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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.
Understanding the nano-architecture of protein machines in diverse sub-cellular compartments remains a challenge despite rapid progress in super-resolution microscopy. While singlemolecule localization microscopy techniques allow the visualization and identification of cellular structures with near-molecular resolution, multiplex-labeling of tens of target proteins within the same sample has not yet been achieved routinely. However, single sample multiplexing is essential to detect patterns that threaten to get lost in multi-sample averaging. Here, we report maS3TORM (multiplexed automated serial staining stochastic optical reconstruction microscopy), a microscopy approach capable of fully automated 3D dSTORM imaging and solution exchange employing a re-staining protocol to achieve highly multiplexed protein localization within individual biological samples. We demonstrate 3D super-resolution images of 15 target proteins in single cultured cells and 16 targets in individual neuronal tissue samples with <10 nm localization precision. This allowed us to define novel nano-architectural features of protein distribution within the presynaptic nerve terminal.
Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia) on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent) and red foxes (in the south). Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall), our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.
Therapy resistance in leukemia may be due to cancer cell-intrinsic and/or -extrinsic mechanisms. Mutations within BCR-ABL1, the oncogene giving rise to chronic myeloid leukemia (CML), lead to resistance to tyrosine kinase inhibitors (TKI), and some are associated with clinically more aggressive disease and worse outcome. Using the retroviral transduction/transplantation model of CML and human cell lines we faithfully recapitulate accelerated disease course in TKI resistance. We show in various models, that murine and human imatinib-resistant leukemia cells positive for the oncogene BCR-ABL1T315I differ from BCR-ABL1 native (BCR-ABL1) cells with regards to niche location and specific niche interactions. We implicate a pathway via integrin β3, integrin-linked kinase (ILK) and its role in deposition of the extracellular matrix (ECM) protein fibronectin as causative of these differences. We demonstrate a trend towards a reduced BCR-ABL1T315I+ tumor burden and significantly prolonged survival of mice with BCR-ABL1T315I+ CML treated with fibronectin or an ILK inhibitor in xenogeneic and syngeneic murine transplantation models, respectively. These data suggest that interactions with ECM proteins via the integrin β3/ILK-mediated signaling pathway in BCR-ABL1T315I+ cells differentially and specifically influence leukemia progression. Niche targeting via modulation of the ECM may be a feasible therapeutic approach to consider in this setting.
The idea of slow-neutron capture nucleosynthesis formulated in 1957 triggered a tremendous experimental effort in different laboratories worldwide to measure the relevant nuclear physics input quantities, namely (n,γ) cross sections over the stellar temperature range (from few eV up to several hundred keV) for most of the isotopes involved from Fe up to Bi. A brief historical review focused on total energy detectors will be presented to illustrate how, advances in instrumentation have led, over the years, to the assessment and discovery of many new aspects of s-process nucleosynthesis and to the progressive refinement of theoretical models of stellar evolution. A summary will be presented on current efforts to develop new detection concepts, such as the Total-Energy Detector with γ-ray imaging capability (i-TED). The latter is based on the simultaneous combination of Compton imaging with neutron time-of-flight (TOF) techniques, in order to achieve a superior level of sensitivity and selectivity in the measurement of stellar neutron capture rates.
Fission program at n_TOF
(2019)
Since its start in 2001 the n_TOF collaboration developed a measurement program on fission, in view of advanced fuels in new generation reactors. A special effort was made on measurement of cross sections of actinides, exploiting the peculiarity of the n_TOF neutron beam which spans a huge energy domain, from the thermal region up to GeV. Moreover fission fragment angular distributions have also been measured. An overview of the cross section results achieved with different detectors is presented, including a discussion of the 237Np case where discrepancies showed up between different detector systems. The results on the anisotropy of the fission fragments and its implication on the mechanism of neutron absorption, and in applications, are also shown.
During the measurement campaign FROST 2 (FReezing Of duST 2), the Leipzig Aerosol Cloud Interaction Simulator (LACIS) was used to investigate the influence of various surface modifications on the ice nucleating ability of Arizona Test Dust (ATD) particles in the immersion freezing mode. The dust particles were exposed to sulfuric acid vapor, to water vapor with and without the addition of ammonia gas, and heat using a thermodenuder operating at 250 °C. Size selected, quasi monodisperse particles with a mobility diameter of 300 nm were fed into LACIS and droplets grew on these particles such that each droplet contained a single particle. Temperature dependent frozen fractions of these droplets were determined in a temperature range between −40 °C ≤T≤−28 °C. The pure ATD particles nucleated ice over a broad temperature range with their freezing behavior being separated into two freezing branches characterized through different slopes in the frozen fraction vs. temperature curves. Coating the ATD particles with sulfuric acid resulted in the particles' IN potential significantly decreasing in the first freezing branch (T>−35 °C) and a slight increase in the second branch (T≤−35 °C). The addition of water vapor after the sulfuric acid coating caused the disappearance of the first freezing branch and a strong reduction of the IN ability in the second freezing branch. The presence of ammonia gas during water vapor exposure had a negligible effect on the particles' IN ability compared to the effect of water vapor. Heating in the thermodenuder led to a decreased IN ability of the sulfuric acid coated particles for both branches but the additional heat did not or only slightly change the IN ability of the pure ATD and the water vapor exposed sulfuric acid coated particles. In other words, the combination of both sulfuric acid and water vapor being present is a main cause for the ice active surface features of the ATD particles being destroyed. A possible explanation could be the chemical transformation of ice active metal silicates to metal sulfates. The strongly enhanced reaction between sulfuric acid and dust in the presence of water vapor and the resulting significant reductions in IN potential are of importance for atmospheric ice cloud formation. Our findings suggest that the IN concentration can decrease by up to one order of magnitude for the conditions investigated.
