Comparative analysis of the dispersion modeling and dose projection results performed under BARCO international project.

Radiological assessments on zones to take protective actions in case of a nuclear or radiological emergency involve a series of real-time forecasts of radiological impact on the public at various distances from the release point, using actual weather or forecast data, information on the source term or facility status, and primary radiation monitoring data. This practice is implemented during the operation of emergency centers around the world in order to promptly report the occurrence and possible consequences of radiological accidents in the country and abroad in the event of a possible transboundary impact. Since the Chornobyl disaster, a lot of emergency exercises, research programs and projects, in particular, benchmarking, have served as international platforms for improving modeling capacity in atmospheric dispersion. This activity is carried out both on the basis of past severe accidents with significant atmospheric releases and corresponding radiological consequences, and on the basis of specific conditional (hypothetical) events that are developed in accordance with the purpose of the study. The paper is focused on the comparison results performed under the international project "Benchmarking on Assessment of Radiological COnsequences" (BARCO) conducted in 2020-2021 between five technical support organisations - members of the European Technical Safety Organisations Network (ETSON). The work contains a short overview of relevant international activity conducted in the past, a description of the BARCO project and its objectives, a list of participants, project tasks, initial data (source term, meteorology, list of benchmarking quantities, approach to data exchange, codes used). The study presents some of comparative analysis results obtained via two techniques such as code-to-code analysis (CTCA) and matched-pair analysis (MPA). The results discussion concentrates on the overall recommendations for code users. Conclusions provide the main outputs of the project.

Is HCMV vaccine an unmet need? The state of art of vaccine development.

Congenital HCMV infection is the most frequent congenital infection, with an incidence of 0.2- 2.5 percent among all live births. About 11 percent of infected newborns show symptoms at birth, including hepato-splenomegaly, thrombocytopenia, neurologic involvement, hearing impairment and visual deficit. Moreover, 5-25 percent of the asymptomatic congenital HCMV-infected neonates will develop sequelae over months or even years. The relevant social burden, the economic costs of pre-natal screening, post-natal diagnosis, follow-up and possible therapy, although still limited, are the major factors to be considered. Several types of vaccines have been explored in order to develop an effective and safe HCMV vaccine: live attenuated, subunit, vectored, peptide, DNA, and subviral ones, but none are available for use. This review illustrates the different vaccine types studied to date, focusing on the possible vaccination strategy to be implemented once the HCMV vaccine is available, in terms of target population.

Preliminary results on the production of short-lived radioisotopes with a Plasma Focus device.

An experimental campaign was conducted to assess the feasibility of short-lived radioisotope (SLR) production within the pulsed discharges of a Plasma Focus (PF) device. This so-called "endogenous production" technique rests on the exploitation of nuclear reactions for the creation of SLR directly within the plasma, rather than on irradiating an external target. Until now only one research group has published data relevant to PF endogenous production of SLR, and the data seem to confirm that the PF has the capability to breed SLR. The campaign demonstrated production of (15)O, (17)F and (13)N from the (14)N(d,n)(15)O, (12)C(d,n)(13)N and (16)O(d,n)(17)F reactions. A 7kJ, 17kV Mather-type PF was operated with natural nitrogen, oxygen, CO(2) and deuterium in the vacuum chamber. Results to date confirm that, with a PF of this type, up to 1microCi of SLRs per discharge can be obtained.

Monte Carlo simulation of neutron backscattering from concrete walls in the dense plasma focus laboratory of Bologna University.

Between 2001 and 2003 a 3.2 kJ dense plasma focus (DPF) device has been built at the Montecuccolino Laboratory of the Department of Energy, Nuclear and Environmental Control Engineering (DIENCA) of the University of Bologna. A DPF is a pulsed device in which deuterium nuclear fusion reactions can be obtained through the pinching effects of electromagnetic fields upon a dense plasma. The empirical scale law that governs the total D-D neutron yield from a single pulse of a DPF predicts for this machine a figure of approximately 10(7) fast neutrons per shot. The aim of the present work is to evaluate the role of backscattering of neutrons from the concrete walls surrounding the Montecuccolino DPF in total neutron yield measurements. The evaluation is performed by MCNP-5 simulations that are aimed at estimating the neutron spectra at a few points of interest in the laboratory, where neutron detectors will be placed during the experimental campaigns. Spectral information from the simulations is essential because the response of detectors is influenced by neutron energy. Comparisons are made with the simple r(-2) law, which holds for a DPF in infinite vacuum. The results from the simulations will ultimately be used both in the design and optimisation of the neutron detectors and in their final calibration and placement inside the laboratory.

