Moritz Klinik

Abstract The uniform orientation of π‐conjugated chromophores in thin films is critical for anisotropic charge, energy, and mass transport, with direct implications for optoelectronic and sensing applications. In this study, the molecular orientation and supramolecular organization of a linear amphiphilic BOPHY dye in Langmuir monolayers at the air‐water interface are investigated. By combining in situ X‐ray reflectivity (XRR), grazing incidence X‐ray diffraction (GIXD), and classical molecular dynamics (MD) simulations, the structural evolution of the monolayer through two distinct condensed phases is elucidated. GIXD reveals that the alkyl chains primarily determine the packing density, forming short‐range hexagonal domains upon compression, while the chromophores remain locally ordered but lack long‐range crystallinity. These results indicate that molecular tilting and bending arise from asymmetries between the BOPHY chromophore and the three alkyl chains. MD simulations further reveal coplanar π‐stacked BOPHY dimers or small aggregates with angular distributions that differ between the two phases. The strong agreement between experiment and simulation provides a comprehensive understanding of the alignment of the linear chromophores at the air‐water interface and establishes this integrated approach as a powerful framework for predicting and designing functional chromophore assemblies in 2D molecular films.

Introduction Treatment of schizophrenia remains a challenge despite the development of numerous antipsychotics (AP) (Pompili et al CNS NDDT 2017; 16 870-884). The various strategies to address patients’ unmet needs, such as AP polypharmacy or switching AP, do not seem to provide adequate benefit. A reason for this may reside in the similarity of mechanisms of action of most APs. However, the monoaminergic systems targeted by these drugs are not always disrupted in schizophrenia, as it is widely accepted that patients who fail to respond to AP have glutamatergic, but not dopaminergic dysfunctions (Moghaddam et al NPP 2012; 37 4-15). Evenamide normalizes excessive glutamate release without affecting its basal levels, and it does not interact with >150 CNS targets. It has been shown to be effective in animal models of psychosis as monotherapy and add-on to AP. Previous trials indicate that evenamide benefits patients with schizophrenia with inadequate response and have shown clinically important benefits lasting up to 1-year in TRS (Anand et al IJNPP 2023; 26 523-528). Objectives Study 008A, a phase 2/3 international, randomized, double-blind, placebo-controlled, 4-week trial, assessed the efficacy and safety of evenamide 30 mg bid as add-on in patients poorly responding to an SGA. Methods Outpatients with a diagnosis of schizophrenia, still symptomatic (PANSS 70-85; CGI-S 4-6) despite treatment with an SGA at a therapeutic dose (confirmed through plasma levels) for an adequate period, were enrolled. Efficacy was assessed on the PANSS, CGI-S, and LOF through the comparison of changes from baseline to Day 29 between evenamide and placebo groups using a MMRM analysis. Moreover, the proportion of patients reaching a clinically important improvement on the PANSS and CGI-C were compared between groups using a logistic regression model (chi-square test). Safety measures comprised: TEAEs, vital signs, labs, ECG/EEG, seizure checklist, physical/neurological/eye examinations, C-SSRS, ESRS-A, CDSS. Results 291 patients were randomized in the study in 11 countries (EU, Asia and LATAM), and 280 completed the study. The low attrition rate (<4%), and proportion of patients with TEAEs (~25% in both groups) indicate that evenamide was well tolerated. A statistically significant greater improvement was found on the PANSS total score and on the CGI-S in the evenamide compared to the placebo group. Furthermore, a significantly higher proportion of patients treated with evenamide, compared to those receiving placebo, experienced clinically meaningful benefit measured on the PANSS (≥20% improvement) and CGI-C (at least much improved). Conclusions This is the first randomized, placebo-controlled trial to demonstrate the clinical benefit of adding a NCE modulating glutamate in patients with schizophrenia who did not experience adequate response from treatment with a SGA. Disclosure of Interest R. Anand Consultant of: AbbVie, Acadia, BiolineRx, Domain, Enkam, Erydel, Forest, Janssen, Hoffman La Roche, Lundbeck, Noema, Ono, Pfizer, UCB, Shire, Sigma-Tau, Takeda, Teva, A. Turolla Employee of: Newron Pharmaceuticals SpA, G. Chinellato Employee of: Newron Pharmaceuticals SpA, R. Giuliani Employee of: Newron Pharmaceuticals SpA, F. Sansi Employee of: Newron Pharmaceuticals SpA, R. Hartman Consultant of: Newron Pharmaceuticals SpA.

