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In July 2017, the International Commission on Radiation Units and Measurements (ICRU) and the International Commission on Radiological Protection (ICRP) proposed the introduction of new operational quantities for external radiation exposure, with the aim of improving coherence between protection quantities and operational quantities within the system of radiological protection. A change in operational quantities will impact both instrumentation and reference radiation fields used for their calibration. This paper evaluates the potential impact of the new quantity ambient dose, H*, meant to replace ambient dose equivalent, H*(10), on two neutron reference fields, the Am-Be source and the CERF high-energy workplace field, and on the response of two models of extended-range neutron rem counters (LINUS and LUPIN). The conclusions are that calibration procedures should in general not be affected and that changes should only be expected in calibration coefficients. Considering the acceptable measurement uncertainties for operational radiation protection, for the extended-range rem counters changes in their design would not be required for measurements outside particle accelerators shielding and for aircrew dosimetry. One can expect that this type of instrument can still be calibrated with Am-Be source neutrons and employed in neutron fields with energy distributions spanning several decades. For uses in radiation fields with very peculiar neutron energy distribution, a specific workplace field calibration may instead be required.

Since the first particle accelerator’s construction in 1931, an exponential spread of these machines occurred worldwide, in different kinds of applications. Nowadays, these are mainly used for industrial (60%) and medical (35%) purposes and for scientific research (5%). High energy secondary mixed fields produced by the particle beams interaction with matter imply a complex environmental dosimetry and special radiation protection regulations able to guarantee workers and population safety. In the medical field, this aspect is particularly emphasized in hadrontherapy centres, where high energy charged particles such as protons and carbon ions modify environmental doses, with a significant increase in the neutron contribution. This work proposes a technique to identify points of losses of the primary particle beam around an acceleration ring and has been developed within the radiation protection section at the National Centre for Oncological Hadrontherapy situated in Pavia. In the first part, the radiation field produced by protons and carbon ions interactions with structural materials at different energies was investigated. The main instrument of analysis is the Monte Carlo code for particle transport FLUKA, supported by experimental measurements in the treatment room carried out with the rem counter LUPIN, designed for pulsed neutron fields dosimetry. This first step allowed an analysis of both the angular and energetic instrumental response and a comparison of experimental results with simulations. The second part proposes a description of the technique for beam loss positions reconstruction around the acceleration ring at CNAO based on the application of unfolding codes.

Carbon-ion beams are increasingly used in the clinical practice for external radiotherapy treatments of deep-seated tumors. At therapeutic energies, carbon ions yield significant secondary products, including neutrons, which may be of concern for the radiation protection of the patient and personnel. We simulated the neutron yield produced by proton and carbon-ion pencil beams impinging on a clinical phantom at three different angles: 15°, 45° and 90°, with respect to the beam axis. We validated the simulated results using the measured response of organic scintillation detectors. We compared the results obtained with FLUKA 2011.2 and MCNPX 2.7.0 based on three different physics models: Bertini, Isabel, and CEM. Over the different ions, energies, and angles, the FLUKA simulation results agree better with the measured data, compared to the MCNPX results. Simulations of carbon ions at low angles exhibit both the highest deviation from measured data and inter-model discrepancy, which is probably due to the different treatment of the pre-equilibrium stage. The reported neutron yield results could help in the comparison of carbon-ion and proton treatments in terms of secondary neutron production for radiation protection applications.

Purpose Radiation therapy with ion beams provides a better conformation and effectiveness of the dose delivered to the tumor with respect to photon beams. This implies that a small uncertainty or variation in the crossed tissue shape and density may lead to a more important underdosage of the tumor and/or an overdosage of the surrounding healthy tissue. Although the online control of beam fluence and transverse position is well managed by an appropriate beam delivery system, the online measurement of the longitudinal position of the Bragg peak inside the patient is still an open issue. In this paper we propose a proof-of-concept study of a technique that would allow the online verification of the patient thickness along the beam direction, which could permit detecting a subset of possible range error causes, such as morphological variations. Methods The nuclei 12 C and 4 He have the same magnetic rigidity: the two species could be accelerated together in an accelerator and a mixed particle beam delivered to the patient. In the same medium and with the same energy per nucleon, the range of 4 He2+ is about three times the 12 C6+ one. It is, thus, conceivable to achieve a dual goal with a single mixed beam: carbon, stopping into the tumor, is appointed to cure, while helium, emerging from the patient, to control: by detecting and measuring the residual range and position of He, it would be possible to determine the integrated relative stopping power of the patient and prove that it is the expected one. For the detection of helium particles, a plastic scintillator and an optical sensor are proposed. Being helium ions not available at CNAO, the detection system has been characterized using a proton beam. Nevertheless, since the light emitted by a proton is less than the one produced by a helium ion, the helium signal is expected to be more pronounced than the proton one (for the same number of particles). To predict the magnitude of the light signal measured by the sensor, two Monte Carlo models have been setup and validated by measuring the photons per pixel impinging on the sensor. To deal with the many optical issues and to reliably describe the physical process, some corrections have been included into the models. Results The predictions of both the models are in good agreement with the measurements (within the 20% in terms of absolute photons per pixel). The proposed detection system is able to measure the range of a proton beam with sub-millimetrical precision also in the presence of the background produced by carbon ion fragments and discrepancies in the expected range were detected with a resolution better than 1 mm. Conclusions Although many technical issues have still to be addressed for a real implementation in a clinical environment, the preliminary results of this study suggest that a surrogate of real-time verification of the beam range inside the patient during a treatment with carbon ions is possible by adding a small fraction of helium ions to the primary beam.