Early effects comparison of X-rays delivered at high-dose-rate pulses by a plasma focus device and at low dose rate on human tumour cells.

A comparative study has been performed on the effects of high-dose-rate (DR) X-ray beams produced by a plasma focus device (PFMA-3), to exploit its potential medical applications (e.g. radiotherapy), and low-DR X-ray beams produced by a conventional source (XRT). Experiments have been performed at 0.5 and 2 Gy doses on a human glioblastoma cell line (T98G). Cell proliferation rate and potassium outward currents (IK) have been investigated by time lapse imaging and patch clamp recordings. The results showed that PFMA-3 irradiation has a greater capability to reduce the proliferation rate activity with respect to XRT, while it does not affect IK of T98G cells at any of the dose levels tested. XRT irradiation significantly reduces the mean IK amplitude of T98G cells only at 0.5 Gy. This work confirms that the DR, and therefore the source of radiation, is crucial for the planning and optimisation of radiotherapy applications.

Peripheral vascular resistance limits exercise functional capacity of mild hypertensives.

To evaluate the physiological basis for suboptimal peak exercise oxygen consumption (VO2p) observed in the early stage of hypertension, 25 WHO Stage I hypertensive men with normal left ventricular mass and 10 healthy control subjects of equivalent age underwent the maximal cardiopulmonary exercise test with contemporary measurement of cardiac output with Tc99m angiocardiography. At peak exercise hypertensive patients had lower VO2p (p < 0.045) and cardiac output (p < 0.014) and higher vascular resistance (p < 0.010) than controls. At multiple regression analysis VO2 was positively related to cardiac output in controls (r = 0.80, p < 0.02), whereas in hypertensives the best (negative) correlation was observed with peripheral vascular resistance (r = -0.72, p < 0.04). Thus reduced cardiopulmonary function during physical exercise in hypertensives seems to be mainly related to impaired peripheral vascular autoregulation.

Survey of unlicensed and off label drug use in paediatric wards in European countries. European Network for Drug Investigation in Children.

OBJECTIVE: To determine the extent of use of unlicensed and off label drugs in children in hospital in five European countries. DESIGN: Prospective study of drugs administered to children in general paediatric medical wards over four weeks. SETTING: Children's wards in five hospitals (one each in the United Kingdom, Sweden, Germany, Italy, and the Netherlands). SUBJECTS: Children aged 4 days to 16 years admitted to general paediatric medical wards. MAIN OUTCOME MEASURE: Proportion of drugs that were used in an unlicensed or off label manner. RESULTS: 2262 drug prescriptions were administered to 624 children in the five hospitals. Almost half of all drug prescriptions (1036; 46%) were either unlicensed or off label. Of these 1036, 872 were off label and 164 were unlicensed. Over half of the patients (421; 67%) received an unlicensed or off label drug prescription. CONCLUSIONS: Use of off label or unlicensed drugs to treat children is widespread. This problem is likely to affect children throughout Europe and requires European action.

A range-based method to calibrate a magnetic spectrometer measuring the energy spectrum of the backward electron beam of a plasma focus.

The electron beam emitted from the back of plasma focus devices is being studied as a radiation source for intraoperative radiation therapy applications. A plasma focus device is being developed for this purpose, and there is a need for characterizing its electron beam, particularly, insofar as the energy spectrum is concerned. The instrument used is a magnetic spectrometer. To calibrate this spectrometer, a procedure relying on the energy-range relation in Mylar® has been devised and applied. By measuring the transmission through increasing thicknesses of the material, electron energies could be assessed and compared to the spectrometer readings. Thus, the original calibration of the instrument has been extended to higher energies and also to better accuracy. Methods and results are presented.

