Creating a common ground for professional development of university chemistry (STEM) lecturers in Europe

Today, we are faced with immense global challenges in finding sustainable equilibria between socio-economic, political, and ecological concerns. The European Chemistry Thematic Network (ECTN), the European University Association (EUA) and the European Commission are committed to sustainable improvement of the quality of university chemistry education to cope with these challenges. In this position paper, we advocate the creation of the Eurolecturer Academy (ELA), an innovative, European state of the art higher education learning platform serving academics in their continuous professional development of teaching competences and thereby supporting academics to educate students to be successful in the changing world. Within this newly established educational entity, there will be two levels of membership, Associated membership and Full membership. The ELA will not only facilitate continuous professional development of university teaching staff but will at the same time create a structure to support recognition of teaching competences of lecturers within the European dimension in teaching and learning. The certification will profit from the new 5th European Qualification Framework for micro-credentials, providing a much needed “academic currency” for the purpose of recognition of academic credentials. The ELA micro-credentials will be issued by certifying the learning outcomes of short-term learning experiences in the field of teaching and learning in higher education. The ELA will provide a micro-credentials catalogue that will address the needs for professional development of lecturers and ensure the quality of the micro-credentials through close cooperation with the internationally operating accreditation organization ASIIN (https://www.asiin.de/en/) using quality standards and valid assessment according to international best practice

Prediction of ventricular arrhythmia in phospholamban p.Arg14del mutation carriers-reaching the frontiers of individual risk prediction

AIMS: This study aims to improve risk stratification for primary prevention implantable cardioverter defibrillator (ICD) implantation by developing a new mutation-specific prediction model for malignant ventricular arrhythmia (VA) in phospholamban (PLN) p.Arg14del mutation carriers. The proposed model is compared to an existing PLN risk model. METHODS AND RESULTS: Data were collected from PLN p.Arg14del mutation carriers with no history of malignant VA at baseline, identified between 2009 and 2020. Malignant VA was defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. A prediction model was developed using Cox regression. The study cohort consisted of 679 PLN p.Arg14del mutation carriers, with a minority of index patients (17%) and male sex (43%), and a median age of 42 years [interquartile range (IQR) 27–55]. During a median follow-up of 4.3 years (IQR 1.7–7.4), 72 (10.6%) carriers experienced malignant VA. Significant predictors were left ventricular ejection fraction, premature ventricular contraction count/24 h, amount of negative T waves, and presence of low-voltage electrocardiogram. The multivariable model had an excellent discriminative ability {C-statistic 0.83 [95% confidence interval (CI) 0.78–0.88]}. Applying the existing PLN risk model to the complete cohort yielded a C-statistic of 0.68 (95% CI 0.61–0.75). CONCLUSION: This new mutation-specific prediction model for individual VA risk in PLN p.Arg14del mutation carriers is superior to the existing PLN risk model, suggesting that risk prediction using mutation-specific phenotypic features can improve accuracy compared to a more generic approach

CFTR Correctors and Antioxidants Partially Normalize Lipid Imbalance but not Abnormal Basal Inflammatory Cytokine Profile in CF Bronchial Epithelial Cells

A deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) function in CF leads to chronic lung disease. CF is associated with abnormalities in fatty acids, ceramides, and cholesterol, their relationship with CF lung pathology is not completely understood. Therefore, we examined the impact of CFTR deficiency on lipid metabolism and pro-inflammatory signaling in airway epithelium using mass spectrometric, protein array. We observed a striking imbalance in fatty acid and ceramide metabolism, associated with chronic oxidative stress under basal conditions in CF mouse lung and well-differentiated bronchial epithelial cell cultures of CFTR knock out pig and CF patients. Cell-autonomous features of all three CF models included high ratios of ω-6- to ω-3-polyunsaturated fatty acids and of long- to very long-chain ceramide species (LCC/VLCC), reduced levels of total ceramides and ceramide precursors. In addition to the retinoic acid analog fenretinide, the anti-oxidants glutathione (GSH) and deferoxamine partially corrected the lipid profile indicating that oxidative stress may promote the lipid abnormalities. CFTR-targeted modulators reduced the lipid imbalance and oxidative stress, confirming the CFTR dependence of lipid ratios. However, despite functional correction of CF cells up to 60% of non-CF in Ussing chamber experiments, a 72-h triple compound treatment (elexacaftor/tezacaftor/ivacaftor surrogate) did not completely normalize lipid imbalance or oxidative stress. Protein array analysis revealed differential expression and shedding of cytokines and growth factors from CF epithelial cells compared to non-CF cells, consistent with sterile inflammation and

Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation w

ACTION TYPES AND ACT TOKENS IN DEONTIC LOGIC OF THE OUGHT-TO-DO TYPE

In this paper we argue that the distinction between action types and act tokens is relevant for a proper understanding of the distinction between prima facie obligations and all out obligations. After a discussion of the approach in which norms that deal with action types are analysed in terms of the deontic classification of individual acts, we explore the opposite approach. We take norms that deal with action types as primitive, and show how the evaluation of individual acts is influenced (but not determined) by the deontic status of the several action types which these acts instantiate. This view is formalised, first in a simple version which disregards exceptions to norms, and then in a more complex variant, which takes exceptions into account. Finally the distinction between action types and act tokens is used to characterise the distinction between weak and strong permissions. content areas: ought-to-do logic, action types, act tokens, prima facie obligations, exceptions, weak and strong permissio