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Background: The photon strength functions (PSFs) and nuclear level density (NLD) are key ingredients for calculation of the photon interaction with nuclei, in particular the reaction cross sections. These cross sections are important especially in nuclear astrophysics and in the development of advanced nuclear technologies.
Purpose: The role of the scissors mode in the M1 PSF of (well-deformed) actinides was investigated by several experimental techniques. The analyses of different experiments result in significant differences, especially on the strength of the mode. The shape of the low-energy tail of the giant electric dipole resonance is uncertain as well. In particular, some works proposed a presence of the E1 pygmy resonance just above 7 MeV. Because of these inconsistencies additional information on PSFs in this region is of great interest.
Methods: The γ-ray spectra from neutron-capture reactions on the 234U, 236 U, and 238 U nuclei have been measured with the total absorption calorimeter of the n_TOF facility at CERN. The background-corrected sum-energy and multi-step-cascade spectra were extracted for several isolated s-wave resonances up to about 140 eV.
Results: The experimental spectra were compared to statistical model predictions coming from a large selection of models of photon strength functions and nuclear level density. No combination of PSF and NLD models from literature is able to globally describe our spectra. After extensive search we were able to find model combinations with modified generalized Lorentzian (MGLO) E1 PSF, which match the experimental spectra as well as the total radiative widths.
Conclusions: The constant temperature energy dependence is favored for a NLD. The tail of giant electric dipole resonance is well described by the MGLO model of the E1 PSF with no hint of pygmy resonance. The M1 PSF must contain a very strong, relatively wide, and likely double-resonance scissors mode. The mode is responsible for about a half of the total radiative width of neutron resonances and significantly affects the radiative cross section.
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.
The neutron capture cross section of 154Gd was measured from 1 eV to 300 keV in the experimental area located 185 m from the CERN n_TOF neutron spallation source, using a metallic sample of gadolinium, enriched to 67% in 154Gd. The capture measurement, performed with four C6D6 scintillation detectors, has been complemented by a transmission measurement performed at the GELINA time-of-flight facility (JRC-Geel), thus minimising the uncertainty related to sample composition. An accurate Maxwellian averaged capture cross section (MACS) was deduced over the temperature range of interest for s process nucleosynthesis modelling. We report a value of 880(50) mb for the MACS at kT = 30 keV, significantly lower compared to values available in literature. The new adopted 154Gd(n,γ) cross section reduces the discrepancy between observed and calculated solar s-only isotopic abundances predicted by s-process nucleosynthesis models.
Objectives: The SAVI-TF (Symetis ACURATE neo Valve Implantation Using Transfemoral Access) registry was initiated to study the ACURATE neo transcatheter heart valve in a large patient population treated under real-world conditions.
Background: The self-expanding, supra-annular ACURATE neo prosthesis is a transcatheter heart valve that gained the Conformité Européene mark in 2014, but only limited clinical data are available so far.
Methods: This prospective, multicenter registry enrolled 1,000 patients at 25 European centers who were followed for 1 year post-procedure.
Results: Mean patient age was 81.1 ± 5.2 years; mean logistic European System for Cardiac Operative Risk Evaluation I score, European System for Cardiac Operative Risk Evaluation II score, and Society of Thoracic Surgeons score were 18.1 ± 12.5%, 6.6 ± 7.5%, and 6.0 ± 5.6%, respectively. At 1 year, 8.0% (95% confidence interval [CI]: 6.3% to 9.7%) of patients had died, 2.3% (95% CI: 1.3% to 3.2%) had disabling strokes, and 9.9% (95% CI: 8.1% to 11.8%) had permanent pacemaker implantations. Through 1 year, 5 reinterventions (0.5%; 95% CI: 0.1% to 1.0%) were performed: 3 valve-in-valve and 2 surgical aortic valve replacements. Mean effective orifice area was 1.84 ± 0.43 cm2, mean gradient was 7.3 ± 3.7 mm Hg, and greater than mild paravalvular leakage was observed in 3.6% of patients.
