Peri-interventional combined anticoagulation and antithrombotic therapy in atrial fibrillation ablation: A retrospective safety analysis

   Background: Catheter ablation (CA) of atrial fibrillation (AF) requires an intensified peri-inter­ventional anticoagulation scheme to avoid thromboembolic complications. In patients with cardiac or extracardiac artery disease, an additional antiplatelet treatment (AAT) is at least temporally necessary especially after a percutaneous intervention with stent implantation. This raises the question whether these patients have a higher peri-interventional bleeding risk during CA of AF. Methods: The data of 1235 patients with CA of AF were retrospectively analyzed in terms of bleeding events, ablation type, antithrombotic medication and comorbidities such as coronary artery disease and components of the HAS- BLED score. Peri-interventional bleeding events were classified in accordance with the BARC classification. Differentiations were made between slight femoral bleeding (based on type 1), severe femoral bleeding and pericardial effusion without pericardiocentesis (based on type 2) with the need of further hospitalization, the need of transfusion (based on type 3a) and pericardial tamponades requiring pericardiocentesis (based on type 3b). Results: 1131/1235 (91.6%) patients were exclusively under anticoagulation and 187 (15.3%) patients were also on AAT. There were no statistically significant differences in type 1 and 3b bleeding complica­tions or the occurrence of femoral pseudoaneurysms between both groups. However, type 2/3a bleeding complications, mostly femoral bleedings, were significantly more frequent in the patient group with AAT (3.2% vs. 7.5%, p = 0.006). Conclusions: An additional antiplatelet therapy increases the risk of severe femoral bleeding events during CA of AF. It appears reasonable to perform the elective procedure of AF ablation after the dis­continuation of AAT.

Haloquadratum walsbyi : Limited Diversity in a Global Pond

BACKGROUND: Haloquadratum walsbyi commonly dominates the microbial flora of hypersaline waters. Its cells are extremely fragile squares requiring >14%(w/v) salt for growth, properties that should limit its dispersal and promote geographical isolation and divergence. To assess this, the genome sequences of two isolates recovered from sites at near maximum distance on Earth, were compared. PRINCIPAL FINDINGS: Both chromosomes are 3.1 MB in size, and 84% of each sequence was highly similar to the other (98.6% identity), comprising the core sequence. ORFs of this shared sequence were completely synteneic (conserved in genomic orientation and order), without inversion or rearrangement. Strain-specific insertions/deletions could be precisely mapped, often allowing the genetic events to be inferred. Many inferred deletions were associated with short direct repeats (4-20 bp). Deletion-coupled insertions are frequent, producing different sequences at identical positions. In cases where the inserted and deleted sequences are homologous, this leads to variant genes in a common synteneic background (as already described by others). Cas/CRISPR systems are present in C23(T) but have been lost in HBSQ001 except for a few spacer remnants. Numerous types of mobile genetic elements occur in both strains, most of which appear to be active, and with some specifically targetting others. Strain C23(T) carries two ∼6 kb plasmids that show similarity to halovirus His1 and to sequences nearby halovirus/plasmid gene clusters commonly found in haloarchaea. CONCLUSIONS: Deletion-coupled insertions show that Hqr. walsbyi evolves by uptake and precise integration of foreign DNA, probably originating from close relatives. Change is also driven by mobile genetic elements but these do not by themselves explain the atypically low gene coding density found in this species. The remarkable genome conservation despite the presence of active systems for genome rearrangement implies both an efficient global dispersal system, and a high selective fitness for this species

München als 8. bayerischer Regierungsbezirk?! Überlegungen und Vorschläge zu einer Verwaltungsstrukturreform auf der mittleren staatlichen Ebene in Oberbayern

Im vorliegenden Positionspapier geht es um die Abgrenzung der Großstadtregion München sowie die Teilung des Regierungsbezirks Oberbayern vor dem Hintergrund der Optimierung des Verwaltungshandelns in den aktuellen Aufgabenbereichen einer Regierung in Bayern

Edge-Graph Diameter Bounds for Convex Polytopes with Few Facets

We show that the edge graph of a 6-dimensional polytope with 12 facets has diameter at most 6, thus verifying the d-step conjecture of Klee and Walkup in the case of d=6. This implies that for all pairs (d,n) with n-d \leq 6 the diameter of the edge graph of a d-polytope with n facets is bounded by 6, which proves the Hirsch conjecture for all n-d \leq 6. We show this result by showing this bound for a more general structure -- so-called matroid polytopes -- by reduction to a small number of satisfiability problems.Comment: 9 pages; update shortcut constraint discussio

Evaluation der Experimentierklausel nach § 6c SGB II - Untersuchungsfeld 4: Makroanalyse und regionale Vergleiche: Zwischenbericht 2007

