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Bayesian Data Assimilation to Support Informed Decision Making in Individualized Chemotherapy
(2020)
An essential component of therapeutic drug/biomarker monitoring (TDM) is to combine patient data with prior knowledge for model-based predictions of therapy outcomes. Current Bayesian forecasting tools typically rely only on the most probable model parameters (maximum a posteriori (MAP) estimate). This MAP-based approach, however, does neither necessarily predict the most probable outcome nor does it quantify the risks of treatment inefficacy or toxicity. Bayesian data assimilation (DA) methods overcome these limitations by providing a comprehensive uncertainty quantification. We compare DA methods with MAP-based approaches and show how probabilistic statements about key markers related to chemotherapy-induced neutropenia can be leveraged for more informative decision support in individualized chemotherapy. Sequential Bayesian DA proved to be most computationally efficient for handling interoccasion variability and integrating TDM data. For new digital monitoring devices enabling more frequent data collection, these features will be of critical importance to improve patient care decisions in various therapeutic areas.
We applied the Social Cognitive Theory to investigate whether parent–child relationships, bullying victimization, and teacher–student relationships are directly as well as indirectly via self-efficacy in social conflicts associated with adolescents’ willingness to intervene in a bullying incident. There were 2071 (51.3% male) adolescents between the ages of 12 and 17 from 24 schools in Germany who participated in this study. A mediation test using structural equation modeling revealed that parent–child relationships, bullying victimization, and teacher–student relationships were directly related to adolescents’ self-efficacy in social conflicts. Further, teacher–student relationships and bullying victimization were directly associated with adolescents’ willingness to intervene in bullying. Finally, relationships with parents, peers and teachers were indirectly related to higher levels of students’ willingness to intervene in bullying situations due to self-efficacy in social conflicts. Thus, our analysis confirms the general assumptions of Social Cognitive Theory and the usefulness of applying its approach to social conflicts such as bullying situations.
The pathophysiology of Parkinson’s disease (PD) is still not understood. There are investigations which show a changed oscillatory behaviour of brain circuits or changes in variability of, e.g., gait parameters in PD. The aim of this study was to investigate whether or not the motor output differs between PD patients and healthy controls. Thereby, patients without tremor are investigated in the medication off state performing a special bilateral isometric motor task. The force and accelerations (ACC) were recorded as well as the Mechanomyography (MMG) of the biceps brachii, the brachioradialis and of the pectoralis major muscles using piezoelectric-sensors during the bilateral motor task at 60% of the maximal isometric contraction. The frequency, a specific power ratio, the amplitude variation and the slope of amplitudes were analysed. The results indicate that the oscillatory behaviour of motor output in PD patients without tremor deviates from controls: thereby, the 95%-confidence-intervals of power ratio and of amplitude variation of all signals are disjoint between PD and controls and show significant differences in group comparisons (power ratio: p = 0.000–0.004, r = 0.441–0.579; amplitude variation: p = 0.000–0.001, r = 0.37–0.67). The mean frequency shows a significant difference for ACC (p = 0.009, r = 0.43), but not for MMG. It remains open, whether this muscular output reflects changes of brain circuits and whether the results are reproducible and specific for PD.
Recent research indicates that affective responses during exercise are an important determinant of future exercise and physical activity. Thus far these responses have been measured with standardized self-report scales, but this study used biometric software for automated facial action analysis to analyze the changes that occur during physical exercise. A sample of 132 young, healthy individuals performed an incremental test on a cycle ergometer. During that test the participants’ faces were video-recorded and the changes were algorithmically analyzed at frame rate (30 fps). Perceived exertion and affective valence were measured every two minutes with established psychometric scales. Taking into account anticipated inter-individual variability, multilevel regression analysis was used to model how affective valence and ratings of perceived exertion (RPE) covaried with movement in 20 facial action areas. We found the expected quadratic decline in self-reported affective valence (more negative) as exercise intensity increased. Repeated measures correlation showed that the facial action mouth open was linked to changes in (highly intercorrelated) affective valence and RPE. Multilevel trend analyses were calculated to investigate whether facial actions were typically linked to either affective valence or RPE. These analyses showed that mouth open and jaw drop predicted RPE, whereas (additional) nose wrinkle was indicative for the decline in affective valence. Our results contribute to the view that negative affect, escalating with increasing exercise intensity, may be the body’s essential warning signal that physiological overload is imminent. We conclude that automated facial action analysis provides new options for researchers investigating feelings during exercise. In addition, our findings offer physical educators and coaches a new way of monitoring the affective state of exercisers, without interrupting and asking them.