In the present work, three different techniques are used to separate ice-nucleating particles (INP) and ice particle residuals (IPR) from non-ice-active particles: the Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI), which sample ice particles from mixed phase clouds and allow for the analysis of the residuals, as well as the combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Virtual Impactor (IN-PCVI), which provides ice-activating conditions to aerosol particles and extracts the activated ones for analysis. The collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine their size, chemical composition and mixing state. Samples were taken during January/February 2013 at the High Alpine Research Station Jungfraujoch. All INP/IPR-separating techniques had considerable abundances (median 20–70%) of contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH + IN-PCVI: steel particles). Also, potential measurement artifacts (soluble material) occurred (median abundance < 20%). After removal of the contamination particles, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Minor types include soot and Pb-bearing particles. Sea-salt and sulfates were identified by all three methods as INP/IPR. Lead was identified in less than 10% of the INP/IPR. It was mainly present as an internal mixture with other particle types, but also external lead-rich particles were found. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also sampled many submicron particles. Probably owing to the different meteorological conditions, the INP/IPR composition was highly variable on a sample to sample basis. Thus, some part of the discrepancies between the different techniques may result from the (unavoidable) non-parallel sampling. The observed differences of the particles group abundances as well as the mixing state of INP/IPR point to the need of further studies to better understand the influence of the separating techniques on the INP/IPR chemical composition.
During January/February 2013, at the High Alpine Research Station Jungfraujoch a measurement campaign was carried out, which was centered on atmospheric ice-nucleating particles (INP) and ice particle residuals (IPR). Three different techniques for separation of INP and IPR from the non-ice-active particles are compared. The Ice Selective Inlet (ISI) and the Ice Counterflow Virtual Impactor (Ice-CVI) sample ice particles from mixed phase clouds and allow for the analysis of the residuals. The combination of the Fast Ice Nucleus Chamber (FINCH) and the Ice Nuclei Pumped Counterflow Virtual Impactor (IN-PCVI) provides ice-activating conditions to aerosol particles and extracts the activated INP for analysis.Collected particles were analyzed by scanning electron microscopy and energy-dispersive X-ray microanalysis to determine size, chemical composition and mixing state. All INP/IPR-separating techniques had considerable abundances (median 20 – 70 %) of instrumental contamination artifacts (ISI: Si-O spheres, probably calibration aerosol; Ice-CVI: Al-O particles; FINCH+IN-PCVI: steel particles). Also, potential sampling artifacts (e.g., pure soluble material) occurred with a median abundance of < 20 %. While these could be explained as IPR by ice break-up, for INP their IN-ability pathway is less clear. After removal of the contamination artifacts, silicates and Ca-rich particles, carbonaceous material and metal oxides were the major INP/IPR particle types separated by all three techniques. Soot was a minor contributor. Lead was detected in less than 10 % of the particles, of which the majority were internal mixtures with other particle types. Sea-salt and sulfates were identified by all three methods as INP/IPR. Most samples showed a maximum of the INP/IPR size distribution at 400 nm geometric diameter. In a few cases, a second super-micron maximum was identified. Soot/carbonaceous material and metal oxides were present mainly in the submicron range. ISI and FINCH yielded silicates and Ca-rich particles mainly with diameters above 1 μm, while the Ice-CVI also separated many submicron IPR. As strictly parallel sampling could not be performed, a part of the discrepancies between the different techniques may result from variations in meteorological conditions and subsequent INP/IPR composition. The observed differences in the particle group abundances as well as in the mixing state of INP/IPR express the need for further studies to better understand the influence of the separating techniques on the INP/IPR chemical
composition.
During the measurement campaign FROST 2 (FReezing Of duST 2), the Leipzig Aerosol Cloud Interaction Simulator (LACIS) was used to investigate the influences of various surface modifications on the immersion freezing behavior of Arizona Test Dust (ATD) particles. The dust particles were exposed to sulfuric acid vapor, to water vapor with and without the addition of ammonia gas, and heat using a thermodenuder operating at 250 °C. Size selected, quasi monodisperse particles with a mobility diameter of 300 nm were fed into LACIS and droplets grew on these particles such that each droplet contained a single particle. Temperature dependent frozen fractions of these droplets were determined in a temperature range between −40 °C ≤ T ≤ −28 °C. The pure ATD particles nucleated ice over a~broad temperature range with their freezing behavior being separated into two freezing branches characterized through different slopes in the frozen fraction vs. temperature curves. Coating the ATD particles with sulfuric acid resulted in the particles' IN potential significantly decreasing in the first freezing branch (T > −35 °C) and a slight increase in the second branch (T≤ −35 °C). The addition of water vapor after the sulfuric acid coating caused the disappearance of the first freezing branch and a strong reduction of the IN ability in the second freezing branch. The presence of ammonia gas during water vapor exposure had a negligible effect on the particles' IN ability compared to the effect of water vapor. Heating in the thermodenuder led to a decreased IN ability of the sulfuric acid coated particles for both branches but the additional heat did not or only slightly change the IN ability of the pure ATD and the water vapor exposed sulfuric acid coated particles. In other words, the combination of both sulfuric acid and water vapor being present is a main cause for the ice active surface features of the ATD particles being destroyed. A possible explanation could be the chemical transformation of ice active metal silicates to metal sulfates. From an atmospheric point of view, and here specifically the influences of atmospheric aging on the IN ability of dust particles, the strongly enhanced reaction between sulfuric acid and dust in the presence of water vapor, and the resulting significant reductions in IN potential, are certainly very interesting.
The neutron capture cross section of some unstable nuclei is especially relevant for s-process nucleosynthesis studies. This magnitude is crucial to determine the local abundance pattern, which can yield valuable information of the s-process stellar environment. In this work we describe the neutron capture (n,γ) measurement on two of these nuclei of interest, 204Tl and 171Tm, from target production to the final measurement, performed successfully at the n_TOF facility at CERN in 2014 and 2015. Preliminary results on the ongoing experimental data analysis will also be shown. These results include the first ever experimental observation of capture resonances for these two nuclei.
The slow neutron capture process (s-process) is responsible for producing about half of the elemental abundances heavier than iron in the universe. Neutron capture cross sections on stable isotopes are a key nuclear physics input for s-process studies. The 72Ge(n, γ) cross section has an important influence on production of isotopes between Ge and Zr during s-process in massive stars and therefore experimental data are urgently required. 72Ge(n, γ) was measured at the neutron time-of-flight facility n_TOF (CERN) for the first time at stellar energies. The measurement was performed using an enriched 72GeO2 sample at a flight path of 185m with a set of liquid scintillation detectors (C6D6). The motivation, experiment and current status of the data analysis are reported.
