic method. Radiolabelled albumin macroaggregates, used as a nondiffusible marker molecule, were added to the blood in an in vitro circuit and circulated through cuprophan and polysulphon dialyzers. Since the marker molecule was too big to cross the dialysis membrane, its changes in concentration were assumed to occur in response to the variation of the blood water content (filtration or back-filtration). These changes in concentration, recorded by a gamma camera, were evaluated to establish the cumulative values of filtration and back-filtration and their relevant profiles along the length of the dialyzer. The achieved data were compared with the experimental values of ultrafiltration empirically measured and with the theoretical values predicted by a classic linear method. Two conditions were analyzed: A) the minimal filtration rate necessary to avoid back-filtration (critical filtration); and B) the condition of zero net filtration in which filtration equals back-filtration. The nuclear method proved to be extremely precise in predicting the ultrafiltration values and significantly more precise than the linear method, especially for the highly permeable dialyzer. The reason for that probably depends on the non-linear pressure and ultrafiltration profile observed with the scintigraphic pattern of the dialyzer. Viscosity changes and local variations in blood flow may in fact interfere with the pressure drop inside the hollow fibers and result in such a complex behavior. The other interesting aspect of this method is the possibility of accurate measurement of the amount of back-filtration that wouldn't be possible with simple calculations. In conclusion, the complex nature of the phenomena regulating the water fluxes in hollow fiber dialyzers requires more complex calculation than a simple linear model to achieve an accurate range of predictability.

[The role of intra- and extracellular Ca++ in coronary vessel contraction induced in vitro by noradrenaline following a beta-adrenergic block]. / Ruolo del Ca++ intra ed extracellulare nella contrazione dei vasi coronarici indotta in vitro dalla noradrenalina, dopo blocco beta-adrenergico.

Previous studies reported that norepinephrine (NE) induces contraction of the calf isolated coronary arteries after beta-adrenergic blockade with propranolol (PR), and that the effect disappeared after phentolamine. An higher Ca++ concentration increased the response of preparation to NE, whereas the reduction of the concentration reduced the response. In isolated coronary arteries the baseline tone and contractile response to NE after PR were studied as influenced by DA and nicardipine (NI). NI always induced vessel relaxation and DA induced a contraction followed by relaxation. The NE contraction was not abolished in calcium-free medium but in presence of DA and was reduced by NI in the medium containing Ca++. We conclude that NE induces contractions by facilitating the influx of the extracellular Ca++ and by promoting the liberation of intracellular bound Ca++.