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The neutron sensitivity of the C6D6 detector setup used at n_TOF facility for capture measurements has been studied by means of detailed GEANT4 simulations. A realistic software replica of the entire n_TOF experimental hall, including the neutron beam line, sample, detector supports and the walls of the experimental area has been implemented in the simulations. The simulations have been analyzed in the same manner as experimental data, in particular by applying the Pulse Height Weighting Technique. The simulations have been validated against a measurement of the neutron background performed with a natC sample, showing an excellent agreement above 1 keV. At lower energies, an additional component in the measured natC yield has been discovered, which prevents the use of natC data for neutron background estimates at neutron energies below a few hundred eV. The origin and time structure of the neutron background have been derived from the simulations. Examples of the neutron background for two different samples are demonstrating the important role of accurate simulations of the neutron background in capture cross-section measurements.
The neutron capture cross section of 58Ni was measured at the neutron time of flight facility n_TOF at CERN, from 27 meV to 400 keV neutron energy. Special care has been taken to identify all the possible sources of background, with the so-called neutron background obtained for the first time using high-precision GEANT4 simulations. The energy range up to 122 keV was treated as the resolved resonance region, where 51 resonances were identified and analyzed by a multilevel R-matrix code SAMMY. Above 122 keV the code SESH was used in analyzing the unresolved resonance region of the capture yield. Maxwellian averaged cross sections were calculated in the temperature range of kT = 5 – 100 keV, and their astrophysical implications were investigated.
Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting.
Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators.
Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm).
Conclusions: Data from this registry indicate that rituximab is a commonly employed, well-tolerated therapy with potential beneficial effects in standard of care-refractory autoimmune diseases, and support the results from other open-label, uncontrolled studies.
The accurate knowledge of the neutron-induced fission cross-sections of actinides and other isotopes involved in the nuclear fuel cycle is essential for the design of advanced nuclear systems, such as Generation-IV nuclear reactors. Such experimental data can also provide the necessary feedback for the adjustment of nuclear model parameters used in the evaluation process, resulting in the further development of nuclear fission models. In the present work, the 240Pu(n,f) cross-section was measured at CERN's n_TOF facility relative to the well-known 235U(n,f) cross section, over a wide range of neutron energies, from meV to almost MeV, using the time-of-flight technique and a set-up based on Micromegas detectors. This measurement was the first experiment to be performed at n_TOF's new experimental area (EAR-2), which offers a significantly higher neutron flux compared to the already existing experimental area (EAR-1). Preliminary results as well as the experimental procedure, including a description of the facility and the data handling and analysis, are presented.