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 centrosome linker proteins C-Nap1, rootletin, and CEP68 connect the two centrosomes of a cell during interphase into one microtubule-organizing center. This coupling is important for cell migration, cilia formation, and timing of mitotic spindle formation. Very little is known about the structure of the centrosome linker. Here, we used stimulated emission depletion (STED) microscopy to show that each C-Nap1 ring at the proximal end of the two centrioles organizes a rootletin ring and, in addition, multiple rootletin/CEP68 fibers. Rootletin/CEP68 fibers originating from the two centrosomes form a web-like, interdigitating network, explaining the flexible nature of the centrosome linker. The rootletin/CEP68 filaments are repetitive and highly ordered. Staggered rootletin molecules (N-to-N and C-to-C) within the filaments are 75 nm apart. Rootletin binds CEP68 via its C-terminal spectrin repeat-containing region in 75-nm intervals. The N-to-C distance of two rootletin molecules is ∼35 to 40 nm, leading to an estimated minimal rootletin length of ∼110 nm. CEP68 is important in forming rootletin filaments that branch off centrioles and to modulate the thickness of rootletin fibers. Thus, the centrosome linker consists of a vast network of repeating rootletin units with C-Nap1 as ring organizer and CEP68 as filament modulator.
Previous studies in developing Xenopus and zebrafish reported that the phosphate transporter slc20a1a is expressed in pronephric kidneys. The recent identification of SLC20A1 as a monoallelic candidate gene for cloacal exstrophy further suggests its involvement in the urinary tract and urorectal development. However, little is known of the functional role of SLC20A1 in urinary tract development. Here, we investigated this using morpholino oligonucleotide knockdown of the zebrafish ortholog slc20a1a. This caused kidney cysts and malformations of the cloaca. Moreover, in morphants we demonstrated dysfunctional voiding and hindgut opening defects mimicking imperforate anus in human cloacal exstrophy. Furthermore, we performed immunohistochemistry of an unaffected 6-week-old human embryo and detected SLC20A1 in the urinary tract and the abdominal midline, structures implicated in the pathogenesis of cloacal exstrophy. Additionally, we resequenced SLC20A1 in 690 individuals with bladder exstrophy-epispadias complex (BEEC) including 84 individuals with cloacal exstrophy. We identified two additional monoallelic de novo variants. One was identified in a case-parent trio with classic bladder exstrophy, and one additional novel de novo variant was detected in an affected mother who transmitted this variant to her affected son. To study the potential cellular impact of SLC20A1 variants, we expressed them in HEK293 cells. Here, phosphate transport was not compromised, suggesting that it is not a disease mechanism. However, there was a tendency for lower levels of cleaved caspase-3, perhaps implicating apoptosis pathways in the disease. Our results suggest SLC20A1 is involved in urinary tract and urorectal development and implicate SLC20A1 as a disease-gene for BEEC.
Recombinase-mediated cassette exchange (RMCE) exploits the possibility to unidirectionally exchange any genetic material flanked by heterotypic recombinase recognition sites (RRS) with target sites in the genome. Due to a limited number of available pre-fabricated target sites, RMCE in mouse embryonic stem (ES) cells has not been tapped to its full potential to date. Here, we introduce a universal system, which allows the targeted insertion of any given transcriptional unit into 85 742 previously annotated retroviral conditional gene trap insertions, representing 7013 independent genes in mouse ES cells, by RMCE. This system can be used to express any given cDNA under the control of endogenous trapped promoters in vivo, as well as for the generation of transposon ‘launch pads’ for chromosomal region-specific ‘Sleeping Beauty’ insertional mutagenesis. Moreover, transcription of the gene-of-interest is only activated upon Cre-recombinase activity, a feature that adds conditionality to this expression system, which is demonstrated in vivo. The use of the RMCE system presented in this work requires one single-cloning step followed by one overnight gateway clonase reaction and subsequent cassette exchange in ES cells with efficiencies of 40% in average.
Wastewater-based SARS-CoV-2 epidemiology (WBE) has been established as an important tool to support individual testing strategies. Omicron sub-variants BA.4/5 have spread globally displacing the predeceasing variants. Due to the severe transmissibility and immune escape potential of BA.4/5, early monitoring was required to asses and implement countermeasures in time.
In this study, we monitored the prevalence of SARS-CoV-2 BA.4/5 at six municipal wastewater treatment plants (WWTPs) in the Federal State of North-Rhine-Westphalia (NRW, Germany) in May and June 2022. Initially, L452R-specific primers/probes originally designed for SARS-CoV-2 Delta detection were validated using inactivated authentic viruses and evaluated for their suitability to detect BA.4/5. Subsequently, the assay was used for RT-qPCR analysis of RNA purified from wastewater obtained twice a week at six WWTPs. The occurrence of L452R carrying RNA was detected in early May 2022 and the presence of BA.4/5 was confirmed by variant-specific single nucleotide polymorphism PCR (SNP-PCR) targeting E484A/F486V. Finally, the mutant fractions were quantitatively monitored by digital PCR confirming BA.4/5 as the majority variant by 5th June 2022.
In conclusions, the successive workflow using RT-qPCR, variant-specific SNP-PCR, and RT-dPCR demonstrates the strength of WBE as a versatile tool to rapidly monitor variant spreading independent of individual test capacities.
The emerging disciplines of lipidomics and metabolomics show great potential for the discovery of diagnostic biomarkers, but appropriate pre-analytical sample-handling procedures are critical because several analytes are prone to ex vivo distortions during sample collection. To test how the intermediate storage temperature and storage period of plasma samples from K3EDTA whole-blood collection tubes affect analyte concentrations, we assessed samples from non-fasting healthy volunteers (n = 9) for a broad spectrum of metabolites, including lipids and lipid mediators, using a well-established LC-MS-based platform. We used a fold change-based approach as a relative measure of analyte stability to evaluate 489 analytes, employing a combination of targeted LC-MS/MS and LC-HRMS screening. The concentrations of many analytes were found to be reliable, often justifying less strict sample handling; however, certain analytes were unstable, supporting the need for meticulous processing. We make four data-driven recommendations for sample-handling protocols with varying degrees of stringency, based on the maximum number of analytes and the feasibility of routine clinical implementation. These protocols also enable the simple evaluation of biomarker candidates based on their analyte-specific vulnerability to ex vivo distortions. In summary, pre-analytical sample handling has a major effect on the suitability of certain metabolites as biomarkers, including several lipids and lipid mediators. Our sample-handling recommendations will increase the reliability and quality of samples when such metabolites are necessary for routine clinical diagnosis.