The work presents a self-consistent algorithm to study the response of passive neutron dosimeters based on CR-39 detectors, through simulations with the FLUKA code (version 2011.2x.5). The various assumptions and features of the algorithm are described and the simulated results are compared to some experimental data referred to monochromatic and quasi-monochromatic neutron fields to show the potentialities and the limits of the procedure. Moreover, the response function of the dosimeter for normally impinging neutron fields is shown. In general, the algorithm turns out to work properly in estimating the dosimeter response, thus allowing to characterize the device in various situations in the frame of possible applications as an environmental and/or personal dosimeter.

The response in terms of personal dose equivalent of a passive fast neutron dosimeter composed of a CR-39 detector coupled with a 1 -cm-thick PMMA radiator is investigated in monochromatic neutron fields via simulations and experiments. In particular, the simulations were performed through the Monte Carlo FLUKA code (version 2011.2x.5), while the experimental fields were produced at the AMANDE facility (IRSN, France). The dosimeter response is studied with respect to both the energy and the angle of incidence of the radiation field on the device. The simulated response shows a quite stationary trend, that is, minimal variation across a wide energy range, also for different irradiation angles. The agreement between simulated and experimental responses indicates the simple and cheap dosimeter presented as promising for personal dosimetry applications in practical situations.

In this article, the in vivo study performed to evaluate the uniformity of biological doses within an hypothetical target volume and calculate the values of relative biological effectiveness (RBE) at different depths in the spread-out Bragg peak (SOBP) of the new CNAO (National Centre for Oncological Hadrontherapy) carbon beams is presented, in the framework of a typical radiobiological beam calibration procedure. The RBE values (relative to (60)Co γ rays) of the CNAO active scanning carbon ion beams were determined using jejunal crypt regeneration in mice as biological system at the entrance, centre and distal end of a 6-cm SOBP. The RBE values calculated from the iso-effective doses to reduce crypt survival per circumference to 10, ranged from 1.52 at the middle of the SOBP to 1.75 at the distal position and are in agreement with those previously reported from other carbon ion facilities. In conclusion, this first set of in vivo experiments shows that the CNAO carbon beam is radiobiologically comparable with the NIRS (National Institute of Radiological Sciences, Chiba, Japan) and GSI (Helmholtzzentrum für Schwerionenforschung, Darmstadt, Germany) ones.

Rem-Counters are widely used in radiation protection practice for environmental neutron detection. They are usually based on both an active and a passive thermal neutron detector surrounded by a hydrogenate moderator designed to obtain a response function as close as possible to the H *(10) curve. Inclusion of high Z material is also used to extend the response function up to 1 GeV of neutron energy. Recently a dual detector Rem-Counter, both active and passive, was proposed by Agosteo et al. (2010) . The present paper focuses on the passive version that is based on a CR-39 track detector coupled to an enriched 10 B converter. A technique was developed for the track analysis based on the measurement of the mean LET of the charged particles produced by the neutron reaction on 10 B that has proven to be very effective in the background reduction. Moreover the simulated response function of the Rem-Counter was compared with the experimental results obtained with irradiations carried out with monoenergetic neutron beams, showing a quite good agreement.

Bonner Spheres Spectrometry in its high-energy extended version is an established method to quantify neutrons at a wide energy range from several meV up to more than 1 GeV. In order to allow for quantitative measurements, the responses of the various spheres used in a Bonner Sphere Spectrometer (BSS) are usually simulated by Monte Carlo (MC) codes over the neutron energy range of interest. Because above 20 MeV experimental cross section data are scarce, intra-nuclear cascade (INC) and evaporation models are applied in these MC codes. It was suspected that this lack of data above 20 MeV may translate to differences in simulated BSS response functions depending on the MC code and nuclear models used, which in turn may add to the uncertainty involved in Bonner Sphere Spectrometry, in particular for neutron energies above 20 MeV. In order to investigate this issue in a systematic way, EURADOS (European Radiation Dosimetry Group) initiated an exercise where six groups having experience in neutron transport calculations with the MC codes (MCNP, MCNPX, FLUKA, PHITS, MARS, or GEANT4) calculated the responses of a bare 3 He proportional counter, a 3 He proportional counter embedded in the middle of a 9 inch polyethylene sphere, and a 3 He proportional counter centred in a 9 inch polyethylene sphere containing a lead shell, at neutron energies of 1, 10, 100, and 1000 MeV. In general, calculated responses agreed very well for neutron energies below 20 MeV, whatever MC code used. At higher energies, however, certain differences were observed among the different calculations, which may mainly be attributed to the application of different INC models and their parameters. It was found that up to 1 GeV most of the results ranged between calculations previously published that were obtained with MCNP/LAHET using the Bertini INC model and GEANT4 using the Binary and Bertini INC models. These results indicate that use of different MC codes and INC models for the calculation of BSS response functions may result in an uncertainty of unfolded neutron fluences above 20 MeV of about 20%.

It is well-known that neutron detectors generally suffer from dead-time effects and have strong limitations when measuring in pulsed radiation fields. An active neutron monitor based on a BF3 proportional counter and logarithmic electronics was developed to withstand pulsed fields with high intensity, very short duration and high repetition rate. This paper discusses results of preliminary measurements carried out at the Italian National Hadrontherapy Center (CNAO) in Pavia and at the San Raffaele Hospital in Milan. In the first case neutrons were produced by 7 MeV protons accelerated by a LINAC and impinging on a copper Faraday cup. In the second case an electron radiotherapy LINAC produced energy-tunable bremsstrahlung x-rays beams up to 18 MV with an associated neutron component. The neutron monitor was capable to withstand neutron reaction rates up to 2·10 6 s -1 without showing saturation effects. A promising technique is also shown to reject very intense, pulsed gamma fields, due to the innovative operating principle of the detector.