Dihydrocodein wird im wesentlichen zu Dihydrocodein-6-O-43-ß-glucuronid (DHC6G), Dihydromorphin (DHM), Dihydromorpbin-3-O-ß-D-glucuronid (DHM3G), Dihydromorphin-6-O-ß-D-glucuronid (DHM6G) und Nordihydrocodein (NDHC) biotransformiert. In Analogie zu Codein wird vermutet, dass die Metaboliten DHM und DHM6G pharmkologisch deutlich aktiver als die Muttersubstanz sind und somit zur Wirkung von DHC wesentlich beitragen können, auch wenn sie nur in geringen Mengen gebildet werden. Da die O-Demethylierung von Dihydrocodein zu Dihydromorphin durch das polymorphe Cytochrom P450-Enzym CYP2D6 katalysiert wird, sind in EM (schnelle Metabolisierer) und PM (langsame Metabolisierer, weisen kein funktionelles CYP2D6-Enzym auf) unterschiedliche Metabolitenprofile zu beobachten. In etwa 5-10% der Kaukasier, die PM für CYP2D6 sind, könnte sich somit ein Therapiemisserfolg nach Gabe von therapeutisch empfohlenen Standarddosen an DHC einstellen. Es war daher Ziel der vorliegenden Arbeit, die Bedeutung der Biotransformation für die Wirkung von Dihydrocodein beim Menschen zu untersuchen. Im Rahmen dieser Untersuchung wurden Affinitätsprofile an Hirnmembranpräparationen und Affinitäts- und Aktivitätsprofile an humanen Neuroblastomzellen für DHC und seine Metaboliten erstellt. Des weiteren wurden pharmakokinetische und pharmakodynamische Parameter (und deren Zusammenhang) von Dihydrocodein und seinen Metaboliten beim gesunden Menschen unter Berücksichtigung des CYP2D6-Phänotyps mit Hilfe einer Pilot-Probandenstudie bestimmt. Zuletzt wurden die Ergebnisse der Affinitäts- und Aktivitätsversuche mit den Ergebnissen der Probandenstudie unter Berücksichtigung der verfügbaren Literaturdaten in Zusammenhang gebracht. Di in vitro-Untersuchungen zeigten, dass alls Prüfsubstanzen mit Ausnahme des unwirksamen DHM3G vorwiegend u-selektive Agonisten waren und dass das prinzipielle Verhältnis der Affinitäten bzw. Aktivitäten der einzelnen aktiven Prüfsubstanzen zueinander in allen Untersuchungen annähernd gleich war. Auf Grundlage dieser Daten konnte folgender Grundsatz formuliert werden; Die Affinitäten/Aktivitäten von DHM und DHM6G waren etwa um den Faktor 100 größer als die von DHC, während die anderen Metaboliten (mit Ausnahme des unwirksamen DHM3G) vergleichbare Affinitäten/Aktivitäten besaßen. Die im Rahmen der Probandenstudie ermittelten pharmakokinetischen Werte bestätigten verfügbare Literaturdaten, insbesondere dass CYP2D6 wesentlich für die Bildung von DHM war. So konnten weder DHM, DHM3G noch DHM6G in Plasma und Urin von PM detektiert werden. Die pharmakodynamischep Untersuchungen mittels Pupillometrie zeigten einen signifikanten Unterschied im ursprünglichen Pupillendurchmesser an den Zeitpunkten 1 bis 6 Stunden zwischen Placebo einerseits und EM bzw. PM andererseits. Damit konnte zunächst eine eigene in vivo-Wirkung von DHC beim Menschen nachgewiesen werden. Jedoch ergab sich kein signifikanter Unterschied zwischen EM und PM. Im zweiten pharmakodynamischen Modell (Schmerzmodell) konnten bezüglich der Parameter R-III-Reflexschwelle und VAS-EC30 keine Unterschiede sowohl zwischen EM und PM als auch zwischen Placebo und EM bzw. PM festgestellt werden, so dass 60 mg DHC keine analgetische Wirkung hatte oder das Modell für die Ermittlung der analgetischen Potenz von 60 mg DHC ungeeignet war. Einschränkend muss jedoch hier erwähnt werden, dass die Studie aufgrund der kleinen Fallzahl nur Pilotcharakter aufwies. Die Ergebnisse der vorliegenden Arbeit in Zusammenhang mit den verfügbaren Literaturdaten lassen die Schlussfolgerung zu, dass die pharmakologisch wesentlich aktiveren Metaboliten DHM und DHM6G nicht oder nur geringfügig zur Wirkung von DHC nach oraler Einzelgabe von 60 mg DHC beitragen. Gründe hierfür könnten die geringe Bildung von DHM und seinen Metaboliten (ca. 9%) und/oder durch Verteilung und Ausscheidung bedingte niedrige Konzentrationen am Rezeptor in vivo sein. Somit scheint die Biotransformation keine Bedeutung für die Wirkung von DHC zu haben. Entsprechend sind keine Unterschiede in der Therapie von EM und PM mit niedrigen therapierelevanten DHC-Dosen zu erwarten.
The 33S(n,α)30Si cross section measurement, using 10B(n,α) as reference, at the n_TOF Experimental Area 2 (EAR2) facility at CERN is presented. Data from 0.01 eV to 100 keV are provided and, for the first time, the cross section is measured in the range from 0.01 eV to 10 keV. These data may be used for a future evaluation of the cross section because present evaluations exhibit large discrepancies. The 33S(n,α)30Si reaction is of interest in medical physics because of its possible use as a cooperative target to boron in Neutron Capture Therapy (NCT).
