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Bipolar disorder (BD) is a highly heritable neuropsychiatric disease characterized by recurrent episodes of mania and depression. BD shows substantial clinical and genetic overlap with other psychiatric disorders, in particular schizophrenia (SCZ). The genes underlying this etiological overlap remain largely unknown. A recent SCZ genome wide association study (GWAS) by the Psychiatric Genomics Consortium identified 128 independent genome-wide significant single nucleotide polymorphisms (SNPs). The present study investigated whether these SCZ-associated SNPs also contribute to BD development through the performance of association testing in a large BD GWAS dataset (9747 patients, 14278 controls). After re-imputation and correction for sample overlap, 22 of 107 investigated SCZ SNPs showed nominal association with BD. The number of shared SCZ-BD SNPs was significantly higher than expected (p = 1.46x10-8). This provides further evidence that SCZ-associated loci contribute to the development of BD. Two SNPs remained significant after Bonferroni correction. The most strongly associated SNP was located near TRANK1, which is a reported genome-wide significant risk gene for BD. Pathway analyses for all shared SCZ-BD SNPs revealed 25 nominally enriched gene-sets, which showed partial overlap in terms of the underlying genes. The enriched gene-sets included calcium- and glutamate signaling, neuropathic pain signaling in dorsal horn neurons, and calmodulin binding. The present data provide further insights into shared risk loci and disease-associated pathways for BD and SCZ. This may suggest new research directions for the treatment and prevention of these two major psychiatric disorders.
Intensive land use is a driving force for biodiversity decline in many ecosystems. In semi-natural grasslands, land-use activities such as mowing, grazing and fertilization affect the diversity of plants and arthropods, but the combined effects of different drivers and the chain of effects are largely unknown. In this study we used structural equation modelling to analyse how the arthropod communities in managed grasslands respond to land use and whether these responses are mediated through changes in resource diversity or resource quantity (biomass). Plants were considered resources for herbivores which themselves were considered resources for predators. Plant and arthropod (herbivores and predators) communities were sampled on 141 meadows, pastures and mown pastures within three regions in Germany in 2008 and 2009. Increasing land-use intensity generally increased plant biomass and decreased plant diversity, mainly through increasing fertilization. Herbivore diversity decreased together with plant diversity but showed no response to changes in plant biomass. Hence, land-use effects on herbivore diversity were mediated through resource diversity rather than quantity. Land-use effects on predator diversity were mediated by both herbivore diversity (resource diversity) and herbivore quantity (herbivore biomass), but indirect effects through resource quantity were stronger. Our findings highlight the importance of assessing both direct and indirect effects of land-use intensity and mode on different trophic levels. In addition to the overall effects, there were subtle differences between the different regions, pointing to the importance of regional land-use specificities. Our study underlines the commonly observed strong effect of grassland land use on biodiversity. It also highlights that mechanistic approaches help us to understand how different land-use modes affect biodiversity.
We report measurements of Xi and Xi-bar hyperon absolute yields as a function of rapidity in 158 GeV/c Pb+Pb collisions. At midrapidity, dN/dy = 2.29 +/- 0.12 for Xi, and 0.52 +/- 0.05 for Xi-bar, leading to the ratio of Xi-bar/Xi = 0.23 +/- 0.03. Inverse slope parameters fitted to the measured transverse mass spectra are of the order of 300 MeV near mid-rapidity. The estimated total yield of Xi particles in Pb+Pb central interactions amounts to 7.4 +/- 1.0 per collision. Comparison to Xi production in properly scaled p+p reactions at the same energy reveals a dramatic enhancement (about one order of magnitude) of Xi production in Pb+Pb central collisions over elementary hadron interactions.
The large acceptance TPCs of the NA49 spectrometer allow for a systematic multidimensional study of two-particle correlations in different part of phase space. Results from Bertsch-Pratt and Yano-Koonin-Podgoretskii parametrizations are presented differentially in transverse pair momentum and pair rapidity. These studies give an insight into the dynamical space-time evolution of relativistic Pb+Pb collisions, which is dominated by longitudinal expansion.