In this paper, the evaluation of the dosimetric capability of a detector based on a CR-39 solid-state nuclear track detector coupled to a 1 cm thickness of PMMA radiator was made with the aim of understanding the applicability of this technique to personal and environmental neutron dosimetry. The dosemeter has been exposed to monoenergetic and quasi-monoenergetic neutron beams at PTB in Braunschweig, Germany and at Ithemba Laboratories, in Faure, South Africa, with peak energies ranging from 0.565 to 100 MeV. The results showed a response that is almost independent of the neutron energy in the whole energy range.

A number of studies focused in the last decades on the development of survey meters to be used in pulsed radiation fields. This is a topic attracting widespread interest for applications such as radiation protection and beam diagnostics in accelerators. This paper describes a new instrument specifically conceived for applications in pulsed neutron fields (PNF). The detector, called LUPIN, is a rem counter type instrument consisting of a 3He proportional counter placed inside a spherical moderator. It works in current mode with a front-end electronics consisting of a current–voltage logarithmic amplifier, whose output signal is acquired with an ADC and processed on a PC. This alternative signal processing allows the instrument to be used in PNF without being affected by saturation effects. Moreover, it has a measurement capability ranging over many orders of burst intensity. Despite the fact that it works in current mode, it can measure a single neutron interaction. The LUPIN was first calibrated in CERN's calibration laboratory with a PuBe source. Measurements were carried out under various experimental conditions at the Helmholtz-Zentrum in Berlin, in the stray field at various locations of the CERN Proton Synchrotron complex and around a radiotherapy linear accelerator at the S. Raffaele hospital in Milan. The detector can withstand single bursts with values of H⁎(10) up to 16 nSv/burst without showing any saturation effect. It efficiently works in pulsed stray fields, where a conventional rem-counter underestimates by a factor of 2. It is also able to reject the very intense and pulsed photon contribution that often accompanies the neutron field with good reliability.

Chronic lymphocytic leukemia (CLL) is a clinically heterogeneous disease, as some patients progress rapidly toward the more advanced studies, whereas others survive for a long period without the need for treatment. This heterogeneity of clinical course was somehow unexplained until studies on the CLL cell features disclosed that the CLL clones were heterogeneous and were characterized by different phenotypic and genotypic features in the different patients. On the basis of these observations, it was determined in retrospective studies that clones characterized by unmutated IGHV genes, and/or CD38 and/or ZAP-70 expression conferred a more severe prognosis to the CLL patients. Here, we present data on prospective studies carried out on Binet A-stage patients, in whom the markers were determined at diagnosis and their predictive value was assessed in comparison with chromosomal abnormalities and gene expression or micro RNA profiles. In addition, hypothesis on the potential pathogenetic role of these markers will be presented.

The accurate determination of the ambient dose equivalent in the mixed neutron-photon fields encountered around high-energy particle accelerators still represents a challenging task. The main complexity arises from the extreme variability of the neutron energy, which spans over ten orders of magnitude or more. Operational survey instruments, which response function attempts to mimic the fluence-to-ambient dose equivalent conversion coefficient up to GeV neutrons, are available on the market, but their response is not fully reliable over the entire energy range. Extended range rem counters (ERRC) do not require the exact knowledge of the energy distribution of the neutron field and the calibration can be done with a source spectrum. If the actual neutron field has an energy distribution different from the calibration spectrum, the measurement is affected by an added uncertainty related to the partial overlap of the fluence-to- ambient dose equivalent conversion curve and the response function. For this reason their operational use should always be preceded by an “in-field” calibration, i.e. a calibration made against a reference instrument exposed in the same field where the survey-meter will be employed. In practice the extended-range Bonner Sphere Spectrometer (ERBSS) is the only device which can serve as reference instrument in these fields, because of its wide energy range and the possibility to assess the neutron fluence and the ambient dose equivalent (H⁎(10)) values with the appropriate accuracy. Nevertheless, the experience gained by a number of experimental groups suggests that mandatory conditions for obtaining accurate results in workplaces are: (1) the use of a well-established response matrix, thus implying validation campaigns in reference monochromatic neutrons fields, (2) the expert and critical use of suitable unfolding codes, and (3) the performance test of the whole system (experimental set-up, elaboration and unfolding procedures) in a well controlled workplace field. The CERF (CERN-EU high-energy reference field) facility is a unique example of such a field, where a number of experimental campaigns and Monte Carlo simulations have been performed over the past years. With the aim of performing this kind of workplace performance test, four different ERBSS with different degrees of validation, operated by three groups (CERN, INFN-LNF and Politecnico of Milano), were exposed in two fixed positions at CERF. By using different unfolding codes (MAXED, GRAVEL, FRUIT and FRUIT SGM), the experimental data were analyzed to provide the neutron spectra and the related dosimetric quantities. The results allow assessing the overall performance of each ERBSS and of the unfolding codes, as well as comparing the performance of three ERRCs when used in a neutron field with energy distribution different from the calibration spectrum.

SSNTDs (solid-state nuclear track detectors), primarily made from PADC (poly(allyl diglycol carbonate)), are attractive detectors for dosimetric purposes. SSNTDs are more similar to human tissue than other passive detectors and the measurement of the track parameters provides information about the energy deposition of the incident particle. This paper describes a method for LET measurement based on the measurements of the major and minor axes of the track opening. The method was experimentally tested using alpha particles with energies ranging from 4.2 MeV to 6 MeV. The experimental results show that PADC can measure the total energy lost by a particle along a path of length Δ x divided by the length itself, a quantity strictly related to the LET .