Background: Although childhood sexual and/or physical abuse (CSA/CPA) is known to have severe psychopathological consequences, there is little evidence on psychotherapeutic interventions for adolescents and young adults suffering from post-traumatic stress disorder (PTSD). Equally sparse are data on moderators of treatment response on PTSD-related epigenetic changes, health care costs and loss of productivity, alterations in cognitive processing, and on how successful interventions affect all of these factors. Early treatment may prevent later (co)morbidity. In this paper, we present a study protocol for the evaluation of a newly developed psychotherapeutic manual for PTSD after CSA/CPA in adolescents and young adults – the Developmentally Adapted Cognitive Processing Therapy (D-CPT).
Methods/design: In a multicenter randomized controlled trial (RCT) D-CPT is compared to treatment as usual (TAU). A sample of 90 adolescent outpatients aged 14 to 21 years will be randomized to one of these conditions. Four assessments will be carried out at baseline, at end of treatment, and 3 and 6 months after end of therapy. Each time, patients will be assessed via clinical interviews and a wide range of questionnaires. In addition to PTSD symptoms and comorbidities, we will evaluate moderators of treatment response, epigenetic profiles, direct and indirect costs of this disorder, and neurophysiological processing of threat cues in PTSD and their respective changes in the course of these two treatments (D-CPT and TAU).
Discussion: The study will provide new insights in the understudied field of PTSD in adolescents and young adults. A newly developed intervention will be evaluated in this therapeutically underserved population. Results will provide data on treatment efficacy, direct and indirect treatment costs, as well as on associations of treatment outcome and PTSD intensity both to epigenetic profiles and to the neurobiological processing of threat cues. Besides, they will help to learn more about the psychopathology and possible new objective correlates of PTSD.
Trial registration: Germanctr.de identifier: DRKS00004787.
The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process β-decay chains. These nuclei are attributed to the p and rp process.
For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections.
The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
n this paper we report on the investigation of baryonic resonance production in proton-proton collisions at the kinetic energies of 1.25 GeV and 3.5 GeV, based on data measured with HADES. Exclusive channels npπ+ and ppπ0 as well as ppe+e− were studied simultaneously in the framework of a one-boson exchange model. The resonance cross sections were determined from the one-pion channels for Δ(1232) and N(1440) (1.25 GeV) as well as further Δ and N* resonances up to 2 GeV/c2 for the 3.5 GeV data. The data at 1.25 GeV energy were also analysed within the framework of the partial wave analysis together with the set of several other measurements at lower energies. The obtained solutions provided the evolution of resonance production with the beam energy, showing a sizeable non-resonant contribution but with still dominating contribution of Δ(1232)P33. In the case of 3.5 GeV data, the study of the ppe+e− channel gave the insight on the Dalitz decays of the baryon resonances and, in particular, on the electromagnetic transition form-factors in the time-like region. We show that the assumption of a constant electromagnetic transition form-factors leads to underestimation of the yield in the dielectron invariant mass spectrum below the vector mesons pole. On the other hand, a comparison with various transport models shows the important role of intermediate ρ production, though with a large model dependency. The exclusive channels analysis done by the HADES collaboration provides new stringent restrictions on the parameterizations used in the models.
The Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO) here presents its updated recommendations for the treatment of documented fungal infections. Invasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. In recent years, new antifungal agents have been licensed, and agents already approved have been studied in new indications. The choice of the most appropriate antifungal treatment depends on the fungal species suspected or identified, the patient’s risk factors (e.g., length and depth of neutropenia), and the expected side effects. This guideline reviews the clinical studies that served as a basis for the following recommendations. All recommendations including the levels of evidence are summarized in tables to give the reader rapid access to the information.
