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Institute
Wir untersuchen eine neuartige Gruppe von Polarisationsmitteln – gemischtvalente Verbindungen – mittels theoretischer und experimenteller Methoden und demonstrieren ihre Leistungsfähigkeit in NMR-Experimenten mit Hochfeld-DNP (DNP=Dynamic Nuclear Polarization, dynamische Kernpolarisation) im festen Zustand. Diese gemischtvalenten Verbindungen stellen eine Gruppe von Molekülen dar, bei denen die molekulare Mobilität auch in Festkörpern erhalten bleibt. Folglich können solche Polarisationsmittel unter günstigen Bedingungen für die dynamische Kernpolarisationsbildung bei ultrahohen Magnetfeldern verwendet werden, um Overhauser-DNP-Experimente im Festkörper durchzuführen.
Mixed-valence compounds as polarizing agents for overhauser dynamic nuclear polarization in solids
(2021)
Herein, we investigate a novel set of polarizing agents—mixed-valence compounds—by theoretical and experimental methods and demonstrate their performance in high-field dynamic nuclear polarization (DNP) NMR experiments in the solid state. Mixed-valence compounds constitute a group of molecules in which molecular mobility persists even in solids. Consequently, such polarizing agents can be used to perform Overhauser-DNP experiments in the solid state, with favorable conditions for dynamic nuclear polarization formation at ultra-high magnetic fields.
Co-design of a trustworthy AI system in healthcare: deep learning based skin lesion classifier
(2021)
This paper documents how an ethically aligned co-design methodology ensures trustworthiness in the early design phase of an artificial intelligence (AI) system component for healthcare. The system explains decisions made by deep learning networks analyzing images of skin lesions. The co-design of trustworthy AI developed here used a holistic approach rather than a static ethical checklist and required a multidisciplinary team of experts working with the AI designers and their managers. Ethical, legal, and technical issues potentially arising from the future use of the AI system were investigated. This paper is a first report on co-designing in the early design phase. Our results can also serve as guidance for other early-phase AI-similar tool developments.
Hereditary angioedema (HAE) in children and adolescents : a consensus on therapeutic strategies
(2012)
Hereditary angioedema due to C1 inhibitor (C1 esterase inhibitor) deficiency (types I and II HAE-C1-INH) is a rare disease that usually presents during childhood or adolescence with intermittent episodes of potentially life-threatening angioedema. Diagnosis as early as possible is important to avoid ineffective therapies and to properly treat swelling attacks. At a consensus meeting in June 2011, pediatricians and dermatologists from Germany, Austria, and Switzerland reviewed the currently available literature, including published international consensus recommendations for HAE therapy across all age groups. Published recommendations cannot be unconditionally adopted for pediatric patients in German-speaking countries given the current approval status of HAE drugs. This article provides an overview and discusses drugs available for HAE therapy, their approval status, and study results obtained in adult and pediatric patients. Recommendations for developing appropriate treatment strategies in the management of HAE in pediatric patients in German-speaking countries are provided.Conclusion Currently, plasma-derived C1 inhibitor concentrate is considered the best available option for the treatment of acute HAE-C1-INH attacks in pediatric patients in German-speaking countries, as well as for short-term and long-term prophylaxis.
Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Commission (EC), recently published ethics guidelines for what it terms “trustworthy” AI. These guidelines are aimed at a variety of stakeholders, especially guiding practitioners toward more ethical and more robust applications of AI. In line with efforts of the EC, AI ethics scholarship focuses increasingly on converting abstract principles into actionable recommendations. However, the interpretation, relevance, and implementation of trustworthy AI depend on the domain and the context in which the AI system is used. The main contribution of this paper is to demonstrate how to use the general AI HLEG trustworthy AI guidelines in practice in the healthcare domain. To this end, we present a best practice of assessing the use of machine learning as a supportive tool to recognize cardiac arrest in emergency calls. The AI system under assessment is currently in use in the city of Copenhagen in Denmark. The assessment is accomplished by an independent team composed of philosophers, policy makers, social scientists, technical, legal, and medical experts. By leveraging an interdisciplinary team, we aim to expose the complex trade-offs and the necessity for such thorough human review when tackling socio-technical applications of AI in healthcare. For the assessment, we use a process to assess trustworthy AI, called 1Z-Inspection® to identify specific challenges and potential ethical trade-offs when we consider AI in practice.
Aims: The primary safety and efficacy endpoints of the randomized FIRE AND ICE trial have recently demonstrated non-inferiority of cryoballoon vs. radiofrequency current (RFC) catheter ablation in patients with drug-refractory symptomatic paroxysmal atrial fibrillation (AF). The aim of the current study was to assess outcome parameters that are important for the daily clinical management of patients using key secondary analyses. Specifically, reinterventions, rehospitalizations, and quality-of-life were examined in this randomized trial of cryoballoon vs. RFC catheter ablation.
Methods and results: Patients (374 subjects in the cryoballoon group and 376 subjects in the RFC group) were evaluated in the modified intention-to-treat cohort. After the index ablation, log-rank testing over 1000 days of follow-up demonstrated that there were statistically significant differences in favour of cryoballoon ablation with respect to repeat ablations (11.8% cryoballoon vs. 17.6% RFC; P = 0.03), direct-current cardioversions (3.2% cryoballoon vs. 6.4% RFC; P = 0.04), all-cause rehospitalizations (32.6% cryoballoon vs. 41.5% RFC; P = 0.01), and cardiovascular rehospitalizations (23.8% cryoballoon vs. 35.9% RFC; P < 0.01). There were no statistical differences between groups in the quality-of-life surveys (both mental and physical) as measured by the Short Form-12 health survey and the EuroQol five-dimension questionnaire. There was an improvement in both mental and physical quality-of-life in all patients that began at 6 months after the index ablation and was maintained throughout the 30 months of follow-up.
Conclusion: Patients treated with cryoballoon as opposed to RFC ablation had significantly fewer repeat ablations, direct-current cardioversions, all-cause rehospitalizations, and cardiovascular rehospitalizations during follow-up. Both patient groups improved in quality-of-life scores after AF ablation.
Clinical trial registration: ClinicalTrials.gov identifier: NCT01490814.
Pathogenic variants in PRRT2, encoding the proline-rich transmembrane protein 2, have been associated with an evolving spectrum of paroxysmal neurologic disorders. Based on a cohort of children with PRRT2-related infantile epilepsy, this study aimed at delineating the broad clinical spectrum of PRRT2-associated phenotypes in these children and their relatives. Only a few recent larger cohort studies are on record and findings from single reports were not confirmed so far. We collected detailed genetic and phenotypic data of 40 previously unreported patients from 36 families. All patients had benign infantile epilepsy and harbored pathogenic variants in PRRT2 (core cohort). Clinical data of 62 family members were included, comprising a cohort of 102 individuals (extended cohort) with PRRT2-associated neurological disease. Additional phenotypes in the cohort of patients with benign sporadic and familial infantile epilepsy consist of movement disorders with paroxysmal kinesigenic dyskinesia in six patients, infantile-onset movement disorders in 2 of 40 individuals, and episodic ataxia after mild head trauma in one girl with bi-allelic variants in PRRT2. The same girl displayed a focal cortical dysplasia upon brain imaging. Familial hemiplegic migraine and migraine with aura were reported in nine families. A single individual developed epilepsy with continuous spikes and waves during sleep. In addition to known variants, we report the novel variant c.843G>T, p.(Trp281Cys) that co-segregated with benign infantile epilepsy and migraine in one family. Our study highlights the variability of clinical presentations of patients harboring pathogenic PRRT2 variants and expands the associated phenotypic spectrum.