Prävention von moralischen Problemen in der Patientenversorgung

Hintergrund und Zielsetzung: Gesundheitsfachpersonen sind in der Patientenversorgung regelmässig mit moralischen Problemen konfrontiert. Diese können die Qualität der Behandlung und die Patientensicherheit gefährden, bei Fachpersonen moralischen Distress auslösen oder bei Patient*innen und Angehörigen zu psychischen Belastungen und Unzufriedenheit führen. Die Schweizerische Akademie der Medizinischen Wissenschaften empfiehlt daher, an Gesund-heitsinstitutionen Strukturen zur klinischen Ethikunterstützung zu etablieren, die Behandelnde, Patient*innen und Angehörige bei der ethischen Entscheidungsfindung unterstützen können. Eine bisher in der Schweiz wenig implementierte und evaluierte Form ist die präventive Ethikunterstützung, deren Ziel es ist, moralische Probleme im Klinikalltag bereits in einem frühen Entwicklungsstadium zu erkennen und anzugehen. In dieser Arbeit wird ein Instrument zur Früherkennung und Frühintervention moralischer Probleme entwickelt, ein Prozessmodell zur präventiven Ethikunterstützung erarbeitet und dessen Kernelemente – insbesondere Risikofak-toren für moralische Probleme – werden empirisch untersucht. Methoden: Die genannten Forschungsziele werden in drei separaten, aber aufeinander bezogenen Studien untersucht. In der ersten Studie wird auf der Basis einer systematischen Litera-turrecherche und einer Beobachtungsstudie auf der Abteilung Jugendforensik an den Universitären Psychiatrischen Kliniken Basel ein Instrument zur Früherkennung und -intervention erar-beitet. Die zweite Studie folgt einem Mixed-Methods-Design, wobei in halbstrukturierten Inter-views klinische Experten (n = 20) am Universitätsspital Basel und an den Universitären Psychiat-rischen Kliniken Basel zu ihren Erfahrungen mit der Prävention von moralischen Problemen befragt werden. In den Interviewleitfaden ist ein Likert-skalierter Fragebogen integriert, der deskriptiv-statistisch ausgewertet wird. In der dritten Studie werden in einem Scoping-Review Risikofaktoren für moralische Probleme in der Patientenversorgung zusammengetragen. Diese Risikofaktoren werden anschliessend anhand einer konsekutiven Fallserie von Ethikkonsultationen (n = 204) untersucht, die zwischen 2012 und 2020 an zwei universitären Spitälern in Basel durchgeführt wurden. Resultate: In der ersten Studie wurden für die forensische Kinder- und Jugendpsychiatrie 24 moralische Problemfelder in den Bereichen Autonomie, Hilfeleisten und Nichtschaden, Gerechtigkeit, Moralkompetenz, Professionalität sowie Diagnostik und Einschätzung identifiziert. Besonders häufig treten dabei Fragen zum angemessenen Umgang mit Moralkompetenz und Moralerziehung, mit Regeln und Sanktionen, zu Chancen und Risken der Behandlung und zur Freiheit- und Privatsphäre der Jugendlichen auf. Das Instrument der Früherkennung und -intervention enthält spezifische Risikofaktoren und Indikatoren für moralische Probleme in der Jugendforensik sowie Verfahren zur Interventionsplanung und Entscheidungsfindung. Das in der zweiten Studie vorgestellte Prozessmodell der präventiven Ethikunterstützung integriert alle Kernelemente der Prävention: Phasen, Risikofaktoren und Indikatoren moralischer Probleme sowie Entscheidungsparametern, Folgen und präventive Massnahmen. Es wird eine Vielzahl an Risikofaktoren, Indikatoren, Entscheidungsparameter, Folgen und präventiven Interventionen identifiziert. Als besonders hilfreich werden frühzeitige Ethikgespräche mit Kolleg*innen, frühzeitige teaminterne ethische Fallbesprechungen, Ethik-Ansprechpersonen auf der Station, Ethikfortbildung, Ethikrichtlinien, Ad-hoc-Ethikberatung, proaktive Ethikkonsultationen, Ethikvisiten und Früherkennung sowie Projekte zur Verbesserung von Prozessen, Kommunikationswe-gen und ethischem Klima beurteilt. In der dritten Studie wurden 99 moralische Risikofaktoren in der Patientenversorgung identifiziert. Von diesen liegen 87 in den untersuchten Ethikkonsul-tationsfällen vor, wovon zehn hoch prävalent (≥ 50 %) sind: Patientenvulnerabilität, fehlende oder unklare Ethikrichtlinien, Schichtarbeit, unzureichende Verständigung zwischen Patient*innen und Behandelnden, unzureichende Kommunikation, Multimorbidität, Uneinigkeit zwischen Patient*innen und Behandelnden und mehrere Behandlungsteams. In allen medizinischen Fachbereichen gibt es darüber hinaus spezifische, hoch prävalente Risikofaktoren. Schlussfolgerungen: Das integrative Modell der präventiven Ethikunterstützung umfasst ein breites Spektrum an präventiven Interventionen, um moralische Probleme proaktiv, frühzeitig, niederschwellig und systemisch anzugehen. Ein zentraler Bestandteil ist dabei die Früherkennung moralischer Probleme mittels geeigneter Risikofaktoren und früher Indikatoren, die in dieser Arbeit identifiziert werden. Exemplarisch für eine präventive Intervention wird ein Instrument zur Früherkennung und Frühintervention von moralischen Problemen in der Jugendforensik entwickelt. Die vorliegende Arbeit kann somit als Grundlage für die Etablierung neuer Angebote der Ethikunterstützung in der Gesundheitsversorgung und als Ausgangspunkt für weitere Forschung zur präventiven Ethikunterstützung dienen

