Calibration of the low-energy channel Thomson parabola of the LMJ-PETAL diagnostic SEPAGE with protons and carbon ions.

The SEPAGE diagnostic will detect charged particles (electrons, protons, and ions) accelerated in the interaction of the PETAL (PETawatt Aquitaine Laser) laser with its targets on the LMJ (Laser MegaJoule)-PETAL laser facility. SEPAGE will be equipped with a proton-radiography front detector and two Thomson parabolas (TP), corresponding to different ranges of the particle energy spectra: Above 0.1 MeV for electrons and protons in the low-energy channel, with a separation capability between protons and 12C6+ up to 20 MeV proton energy and above 8 MeV for the high-energy channel, with a separation capability between protons and 12C6+ up to 200 MeV proton kinetic energy. This paper presents the calibration of the SEPAGE's low-energy channel TP at the Tandem facility of Orsay (France) with proton beams between 3 and 22 MeV and carbon-ion beams from 5.8 to 84 MeV. The magnetic and electric fields' integrals were determined with an accuracy of 10-3 by combining the deflections measured at different energies with different target thicknesses and materials, providing different in-target energy losses of the beam particles and hence different detected energies for given beam energies.

Calibration of imaging plate detectors to mono-energetic protons in the range 1-200 MeV.

Responses of Fuji Imaging Plates (IPs) to proton have been measured in the range 1-200 MeV. Mono-energetic protons were produced with the 15 MV ALTO-Tandem accelerator of the Institute of Nuclear Physics (Orsay, France) and, at higher energies, with the 200-MeV isochronous cyclotron of the Institut Curie-Centre de Protonthérapie d'Orsay (Orsay, France). The experimental setups are described and the measured photo-stimulated luminescence responses for MS, SR, and TR IPs are presented and compared to existing data. For the interpretation of the results, a sensitivity model based on the Monte Carlo GEANT4 code has been developed. It enables the calculation of the response functions in a large energy range, from 0.1 to 200 MeV. Finally, we show that our model reproduces accurately the response of more complex detectors, i.e., stack of high-Z filters and IPs, which could be of great interest for diagnostics of Petawatt laser accelerated particles.

The GEMpix detector as new soft X-rays diagnostic tool for laser produced plasmas.

Laser produced plasmas lend to several interesting applications. The study of X-ray emission from this kind of plasmas is important not only to characterize plasmas itself but also to study the application of these particular plasmas as intense X-ray sources. In particular several emission configurations can be obtained using different kinds of targets and tuning the characteristics of the laser pulse delivered to the target. Typically, laser pulse duration ranges between a few tens of femtoseconds and tens of nanoseconds, with energies from few mJ to tens of kJ. X-ray photon emissions last for times comparable to the laser pulses and during this time a great number of photons can be emitted. The following paper presents a measure of the soft-X-ray emission on the ECLIPSE laser facility realized with a new triple-GEM gas detector (GEMpix). It is a hybrid gas detector with a C-MOS front-end electronics based on Medipix chips. In the present work, different targets have been used in order to test X-rays of different energies. In this paper, in particular, we present results obtained for copper and iron targets. GEMpix is able to realize a 2D imaging of the X-ray emission from plasma with a signal proportional to the energy released in the gas of the detector active volume. Then through a preliminary single photon equalization realized at the NIXT lab (ENEA), also the number of photons reaching the area of the detector has been estimated.

Calibration of imaging plates to electrons between 40 and 180 MeV.

This paper presents the response calibration of Imaging Plates (IPs) for electrons in the 40-180 MeV range using laser-accelerated electrons at Laboratoire d'Optique Appliquée (LOA), Palaiseau, France. In the calibration process, the energy spectrum and charge of electron beams are measured by an independent system composed of a magnetic spectrometer and a Lanex scintillator screen used as a calibrated reference detector. It is possible to insert IPs of different types or stacks of IPs in this spectrometer in order to detect dispersed electrons simultaneously. The response values are inferred from the signal on the IPs, due to an appropriate charge calibration of the reference detector. The effect of thin layers of tungsten in front and/or behind IPs is studied in detail. GEANT4 simulations are used in order to analyze our measurements.

Validation of modelled imaging plates sensitivity to 1-100 keV x-rays and spatial resolution characterisation for diagnostics for the "PETawatt Aquitaine Laser".

Thanks to their high dynamic range and ability to withstand electromagnetic pulse, imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. In the framework of the development of the diagnostics for the Petawatt Aquitaine Laser facility, we present an absolute calibration and spatial resolution study of five different available types of IP (namely, MS-SR-TR-MP-ND) performed by using laser-induced K-shell X-rays emitted by a solid silver target irradiated by the laser ECLIPSE at CEntre Lasers Intenses et Applications. In addition, IP sensitivity measurements were performed with a 160 kV X-ray generator at CEA DAM DIF, where the absolute response of IP SR and TR has been calibrated to X-rays in the energy range 8-75 keV with uncertainties of about 15%. Finally, the response functions have been modeled in Monte Carlo GEANT4 simulations in order to reproduce experimental data. Simulations enable extrapolation of the IP response functions to photon energies from 1 keV to 1 GeV, of interest, e.g., for laser-driven radiography.

