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A new method for improving REM counter performance in Pulsed Neutron Fields (PNFs) has been developed. This method uses an analysis of the build-up of space charge in the counter to compensate for an underestimation of Ambient Dose Equivalent (H*(10)) in intense pulsed fields. It was applied to three sets of experimental data acquired using the LUPIN-II REM counter device, which is designed for use in PNFs. The data was acquired using the cyclotron at Helmholtz-Zentrum Berlin für Materialien und Energie GmbH (HZB), at the HiRadMat facility at CERN and at the ‘Elettra Sincrotrone Trieste’ (ELETTRA), Italy. A comparison of the data with and without this compensation method is used to highlight its effectiveness. The LUPIN-II performance, which has already been shown to be able to cope with fields of up to hundreds of nSv/burst, is improved by at least one order of magnitude, with further potential for improvement. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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 16nSv/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. [Copyright &y& Elsevier]

Abstract: 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 4.2MeV to 6MeV. The experimental results show that PADC can measure the total energy lost by a particle along a path of length Δx divided by the length itself, a quantity strictly related to the LET. [Copyright &y& Elsevier]

Abstract: 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 100keV to 10MeV. [Copyright &y& Elsevier]

Abstract: 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 Vt . 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. [Copyright &y& Elsevier]

Abstract: 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). 400MeV/u carbon ion and 250MeV 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. [Copyright &y& Elsevier]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [ABSTRACT FROM AUTHOR]

Abstract: 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 MBqhm−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. [Copyright &y& Elsevier]

Abstract: 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. [Copyright &y& Elsevier]

OBJECTIVE: Erdheim-Chester disease (ECD) is a rare form of non-Langerhans' cell histiocytosis (LCH) of unknown etiology, characterized by diffuse histiocyte infiltration of bones and soft tissue. The purpose of this study was to assess cell proliferation and expression of cytokines, chemokines, and chemokine receptors that may potentially be important in histiocyte accumulation in ECD lesions. METHODS: Biopsies were performed on 3 patients with ECD. The diagnosis of the disease was based on clinical signs including typical radiologic osteosclerosis, and on the detection of foamy CD68+,CD1a- non-Langerhans' cell histiocytes on histologic examination. The expression of the proliferation marker Ki-67 as well as of selected chemokine/chemokine receptor pairs and cytokines was analyzed by immunohistochemistry. RESULTS: In all samples, Ki-67 was undetectable in CD68+ histiocytes. Conversely, these cells expressed the chemokines CCL2 (monocyte chemotactic protein 1), CCL4/macrophage inflammatory protein 1beta (MIP-1beta), CCL5/RANTES, CCL20/MIP-3alpha, and CCL19/MIP-3beta, and their counter-receptors CCR1, CCR2, CCR3, CCR5, CCR6, and CCR7. Moreover, ECD histiocytes expressed interferon-gamma-inducible 10-kd protein (CXCL10), which is specifically induced by interferon-gamma, and interleukin-6 and RANKL, which are both implicated in bone remodeling. Finally, all cases showed a Th1-type lymphocyte infiltrate. CONCLUSION: Our data indicate that, similar to LCH, ECD lesions are characterized by a complex cytokine and chemokine network, which may orchestrate histiocyte activation and accumulation through an autocrine loop and contribute to the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Serum IgD concentrations have been determined in twenty-one patients with Hodgkin's disease, in eight patients with non-Hodgkin's lymphomas and in twenty-eight normal (control) individuals by both a solid-phase radio-immuno-assay and radial-immunodiffusion. Fourteen of the Hodgkin's patients displayed three to forty-five-fold increased serum IgD levels as compared to control individuals, while in the remaining seven patients IgD concentrations were practically normal. Patients with non-Hodgkin's lymphomas had decreased IgD Concentrations. [ABSTRACT FROM AUTHOR]

