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Tacrolimus—why pharmacokinetics matter in the clinic
No full textThe calcineurin inhibitor (CNI) Tacrolimus (Tac) is the most prescribed immunosuppressant drug after solid organ transplantation. After renal transplantation (RTx) approximately 95% of recipients are discharged with a Tac-based immunosuppressive regime. Despite the high immunosuppressive efficacy, its adverse effects, narrow therapeutic window and high intra- and interpatient variability (IPV) in pharmacokinetics require therapeutic drug monitoring (TDM), which makes treatment with Tac a major challenge for physicians. The C/D ratio (full blood trough level normalized by daily dose) is able to classify patients receiving Tac into two major metabolism groups, which were significantly associated with the clinical outcomes of patients after renal or liver transplantation. Therefore, the C/D ratio is a simple but effective tool to identify patients at risk of an unfavorable outcome. This review highlights the challenges of Tac-based immunosuppressive therapy faced by transplant physicians in their daily routine, the underlying causes and pharmacokinetics (including genetics, interactions, and differences between available Tac formulations), and the latest data on potential solutions to optimize treatment of high-risk patients
Text quality and changing perceptions of teacher feedback and affective-motivational variables: a study with secondary EFL students
No full textIntroduction: Feedback can support students' writing and has the potential to enhance writing motivation and reduce writing anxiety. However, for feedback to fulfill its potential, it has to be accepted by students and perceived as motivating. Methods: In this study, we investigate changes in less proficient English as a foreign language (EFL) students' (N = 53) writing motivation and affect, as well as their perceptions of teacher feedback and how these relate to students’ argumentative text quality. Measurements were taken before EFL teachers attended a professional learning intervention on feedback (T1) and 8 months later (T2). Results: From T1 to T2, students felt that general feedback quality improved, their writing self-efficacy increased, and their writing anxiety decreased. However, no significant changes in text quality could be observed between T1 and T2, and students continued to struggle with creating structure and coherence in their texts. Regression analyses revealed that feedback perceptions and affective-motivational variables did not predict students' text quality at T1. Yet at T2, students' perception of general feedback quality and the effect of feedback on writing motivation were significant predictors of text quality; self-efficacy and writing anxiety were not.
Discussion: Our results suggest that more attention needs to be paid to feedback’s motivational impact, especially among less proficient EFL writers
A grammar of Muyu
No full textDiese Dissertation ist eine Grammatik des Muyu, einer Papua-Sprache aus West-Neuguinea im Osten Indonesiens. Sie wird von etwa 2000 Menschen in 22 Dörfern in der Regentschaft Boven Digoel und in Vororten mehrerer Küstenstädte gesprochen. Die Sprache gehört zur Familie der Ok-Sprachen der größeren Familie Trans-Neuguinea und ist stark gefährdet. Das vorliegende Werk ist die erste umfassende Grammatik zu Muyu. Sie basiert auf fast 11 Monaten intensiver Feldforschung, in denen ein Korpus von audiovisuellen Aufnahmen, Transkripten und Übersetzungen zusammengestellt wurde. Der Korpus ist die primäre Datenquelle für alle Analysen in dieser Arbeit.
Diese Studie deckt ein breites Spektrum an Themen ab, die in 12 Kapiteln beschrieben werden. Neben den Kapiteln über Phonologie, Verbmorphologie und Syntax einfacher und komplexer Sätze liegt ein besonderer Schwerpunkt auf komplexen Prädikaten. Die typologisch interessantesten Merkmale sind Verbalnumerus und die extensive Verwendung von Multi-Verb-Konstruktionen (MVCs). Die Wortklasse der Demonstrativa ist besonders reichhaltig und deckt einen weiten Bereich von Funktionen ab. Darüber hinaus finden wir viele typische Trans-Neuguinea-Merkmale: Genuskongruenz am Verb, Verbletztstellung im Satz, fehlende Nominalmorphologie, Switch-Referenz und Tail-Head-Linkage.
Der Anhang dieser Grammatik enthält zwei vollständig glossierte Texte und eine umfangreiche Wortliste (Muyu-Englisch) mit über 2500 Einträgen. Die Grammatik wird von einer frei zugänglichen Sammlung von Sprachmaterial begleitet, das im Endangered Languages Archive (ELAR) archiviert ist.This thesis is a grammar of Muyu, a Papuan language of Western New Guinea in the east of Indonesia. It is spoken by around 2000 people in 22 villages in the Boven Digoel regency and in suburbs of several coastal cities. The language belongs to the Ok language family of the Trans New Guinea phylum and is severly endangered. This work is the first comprehensive grammar on
Muyu. It is based on nearly 11 months of fieldwork during which a corpus of audio-visual recordings, transcripts and translations has been compiled. The corpus is the primary data source for all analyses in the thesis.
