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The electron-capture process was studied for Xe54+ colliding with H2 molecules at the internal gas target of the Experimental Storage Ring (ESR) at GSI, Darmstadt. Cross-section values for electron capture into excited projectile states were deduced from the observed emission cross section of Lyman radiation, being emitted by the hydrogenlike ions subsequent to the capture of a target electron. The ion beam energy range was varied between 5.5 and 30.9 MeV/u by applying the deceleration mode of the ESR. Thus, electron-capture data were recorded at the intermediate and, in particular, the low-collision-energy regime, well below the beam energy necessary to produce bare xenon ions. The obtained data are found to be in reasonable qualitative agreement with theoretical approaches, while a commonly applied empirical formula significantly overestimates the experimental findings.
NeuLAND (New Large-Area Neutron Detector) is the next-generation neutron detector for the R3B (Reactions with Relativistic Radioactive Beams) experiment at FAIR (Facility for Antiproton and Ion Research). NeuLAND detects neutrons with energies from 100 to 1000 MeV, featuring a high detection efficiency, a high spatial and time resolution, and a large multi-neutron reconstruction efficiency. This is achieved by a highly granular design of organic scintillators: 3000 individual submodules with a size of 5 × 5 × 250 cm3 are arranged in 30 double planes with 100 submodules each, providing an active area of 250 × 250 cm2 and a total depth of 3 m. The spatial resolution due to the granularity together with a time resolution of 150 ps ensures high-resolution capabilities. In conjunction with calorimetric properties, a multi-neutron reconstruction efficiency of 50% to 70% for four-neutron events will be achieved, depending on both the emission scenario and the boundary conditions allowed for the reconstruction method. We present in this paper the final design of the detector as well as results from test measurements and simulations on which this design is based.
We measured the Coulomb dissociation of 16O into 4He and 12C at the R3B setup in a first campaign within FAIR Phase 0 at GSI Helmholtzzentrum für Schwerionenforschung, Darmstadt. The goal was to improve the accuracy of the experimental data for the 12C(α,γ)16O fusion reaction and to reach lower center-ofmass energies than measured so far.
The experiment required beam intensities of 109 16O ions per second at an energy of 500 MeV/nucleon. The rare case of Coulomb breakup into 12C and 4He posed another challenge: The magnetic rigidities of the particles are so close because of the same mass-to-charge-number ratio A/Z = 2 for 16O, 12C and 4He. Hence, radical changes of the R3B setup were necessary. All detectors had slits to allow the passage of the unreacted 16O ions, while 4He and 12C would hit the detectors' active areas depending on the scattering angle and their relative energies. We developed and built detectors based on organic scintillators to track and identify the reaction products with sufficient precision.
We present the first measurement of fluctuations from event to event in the production of strange particles in collisions of heavy nuclei. The ratio of charged kaons to charged pions is determined for individual central Pb+Pb collisions. After accounting for the fluctuations due to detector resolution and finite number statistics we derive an upper limit on genuine non-statistical fluctuations, perhaps related to a first or second order QCD phase transition. Such fluctuations are shown to be very small.
The large acceptance and high momentum resolution as well as the significant particle identification capabilities of the NA49 experiment at the CERN SPS allow for a broad study of fluctuations and correlations in hadronic interactions. In the first part recent results on event-by-event charge and p_t fluctuations are presented. Charge fluctuations in central Pb+Pb reactions are investigated at three different beam energies (40, 80, and 158 AGeV), while for the p_t fluctuations the focus is put on the system size dependence at 158 AGeV. In the second part recent results on Bose Einstein correlations of h-h- pairs in minimum bias Pb+Pb reactions at 40 and 158 AGeV, as well as of K+K+ and K-K- pairs in central Pb+Pb collisions at 158 AGeV are shown. Additionally, other types of two particle correlations, namely pi p, Lambda p, and Lambda Lambda correlations, have been measured by the NA49 experiment. Finally, results on the energy and system size dependence of deuteron coalescence are discussed.
The COVID-19 pandemic is affecting countries across the globe. Only a globally coordinated response, however, will enable the containment of the virus. Responding to a request from policy makers for ethics input for a global resource pledging event as a starting point, this paper outlines normative and procedural principles to inform a coordinated global coronavirus response. Highlighting global connections and specific vulnerabilities from the pandemic, and proposing standards for reasonable and accountable decision-making, the ambition of the paper is two-fold: to raise awareness for the justice dimensions in the global response, and to argue for moving health from the periphery to the centre of philosophical debates about social and global justice.