Study of imaging plate detector sensitivity to 5-18 MeV electrons.

Imaging plates (IPs) are commonly used as passive detectors in laser-plasma experiments. We calibrated at the ELSA electron beam facility (CEA DIF) the five different available types of IPs (namely, MS-SR-TR-MP-ND) to electrons from 5 to 18 MeV. In the context of diagnostic development for the PETawatt Aquitaine Laser (PETAL), we investigated the use of stacks of IP in order to increase the detection efficiency and get detection response independent from the neighboring materials such as X-ray shielding and detector supports. We also measured fading functions in the time range from a few minutes up to a few days. Finally, our results are systematically compared to GEANT4 simulations in order to provide a complete study of the IP response to electrons over the energy range relevant for PETAL experiments.

CR-39 track detector calibration for H, He, and C ions from 0.1-0.5 MeV up to 5 MeV for laser-induced nuclear fusion product identification.

Laser-accelerated ion beams can be used in many applications and, especially, to initiate nuclear reactions out of thermal equilibrium. We have experimentally studied aneutronic fusion reactions induced by protons accelerated by the Target Normal Sheath Acceleration mechanism, colliding with a boron target. Such experiments require a rigorous method to identify the reaction products (alpha particles) collected in detectors among a few other ion species such as protons or carbon ions, for example. CR-39 track detectors are widely used because they are mostly sensitive to ions and their efficiency is near 100%. We present a complete calibration of CR-39 track detector for protons, alpha particles, and carbon ions. We give measurements of their track diameters for energy ranging from hundreds of keV to a few MeV and for etching times between 1 and 8 h. We used these results to identify alpha particles in our experiments on proton-boron fusion reactions initiated by laser-accelerated protons. We show that their number clearly increases when the boron fuel is preformed in a plasma state.

Near normalization of final height with adapted doses of growth hormone in Turner's syndrome.

An adapted GH dose regimen was evaluated in 14 untreated patients with Turner's syndrome. The initial GH dose (0.7 U/kg.BW) was increased by 0.7 U/kg.BW, up to a maximum of 2.1 U/kg.BW, when growth velocity (GV) declined to less than 200% of the pretreatment level. These patients were compared to a group of 17 patients with similar initial characteristics, who received a fixed dose of 0.9 U/kg.BW GH. Tolerance to both GH regimens was excellent. The adapted GH doses only partially prevented the waning effect observed with conventional doses of GH, and the initial goal of doubling GV was only achieved in 42% of the 112 patient-semesters. Doubling the GH dose from 0.7 to 1.4 U/kg.BW increased the GV by 1.6 +/- 1.8 cm/yr (P < 0.006); increasing the GH dose from 1.4 to 2.1 U/kg.BW increased GV by 0.8 +/- 1.3 cm/yr (P = NS). The overall height gain during the 4-yr trial was 25.6 +/- 3.9 cm in the adapted dose group and 21.8 +/- 3.9 cm in the conventional group (P < 0.02). Final height (FH) results were obtained in 12 of 14 patients in the adapted dose group and all 17 patients in the conventional group and compared to the predicted FH using Lyon's method. The estimated height benefit was 10.6 +/- 3.8 cm in the adapted dose group compared to 5.2 +/- 3.7 cm in the conventional group (P < 0.01). Eighty-three percent of the patients in the adapted dose group had an FH superior or equal to -2 SD score for the general population compared to 29% in the conventional group. In conclusion, a marked increment in the GH dose in girls with Turner's syndrome associated with a relatively late age at introduction of estrogen therapy brought 83% of the patients into the lower range of the normal height distribution of the general population.

Dose-dependent catch-up growth after 2 years of growth hormone treatment in intrauterine growth-retarded children. Belgian and French Pediatric Clinics and Sanofi-Choay (France).

This study reports the results of a 2-yr clinical trial with GH in 95 short prepubertal children with non-GH-deficient intrauterine growth retardation. This randomized, double blind, controlled study compared the effects of placebo (restricted to the first 6 months) and two doses of GH (0.4 and 1.2 IU/kg.week) given sc 6 days/week for 2 yr. A significant GH dose-dependent growth acceleration was observed. Mean height gain (SDS/CA) was 0.66 +/- 0.07 in group I (low dose, 0.4 IU/kg.week) compared to 1.25 +/- 0.07 in group II (high dose, 1.2 IU/kg.week). Mean bone maturation progression (expressed in months) was 26.2 +/- 1.7 and 30.2 +/- 1.5 over 24 months in groups I and II, respectively. Onset of puberty was observed in some patients of both groups. Whether chronic use of a high GH dose will advance the onset of puberty remains to be established. A great variability of growth acceleration was seen among GH dose groups, suggesting that factors in addition to GH dose might modulate individual responses to treatment. In conclusion, it is suggested that in these patients, dose-dependent catch-up growth could be induced by GH treatment.