This study covers a wide range of topics that are described in 12 chapters. Beyond the expected chapters on phonology, verb morphology and clause syntax, the description has a special focus on complex predicates. Typologically, the most interesting features are verbal number and the extensive use of multi-verb constructions (MVCs). The word class of demonstratives is especially rich and covers a wide area of functions. Furthermore, we find many typical TNG features: gender agreement on the verb, verb-final clause syntax, a lack of nominal morphology, switch reference and tail-head linkage.
The appendix of this grammar includes two fully glossed texts and a large word list (Muyu-English) with over 2500 entries. The grammar is accompanied by an openly accessible collection of language material archived in the Endangered Languages Archive (ELAR)
Barriers and enablers of 1.5° lifestyles: Shallow and deep structural factors shaping the potential for sustainable consumption
No full textIntroduction: Transforming consumption and lifestyles toward sustainability cannot be achieved by individual behavior change alone but requires changes in the structures in which this behavior is embedded. However, “structure” is a blurry concept and scholars use it in a multitude of ways. What often remains implicit in studies on structural phenomena are different types of structures, how they may or may not restrict the agency of individuals in particular ways, and how these restrictions support sustainable consumption patterns at the societal level. To move beyond the current state of research, this article systematizes political, economic, technological, and societal structural factors the literature identifies as impactful regarding the sustainability of consumption and lifestyles compatible with the targets of the Paris Agreement. Methods: We draw on a systematic review of existing research and use empirical observations to develop conceptual terms that revisit the structure-agency dilemma and offer ways going forward about (un)sustainable consumption. Results: We do so based on the material or ideational, as well as shallow or deep nature of these factors. Thereby, the article throws light on the deep and opaque material and ideational structural factors lying underneath and shaping the sustainability impact of the more visible, shallow structural factors typically considered in public debates about sustainability governance. Discussion: The article, thus, highlights the need to consider and address these deep structural factors for any effective pursuit of transformation
Beiträge zum Mathematikunterricht 2024:57. Jahrestagung der Gesellschaft für Didaktik der Mathematik
No full textDer Band enthält die Beiträge 57. Jahrestagung der Gesellschaft für Didaktik der Mathematik vom 04.03.2024 bis 08.03.2024 in Essen. Dabei handelt es sich um die Fokus- und Hauptvorträge, die Beiträge aus den Minisymposien, die Einzelvorträge, die Kurzvorträge und die Berichte der Arbeitskreise
Drosophila hedgehog signaling range and robustness depend on direct and sustained heparan sulfate interactions
No full textMorphogens determine cellular differentiation in many developing tissues in a concentration dependent manner. As a central model for gradient formation during animal development, Hedgehog (Hh) morphogens spread away from their source to direct growth and pattern formation in the 'Drosophila' wing disc. Although heparan sulfate (HS) expression in the disc is essential for this process, it is not known whether HS regulates Hh signaling and spread in a direct or in an indirect manner. To answer this question, we systematically screened two composite Hh binding areas for HS in vitro and expressed mutated proteins in the 'Drosophila' wing disc. We found that selectively impaired HS binding of the second site reduced Hh signaling close to the source and caused striking wing mispatterning phenotypes more distant from the source. These observations suggest that HS constrains Hh to the wing disc epithelium in a direct manner, and that interfering with this constriction converts Hh into freely diffusing forms with altered signaling ranges and impaired gradient robustness
Ethylene Production in the Petrochemical Industry: Competitive Risks and Impacts of the EU Emission Trading Scheme
No full textThe European petrochemical industry is facing significant challenges that threaten its global competitiveness. Key challenges are the rising energy costs and a global increase in overcapacity for critical petrochemical building blocks, including ethylene, propylene, butadiene, benzene, mixed xylol, and toluene (Berry C., 2024). The European Union Emissions Trading Scheme (EU ETS), established with the aim to facilitate the reduction of greenhouse gas emissions in the face of climate change, also imposes further economic burdens on the industry. European emitters must purchase CO2 allowances (EUAs), while the Carbon Boarder Adjustment Mechanism (CBAM) does not provide full compensation for imports of chemicals from non-EU countries, exacerbating competitive disadvantages. This study conducts a comparative analysis of the competitiveness between the EU and the US in 2023, focusing on naphtha- and ethane-based steam cracking. The calculation of variable production costs for 2023 shows a competitive disadvantage for EU producers, with variable production costs in Europe being 380 higher per ton compared to the US. The situation is further exacerbated by the cost of EUAs, which could increase production costs by up to 11.5% by 2030. The introduction of the EUAs for European CO2 emitters without cost compensation by considering imports via the CBAM leads to a further deterioration of the competitive situation. EUAs costs could represent up to 11.5% of variable production costs by 2030, depending on the technology and forecast. This study highlights the compounded impact of rising production costs and environmental regulations on the competitiveness of European ethylene production