This report provides a brief review of the 20th annual meeting of the German Language Branch of the Society of Environmental Toxicology and Chemistry (SETAC GLB) held from September 7th to 10th 2015 at ETH (Swiss Technical University) in Zurich, Switzerland. The event was chaired by Inge Werner, Director of the Swiss Centre for Applied Ecotoxicology (Ecotox Centre) Eawag-EPFL, and organized by a team from Ecotox Centre, Eawag, Federal Office of the Environment, Federal Office of Agriculture, and Mesocosm GmbH (Germany). Over 200 delegates from academia, public agencies and private industry of Germany, Switzerland and Austria attended and discussed the current state of science and its application presented in 75 talks and 83 posters. In addition, three invited keynote speakers provided new insights into scientific knowledge ‘brokering’, and—as it was the International Year of Soil—the important role of healthy soil ecosystems. Awards were presented to young scientists for best oral and poster presentations, and for best 2014 master and doctoral theses. Program and abstracts of the meeting (mostly in German) are provided as Additional file 1.
Men and women differ substantially regarding height, weight, and body fat. Interestingly, previous work detecting genetic effects for waist-to-hip ratio, to assess body fat distribution, has found that many of these showed sex-differences. However, systematic searches for sex-differences in genetic effects have not yet been conducted. Therefore, we undertook a genome-wide search for sexually dimorphic genetic effects for anthropometric traits including 133,723 individuals in a large meta-analysis and followed promising variants in further 137,052 individuals, including a total of 94 studies. We identified seven loci with significant sex-difference including four previously established (near GRB14/COBLL1, LYPLAL1/SLC30A10, VEGFA, ADAMTS9) and three novel anthropometric trait loci (near MAP3K1, HSD17B4, PPARG), all of which were significant in women, but not in men. Of interest is that sex-difference was only observed for waist phenotypes, but not for height or body-mass-index. We found no evidence for sex-differences with opposite effect direction for men and women. The PPARG locus is of specific interest due to its link to diabetes genetics and therapy. Our findings demonstrate the importance of investigating sex differences, which may lead to a better understanding of disease mechanisms with a potential relevance to treatment options.
The current study tested the assumption that floristic and functional diversity patterns are negatively related to soil nitrogen content. We analyzed 20 plots with soil N-contents ranging from 0.63% to 1.06% in a deciduous forest near Munich (Germany). To describe species adaptation strategies to different nitrogen availabilities, we used a plant functional type (PFT) approach. Each identified PFT represents one realized adaptation strategy to the current environment. These were correlated, next to plant species richness and evenness, to soil nitrogen contents. We found that N-efficient species were typical for low soil nitrogen contents, while N-requiring species occur at high N-contents. In contrast to our initial hypotheses, floristic and functional diversity measures (number of PFTs) were positively related to nitrogen content in the soil. Every functional group has its own adaptation to the prevailing environmental conditions; in consequence, these functional groups can co-exist but do not out-compete one another. The increased number of functional groups at high N-contents leads to increased species richness. Hence, for explaining diversity patterns we need to consider species groups representing different adaptations to the current environmental conditions. Such co-existing ecological strategies may even overcome the importance of competition in their effect on biodiversity.
Planar cell polarity (PCP)–the coordinated polarisation of a whole field of cells within the plane of a tissue–relies on the interaction of three modules: a global module that couples individual cellular polarity to the tissue axis, a local module that aligns the axis of polarisation of neighbouring cells, and a readout module that directs the correct outgrowth of PCP-regulated structures such as hairs and bristles. While much is known about the molecular components that are required for PCP, the functional details of–and interactions between–the modules remain unclear. In this work, we perform a mathematical and computational analysis of two previously proposed computational models of the local module (Amonlirdviman et al., Science, 307, 2005; Le Garrec et al., Dev. Dyn., 235, 2006). Both models can reproduce wild-type and mutant phenotypes of PCP observed in the Drosophila wing under the assumption that a tissue-wide polarity cue from the global module persists throughout the development of PCP. We demonstrate that both models can also generate tissue-level PCP when provided with only a transient initial polarity cue. However, in these models such transient cues are not sufficient to ensure robustness of the resulting cellular polarisation.
The vast majority of European grasslands strongly depend on the regular removal of aboveground biomass by agricultural land use, mostly grazing or mowing or a combination of both. These specific management schemes have strong influence on plant diversity and vegetation composition, depending on their particular characteristics and their intensity. For example, the presence or absence of fertilization will favour some species over others, changing plant communities accordingly. Additionally, the farmer’s choice of a specific management scheme will also depend on the abiotic site conditions. This leads to a complex set of associated factors potentially affecting the structure and diversity of grasslands.