Background: 15-20% of all patients initially diagnosed with colorectal cancer develop metastatic disease and surgical resection remains the only potentially curative treatment available. Current 5-year survival following R0-resection of liver metastases is 28-39%, but recurrence eventually occurs in up to 70%. To date, adjuvant chemotherapy has not improved clinical outcomes significantly. The primary objective of the ongoing LICC trial (L-BLP25 In Colorectal Cancer) is to determine whether L-BLP25, an active cancer immunotherapy, extends recurrence-free survival (RFS) time over placebo in colorectal cancer patients following R0/R1 resection of hepatic metastases. L-BLP25 targets MUC1 glycoprotein, which is highly expressed in hepatic metastases from colorectal cancer. In a phase IIB trial, L-BLP25 has shown acceptable tolerability and a trend towards longer survival in patients with stage IIIB locoregional NSCLC.
Methods: This is a multinational, phase II, multicenter, randomized, double-blind, placebo-controlled trial with a sample size of 159 patients from 20 centers in 3 countries. Patients with stage IV colorectal adenocarcinoma limited to liver metastases are included. Following curative-intent complete resection of the primary tumor and of all synchronous/metachronous metastases, eligible patients are randomized 2:1 to receive either L-BLP25 or placebo. Those allocated to L-BLP25 receive a single dose of 300 mg/m2 cyclophosphamide (CP) 3 days before first L-BLP25 dose, then primary treatment with s.c. L-BLP25 930 mug once weekly for 8 weeks, followed by s.c. L-BLP25 930 mug maintenance doses at 6-week (years 1&2) and 12-week (year 3) intervals unless recurrence occurs. In the control arm, CP is replaced by saline solution and L-BLP25 by placebo. Primary endpoint is the comparison of recurrence-free survival (RFS) time between groups. Secondary endpoints are overall survival (OS) time, safety, tolerability, RFS/OS in MUC-1 positive cancers. Exploratory immune response analyses are planned. The primary endpoint will be assessed in Q3 2016. Follow-up will end Q3 2017. Interim analyses are not planned.
Discussion: The design and implementation of such a vaccination study in colorectal cancer is feasible. The study will provide recurrence-free and overall survival rates of groups in an unbiased fashion. Trial Registration EudraCT Number 2011-000218-20
Hypersecretion and chronic phlegm are major symptoms of chronic obstructive pulmonary disease (COPD) but animal models of COPD with a defined functional hypersecretion have not been established so far. To identify an animal model of combined morphological signs of airway inflammation and functional hypersecretion, rats were continuously exposed to different levels of sulfur dioxide (SO2, 5 ppm, 10 ppm, 20 ppm, 40 ppm, 80 ppm) for 3 (short-term) or 20–25 (long-term) days. Histology revealed a dose-dependent increase in edema formation and inflammatory cell infiltration in short-term-exposed animals. The submucosal edema was replaced by fibrosis after long-term-exposure. The basal secretory activity was only significantly increased in the 20 ppm group. Also, stimulated secretion was significantly increased only after exposure to 20 ppm. BrdU-assays and AgNOR-analysis demonstrated cellular metaplasia and glandular hypertrophy rather than hyperplasia as the underlying morphological correlate of the hypersecretion.
In summary, SO2-exposure can lead to characteristic airway remodeling and changes in mucus secretion in rats. As only long-term exposure to 20 ppm leads to a combination of hypersecretion and airway inflammation, only this mode of exposure should be used to mimic human COPD. Concentrations less or higher than 20 ppm or short term exposure do not induce the respiratory symptom of hypersecretion. The present model may be used to characterize the effects of new compounds on mucus secretion in the background of experimental COPD.
Background: There is no international consensus up to which age women with a diagnosis of triple-negative breast cancer (TNBC) and no family history of breast or ovarian cancer should be offered genetic testing for germline BRCA1 and BRCA2 (gBRCA) mutations. Here, we explored the association of age at TNBC diagnosis with the prevalence of pathogenic gBRCA mutations in this patient group.
Methods: The study comprised 802 women (median age 40 years, range 19–76) with oestrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 negative breast cancers, who had no relatives with breast or ovarian cancer. All women were tested for pathogenic gBRCA mutations. Logistic regression analysis was used to explore the association between age at TNBC diagnosis and the presence of a pathogenic gBRCA mutation.