Conclusions: Transfemoral implantation of the ACURATE neo prosthesis resulted in favorable 1-year clinical and echocardiographic outcomes with very low mortality and new pacemaker rates.
Simple Summary: The introduction of BRAF/MEK-directed targeted therapy (TT) has significantly improved the management of patients with advanced BRAF-V600-mutant melanoma. Although resistance occurs, there is a subgroup of patients showing a complete response (CR) to TT and who maintain durable disease control. For these patients with durable CR, it is not clear whether it is safe to cease therapy. In this retrospective, multicenter study we have analyzed 37 patients who received TT and achieved a CR upon treatment. We identified 15 patients with a durable CR to TT. Overall, patients who discontinued TT (n = 26) were at higher risk of tumor progression compared to patients receiving ongoing TT. Sustained CR was however not restricted to patients with ongoing TT (n = 11) but was also found in patients who ceased TT (n = 4). Finally, our analysis indicated which patients with an initial CR might be most likely to maintain durable CR upon discontinuation of TT.
Abstract: The advent of BRAF/MEK inhibitors (BRAFi/MEKi) has significantly improved progression-free (PFS) and overall survival (OS) for patients with advanced BRAF-V600-mutant melanoma. Long-term survivors have been identified particularly among patients with a complete response (CR) to BRAF/MEK-directed targeted therapy (TT). However, it remains unclear which patients who achieved a CR maintain a durable response and whether treatment cessation might be a safe option in these patients. Therefore, this study investigated the impact of treatment cessation on the clinical course of patients with a CR upon BRAF/MEK-directed-TT. We retrospectively selected patients with BRAF-V600-mutant advanced non-resectable melanoma who had been treated with BRAFi ± MEKi therapy and achieved a CR upon treatment out of the multicentric skin cancer registry ADOReg. Data on baseline patient characteristics, duration of TT, treatment cessation, tumor progression (TP) and response to second-line treatments were collected and analyzed. Of 461 patients who received BRAF/MEK-directed TT 37 achieved a CR. TP after initial CR was observed in 22 patients (60%) mainly affecting patients who discontinued TT (n = 22/26), whereas all patients with ongoing TT (n = 11) maintained their CR. Accordingly, patients who discontinued TT had a higher risk of TP compared to patients with ongoing treatment (p < 0.001). However, our data also show that patients who received TT for more than 16 months and who discontinued TT for other reasons than TP or toxicity did not have a shorter PFS compared to patients with ongoing treatment. Response rates to second-line treatment being initiated in 21 patients, varied between 27% for immune-checkpoint inhibitors (ICI) and 60% for BRAFi/MEKi rechallenge. In summary, we identified a considerable number of patients who achieved a CR upon BRAF/MEK-directed TT in this contemporary real-world cohort of patients with BRAF-V600-mutant melanoma. Sustained PFS was not restricted to ongoing TT but was also found in patients who discontinued TT.
Einleitung:
Wahrscheinlich hat es seit den 1970er Jahren nicht mehr so viele kritische Initiativen von Geographiestudierenden an Hochschulen in deutschsprachigen Ländern gegeben wie heute. Ihre Aktivitäten reichen von Lesekreisen, Tutorien, Exkursionen, Film- und Vortragsreihen bis zu politischen Aktionen, wobei viele Initiativen über den Arbeitskreis (AK) Kritische Geographie vernetzt sind. Parallel zu dieser erfreulichen Beobachtung findet ein fundamentaler Umbau der Hochschule statt. Die zunehmende Ökonomisierung des Studiums durch den Bologna-Prozess birgt die Gefahr, Gesellschaftskritik auf dem Altar der Verwertbarkeit und der "Praxisrelevanz" zu opfern. Diese Entwicklungen geben Anlass, das Verhältnis zwischen der Arbeit kritischer Initiativen und den reformierten Universitäten kritisch zu hinterfragen und damit den Zusammenhang zwischen Bologna-Prozess, Neoliberalisierung und kritischer Wissenschaft für die geographische Hochschullehre aus einer studentischen Perspektive zu beleuchten, wird doch ein nicht unbedeutender Teil der kritischen Geographie von Studierenden getragen.