Background: The treatment of high-risk neuroblastoma patients consists of multimodal induction therapy to achieve remission followed by consolidation therapy to prevent relapses. However, the type of consolidation therapy is still discussed controversial. We applied metronomic chemotherapy in the prospective NB90 trial and monoclonal anti-GD2-antibody (MAB) ch14.18 in the NB97 trial. Here, we present the long term outcome data of the patient cohort. Methods: A total of 334 stage 4 neuroblastoma patients one year or older were included. All patients successfully completed the induction therapy. In the NB90 trial, 99 patients received at least one cycle of the oral maintenance chemotherapy (NB90 MT, 12 alternating cycles of oral melphalan/etoposide and vincristine/cyclophosphamide). In the NB97 trial, 166 patients commenced the MAB ch14.18 consolidation therapy (six cycles over 12 months). Patients who received no maintenance therapy according to the NB90 protocol or by refusal in NB97 (n = 69) served as controls. Results: The median observation time was 11.11 years. The nine-year event-free survival rates were 41 ± 4%, 31 ± 5%, and 32 ± 6% for MAB ch14.18, NB90 MT, and no consolidation, respectively (p = 0.098). In contrast to earlier reports, MAB ch14.18 treatment improved the long-term outcome compared to no additional therapy (p = 0.038). The overall survival was better in the MAB ch14.18-treated group (9-y-OS 46 ± 4%) compared to NB90 MT (34 ± 5%, p = 0.026) and to no consolidation (35 ± 6%, p = 0.019). Multivariable Cox regression analysis revealed ch14.18 consolidation to improve outcome compared to no consolidation, however, no difference between NB90 MT and MAB ch14.18-treated patients was found. Conclusions: Follow-up analysis of the patient cohort indicated that immunotherapy with MAB ch14.18 may prevent late relapses. Finally, metronomic oral maintenance chemotherapy also appeared effective.
Hintergrund: Die Ophthalmoskopie ist Bestandteil des medizinischen Curriculums, jedoch das Vermitteln der Inhalte oft unbefriedigend, da ein systematisches Lernen von Pathologien und deren Behandlungen dadurch erschwert ist, dass oftmals das passende Patientengut nicht zur Verfügung steht und dadurch gesunde Studenten einander untersuchen müssen. Aus diesem Grund haben wir eine Online-Plattform entwickelt, die in Kombination mit simulationsgestütztem Training sowohl das eigenständige als auch das angeleitete Lernen von Untersuchungsmethoden und Pathologien ermöglicht.
Ziel der Arbeit: Ziel der vorliegenden Arbeit war, ein Format für die Verbesserung der Lehre der direkten und indirekten Ophthalmoskopie im Studierendenunterricht zu evaluieren. Dabei wurden praktische Übungen an Virtual-Reality-basierten Simulatoren mit neu entwickelten und an den Lehrkatalog angepassten theoretischen Inhalten in der Online-Plattform EyesiNet verschränkt.
Material und Methoden: Die Studierenden bearbeiteten am ersten sowie am letzten Praktikumstag zufällig ausgewählte Fälle, die ihnen von den Eyesi Direct- und Eyesi Indirect-Simulatoren präsentiert wurden. Zwischen diesen beiden Einheiten konnten sie sich auf freiwilliger Basis mit den theoretischen Grundlagen typischer ophthalmologischer Krankheitsbilder im EyesiNet beschäftigen.
Ergebnisse: Eyesi Direct: Die Bewertung des Simulators ergab am ersten Praktikumstag für beide Gruppen keinen signifikant unterschiedlichen Wissensstand (p = 0,29). In der Gruppe OHNE Training (n = 54) ergab sich am letzten Praktikumstag mit p = 0,02 eine signifikante Verbesserung dieser Bewertung, jedoch mit einer geringen Effektgröße von 0,1. In der Gruppe MIT Training (n = 32) konnte mit p = 0,0004 eine hoch signifikante Verbesserung mit einer Effektgröße von 0,3 nach Rosenthal festgestellt werden. Eyesi Indirect: Die simulatorgestützte Bewertung ergab am ersten Praktikumstag keinen signifikanten Unterschied im Wissensstand der beiden Gruppen (p = 0,1). Nach dem Training schnitten zwar beide Gruppen etwas besser ab, jedoch ohne signifikanten Unterschied (OHNE Training p = 0,41/MIT Training p = 0,17).
Diskussion: Die Online-Plattform EyesiNet unterstützt beim Erlernen der wichtigsten Erkrankungsbilder. Lerninhalte werden reproduzierbar und auf für alle Lernenden standardisierte Weise zur Verfügung gestellt. Die Fertigkeiten der direkten Ophthalmoskopie sind hierbei deutlich schneller als die der indirekten Ophthalmoskopie zu erlernen.
Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
Purpose: Acute elbow dislocations are complex injuries that predispose to chronic instability and pain. The ideal treatment strategy is part of controversial discussion and evidence-based recommendations for the treatment could not be concluded from the literature. The purpose of the present study was to assess current epidemiological data, injury pattern, and the changing trend for treatment.
Methods: This study presents a retrospective review of 72 patients ≥ 18 years of age who were treated in our level I trauma centre with acute elbow dislocations from 2014 to 2018. The data were acquired by analysis of the institution’s database, and radiological examinations.
Results: The average age of the patients was 48.5 years (range 18–86). The ratio of male to female patients was 1.9:1. A fall onto the outstretched arm (42%) was the most common injury mechanism. By classification, 42% of the elbow dislocations were simple, and 58% complex. A total of 85% of patients underwent surgery including 73% of the simple elbow dislocations due to remaining instability or non-congruency of the reduced elbow. The indication for surgical treatment correlated merely with the grade of instability and displacement, but not with age.
Conclusion: Acute elbow dislocations need identification of the precise injury pattern and instability after reduction of the elbow joint. To achieve a congruent and stable joint, we recommend primary surgical repair as first-line treatment for patients with unstable simple and complex elbow dislocation independent of age.
Background: Rare diseases are, by definition, very serious and chronic diseases with a high negative impact on quality of life. Approximately 350 million people worldwide live with rare diseases. The resulting high disease burden triggers health information search, but helpful, high-quality, and up-to-date information is often hard to find. Therefore, the improvement of health information provision has been integrated in many national plans for rare diseases, discussing the telephone as one access option. In this context, this study examines the need for a telephone service offering information for people affected by rare diseases, their relatives, and physicians.