Abiotic stresses cause oxidative damage in plants. Here, we demonstrate that foliar application of an extract from the seaweed Ascophyllum nodosum, SuperFifty (SF), largely prevents paraquat (PQ)-induced oxidative stress in Arabidopsis thaliana. While PQ-stressed plants develop necrotic lesions, plants pre-treated with SF (i.e., primed plants) were unaffected by PQ. Transcriptome analysis revealed induction of reactive oxygen species (ROS) marker genes, genes involved in ROS-induced programmed cell death, and autophagy-related genes after PQ treatment. These changes did not occur in PQ-stressed plants primed with SF. In contrast, upregulation of several carbohydrate metabolism genes, growth, and hormone signaling as well as antioxidant-related genes were specific to SF-primed plants. Metabolomic analyses revealed accumulation of the stress-protective metabolite maltose and the tricarboxylic acid cycle intermediates fumarate and malate in SF-primed plants. Lipidome analysis indicated that those lipids associated with oxidative stress-induced cell death and chloroplast degradation, such as triacylglycerols (TAGs), declined upon SF priming. Our study demonstrated that SF confers tolerance to PQ-induced oxidative stress in A. thaliana, an effect achieved by modulating a range of processes at the transcriptomic, metabolic, and lipid levels.
Am Beispiel der Erd- und Umweltwissenschaften (einschließlich der landschafts- und standortbezogenen Teilgebiete der Agrarwissenschaften) zeigt dieser Beitrag, dass auch in scheinbar „unverdächtigen“ Disziplinen personenbezogene Forschungsdaten vorkommen. Eine Auswertung der Literatur zeigt, dass allgemeine Handreichungen zum Datenschutz in der Forschung kaum Unterstützung bei der Arbeit mit den für diese Disziplinen besonders relevanten Fällen bieten. Für die in den Erd- und Umweltwissenschaften besonders relevanten raumbezogenen Daten kommt hinzu, dass selbst unter Fachjuristinnen Uneinigkeit über die datenschutzrechtliche Bewertung herrscht. Die Ergebnisse einer empirischen Vorstudie zeigen eine ganze Reihe verschiedener Arten personenbezogener Forschungsdaten auf, die in der Forschungspraxis der Erd- und Umweltwissenschaften eine Rolle spielen. Sie legen außerdem nahe, dass der Umgang mit personenbezogenen Daten in der Forschungspraxis der Erd- und Umweltwissenschaften auf Grund der mangelnden Vertrautheit mit dem Datenschutz nicht immer den rechtlichen Anforderungen entspricht. Auch Unterstützung durch Fachgesellschaften und Infrastruktureinrichtungen – etwa in Form disziplinspezifischer Handreichungen, qualifizierter Beratung oder institutionalisierten Möglichkeiten, Daten sicher zu archivieren und gegebenenfalls zugangsbeschränkt zu publizieren – bestehen kaum. Aus dieser Situation ergeben sich Herausforderungen an die Weiterentwicklung der disziplinären Datenkultur und Dateninfrastruktur, beispielsweise im Rahmen des Prozesses zum Aufbau einer Nationalen Forschungsdateninfrastruktur (NFDI). Zu den Möglichkeiten für Infrastruktureinrichtungen, diese Weiterentwicklung zu unterstützen, zeigt dieser Beitrag Handlungsoptionen auf.
Social comparison processes and the social position within a school class already play a major role in performance evaluation as early as in elementary school. The influence of contrast and assimilation effects on self-evaluation of performance as well as task interest has been widely researched in observational studies under the labels big-fish-little-pond and basking-in-reflected-glory effect. This study examined the influence of similar contrast and assimilation effects in an experimental paradigm. Fifth and sixth grade students (n = 230) completed a computer-based learning task during which they received social comparative feedback based on 2 × 2 experimentally manipulated feedback conditions: social position (high vs. low) and peer performance (high vs. low). Results show a more positive development of task interest and self-evaluation of performance in both the high social position and the high peer performance condition. When applied to the school setting, results of this study suggest that students who already perform well in comparison to their peer group are also the ones who profit most from social comparative feedback, given that they are the ones who usually receive the corresponding positive performance feedback.
Instructions given prior to extinction training facilitate the extinction of conditioned skin conductance (SCRs) and fear-potentiated startle responses (FPSs) and serve as laboratory models for cognitive interventions implemented in exposure-based treatments of pathological anxiety. Here, we investigated how instructions given prior to extinction training, with or without the additional removal of the electrode used to deliver the unconditioned stimulus (US), affect the return of fear assessed 24 hours later. We replicated previous instruction effects on extinction and added that the additional removal of the US electrode slightly enhanced facilitating effects on the extinction of conditioned FPSs. In contrast, extinction instructions hardly affected the return of conditioned fear responses. These findings suggest that instruction effects observed during extinction training do not extent to tests of return of fear 24 hours later which serve as laboratory models of relapse and improvement stability of exposure-based treatments.
