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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.
We present measurements of exclusive ensuremathπ+,0 and η production in pp reactions at 1.25GeV and 2.2GeV beam kinetic energy in hadron and dielectron channels. In the case of π+ and π0 , high-statistics invariant-mass and angular distributions are obtained within the HADES acceptance as well as acceptance-corrected distributions, which are compared to a resonance model. The sensitivity of the data to the yield and production angular distribution of Δ (1232) and higher-lying baryon resonances is shown, and an improved parameterization is proposed. The extracted cross-sections are of special interest in the case of pp → pp η , since controversial data exist at 2.0GeV; we find \ensuremathσ=0.142±0.022 mb. Using the dielectron channels, the π0 and η Dalitz decay signals are reconstructed with yields fully consistent with the hadronic channels. The electron invariant masses and acceptance-corrected helicity angle distributions are found in good agreement with model predictions.
Background & Aims: Spontaneous portosystemic shunts (SPSS) frequently develop in liver cirrhosis. Recent data suggested that the presence of a single large SPSS is associated with complications, especially overt hepatic encephalopathy (oHE). However, the presence of >1 SPSS is common. This study evaluates the impact of total cross-sectional SPSS area (TSA) on outcomes in patients with liver cirrhosis.
Methods: In this retrospective international multicentric study, CT scans of 908 cirrhotic patients with SPSS were evaluated for TSA. Clinical and laboratory data were recorded. Each detected SPSS radius was measured and TSA calculated. One-year survival was the primary endpoint and acute decompensation (oHE, variceal bleeding, ascites) was the secondary endpoint.
Results: A total of 301 patients (169 male) were included in the training cohort. Thirty percent of all patients presented with >1 SPSS. A TSA cut-off of 83 mm2 was used to classify patients with small or large TSA (S-/L-TSA). Patients with L-TSA presented with higher model for end-stage liver disease score (11 vs. 14) and more commonly had a history of oHE (12% vs. 21%, p <0.05). During follow-up, patients with L-TSA experienced more oHE episodes (33% vs. 47%, p <0.05) and had lower 1-year survival than those with S-TSA (84% vs. 69%, p <0.001). Multivariate analysis identified L-TSA (hazard ratio 1.66; 95% CI 1.02–2.70, p <0.05) as an independent predictor of mortality. An independent multicentric validation cohort of 607 patients confirmed that patients with L-TSA had lower 1-year survival (77% vs. 64%, p <0.001) and more oHE development (35% vs. 49%, p <0.001) than those with S-TSA.
Conclusion: This study suggests that TSA >83 mm2 increases the risk for oHE and mortality in patients with cirrhosis. Our results support the clinical use of TSA/SPSS for risk stratification and decision-making in the management of patients with cirrhosis.
Lay summary: The prevalence of spontaneous portosystemic shunts (SPSS) is higher in patients with more advanced chronic liver disease. The presence of more than 1 SPSS is common in advanced chronic liver disease and is associated with the development of hepatic encephalopathy. This study shows that total cross-sectional SPSS area (rather than diameter of the single largest SPSS) predicts survival in patients with advanced chronic liver disease. Our results support the clinical use of total cross-sectional SPSS area for risk stratification and decision-making in the management of SPSS.
Background Reward processing has been proposed to underpin atypical social behavior, a core feature of autism spectrum disorder (ASD). However, previous neuroimaging studies have yielded inconsistent results regarding the specificity of atypicalities for social rewards in ASD. Utilizing a large sample, we aimed to assess altered reward processing in response to reward type (social, monetary) and reward phase (anticipation, delivery) in ASD.
Methods Functional magnetic resonance imaging during social and monetary reward anticipation and delivery was performed in 212 individuals with ASD (7.6-30.5 years) and 181 typically developing (TD) participants (7.6-30.8 years).
Results Across social and monetary reward anticipation, whole-brain analyses (p<0.05, family-wise error-corrected) showed hypoactivation of the right ventral striatum (VS) in ASD. Further, region of interest (ROI) analysis across both reward types yielded hypoactivation in ASD in both the left and right VS. Across delivery of social and monetary reward, hyperactivation of the VS in individuals with ASD did not survive correction for multiple comparisons. Reward type by diagnostic group interactions, and a dimensional analysis of autism trait scores were not significant during anticipation or delivery. Levels of attention-deficit/hyperactivity disorder (ADHD) symptoms did not affect reward processing in ASD.