A passive neutron dosimeter based on CR-39 track detectors has been successfully tested at the CERF facility at CERN. Former calibration campaigns in monoenergetic and quasi-monoenergetic neutron beams have shown an almost energy independent response function of the detector in the energy range 0.5 MeV–100 MeV. This feature allows to obtain a “rem counter like” personal neutron detector, where a single calibration coefficient is valid for a wide energy range. In order to confirm his feature the detector has been tested in the CERF facility at CERN that generates a workplace neutron field similar to the one encountered at commercial flight altitude. The results show a very good agreement with the reference value permitting to conclude that the detectors have a good reliability also for this kind of radiation field.

LR115 cellulose nitrate SSNTD are routinely used for Radon detection. A reading technique with high resolution optical microscope coupled with a scanning system has been recently proposed. In this technique, the efficiency correction that was formerly performed on the residual thickness of the detector is performed on the track area distribution. So all the information that is needed for the measurement is obtained directly during the scanning. This leads to a much simpler and faster reading procedure, when compared to the classical technique that required both spark counting and micrometer residual thickness measure. A complete characterization and performance evaluation of the detector response is discussed, including a measuring range evaluation, a combined uncertainty theoretical calculation and a blind test validation at HPA.

The paper describes the experimental characterization of a neutron spectrometer based on a CR39 SSNTD coupled to a polyethylene radiator and an aluminium degrader. The response function of the spectrometer is calculated by using two analytical codes: the first one, written in Labview, permits to evaluate the critical angle of a particle (proton, alpha or recoil nucleus) impinging on the detector surface, as a function of the particle energy; the second code, written in Mathcad, calculates the recoil proton distribution generated by a monoenergetic neutron beam impinging on the polyethylene converter. The simulation software also accounts for the self radiator effect due to the recoil protons and to the oxygen and carbon recoil nuclei. The calculated response functions are compared with experimental data showing a fairly good agreement. Also the experimental reproducibility is satisfactory.

PADC detectors are widely used as air radon concentration measurement devices and the typical procedure that a Radon Service Laboratory uses to manage the detectors provides a calibration phase followed by the field measurement. The calibration is performed in a reference radon concentration atmosphere, using high radon concentration values in order to achieve typical exposure values of few MBq h m −3 with an exposure time of few days. On the other hand the field measurement is characterized by long term exposures lasting up to six months and by radon concentrations that are quite lower than the ones used in the calibration. The aim of this study is to check whether the calibration procedure is actually representative of a field measurement, or, in other words, whether and how much ageing or fading can affect the calibration factor. We found that the ageing and fading effect can produce a decrease in the detector sensitivity leading to an underestimation of the radon concentration up to 40% for exposure lasting few months. An important issue is that both ageing and fading can be ascribed to a decrease in the track etching velocity V t . In the paper we also provide an algorithm to compensate for the sensitivity variation due to fading/ageing effect.

This paper describes a wide dynamic range neutron monitor based on a BF3 neutron detector. The detector is used in current mode, and front-end electronics based on a logarithmic amplifier are used in order to have a measurement capability ranging over many orders of magnitude. The system has been calibrated at the Polytechnic of Milan, CESNEF, with an AmBe neutron source, and has been tested in a pulsed field at the PUNITA facility at JRC, Ispra. The detector has achieved a dynamic range of over 6 orders of magnitude, being able to measure single neutron pulses and showing saturation-free response for a reaction rate up to 106 s−1. It has also proved effective in measuring the PUNITA facility pulse integral fluence.

The European Commission has funded within its 6th Framework Programme a three-year project (2005–2007) called CONRAD, COordinated Network for RAdiation Dosimetry. The organizational framework for this project was provided by the European radiation Dosimetry Group EURADOS. Work Package 6 of CONRAD dealt with “complex mixed radiation fields at workplaces” and in this context it organised a benchmark exercise, which included both measurements and calculations, in a stray radiation field at a high-energy particle accelerator at GSI, Germany. The aim was to intercompare the response of several types of active detectors and passive dosemeters in a well-characterised workplace field. The Monte Carlo simulations of the radiation field and the experimental determination of the neutron spectra with various Bonner Sphere Spectrometers are discussed in Rollet et al. (2008) and in Wiegel et al. (2008). This paper focuses on the intercomparison of the response of the dosemeters in terms of ambient dose equivalent. The paper describes in detail the detectors employed in the experiment, followed by a discussion of the results. A comparison is also made with the H*(10) values predicted by the Monte Carlo simulations and those measured by the BSS systems.

We reviewed retrospectively 793 consecutive patients discharged with ALS diagnosis between 1971 and 1998 to identify survival predictors. Vital status in July 2001 was known for all patients. Mean age at onset was 56 (SD 11.7) years and mean age at diagnosis was 57.4 (SD 11.5) years. Onset symptoms were bulbar in 20.8% of patients. The median survival time from symptoms onset was 2.9 years (95% CI 2.7-3.1). Survival from onset was 93% after one, 48% after three and 24% after five years. Median survival was shorter in patients with time between onset and diagnosis12 months than in those diagnosed23 months; (2.1 years vs. 5.9 years; P0.001). Patients with onset after age 65 had a 4.2 times greater risk of death than patients less than 40 years. Bulbar onset was associated with 1.4 times greater risk of death than spinal onset. Patients diagnosed after 1990 had longer median survival (3.3 years) than those diagnosed in 1971-1979 (2.4 years) (P0.001). As expected, age, bulbar onset and short time from onset to diagnosis were independent predictors of survival. We also found a significant increase in survival over time, probably due to improved comprehensive treatment of ALS patients in Italy.