In this study, we compiled a unique dataset of 169 differently managed grasslands (in total 202 plots), which were sampled in five regions across Germany. For each plot, we documented management characteristics, measured plant diversity and functional group composition, recorded endangered species according to red lists, and calculated Ellenberg indicator values. We assessed patterns in vegetation composition and diversity in relation to the particular management scheme, which was categorized as meadow, meadow with autumn or winter grazing (with mowing as predominant management), mown pasture (where mowing and grazing are used at roughly equal intensity), seasonal pasture (with grazing as predominant management) and year-round pasture.
Our study showed that grasslands of different management schemes significantly differed in diversity, structure and functional composition. However, it also became obvious that vegetation composition was not strictly distinguished by management alone. Local and regional characteristics such as soil conditions, size of the grassland species pool or land-use history, often played a more prominent role than land use alone. Assumingly, the interplay of those local and regional characteristics with the proportion of grazing and mowing at a particular site inhibit clear differences among our predefined management schemes. Nevertheless, species richness was the lowest in year-round pastures, moderate in meadows and highest in seasonal pastures. In contrast, year-round pastures harboured the highest mean numbers of endangered species. The dependency of a certain management scheme on site-specific environmental factors such as soil fertility, further complicated the clear separation of management effects from those of the environmental background. In summary, modern grassland management strongly shaped grassland vegetation, but today’s combination of different management practices complicated the assessment of specific land-use effects on plant diversity. Thus, neither mowing nor grazing turned out to be “the one and only” management for nature conservation. Although our results challenge long-term prognoses for future vegetation development under modern grassland management, we clearly showed that low-intensity management and the absence of fertilization promoted plant diversity, with higher values in pastures compared to meadows and mown pastures.
Mountains, with their isolated position and altitudinal belts, are hotspots of biodiversity. Their flora and fauna have been observed worldwide since the days of Alexander von Humboldt, which has led to basic knowledge and understanding of species composition and the most important driving forces of ecosystem differentiation in such altitudinal gradients. Systematically designed analyses of changes in species composition with increasing elevation have been increasingly implemented since the 1990s. Since global climate change is one of the most important problems facing the world this century, a focus on such ecosystem studies is urgently needed. To identify the main future needs of such research we analyze the studies dealing with species changes of diverse taxonomical groups along altitudinal gradients (0 to 6,400 m a.s. l.) on all continents, published during the past one to two decades. From our study we can conclude that although mountains are powerful for climate change research most studies have to face the challenge of separating confounding effects driving species assemblages along altitudinal gradients. Our study therefore supports the view of the need of a global altitudinal concept including that (1) not only one or a few taxonomical groups should be analyzed, but rather different taxonomical groups covering all ecosystem functions simultaneously; (2) relevant site conditions should be registered to reveal direct environmental variables responsible for species distribution patterns and to resolve inconsistent effects along the altitudinal gradients; (3) transect design is appropriate for analyzing ecosystem changes in site gradients and over time; (4) both the study design and the individual methods should be standardized to compare the data collected worldwide; and (5) a long-term perspective is important to quantify the degree and direction of species changes and to validate species distribution models. (6) Finally we suggest to develop experimental altitudinal approaches to overcome the addressed problems of biodiversity surveys.
TRADITIONALLY, THE COST OF DEBT IS SOLELY SEEN DEPENDENT ON FIRM OR DEBT CHARACTERISTICS. HOWEVER, INCREASED PRICE TRANSPARENCY AS CAN BE FOUND IN THE U.S. CORPORATE BOND MARKET HAS REDUCED CORPORATE BOND YIELDS. THE OBJECTIVE OF THIS WORK IS TO MEASURE THE SPILL-OVER EFFECT OF INCREASED PRICE TRANSPARENCY IN CORPORATE BONDS ON THE COST OF CORPORATE BORROWING OF SYNDICATED LOANS BY MAKING USE OF A NATURAL EXPERIMENT, I.E., THE INTRODUCTION OF THE TRACE SYSTEM FOR BONDS.
Two-particle correlation functions of negative hadrons over wide phase space, and transverse mass spectra of negative hadrons and deuterons near mid-rapidity have been measured in central Pb+Pb collisions at 158 GeV per nucleon by the NA49 experiment at the CERN SPS. A novel Coulomb correction procedure for the negative two-particle correlations is employed making use of the measured oppositely charged particle correlation. Within an expanding source scenario these results are used to extract the dynamic characteristics of the hadronic source, resolving the ambiguities between the temperature and transverse expansion velocity of the source, that are unavoidable when single and two particle spectra are analysed separately. The source shape, the total duration of the source expansion, the duration of particle emission, the freeze-out temperature and the longitudinal and transverse expansion velocities are deduced.