Radiation protection of PFMA-1, a plasma focus for medical applications.

A plasma focus is being developed for breeding short-lived radionuclides. The different radiation protection issues and concerns posed by the machine once in operation are analysed and discussed. Activation is shown to be totally negligible and likewise neutron emission is found to pose no concern at all. The only source of radiation risk is found to rest in the radionuclides produced, 18F and 15 O, generating a peak exposure of 1.114 Sv y(-1) at the distance of closest approach of 2.5 m. Shielding to protect against this hazard is calculated to be 5 cm Pb or 54 cm concrete for the operation area and 5.5 cm Pb for the transportation flask.

Off-label use of drugs in Italy: a prospective, observational and multicentre study.

UNLABELLED: The aims of the study were to measure the paediatric, off-label use of drugs in the Italian hospital setting and to reveal areas for priority intervention by investigating the therapeutic indications most involved. Prescriptions given to all children admitted to nine general paediatric hospital wards from December 1998 to February 1999 were analysed. In total, 4265 prescriptions were given to 1461 children, 10 of which were unlicensed and excluded from further analysis. Sixty percent of prescriptions (range between centres: 44-71%) were off-label and concerned 89% of children receiving medications (80-96%). The main drug classes were antibacterials, antiasthmatics and analgesics, and represented 56% of off-label prescriptions. Paracetamol (385 prescriptions) and beclomethasone (339) were the generic substances most often used off-label. The most common off-label categories were dosage/frequency (50% of prescriptions), indication and lack of paediatric licence (7% each). Fifty-four per cent of all indications that led to off-label prescribing involved only respiratory problems, fever, respiratory tract infections and bronchospasm. CONCLUSIONS: Despite prescription profile differences among centres, off-label use was high everywhere. Immediate action for more rational drug use is necessary and requires not only regulatory intervention but also a more evidence-based, therapeutic approach.

Creutzfeld-Jakob disease in the province of Siena: two cases transmitted to monkeys.

Two cases of histopathologically documented Creutzfeldt-Jakob disease were observed in the same area of the province of Siena in 1974-1975. The transmission of the disease was obtained through brain homogenates and lymphnodes in one of the two cases. This confirms that the agent is present in other tissues besides the brain and underlines further the analogies between Creutzfeld-Jakob disease and scrapie.

Endothelin-1 urinary excretion, but not endothelin-1 plasma concentration, is increased in renovascular hypertension.

Animal experiments have shown an increase in prepro-endothelin-1 (prepro-ET-1) mRNA expression in the clipped kidney but none in the aortic and mesenteric arteries in 2-kidney, 1-clip Goldblatt hypertensive rats. The present study was aimed at investigating whether plasma and renal endothelin-1 (ET-1) systems are differently activated in patients with renovascular hypertension (RH). The plasma concentration and urinary excretion of ET-1 were measured in 5 patients with RH (before and after successful renal angioplasty), in 7 patients with essential hypertension (EH), and in 8 normotensive control subjects. Immediately before renal angioplasty, plasma samples for ET-1 and plasma renin activity (PRA) measurements were withdrawn from the aorta and both renal veins. Unlike the PRA, the plasma ET-1 concentration did not significantly differ between the involved and the uninvolved sides. The urinary ET-1 excretion level (Fig 1) was markedly increased in patients with RH (30+/-4 ng/g urinary creatinine (UC) vs. 2.5+/-0.2 ng/g UC and 2.6+/-0.5 ng/g UC in control subjects and patients with EH, respectively; P<.001), whereas the plasma ET-1 concentration was normal (0.8+/-0.2 pg/mL vs. 0.65+/-0.3 pg/mL and 0.8+/-0.2 pg/mL in control subjects and EH, respectively, not significant). Renal angioplasty was followed in all patients by normalization of blood pressure and PRA. One week after angioplasty, urinary ET-1 decreased to one fourth of baseline (8.04+/-5.23 ng/g UC, P<.001 vs. values before angioplasty and P<.04 vs. control subjects) and normalized 1 month thereafter (3.13+/-1.62 ng/g UC, not significant vs. control subjects), whereas plasma ET-1 remained steady. The present findings clearly indicate that in patients with RH, urinary ET-1 excretion is increased, whereas plasma ET-1 concentration remains normal. Successful percutaneous transluminal renal angioplasty induced a notable reduction in ET-1 urinary excretion, whereas it did not affect ET-1 plasma concentration.

