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Context
For a given body mass index (BMI), both impaired metabolic health (MH) and reduced cardiorespiratory fitness (CRF) associate with increased risk of cardiovascular disease (CVD).
Objective
It remains unknown whether both risk phenotypes relate to CVD independently of each other, and whether these relationships differ in normal weight, overweight, and obese subjects.
Methods
Data from 421 participants from the Tubingen Diabetes Family Study, who had measurements of anthropometrics, metabolic parameters, CRF (maximal aerobic capacity [VO2max]) and carotid intima-media thickness (cIMT), an early marker of atherosclerosis, were analyzed. Subjects were divided by BMI and MH status into 6 phenotypes.
Results
In univariate analyses, older age, increased BMI, and a metabolic risk profile correlated positively, while insulin sensitivity and VO2max negatively with cIMT. In multivariable analyses in obese subjects, older age, male sex, lower VO2max (std. ss -0.21, P = 0.002) and impaired MH (std. ss 0.13, P = 0.02) were independent determinants of increased cIMT. After adjustment for age and sex, subjects with metabolically healthy obesity (MHO) had higher cIMT than subjects with metabolically healthy normal weight (MHNW; 0.59 +/- 0.009 vs 0.52 +/- 0.01 mm; P < 0.05). When VO2max was additionally included in this model, the difference in cIMT between MHO and MHNW groups became statistically nonsignificant (0.58 +/- 0.009 vs 0.56 +/- 0.02 mm; P > 0.05).
Conclusion
These data suggest that impaired MH and low CRF independently determine increased cIMT in obese subjects and that low CRF may explain part of the increased CVD risk observed in MHO compared with MHNW.
Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18% of the maximum diversity across all grasslands when LUI was static over time but increased to 31% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.
BIOMEX (BIOlogy and Mars EXperiment) is an ESA/Roscosmos space exposure experiment housed within the exposure facility EXPOSE-R2 outside the Zvezda module on the International Space Station (ISS). The design of the multiuser facility supports-among others-the BIOMEX investigations into the stability and level of degradation of space-exposed biosignatures such as pigments, secondary metabolites, and cell surfaces in contact with a terrestrial and Mars analog mineral environment. In parallel, analysis on the viability of the investigated organisms has provided relevant data for evaluation of the habitability of Mars, for the limits of life, and for the likelihood of an interplanetary transfer of life (theory of lithopanspermia). In this project, lichens, archaea, bacteria, cyanobacteria, snow/permafrost algae, meristematic black fungi, and bryophytes from alpine and polar habitats were embedded, grown, and cultured on a mixture of martian and lunar regolith analogs or other terrestrial minerals. The organisms and regolith analogs and terrestrial mineral mixtures were then exposed to space and to simulated Mars-like conditions by way of the EXPOSE-R2 facility. In this special issue, we present the first set of data obtained in reference to our investigation into the habitability of Mars and limits of life. This project was initiated and implemented by the BIOMEX group, an international and interdisciplinary consortium of 30 institutes in 12 countries on 3 continents. Preflight tests for sample selection, results from ground-based simulation experiments, and the space experiments themselves are presented and include a complete overview of the scientific processes required for this space experiment and postflight analysis. The presented BIOMEX concept could be scaled up to future exposure experiments on the Moon and will serve as a pretest in low Earth orbit.
Background Anxiety and depressive disorders share common features of mood dysfunctions. This has stimulated interest in transdiagnostic dimensional research as proposed by the Research Domain Criteria (RDoC) approach by the National Institute of Mental Health (NIMH) aiming to improve the understanding of underlying disease mechanisms. The purpose of this study was to investigate the processing of RDoC domains in relation to disease severity in order to identify latent disorder-specific as well as transdiagnostic indicators of disease severity in patients with anxiety and depressive disorders.
Methods Within the German research network for mental disorders, 895 participants (n = 476 female, n = 602 anxiety disorder, n = 257 depressive disorder) were recruited for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) and included in this cross-sectional study. We performed incremental regression models to investigate the association of four RDoC domains on disease severity in patients with affective disorders: Positive (PVS) and Negative Valance System (NVS), Cognitive Systems (CS) and Social Processes (SP).
Results The results confirmed a transdiagnostic relationship for all four domains, as we found significant main effects on disease severity within domain-specific models (PVS: & beta; = -0.35; NVS: & beta; = 0.39; CS: & beta; = -0.12; SP: & beta; = -0.32). We also found three significant interaction effects with main diagnosis showing a disease-specific association.