Results: A total of 127 women with TNBC (15.8%) were gBRCA mutation carriers (BRCA1: n = 118, 14.7%; BRCA2: n = 9, 1.1%). The mutation prevalence was 32.9% in the age group 20–29 years compared to 6.9% in the age group 60–69 years. Logistic regression analysis revealed a significant increase of mutation frequency with decreasing age at diagnosis (odds ratio 1.87 per 10 year decrease, 95%CI 1.50–2.32, p < 0.001). gBRCA mutation risk was predicted to be > 10% for women diagnosed below approximately 50 years.
Conclusions: Based on the general understanding that a heterozygous mutation probability of 10% or greater justifies gBRCA mutation screening, women with TNBC diagnosed before the age of 50 years and no familial history of breast and ovarian cancer should be tested for gBRCA mutations. In Germany, this would concern approximately 880 women with newly diagnosed TNBC per year, of whom approximately 150 are expected to be identified as carriers of a pathogenic gBRCA mutation.
Regeneration of large bone defects is a major objective in trauma surgery. Bone marrow mononuclear cell (BMC)-supported bone healing was shown to be efficient after immobilization on a scaffold. We hypothesized that fibrous demineralized bone matrix (DBM) in various forms with BMCs is superior to granular DBM. A total of 65 male SD rats were assigned to five treatment groups: syngenic cancellous bone (SCB), fibrous demineralized bone matrix (f-DBM), fibrous demineralized bone matrix densely packed (f-DBM 120%), DBM granules (GDBM) and DBM granules 5% calcium phosphate (GDBM5%Ca2+). BMCs from donor rats were combined with different scaffolds and placed into 5 mm femoral bone defects. After 8 weeks, bone mineral density (BMD), biomechanical stability and histology were assessed. Similar biomechanical properties of f-DBM and SCB defects were observed. Similar bone and cartilage formation was found in all groups, but a significantly bigger residual defect size was found in GDBM. High bone healing scores were found in f-DBM (25) and SCB (25). The application of DBM in fiber form combined with the application of BMCs shows promising results comparable to the gold standard, syngenic cancellous bone. Denser packing of fibers or higher amount of calcium phosphate has no positive effect.
Bone marrow mononuclear cells (BMCs) are suitable for bone tissue engineering. Comparative data regarding the needs of BMC for the adhesion on biomaterials and biocompatibility to various biomaterials are lacking to a large extent. Therefore, we evaluated whether a surface coating would enhance BMC adhesion and analyze the biocompatibility of three different kinds of biomaterials. BMCs were purified from human bone marrow aspirate samples. Beta tricalcium phosphate (β-TCP, without coating or coated with fibronectin or human plasma), demineralized bone matrix (DBM), and bovine cancellous bone (BS) were assessed. Seeding efficacy on β-TCP was 95% regardless of the surface coating. BMC demonstrated a significantly increased initial adhesion on DBM and β-TCP compared to BS. On day 14, metabolic activity was significantly increased in BMC seeded on DBM in comparison to BMC seeded on BS. Likewise increased VEGF-synthesis was observed on day 2 in BMC seeded on DBM when compared to BMC seeded on BS. The seeding efficacy of BMC on uncoated biomaterials is generally high although there are differences between these biomaterials. Beta-TCP and DBM were similar and both superior to BS, suggesting either as suitable materials for spatial restriction of BMC used for regenerative medicine purposes in vivo.
Dieser Entwurf eines Verhaltenskodex richtet sich an Hochschulen, die mittels Learning Analytics die Qualität des Lernens und Lehrens verbessern wollen. Der Kodex kann als Vorlage zur Erstellung von organisationsspezifischen Verhaltenskodizes dienen. Er sollte an Hochschulen, die Learning Analytics einführen wollen, durch Konsultationen mit allen Interessengruppen überprüft und an die Ziele sowie die bestehende Praxis innerhalb der jeweiligen Hochschulen angepasst werden. Der Kodex wurde auf Grundlage einer Analyse bestehender europäischer Kodizes (Engelfriet, Manderveld & Jeunink, 2017; Westerlaken, Manderveld & Jorna, 2019; Sclater & Bailey, 2015; Open University UK, 2014; University of Edinburgh, 2018) und der in Deutschland geltenden Rechtsgrundlage vom Innovationsforum Trusted Learning Analytics des hessenweiten Projektes „Digital gestütztes Lehren und Lernen in Hessen“ entwickelt.