We have developed and characterized the novel PTR3, a proton transfer reaction-time-of-flight mass spectrometer (PTR-TOF) using a new gas inlet and an innovative reaction chamber design. The reaction chamber consists of a tripole operated with rf voltages generating an electric field only in the radial direction. An elevated electrical field is necessary to reduce clustering of primary hydronium (H3O+) and product ions with water molecules present in the sample gas. The axial movement of the ions is achieved by the sample gas flow only. Therefore, the new design allows a 30-fold longer reaction time and a 40-fold increase in pressure compared to standard PTR-TOF-MS. First calibration tests show sensitivities of up to 18000 counts per second/parts per billion and volume (cps/ppbv) at a mass resolution of >8000 m/Δm (fwhm). The new inlet using center-sampling through a critical orifice reduces wall losses of low volatility compounds. Therefore, the new PTR3 instrument is sensitive to VOC typically present in the ppbv range as well as to semivolatile organic compounds (SVOC) and even highly oxidized organic molecules (HOMs) present in the parts per quadrillion per volume (ppqv) range in the atmosphere.
Consensus on definition and severity grading of lymphatic complications after kidney transplantation
(2020)
Background: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy.
Methods: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres.
Results: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention.
Conclusion: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.
Apheresis therapies for NMOSD attacks : a retrospective study of 207 therapeutic interventions
(2018)
Objective: To analyze whether 1 of the 2 apheresis techniques, therapeutic plasma exchange (PE) or immunoadsorption (IA), is superior in treating neuromyelitis optica spectrum disorder (NMOSD) attacks and to identify predictive factors for complete remission (CR).
Methods: This retrospective cohort study was based on the registry of the German Neuromyelitis Optica Study Group, a nationwide network established in 2008. It recruited patients with neuromyelitis optica diagnosed according to the 2006 Wingerchuk criteria or with aquaporin-4 (AQP4-ab)-antibody–seropositive NMOSD treated at 6 regional hospitals and 16 tertiary referral centers until March 2013. Besides descriptive data analysis of patient and attack characteristics, generalized estimation equation (GEE) analyses were applied to compare the effectiveness of the 2 apheresis techniques. A GEE model was generated to assess predictors of outcome.
Results: Two hundred and seven attacks in 105 patients (87% AQP4-ab-antibody seropositive) were treated with at least 1 apheresis therapy. Neither PE nor IA was proven superior in the therapy of NMOSD attacks. CR was only achieved with early apheresis therapy. Strong predictors for CR were the use of apheresis therapy as first-line therapy (OR 12.27, 95% CI: 1.04–144.91, p = 0.047), time from onset of attack to start of therapy in days (OR 0.94, 95% CI: 0.89–0.99, p = 0.014), the presence of AQP4-ab-antibodies (OR 33.34, 95% CI: 1.76–631.17, p = 0.019), and monofocal attack manifestation (OR 4.71, 95% CI: 1.03–21.62, p = 0.046).
Conclusions: Our findings suggest early use of an apheresis therapy in NMOSD attacks, particularly in AQP4-ab-seropositive patients. No superiority was shown for one of the 2 apheresis techniques.
Classification of evidence: This study provides Class IV evidence that for patients with NMOSD, neither PE nor IA is superior in the treatment of attacks.
Nucleation and growth of aerosol particles from atmospheric vapors constitutes a major source of global cloud condensation nuclei (CCN). The fraction of newly formed particles that reaches CCN sizes is highly sensitive to particle growth rates, especially for particle sizes <10 nm, where coagulation losses to larger aerosol particles are greatest. Recent results show that some oxidation products from biogenic volatile organic compounds are major contributors to particle formation and initial growth. However, whether oxidized organics contribute to particle growth over the broad span of tropospheric temperatures remains an open question, and quantitative mass balance for organic growth has yet to be demonstrated at any temperature. Here, in experiments performed under atmospheric conditions in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN), we show that rapid growth of organic particles occurs over the range from −25 ∘C to 25 ∘C. The lower extent of autoxidation at reduced temperatures is compensated by the decreased volatility of all oxidized molecules. This is confirmed by particle-phase composition measurements, showing enhanced uptake of relatively less oxygenated products at cold temperatures. We can reproduce the measured growth rates using an aerosol growth model based entirely on the experimentally measured gas-phase spectra of oxidized organic molecules obtained from two complementary mass spectrometers. We show that the growth rates are sensitive to particle curvature, explaining widespread atmospheric observations that particle growth rates increase in the single-digit-nanometer size range. Our results demonstrate that organic vapors can contribute to particle growth over a wide range of tropospheric temperatures from molecular cluster sizes onward.