Measurement of tensor polarization in elastic electron-deuteron scattering at large momentum transfer

Tensor polarization observables ( t(20), t(21), and t(22)) have been measured in elastic electron-deuteron scattering for six values of momentum transfer between 0.66 and 1.7 (GeV/c)(2). The experiment was performed at the Jefferson Laboratory in Hall C using the electron High Momentum Spectrometer, a specially designed deuteron magnetic channel and the recoil deuteron polarimeter POLDER. The new data determine to much larger Q2 the deuteron charge form factors G(C) and G(Q). They are in good agreement with relativistic calculations and disagree with perturbative QCD predictions.

Preliminary phase I clinical study and pharmacokinetics of (1,2-diaminocyclohexane) (isocitrato) platinum (II) or PHIC.

PHIC [NSC-350602; (1,2-diaminocyclohexane) (isocitrato) platinum (II)] is a new highly water-soluble platinum derivative. Preclinical studies showed antitumor activity on a wide range of tumors, no cross-resistance with cisplatin and little or no nephrotoxicity in mice and baboons. A phase I clinical trial was then initiated at doses of 300 mg/m2 infused intravenously over one hour without induced diuresis or hydration. Dosages were escalated up to 1500 mg/m2. A total of 29 patients received 52 courses of treatment. The most important side-effect is thrombocytopenia which is rapidly reversible. Nausea and/or vomiting were mild or moderate with onset 1 hr after the end of the infusion and seldom persisted beyond 24 hrs. Measurements of biological parameters did not reveal significant evidence of nephrotoxicity except in one patient who developed urinary tract infection and for whom hemodialysis became necessary. No change in the audiogram could be demonstrated. Peripheral neuropathy was documented in one patient, and in two other patients to whom morphine was given confusional episodes were observed. Although no antitumor effect was observed, there was apparent stabilization of disease. Pharmacokinetic parameters were calculated in twelve out of these 29 patients. Based upon total platinum plasma concentrations, the elimination half-life is 58.3 hrs and the plasma clearance is 21.2 ml/min with an apparent volume of distribution of 7.6 liters. However, considering both plasma concentrations and urinary excretion, we could estimate the half-life of free filterable species (60 min), the plasma clearance (125 ml/min) and the renal clearance (86 ml/min). Mean urinary excretion is 64.4% of the dose after 6 days and 53.1% at 24 hrs. Other administration protocols are suggested, based upon these pharmacokinetic parameters.

Adult height in children with prepubertal short stature secondary to intrauterine growth retardation.

In a retrospective study of 47 children seen before puberty for growth retardation secondary to intrauterine growth retardation (IUGR), 23 boys had a final height of 161.9 +/- 8.0 cm and 24 girls a final height of 147.6 +/- 7.2 cm, values that were significantly lower than the target heights of these patients (p < 0.001). This reduction in adult height indicates the possible usefulness of growth hormone therapy in children with IUGR.

[Treatment of metastatic renal cancer in adults with elliptinium acetate]. / Traitement des cancers du rein métastasés de l'adulte par l'acétate d'elliptinium.

The results obtained with N-methyl-hydroxy-elliptinium acetate (NMHE) in the treatment of 22 assessable adult patients with metastatic renal cancer are reported. According to the WHO criteria, there were 10 responses, including 7 stabilizations, 2 partial remissions (greater than 50%) and one complete and durable remission. Since there is no other effective medical treatment for this type of tumour, and since the protocol used so far appears to have low toxicity and makes it possible to evaluate the value of the drug within 4 to 6 weeks, the trial will be extended in order to determine more precisely (+/- 5%) the degree of effectiveness of NMHE.

Positioning, labelling and control of medical information: artesunate strategy and Arsumax development story.

Sanofi decided, some years ago, to help developing a molecule of a new type called artesunate, a semisynthetic derivative from Qinghaosu, or artemisinine, a sesquiterpenic lactone extracted from the leaves of a world wide spread plant: Artemisia annua. After having signed a secrecy agreement with a local pharmaceutical company in China manufacturing artesunate, Sanofi started, in 1993, the assessment of all the data transmitted as well as the plant involved in the artesunate tablet manufacturing. As conclusions of the whole audit performed on this project were judged satisfactory, Sanofi signed a cooperation agreement with this Chinese pharmaceutical firm in order to be allowed to start further development work required to guarantee quality and safety of artesunate 50 mg tablets called Arsumax, and to complete a registration dossier acceptable for Health Authorities in French-speaking Africa. Pharmaceutical, pharmacotoxicological and clinical documentation were widely completed, and entirely reformated according to European guidelines. The registration dossier was submitted in all French speaking African countries. The approval has been obtained in 13 countries. Due to its fast efficacy, its absence of undesirable effects, its presentation in tablets, its quite simple dosage (one box for a treatment), Arsumax positioned itself as an accurate second line antimalaric treatment.