The aim of this work is to provide a precise and accurate measurement of the 238U(n,γ) reaction cross section in the energy region from 1 eV to 700 keV. This reaction is of fundamental importance for the design calculations of nuclear reactors, governing the behavior of the reactor core. In particular, fast reactors, which are experiencing a growing interest for their ability to burn radioactive waste, operate in the high energy region of the neutron spectrum. In this energy region most recent evaluations disagree due to inconsistencies in the existing measurements of up to 15%. In addition, the assessment of nuclear data uncertainty performed for innovative reactor systems shows that the uncertainty in the radiative capture cross section of 238U should be further reduced to 1–3% in the energy region from 20 eV to 25 keV. To this purpose, addressed by the Nuclear Energy Agency as a priority nuclear data need, complementary experiments, one at the GELINA and two at the n_TOF facility, were proposed and carried out within the 7th Framework Project ANDES of the European Commission. The results of one of these 238U(n,γ) measurements performed at the n_TOF CERN facility are presented in this work. The γ-ray cascade following the radiative neutron capture has been detected exploiting a setup of two C6D6 liquid scintillators. Resonance parameters obtained from this work are on average in excellent agreement with the ones reported in evaluated libraries. In the unresolved resonance region, this work yields a cross section in agreement with evaluated libraries up to 80 keV, while for higher energies our results are significantly higher.
The radiative capture cross section of 238U is very important for the developing of new reactor technologies and the safety of existing ones. Here the preliminary results of the 238U(n,γ) cross section measurement performed at n_TOF with C6D6 scintillation detectors are presented, paying particular attention to data reduction and background subtraction.
High precision measurement of the radiative capture cross section of 238U at the n_TOF CERN facility
(2017)
The importance of improving the accuracy on the capture cross-section of 238U has been addressed by the Nuclear Energy Agency, since its uncertainty significantly affects the uncertainties of key design parameters for both fast and thermal nuclear reactors. Within the 7th framework programme ANDES of the European Commission three different measurements have been carried out with the aim of providing the 238U(n,γ) cross-section with an accuracy which varies from 1 to 5%, depending on the energy range. Hereby the final results of the measurement performed at the n_TOF CERN facility in a wide energy range from 1 eV to 700 keV will be presented.
he study of the resonant structures in neutron-nucleus cross-sections, and therefore of the compound-nucleus reaction mechanism, requires spectroscopic measurements to determine with high accuracy the energy of the neutron interacting with the material under study.
To this purpose, the neutron time-of-flight facility n_TOF has been operating since 2001 at CERN. Its characteristics, such as the high intensity instantaneous neutron flux, the wide energy range from thermal to few GeV, and the very good energy resolution, are perfectly suited to perform high-quality measurements of neutron-induced reaction cross sections. The precise and accurate knowledge of these cross sections plays a fundamental role in nuclear technologies, nuclear astrophysics and nuclear physics.
Two different measuring stations are available at the n_TOF facility, called EAR1 and EAR2, with different characteristics of intensity of the neutron flux and energy resolution. These experimental areas, combined with advanced detection systems lead to a great flexibility in performing challenging measurement of high precision and accuracy, and allow the investigation isotopes with very low cross sections, or available only in small quantities, or with very high specific activity.
The characteristics and performances of the two experimental areas of the n_TOF facility will be presented, together with the most important measurements performed to date and their physics case. In addition, the significant upcoming measurements will be introduced.
New neutron cross section measurements of minor actinides have been performed recently in order to reduce the uncertainties in the evaluated data, which is important for the design of advanced nuclear reactors and, in particular, for determining their performance in the transmutation of nuclear waste. We have measured the 241Am(n,γ) cross section at the n_TOF facility between 0.2 eV and 10 keV with a BaF2 Total Absorption Calorimeter, and the analysis of the measurement has been recently concluded. Our results are in reasonable agreement below 20 eV with the ones published by C. Lampoudis et al. in 2013, who reported a 22% larger capture cross section up to 110 eV compared to experimental and evaluated data published before. Our results also indicate that the 241Am(n,γ) cross section is underestimated in the present evaluated libraries between 20 eV and 2 keV by 25%, on average, and up to 35% for certain evaluations and energy ranges.