Radiation Protection Dosimetry, 161 (1-4), ISSN:0144-8420, ISSN:1742-3406

La Fondazione CNAO ha tra i suoi scopi anche lo svolgimento di attività di ricerca. Il centro CNAO è stato concepito sin dall'inizio con tre sale di trattamento, espandibili fino a cinque, ed una 'sala sperimentale' nella quale le attività di ricerca possano venire svolte senza intralciare e senza essere intralciate dalla attività clinica.Tale sala sperimentale deve essere progettata per essere 'multi-uso', cioè tale da poter venire utilizzata per attività di ricerca nei campi più disparati e non specializzata in un tipo di attività particolare. Possibili argomenti di ricerca sono radiobiologia, sviluppo di monitor di fascio, sviluppo di dosimetri, studi di radiation hardness e molti altri ancora.Lo studio di tale facility ed in particolare lo studio degli aspetti tecnici legati all'ampliamento del complesso dell'acceleratore è stato portato avanti congiuntamente da CNAO e INFN, nell'ambito dell'accordo quadro approvato nel 2009 e del nuovo accordo quadro stipulato nel 2013. Per meglio identificare le necessità dei possibili utenti è stato svolto un sondaggio i cui risultati sono stati considerati nella definizione delle specifiche funzionali della linea e della sala sperimentale. Tale sondaggio è illustrato più avanti in questo documento. In questo documento viene descritto il progetto della sala sperimentale e delle linee di alta e di bassa energie coinvolte. Nella prima parte del documento viene data una descrizione generale del progetto, mentre i dettagli sono generalmente riportati nelle appendici e nei documenti allegati.

In order to identify early clinical features and survival predictors of supranuclear palsy (PSP) and multiple system atrophy (MSA), we compared the disease course of patients consecutively referred between 1987 and 1999 and followed to December 1999. Thirty-nine PSP and 74 MSA patients were diagnosed according to commonly accepted clinical criteria. Length of survival was ascertained from death certificates or by contacting relatives. Ten-year survival after disease onset was 29% for both disorders. Median survival was 7.0 years (PSP) and 7.5 (MSA). Neither age, symptoms at onset, or disability at diagnosis predicted survival. At diagnosis, all PSP patients had oculomotor palsy, whereas 89% of MSA patients had dysautonomia; bradykinesia and falls were the most frequent common signs. Distinctive early signs were palilalia, cognitive impairment and hyperreflexia in PSP; hypophonia, anterocollis and dysautonomia in MSA. MSA patients responded better to levodopa. Attention to early distinctive features can improve differential diagnosis and inform subsequent management.

Study design Case report. Objective To describe the case of a Klippel-Feil anomaly associated with carotid agenesis. Summary of background data Klippel-Feil anomaly is a spinal malformation characterized by fusion of the cervical vertebrae. Four subtypes have been identified for this congenital disorder with different severity of vertebral fusion and different extra-axial anomalies. Most cases are sporadic, although autosomal dominant and autosomal recessive cases are recognized. It can cause neurologic disorders and is associated to vascular abnormalities. However, agenesis of internal carotid and Klippel-Feil syndrome is an unusual association. Methods A 49-year-old woman came to our attention for recurrent transitory ischemic attacks presenting with weakness of left limbs associated with sensory abnormalities. Neurologic examination revealed mild left limb weakness and tactile hypoesthesia. Results Brain magnetic resonance (MR) and MR angiography demonstrated absence of the right internal carotid and the middle right cerebral artery was filled from the basilar artery. Fusion of vertebral bodies was documented at MR and confirmed at spinal CT scan. The day after the admission the neurologic examination became normal. Ticlopidine was then started. Conclusion Literature of vascular abnormalities in association with Klippel-Feil syndrome takes the form of anecdotal reports. Aortic coarctation, vertebral artery dissection, aneurysms, persistent trigeminal artery, and abnormal origin of internal carotid are described. An unusual association of carotid internal agenesis and Klippel-Feil syndrome is reported with a literature review.

Incidence rates for CNS tumours in children of age 0-14 years in the Region of Lombardy, Italy, during the period 1988-93 were analysed; survival probability updated to December 1995 was also estimated. CNS tumours defined according to the International Classification of Diseases for Oncology codes were actively searched for. CNS tumours were diagnosed in 296 children. The age-standardized rates were 40.0 per million child years for both sexes together, and 45.3 for boys and 34.4 for girls. In all age groups, boys had a higher incidence than girls. The annual incidences were 13.7, 7.0, 5.8 for astrocytoma, medulloblastoma and ependymoma, respectively. The overall survival percentages at 5 and 8 years after diagnosis were 68 and 66, respectively. Prognosis was good for astrocytoma (5-year survival, 81%), and declined in the order: other gliomas (5-year survival, 76%); ependymoma (5-year survival, 62%), and medulloblastoma (5-year survival, 43%). The histological type of the tumour was the most powerful independent predictor of survival in children with a CNS tumour. Medulloblastoma/primitive neuroectodermal tumours appeared to have the highest risk of a poor prognosis compared with astrocytoma (relative risk, 3.27; 95% confidence interval, 1.81-5.91). Age at diagnosis and sex had no significant effect on survival. The incidence of childhood CNS tumours found in this study is higher than previously reported in Italy, and is one of the highest in the world from population-based data. Survival of children with brain tumours has improved greatly in recent years. These results suggest that children in Lombardy with CNS tumours had a good survival experience compatible with high quality of care.