Limitations The cross-sectional study design prevents causal conclusions. Further limitations include possible outliers and heteroskedasticity in all regression models which we appropriately controlled for.
Conclusion Our key results show that symptom burden in anxiety and depressive disorders is associated with latent RDoC indicators in transdiagnostic and disease-specific ways.
This study aimed to build on the relationship of well-established self-report and behavioral assessments to the latent constructs positive (PVS) and negative valence systems (NVS), cognitive systems (CS), and social processes (SP) of the Research Domain Criteria (RDoC) framework in a large transnosological population which cuts across DSM/ICD-10 disorder criteria categories. One thousand four hundred and thirty one participants (42.1% suffering from anxiety/fear-related, 18.2% from depressive, 7.9% from schizophrenia spectrum, 7.5% from bipolar, 3.4% from autism spectrum, 2.2% from other disorders, 18.4% healthy controls, and 0.2% with no diagnosis specified) recruited in studies within the German research network for mental disorders for the Phenotypic, Diagnostic and Clinical Domain Assessment Network Germany (PD-CAN) were examined with a Mini-RDoC-Assessment including behavioral and self-report measures. The respective data was analyzed with confirmatory factor analysis (CFA) to delineate the underlying latent RDoC-structure. A revised four-factor model reflecting the core domains positive and negative valence systems as well as cognitive systems and social processes showed a good fit across this sample and showed significantly better fit compared to a one factor solution. The connections between the domains PVS, NVS and SP could be substantiated, indicating a universal latent structure spanning across known nosological entities. This study is the first to give an impression on the latent structure and intercorrelations between four core Research Domain Criteria in a transnosological sample. We emphasize the possibility of using already existing and well validated self-report and behavioral measurements to capture aspects of the latent structure informed by the RDoC matrix.
Over the past years, NGS has become a crucial workhorse for open-view pathogen diagnostics.
Yet, long turnaround times result from using massively parallel high-throughput technologies as the analysis can only be performed after sequencing has finished. The interpretation of results can further be challenged by contaminations, clinically irrelevant sequences, and the sheer amount and complexity of the data.
We implemented PathoLive, a real-time diagnostics pipeline for the detection of pathogens from clinical samples hours before sequencing has finished.
Based on real-time alignment with HiLive2, mappings are scored with respect to common contaminations, low-entropy areas, and sequences of widespread, non-pathogenic organisms.
The results are visualized using an interactive taxonomic tree that provides an easily interpretable overview of the relevance of hits. For a human plasma sample that was spiked in vitro with six pathogenic viruses, all agents were clearly detected after only 40 of 200 sequencing cycles.
For a real-world sample from Sudan, the results correctly indicated the presence of Crimean-Congo hemorrhagic fever virus. In a second real-world dataset from the 2019 SARS-CoV-2 outbreak in Wuhan, we found the presence of a SARS coronavirus as the most relevant hit without the novel virus reference genome being included in the database.
For all samples, clinically irrelevant hits were correctly de-emphasized.
Our approach is valuable to obtain fast and accurate NGS-based pathogen identifications and correctly prioritize and visualize them based on their clinical significance: PathoLive is open source and available on GitLab and BioConda.
Supermassive black holes are a fundamental component of the universe in general and of galaxies in particular. Almost every massive galaxy harbours a supermassive black hole (SMBH) in its center. Furthermore, there is a close connection between the growth of the SMBH and the evolution of its host galaxy, manifested in the relationship between the mass of the black hole and various properties of the galaxy's spheroid component, like its stellar velocity dispersion, luminosity or mass. Understanding this relationship and the growth of SMBHs is essential for our picture of galaxy formation and evolution. In this thesis, I make several contributions to improve our knowledge on the census of SMBHs and on the coevolution of black holes and galaxies. The first route I follow on this road is to obtain a complete census of the black hole population and its properties. Here, I focus particularly on active black holes, observable as Active Galactic Nuclei (AGN) or quasars. These are