Methods: In total, 107 individuals participated in a qualitative interview study conducted in Germany. Sixty-eight individuals suffering from a rare disease or related to somebody with rare diseases and 39 health care professionals took part. Individual interviews were conducted using a standardized semi-structured questionnaire. Interviews were analysed using the qualitative content analysis, triangulating patients, relatives, and health care professionals. The fulfilment of qualitative data processing standards has been controlled for.
Results: Out of 68 patients and relatives and 39 physicians, 52 and 18, respectively, advocated for the establishment of a rare diseases telephone service. Interviewees expected a helpline to include expert staffing, personal contact, good availability, low technical barriers, medical and psychosocial topics of counselling, guidance in reducing information chaos, and referrals. Health care professionals highlighted the importance of medical topics of counselling—in particular, differential diagnostics—and referrals.
Conclusions: Therefore, the need for a national rare diseases helpline was confirmed in this study. Due to limited financial resources, existing offers should be adapted in a stepwise procedure in accordance with the identified attributes.
Background: Recently, public and political interest has focused on people living with rare diseases and their health concerns. Due to the large number of different types of rare diseases and the sizable number of patients, taking action to improve the life of those affected is gaining importance. In 2013, the federal government of Germany adopted a national action plan for rare diseases, including the call to establish a central information portal on rare diseases (Zentrales Informationsportal über seltene Erkrankungen, ZIPSE).
Objective: The objective of this study, therefore, was to conduct scientific research on how such a portal must be designed to meet the needs of patients, their families, and medical professionals, and to provide high-quality information for information seekers.
Methods: We chose a 3-step procedure to develop a needs-based prototype of a central information portal. In the first step, we determined the information needs of patients with rare diseases, their relatives, and health care professionals by means of qualitative interviews and their content-analytical evaluation. On the basis of this, we developed the basic structure of the portal. In the second step, we identified quality criteria for websites on rare diseases to ensure that the information linked with ZIPSE meets the quality demands. Therefore, we gathered existing criteria catalogs and discussed them in an expert workshop. In the third step, we implemented and tested the developed prototypical information portal.
Results: A portal page was configured and made accessible on the Web. The structure of ZIPSE was based on the findings from 108 qualitative interviews with patients, their relatives, and health care professionals, through which numerous information needs were identified. We placed particularly important areas of information, such as symptoms, therapy, research, and advisory services, on the start page. Moreover, we defined 13 quality criteria, referring to factors such as author information, creation date, and privacy, enabling links with high-quality information. Moreover, 19 users tested all the developed routines based on usability and comprehensibility. Subsequently, we improved the visual presentation of search results and other important search functions.
Conclusions: The implemented information portal, ZIPSE, provides high-quality information on rare diseases from a central point of access. By integrating the targeted groups as well as different experts on medical information during the construction, the website can assure an improved search for information for users. ZIPSE can also serve as a model for other Web-based information systems in the field of rare diseases.
Registered Report Identifier: RR1-10.2196/7425.
Crista junctions (CJs) are important for mitochondrial organization and function, but the molecular basis of their formation and architecture is obscure. We have identified and characterized a mitochondrial membrane protein in yeast, Fcj1 (formation of CJ protein 1), which is specifically enriched in CJs. Cells lacking Fcj1 lack CJs, exhibit concentric stacks of inner membrane in the mitochondrial matrix, and show increased levels of F1FO–ATP synthase (F1FO) supercomplexes. Overexpression of Fcj1 leads to increased CJ formation, branching of cristae, enlargement of CJ diameter, and reduced levels of F1FO supercomplexes. Impairment of F1FO oligomer formation by deletion of its subunits e/g (Su e/g) causes CJ diameter enlargement and reduction of cristae tip numbers and promotes cristae branching. Fcj1 and Su e/g genetically interact. We propose a model in which the antagonism between Fcj1 and Su e/g locally modulates the F1FO oligomeric state, thereby controlling membrane curvature of cristae to generate CJs and cristae tips.
There are strong indications that particles containing secondary organic aerosol (SOA) exhibit amorphous solid or semi-solid phase states in the atmosphere. This may facilitate heterogeneous ice nucleation and thus influence cloud properties. However, experimental ice nucleation studies of biogenic SOA are scarce. Here, we investigated the ice nucleation ability of viscous SOA particles.
The SOA particles were produced from the ozone initiated oxidation of α-pinene in an aerosol chamber at temperatures in the range from −38 to −10 °C at 5–15 % relative humidity with respect to water to ensure their formation in a highly viscous phase state, i.e. semi-solid or glassy. The ice nucleation ability of SOA particles with different sizes was investigated with a new continuous flow diffusion chamber. For the first time, we observed heterogeneous ice nucleation of viscous α-pinene SOA for ice saturation ratios between 1.3 and 1.4 significantly below the homogeneous freezing limit. The maximum frozen fractions found at temperatures between −39.0 and −37.2 °C ranged from 6 to 20 % and did not depend on the particle surface area. Global modelling of monoterpene SOA particles suggests that viscous biogenic SOA particles are indeed present in regions where cirrus cloud formation takes place. Hence, they could make up an important contribution to the global ice nucleating particle budget.
Cloud microphysical processes involving the ice phase in tropospheric clouds are among the major uncertainties in cloud formation, weather and General Circulation Models (GCMs). The simultaneous detection of aerosol particles, liquid droplets, and ice crystals, especially in the small cloud-particle size range below 50 µm, remains challenging in mixed phase, often unstable ice-water phase environments. The Cloud Aerosol Spectrometer with Polarisation (CASPOL) is an airborne instrument that has the ability to detect such small cloud particles and measure their effects on the backscatter polarisation state. Here we operate the versatile Cosmics-Leaving- OUtdoor-Droplets (CLOUD) chamber facility at the European Organisation for Nuclear Research (CERN) to produce controlled mixed phase and other clouds by adiabatic expansions in an ultraclean environment, and use the CASPOL to discriminate between different aerosols, water and ice particles. In this paper, optical property measurements of mixed phase clouds and viscous Secondary Organic Aerosol (SOA) are presented. We report observations of significant liquid – viscous SOA particle polarisation transitions under dry conditions using CASPOL. Cluster analysis techniques were subsequently used to classify different types of particles according to their polarisation ratios during phase transition. A classification map is presented for water droplets, organic aerosol (e.g., SOA and oxalic acid), crystalline substances such as ammonium sulphate, and volcanic ash. Finally, we discuss the benefits and limitations of this classi- fication approach for atmospherically relevant concentration and mixtures with respect to the CLOUD 8–9 campaigns and its potential contribution to Tropical Troposphere Layer (TTL) analysis.