Activated T lymphocytes often accumulate in the lower dermis of patients with systemic selerosis (Seleroderma) and may play a role in the development of dermal fibrosis. We propagnted and cloned these cells directly from skin biopsies in four of eight cases of early, untreated systemic selerosis with diffuse selerodenna. The cloning frequency estimates were f=0.20 and f=0.48 for T cells derived from the skin of two patients results f=0.68 and f=0.96 for autologous blood T lymphocytes. All but one of 24 skin-derived scleroderma clones were CD4+. Clonal analyses performed with CD4+ clones from patients and normal controls showed that all but one skin-derived clones synthesized either interferon-gamma (60%), glycosaminoglycan-stimulatory factor (26%) or both (9%) when induced in vitro by a mitogen, concannavalin A, but not by autologous dermal fibroblasts. In contrast, blood-derived clones had a different functional phenotype. All skin-derived clones produced tumour necrosis factor-alpha. Our results demonstrate that T lymphocytes obtained from the skin of patients with systemic scelerosis synthesized cytokines which could modulated functions of human dermal fibroblasts. [ABSTRACT FROM AUTHOR]

in seven human adenocarcinomas and a non-neoplastic granulomatous disease of the lung, γδ+ infiltrating lymphocytes (TIL) could be isolated and selectively expanded in vitro upon culture in interleukin-2 (IL-2), without any additional stimuli, indicating a prior activation in vivo. In most cases γδ TIL were predominantly Vδ1+, despite a normal Vδ2:Vδ1 ratio in paired peripheral blood lymphocytes, suggesting a possible expansion of this subset in response to localized antigens/ superantigens. Moreover, in five patients it was possible to identify a Vδ1- Vδ2- TIL population which by polymerase chain reaction (PCR) analysis was shown to be heterogeneous as Vδ gene usage, inclusive of Vδ 3,4,5,6,7 and 8. Of note, these Vδ regions have not been found in peripheral blood so far. Finally, in all cases, γδ TIL displayed killing activity of the autologous turnout, which appeared to be more restricted in the case of Vδ1+ cells. Altogether, these findings suggest a preferential expansion, at the tumour site, of Vδ1+ cells and of cells expressing Vδ genes other than Vδ2. [ABSTRACT FROM AUTHOR]

Background: Charcot-Marie-Tooth disease type 1 (CMT1) and related Dejerine-Sottas syndrome (DSS) and Hereditary Neuropathy with liability to Pressure Palsy (HNPP) have a high degree of genetic heterogeneity; mutation analysis performed by direct nucleotide sequencing is highly sensitive but time-consuming and expensive. Objective: To evaluate the sensitivity of denaturing high performance liquid chromatography (DHPLC), a recently developed technology for fast mutational analysis. Methods: Optimal conditions for analysing Cx32, P0 and PMP22 genes by DHPLC were developed on the basis of 39 mutations (Cx32 = 21; P0 = 10; PMP22 = 8) detected in the period 1997–2002. Patients: During 2003, 44 patients fitting the clinical and electrophysiological criteria of CMT1, DSS or HNPP who were negative for the 17p11.2 duplication/deletion were analysed either by nucleotide sequencing or by DHPLC. Results: In the last year we identified a total of 3 mutations in Cx32, 3 mutations in MP0 (2 novels mutations, one recessive) and 2 mutations in PMP22 (2 novels nonsense mutations). Conclusions: DHPLC was capable of detecting all mutations identified by sequencing, thus appearing as a reliable approach for the mutational analysis of CMT1. [ABSTRACT FROM AUTHOR]