The DNA in living cells can be effectively damaged by high-energy radiation, which can lead to cell death. Through the ionization of water molecules, highly reactive secondary species such as low-energy electrons (LEEs) with the most probable energy around 10 eV are generated, which are able to induce DNA strand breaks via dissociative electron attachment. Absolute DNA strand break cross sections of specific DNA sequences can be efficiently determined using DNA origami nanostructures as platforms exposing the target sequences towards LEEs. In this paper, we systematically study the effect of the oligonucleotide length on the strand break cross section at various irradiation energies. The present work focuses on poly-adenine sequences (d(A₄), d(A₈), d(A₁₂), d(A₁₆), and d(A₂₀)) irradiated with 5.0, 7.0, 8.4, and 10 eV electrons. Independent of the DNA length, the strand break cross section shows a maximum around 7.0 eV electron energy for all investigated oligonucleotides confirming that strand breakage occurs through the initial formation of negative ion resonances. When going from d(A₄) to d(A₁₆), the strand break cross section increases with oligonucleotide length, but only at 7.0 and 8.4 eV, i.e., close to the maximum of the negative ion resonance, the increase in the strand break cross section with the length is similar to the increase of an estimated geometrical cross section. For d(A₂₀), a markedly lower DNA strand break cross section is observed for all electron energies, which is tentatively ascribed to a conformational change of the dA₂₀ sequence. The results indicate that, although there is a general length dependence of strand break cross sections, individual nucleotides do not contribute independently of the absolute strand break cross section of the whole DNA strand. The absolute quantification of sequence specific strand breaks will help develop a more accurate molecular level understanding of radiation induced DNA damage, which can then be used for optimized risk estimates in cancer radiation therapy.
Ein wichtiges Anliegen aller Privatrechtsordnungen ist die Sicherheit und Verlässlichkeit des Gütertransfers. In einer entwickelten Wirtschaft, die auf Arbeitsteilung und Umsatz basiert, gibt es lange Lieferketten. Person A liefert ein Gut an B, dann liefert B an C und immer so weiter. Die einzelnen Glieder in der Kette müssen das Gut sicher und verlässlich erwerben können. Wenn nun aber das Geschäft zwischen A und B von Anfang an ungültig ist oder nachträglich hinfällig wird, stellt sich die Frage, wem das Gut gehört. Das deutsche Recht begegnet dieser Frage unter anderem mit dem Trennungs- und Abstraktionsprinzip: Kauf und Übereignung sind zwei gesonderte Verträge, und die Wirksamkeit der Übereignung ist unabhängig vom Bestand und von der Wirksamkeit des Kaufvertrag. Das wird von deutschen Juristen als Schlüssel wissenschaftlichen Rechtsdenkens hochgehalten, stößt aber außerhalb Deutschlands und speziell in Frankreich auf Unverständnis. Denn im französischen Recht sind Kauf und Übereignung Eins.
Im Folgenden geht es nicht so sehr um die geistige Qualität des deutschen Trennungs- und Abstraktionsprinzips, die unbestreitbar ist, sondern vor allem um die Frage, ob diese Prinzi-pien im Vergleich zur französischen Einheit von Kauf und Übereignung praktische Vorteile haben. Die Untersuchung konzentriert sich auf die Übertragung von beweglichen Sachen und von Rechten. Das Grundstücksrecht bleibt dagegen ausgeklammert, denn es ist wegen seiner Formalien schwerer zu vergleichen und trägt keine grundlegend neuen Erkenntnisse bei.
Vor achtzig Jahren
(2020)
Die Locarno-Verträge haben in der völkerrechtlichen Literatur der 1920er und 1930er Jahre viel Aufmerksamkeit erfahren. Auch die zeitgenössische Publizistik beschäftigte sich ausführlich mit diesem Thema, wobei das Verhältnis von Verständigung mit den Nachbarn und Revision der Grenzregelungen im Mittelpunkt der Debatte stand.
Später gehörte Locarno zur Geschichte der Zwischenkriegszeit und wurde im Rahmen der Völkerbundsgeschichte, der Völkerrechts- und Diplomatiegeschichte und der Geschichte der Weimarer Republik behandelt. Für die politikwissenschaftliche Literatur spielte Locarno fast ausschließlich auf dem Gebiet der Sicherheits- und Abrüstungspolitik eine Rolle; eine (system)theoretische Erörterung steht bislang aus.
In diesem Beitrag sollen nach einem kurzen Überblick über das Vertragswerk zunächst die geschichtliche Ausgangslage knapp umrissen und Vorgeschichte und Ergebnis der Konferenz von Locarno skizziert werden. Anschließend werden Inhalte und Lösungsansätze des Vertragswerkes beleuchtet, bevor zum Schluß eine kurze Einordnung in das System des Völkerbundes erfolgt.