The growth of aerosol due to the aqueous phase oxidation of sulfur dioxide by ozone was measured in laboratory-generated clouds created in the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN). Experiments were performed at 10 and −10 °C, on acidic (sulfuric acid) and on partially to fully neutralised (ammonium sulfate) seed aerosol. Clouds were generated by performing an adiabatic expansion – pressurising the chamber to 220 hPa above atmospheric pressure, and then rapidly releasing the excess pressure, resulting in a cooling, condensation of water on the aerosol and a cloud lifetime of approximately 6 min. A model was developed to compare the observed aerosol growth with that predicted using oxidation rate constants previously measured in bulk solutions. The model captured the measured aerosol growth very well for experiments performed at 10 and −10 °C, indicating that, in contrast to some previous studies, the oxidation rates of SO2 in a dispersed aqueous system can be well represented by using accepted rate constants, based on bulk measurements. To the best of our knowledge, these are the first laboratory-based measurements of aqueous phase oxidation in a dispersed, super-cooled population of droplets. The measurements are therefore important in confirming that the extrapolation of currently accepted reaction rate constants to temperatures below 0 °C is correct.
The growth of aerosol due to the aqueous phase oxidation of sulfur dioxide by ozone was measured in laboratory-generated clouds created in the Cosmics Leaving OUtdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN). Experiments were performed at 10 and −10 °C, on acidic (sulfuric acid) and on partially to fully neutralised (ammonium sulfate) seed aerosol. Clouds were generated by performing an adiabatic expansion – pressurising the chamber to 220 hPa above atmospheric pressure, and then rapidly releasing the excess pressure, resulting in a cooling, condensation of water on the aerosol and a cloud lifetime of approximately 6 min. A model was developed to compare the observed aerosol growth with that predicted using oxidation rate constants previously measured in bulk solutions. The model captured the measured aerosol growth very well for experiments performed at 10 and −10 °C, indicating that, in contrast to some previous studies, the oxidation rates of SO2 in a dispersed aqueous system can be well represented by using accepted rate constants, based on bulk measurements. To the best of our knowledge, these are the first laboratory-based measurements of aqueous phase oxidation in a dispersed, super-cooled population of droplets. The measurements are therefore important in confirming that the extrapolation of currently accepted reaction rate constants to temperatures below 0 °C is correct.
Cloud microphysical processes involving the ice phase in tropospheric clouds are among the major uncertainties in cloud formation, weather, and general circulation models. The detection of aerosol particles, liquid droplets, and ice crystals, especially in the small cloud particle-size range below 50 μm, remains challenging in mixed phase, often unstable environments. The Cloud Aerosol Spectrometer with Polarization (CASPOL) is an airborne instrument that has the ability to detect such small cloud particles and measure the variability in polarization state of their backscattered light. Here we operate the versatile Cosmics Leaving OUtdoor Droplets (CLOUD) chamber facility at the European Organization for Nuclear Research (CERN) to produce controlled mixed phase and other clouds by adiabatic expansions in an ultraclean environment, and use the CASPOL to discriminate between different aerosols, water, and ice particles. In this paper, optical property measurements of mixed-phase clouds and viscous secondary organic aerosol (SOA) are presented. We report observations of significant liquid–viscous SOA particle polarization transitions under dry conditions using CASPOL. Cluster analysis techniques were subsequently used to classify different types of particles according to their polarization ratios during phase transition. A classification map is presented for water droplets, organic aerosol (e.g., SOA and oxalic acid), crystalline substances such as ammonium sulfate, and volcanic ash. Finally, we discuss the benefits and limitations of this classification approach for atmospherically relevant concentrations and mixtures with respect to the CLOUD 8–9 campaigns and its potential contribution to tropical troposphere layer analysis.
There are strong indications that particles containing secondary organic aerosol (SOA) exhibit amorphous solid or semi-solid phase states in the atmosphere. This may facilitate deposition ice nucleation and thus influence cirrus cloud properties. However, experimental ice nucleation studies of biogenic SOA are scarce. Here, we investigated the ice nucleation ability of viscous SOA particles.
The SOA particles were produced from the ozone initiated oxidation of α-pinene in an aerosol chamber at temperatures in the range from −38 to −10 ◦C at 5–15 % relative humidity with respect to water to ensure their formation in a highly viscous phase state, i.e. semi-solid or glassy. The ice nucleation ability of SOA particles with different sizes was investigated with a new continuous flow diffusion chamber. For the first time, we observed heterogeneous ice nucleation of viscous α-pinene SOA in the deposition mode for ice saturation ratios between 1.3 and 1.4 significantly below the homogeneous freezing limit. The maximum frozen fractions found at temperatures between −36.5 and −38.3 °C ranged from 6 to 20 % and did not depend on the particle surface area. Global modelling of monoterpene SOA particles suggests that viscous biogenic SOA particles are indeed present in regions where cirrus cloud formation takes place. Hence, they could make up an important contribution to the global ice nuclei (IN) budget.
Background: Chronic congestive heart failure (CHF) is a complex disease with rising prevalence, compromised quality of life (QoL), unplanned hospital admissions, high mortality and therefore high burden of illness. The delivery of care for these patients has been criticized and new strategies addressing crucial domains of care have been shown to be effective on patients' health outcomes, although these trials were conducted in secondary care or in highly organised Health Maintenance Organisations. It remains unclear whether a comprehensive primary care-based case management for the treating general practitioner (GP) can improve patients' QoL. Methods/Design: HICMan is a randomised controlled trial with patients as the unit of randomisation. Aim is to evaluate a structured, standardized and comprehensive complex intervention for patients with CHF in a 12-months follow-up trial. Patients from intervention group receive specific patient leaflets and documentation booklets as well as regular monitoring and screening by a prior trained practice nurse, who gives feedback to the GP upon urgency. Monitoring and screening address aspects of disease-specific selfmanagement, (non)pharmacological adherence and psychosomatic and geriatric comorbidity. GPs are invited to provide a tailored structured counselling 4 times during the trial and receive an additional feedback on pharmacotherapy relevant to prognosis (data of baseline documentation). Patients from control group receive usual care by their GPs, who were introduced to guidelineoriented management and a tailored health counselling concept. Main outcome measurement for patients' QoL is the scale physical functioning of the SF-36 health questionnaire in a 12-month follow-up. Secondary outcomes are the disease specific QoL measured by the Kansas City Cardiomyopathy questionnaire (KCCQ), depression and anxiety disorders (PHQ-9, GAD-7), adherence (EHFScBS and SANA), quality of care measured by an adapted version of the Patient Chronic Illness Assessment of Care questionnaire (PACIC) and NTproBNP. In addition, comprehensive clinical data are collected about health status, comorbidity, medication and health care utilisation. Discussion: As the targeted patient group is mostly cared for and treated by GPs, a comprehensive primary care-based guideline implementation including somatic, psychosomatic and organisational aspects of the delivery of care (HICMAn) is a promising intervention applying proven strategies for optimal care. Trial registration: Current Controlled Trials ISRCTN30822978.