Im Folgenden werden wir kurz auf den Bologna-Prozess eingehen, anschließend die Fragestellung und das methodische Vorgehen erläutern, um darauf aufbauend die empirischen Ergebnisse vorzustellen und zu diskutieren.
Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de).
Purpose: Molecular diagnostics including next generation gene sequencing are increasingly used to determine options for individualized therapies in brain tumor patients. We aimed to evaluate the decision-making process of molecular targeted therapies and analyze data on tolerability as well as signals for efficacy.
Methods: Via retrospective analysis, we identified primary brain tumor patients who were treated off-label with a targeted therapy at the University Hospital Frankfurt, Goethe University. We analyzed which types of molecular alterations were utilized to guide molecular off-label therapies and the diagnostic procedures for their assessment during the period from 2008 to 2021. Data on tolerability and outcomes were collected.
Results: 413 off-label therapies were identified with an increasing annual number for the interval after 2016. 37 interventions (9%) were targeted therapies based on molecular markers. Glioma and meningioma were the most frequent entities treated with molecular matched targeted therapies. Rare entities comprised e.g. medulloblastoma and papillary craniopharyngeoma. Molecular targeted approaches included checkpoint inhibitors, inhibitors of mTOR, FGFR, ALK, MET, ROS1, PIK3CA, CDK4/6, BRAF/MEK and PARP. Responses in the first follow-up MRI were partial response (13.5%), stable disease (29.7%) and progressive disease (46.0%). There were no new safety signals. Adverse events with fatal outcome (CTCAE grade 5) were not observed. Only, two patients discontinued treatment due to side effects. Median progression-free and overall survival were 9.1/18 months in patients with at least stable disease, and 1.8/3.6 months in those with progressive disease at the first follow-up MRI.
Conclusion: A broad range of actionable alterations was targeted with available molecular therapeutics.
However, efficacy was largely observed in entities with paradigmatic oncogenic drivers, in particular with BRAF mutations. Further research on biomarker-informed molecular matched therapies is urgently necessary.
We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24% (95% CI: 20–27%) and a median OS of 3.3 months (95% CI: 2.8–3.6) in the historical cohort compared with a CR/CRh rate of 43% (95% CI: 36–50%) and a median OS of 6.1 months (95% CI: 4.2–7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95% CI: 1.67–4.31) and improved OS (HR=0.536, 95% CI: 0.394–0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.
Accurate neutron capture cross section data for minor actinides (MAs) are required to estimate the production and transmutation rates of MAs in light water reactors with a high burnup, critical fast reactors like Gen-IV systems and other innovative reactor systems such as accelerator driven systems (ADS). Capture reactions of 244Cm open the path for the formation of heavier Cm isotopes and of heavier elements such as Bk and Cf. In addition, 244Cm shares nearly 50% of the total actinide decay heat in irradiated reactor fuels with a high burnup, even after three years of cooling.
Experimental data for this isotope are very scarce due to the difficulties of providing isotopically enriched samples and because the high intrinsic activity of the samples requires the use of neutron facilities with high instantaneous flux. The only two previous experimental data sets for this neutron capture cross section have been obtained in 1969 using a nuclear explosion and, more recently, at J-PARC in 2010. The neutron capture cross sections have been measured at n_TOF with the same samples that the previous experiments in J-PARC. The samples were measured at n_TOF Experimental Area 2 (EAR-2) with three C6D6 detectors and also in Experimental Area 1 (EAR-1) with the Total Absorption Calorimeter (TAC). Preliminary results assessing the quality and limitations of these new experimental datasets are presented for the experiments in both areas. Preliminary yields of both measurements will be compared with evaluated libraries for the first time.