"Im Rahmen der Evaluation der Experimentierklausel nach Paragraph 6c SGB II umfasst die Aufgabenstellung des Forschungsfeldes 4 - Makroanalyse und regionale Vergleiche - eine Analyse der regionalen Wirkungen von ARGEn und zkT (zugelassene kommunale Träger), die Analyse der gesamtwirtschaftlichen Wirkungen und ein Performancevergleich der Regionen. Insbesondere im Rahmen der Makroanalyse gilt es die Frage zu beantworten, 'Was wäre geschehen, wenn zum 1. 1. 2005 deutschlandweit entweder das ARGE-Modell oder die kommunale Trägerschaft eingeführt worden wäre?' und zwar unter besonderer Berücksichtigung regionaler Besonderheiten und Verflechtungen, sowie Substitutions-, Verdrängungs- und Mitnahmeeffekten. Bei einem Vergleich der ARGEn mit den zkT muss berücksichtigt werden, ob sich Kreise mit spezifischen Merkmalen für die eine oder die andere Form der Aufgabenwahrnehmung entschieden haben. Auf Grundlage der Vorarbeiten des Paragraph 6c-Forschungsverbundes dürften folgende Faktoren die Optionsneigung beeinflusst haben: Lokale Arbeitsmarktlage, Größe der Kommune, Finanzkraft, Sozio-geographische Merkmale, Politische Merkmale und Vorerfahrungen. Die regionalen Vergleiche dienen der Darstellung und der deskriptiven Beschreibung der Entwicklung zentraler Indikatoren für die Zielgrößen 'Integration in Erwerbstätigkeit', 'Verbesserung der Beschäftigungsfähigkeit' und 'soziale Stabilisierung' im Vergleich der drei Formen der Aufgabenwahrnehmung sowie der unterschiedlichen Organisationstypen." (Autorenreferat

Flavour compounds in tomato fruits: identification of loci and potential pathways affecting volatile composition

The unique flavour of a tomato fruit is the sum of a complex interaction among sugars, acids, and a large set of volatile compounds. While it is generally acknowledged that the flavour of commercially produced tomatoes is inferior, the biochemical and genetic complexity of the trait has made breeding for improved flavour extremely difficult. The volatiles, in particular, present a major challenge for flavour improvement, being generated from a diverse set of lipid, amino acid, and carotenoid precursors. Very few genes controlling their biosynthesis have been identified. New quantitative trait loci (QTLs) that affect the volatile emissions of red-ripe fruits are described here. A population of introgression lines derived from a cross between the cultivated tomato Solanum lycopersicum and its wild relative, S. habrochaites, was characterized over multiple seasons and locations. A total of 30 QTLs affecting the emission of one or more volatiles were mapped. The data from this mapping project, combined with previously collected data on an IL population derived from a cross between S. lycopersicum and S. pennellii populations, were used to construct a correlational database. A metabolite tree derived from these data provides new insights into the pathways for the synthesis of several of these volatiles. One QTL is a novel locus affecting fruit carotenoid content on chromosome 2. Volatile emissions from this and other lines indicate that the linear and cyclic apocarotenoid volatiles are probably derived from separate carotenoid pools

Replication and validation of higher order models demonstrated that a summary score for the EORTC QLQ-C30 is robust.

Objective: To further evaluate the higher-order measurement structure of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) questionnaire, with the aim of generating a summary score. Study design and setting: Using pretreatment QLQ-C30 data (N=3,282), we conducted confirmatory factor analyses to test seven previously evaluated higher-order models. We compared the summary score(s) derived from the best performing higher-order model with the original QLQ-C30 scale scores, using tumor stage, performance status and change over time (N=244) as grouping variables. Results: Whereas all models showed acceptable fit, we continued in the interest of parsimony with known-groups validity and responsiveness analyses using a summary score derived from the single higher-order factor model. The validity and responsiveness of this QLQ-C30 Summary Score was equal to, and in many cases superior to the original, underlying QLQ-C30 scale scores. Conclusion: Our results provide empirical support for a measurement model for the QLQ-C30 yielding a single summary score. The availability of this Summary Score can avoid problems with potential Type I errors that arise due to multiple testing when making comparisons based on the 15 outcomes generated by this questionnaire, and may reduce sample size requirements for HRQL studies using the QLQ-C30 questionnaire when an overall summary score is a relevant primary outcome

Exploring urban metabolism—Towards an interdisciplinary perspective

© 2017 The Author(s) The discussion on urban metabolism has been long dominated by natural scientists focussing on natural forces shaping the energy and material flows in urban systems. However, in the anthropocene human forces such as industrialization and urbanization are mobilizing people, goods and information at an increasing pace and as such have a large impact on urban energy and material flows. In this white paper, we develop a combined natural and social science perspective on urban metabolism. More specifically, innovative conceptual and methodological interdisciplinary approaches are identified and discussed to enhance the understanding of the forces that shape urban metabolism, and how these forces affect urban living and the environment. A challenging research agenda on urban metabolism is also presented

Framework and baseline examination of the German National Cohort (NAKO)

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10654-022-00890-5

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p