Von Wissen zur Performanz in der Ausbildung von sportunterrichtenden Lehrpersonen: Eine Delphi-Studie und ein Pretest zur inhaltlichen Validierung der Testinstrumente

The basis for evaluating the effectiveness of interventions in the education and continuing professional development of physical education (PE) teachers involves valid, reliable, and objective instruments, which are largely lacking. Content validity is a necessary basis for the development of such instruments. Accordingly, this study presents the content validation of a test for the assessment of (classroom management-related) professional knowledge and the perception, interpretation, and decision-making (PID) of prospective PE teachers. The result is a content-validated knowledge test (110 test items) as well as a video-based test for the assessment of PID (ten vignettes, 217 items). In a next step, the instruments are empirically validated. (DIPF/Orig.)Die Basis zur Eruierung der Effektivität von Interventionen in der Aus- und Weiterbildung von sportunterrichtenden Lehrpersonen stellen valide, reliable und objektive Instrumente dar, die weitgehend fehlen. Zur Entwicklung derartiger Instrumente ist die Inhaltsvalidität eine notwendige Grundlage. In vorliegender Studie wird dementsprechend die inhaltliche Validierung eines Tests zur Erfassung des (jeweils klassenführungsbezogenen) professionellen Wissens und der Wahrnehmung, Interpretation und Entscheidung (PID) bei (angehenden) sportunterrichtenden Lehrpersonen dargestellt. Es resultiert ein inhaltlich validierter Wissenstest (110 Testitems) sowie ein videobasierter Test zur Erfassung der PID (zehn Vignetten, 217 Items). In einem nächsten Schritt werden die Instrumente empirisch validiert. (DIPF/Orig.

A new polymorph of dimesitylborinic acid

A new polymorph of dimesitylborinic acid (or hydroxy­dimesitylborane), C18H23BO, showcasing different crystal packing and symmetry, complements the previously reported polymorph [Weese, Bartlett, Murray, Olmstead & Power (1987 ▶). Inorg. Chem. 26, 2409–2413; Entwistle, Batsanov & Marder (2007 ▶). Acta Cryst. E63, o2639–o2641]. The structure of the title compound contains only one mol­ecule in the asymmetric unit, and no O—H⋯O inter­actions are observed. However, mol­ecules are linked by weak inter­molecuar O—H⋯π(arene) inter­actions to form centrosymmetric dimers

Vitamin B12, folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation

Vitamin B12 (cobalamin, Cbl) is a nutrient essential to human health. Due to its complex structure and dual cofactor forms, Cbl undergoes a complicated series of absorptive and processing steps before serving as cofactor for the enzymes methylmalonyl-CoA mutase and methionine synthase. Methylmalonyl-CoA mutase is required for the catabolism of certain (branched-chain) amino acids into an anaplerotic substrate in the mitochondrion, and dysfunction of the enzyme itself or in production of its cofactor adenosyl-Cbl result in an inability to successfully undergo protein catabolism with concomitant mitochondrial energy disruption. Methionine synthase catalyzes the methyl-Cbl dependent (re)methylation of homocysteine to methionine within the methionine cycle; a reaction required to produce this essential amino acid and generate S-adenosylmethionine, the most important cellular methyl-donor. Disruption of methionine synthase has wide-ranging implications for all methylation-dependent reactions, including epigenetic modification, but also for the intracellular folate pathway, since methionine synthase uses 5-methyltetrahydrofolate as a one-carbon donor. Folate-bound one-carbon units are also required for deoxythymidine monophosphate and de novo purine synthesis; therefore, the flow of single carbon units to each of these pathways must be regulated based on cellular needs. This review provides an overview on Cbl metabolism with a brief description of absorption and intracellular metabolic pathways. It also provides a description of folate-mediated one-carbon metabolism and its intersection with Cbl at the methionine cycle. Finally, a summary of recent advances in understanding of how both pathways are regulated is presented

Interaction of standardized mistletoe (Viscum album) extracts with chemotherapeutic drugs regarding cytostatic and cytotoxic effects in vitro