In the framework of the EURADOS working group 11, an intercomparison of active neutron survey meters was performed in a pulsed neutron field (PNF). The aim of the exercise was to evaluate the performances of various neutron instruments, including commercially available rem-counters, personal dosemeters and instrument prototypes. The measurements took place at the cyclotron of the Helmholtz-Zentrum Berlin für Materialien und Energie GmbH. The cyclotron is routinely used for proton therapy of ocular tumours, but an experimental area is also available. For the therapy the machine accelerates protons to 68 MeV. The interaction of the proton beam with a thick tungsten target produces a neutron field with energy up to about 60 MeV. One interesting feature of the cyclotron is that the beam can be delivered in bursts, with the possibility to modify in a simple and flexible way the burst length and the ion current. Through this possibility one can obtain radiation bursts of variable duration and intensity. All instruments were placed in a reference position and irradiated with neutrons delivered in bursts of different intensity. The analysis of the instrument response as a function of the burst charge (the total electric charge of the protons in the burst shot onto the tungsten target) permitted to assess for each device the dose underestimation due to the time structure of the radiation field. The personal neutron dosemeters were exposed on a standard PMMA slab phantom and the response linearity was evaluated., Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 737, ISSN:0168-9002, ISSN:1872-9576

Engagement of the CD95 (Apo-1, Fas) membrane receptor is known to induce apoptosis in a variety of sensitive cells, even in the absence of extracellular Ca2+. The signal transduction events implicated in this pathway are poorly understood. We have recently characterized normal human Vgamma9/Vdelta2+ T cell clones that maintain similar levels of CD95 membrane expression throughout the culture. Here we show that 3 wk of culture after in vitro restimulation are necessary for the cells both to die and to acquire the ability to mobilize intracellular Ca2+ upon CD95 ligation. Buffering of intracellular Ca2+ by accumulation of the chelator 1,2-bis(2-amino phenoxy)ethane-N,N,N1,N-tetraacetic acid protects from CD95-triggered apoptosis, suggesting that the two phenomena are causally related. As intracellular Ca2+ release by inhibition of endoplasmic reticulum ATPases induces apoptosis in both recently and long term activated gamma delta cells, the molecular regulation of activation-dependent apoptosis is likely to involve events upstream of CD95-dependent Ca2+ release. The CD95-triggered increase in the intracellular Ca2+ concentration depends on depletion of the same intracellular Ca2+ stores mobilized by ligation of the TCR, and Ca2+ release does not depend on inositol 1,4,5-trisphosphate generation.

A common feature of human V gamma 9/V delta 2 gamma delta T lymphocytes is their ability to kill Daudi lymphoma cells. We show here that during this killing a substantial fraction of cytotoxic gamma delta T cells dies as well. Their death has morphologic, cytometric, and biochemical features of apoptosis and depends on TCR triggering. We suggest that interaction with the target physiologically induces the programmed death of the cytotoxic gamma delta effector. The death of activated gamma delta T cells upon challenge with the relevant Ag may represent a negative feedback mechanism and contribute to explain the limited time span of gamma delta T cell expansions during infectious diseases, even when pathogens are not eliminated and persist in the host.

Phlogopite and biotite coexist in the ultrapotassic rocks from Cabezo Negro de Zeneta (SE Spain). The compositional range of the early crystallizing phlogopite is comparable to other Spanish lamproitic occurrences, except that it is higher in Al2O3, probably reflecting the higher Al2O3 and/or different oxygen fugacity of the Zeneta magma. Magmatic Al-rich and metamorphic Al-poor biotites also occur in these rocks. The magmatic biotite probably crystallised from intermediate to silicic peraluminous magma(s), whereas the metamorphic type comes from crustal relics of metapelitic rocks entrained and dismembered into the lamproitic melt. It is concluded that the melt of Zeneta was generated through the mixing of a Mg-rich lamproitic component, quantitatively dominant, with a crustal-derived anatectic component, both already partially crystallised before mixing. The “mixed” melt attained chemical homogenization as suggested by the development of late overgrowths of similar composition on the two micas.

The paper describes the evaluation of the performances of an innovative neutron spectrometer based on a CR39 SSNTD (Solid State Nuclear Track Detector) coupled to a polyethylene radiator and an aluminum degrader. The spectrometer was experimentally characterized in a previous paper, in this work the interest focuses on the unfolding capability. The evaluation is performed using both simulated and experimental input data. The unfolding code used is based on the well-known Gravel algorithm. The results are encouraging and show an acceptably good spectrometric capability in the neutron energy range from 100 keV to 10 MeV.

Survival of patients affected by Multiple Myeloma (MM), a B-cell tumor of malignant plasma cells, has dramatically improved, owing to the recent introduction of the proteasome inhibitor (PI) Bortezomib and of the immunomodulatory drugs (IMiDs). This major advance originates from accumulating knowledge on MM biology, leading to the development of drugs targeting not only MM cells, but also their microenvironment. Indeed, the disease develops as a result of genetic abnormalities and of reciprocal interactions between MM cells and the permissive BM microenvironment, which delivers growth- and pro-survival signals and confers resistance to drugs. As for solid tumors, bone marrow (BM) angiogenesis is emerging as a critical component of MM development and progression, and hence as an attractive therapeutic target for the disease. The patho-physiology of MM associated angiogenesis is complex and involves a plethora of soluble factors, cellular players and mechanisms. Moreover, the hypoxic microenvironment inside the BM might significantly contribute to the induction and maintenance of a pro-angiogenic profile, given the well-known role of hypoxia in promoting angiogenesis in all its forms. Here we present an overview of the literature focusing on the mechanisms implicated in the "angiogenic switch", which corresponds to the transition from the avascular to the vascular phase of the disease. We also review evidence on the anti-angiogenic effects of PI and IMiDs, which substantially contribute to their anti-MM activity. Finally, we summarize possible caveats and perspectives about antiangiogenic strategies that could be addressed to improve the efficacy of treatments for MM patients.