found in large surveys of the sky. In this thesis, I use one of these surveys, the Hamburg/ESO survey (HES), to study the AGN population in the local volume (z~0). The demographics of AGN are traditionally represented by the AGN luminosity function, the distribution function of AGN at a given luminosity. I determined the local (z<0.3) optical luminosity function of so-called type 1 AGN, based on the broad band B_J magnitudes and AGN broad Halpha emission line luminosities, free of contamination from the host galaxy. I combined this result with fainter data from the Sloan Digital Sky Survey (SDSS) and constructed the best current optical AGN luminosity function at z~0. The comparison of the luminosity function with higher redshifts supports the current notion of 'AGN downsizing', i.e. the space density of the most luminous AGN peaks at higher redshifts and the space density of less luminous AGN peaks at lower redshifts. However, the AGN luminosity function does not reveal the full picture of active black hole demographics. This requires knowledge of the physical quantities, foremost the black hole mass and the accretion rate of the black hole, and the respective distribution functions, the active black hole mass function and the Eddington ratio distribution function. I developed a method for an unbiased estimate of these two distribution functions, employing a maximum likelihood technique and fully account for the selection function. I used this method to determine the active black hole mass function and the Eddington ratio distribution function for the local universe from the HES. I found a wide intrinsic distribution of black hole accretion rates and black hole masses. The comparison of the local active black hole mass function with the local total black hole mass function reveals evidence for 'AGN downsizing', in the sense that in the local universe the most massive black holes are in a less active stage then lower mass black holes. The second route I follow is a study of redshift evolution in the black hole-galaxy relations. While theoretical models can in general explain the existence of these relations, their redshift evolution puts strong constraints on these models. Observational studies on the black hole-galaxy relations naturally suffer from selection effects. These can potentially bias the conclusions inferred from the observations, if they are not taken into account. I investigated the issue of selection effects on type 1 AGN samples in detail and discuss various sources of bias, e.g. an AGN luminosity bias, an active fraction bias and an AGN evolution bias. If the selection function of the observational sample and the underlying distribution functions are known, it is possible to correct for this bias. I present a fitting method to obtain an unbiased estimate of the intrinsic black hole-galaxy relations from samples that are affected by selection effects. Third, I try to improve our census of dormant black holes and the determination of their masses. One of the most important techniques to determine the black hole mass in quiescent galaxies is via stellar dynamical modeling. This method employs photometric and kinematic observations of the galaxy and infers the gravitational potential from the stellar orbits. This method can reveal the presence of the black hole and give its mass, if the sphere of the black hole's gravitational influence is spatially resolved. However, usually the presence of a dark matter halo is ignored in the dynamical modeling, potentially causing a bias on the determined black hole mass. I ran dynamical models for a sample of 12 galaxies, including a dark matter halo. For galaxies for which the black hole's sphere of influence is not well resolved, I found that the black hole mass is systematically underestimated when the dark matter halo is ignored, while there is almost no effect for galaxies with well resolved sphere of influence.
1. Problemstellung Die Liberalisierung von Netzindustrien stellt eine volkswirtschaftliche Problematik dar, die einerseits eine Vielzahl theoretisch ungelöster Fragen aufwirft und für die andererseits nunmehr auch in Deutschland wirtschaftspolitische Erfahrungen vorliegen. Die Ursachen der ökonomischen Probleme sind dabei nicht nur in bestimmten Branchenbesonderheiten der Netzindustrien zu suchen, sondern auch in einer verfehlten ordnungspolitischen Sonderbehandlung der netzgebundenen Wirtschaftsbereiche in der Vergangenheit. Entgegen den für eine marktwirtschaftliche Ordnung charakteristischen Prinzipien Wettbewerb und Privateigentum wurden Netzindustrien traditionell als wettbewerbliche Ausnahmebereiche behandelt und zumeist in Form öffentlicher Unternehmen geführt. Die Folge dessen waren (staatliche) Monopole, die eine relativ hohe Ineffizienz aufwiesen. Die ordnungspolitische Konsequenz dieses