LUPIN-II is an upgraded version of LUPIN, a novel rem counter first developed in 2010 specifically conceived to work in pulsed neutron fields (PNFs). The new version introduces some modifications that improve the performance of the detector, in particular extending its upper detection limit in PNFs. This paper discusses the characteristics and the performance of the instrument. Measurements have been carried out in radiation fields characterized by very different conditions: the detector has first been exposed in PNFs with intensity up to 5 μSv per burst, where it could keep the H*(10) underestimation below 20% up to 500 nSv per burst. It has then been tested in operational conditions around particle accelerators, where it has shown performances similar to that of ionization chambers. Its proper functioning has also been verified in high energy mixed fields, where the experimental results matched the Monte Carlo predictions. Its neutron/photon discrimination capability has been tested in a steady-state photon field where, via an innovative technique based on a threshold set on the derivative of the current signal, it was capable of rejecting a photon H*(10) rate of about 25 mSv/h, and in a mixed neutron/photon field, where a time-based discrimination method was employed. [ABSTRACT FROM AUTHOR]

Abstract: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common form of familial vascular dementia, is caused by mutations of the NOTCH3 gene. Approximately two hundred pathogenic mutations have been reported within five exons (exons 3, 4, 6, 11 and 19) which accounted for 78% of known mutations in worldwide series. We reported twenty-one NOTCH3 pathogenic mutations (including five novel ones) identified in 53 index Italian patients. Exons 4 (28%), 7 (21%) and 19 (24%) were the most frequently involved. To dissect genetic heterogeneity, we analyzed five haplotyped tagging single nucleotide polymorphisms (rs1044009, rs4809030, rs10426042, rs10423702 and rs3815188) in 95 patients, 39 unaffected pedigree members and 50 healthy controls. SNPs were analyzed using the Illumina VeraCode Universal Capture Beads technology by Allele Specific Primer Extension (ASPE). We identified ten different haplotypes named H1–H10; H1 was the most common haplotype in patients and controls and it was associated with at least twelve out of the twenty-one mutations. Detected mutations were not associated to specific haplotypes while genotyping was compatible with a possible founder effect for the novel p.S396C mutation which clustered in a restricted geographical area of northeast Italy. The results added on to the genetic heterogeneity of CADASIL and emphasized difficulties in designing algorithms for molecular diagnosis. [Copyright &y& Elsevier]

Background /Aims: Up to more than 50% of cryptogenetic stroke patients and patients with migraine with aura (MA) are found to have a right-to-left shunt (RLS), which is usually due to a patent foramen ovale. Moreover, both MA and stroke are cardinal features of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Notch3 mutations have been suggested to induce an abnormally high incidence of atrial septal defects in a family harbouring an Arg141Cys pathogenetic mutation. We sought to determine the prevalence of RLS in CADASIL patients with different Notch3 mutations, both with and without migraine as a clinical feature. Methods: Subjects with a molecular diagnosis of CADASIL were tested for the presence of an RLS by means of contrast-enhanced transcranial Doppler (TCD). The diagnosis of migraine was made according to the 2004 International Headache Classification. Results: Sixteen CADASIL patients were tested; 6 had MA. Four patients displayed an RLS on contrast-enhanced TCD examination. Three of these patients had MA. Both patients with Arg141Cys displayed a large RLS. Conclusion: We conclude that RLS is not necessarily linked to CADASIL as a comorbidity factor. Nevertheless, there could be a relation between RLS and specific Notch3 mutations, such as Arg141Cys. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: In X-linked Charcot-Marie-Tooth disease (CMTX), electrophysiological and histopathological studies have suggested either a demyelinating or an axonal polyneuropathy. We report a CMTX family with a striking heterogeneity of nerve conductions between and within nerves.Methods: Two men and one woman have been studied by conduction velocities, sural nerve biopsy with morphometry (one man) and DNA analysis.Results: In both men motor conduction velocities were slowed in the demyelinating range, conduction velocity differences among nerves in the same subject varied from 13 to 24 m/s, and distal median compound muscle action potential (CMAP) amplitudes were 3–5 times reduced compared to ulnar CMAPs. Abnormal area reduction or excessive temporal dispersion of proximal CMAP was present in at least two nerves in all patients. Sural nerve biopsy showed reduction of large myelinated fibres, cluster formations, occasional onion bulbs. Teased fibres study revealed short internodes for fibre diameter, enlarged Ranvier nodes but no evidence of segmental demyelination and remyelination. DNA analysis showed an Arg(15)Gln mutation in connexin32 gene in all patients.Conclusions: In this family conduction slowing and segmental conduction abnormalities, in absence of morphological evidence of de-remyelination, may be related to short internodes, widened Ranvier nodes and the specific effect of the mutation. The occurrence in some CMTX patients of a non uniform involvement between and within nerves, as in acquired demyelinating neuropathies, should be kept in mind to avoid misdiagnoses. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. • Characterization of the dosimeter response in terms of personal dose equivalent H p (10). • Investigation of the angular dependence of the response. • Response function in terms of personal dose equivalent is obtained in an extended energy range (100 keV ÷ 1 GeV). [ABSTRACT FROM AUTHOR]