Enzymatic Synthesis of Trimethyl-ϵ-caprolactone : Process Intensification and Demonstration on a 100 L Scale

Optimization and scaling up of the Baeyer-Villiger oxidation of 3,3,5-trimethyl-cyclohexanone to trimethyl-ε-caprolactones (CHLs) were studied to demonstrate this technology on a 100 L pilot plant scale. The reaction was catalyzed by a cyclohexanone monooxygenase from Thermocrispum municipale that utilizes the costly redox cofactor nicotinamide adenine dinucleotide phosphate (reduced form), which was regenerated by a glucose dehydrogenase (GDH). As a first stage, different cyclohexanone monooxygenase formulations were tested: cell-free extract, whole cells, fermentation broth, and sonicated fermentation broth. Using broth resulted in the highest yield (63%) and required the least biocatalyst preparation effort. Two commercial glucose dehydrogenases (GDH-105 and GDH-01) were evaluated, resulting in similar performances. Substrate dosing rates and biocatalyst loadings were optimized. On a 30 mL scale, the best conditions were found when 30 mM h-1 dosing rate, 10% (v/v) cyclohexanone monooxygenase broth, and 0.05% (v/v) of glucose dehydrogenase (GDH-01) liquid enzyme formulation were applied. These same conditions (with oxygen instead of air) were applied on a 1 L scale with 92% conversion, achieving a specific activity of 13.3 U gcell wet weight (cww)-1, a space time yield of 3.4 gCHL L-1 h-1, and a biocatalyst yield of 0.83 gCHL gcww-1. A final 100 L demonstration was performed in a pilot plant facility. After 9 h, the reaction reached 85% conversion, 12.8 U gcww-1, a space time yield of 2.7 g L-1 h-1, and a biocatalyst yield of 0.60 gCHL gcww-1. The extraction of product resulted in 2.58 kg of isolated final product. The overall isolated CHL yield was 76% (distal lactone 47% and proximal lactone 53%)