High-throughput gene trapping is a random approach for inducing insertional mutations across the mouse genome. This approach uses gene trap vectors that simultaneously inactivate and report the expression of the trapped gene at the insertion site, and provide a DNA tag for the rapid identification of the disrupted gene. Gene trapping has been used by both public and private institutions to produce libraries of embryonic stem (ES) cells harboring mutations in single genes. Presently,~ 66% of the protein coding genes in the mouse genome have been disrupted by gene trap insertions. Among these, however, genes encoding signal peptides or transmembrane domains (secretory genes) are underrepresented because they are not susceptible to conventional trapping methods. Here, we describe a high-throughput gene trapping strategy that effectively targets secretory genes. We used this strategy to assemble a library of ES cells harboring mutations in 716 unique secretory genes, of which 61% were not trapped by conventional trapping, indicating that the two strategies are complementary. The trapped ES cell lines, which can be ordered from the International Gene Trap Consortium (http://www.genetrap.org), are freely available to the scientific community.
Peptide receptor radionuclide therapy (PRRT) of metastatic neuroendocrine tumors (NET) can be successfully repeated but may eventually be dose-limited. Since 177Lu-DOTATATE dose limitation may come from hematological rather than renal function, hematological peripheral blood stem cell backup might be desirable. Here, we report our initial experience of peripheral blood stem-cell collection (PBSC) in patients with treatment-related cytopenia and therefore high risk of bone-marrow failure. Five patients with diffuse bone-marrow infiltration of NET and relevant myelosuppression (≥grade 2) received PBSC before one PRRT cycle with 177Lu-DOTATATE (7.6 ± 0.8 GBq/cycle). Standard stem-cell mobilization with Granulocyte-colony stimulating factor (G-CSF) was applied, and successful PBSC was defined as a collection of >2 × 106/kg CD34+ cells. In case of initial failure, Plerixafor was administered in addition to G-CSF prior to apheresis. PBSC was successfully performed in all patients with no adverse events. Median cumulative activity was 44.8 GBq (range, 21.3–62.4). Three patients had been previously treated with PRRT, two of which needed the addition of Plerixafor for stem-cell mobilization. Only one of five patients required autologous peripheral blood stem-cell transplantation during the median follow up time of 28 months. PBSC collection seems to be feasible in NET with bone-marrow involvement and might be worth considering as a backup strategy prior to PRRT, in order to overcome dose-limiting bone-marrow toxicity.
Background: Although being considered as a rarely observed HIV-1 protease mutation in clinical isolates, the L76V-prevalence increased 1998-2008 in some European countries most likely due to the approval of Lopinavir, Amprenavir and Darunavir which can select L76V. Beside an enhancement of resistance, L76V is also discussed to confer hypersusceptibility to the drugs Atazanavir and Saquinavir which might enable new treatment strategies by trying to take advantage of particular mutations. Results: Based on a cohort of 47 L76V-positive patients, we examined if there might exist a clinical advantage for L76V-positive patients concerning long-term success of PI-containing regimens in patients with limited therapy options. Genotypic- and phenotypic HIV-resistance tests from 47 mostly multi-resistant, L76V-positive patients throughout Germany were accomplished retrospectively 1999-2009. Five genotype-based drug-susceptibility predictions received from online interpretation-tools for Atazanavir, Saquinavir, Amprenavir and Lopinavir, were compared to phenotype-based predictions that were determined by using a recombinant virus assay along with a Virtual Phenotype™(Virco). The clinical outcome of the L76V-adapted follow-up therapy was determined by monitoring viral load for 96 weeks. Conclusions: In this analysis, the mostly used interpretation systems overestimated the L76V-mutation concerning Atazanavir- and SQV resistance. In fact, a clear benefit in drug susceptibility for these drugs was observed in phenotype analysis after establishment of L76V. More importantly, long-term therapy success was significantly higher in patients receiving Atazanavir and/or Saquinavir plus one L76V-selecting drug compared to patients without L76V-selecting agents (p = 0.002). In case of L76V-occurrence ATV and/or SQV may represent encouraging options for patients in deep salvage situations.
Background: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. Methods: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. Results: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict “survival”. Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients’ age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. Conclusions: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration “ClinicalTrials” (clinicaltrials.gov) under NCT04455451.
Accurate measurement of the standard 235U(n,f) cross section from thermal to 170 keV neutron energy
(2020)
An accurate measurement of the 235U(n,f) cross section from thermal to 170 keV of neutron energy has recently been performed at n_TOF facility at CERN using 6Li(n,t)4He and 10B(n,α)7Li as references. This measurement has been carried out in order to investigate a possible overestimation of the 235U fission cross section evaluation provided by most recent libraries between 10 and 30 keV. A custom experimental apparatus based on in-beam silicon detectors has been used, and a Monte Carlo simulation in GEANT4 has been employed to characterize the setup and calculate detectors efficiency. The results evidenced the presence of an overestimation in the interval between 9 and 18 keV and the new data may be used to decrease the uncertainty of 235U(n,f) cross section in the keV region.
233U is the fissile nuclei in the Th-U fuel cycle with a particularily small neutron capture cross setion which is on average about one order of magnitude lower than its fission cross section. Hence, the measurement of the 233U(n, γ) cross section relies on a method to accurately distinguish between capture and fission γ-rays. A measurement of the 233U α-ratio has been performed at the n_TOF facility at CERN using a so-called fission tagging setup, coupling n_TOF 's Total Absorption Calorimeter with a novel fission chamber to tag the fission γ-rays. The experimental setup is described and essential parts of the analysis are discussed. Finally, a preliminary 233U α-ratio is presented.
