Inelastic cotunneling in quantum dots and molecules with weakly broken degeneracies

We calculate the nonlinear cotunneling conductance through interacting quantum dot systems in the deep Coulomb blockade regime using a rate equation approach based on the T-matrix formalism, which shows in the concerned regions very good agreement with a generalized master equation approach. Our focus is on inelastic cotunneling in systems with weakly broken degeneracies, such as complex quantum dots or molecules. We find for these systems a characteristic gate dependence of the non-equilibrium cotunneling conductance. While on one side of a Coulomb diamond the conductance decreases after the inelastic cotunneling threshold towards its saturation value, on the other side it increases monotonously even after the threshold. We show that this behavior originates from an asymmetric gate voltage dependence of the effective cotunneling amplitudes.Comment: 12 pages, 12 figures; revised published versio

Influence of CYP2D6 Phenotypes on the Pharmacokinetics of Aripiprazole and Dehydro-Aripiprazole Using a Physiologically Based Pharmacokinetic Approach

Background and Objectives Aripiprazole is an atypical antipsychotic drug that is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, which mainly form its active metabolite dehydro-aripiprazole. Because of the genetic polymorphism of CYP2D6, plasma concentrations are highly variable between different phenotypes. In this study, phenotype-related physiologically based pharmacokinetic models were developed and evaluated to suggest phenotype-guided dose adjustments. Methods Physiologically based pharmacokinetic models for single dose (oral and orodispersible formulation), multiple dose, and steady-state condition were built using trial data from genotyped healthy volunteers. Based on evaluated models, dose adjustments were simulated to compensate for genetically caused differences. Results Physiologically based pharmacokinetic models were able to accurately predict the pharmacokinetics of aripiprazole and dehydro-aripiprazole according to CYP2D6 phenotypes, illustrated by a minimal bias and a good precision. For single-dose administration, 92.5% (oral formulation) and 79.3% (orodispersible formulation) of the plasma concentrations of aripiprazole were within the 1.25-fold error range. In addition, physiologically based pharmacokinetic steady-state simulations demonstrate that the daily dose for poor metabolizer should be adjusted, resulting in a maximum recommended dose of 10 mg, but no adjustment is necessary for intermediate and ultra-rapid metabolizers. Conclusions In clinical practice, CYP2D6 genotyping in combination with therapeutic drug monitoring should be considered to personalize aripiprazole dosing, especially in CYP2D6 poor metabolizers, to ensure therapy effectiveness and safetyOpen Access funding enabled and organized by Projekt DEAL. Dora Koller and the multiple-dose phase I trial (EUDRA-CT: 2018-000744-26) were co-financed by the H2020 Marie Sklodowska-Curie Innovative Training Network 721236 gran

Geografische Ansätze in der Gesundheitsberichterstattung

The interest in using geographic methods for health monitoring has grown strongly over the last two decades. Through these methods, analysis and visualization of health data can be more focused and target-group specific. The application in health monitoring is possible mostly due to broader technical possibilities and more available datasets. In this article, we show which geographic aspects are adapted in health monitoring at different levels (federal, state, municipality). For example, at the federal level, surveillance methods are used; at the state level health atlases are created; and on the municipality level geographic analyses are performed for possible public health interventions.Methods range from simple maps on different levels of aggregation to more complex methods like space-temporal visualization or spatial-smoothing methods. While the technical possibilities are in place, a broader implementation of geographic methods is mostly hindered by missing data access to small-area information and data protection policies. Better access to data could especially improve the possibility for geographic methods in health monitoring and could inform the population and decision makers to inform and improve population health or healthcare.Das Interesse an geografischen Darstellungen in der Gesundheitsberichterstattung (GBE) ist in den letzten beiden Jahrzehnten stark gewachsen. Gesundheitsdaten können mit diesen Methoden anschaulich und zielgruppenorientiert visualisiert werden. Neue technische Möglichkeiten und die breitere Verfügbarkeit von Daten tragen zur verstärkten Anwendung in der GBE bei. In diesem Artikel soll gezeigt werden, welche geografischen Ansätze in der GBE auf Bundes‑, Länder- und Kommunalebene jeweils aktuell verfolgt werden. Insbesondere soll dabei auf die verwendeten Methoden fokussiert werden. Es wird gezeigt, dass auf Bundesebene geografische Methoden z. B. in der Surveillance angewendet werden; auf Länderebene gibt es z. B. Gesundheitsatlanten und auf der Kommunalebene verschiedene geografische Analysen. Die methodische Spannweite reicht von einfacheren Kartendarstellungen auf unterschiedlichen Aggregationsebenen bis hin zu komplexeren Verfahren wie raum-zeitlichen Darstellungen und räumlichen Glättungsverfahren. Fehlender Datenzugang oder datenschutzrechtliche Aspekte behindern noch häufig die Verbindung mit weiteren Datenquellen oder kleinräumigere Darstellungen. Vor allem ein besserer Zugang zu Daten auf kleinräumiger Ebene könnte die GBE aber erheblich erleichtern. Die Bevölkerung und Entscheidungsträger könnten dadurch noch umfassender informiert und folglich die Gesundheit und die gesundheitliche Versorgung der Bevölkerung verbessert werden

Competing risks analyses: objectives and approaches

Studies in cardiology often record the time to multiple disease events such as death, myocardial infarction, or hospitalization. Competing risks methods allow for the analysis of the time to the first observed event and the type of the first event. They are also relevant if the time to a specific event is of primary interest but competing events may preclude its occurrence or greatly alter the chances to observe it. We give a non-technical overview of competing risks concepts for descriptive and regression analyses. For descriptive statistics, the cumulative incidence function is the most important tool. For regression modelling, we introduce regression models for the cumulative incidence function and the cause-specific hazard function, respectively. We stress the importance of choosing statistical methods that are appropriate if competing risks are present. We also clarify the role of competing risks for the analysis of composite endpoint

Uptake of Radionuclides by Bryophytes in the Chornobyl Exclusion Zone

The “Chernobyl nuclear disaster” released huge amounts of radionuclides, which are still detectable in plants and sediments today. Bryophytes (mosses) are primitive land plants lacking roots and protective cuticles and therefore readily accumulate multiple contaminants, including metals and radionuclides. This study quantifies 137Cs and 241Am in moss samples from the cooling pond of the power plant, the surrounding woodland and the city of Prypiat. Activity concentrations of up to 297 Bq/g (137Cs) and 0.43 Bq/g (241Am) were found. 137Cs contents were significantly higher at the cooling pond, where 241Am was not detectable. Distance to the damaged reactor, amount of original fallout, presence of vascular tissue in the stem or taxonomy were of little importance. Mosses seem to absorb radionuclides rather indiscriminately, if available. More than 30 years after the disaster, 137Cs was washed out from the very top layer of the soil, where it is no more accessible for rootless mosses but possibly for higher plants. On the other hand, 137Cs still remains solved and accessible in the cooling pond. However, 241Am remained adsorbed to the topsoil, thus accessible to terrestrial mosses, but precipitated in the sapropel of the cooling pond