Prescribing information in 26 countries: a comparative study.

This study was set up to document the variability of prescribing information from different sources concerning indications, side effects and cautions of selected drugs. An original method to measure the degree of information agreement among different written materials, such as summaries of product characteristics, package inserts and data sheets, and a widely accepted reference text was developed. The results show that there is substantial disagreement in the materials available to prescribers and patients in different countries. Disagreement was even found within a single country when written materials from different brands of the same drug were compared. The discordance can be explained by the fact that the evidence available for each drug is considered/assessed differently by separate countries. It is argued that the discrepancies found may mislead prescribers, patients and those comparing drug-use patterns across countries. National regulatory authorities have a key role to play in remedying this situation, and a two-pronged approach is proposed. At the international level, national authorities should strengthen collaboration and information interchange and, at the national level, should implement appropriate measures aimed at removing contradictory statements on drug-information materials that have no reason to be different. Finally, further training and continued education aimed at drug regulatory officials could provide the necessary knowledge and enable national authorities to meet the need for drug information that is independent of commercial interests.

Spectral analysis of 24 h blood pressure monitoring in the assessment of trough: peak ratio. A randomized, placebo-controlled, cross-over comparison of ramipril and enalapril.

BACKGROUND: The ratio between the magnitude of blood pressure reduction during the steady-state dosage interval (trough) and the maximum blood pressure reduction (peak) is an integrated in-vivo index both of the pharmacokinetic properties and of pharmacodynamic activity of an antihypertensive drug. Angiotensin converting enzyme inhibitors are often characterized by a low (often lower than 50%) trough: peak ratio but no direct drug comparisons are available. OBJECTIVE: To compare the absolute blood pressure reduction and the trough: peak ratio of daily doses of two angiotensin converting enzyme inhibitors, 5 mg ramipril and 10 mg enalapril. METHOD: After a 1-month wash-out and a 2-week placebo run-in, 25 mild hypertensives aged 47 +/- 4 years (17 men and eight women) were randomly assigned to treatments separated by a 2-week interval. Ambulatory blood pressure monitoring was performed and trough: peak ratio was calculated by the fast Fourier transform analysis of placebo-effect-subtracted data. RESULTS: After 1 month of ramipril treatment, 24 h blood pressure decreased from 139 +/- 10 to 129 +/- 11 mmHg for systolic (P < 0.05) and from 89 +/- 8 to 81 +/- 5 mmHg for diastolic blood pressure (P < 0.01). Also enalapril treatment caused a significant 24 h reduction in blood pressure both for systolic (to 132 +/- 7 mmHg, P < 0.05) and for diastolic blood pressure (to 84 +/- 5 mmHg, P < 0.05). Placebo caused a 24 h reduction in blood pressure (to 136 +/- 8 mmHg for systolic and 87 +/- 5 mmHg for diastolic blood pressure, NS, versus wash-out period). The two drugs were equally effective in reducing ambulatory blood pressure, but ramipril produced a trough: peak ratio significantly higher than that with enalapril both for systolic (48 +/- 11%, range 34-74%, versus 38 +/- 11%, range 21-67%, P < 0.005)and for diastolic blood pressure (47 +/- 11%, range 30-79 %, versus 37 +/- 12%, range 21-68%, P < 0.05). CONCLUSION: The low trough : peak ratios could have been due to the daily pattern of blood pressure of mild hypertensives, many of whom are normotensives at night-time, so that the main antihypertensive effect is exerted during daytime rather than during the night or early morning.