Six different immune complex test systems for the detection of IgG Fc receptors were applied to the study of various human lymphocyte populations. The extent of binding varied widely according to the system and the cell type employed. Two systems bound preferentially to a high proportion of B lymphocytes from peripheral blood or tonsils, one of which bound with only a very few T cells. In contrast, four other test systems which bound well with the Fc receptors on T lymphocytes gave weaker reactions with Fc receptors on B cells. The reactivity of Fc receptors on null or third population lymphocytes was similar to that of the Fc-positive T cells. Pronase digestion experiments showed a graded selective loss of reactivity with the different Fc reagents. No one system was optimal for all of the lymphocyte populations, although aggregated IgG exhibited the broadest spectrum of reactivity. A pronounced effect of temperature was evident on the binding reactions, and native IgG showed strong binding at 4°C, particularly to the Fc receptors on T cells. [ABSTRACT FROM AUTHOR]

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. a) Algorithm for simulating successfully the response of dosimeters based on CR-39 devices is discussed. b) Response function in terms of ambient dose equivalent is obtained. c) Results are consistent with experiments, and extend the energy range. [ABSTRACT FROM AUTHOR]

Abstract: 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 (3He SP9 proportional counter) or a passive (CR39 + 10B 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. [ABSTRACT FROM AUTHOR]

Abstract: 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 1GeV. 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. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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 3He proportional counter, a 3He proportional counter embedded in the middle of a 9 inch polyethylene sphere, and a 3He 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%. [ABSTRACT FROM AUTHOR]

Abstract: 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 68MeV. The interaction of the proton beam with a thick tungsten target produces a neutron field with energy up to about 60MeV. 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. [Copyright &y& Elsevier]

Abstract: 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 10 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. 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. [Copyright &y& Elsevier]

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. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Mutations in the gene encoding 27-kDa small heat-shock protein B1 (HSPB1) have been reported in association with Charcot-Marie-Tooth disease type 2F or dHMN type II. We describe an Italian patient with wasting and weakness of distal muscles, involving primarily and mostly the lower limbs and later the upper limbs, in which a novel mutation of HSPB1, T180I, was detected. Electrophysiological evaluation disclosed a pure motor axonal neuropathy. Sural nerve biopsy showed a mild reduction of myelinated fibre density. All these findings suggested a CMT2/dHMN phenotype. [ABSTRACT FROM AUTHOR]

Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy ( BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement. We studied an Italian family with a CMT2 phenotype with pyramidal signs that had subclinical sensory involvement on sural nerve biopsy. Direct sequencing analysis of the BSCL2 gene in the three affected siblings revealed an S90L mutation. This report confirms the variability of clinical phenotypes associated with a BSCL2 Ser90Leu mutation and describes the first Italian family with this mutation. Muscle Nerve, 2010 [ABSTRACT FROM AUTHOR]