PADC detectors are commonly used both as radon detectors and as personal dosemeters for neutron radiation. In both cases the measurement in workplace fields are characterized by long term irradiations, lasting up to several months. During this period the detectors undergo to uncontrolled and unmonitored environmental conditions. In a recent work the same authors demonstrated that the environmental conditions, mainly temperature, can seriously affect the detector sensitivity. The temperature effect is to reduce the V ratio by decreasing the track etching velocity V t . This causes a decrease in limit angle and efficiency. This paper describes the same ageing/fading test made with CR39 from a different supplier. In this case it seems that the temperature has a negligible effect, so no compensation algorithm is needed.

Objective: The outcome of advanced ovarian cancer patients has not significantly improved since the introduction of platinum. One of the major reasons for this failure is the lack of an effective second-line treatment. In this phase II trial we tested the combination of gemcitabine and etoposide in 2 different groups of patients. Group 1 consisted of patients showing disease progression or relapse within 6 months of first-line platinum-based chemotherapy. Group 2 comprised heavily pretreated patients showing progression during the last chemotherapy attempt. Methods: Thirty-four patients were enrolled. Gemcitabine was administered at a dose of 1,000 mg/m2 on days 1 and 8 and etoposide was administered orally at 100 mg/day on days 8–12 for 6 courses. Results: Eighteen patients (52.9%) had an objective response and the median duration of the response was 10.3 months. Our chemotherapy regimen showed a low toxicity and good patient compliance. In 5 patients the treatment had to be delayed and in only 2 patients it was discontinued. Conclusions: The combination of gemcitabine and oral etoposide seems to be a safe and effective second-line treatment for platinum-resistant ovarian cancer patients. Additional data on larger series are warranted to better define the activity of this combination regimen.

The double differential particle yield produced by hadron beams striking thick targets of copper, tungsten and ICRU tissue, have been determined by means of the Monte Carlo transport code FLUKA (version FLUKA 2008.3b.1). 400 MeV/u carbon ion and 250 MeV proton pencil beams have been considered. Secondary neutrons, photons, and protons have been scored. In order to validate the obtained data, a few simulations have been also repeated with MCNPX 2.6.0. The calculated results are presented and compared with the experimental data reported in literature. They should be very useful to solve a number of problems related to technological aspects of hadrontherapy.

The current drug research techniques, combinatorial synthesis and high throughput screening, enabled the obtaining and pre-evaluation of thousands of compounds in short time. In order to chose the best hits to become leads, observation of drug-likeness tries to optimize this selection. Probably, the most widely used filter is Lipinski's Rule-of-five, which proposes that molecules with poor permeation and oral absorption have molecular weight500, Clog P5, hydrogen-bond donor5 and hydrogen-bond acceptor10. In order to evaluate the Rule-of-five, the top pharmaceutical products in 2007 were analyzed. Among 60 drugs, 7 (atorvastatin, montelukast, docetaxel, telmisartan, tacrolimus, leuprolide and olmesartan) did not fit the rule, and 5 failed only one of the threshold values. It was possible to conclude that the rule is very useful to select better compounds in chemolibraries, but it must be used carefully and with criteria, to avoid a possible exclusion of promising compounds.

The design and characterization of a dual-detector spherical rem counter is discussed in this paper. The rem counter is based on a polythene sphere with lead and cadmium insets, designed to host at its centre either an active ( 3 He SP9 proportional counter) or a passive (CR39 + 10 B radiator) thermal neutron detector. Its sensitivity ranges from thermal energies up to 1 GeV. A Monte Carlo characterization of this dual-detector rem counter has shown no significant change in the shape of the response curve obtained with the two detectors. The rem counter has been calibrated with a Pu–Be source. An intercomparison in a high-energy neutron field has been carried out at the CERF facility at CERN among the rem counter in the two configurations, two commercial units and the original version of the active LINUS in use at CERN. Both the active and passive versions of the rem counter agree, within the statistical uncertainties, with the CERN LINUS and with the facility reference values. Both versions of the instrument have proved to be capable of measuring the cosmic neutron background, thus providing a nonzero background measurement in environmental monitoring application.

The ability of human B cells to produce granulocyte-macrophage (GM)-CSF and IL-3 was investigated. B cells, isolated from tonsils or from the peripheral blood of patients with B cell chronic lymphocytic leukemia using mAb and immune rosettes, were cultured with or without Staphylococcus aureus Cowan strain I. GM-CSF and IL-3 were measured in the culture supernatants using a bioassay based on the selective proliferative response of the MO7e megakaryoblastic cell line to IL-3 or GM-CSF. S. aureus Cowan I-stimulated normal B cells released measurable amounts of GM-CSF but not of IL-3 as determined in neutralization assays with specific mAb in the MO7e cell line test. Some of the unstimulated normal B suspensions also produced GM-CSF, albeit in lower quantities. When normal B cells were fractionated into small (resting) and large (activated) B cells by Percoll density gradients, spontaneous GM-CSF production was detected only in the large cell fractions, but small cells were induced to produce GM-CSF upon S. aureus Cowan I stimulation. On a per cell basis, tonsillar B cells were found capable of releasing more GM-CSF than activated peripheral blood monocytes. The amount of GM-CSF produced by B cells was always inferior to that released by stimulated peripheral blood T cells or NK cells. The purified B cell suspensions from all 14 B cell chronic lymphocytic leukemia patients studied released GM-CSF but not IL-3 in the culture supernatants, sometimes even in the absence of stimuli. Northern blot analysis on total or poly(A)+ RNA confirmed the presence of GM-CSF, but not of IL-3, mRNA transcripts in both normal and malignant B cells. The results of these studies support the notion that activated human B lymphocytes release sufficient GM-CSF to play a role in the control of both hematopoiesis and the inflammatory process.

