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International audience; Ion beam therapy enables a highly accurate dose conformation delivery to the tumor due to the finite range of charged ions in matter (i.e. Bragg peak (BP)). Consequently, the dose profile is very sensitive to patients anatomical changes as well as minor mispositioning, and so it requires improved dose control techniques. Proton interaction vertex imaging (IVI) could offer an online range control in carbon ion therapy. In this paper, a statistical method was used to study the sensitivity of the IVI technique on experimental data obtained from the Heidelberg Ion-Beam Therapy Center.The vertices of secondary protons were reconstructed with pixelized silicon detectors. The statistical study used the x2 test of the reconstructed vertex distributions for a given displacement of the BP position as a function of the impinging carbon ions. Different phantom configurations were used with or without bone equivalent tissue and air inserts.The inflection points in the fall-off region of the longitudinal vertex distribution were computed using different methods, while the relation with the BP position was established. In the present setup, the resolution of the BP position was about 4–5 mm in the homogeneous phantom under clinical conditions (106 incident carbon ions). Our results show that the IVI method could therefore monitor the BP position with a promising resolution in clinical conditions.

In many dual-task situations, responses to the second of two tasks are slowed when the time between tasks is short. The response-selection bottleneck model of dual-task performance accounts for this phenomenon by assuming that central processing of the second task is blocked by a bottleneck until central processing of Task 1 is complete. This assumption could be called into question if it could be demonstrated that the response to Task 2 affected the central processing of Task 1, a backward response compatibility effect. Such effects are well-established in younger adults. Backward compatibility effects in older (as well as younger) adults were explored in two experiments. The first experiment found clear backward response compatibility effects for younger adults but no evidence of them for older adults. The second experiment explored backward stimulus compatibility and found similar effects in both younger and older adults. Evidence possibly consistent with some pre-bottleneck processing of Task 2 central stages also was found in the second experiment in both age groups. For younger adults, the results provide further evidence falsifying the claim of an immutable response selection bottleneck. For older adults, the evidence suggested that Task 2 affects Task 1 when there is stimulus compatibility but not when there is response compatibility.

Purpose: The purpose of this study was to experimentally assess the possibility to monitor carbon ion range variations—due to tumor shift and/or elongation or shrinking—using prompt-gamma (PG) emission with inhomogeneous phantoms. Such a study is related to the development of PG monitoring techniques to be used in a carbon ion therapy context. Methods: A 95 MeV/u carbon ion beam was used to irradiate phantoms with a variable density along the ion path to mimic the presence of bone and lung in homogeneous humanlike tissue. PG profiles were obtained after a longitudinal scan of the phantoms. A setup comprising a narrow single-slit collimator and two detectors placed at 90° with respect to the beam axis was used. The time of flight technique was applied to allow the selection between PG and background events. Results: Using the positions at 50% entrance and 50% falloff of the PG profiles, a quantity called prompt-gamma profile length (PGPL) is defined. It is possible to observe shifts in the PGPL when there are absolute ion range shifts as small as 1–2 mm. Quantitatively, for an ion range shift of −1.33 ± 0.46 mm (insertion of a Teflon slab), a PGPL difference of −1.93 ± 0.58 mm and −1.84 ± 1.27 mm is obtained using a BaF2 and a NaI(Tl) detector, respectively. In turn, when an ion range shift of 4.59 ± 0.42 mm (insertion of a lung-equivalent material slab) is considered, the difference is of 4.10 ± 0.54 and 4.39 ± 0.80 mm for the same detectors. Conclusions: Herein, experimental evidence of the usefulness of employing PG to monitor carbon ion range using inhomogeneous phantoms is presented. Considering the homogeneous phantom as reference, the results show that the information provided by the PG emission allows for detecting ion range shifts as small as 1–2 mm. When considering the expected PG emission from an energy slice in a carbon ion therapy scenario, the experimental setup would allow to retrieve the same PGPL as the high statistics of the full experimental dataset in 58% of the times. However, this success rate increases to 93% when using a better optimized setup by means of Monte Carlo simulations.