We have measured the capture cross section of the 155Gd and 157Gd isotopes between 0.025 eV and 1 keV. The capture events were recorded by an array of 4 C6D6 detectors, and the capture yield was deduced exploiting the total energy detection system in combination with the Pulse Height Weighting Techniques. Because of the large cross section around thermal neutron energy, 4 metallic samples of different thickness were used to prevent problems related to self-shielding. The samples were isotopically enriched, with a cross contamination of the other isotope of less than 1.14%. The capture yield was analyzed with an R-Matrix code to describe the cross section in terms of resonance parameters. Near thermal energies, the results are significantly different from evaluations and from previous time-of-flight experiments. The data from the present measurement at n_TOF are publicly available in the experimental nuclear reaction database EXFOR.
Feasibility, design and sensitivity studies on innovative nuclear reactors that could address the issue of nuclear waste transmutation using fuels enriched in minor actinides, require high accuracy cross section data for a variety of neutron-induced reactions from thermal energies to several tens of MeV. The isotope 241Am (T1/2= 433 years) is present in high-level nuclear waste (HLW), representing about 1.8 % of the actinide mass in spent PWR UOx fuel. Its importance increases with cooling time due to additional production from the β-decay of 241Pu with a half-life of 14.3 years. The production rate of 241 Am in conventional reactors, including its further accumulation through the decay of 241Pu and its destruction through transmutation/incineration are very important parameters for the design of any recycling solution. In the present work, the 241 Am(n,f) reaction cross-section was measured using Micromegas detectors at the Experimental Area 2 of the n_TOF facility at CERN. For the measurement, the 235U(n,f) and 238U(n,f) reference reactions were used for the determination of the neutron flux. In the present work an overview of the experimental setup and the adopted data analysis techniques is given along with preliminary results.
Measurement of the 244Cm and 246Cm neutron-induced capture cross sections at the n_TOF facility
(2019)
The neutron capture reactions of the 244Cm and 246Cm isotopes open the path for the formation of heavier Cm isotopes and heavier elements such as Bk and Cf in a nuclear reactor. In addition, both isotopes belong to the minor actinides with a large contribution to the decay heat and to the neutron emission in irradiated fuels. There are only two previous 244Cm and 246Cm capture cross section measurements: one in 1969 using a nuclear explosion [1] and the most recent data measured at J-PARC in 2010 [2]. The data for both isotopes are very scarce due to the difficulties in performing the measurements: high intrinsic activity of the samples and limited facilities capable of providing isotopically enriched samples.
We have measured both neutron capture cross sections at the n_TOF Experimental Area 2 (EAR-2) with three C6 D6 detectors and also at Area 1 (EAR-1) with the TAC. Preliminary results assessing the quality and limitations (back-ground subtraction, measurement technique and counting statistics) of this new experimental datasets are presented and discussed.
233U is of key importance among the fissile nuclei in the Th-U fuel cycle. A particularity of 233U is its small neutron capture cross-section, which is on average about one order of magnitude lower than the fission cross-section. The accuracy in the measurement of the 233U capture cross-section depends crucially on an efficient capture-fission discrimination, thus a combined set-up of fission and γ-detectors is needed. A measurement of the 233U capture cross-section and capture-to-fission ratio was performed at the CERN n_TOF facility. The Total Absorption Calorimeter (TAC) of n_TOF was employed as γ-detector coupled with a novel compact ionization chamber as fission detector. A brief description of the experimental set-up will be given, and essential parts of the analysis procedure as well as the preliminary response of the set-up to capture are presented and discussed.
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 (n, γ) cross sections of the gadolinium isotopes play an important role in the study of the stellar nucleosynthesis. In particular, among the isotopes heavier than Fe, 154Gd together with 152Gd have the peculiarity to be mainly produced by the slow capture process, the so-called s-process, since they are shielded against the β-decay chains from the r-process region by their stable samarium isobars. Such a quasi pure s-process origin makes them crucial for testing the robustness of stellar models in galactic chemical evolution (GCE). According to recent models, the 154Gd and 152Gd abundances are expected to be 15-20% lower than the reference un-branched s-process 150Sm isotope. The close correlation between stellar abundances and neutron capture cross sections prompted for an accurate measurement of 154Gd cross section in order to reduce the uncertainty attributable to nuclear physics input and eventually rule out one of the possible causes of present discrepancies between observation and model predictions. To this end, the neutron capture cross section of 154Gd was measured in a wide neutron energy range (from thermal up to some keV) with high resolution in the first experimental area of the neutron time-of-flight facility n_TOF (EAR1) at CERN. In this contribution, after a brief description of the motivation and of the experimental setup used in the measurement, the preliminary results of the 154Gd neutron capture reaction as well as their astrophysical implications are presented.
Monte Carlo simulations and n-p differential scattering data measured with Proton Recoil Telescopes
(2020)
The neutron-induced fission cross section of 235U, a standard at thermal energy and between 0.15 MeV and 200 MeV, plays a crucial role in nuclear technology applications. The long-standing need of improving cross section data above 20 MeV and the lack of experimental data above 200 MeV motivated a new experimental campaign at the n_TOF facility at CERN. The measurement has been performed in 2018 at the experimental area 1 (EAR1), located at 185 m from the neutron-producing target (the experiment is presented by A. Manna et al. in a contribution to this conference). The 235U(n,f) cross section from 20 MeV up to about 1 GeV has been measured relative to the 1H(n,n)1H reaction, which is considered the primary reference in this energy region. The neutron flux impinging on the 235U sample (a key quantity for determining the fission events) has been obtained by detecting recoil protons originating from n-p scattering in a C2H4 sample. Two Proton Recoil Telescopes (PRT), consisting of several layers of solid-state detectors and fast plastic scintillators, have been located at proton scattering angles of 25.07° and 20.32°, out of the neutron beam. The PRTs exploit the ΔE-E technique for particle identification, a basic requirement for the rejection of charged particles from neutron-induced reactions in carbon. Extensive Monte Carlo simulations were performed to characterize proton transport through the different slabs of silicon and scintillation detectors, to optimize the experimental set-up and to deduce the efficiency of the whole PRT detector. In this work we compare measured data collected with the PRTs with a full Monte Carlo simulation based on the Geant-4 toolkit.