Conclusions Our results do not support current theories linking atypical social interaction in ASD to specific alterations in processing of social rewards. Instead, they point towards a generalized hypoactivity of VS in ASD during anticipation of both social and monetary rewards. We suggest that this indicates attenuated subjective reward value in ASD independent of social content and ADHD symptoms.
Abrasion-ablation models and the empirical EPAX parametrization of projectile fragmentation are described. Their cross section predictions are compared to recent data of the fragmentation of secondary beams of neutron-rich, unstable 19,20,21O isotopes at beam energies near 600 MeV/nucleon as well as data for stable 17,18O beams.
Archaeological evidence indicates that pig domestication had begun by ∼10,500 y before the present (BP) in the Near East, and mitochondrial DNA (mtDNA) suggests that pigs arrived in Europe alongside farmers ∼8,500 y BP. A few thousand years after the introduction of Near Eastern pigs into Europe, however, their characteristic mtDNA signature disappeared and was replaced by haplotypes associated with European wild boars. This turnover could be accounted for by substantial gene flow from local European wild boars, although it is also possible that European wild boars were domesticated independently without any genetic contribution from the Near East. To test these hypotheses, we obtained mtDNA sequences from 2,099 modern and ancient pig samples and 63 nuclear ancient genomes from Near Eastern and European pigs. Our analyses revealed that European domestic pigs dating from 7,100 to 6,000 y BP possessed both Near Eastern and European nuclear ancestry, while later pigs possessed no more than 4% Near Eastern ancestry, indicating that gene flow from European wild boars resulted in a near-complete disappearance of Near East ancestry. In addition, we demonstrate that a variant at a locus encoding black coat color likely originated in the Near East and persisted in European pigs. Altogether, our results indicate that while pigs were not independently domesticated in Europe, the vast majority of human-mediated selection over the past 5,000 y focused on the genomic fraction derived from the European wild boars, and not on the fraction that was selected by early Neolithic farmers over the first 2,500 y of the domestication process.
Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASDs), the contribution of common variation to the risk of developing ASD is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating the association of individual single nucleotide polymorphisms (SNPs), we also sought evidence that common variants, en masse, might affect the risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest P-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. In contrast, allele scores derived from the transmission of common alleles to Stage 1 cases significantly predict case status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele score results, it is reasonable to conclude that common variants affect the risk for ASD but their individual effects are modest.
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
The proton drip-line nucleus 17Ne is investigated experimentally in order to determine its two-proton halo character. A fully exclusive measurement of the 17Ne(p, 2p)16F∗ →15O+p quasi-free one-proton knockout reaction has been performed at GSI at around 500 MeV/nucleon beam energy. All particles resulting from the scattering process have been detected. The relevant reconstructed quantities are the angles of the two protons scattered in quasi-elastic kinematics, the decay of 16F into 15O (including γ decays from excited states) and a proton, as well as the 15O+p relative-energy spectrum and the 16F momentum distributions. The latter two quantities allow an independent and consistent determination of the fractions of l = 0 and l = 2 motion of the valence protons in 17Ne. With a resulting relatively small l = 0 component of only around 35(3)%, it is concluded that 17Ne exhibits a rather modest halo character only. The quantitative agreement of the two values deduced from the energy spectrum and the momentum distributions supports the theoretical treatment of the calculation of momentum distributions after quasi-free knockout reactions at high energies by taking into account distortions based on the Glauber theory. Moreover, the experimental data allow the separation of valence-proton knockout and knockout from the 15O core. The latter process contributes with 11.8(3.1) mb around 40% to the total proton-knockout cross section of 30.3(2.3) mb, which explains previously reported contradicting conclusions derived from inclusive cross sections.
The evolution of the traditional nuclear magic numbers away from the valley of stability is an active field of research. Experimental efforts focus on providing key spectroscopic information that will shed light into the structure of exotic nuclei and understanding the driving mechanism behind the shell evolution. In this work, we investigate the spin-orbit shell gap towards the neutron dripline. To do so, we employed (p,2p) quasi-free scattering reactions to measure the proton component of the state of 16,18,20C. The experimental findings support the notion of a moderate reduction of the proton spin-orbit splitting, at variance to recent claims for a prevalent magic number towards the neutron dripline.