International audience; Prompt-gamma emission detection is a promising technique for hadrontherapy monitoring purposes. In this regard, obtaining prompt-gamma yields that can be used to develop monitoring systems based on this principle is of utmost importance since any camera design must cope with the available signal. Herein, a comprehensive study of the data from ten single-slit experiments is presented, five consisting in the irradiation of either PMMA or water targets with lower and higher energy carbon ions, and another five experiments using PMMA targets and proton beams. Analysis techniques such as background subtraction methods, geometrical normalization, and systematic uncertainty estimation were applied to the data in order to obtain absolute prompt-gamma yields in units of prompt-gamma counts per incident ion, unit of field of view, and unit of solid angle. At the entrance of a PMMA target, where the contribution of secondary nuclear reactions is negligible, prompt-gamma counts per incident ion, per millimetre and per steradian equal to (124 ± 0.7stat ± 30sys) × 10−6 for 95 MeV u−1 carbon ions, (79 ± 2stat ± 23sys) × 10−6 for 310 MeV u−1 carbon ions, and (16 ± 0.07stat ± 1sys) × 10−6 for 160 MeV protons were found for prompt gammas with energies higher than 1 MeV. This shows a factor 5 between the yields of two different ions species with the same range in water (160 MeV protons and 310 MeV u−1 carbon ions). The target composition was also found to influence the prompt-gamma yield since, for 300/310 MeV u−1 carbon ions, a 42% greater yield ((112 ± 1stat ± 22sys) × 10−6 counts ion−1 mm−1 sr−1) was obtained with a water target compared to a PMMA one.

International audience; Hadrontherapy is an innovative radiation therapy modality for which one of the main key advantages is the target conformality allowed by the physical properties of ion species. However, in order to maximise the exploitation of its potentialities, online monitoring is required in order to assert the treatment quality, namely monitoring devices relying on the detection of secondary radiations. Herein is presented a method based on Monte Carlo simulations to optimise a multi-slit collimated camera employing time-of-flight selection of prompt-gamma rays to be used in a clinical scenario. In addition, an analytical tool is developed based on the Monte Carlo data to predict the expected precision for a given geometrical configuration. Such a method follows the clinical workflow requirements to simultaneously have a solution that is relatively accurate and fast. Two different camera designs are proposed, considering different endpoints based on the trade-off between camera detection efficiency and spatial resolution to be used in a proton therapy treatment with active dose delivery and assuming a homogeneous target.

Introduction Single Photon Emission Computed Tomography (SPECT) is at present one of the major techniques for non-invasive diagnostics in nuclear medicine. Almost the whole clinical routine is based on collimated cameras, originally proposed by Anger. Due to the presence of mechanical collimation, detection efficiency and energy acceptance are limited and fixed by the system geometrical features. In order to overcome these limitations, the application of Compton cameras for SPECT is being investigated for several years. Methods We propose in this study to compare a commercial SPECT-Anger device, the GE Healthcare Infinia system with HEGP collimator, and the Compton camera prototype under development by our collaboration [1] , through Monte Carlo simulations (GATE v7.1 and Geant4 9.6 respectively). Given the possible introduction of new radio-emitters at higher energies intrinsically allowed by the Compton camera detection principle, the detectors are exposed to point-like sources at increasing primary gamma energies, from actual isotopes already proposed for nuclear medicine applications. The detector performances are studied in terms of radial event distribution, detection efficiency and final image, obtained by gamma transmission analysis for the Anger system, and with an iterative LM-MLEM algorithm for the Compton reconstruction. Results Preliminary results show for the Compton camera a detection efficiency increased of a factor greater than an order of magnitude, associated with an enhanced spatial resolution for energies beyond 500 keV. Conclusion We discuss then the proven advantages of Compton camera application with particular focus on dose delivered to the patient, examination time and spatial uncertainties.

The first measurement of the helicity dependence of the total inclusive 3He photo-absorption cross section and of the partial cross sections for several reaction channels was carried out at MAMI (Mainz) in the photon energy range between 150 and 500 MeV. The experiment used the large acceptance Crystal Ball spectrometer, complemented by charged particle and vertex detectors, a circularly polarised tagged photon beam and a longitudinally polarised high-pressure 3He gas target. The results obtained give information on the GDH integral on 3He and on the neutron and allow an investigation of the modifications of nucleon properties inside 3He.