VTE Risk assessment – a prognostic Model: BATER Cohort Study of young women

BACKGROUND: Community-based cohort studies are not available that evaluated the predictive power of both clinical and genetic risk factors for venous thromboembolism (VTE). There is, however, clinical need to forecast the likelihood of future occurrence of VTE, at least qualitatively, to support decisions about intensity of diagnostic or preventive measures. MATERIALS AND METHODS: A 10-year observation period of the Bavarian Thromboembolic Risk (BATER) study, a cohort study of 4337 women (18–55 years), was used to develop a predictive model of VTE based on clinical and genetic variables at baseline (1993). The objective was to prepare a probabilistic scheme that discriminates women with virtually no VTE risk from those at higher levels of absolute VTE risk in the foreseeable future. A multivariate analysis determined which variables at baseline were the best predictors of a future VTE event, provided a ranking according to the predictive power, and permitted to design a simple graphic scheme to assess the individual VTE risk using five predictor variables. RESULTS: Thirty-four new confirmed VTEs occurred during the observation period of over 32,000 women-years (WYs). A model was developed mainly based on clinical information (personal history of previous VTE and family history of VTE, age, BMI) and one composite genetic risk markers (combining Factor V Leiden and Prothrombin G20210A Mutation). Four levels of increasing VTE risk were arbitrarily defined to map the prevalence in the study population: No/low risk of VTE (61.3%), moderate risk (21.1%), high risk (6.0%), very high risk of future VTE (0.9%). In 10.6% of the population the risk assessment was not possible due to lacking VTE cases. The average incidence rates for VTE in these four levels were: 4.1, 12.3, 47.2, and 170.5 per 10(4 )WYs for no, moderate, high, and very high risk, respectively. CONCLUSION: Our prognostic tool – containing clinical information (and if available also genetic data) – seems to be worthwhile testing in medical practice in order to confirm or refute the positive findings of this study. Our cohort study will be continued to include more VTE cases and to increase predictive value of the model

How Cognitive Models of Human Body Experience Might Push Robotics

In the last decades, cognitive models of multisensory integration in human beings have been developed and applied to model human body experience. Recent research indicates that Bayesian and connectionist models might push developments in various branches of robotics: assistive robotic devices might adapt to their human users aiming at increased device embodiment, e.g., in prosthetics, and humanoid robots could be endowed with human-like capabilities regarding their surrounding space, e.g., by keeping safe or socially appropriate distances to other agents. In this perspective paper, we review cognitive models that aim to approximate the process of human sensorimotor behavior generation, discuss their challenges and potentials in robotics, and give an overview of existing approaches. While model accuracy is still subject to improvement, human-inspired cognitive models support the understanding of how the modulating factors of human body experience are blended. Implementing the resulting insights in adaptive and learning control algorithms could help to taylor assistive devices to their user's individual body experience. Humanoid robots who develop their own body schema could consider this body knowledge in control and learn to optimize their physical interaction with humans and their environment. Cognitive body experience models should be improved in accuracy and online capabilities to achieve these ambitious goals, which would foster human-centered directions in various fields of robotics

Solidarität und Verantwortung in der Pandemie

Die Corona-Pandemie berührt weite Bereiche des gesellschaftlichen, wirtschaftlichen und politischen Lebens. Mit hoher Dringlichkeit stellt sich angesichts der Ressourcenknappheit die Forderung nach einer konkret gelebten Solidarität und verantwortungsvollen ­Koordination zwischen Behörden, Organisationen, Institutionen, Generationen und Individuen. Medizinethikerinnen und -ethiker der Schweiz formulieren dazu vier Postulate

"What's (the) Matter?", A Show on Elementary Particle Physics with 28 Demonstration Experiments

We present the screenplay of a physics show on particle physics, by the Physikshow of Bonn University. The show is addressed at non-physicists aged 14+ and communicates basic concepts of elementary particle physics including the discovery of the Higgs boson in an entertaining fashion. It is also demonstrates a successful outreach activity heavily relying on the university physics students. This paper is addressed at anybody interested in particle physics and/or show physics. This paper is also addressed at fellow physicists working in outreach, maybe the experiments and our choice of simple explanations will be helpful. Furthermore, we are very interested in related activities elsewhere, in particular also demonstration experiments relevant to particle physics, as often little of this work is published. Our show involves 28 live demonstration experiments. These are presented in an extensive appendix, including photos and technical details. The show is set up as a quest, where 2 students from Bonn with the aid of a caretaker travel back in time to understand the fundamental nature of matter. They visit Rutherford and Geiger in Manchester around 1911, who recount their famous experiment on the nucleus and show how particle detectors work. They travel forward in time to meet Lawrence at Berkeley around 1950, teaching them about the how and why of accelerators. Next, they visit Wu at DESY, Hamburg, around 1980, who explains the strong force. They end up in the LHC tunnel at CERN, Geneva, Switzerland in 2012. Two experimentalists tell them about colliders and our heroes watch live as the Higgs boson is produced and decays. The show was presented in English at Oxford University and University College London, as well as Padua University and ICTP Trieste. It was 1st performed in German at the Deutsche Museum, Bonn (5/'14). The show has eleven speaking parts and involves in total 20 people.Comment: 113 pages, 88 figures. An up to date version of the paper with high resolution pictures can be found at http://www.th.physik.uni-bonn.de/People/dreiner/Downloads/. In v2 the acknowledgements and a citation are correcte