New experimental data for dissociation of relativistic 17Ne projectiles incident on targets of lead, carbon, and polyethylene targets at GSI are presented. Special attention is paid to the excitation and decay of narrow resonant states in 17Ne. Distributions of internal energy in the three-body system have been determined together with angular and partial-energy correlations between the decay products in different energy regions. The analysis was done using existing experimental data on 17Ne and its mirror nucleus 17N. The isobaric multiplet mass equation is used for assignment of observed resonances and their spins and parities. A combination of data from the heavy and light targets yielded cross sections and transition probabilities for the Coulomb excitations of the narrow resonant states. The resulting transition probabilities provide information relevant for a better understanding of the 17Ne structure.
Under certain conditions, secondary organic aerosol (SOA) particles can exist in the atmosphere in an amorphous solid or semi-solid state. To determine their relevance to processes such as ice nucleation or chemistry occurring within particles requires knowledge of the temperature and relative humidity (RH) range for SOA to exist in these states. In the Cosmics Leaving Outdoor Droplets (CLOUD) experiment at The European Organisation for Nuclear Research (CERN), we deployed a new in situ optical method to detect the viscous state of α-pinene SOA particles and measured their transition from the amorphous highly viscous state to states of lower viscosity. The method is based on the depolarising properties of laboratory-produced non-spherical SOA particles and their transformation to non-depolarising spherical particles at relative humidities near the deliquescence point. We found that particles formed and grown in the chamber developed an asymmetric shape through coagulation. A transition to a spherical shape was observed as the RH was increased to between 35 % at −10 °C and 80 % at −38 °C, confirming previous calculations of the viscosity-transition conditions. Consequently, α-pinene SOA particles exist in a viscous state over a wide range of ambient conditions, including the cirrus region of the free troposphere. This has implications for the physical, chemical, and ice-nucleation properties of SOA and SOA-coated particles in the atmosphere.
Under certain conditions, secondary organic aerosol (SOA) particles can exist in the atmosphere in an amorphous solid or semi-solid state. To determine their relevance to processes such as ice nucleation or chemistry occurring within particles requires knowledge of the temperature and relative humidity (RH) range for SOA to exist in these states. In the CLOUD experiment at CERN, we deployed a new in-situ optical method to detect the viscosity of α-pinene SOA particles and measured their transition from the amorphous viscous to liquid state. The method is based on the depolarising properties of laboratory-produced non-spherical SOA particles and their transformation to non-depolarising spherical liquid particles during deliquescence. We found that particles formed and grown in the chamber developed an asymmetric shape through coagulation. A transition to spherical shape was observed as the RH was increased to between 35 % at −10 ◦C and 80 % at −38 ◦C, confirming previous calculations of the viscosity transition conditions. Consequently, α-pinene SOA particles exist in a viscous state over a wide range of ambient conditions, including the cirrus region of the free troposphere. This has implications for the physical, chemical and ice-nucleation properties of SOA and SOA-coated particles in the atmosphere.
The radiative electron capture (REC) into the K shell of bare Xe ions colliding with a hydrogen gas target has been investigated. In this study, the degree of linear polarization of the K-REC radiation was measured and compared with rigorous relativistic calculations as well as with the previous results recorded for U92+. Owing to the improved detector technology, a significant gain in precision of the present polarization measurement is achieved compared to the previously published results. The obtained data confirms that for medium-Z ions such as Xe, the REC process is a source of highly polarized x rays which can easily be tuned with respect to the degree of linear polarization and the photon energy. We argue, in particular, that for relatively low energies the photons emitted under large angles are almost fully linear polarized.
Die Bestände des in Deutschland stark gefährdeten Sand-Zwerggrases Mibora minima, für deren Erhalt das Land Hessen eine besondere Verantwortung trägt, gehen seit vielen Jahren zurück. In dieser Arbeit wurden als Beitrag zum Artenhilfsprogramm der Botanischen Vereinigung für Naturschutz in Hessen (BVNH) die noch vorhandenen Populationen erfasst sowie die botanischen und edaphischen Gegebenheiten an den Standorten untersucht. Dabei wurde durch Vergleich von Flächen mit und ohne Bewuchs des Zwerggrases der Frage nachgegangen, ob und inwieweit die Verbreitung der Art durch die Beschaffenheit und Nährstoffversorgung des Bodens bestimmt wird. Es wurde ein weiterer deutlicher Rückgang der südhessischen Populationen um etwa 60 % seit 1999 festgestellt, der am stärksten die Standorte um Mörfelden-Walldorf betrifft. Dagegen haben sich die Bestände bei Rüsselsheim-Königstädten möglicherweise durch Pflegemaßnahmen stabilisiert. Ein bestimmender Einfluss edaphischer Parameter auf die Verteilung der Art innerhalb der kalkfreien Flugsande konnte nicht festgestellt werden. Der indigene floristische Status der Art wird in Frage gestellt und stattdessen ihre Einstufung als Epökophyt westmediterraner Herkunft angenommen.