A detailed knowledge of the light ions interaction processes with matter is of great interest in basic and applied physics. As an example, particle therapy and space radioprotection require highly accurate fragmentation cross-section measurements to develop shielding materials and estimate acute and late health risks for manned missions in space and for treatment planning in particle therapy. The Fragmentation of Ions Relevant for Space and Therapy experiment at the Helmholtz Center for Heavy Ion research (GSI) was designed and built by an international collaboration from France, Germany, Italy, and Spain for studying the collisions of a C12 ion beam with thin targets. The collaboration's main purpose is to provide the double-differential cross-section measurement of carbon-ion fragmentation at energies that are relevant for both tumor therapy and space radiation protection applications. Fragmentation cross sections of light ions impinging on a wide range of thin targets are also essential to validate the nuclear models implemented in MC simulations that, in such an energy range, fail to reproduce the data with the required accuracy. This paper presents the single differential carbon-ion fragmentation cross sections on a thin gold target, measured as a function of the fragment angle and kinetic energy in the forward angular region (θ≲6∘), aiming to provide useful data for the benchmarking of the simulation softwares used in light ions fragmentation applications. The C12 ions used in the measurement were accelerated at the energy of 400 MeV/nucleon by the SIS (heavy ion synchrotron) GSI facility.

International audience; This paper addresses the problem of evaluating the system matrix and the sensitivity for iterative reconstruction in Compton camera imaging. Proposed models and numerical calculation strategies are compared through the influence they have on the three-dimensional reconstructed images. The study attempts to address four questions. First, it proposes an analytic model for the system matrix. Second, it suggests a method for its numerical validation with Monte Carlo simulated data. Third, it compares analytical models of the sensitivity factors with Monte Carlo simulated values. Finally, it shows how the system matrix and the sensitivity calculation strategies influence the quality of the reconstructed images.

We present novel types of permanently magnetized as well as current powered boxes built from soft-ferromagnetic materials. They provide shielded magnetic fields which are homogeneous within a large fraction of the enclosed volume, thus minimizing size, weight, and costs. For the permanently magnetized solutions, homogenization is achieved either by an optimized distribution of the permanent field sources or by jacketing the field with a soft-ferromagnetic cylindrical shell which is magnetized in parallel to the enclosed field. The latter principle may be applied up to fields of about 0.1 T. With fields of about 1 mT, such boxes are being used for shipping spin-polarized 3 He worldwide for MRI purposes. For current powered boxes, we present concepts and realizations of uniaxial and tri-axial shielded magnetic fields which are homogeneous on the level of 10 −4 within the entire shielded volume. This is achieved by inserting tightly fitting solenoids into a box from soft-magnetic material. The flexible tri-axial solution suits in particular laboratory applications, e.g. for establishing a spin quantization axis.

International audience; The MoniDiam project is part of the French national collaboration CLaRyS (Contrôle en Ligne de l'hAdronthérapie par RaYonnements Secondaires) for on-line monitoring of hadron therapy. It relies on the imaging of nuclear reaction products that is related to the ion range. The goal here is to provide large area beam detectors with a high detection efficiency for carbon or proton beams giving time and position measurement at 100 MHz count rates (beam tagging hodoscope). High radiation hardness and intrinsic electronic properties make diamonds reliable and very fast detectors with a good signal to noise ratio. Commercial Chemical Vapor Deposited (CVD) poly-crystalline, heteroepitaxial and monocrystalline diamonds were studied. Their applicability as a particle detector was investigated using α and β radioactive sources, 95 MeV/u carbon ion beams at GANIL and 8.5 keV X-ray photon bunches from ESRF. This facility offers the unique capability of providing a focused (~1 µm) beam in bunches of 100 ps duration, with an almost uniform energy deposition in the irradiated detector volume, therefore mimicking the interaction of single ions. A signal rise time resolution ranging from 20 to 90 ps rms and an energy resolution of 7 to 9% were measured using diamonds with aluminum disk shaped surface metallization. This enabled us to conclude that polycrystalline CVD diamond detectors are good candidates for our beam tagging hodoscope development. Recently, double-side stripped metallized diamonds were tested using the XBIC (X Rays Beam Induced Current) setup of the ID21 beamline at ESRF which permits us to evaluate the capability of diamond to be used as position sensitive detector. The final detector will consist in a mosaic arrangement of double-side stripped diamond sensors read out by a dedicated fast-integrated electronics of several hundreds of channels. Index Terms— Synthetic diamond detectors, on-line monitoring of hadron therapy, charge collection efficiency, time resolution, integrated fast read out electronics

Polarized He 3 from metastability exchange optical pumping (MEOP) is used as an effective polarized neutron target for electron scattering experiments at the MAinz MIcrotron (MAMI). With the present setup an initial polarization of up to 72% has been obtained at the experimental area. A novel calibration technique will be presented which allows the determination of the absolute polarization within a relative uncertainty of 3%.