[African Quin: results of a pragmatic study on the diagnosis of uncomplicated malaria attacks and treatment using quinine in French-speaking Africa]. / African-Quin: résultats d'une étude pragmatique sur le diagnostic de l'accès palustre simple et son traitement par la quinine en Afrique francophone.

Management and treatment of disease do not always conform with official recommendations. African-quin is a pragmatic multicentric study carried out in 13 African countries to evaluate non-conformities in the management and treatment of uncomplicated malarial attacks using quinine. This study involved a total of 3,981 patients with documented uncomplicated malarial attacks diagnosed by 500 clinical physicians. Physicians were supplied with quinine tablets (125 mg et 500 mg Quinimax containing 125 mg and 500 mg of quinine base respectively) to allow treatment according to the dose recommendations of the WHO (24 mg/kg/day of quinine base). In 38% of the 3,981 patients, diagnosis was based on clinical findings without measurement of parasitemia. The median dose of Quinimax was 15.4 mg/kg/day in 3 intakes in 67% and 2 intakes in 33%. The dose was 23.2 mg/kg/day for patients under 12 years and 14.7 mg/kg/day for patients over 18 years (p < 0.001). Treatment lasted for at least 5 days in 62% of patients. Fever control was achieved within a mean delay of 3.9 +/- 1.5 days and was followed by a rapid decrease in clinical symptoms. Clinical control (normal temperature) was obtained in 96% of patients. The dose of Quinimax was the same regardless of whether treatment was a success or failure. The results of this study demonstrate the gap between official recommendations and everyday clinical practice and raise several important questions concerning the basis for decision-making, treatment goals, drug dosage, and treatment duration.

[Rapid resolution of Plasmodium ovale malarial attacks using artesunate (Arsumax)]. / Resolution rapide des acces palustres à Plasmodium ovale par l'artésunate (Arsumax).

This randomized, non-comparative clinical trial without placebo was carried out to assess the efficacy and tolerance of artesunate for treatment of acute Plasmodium ovale malarial attacks. Thirty Cameroonese patients were included. All presented acute Plasmodium ovale malarial attacks with parasitemia in excess of 500 asexual forms per mm3. Four days after treatment with artesunate, all 30 patients were asymptomatic with no parasitemia. Reduction rates were 93.9 p. 100 for asexual forms and 75.4 p. 100 for gametocytes. Parasite clearance was achieved within 38.8 hours and fever disappeared within 36.6 hours. Tolerance was excellent in 29 patients. The remaining patient briefly complained of mild vertigo. A transient decrease in reticulocyte levels was observed in one patient initially presenting anemia. Artesunate appears to achieve rapid and complete resolution of acute Plasmodium ovale malarial attacks. Since artesunate eliminates both asexual forms and gametocytes, it also acts on transmission by limiting the duration of survival of asexual forms.

X-ray grating spectrometer for opacity measurements in the 50 eV to 250 eV spectral range at the LULI 2000 laser facility.

An x-ray grating spectrometer was built in order to measure opacities in the 50 eV to 250 eV spectral range with an average spectral resolution ∼ 50. It has been used at the LULI-2000 laser facility at École Polytechnique (France) to measure the Δn = 0, n = 3 transitions of several elements with neighboring atomic number: Cr, Fe, Ni, and Cu in the same experimental conditions. Hence a spectrometer with a wide spectral range is required. This spectrometer features one line of sight looking through a heated sample at backlighter emission. It is outfitted with one toroidal condensing mirror and several flat mirrors cutting off higher energy photons. The spectral dispersion is obtained with a flatfield grating. Detection consists of a streak camera sensitive to soft x-ray radiation. Some experimental results showing the performance of this spectrometer are presented.

Isotopic dependence of the nuclear caloric curve.

The A/Z dependence of projectile fragmentation at relativistic energies has been studied with the ALADIN forward spectrometer at SIS. A stable beam of (124)Sn and radioactive beams of (124)La and (107)Sn at 600 MeV per nucleon have been used in order to explore a wide range of isotopic compositions. Chemical freeze-out temperatures are found to be nearly invariant with respect to the A/Z of the produced spectator sources, consistent with predictions for expanded systems. Small Coulomb effects (DeltaT approximately 0.6 MeV) appear for residue production near the onset of multifragmentation.