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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.
Bipolar disorder (BD) is a major psychiatric illness affecting around 1% of the global population. BD is characterized by recurrent manic and depressive episodes, and has an estimated heritability of around 70%. Research has identified the first BD susceptibility genes. However, the underlying pathways and regulatory networks remain largely unknown. Research suggests that the cumulative impact of common alleles with small effects explains only around 25–38% of the phenotypic variance for BD. A plausible hypothesis therefore is that rare, high penetrance variants may contribute to BD risk. The present study investigated the role of rare, nonsynonymous, and potentially functional variants via whole exome sequencing in 15 BD cases from two large, multiply affected families from Cuba. The high prevalence of BD in these pedigrees renders them promising in terms of the identification of genetic risk variants with large effect sizes. In addition, SNP array data were used to calculate polygenic risk scores for affected and unaffected family members. After correction for multiple testing, no significant increase in polygenic risk scores for common, BD-associated genetic variants was found in BD cases compared to healthy relatives. Exome sequencing identified a total of 17 rare and potentially damaging variants in 17 genes. The identified variants were shared by all investigated BD cases in the respective pedigree. The most promising variant was located in the gene SERPING1 (p.L349F), which has been reported previously as a genome-wide significant risk gene for schizophrenia. The present data suggest novel candidate genes for BD susceptibility, and may facilitate the discovery of disease-relevant pathways and regulatory networks.
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.
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.
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.
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.
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.
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.