Objectives – To explore effectiveness, tolerability and quality of life in elderly patients with epilepsy treated with topiramate. Methods – One year, open-label, flexible-dosing clinical trial. Results – One hundred and seven patients (mean age 69 years, 53% men) were studied during 273 ± 141 days. The average final dose in monotherapy was 98 mg/day vs 153 mg/day in adjunctive treatment. Mean monthly cumulative seizure frequency decreased from 3.7 ± 15 to 1.6 ± 7.7 (n = 101, P

The purpose of this study was to experimentally assess the possibility to monitor carbon ion range variations--due to tumor shift and/or elongation or shrinking--using prompt-gamma (PG) emission with inhomogeneous phantoms. Such a study is related to the development of PG monitoring techniques to be used in a carbon ion therapy context.A 95 MeV/u carbon ion beam was used to irradiate phantoms with a variable density along the ion path to mimic the presence of bone and lung in homogeneous humanlike tissue. PG profiles were obtained after a longitudinal scan of the phantoms. A setup comprising a narrow single-slit collimator and two detectors placed at 90° with respect to the beam axis was used. The time of flight technique was applied to allow the selection between PG and background events.Using the positions at 50% entrance and 50% falloff of the PG profiles, a quantity called prompt-gamma profile length (PGPL) is defined. It is possible to observe shifts in the PGPL when there are absolute ion range shifts as small as 1-2 mm. Quantitatively, for an ion range shift of -1.33 ± 0.46 mm (insertion of a Teflon slab), a PGPL difference of -1.93 ± 0.58 mm and -1.84 ± 1.27 mm is obtained using a BaF2 and a NaI(Tl) detector, respectively. In turn, when an ion range shift of 4.59 ± 0.42 mm (insertion of a lung-equivalent material slab) is considered, the difference is of 4.10 ± 0.54 and 4.39 ± 0.80 mm for the same detectors.Herein, experimental evidence of the usefulness of employing PG to monitor carbon ion range using inhomogeneous phantoms is presented. Considering the homogeneous phantom as reference, the results show that the information provided by the PG emission allows for detecting ion range shifts as small as 1-2 mm. When considering the expected PG emission from an energy slice in a carbon ion therapy scenario, the experimental setup would allow to retrieve the same PGPL as the high statistics of the full experimental dataset in 58% of the times. However, this success rate increases to 93% when using a better optimized setup by means of Monte Carlo simulations.

The G asymmetry of the γp↦Nπ reaction has been measured for the first time for Eγ = 340±14 MeV. This observable, for which very scarce published data exist, plays an important role to disentangle the contributions of the various nucleon resonances. The experiment, performed at the Mainz microtron MAMI, used a 4π-detector system, a linearly polarized, tagged photon beam, and a longitudinally polarized proton target.

The helicity dependence of the total cross section for the (gamma) over right arrow(p) over right arrow -> p pi(0)pi(0) reaction has been measured for the first time at incident photon energies from 400 to 800 MeV. The measurement, performed at the tagged photon beam facility of the MAMI accelerator in Mainz, used the large acceptance detector DAPHNE and a longitudinally polarized frozen-spin target. This channel is found to be excited predominantly when the photon and proton have a parallel spin orientation, most likely due to the intermediate production of the D-13(1520) resonance. However, the contribution of the antiparallel spin configuration, arising from other reaction mechanisms, is also not negligible. This result gives important new information to resolve the existing model discrepancies in the identification of the nucleon resonances contributing to this channel.

Open Access.-- et al., The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at GSI has been designed to study carbon fragmentation, measuring 12C double differential cross sections (∂2σ/∂θ∂E) for different beam energies between 100 and 1000 MeV/u. The experimental setup integrates newly designed detectors in the, so called, Interaction Region around the graphite target. The Interaction Region upstream detectors are a 250 μm thick scintillator and a drift chamber optimized for a precise measurement of the ions interaction time and position on the target. In this article we review the design of the upstream detectors along with the preliminary results of the data taking performed on August 2011 with 400 MeV/u fully stripped carbon ion beam at GSI. Detectors performances will be reviewed and compared to those obtained during preliminary tests, performed with 500 MeV electrons (at the BTF facility in the INFN Frascati Laboratories) and 80 MeV/u protons and carbon ions (at the INFN LNS Laboratories in Catania)., This work has been supported by the European Community FP7 - Capacities, contract ENSAR nº 262010. This work was also supported by Junta de Andalucia and the Spanish Ministerio de Ciencia e Innovacion Contracts P07-FQM-02894, FIS2008-04189 and FPA2008-04972-C03.