Background: To identify variables predicting outcome in neuroblastoma patients assigned to the high-risk group solely by the presence of MYCN oncogene amplification (MNA). Methods: Clinical characteristics, genomic information, and outcome of 190 patients solely assigned to high-risk neuroblastoma by MNA were analyzed and compared to 205 patients with stage 4 neuroblastoma aged ≥18 months with MNA (control group). Results: Event-free survival (EFS) and overall survival (OS) at 10 years were 47% (95%-CI 39–54%) and 56% (95%-CI 49–63%), respectively, which was significantly better than EFS and OS of the control group (EFS 25%, 95%-CI 18–31%, p < 0.001; OS 32% 95%-CI 25–39%, p < 0.001). The presence of RAS-/p53-pathway gene alterations was associated with impaired 10-year EFS and OS (19% vs. 55%, and 19% vs. 67%, respectively; both p < 0.001). In time-dependent multivariable analyses, alterations of RAS-/p53-pathway genes and the extent of the best primary tumor resection were the only independent prognostic variables for OS (p < 0.001 and p = 0.011, respectively). Conclusions: Neuroblastoma patients attributed to high risk solely by MYCN amplification have generally a more favorable outcome. Mutations of genes of the RAS and/or p53 pathways and incomplete resection are the main risk factors predicting poor outcome.
Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to >3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.
As new generations of targeted therapies emerge and tumor genome sequencing discovers increasingly comprehensive mutation repertoires, the functional relationships of mutations to tumor phenotypes remain largely unknown. Here, we measured ex vivo sensitivity of 246 blood cancers to 63 drugs alongside genome, transcriptome, and DNA methylome analysis to understand determinants of drug response. We assembled a primary blood cancer cell encyclopedia data set that revealed disease-specific sensitivities for each cancer. Within chronic lymphocytic leukemia (CLL), responses to 62% of drugs were associated with 2 or more mutations, and linked the B cell receptor (BCR) pathway to trisomy 12, an important driver of CLL. Based on drug responses, the disease could be organized into phenotypic subgroups characterized by exploitable dependencies on BCR, mTOR, or MEK signaling and associated with mutations, gene expression, and DNA methylation. Fourteen percent of CLLs were driven by mTOR signaling in a non–BCR-dependent manner. Multivariate modeling revealed immunoglobulin heavy chain variable gene (IGHV) mutation status and trisomy 12 as the most important modulators of response to kinase inhibitors in CLL. Ex vivo drug responses were associated with outcome. This study overcomes the perception that most mutations do not influence drug response of cancer, and points to an updated approach to understanding tumor biology, with implications for biomarker discovery and cancer care.
Correction to: Nature Communications https://doi.org/10.1038/s41467-017-01045-x, published online 31 October 2017
It has come to our attention that we did not specify whether the stimulation magnitudes we report in this Article are peak amplitudes or peak-to-peak. All references to intensity given in mA in the manuscript refer to peak-to-peak amplitudes, except in Fig. 2, where the model is calibrated to 1 mA peak amplitude, as stated. In the original version of the paper we incorrectly calibrated the computational models to 1 mA peak-to-peak, rather than 1 mA peak amplitude. This means that we divided by a value twice as large as we should have. The correct estimated fields are therefore twice as large as shown in the original Fig. 2 and Supplementary Fig. 11. The corrected figures are now properly calibrated to 1mA peak amplitude. Furthermore, the sentence in the first paragraph of the Results section ‘Intensity ranged from 0.5 to 2.5 mA (current density 0.125–0.625 mA mA/cm2), which is stronger than in previous reports’, should have read ‘Intensity ranged from 0.5 to 2.5 mA peak to peak (peak current density 0.0625–0.3125 mA/cm2), which is stronger than in previous reports.’ These errors do not affect any of the Article’s conclusions. Correct versions of Fig. 2 and Supplementary Fig. 11 are presented below as Figs. 1, 2.