BACKGROUND: Given the importance of complementary and alternative medicine (CAM) to cancer patients, there is an increasing need to learn more about possible interactions between CAM and anticancer drugs. Mistletoe (Viscum album L.) belongs to the medicinal herbs that are used as supportive care during chemotherapy. In the in vitro study presented here the effect of standardized mistletoe preparations on the cytostatic and cytotoxic activity of several common conventional chemotherapeutic drugs was investigated using different cancer cell lines. METHODS: Human breast carcinoma cell lines HCC1937 and HCC1143 were treated with doxorubicin hydrochloride, pancreas adenocarcinoma cell line PA-TU-8902 with gemcitabine hydrochloride, prostate carcinoma cell line DU145 with docetaxel and mitoxantrone hydrochloride and lung carcinoma cell line NCI-H460 was treated with docetaxel and cisplatin. Each dose of the respective chemotherapeutic drug was combined with Viscum album extract (VAE) in clinically relevant concentrations and proliferation and apoptosis were measured. RESULTS: VAE did not inhibit chemotherapy induced cytostasis and cytotoxicity in any of our experimental settings. At higher concentrations VAE showed an additive inhibitory effect. CONCLUSIONS: Our in vitro results suggest that no risk of safety by herb drug interactions has to be expected from the exposition of cancer cells to chemotherapeutic drugs and VAE simultaneously

A systematic review of moral reasons on orphan drug reimbursement

The number of market approvals of orphan medicinal products (OMPs) has been increasing steadily in the last 3 decades. While OMPs can offer a unique chance for patients suffering from rare diseases, they are usually very expensive. The growing number of approved OMPs increases their budget impact despite their low prevalence, making it pressing to find solutions to ethical challenges on how to fairly allocate scarce healthcare resources under this context. One potential solution could be to grant OMPs special status when considering them for reimbursement, meaning that they are subject to different, and less stringent criteria than other drugs. This study aims to provide a systematic analysis of moral reasons for and against such a special status for the reimbursement of OMPs in publicly funded healthcare systems from a multidisciplinary perspective.; With a systematic review of reasons, we identified 39 reasons represented in 243 articles (scientific and grey literature) for and against special status for the reimbursement of OMPs, then categorized them into nine topics. Taking a multidisciplinary perspective, we found that most articles came from health policy (n = 103) and health economics (n = 49). More articles took the position for a special status of OMPs (n = 97) than those against it (n = 31) and there was a larger number of reasons identified in favour (29 reasons) than against (10 reasons) this special status.; Results suggest that OMP reimbursement issues should be assessed and analysed from a multidisciplinary perspective. Despite the higher occurrence of reasons and articles in favour of a special status, there is no clear-cut solution for this ethical challenge. The binary perspective of whether or not OMPs should be granted special status oversimplifies the issue: both OMPs and rare diseases are too heterogeneous in their characteristics for such a binary perspective. Thus, the scientific debate should focus less on the question of disease prevalence but rather on how the important variability of different OMPs concerning e.g. target population, cost-effectiveness, level of evidence or mechanism of action could be meaningfully addressed and implemented in Health Technology Assessments

Tricarboxylic acid cycle enzyme activities in a mouse model of methylmalonic aciduria