A high-quality double-polarization data set for the helicity dependence of the total and differential cross-sections for both gammap --> Npi channels in the Delta region has been obtained in the framework of the GDH experiment. The experiment, performed at the Mainz microtron MAMI, used a 4pi detection system, a circularly polarized photon beam, and a longitudinally polarized frozen-spin target. These data are included in the database to perform a multipole analysis to determine the properties of the Delta(1232)-resonance. For the resonant Delta(1232) multipoles we find a very good agreement with previous analyses, while the nonresonant ones show significant deviations.

The GDH sum rule has been tested for the first time at the electron accelerators MAMI in Mainz and ELSA in Bonn, using circularly polarized photons, a longitudinally polarized nucleon target together with 4 π detector systems. The results agrees within error bars with the sum rule value for the proton.

The helicity dependence of the total cross section for the (γ) over right arrow(p) over right arrownpi(+) pi(0) reaction has been measured for the first time at incident photon energies from 400 to 800 MeV The measurement was performed with the large acceptance detector DAPHNE at the tagged photon beam facility of the MAMI accelerator in Mainz. This channel is found to be excited predominantly when the photon and proton have a parallel spin orientation, due to the intermediate production of the D-13 resonance. (C) 2002 Elsevier Science B.V. All rights reserved.

An apparatus and corresponding software for optimization of photon beams during the beam development phase and for monitoring during experiments is described. The system consists of a scintillator positioned in the beam, an image intensifier and a highly sensitive CCD camera. The CCD camera is read out and controlled by a PC via a frame-grabber card. Software control of the camera and a graphical interface have been developed. The intensity as well as the position of the beam can be constantly supervised online.

International audience; Monte Carlo simulations are nowadays essential tools for a wide range of research topics in the field of radiotherapy. They also play an important role in the effort to develop a real-time monitoring system for quality assurance in proton and carbon ion therapy, by means of prompt-gamma detection. The internal theoretical nuclear models of Monte Carlo simulation toolkits are of decisive importance for the accurate description of neutral or charged particle emission, produced by nuclear interactions between beam particles and target nuclei. We assess the performance of Geant4 nuclear models in the context of prompt-gamma emission, comparing them with experimental data from proton and carbon ion beams. As has been shown in the past and further indicated in our study, the prompt-gamma yields are consistently overestimated by Geant4 by a factor of about 100% to 200% over an energy range from 80 to 310 MeV/u for the case of 12C, and to a lesser extent for 160 MeV protons. Furthermore, we focus on the quantum molecular dynamics (QMD) modeling of ion-ion collisions, in order to optimize its description of light nuclei, which are abundant in the human body and mainly anticipated in hadrontherapy applications. The optimization has been performed by benchmarking QMD free parameters with well established nuclear properties. In addition, we study the effect of this optimization on charged particle emission. With the usage of the proposed parameter values, discrepancies reduce to less than 70%, with the highest values being attributed to the nucleon-ion induced prompt-gammas. This conclusion, also confirmed by the disagreement we observe in the case of proton beams, indicates the need for further investigation on nuclear models which describe proton and neutron induced nuclear reactions.

The helicity dependence of the single pion photoproduction on the proton has been measured in the energy range from 200 to 450 MeV for the first time. The experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a circularly polarized, tagged photon beam, and a frozen-spin target. The data obtained provide new information for multipole analyses of pion photoproduction and determine the main contributions to the Gerasimov-Drell-Hearn sum rule and the forward spin polarizability gamma(0).