Hugo von Hofmannsthal wird nicht müde, in seinem Essay über Victor Eftimiu die Doppelheit des "lateinisch-slawische[n] Wesen[s]" zu betonen: "[D]er Rumäne ist Lateiner und Slawe zugleich." In ihren Ausführungen zur Hofmannsthal-Rezeption in Rumänien bescheinigt die rumänische Germanistin Mariana-Virginia Lazarescu dem österreichischen Dichter eine "genaue Kenntnis des rumänischen Lebensgefühls, der rumänischen Seelen- und Mythenlandschaft und der rumänischen Volksüberlieferungen". Repräsentiert die Latinität bei Hugo von Hofmannsthal also die kulturelle, europäische, ja vielleicht sogar die universale Perspektive, so stehen das Slawische und das Walachische, die jedoch um andere und weitere Volkselemente beliebig zu ergänzen wären, für die partikulare landschafts-, heimat- und volksbezogene Dimension. Dennoch lassen sich bei Hugo von Hofmannsthal auch in dieser letztgenannten Dimension universale Perspektiven erblicken. So spricht er etwa in seinem Geleitwort zu einer Sammlung von Übersetzungen tschechischer und slowakischer Volkslieder von "dem ewig Gleichen und der beharrenden Wurzel" der Volksüberlieferung, der er zugleich eine religiöse Dimension zuspricht. So wie Hofmannsthal bzw. Borchardt im Europabegriff der Renaissance die "Gemeinbürgschaft aller an der Latinität der höheren geistigen Existenz beteiligten für Erweckung und Bewahrung dieses grundlegenden Erbes" sahen, so war Hugo von Hofmannsthals Europabegriff während und in der Zeit nach dem Ersten Weltkrieg von der Idee des Ineinanderklingens der zahlreichen volkshaften und sozialen Partikularismen geprägt.
Two main types of sentences are traditionally distinguished in the context of semantic theories of questions and answers: declarative sentences, corresponding to statements, and interrogative sentences, corresponding to questions. The interrogative forms can be further subdivided into dialectical ones (yes-no-questions) and non-dialectical ones (constituent questions). These distinctions are made for both root and embedded sentences. The predicates that select sentential complements fall into three classes: predicates that license only declaratives, those that allow only for interrogatives, and those that embed both types of sentences. In this connection, verbs of doubt are interesting in that they allow for declaratives as well as dialectical interrogatives, while non-dialectical interrogatives do not seem to be appropriate complements.
In what follows, our main concern will be with the German verb of doubt zweifeln and its possible sentential complements. Speaker intuitions as to which constructions are grammatical or acceptable vary, particularily with respect to rare expressions like zweifeln. Therefore, interviews and corpus analysis were applied as a means to acquire reliable linguistic data. These as well as data from historical sources and from some languages other than German (esp. English and Italian) are presented and analysed. In the last section, based on the notion of ‘subjective probability’, an attempt is made at explaining the observations.
The present contribution deals with the three most recent novels of the Romanian-born Swiss Author Catalin Dorian Florescu: Zaira [Zaira] (2008), Jacob beschließt zu lieben [Jacob Decides to Love] (2011) and Der Mann, der das Glück bringt [The Man who Brings Happiness] (2016). The author unfolds in these novels family sagas spanning centuries which make the destiny of migrants between the poles of east and west a subject of discussion. In contrast to Florescu’s three former novels the reader can detect in these family novels the tendency towards a folkloristic presentation of a multicultural ambience at the expense of an intercultural involvement in the narrative depiction.
According to Arthur Rimbaud’s famous saying “Je est un autre” Max Frisch develops in his early diaries an idea of love which has to orient itself by the ban on images in the Old Testament and which, as a modern concept, has to renounce every image of oneself and the other at all. In Max Frisch’s novel Stiller the roots of this seemingly biblical belief can be found both in an aesthetic attitude towards life (as pointed out in Sören Kierkegaardʼs scriptures, especially in Entweder-Oder) and in an existentialist understanding of life (as set forth in the philosophical work of Jean-Paul Sartre). Max Frisch’s novel Stiller can be read as a literary experiment of achieving the ultimate goal of love and self-acceptance by radical self-negation and negation of the other.