Methylmalonic acidemia (MMA) is a propionate pathway disorder caused by dysfunction of the mitochondrial enzyme methylmalonyl-CoA mutase (MMUT). MMUT catalyzes the conversion of methylmalonyl-CoA to succinyl-CoA, an anaplerotic reaction which feeds into the tricarboxylic acid (TCA) cycle. As part of the pathological mechanisms of MMA, previous studies have suggested there is decreased TCA activity due to a toxic inhibition of TCA cycle enzymes by MMA related metabolites, in addition to reduced anaplerosis. Here, we have utilized mitochondria isolated from livers of a mouse model of MMA (Mut-ko/ki) and their littermate controls (Ki/wt) to examine the amounts and enzyme functions of most of the TCA cycle enzymes. We have performed mRNA quantification, protein semi-quantitation, and enzyme activity quantification for TCA cycle enzymes in these samples. Expression profiling showed increased mRNA levels of fumarate hydratase in the Mut-ko/ki samples, which by contrast had reduced protein levels as detected by immunoblot, while all other mRNA levels were unaltered. Immunoblotting also revealed decreased protein levels of 2-oxoglutarate dehydrogenase and malate dehydrogenase 2. Interesting, the decreased protein amount of 2-oxoglutarate dehydrogenase was reflected in decreased activity for this enzyme while there is a trend towards decreased activity of fumarate hydratase and malate dehydrogenase 2. Citrate synthase, isocitrate dehydrogenase 2/3, succinyl-CoA synthase, and succinate dehydrogenase are not statistically different in terms of quantity of enzyme or activity. Finally, we found decreased activity when examining the function of methylmalonyl-CoA mutase in series with succinate synthase and succinate dehydrogenase in the Mut-ko/ki mice compared to their littermate controls, as expected. This study demonstrates decreased activity of certain TCA cycle enzymes and by corollary decreased TCA cycle function, but it supports decreased protein quantity rather than toxic inhibition as the underlying mechanism of action. SUMMARY: Methylmalonic acidemia (MMA) is an inborn metabolic disorder of propionate catabolism. In this disorder, toxic metabolites are considered to be the major pathogenic mechanism for acute and long-term complications. However, despite optimized therapies aimed at reducing metabolite levels, patients continue to suffer from late complications, including metabolic stroke and renal insufficiency. Since the propionate pathway feeds into the tricarboxylic acid (TCA) cycle, we investigated TCA cycle function in a constitutive MMA mouse model. We demonstrated decreased amounts of the TCA enzymes, Mdh2 and Ogdh as semi-quantified by immunoblot. Enzymatic activity of Ogdh is also decreased in the MMA mouse model compared to controls. Thus, when the enzyme amounts are decreased, we see the enzymatic activity also decreased to a similar extent for Ogdh. Further studies to elucidate the structural and/or functional links between the TCA cycle and propionate pathways might lead to new treatment approaches for MMA patients

Towards Explainability and Fairness in Swiss Judgement Prediction: Benchmarking on a Multilingual Dataset

The assessment of explainability in Legal Judgement Prediction (LJP) systems is of paramount importance in building trustworthy and transparent systems, particularly considering the reliance of these systems on factors that may lack legal relevance or involve sensitive attributes. This study delves into the realm of explainability and fairness in LJP models, utilizing Swiss Judgement Prediction (SJP), the only available multilingual LJP dataset. We curate a comprehensive collection of rationales that `support' and `oppose' judgement from legal experts for 108 cases in German, French, and Italian. By employing an occlusion-based explainability approach, we evaluate the explainability performance of state-of-the-art monolingual and multilingual BERT-based LJP models, as well as models developed with techniques such as data augmentation and cross-lingual transfer, which demonstrated prediction performance improvement. Notably, our findings reveal that improved prediction performance does not necessarily correspond to enhanced explainability performance, underscoring the significance of evaluating models from an explainability perspective. Additionally, we introduce a novel evaluation framework, Lower Court Insertion (LCI), which allows us to quantify the influence of lower court information on model predictions, exposing current models' biases.Comment: Accepted at LREC-COLING 202

The impact of visualizing operational deviations on overall quality in assembly lines

A framework for data collection and visualization of operational deviation at a Volvo truck manufacturing plant implementing Volvo Group\u27s production system, Volvo Production System (VPS), is presented. This includes visualisation of daily quality performance indicators to support decision making and improvement actions at the shop floor team level. The approach is evaluated in a qualitatively study using a survey instrument to collect responses from managers and team leaders, which acted as input for the actual use of the data and as validation of the framework. The results from this evaluation show that potentially operational deviations can be reduced, impacting positively quality performance indicators such as first-time through (FTT). This paper also provides a brief description of the VPS in connection with data analytics and visualization