A measurement of beam helicity asymmetries in the reaction $^{3}\stackrel{\ensuremath{\rightarrow}}{\mathrm{He}}(\stackrel{\ensuremath{\rightarrow}}{e},{e}^{\ensuremath{'}}n)pp$ is performed at the Mainz Microtron in quasielastic kinematics to determine the electric to magnetic form factor ratio of the neutron ${G}_{E}^{n}/{G}_{M}^{n}$ at a four-momentum transfer ${Q}^{2}=1.58\text{ }\text{ }{\mathrm{GeV}}^{2}$. Longitudinally polarized electrons are scattered on a highly polarized $^{3}\mathrm{He}$ gas target. The scattered electrons are detected with a high-resolution magnetic spectrometer, and the ejected neutrons are detected with a dedicated neutron detector composed of scintillator bars. To reduce systematic errors, data are taken for four different target polarization orientations allowing the determination of ${G}_{E}^{n}/{G}_{M}^{n}$ from a double ratio. We find ${\ensuremath{\mu}}_{n}{G}_{E}^{n}/{G}_{M}^{n}=0.250\ifmmode\pm\else\textpm\fi{}0.058(\mathrm{stat})\ifmmode\pm\else\textpm\fi{}0.017(\mathrm{syst})$.

During therapeutic treatment with heavy ions like carbon, the beam undergoes nuclear fragmentation and secondary light charged particles, in particular protons and alpha particles, are produced. To estimate the dose deposited into the tumors and the surrounding healthy tissues, an accurate prediction on the fluences of these secondary fragments is necessary. Nowadays, a very limited set of double di ffential carbon fragmentation cross sections are being measured in the energy range used in hadrontherapy (40 to 400 MeV/u). Therefore, new measurements are performed to determine the double di ffential cross section of carbon on di erent thin targets. This work describes the experimental results of an experiment performed on May 2011 at GANIL. The double di ffential cross sections and the angular distributions of secondary fragments produced in the 12C fragmentation at 95 MeV/u on thin targets (C, CH2, Al, Al2O3, Ti and PMMA) have been measured. The experimental setup will be precisely described, the systematic error study will be explained and all the experimental data will be presented.

A measurement of beam helicity asymmetries in the reaction 3He[over →](e[over →],e'n)pp is performed at the Mainz Microtron in quasielastic kinematics to determine the electric to magnetic form factor ratio of the neutron GEn/GMn at a four-momentum transfer Q2=1.58 GeV2. Longitudinally polarized electrons are scattered on a highly polarized 3He gas target. The scattered electrons are detected with a high-resolution magnetic spectrometer, and the ejected neutrons are detected with a dedicated neutron detector composed of scintillator bars. To reduce systematic errors, data are taken for four different target polarization orientations allowing the determination of GEn/GMn from a double ratio. We find μnGEn/GMn=0.250±0.058(stat)±0.017(syst).

International audience; Prompt secondary radiations such as gamma rays and protons can be used for ion-range monitoring during ion therapy either on an energy-slice basis or on a pencil-beam basis. We present a review of the ongoing activities in terms of detector developments, imaging, experimental and theoretical physics issues concerning the correlation between the physical dose and hadronic processes

The pharmacokinetics of meloxicam were investigated in 12 patients with clinically stable liver cirrhosis after a single oral dose of 15mg. 12 healthy volunteers received the same regimen in earlier studies and the results of both groups were compared. Only minor differences in pharmacokinetic parameters were observed between the 2 groups. However, equivalence between the 2 groups could not be demonstrated, probably because of the large variation in the liver function status of the patients with cirrhosis. Mean maximum plasma concentration (Cmax) in the cirrhotic patients was 0.84 mg/L and the time to Cmax(tmax) was 10.3 hours. The corresponding values for the healthy volunteers were 0.91 mg/L and 7.0 hours, respectively. The elimination half-life (t1/2) was 16.4 hours in the cirrhotic patients and 21.2 hours in the healthy volunteers. The area under the plasma concentration-time curve (AUC) was approximately 25% lower in the cirrhotic patients (25.1 mg/L•h) than in the controls (31.2 mg/L•h). The plasma protein binding of meloxicam showed no relevant difference between the 2 groups. The cirrhotic patients revealed an unbound fraction of 0.35%, compared with 0.28% in the healthy controls. Since the data presented in this report show no substantial change in pharmacokinetics, and the drug is not retained in hepatically impaired patients, no dosage adjustments appear necessary in cirrhotic patients requiring meloxicam treatment.