In human Burkitt's Lymphoma (BL) BRG cells, a t(8;14) translocation, placing c-myc near the Eμ enhancer of the H chain locus, causes tumor expansion. Earlier, we showed that a peptide nucleic acid complementary to the Eμ sequence (PNAEμ), specifically inhibited the expression of translocated c-myc and impaired the growth of BRG cells-induced subcutaneous tumors in mice suffering from severe combined immunodeficiency (SCID). In this study, the therapeutic potential of PNAEμ was evaluated in a systemic mouse model. BRG-BL cells transfected with the luciferase gene were inoculated intravenously into SCID mice resulting in a preferential expansion, similar to the one of human adult patients, in the abdominal cavity, central nervous system and bone marrow. The mice were chronically injected intraperitoneally either with PNAEμ or with control PNA. The treatment was stopped when the control animals developed severe neurological symptoms. As detected both by inspection at necropsy and imaging, overall tumor growth in PNAEμ-treated mice decreased by >80%. Histological and immunohistochemical studies showed, only in PNAEμ-treated mice, a substantially reduced BL cell growth at the major sites of invasion and vast areas of necrosis in the lymphomatous tissues, with concomitant c-myc expression downregulation. Altogether, the data support the therapeutic potential of PNAEμ in human adult BL. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Abstract: 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 für 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. [Copyright &y& Elsevier]

Abstract: Peptide nucleic acids (PNAs) are synthetic homolog of nucleic acids in which the phosphate-sugar polynucleotide backbone is replaced by a flexible polyamide. They bind complementary polynucleotide sequences with higher affinity and specificity than their natural counterparts. PNAs linked to the appropriate nuclear localization signal (NLS) peptide have been used to selectively down-regulate the expression of several genes in viable cells. For example in Burkitt''s lymphoma (BL) cells the c-myc oncogene is translocated in proximity to the Eμ enhancer of the Ig gene locus and upregulated. PNAs complementary to the second exon of c-myc or to the Eμ enhancer sequence (PNAEμ-NLS), selectively and specifically block the expression of the c-myc oncogene and inhibit cell growth in vitro and in vivo. PNAEμ-NLS administration to mice did not exhibit toxic effects even at the highest concentration allowed by the experimental conditions. Because of the accumulating data confirming PNAEμ-NLS potential therapeutic value, PNAEμ-NLS was evaluated for the inability to induce mutations in tester strains of Salmonella typhimurium, Escherichia coli, and at the hprt locus in Chinese hamster ovary cells (CHO). Moreover, the induction of chromosomal aberrations in CHO cells and of micronuclei in human lymphocytes were investigated. We may conclude that PNAEμ-NLS neither induces mutations nor has clastogenic effects as detectable by treatment under the standard test conditions. [Copyright &y& Elsevier]

In Burkitt's lymphoma (BL) cells due to a t(8;14) chromosomal translocation c-myc is often placed in proximity to the Eμ enhancer of the Ig locus and upregulated. We demonstrated that in BL cells a peptide nucleic acid (PNA), complementary to intronic Eμ sequences (PNAEμwt), specifically blocks the expression of the c-myc oncogene under the Eμ enhancer control and inhibits BL cell growth in culture. Here, we investigated whether PNAEμwt was also able to block tumor growth in SCID mice inoculated with human BL cell lines. After subcutaneous inoculum in mice BL cells reproducibly form tumors. Both pre-treatment of BL cells with PNAEμwt before inoculum and chronic intravenous administration of PNAEμwt to mice already inoculated with BL cells selectively caused increased latency of tumor appearance and decreased final tumor size. Tumors from PNAEμwt-treated animals showed substantial areas of cell necrosis and of c-myc downregulation. Inhibition of tumor growth was specific and was not observed with PNAEμmut carrying sequence mutations and in BL cell lines where the translocated c-myc is not under the control of the Eμ enhancer. These data confirm the potential therapeutic value of PNA targeted to regulatory non-coding regions.Cancer Gene Therapy (2007) 14, 220–226. doi:10.1038/sj.cgt.7701002; published online 20 October 2006 [ABSTRACT FROM AUTHOR]