The myocardial-ischaemic-injury-index (MI3) is a novel machine learning algorithm for the early diagnosis of type 1 non-ST-segment elevation myocardial infarction (NSTEMI). The performance of MI3, both when using early serial blood draws (eg, at 1 h or 2 h) and in direct comparison with guideline-recommended algorithms, remains unknown. Our aim was to externally validate MI3 and compare its performance with that of the European Society of Cardiology (ESC) 0/1h-algorithm. In this secondary analysis of a multicentre international diagnostic cohort study, adult patients (age >18 years) presenting to the emergency department with symptoms suggestive of myocardial infarction were prospectively enrolled from April 21, 2006, to Feb 27, 2019 in 12 centres from five European countries (Switzerland, Spain, Italy, Poland, and Czech Republic). Patients were excluded if they presented with ST-segment-elevation myocardial infarction, did not have at least two serial high-sensitivity cardiac troponin I (hs-cTnI) measurements, or if the final diagnosis remained unclear. The final diagnosis was centrally adjudicated by two independent cardiologists using all available medical records, including serial hs-cTnI measurements and cardiac imaging. The primary outcome was type 1 NSTEMI. The performance of MI3 was directly compared with that of the ESC 0/1h-algorithm. Among 6487 patients, (median age 61·0 years [IQR 49·0-73·0]; 2122 [33%] female and 4365 [67%] male), 882 (13·6%) patients had type 1 NSTEMI. The median time difference between the first and second hs-cTnI measurement was 60·0 mins (IQR 57·0-70·0). MI3 performance was very good, with an area under the receiver-operating-characteristic curve of 0·961 (95% CI 0·957 to 0·965) and a good overall calibration (intercept -0·09 [-0·2 to 0·02]; slope 1·02 [0·97 to 1·08]). The originally defined MI3 score of less than 1·6 identified 4186 (64·5%) patients as low probability of having a type 1 NSTEMI (sensitivity 99·1% [95% CI 98·2 to 99·5]; negative predictive value [NPV] 99·8% [95% CI 99·6 to 99·9]) and an MI3 score of 49·7 or more identified 915 (14·1%) patients as high probability of having a type 1 NSTEMI (specificity 95·0% [94·3 to 95·5]; positive predictive value [PPV] 69·1% [66·0-72·0]). The sensitivity and NPV of the ESC 0/1h-algorithm were higher than that of MI3 (difference for sensitivity 0·88% [0·19 to 1·60], p=0·0082; difference for NPV 0·18% [0·05 to 0·32], p=0·016), and the rule-out efficacy was higher for MI3 (11% difference, p<0·0001). Specificity and PPV for MI3 were superior (difference for specificity 3·80% [3·24 to 4·36], p<0·0001; difference for PPV 7·84% [5·86 to 9·97], p<0·0001), and the rule-in efficacy was higher for the ESC 0/1h-algorithm (5·4% difference, p<0·0001). MI3 performs very well in diagnosing type 1 NSTEMI, demonstrating comparability to the ESC 0/1h-algorithm in an emergency department setting when using early serial blood draws. Swiss National Science Foundation, Swiss Heart Foundation, the EU, the University Hospital Basel, the University of Basel, Abbott, Beckman Coulter, Roche, Idorsia, Ortho Clinical Diagnostics, Quidel, Siemens, and Singulex.

Die Autorin stellt einige der historischen Weimarer Hausgärten vor, darunter Goethes Garten am Stern, der Kirms-Krackow-Garten, das Wohnhaus des Architekten Henry van der Welde "Hohe Pappeln" und der Garten des Musterhauses Am Horn, und thematisiert dabei deren Musealisierung.

Die Ordnung einer Dokumentation ausert sich in ihrer Struktur und Gliederung sowie in ihrer Klarheit und Eindeutigkeit.

Abstract Flow control is of interest in many open and wall‐bounded shear flows in order to reduce drag or to avoid sudden large fluctuations that may lead to material failure. An established means of control is the application of suction through a porous wall. Here, we combine suction with a feedback strategy whereby the suction velocity is adjusted in response to either the kinetic energy or the shear stress at the bottom wall. The control procedure is then used in an attempt to stabilize invariant solutions and to carry out direct numerical simulations with a prescribed value of the friction coefficient.

Longevity of complex organic devices critically depends on the supramolecular integrity of the constituting layers and interfaces. Because the latter are soft matter, they can structurally respond to perturbation of their supramolecular structure by relaxing back to a thermodynamically favorable state. To use this response for self-healing of optoelectronically active layers and particularly interfaces, the degraded dyes in these layers need to be exchanged with non-degraded ones. Here, we present a dye layer interfaced between a solid surface and a dye reservoir that autonomously self-heals after photo-degradation of single molecules to restore its optical function. Surface sensitive in situ photothermal deflection spectroscopy reveals that this supramolecular self-healing approach critically depends on the thermodynamic stability of the layer, the chemical change of the dye upon degradation, and the medium dissolving the degraded dye and providing the reservoir dyes. Hence, the interplay of these parameters is key to successfully using this supramolecular self-healing approach to thin layers and interfaces in organic device for increased sustainability of organic optoelectronics and related fields.