submitted to conference record of IEEE NSS-MIC, Anaheim USA, 29 october-3 november 2012; International audience; A 8 channel Front End Electronics (FEE) circuit has been designed and fabricated in 0.35 μm CMOS process from Austria Micro System to be coupled with the Silicon Strip Detector (SSD) of the Compton Camera for quality control of hadrontherapy. Each channel includes a Charge Sensitive Amplifier (CSA) followed by two parallel CR-RC shapers. Slow and fast shapers, with 1 μs and 15 ns shaping time, are used to measure the energy and to time stamp all events respectively. The two sides of the SSD are read thanks to a configurable system for holes and electrons. The CSA presents an open loop gain of 67 dB and 90 degrees phase margin assuring a high stability. The circuit has been successfully tested. The test results are in good agreement with analytic and simulation calculations. Here, we describe the principles and present measured performances of the prototype. A high linearity over the range of 3E3 to 3E6 electrons is reached with a conversion gain of 3.6 mV/fC. The circuit achieves an ENC (Equivalent Noise Charge) of 412 electrons rms. 75% of the total noise is generated by the small value of the feedback resistor chosen to avoid pile up phenomenon due to the 1E5 hits/s occupancy rate. A cross-talk of 2 % was measured, 99% of which is due to the power supply disturbances. The power supply dissipation is 21 mW/channel for 3.3 V supply voltage. The area of this design is 2871×1881 μm2 including pads.

International audience; The use of protons in radiotherapy offers a very precise and effective tool for malignant tumor treatment. In order to fully exploit the benefits of proton therapy, a precise determination of the proton range inside the patient is needed. Currently, this information is provided by conventional X-ray CT. In our work, we explore the theoretical limits of proton CT by means of Monte Carlo simulations. We focus on the accuracy in determining the electron density of different clinical relevant materials and the systematic uncertainties that influence the measurement with an ideal cone beam proton CT scanner.

Purpose: The utilization of protons and carbon ions for radiotherapy purposes provides high conformity and increased biological effectiveness. In order to fully benefit from the advantages, a precise beam range monitoring in real time is vital. The detection of prompt gammas with a collimated scintillating detector makes it possible to locate the Bragg peak position during proton or carbon ion irradiation. Accurate Monte Carlo simulations are essential both for the further development of an optimized detection array and for the accurate estimation of the applicability of the system in clinical conditions. Purpose of the current work is to assess and improve the performance of the Geant4 toolkit in the description of currently available prompt-gamma data.

Polarized {sup 3}He obtained from metastability exchange optical pumping is used for various double polarized experiments at the Mainz Microtron (MAMI). At the experimental area more than 70% initial target polarization is available. Besides a description of the target setup and its performance under electron beam conditions, the status of the polarized {sup 3}He target for the tagged photon beam at MAMI will be given.

Acute myocardial ischemia provokes sensitization of the adenylyl cyclase system. This sensitization can be differentiated in a receptor-specific and an enzyme-specific sensitization. The receptor-linked sensitization is characterized by an increase of β-adrenergic receptors in the plasma membranes after 15 mins of global ischemia (49.8 ± 3.6 to 67 ± 6 fmol/mg protein) followed by a further increase (89 ± 4 fmol/mg protein) after 50 min of ischemia in isolated perfused hearts. Concomitantly functionally coupled receptors which are able to bind the β-agonist with high affinity, increased by 32% after 15 min and by 57% after 50 min of ischemia. The affinities of the receptors for their agonists or their antagonists remain unchanged. Maximally isoproterenol-stimulated adenylyl cyclase activity rose from 66 ± 7 to 101 ± 10 pmol cAMP/min/mg protein after 15 min of global ischemia indicating the β-receptor-specific sensitization of the β-adrenergic system. This sensitization was followed by a gradual decline of the adenylyl cyclase activity after 30 and 50 min of global ischemia. Additionally, 15 min of myocardial ischemia induced an enzyme-linked sesitization of the adenylyl cyclase activity as indicated by an increase of the forskolin-stimulated activity by about 25% (300 ± 20 vs 378 ± 25 pmol cAMP/min/mg protein). In contrast after 50 min of ischemia the total adenylyl cyclase activity declined (232 ± 24 pmol cAMP/min/mg protein) despite the persistent increase of β-adrenergic receptors in the plasma membranes. These data demonstrate that the enzyme-specific sensitization is only transient. The early sensitization and late inactivation of the adenylyl cyclase activity occurred independently of receptor activation and could not be prevented by β-blockade (10−6 m alprenolol). Cyanide perfusion (1 m m), used to block energy metabolism, lead to energy depletion similar to acute myocardial ischemia. This resulted in an increase of functionally coupled receptors with a time course comparable to that of global ischemia. Additional perfusion with desensitizing concentrations of the β-agonist isoproterenol did not induce uncoupling or internalization of β-adrenergic receptors in cyanide treated hearts, suggesting that the rise in functionally coupled receptors is due to a redistribution in part caused by the abolition of continuous receptor internalization. In contrast, the enzyme-linked sensitization is independent of cellular localization of the β-adrenergic receptors. The increased activity was carried by the enzyme even after partial purification with solubilization and wheat germ affinity chromatography. These data suggest an ischemia-induced, covalent modification of the adenylyl cyclase. This enzyme-specific sensitization or its late inactivation of the enzyme does not occur after cyanide perfusion demonstrating that energy depletion is not solely responsible for this sensitization process. The characterization of these distinct pathomechanisms and time courses of the ischemia-induced activation of the β-adrenergic system allowed to differentiate a receptor- versus an enzyme-specific sensitization of the adenylyl cyclase system in acute myocardial ischemia. Such dual sensitization of the β-adrenergic system may contribute to the increased sensitivity of the infarcted heart to catecholamines.