Here we describe clinical, neuropsychological and neuroradiological findings in 6 subjects belonging to two unrelated Italian cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) kindreds from the same geographic area who shared a common Arg1006Cys mutation. Subjects from Family A were virtually asymptomatic, and yet showed MRI pathological findings and a cluster of sub-clinical neuropsychological defects mainly centred on the visuospatial domain; patients from Family B had presented several clinically relevant episodes and showed a general cognitive impairment compatible with the clinical picture of vascular dementia. The present clinical observations are consistent with the hypothesis of a geographical clustering for CADASIL, and highlight that sub-clinical cognitive impairment may help to identify this syndrome in families presenting with only migraine. [ABSTRACT FROM AUTHOR]

Background: Five randomized studies have demonstrated a beneficial effect of adding cisplatin-based chemotherapy to radiation therapy in the treatment of cervical carcinoma. In the present phase II study, we evaluated the response and toxicity of ciplatin-Taxol chemotherapy combined with concomitant radiotherapy in patients with locally advanced cervical carcinoma (LACC) and locally recurrent cervical carcinoma (LRCC). Patients and Methods: In 2000, this phase II study was initiated with a chemotherapy regimen of cisplatin (75 mg/m2) and Taxol (175 mg/m2) every 21 days, for four cycles, concomitant with external radiotherapy and high-dose-rate brachytherapy. Pelvic radiotherapy was started 2 weeks after the first chemotherapy cycle, while the first brachytherapy insertion was carried out during the fourth chemotherapy cycle. SCC marker was determined before treatment and after every chemotherapy cycle. Results: All of the 27 patients treated achieved a complete clinical response. Two patients with LACC experienced distant recurrence 22 and 24 months after complete response, respectively, and 1 patient with LRCC had local progression 6 months after the end of radiotherapy. Although generally tolerable, neutropenia grade 3–4 in 4 patients and anemia grade 3 in 2 patients were observed, and 1 patient experienced grade 2 neurotoxicity; toxicity due to radiotherapy was moderate. Conclusions: Concomitant cisplatin-Taxol chemoradiotherapy seems to be well tolerated, and results, even in this small series, are encouraging. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

A 27-year-old man with the autoimmune lymphoproliferative syndrome and a large-B-cell lymphoma had heterozygous mutations in the Fas and perforin (Prf1) genes. The Fas mutation was inherited from his healthy father and was also carried by his healthy brother, whereas the Prf1 mutation was inherited from his healthy mother. The combined effect of the two mutant genes may have contributed to the development of the autoimmune lymphoproliferative syndrome and lymphoma in this patient. [ABSTRACT FROM AUTHOR]

CD10 constitutes a favourable prognostic marker for childhood acute lymphoblastic leukaemia. Since correlations between CD10, cell cycle and apoptotic abilities were demonstrated in various cell types, we investigated whether differences existed in the cycling/apoptotic abilities of CD10-positive and CD10-negative B acute lymphoblastic leukaemia cells. Twenty-eight cases of childhood acute lymphoblastic leukaemia (mean age of 6.8 years) were subdivided into two groups according to high (17 cases, 93.2+/-4.5%, MRFI 211+/-82 CD10-positive cells) or low (11 cases, 11.5+/-6.2%, MRFI 10+/-7 CD10-negative cells) expression of CD10. CD10-positive acute lymphoblastic leukaemia cells were cycling cells with elevated c-myc levels and propensity to apoptosis, whereas CD10-negative acute lymphoblastic leukaemia cells had lower cycling capacities and c-myc levels, and were resistant to apoptosis in vitro. A close correlation between all these properties was demonstrated by the observations that the few CD10-positive cells found in the CD10-negative acute lymphoblastic leukaemia group displayed elevated c-myc and cycling capacities and were apoptosis prone. Moreover, exposure of CD10-positive acute lymphoblastic leukaemia B cells to a peptide nucleic acid anti-gene specific for the second exon of c-myc caused inhibition of c-myc expression and reduced cell cycling and apoptotic abilities as well as decreased CD10 expression. [ABSTRACT FROM AUTHOR]