A passive neutron rem counter using a CR39 SSNTD coupled with a boron converter has been developed. The rem counter is a polythene sphere with cadmium and lead insets, designed to have a response function proportional to the fluence to ambient dose equivalent conversion coefficients, H*(10)/Φ, for energies ranging from thermal up to 1 GeV. At its centre is a thermal neutron detector made of a CR39 SSNTD coupled with an enriched boron neutron converter. The rem counter was first calibrated at CERN and at the Politecnico di Milano, and then tested in high-energy neutron fields at GSI, Darmstadt, Germany and at the CERF facility at CERN. Its most important features are a very high neutron sensitivity and conversely a complete insensitivity to gamma radiation.

The European Commission has funded within its 6th Framework Programme a three-year project (2005–2007) called CONRAD, COordinated Network for RAdiation Dosimetry . A major task of the CONRAD Work Package “ complex mixed radiation fields at workplaces ” was to organise a benchmark exercise in a workplace field at a high-energy particle accelerator where neutrons are the dominant radiation component. The CONRAD benchmark exercise took place at the Gesellschaft fur Schwerionenforschung mbH (GSI) in Darmstadt, Germany in July 2006. In this paper, the results of the spectrometry using four extended -range Bonner sphere spectrometers of four different institutes are reported. Outside Cave A the neutron spectra were measured with three spectrometers at six selected positions and ambient dose equivalent values were derived for use in the intercomparison with other area monitors and dosemeters. At a common position all three spectrometers were used to allow a direct comparison of their results which acts as an internal quality assurance. The comparison of the neutron spectra measured by the different groups shows very good agreement. A detailed analysis presents some differences between the shapes of the spectra and possible sources of these differences are discussed. However, the ability of Bonner sphere spectrometers to provide reliable integral quantities like fluence and ambient dose equivalent is well demonstrated in this exercise. The fluence and dose results derived by the three groups agree very well within the given uncertainties, not only with respect to the total energy region present in this environment but also for selected energy regions which contribute in certain strength to the total values. In addition to the positions outside Cave A one spectrometer was used to measure the neutron spectrum at one position in the entry maze of Cave A. In this case a comparison was possible to earlier measurements.

The role of CO2 laser in plastic surgery and dermatology is nowadays well established. It has proved to be efficient within different contexts (haemorrhagic-infectious-necrotic ...) or on different tissues as skin, muscles and mucosae. But the role of lasers in oncologic cutaneous surgery is not as precise. The CO2 laser is to be used in a focused mode, to realize the excision of tumour, whatever its size. The advantages lie in minimized blood loss, and in permitting all types of reconstruction (suture, graft or flap). Some clinical cases of photodynamic therapy are reported, but do not appear to be conclusive. Anyhow, PDT is still under investigation and does not seem to be ready yet for routine clinical use. The principle of tissue photo-ablation with excimer of Er-YAG lasers shows some possible interest in the case of tumour treatment. But, here again, this technique has not yet proved to be for any real advantage, as far as technology is concerned. Whatever the type of laser to be used, one basic principle is to completely excise the tumour to meet the classical requirements of oncologic surgery, i.e. to be far enough from the lesion, and to get a microscopic identification of the whole specimen. We therefore think that the use of lasers in case of cutaneous tumour therapy must be considered as follows. The CO2 laser: a useful device (but not a must) which can be used as a normal knife but offering the major advantage of almost bloodless surgery. Until today, spread of metastasis has not been found to be less frequent than with conventional surgery. PDT and photo-ablation: may be of interest in the future, but at the moment

Two series of five consecutive patients with small cell lung cancer were treated with an "accelerated" chemotherapy regimen of cyclophosphamide-doxorubicin-vincristine (CAV) and cisplatin-etoposide (PE) alternated possibly every week. In the first group of patients (median age 49 years, range 46-52) recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) was given as soon as grade IV leukopenia occurred, while in the second group (median age 59 years, 55-68) no growth factor was administered. The mean interval between chemotherapy courses and the mean duration of chemotherapy were 10 and 57 days, respectively, in the patients supported with GM-CSF compared with 13 and 72 days in the control group. One GM-CSF treated patient was withdrawn after the third cycle because of severe toxicity. The mean white blood cell and platelet nadirs were 600 and 46,000/microliters in the first group vs. 840 and 105,000/microliters in the controls. Overall chemotherapy dose-intensity was increased by two fold in the patients given GM-CSF compared with a 1.5 fold increase in the control patients. In all cases, irrespective of their treatment, there was an impaired colony forming capacity of circulating and marrow haemopoietic progenitor cells when grade IV leukopenia occurred, with recovery after the end of leukopenia. This pilot study suggests that accelerated CAV/PE chemotherapy is feasible both with and without GM-CSF. Different GM-CSF schedules as well as combinations of different haemopoietic growth factors may further improve dose-intensity.

Bonner sphere spectrometers (BSS) are being used widely in neutron spectrometry since 1960. The response to neutrons of these moderating detectors spans over a broad energy range. This work discusses the measurement of the sensitivity of an extended range BSS hosting a CR39 nuclear track detector coupled to a boron converter. Two kinds of boron converters were tested, the first made by natural boron and a second one enriched in (10)B. The BSS response functions were calculated with Monte Carlo simulation using the MCNPX 2.4.0. and the FLUKA codes.