Helicity-dependent total photoabsorption cross sections on the deuteron have been measured for the first time at ELSA (Bonn) in the photon energy range from 815 to 1825 MeV. Circularly polarized tagged photons impinging on a longitudinally polarized LiD target have been used together with a highly efficient 4pi detector system. The data around 1 GeV are not compatible with predictions from existing multipole analyses. From the measured energy range an experimental contribution to the GDH integral on the neutron of [33.9 +/- 5.5(stat) +/- 4.5(syst)] microb is extracted.

For the first time we checked the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the proton experimentally in the photon energy range from 0.2-2.9 GeV with the tagged photon facilities at MAMI (Mainz) and ELSA (Bonn). New data of the doubly polarized total cross section difference are presented in the energy range from 1.6 to 2.9 GeV. The contribution to the GDH integral from 0.2-2.9 GeV yields [254+/-5(stat)+/-12(syst)] microb with negative contributions in the Regge regime at photon energies above 2.1 GeV. This trend supports the validity of the GDH sum rule.

To verify the fundamental Gerasimov-Drell-Hearn (GDH) sum rule for the first time experimentally, we measured the helicity dependent total photoabsorption cross section with circularly polarized real photons and longitudinally polarized nucleons in the photon energy range 0.68-1.82 GeV with the tagged photon facility at ELSA. The experiment was carried out with a 4pi detection system, a circularly polarized tagged photon beam, and a frozen spin polarized proton target. The contribution to the GDH sum rule in this photon energy range is [49.9+/-2.4(stat)+/-2.2(syst)] microb.

The helicity dependence of the $\stackrel{\ensuremath{\rightarrow}}{\ensuremath{\gamma}}\stackrel{\ensuremath{\rightarrow}}{p}\ensuremath{\rightarrow}p{\ensuremath{\pi}}^{0}$ reaction has been measured for the first time in the photon-energy range from 550 to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a $4\ensuremath{\pi}$-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target. These data are predominantly sensitive to the ${D}_{13}(1520)$ resonance and are used to determine its helicity amplitudes.

The helicity dependence of the gamma--p----ppi(0) reaction has been measured for the first time in the photon-energy range from 550 to 790 MeV. The experiment, performed at the Mainz microtron MAMI, used a 4pi-detector system, a circularly polarized, tagged photon beam, and a longitudinally polarized frozen-spin target. These data are predominantly sensitive to the D13(1520) resonance and are used to determine its helicity amplitudes.

The experimental check of the GDH sum rule is being performed at the tagged photon facilities of the electron accelerators MAMI (Mainz) and ELSA (Bonn), using circularly polarized photons impinging on a longitudinally polarized proton target, together with detector systems covering almost the whole solid angle range. Results from the MAMI experiment for the double polarized total photoabsorption cross section in the low energy region (200 MeV < Eγ < 800 MeV) will be shown together with their contribution to the GDH sum rule. Furthermore first results from the ELSA experiment in the higher energy region (680 MeV < Eγ < 1900 MeV) will be presented.