The 236U isotope plays an important role in nuclear systems, both for future and currently operating ones. The actual knowledge of the capture reaction of this isotope is satisfactory in the thermal region, but it is considered insufficient for Fast Reactor and ADS applications. For this reason the 236U(n, γ) reaction cross-section has been measured for the first time in the whole energy region from thermal energy up to 1 MeV at the n_TOF facility with two different detection systems: an array of C6D6 detectors, employing the total energy deposited method, and a FX1 total absorption calorimeter (TAC), made of 40 BaF2 crystals. The two n_TOF data sets agree with each other within the statistical uncertainty in the Resolved Resonance Region up to 800 eV, while sizable differences (up to ≃ 20%) are found relative to the current evaluated data libraries. Moreover two new resonances have been found in the n_TOF data. In the Unresolved Resonance Region up to 200 keV, the n_TOF results show a reasonable agreement with previous measurements and evaluated data.
We have measured the radiative neutron-capture cross section and the total neutron-induced cross section of one of the most important isotopes for the s process, the 25Mg. The measurements have been carried out at the neutron time-of-flight facilities n_TOF at CERN (Switzerland) and GELINA installed at the EC-JRC-IRMM (Belgium). The cross sections as a function of neutron energy have been measured up to approximately 300 keV, covering the energy region of interest to the s process. The data analysis is ongoing and preliminary results show the potential relevance for the s process.
The design and operation of innovative nuclear systems requires a better knowledge of the capture and fission cross sections of the Pu isotopes. For the case of capture on 242Pu, a reduction of the uncertainty in the fast region down to 8-12% is required. Moreover, aiming at improving the evaluation of the fast energy range in terms of average parameters, the OECD NEA High Priority Request List (HPRL) requests high-resolution capture measurements with improved accuracy below 2 keV. The current uncertainties also affect the thermal point, where previous experiments deviate from each other by 20%. A fruitful collaboration betwen JGU Mainz and HZ Dresden-Rossendorf within the EC CHANDA project resulted in a 242Pu sample consisting of a stack of seven fission-like targets making a total of 95(4) mg of 242Pu electrodeposited on thin (11.5 μm) aluminum backings. This contribution presents the results of a set of measurements of the 242Pu(n, γ) cross section from thermal to 500 keV combining different neutron beams and techniques. The thermal point was determined at the Budapest Research Reactor by means of Neutron Activation Analysis and Prompt Gamma Analysis, and the resolved (1 eV - 4 keV) and unresolved (1 - 500 keV) resonance regions were measured using a set of four Total Energy detectors at the CERN n_TOF-EAR1.
Above 1 MeV of incident neutron energy the fission fragment angular distribution (FFAD) has generally a strong anisotropic behavior due to the combination of the incident orbital momentum and the intrinsic spin of the fissioning nucleus. This effect has to be taken into account for the efficiency estimation of devices used for fission cross section measurements. In addition it bears information on the spin deposition mechanism and on the structure of transitional states. We designed and constructed a detection device, based on Parallel Plate Avalanche Counters (PPAC), for measuring the fission fragment angular distributions of several isotopes, in particular 232Th. The measurement has been performed at n_TOF at CERN taking advantage of the very broad energy spectrum of the neutron beam. Fission events were recognized by back to back detection in coincidence in two position-sensitive detectors surrounding the targets. The detection efficiency, depending mostly on the stopping of fission fragments in backings and electrodes, has been computed with a Geant4 simulation and validated by the comparison to the measured case of 235U below 3 keV where the emission is isotropic. In the case of 232Th, the result is in good agreement with previous data below 10 MeV, with a good reproduction of the structures associated to vibrational states and the opening of second chance fission. In the 14 MeV region our data are much more accurate than previous ones which are broadly scattered.