Evidence of polygenic regulation of the physiological presence of neurofilament light chain in human serum
No full textIntroduction: The measurement of neurofilament light chain (NfL) in blood is a promising biomarker of neurological injury and disease. We investigated the genetic factors that underlie serum NfL levels (sNfL) of individuals without neurological conditions. Methods: We performed a discovery genome-wide association study (GWAS) of sNfL in participants of the German BiDirect Study (N = 1,899). A secondary GWAS for meta-analysis was performed in a small Austrian cohort (N = 287). Results from the meta-analysis were investigated in relation with several clinical variables in BiDirect. Results: Our discovery GWAS identified 12 genomic loci at the suggestive threshold ((p < 1 × 10−5). After meta-analysis, 7 loci were suggestive of an association with sNfL. Genotype-specific differences in sNfL were observed for the lead variants of meta-analysis loci (rs34523114, rs114956339, rs529938, rs73198093, rs34372929, rs10982883, and rs1842909) in BiDirect participants. We identified potential associations in meta-analysis loci with markers of inflammation and renal function. At least 6 protein-coding genes (ACTG2, TPRKB, DMXL1, COL23A1, NAT1, and RIMS2) were suggested as genetic factors contributing to baseline sNfL levels. Discussion: Our findings suggest that polygenic regulation of neuronal processes, inflammation, metabolism and clearance modulate the variability of NfL in the circulation. These could aid in the interpretation of sNfL measurements in a personalized manner
Excitatory stimulation of the ventromedial prefrontal cortex reduces cognitive gambling biases via improved feedback learning
No full textHumans are subject to a variety of cognitive biases, such as the framing-effect or the gambler's fallacy, that lead to decisions unfitting of a purely rational agent. Previous studies have shown that the ventromedial prefrontal cortex (vmPFC) plays a key role in making rational decisions and that stronger vmPFC activity is associated with attenuated cognitive biases. Accordingly, dysfunctions of the vmPFC are associated with impulsive decisions and pathological gambling. By applying a gambling paradigm in a between-subjects design with 33 healthy adults, we demonstrate that vmPFC excitation via transcranial direct current stimulation (tDCS) reduces the framing-effect and the gambler's fallacy compared to sham stimulation. Corresponding magnetoencephalographic data suggest improved inhibition of maladaptive options after excitatory vmPFC-tDCS. Our analyses suggest that the underlying mechanism might be improved reinforcement learning, as effects only emerge over time. These findings encourage further investigations of whether excitatory vmPFC-tDCS has clinical utility in treating pathological gambling or other behavioral addictions
Informelle Motivationsurteile in der Schule: Urteilsprozesse von Lehrkräften
No full textMotivation spielt eine Schlüsselrolle für das Lernen von Schüler*innen. Lehrkräfte beurteilen deren Motivation jeden Tag intuitiv, jedoch stimmen sie nur gering mit ihren Schüler*innen überein. Die vorliegende Dissertation beleuchtete, welche Mechanismen zu der geringen Übereinstimmung beitragen und, ob die Schüler*innen-Selbstsicht und Lehrkräfte-Fremdsicht angenähert werden kann. In Studie 1 zeigten Schüler*innen im Linsenmodell eine Priorisierung motivationsrelevanter Ziele, um ihre Motivation einzuschätzen, wohingegen Lehrkräfte besonders stark auf Leistungsinformationen achteten. In Studie 2 nutzten Lehrkräfte allerdings Zielinformationen dann besonders stark, wenn diese verfügbar waren. Das Memorieren von Informationen führte jedoch wieder zur Nutzung von Leistung. In Studie 3 sollte individuelles Feedback Lehrkräften helfen, Informationen besser zu nutzen – eine signifikante Verbesserung blieb jedoch aus. In der Dissertation konnte die geringe Übereinstimmung durch differenzielle Informationsnutzung erklärt werden, was möglicherweise am leistungsorientierten schulpolitischen Fokus liegt. Dieser könnte im komplexen Schulalltag verzerrende mentale Abkürzungen beim Beurteilen von Motivation begünstigen. Formatives Assessment könnte helfen, solche Verzerrungen zu verringern.Motivation is crucial for student learning, yet teachers’ judgments of student motivation often differ from students’ self-assessments. This dissertation investigated the mechanisms behind this discrepancy and explores ways to align these perspectives. In Study 1, students judged their motivation with an emphasis on achievement goals, whereas teachers prioritized achievement information. In Study 2, however, making achievement goal information directly available led teachers to rely on it more strongly. Nonetheless, when they had to memorize information, they reverted to using achievement information again. In Study 3, individual feedback was intended to help teachers improve their usage, but no significant change was observed. Overall, the findings suggest that low agreement stems from differential information use, possibly influenced by a performance-oriented school policy. This could encourage biased mental heuristics when judging motivation in the inherently complex everyday school environment. Formative assessment could help to reduce such biases