Suitable and reproducible experimental models of translational research in reconstructive surgery that allow in-vivo investigation of diverse molecular and cellular mechanisms are still limited. To this end we created a novel murine model of acute hindlimb ischemia-reperfusion to mimic a microsurgical free flap procedure. Thirty-six C57BL6 mice (n = 6/group) were assigned to one control and five experimental groups (subject to 6, 12, 96, 120 hours and 14 days of reperfusion, respectively) following 4 hours of complete hindlimb ischemia. Ischemia and reperfusion were monitored using Laser-Doppler Flowmetry. Hindlimb tissue components (skin and muscle) were investigated using histopathology, quantitative immunohistochemistry and immunofluorescence. Despite massive initial tissue damage induced by ischemia-reperfusion injury, the structure of the skin component was restored after 96 hours. During the same time, muscle cells were replaced by young myotubes. In addition, initial neuromuscular dysfunction, edema and swelling resolved by day 4. After two weeks, no functional or neuromuscular deficits were detectable. Furthermore, upregulation of VEGF and tissue infiltration with CD34-positive stem cells led to new capillary formation, which peaked with significantly higher values after two weeks. These data indicate that our model is suitable to investigate cellular and molecular tissue alterations from ischemia-reperfusion such as occur during free flap procedures.
Für die Pflanzenarten der Anhänge II und IV der FFH-Richtlinie wurde im Rahmen der FFH-Berichtspflicht Deutschlands an die EU-Kommission ein Monitoringsystem eingerichtet. Hierfür sind die Bundesländer verantwortlich. In Sachsen-Anhalt gibt es aktuell drei Vorkommen von Angelica palustris, eines von Apium repens, 107 von Cypripedium calceolus, 20 von Jurinea cyanoides, fünf von Liparis loeselii und fünf von Orthotrichum rogeri. Für alle Vorkommen dieser Arten wurden in den Jahren 2011/2012 Monitoringflächen eingerichtet (für Cypripedium calceolus nur an 10 Vorkommen, für Jurinea cyanoides an 18 Vorkommen). Diese Vorkommen wurden erfasst und bewertet. Für Coleanthus subtilis, Lindernia procumbens und Luronium natans konnten die in den zurückliegenden Jahren letztmalig bestätigten Vorkommen aktuell (2011/2012) nicht nachgewiesen werden. Aufgrund des natürlicherweise unsteten Auftretens dieser Arten wurden an den letzten bekannten Fundorten Monitoringflächen eingerichtet. Die drei Hauptkriterien des Monitorings: Zustand der Population, Habitatstruktur und Beeinträchtigungen sowie artspezifische Unterkriterien sind durch bundeseinheitliche Vorgaben festgelegt, ebenso die Häufigkeit der Erfassung dieser Kriterien während der jeweils sechsjährigen Berichtsperiode. Darüber hinaus sieht das Landesmonitoring teilweise eine detailliertere Untersuchungstiefe und -frequenz vor.
Partial cross sections of the 89Y(p, γ )90Zr reaction have been measured to investigate the γ-ray strength function in the neutron–magic nucleus 90Zr. For five proton energies between E p = 3.65 MeV and E p = 4.70 MeV partial cross sections for the population of seven discrete states in 90Zr have been determined by means of in-beam γ-ray spectroscopy. Since these γ-ray transitions are dominantly of E1 character, the present measurement allows an access to the low-lying dipole strength in 90Zr. A γ-ray strength function based on the experimental data could be extracted, which is used to describe the total and partial cross sections of this reaction by Hauser–Feshbach calculations successfully. Significant differences with respect to previously measured strength functions from photoabsorption data point towards deviations from the Brink–Axel hypothesis relating the photo-excitation and de-excitation strength functions.