Befundes lautete daher Liberalisierung von Netzindustrien durch Privatisierung und Marktöffnung, d. h. ein Abbau von Marktzutrittsschranken durch Deregulierung. Wettbewerb stößt in Netzindustrien jedoch an Grenzen, weil die zur Produktion netzgebundener Dienstleistungen erforderliche Infrastruktur typischerweise ein nicht-angreifbares, natürliches Monopol darstellt, das sich in der Hand eines im Markt eingesessenen, vertikal integrierten Anbieters befindet. Daraus ergeben sich weitreichende Möglichkeiten zur Diskriminierung von Konkurrenten, die wettbewerbspolitischen Handlungsbedarf nach sich ziehen. Diesen gilt es in der vorliegenden Arbeit zu analysieren und alternative Lösungsansätze der Diskriminierungsproblematik zu diskutieren. 2. Besonderes Forschungsziel Die vorliegende Dissertation widmet sich der Liberalisierung von Netzindustrien aus ökonomischer Sicht, wobei insbesondere die Interdependenzen zwischen der Eigentums- und der Diskriminierungsproblematik berücksichtigt werden. Gleichwohl bildet die wettbewerbliche Öffnung der Märkte für netzgebundene Dienstleistungen aus volkswirtschaftlicher Sicht das Kernproblem und somit auch den zentralen Untersuchungsgegenstand dieser Arbeit. Die theoretische Analyse bleibt dabei nicht auf einen Forschungsansatz beschränkt, sondern es werden mehrere Facetten der Liberalisierung von der Ordnungs- über die Netzökonomik bis hin zur politischen Ökonomie betrachtet. In empirischer Hinsicht haben die in Deutschland in verschiedenen Netzindustrien realisierten Marktöffnungen bislang zu unterschiedlich intensiven Wettbewerbsprozessen geführt. Daher wird ein problemorientierter, intersektoraler Vergleich der Reformen und eine wettbewerbs-politische Beurteilung anhand der drei Marktmerkmale Marktstruktur, Marktverhalten und Marktergebnis vorgenommen, um die Liberalisierung in einzelnen Netzindustrien zu bewerten. Die Telekommunikation gilt dabei als Musterbeispiel für eine erfolgreiche Liberalisierung, weil die Deregulierung hier durch eine sektorspezifische Marktmachtkontrolle begleitet wird, wofür eigens eine Regulierungsbehörde geschaffen wurde. Vor diesem Hintergrund wird der mangelnde Wettbewerb in der Strom- und vor allem in der Gasversorgung sowie im Schienenverkehr häufig auf das Fehlen solcher Institutionen zurückgeführt. Aufgrund dessen werden hier die Eisenbahn, die Telekommunikation im Festnetz und die leitungsgebundene Energieversorgung als empirische Analyseobjekte ausgewählt, um die im Laufe der Untersuchung gewonnenen theoretischen Erkenntnisse exemplarisch an diesen Netzindustrien aufzuzeigen und die im Folgenden formulierte Arbeitshypothese zu überprüfen. 3. Methodik Die Arbeit gliedert sich in einen theoretischen und einen empirischen Teil. Die theoretisch zu untersuchende Frage bei der Liberalisierung von Netzindustrien lautet: Welcher institutionellen Arrangements bedarf es in Netzindustrien, um vormals monopolistisch organisierte in kompetitive Märkte zu überführen und darin nachhaltig einen effektiven Wettbewerb zu etablieren? Auf der Grundlage der erarbeiteten ordnungs- und wettbewerbsökonomischen Erkenntnisse wird nach allgemeingültigen Kriterien gesucht, um daraus einen Bewertungsmaßstab für den intersektoralen Vergleich von Liberalisierungsprozessen in verschiedenen Netzindustrien zu entwickeln. Als Arbeitsthese der empirischen Überprüfung im zweiten Teil dient die aus verschiedenen ökonomischen Blickwinkeln gewonnene und theoretisch zu fundierende Vermutung, dass es zur wirksamen Marktöffnung in Netzindustrien einer materiellen Privatisierung sowie einer effektiven und effizienten Marktmachtkontrolle im Bereich des Zugangs zur Netzinfrastruktur bedarf. Anhand dieser These werden die Liberalisierungsprozesse in den Netzsektoren Schienenverkehr, Telekommunikation sowie Energieversorgung in der Bundesrepublik Deutschland aus volkswirtschaftlicher Sicht beurteilt, und es wird auf verbleibenden ordnungspolitischen Reformbedarf hingewiesen. Die theoretischen Ergebnisse sind indes auch auf ähnliche, hier nicht dargestellte Infrastruktursektoren übertragbar.
Inhalt 1 Ziele der Liberalisierung von Netzindustrien:Privatisierung staatlicher Monopole und wettbewerbliche Marktöffnung 2 Markt- und wettbewerbstheoretische Aspekte der Netzinfrastruktur 2.1 Netze als Teil der materiellen Infrastruktur 2.2 Netzinfrastruktur als öffentliches Gut oderInstrument der Daseinsvorsorge? 2.3 Netze als natürliche Monopole? 2.3.1 Nutzenrelevante Netzeffekte 2.3.2 Kostenbestimmende Netzeffekte 2.3.3 Wettbewerbspotenziale trotz Wettbewerbsversagen 3 Wettbewerbsökonomische Implikationen für Netzindustrien 3.1 Vertikale Integration in Netzindustrien 3.1.1 Transaktionskosten versus vertikale Integration 3.1.2 Wettbewerbsökonomische Probleme 3.2 Netzzugangsmodelle 3.3 Institutionelle Ausgestaltung der Wettbewerbsaufsicht 4 Fazit