Although B cell chronic lymphocytic leukemia (B-CLL) has been traditionally viewed as a tumor of virgin B cells, this notion has been recently questioned by data suggesting that a fraction of B-CLL derives from antigen experienced B cells. In order to further clarify the histogenetic derivation of this lymphoproliferation, we have analyzed the DNA sequences of the 5' non-coding region of BCL-6 proto-oncogene in 28 cases of B-CLL. Mutations of BCL-6 proto-oncogene, a zinc finger transcription factor implicated in lymphoma development, represent a histogenetic marker of B cell transit through the germinal center (GC) and occur frequently in B cell malignancies derived from GC or post-GC B cells. For comparison, the same tumor panel was analyzed for somatic mutations of the rearranged immunoglobulin variable (IgV) genes, which are known to be acquired at the time of B cell transit through the GC. Sequence analyses of BCL-6 and IgV genes allowed the definition of three groups of B-CLL. Group I B-CLL displayed mutations of both BCL-6 and IgV genes (10/28; 36%). Group II B-CLL displayed mutated IgV genes, but a germline BCL-6 gene (5/28; 18%). Finally, group III B-CLL included the remaining cases (13/28; 46%) that were characterized by the absence of somatic mutations of both BCL-6 and IgV genes. Overall, the distribution of BCL-6 and IgV mutations in B-CLL reinforce the notion that this leukemia is histogenetically heterogeneous and that a substantial subgroup of these lymphoproliferations derives from post-germinal center B cells. [ABSTRACT FROM AUTHOR]

The effects of maternal active and passive smoking during pregnancy on childhood central nervous system (CNS) tumours were assessed in a population-based case-control study. The mothers of 244 children aged 0-15 years with CNS tumours and 502 control mothers were interviewed about their smoking habits. All families were resident in the region of Lombardy, Italy. Risk estimates were calculated by unconditional logistic regression, adjusted for age, sex and area of residence. Active smoking by the parents before pregnancy was not associated with increased risk of CNS tumours in the children. Active smoking by the mother during early pregnancy (approximately the first 5 weeks) was associated with a slightly increased risk of the child developing a CNS tumour (odds ratio [OR] 1.5 [95% CI 1.0, 2.3]). An increased risk of CNS tumours was found in the children of non-smoking mothers exposed regularly to tobacco smoke both in early pregnancy (OR 1.8 [95% CI 1.2, 2.6]) and in late pregnancy (OR 1.7 [95% CI 1.2, 2.5]). Although this study was retrospective, the results confirm our previous findings and suggest an association between the risk of developing CNS tumours in children and regular passive smoking by the mother during pregnancy. [ABSTRACT FROM AUTHOR]

Primary effusion lymphoma (PEL) is a lymphoproliferation of B cells infected by Kaposi's sarcoma-associated herpes-virus/human herpesvirus-8 and reflecting a late stage of B cell differentiation close to plasma cell. Apart from viral infection, the pathogenesis of PEL is currently unclear. The aim of the present study was to investigate the role of antigen stimulation and selection in the evolution of PEL. In order to assess the specific variable heavy (VH) and light (VL) genes used by PEL and to define the heavy and light chain isotypes expressed by these lymphomas, immunoglobulin (Ig) genes from seven AIDS-related PEL were sequenced (three cell lines and four primary samples). Most of the samples (five out of seven) used lambda light chain genes; the majority of these (n = 4) belonged to the V lambda 3 family. Two cases expressed mu chains, whereas gamma chains were found in two cases. In all cases, significant deviations from the presumed germline counterpart were found in both the expressed VH and VL genes. Statistical evidence for antigen selection was evident in four out of seven samples studied. Evidence for selection was more frequent in the light chain genes than in the heavy chain genes. Collectively, these data indicate that PEL originate from mature, antigen-experienced B cells and bear implications for the pathogenesis and histogenesis of this lymphoma. [ABSTRACT FROM AUTHOR]