Candidate Glutamatergic Neurons in the Visual System of Drosophila

The visual system of Drosophila contains approximately 60,000 neurons that are organized in parallel, retinotopically arranged columns. A large number of these neurons have been characterized in great anatomical detail. However, studies providing direct evidence for synaptic signaling and the neurotransmitter used by individual neurons are relatively sparse. Here we present a first layout of neurons in the Drosophila visual system that likely release glutamate as their major neurotransmitter. We identified 33 different types of neurons of the lamina, medulla, lobula and lobula plate. Based on the previous Golgi-staining analysis, the identified neurons are further classified into 16 major subgroups representing lamina monopolar (L), transmedullary (Tm), transmedullary Y (TmY), Y, medulla intrinsic (Mi, Mt, Pm, Dm, Mi Am), bushy T (T), translobula plate (Tlp), lobula intrinsic (Lcn, Lt, Li), lobula plate tangential (LPTCs) and lobula plate intrinsic (LPi) cell types. In addition, we found 11 cell types that were not described by the previous Golgi analysis. This classification of candidate glutamatergic neurons fosters the future neurogenetic dissection of information processing in circuits of the fly visual system

Clinical and virological characteristics of hospitalised COVID-19 patients in a German tertiary care centre during the first wave of the SARS-CoV-2 pandemic: a prospective observational study

Purpose: Adequate patient allocation is pivotal for optimal resource management in strained healthcare systems, and requires detailed knowledge of clinical and virological disease trajectories. The purpose of this work was to identify risk factors associated with need for invasive mechanical ventilation (IMV), to analyse viral kinetics in patients with and without IMV and to provide a comprehensive description of clinical course. Methods: A cohort of 168 hospitalised adult COVID-19 patients enrolled in a prospective observational study at a large European tertiary care centre was analysed. Results: Forty-four per cent (71/161) of patients required invasive mechanical ventilation (IMV). Shorter duration of symptoms before admission (aOR 1.22 per day less, 95% CI 1.10-1.37, p < 0.01) and history of hypertension (aOR 5.55, 95% CI 2.00-16.82, p < 0.01) were associated with need for IMV. Patients on IMV had higher maximal concentrations, slower decline rates, and longer shedding of SARS-CoV-2 than non-IMV patients (33 days, IQR 26-46.75, vs 18 days, IQR 16-46.75, respectively, p < 0.01). Median duration of hospitalisation was 9 days (IQR 6-15.5) for non-IMV and 49.5 days (IQR 36.8-82.5) for IMV patients. Conclusions: Our results indicate a short duration of symptoms before admission as a risk factor for severe disease that merits further investigation and different viral load kinetics in severely affected patients. Median duration of hospitalisation of IMV patients was longer than described for acute respiratory distress syndrome unrelated to COVID-19

Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease

We sought to identify new susceptibility loci for Alzheimer's disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimer's Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ≤ 1 × 10−5. We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10−17; including ADGC data, meta P = 5.0 × 10−21) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10−14; including ADGC data, meta P = 1.2 × 10−16) are new Alzheimer's disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10−4; including ADGC data, meta P = 8.6 × 10−9), CD33 (GERAD+, P = 2.2 × 10−4; including ADGC data, meta P = 1.6 × 10−9) and EPHA1 (GERAD+, P = 3.4 × 10−4; including ADGC data, meta P = 6.0 × 10−10)

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.NovartisEli Lilly and CompanyAstraZenecaAbbViePfizer UKCelgeneEisaiGenentechMerck Sharp and DohmeRocheCancer Research UKGovernment of CanadaArray BioPharmaGenome CanadaNational Institutes of HealthEuropean CommissionMinistère de l'Économie, de l’Innovation et des Exportations du QuébecSeventh Framework ProgrammeCanadian Institutes of Health Researc