Background: Tuberous sclerosis complex (TSC), a multisystem genetic disorder, affects many organs and systems, characterized by benign growths. This German multicenter study estimated the disease-specific costs and cost-driving factors associated with various organ manifestations in TSC patients. Methods: A validated, three-month, retrospective questionnaire was administered to assess the sociodemographic and clinical characteristics, organ manifestations, direct, indirect, out-of-pocket, and nursing care-level costs, completed by caregivers of patients with TSC throughout Germany. Results: The caregivers of 184 patients (mean age 9.8 ± 5.3 years, range 0.7–21.8 years) submitted questionnaires. The reported TSC disease manifestations included epilepsy (92%), skin disorders (86%), structural brain disorders (83%), heart and circulatory system disorders (67%), kidney and urinary tract disorders (53%), and psychiatric disorders (51%). Genetic variations in TSC2 were reported in 46% of patients, whereas 14% were reported in TSC1. Mean total direct health care costs were EUR 4949 [95% confidence interval (95% CI) EUR 4088–5863, median EUR 2062] per patient over three months. Medication costs represented the largest direct cost category (54% of total direct costs, mean EUR 2658), with mechanistic target of rapamycin (mTOR) inhibitors representing the largest share (47%, EUR 2309). The cost of anti-seizure drugs (ASDs) accounted for a mean of only EUR 260 (5%). Inpatient costs (21%, EUR 1027) and ancillary therapy costs (8%, EUR 407) were also important direct cost components. The mean nursing care-level costs were EUR 1163 (95% CI EUR 1027–1314, median EUR 1635) over three months. Total indirect costs totaled a mean of EUR 2813 (95% CI EUR 2221–3394, median EUR 215) for mothers and EUR 372 (95% CI EUR 193–586, median EUR 0) for fathers. Multiple regression analyses revealed polytherapy with two or more ASDs and the use of mTOR inhibitors as independent cost-driving factors of total direct costs. Disability and psychiatric disease were independent cost-driving factors for total indirect costs as well as for nursing care-level costs. Conclusions: This study revealed substantial direct (including medication), nursing care-level, and indirect costs associated with TSC over three months, highlighting the spectrum of organ manifestations and their treatment needs in the German healthcare setting.
The huge neutron fluxes offer the possibility to use research reactors to produce isotopes of interest, which can be investigated afterwards. An example is the half-lives of long-lived isotopes like 129I. A direct usage of reactor neutrons in the astrophysical energy regime is only possible, if the corresponding ions are not at rest in the laboratory frame. The combination of an ion storage ring with a reactor and a neutron guide could open the path to direct measurements of neutron-induced cross sections on short-lived radioactive isotopes in the astrophysically interesting energy regime.
Cross sections for neutron-induced reactions of short-lived nuclei are essential for nuclear astrophysics since these reactions in the stars are responsible for the production of most heavy elements in the universe. These reactions are also key in applied domains like energy production and medicine. Nevertheless, neutron-induced cross-section measurements can be extremely challenging or even impossible to perform due to the radioactivity of the targets involved. Indirect measurements through the surrogate-reaction method can help to overcome these difficulties.
The surrogate-reaction method relies on the use of an alternative reaction that will lead to the formation of the same excited nucleus as in the neutron-induced reaction of interest. The decay probabilities (for fission, neutron and gamma-ray emission) of the nucleus produced via the surrogate reaction allow one to constrain models and the prediction of the desired neutron cross sections.
We propose to perform surrogate reaction measurements in inverse kinematics at heavy-ion storage rings, in particular at the CRYRING@ESR of the GSI/FAIR facility. We present the conceptual idea of the most promising setup to measure for the first time simultaneously the fission, neutron and gamma-ray emission probabilities. The results of the first simulations considering the 238U(d,d') reaction are shown, as well as new technical developments that are being carried out towards this set-up.
Neutron-induced cross sections of short-lived nuclei are highly relevant in many domains such as fundamental nuclear physics, astrophysics and applications in nuclear technology. In particular, these cross sections are essential for understanding the synthesis of elements via the s- and r stellar processes. However, the measurement of such cross sections with current techniques is very difficult or even impossible, because of the difficulties to produce and handle the necessary amounts of radioactive nuclei. Reaching the nuclei of interest is only possible by inverting the reaction kinematics with radioactive beams.
In this contribution we present a project for indirectly determining neutron cross sections via the surrogate-reaction method. This project is based on the measurement of transfer- or inelastic-scattering-induced decay probabilities in inverse kinematics at storage rings. The measured probabilities are then used to tune nuclear-reaction models that will provide much more accurate predictions of the desired neutron cross sections. We also discuss a very ambitious, long-term project to directly measure neutron cross sections in inverse kinematics. It consists in the combination of a radioactive beam facility, an ion storage ring and a spallation neutron source.