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Arzneimittel bei stationärer Aufnahme als prädiktiver Risikofaktor für postoperatives Delir
Get PDFDas postoperative Delir ist die häufigste Komplikation nach chirurgischen Eingriffen bei älteren Patienten und mit negativen Folgen wie einer verminderten funktionellen und kognitiven Leistungsfähigkeit sowie einer erhöhten Mortalität und Morbidität assoziiert. Aufgrund des demographischen Wandels und einer alternden Gesellschaft wird es auch in Zukunft notwendig sein, die begrenzten Ressourcen im Gesundheitssystem zu bündeln und alltagstaugliche Strategien zur Reduktion postoperativer Komplikationen bei älteren Patienten zu etablieren. Für die rechtzeitige Einleitung präventiver Maßnahmen ist die frühzeitige Identifizierung von Risikopatienten bei der stationären Aufnahme erforderlich, die durch die Anwendung von Risikoscores ermöglicht wird. Das Auftreten eines postoperativen Delirs wird durch zahlreiche prädisponierende und auslösende Risikofaktoren, darunter auch Arzneimittel, beeinflusst. Zu den prädisponierenden Risikofaktoren zählen Deliririsko-erhöhende und anticholinerge Arzneimittel in der Aufnahmemedikation. Vor diesem Hintergrund beleuchtet die vorliegende Doktorarbeit die Identifikation von Risikopatienten für ein postoperatives Delir zum Zeitpunkt der Arzneimittelanamnese anhand eines neu entwickelten prädiktiven Risikoscores und vergleicht darüber hinaus verschiedene Scores zur Erfassung der anticholinergen Belastung.
In Veröffentlichung I wurde ein prädiktiver Risikoscore für postoperatives Delir zur Anwendung in der pharmazeutischen Arzneimittelanamnese entwickelt, der die Aufnahmemedikation und weiteren verfügbaren Risikofaktoren berücksichtigt. Der Risikoscore mit delirium risk-increasing drugs (DRD-Score) enthält die vier Risikofaktoren Alter (> 65 Jahre, 2 Punkte; > 75 Jahre, 3 Punkte), eingeschränkte Nierenfunktion (< 60 ml/min/1,73 m2, 1 Punkt), hohe anticholinerge Belastung (German Anticholinergic Burden [GerACB]-Score ≥ 3, 1 Punkt) und Einnahme von Deliririsko-erhöhenden Arzneimitteln (n ≥ 2, 2 Punkte). Patienten ab ≥ 4 Punkten wurden als Risikopatient klassifiziert. Die potenziellen Risikofaktoren männliches Geschlecht, Rauchen und erhöhter Alkoholkonsum [45] waren nicht signifikant mit dem Auftreten eines postoperativen Delirs assoziiert und wurden daher nicht in den Score aufgenommen. Insbesondere für Apotheker bietet der Score einen pragmatischen Ansatz zur schnellen Risikoeinschätzung von Patienten bei der stationären Aufnahme basierend auf den verfügbaren Medikations- und Labordaten.
Der Score erzielte eine gute bis moderate Sensitivität (Entwicklungskohorte [EntK] 83 %, Validierungskohorte [ValK] 63 %) und eine gute Spezifität (EntK 80 %, ValK 77 %). Etwa ein Drittel aller identifizierten Risikopatienten entwickelte ein postoperatives Delir (positive predictive value [PPV] EntK 38 %, ValK 31 %), während Nichtrisikopatienten mit hoher Wahrscheinlichkeit kein postoperatives Delir entwickelten (negative predictive value [NPV] EntK 97 %, ValK 93 %). Die erforderlichen Risikofaktoren sind zum Zeitpunkt der Arzneimittelanamnese routinemäßig verfügbar und ein geschulter Apotheker kann die medikationsbezogenen Faktoren unkompliziert einschätzen. Bei der Erhebung des ACB-Scores können zudem Online-Rechner unterstützen [46]. Das Ziel des Screenings ist es, Patienten mit einem erhöhten Bedarf an pharmazeutischen Interventionen zu identifizieren. Als Konsequenz kann in der Arzneimittelanamnese ein verstärkter Fokus auf Interventionen bei identifizierten Risikopatienten liegen. Ein möglicher pharmazeutischer Beitrag sind Austauschempfehlungen bei zentral wirksamen anticholinergen Wirkstoffen, eine alters- und nierenfunktionsadaptierte Dosisprüfung sowie eine Überprüfung auf potenziell inadäquate Medikation im Alter. Darüber hinaus ist es sinnvoll, durch die Risikokommunikation mit Ärzten und Pflegenden allgemeine nicht-pharmakologische Präventionsmaßnahmen einzuleiten.
Eine Limitation des DRD-Scores ist, dass wichtige prädiktive Risikofaktoren wie Grunderkrankungen sowie funktionelle und kognitive Beeinträchtigungen nicht berücksichtigt werden. Dies lässt sich mit dem Anwendungsziel in der pharmazeutischen Arzneimittelanamnese und dem Fokus auf der Identifikation von Patienten mit pharmazeutischem Interventionsbedarf begründen. Da der DRD-Score in einem orthopädischen und unfallchirurgischen Patientenkollektiv entwickelt und intern validiert wurde, ist eine externe Validierung in einer anderen Patientenpopulation erforderlich, um die Prädiktionsgenauigkeit umfassender bewerten zu können.
Veröffentlichung II befasste sich mit der anticholinergen Belastung der Aufnahmemedikation als prädiktivem Risikofaktor für postoperatives Delir und ging der Frage nach, ob die Dosierung der Arzneimittel hierbei berücksichtigt werden sollte. Zu diesem Zweck wurden drei anticholinergic burden (ACB)-Scores miteinander vergleichen: der GerACB (potenzbezogen), die extended Muscarinic Acetylcholinergic Receptor ANTagonist Exposure (extMARANTE)-Skala (potenz- und dosisbezogen) und der German Drug Burden Index (GerDBI) (dosisbezogen). Insgesamt zeigte sich eine substanzielle Übereinstimmung in der Bewertung der Aufnahmemedikation durch die Scores (Interrater Reliabilität für Patienten mit und ohne postoperativem Delir κ = 0,645 und κ = 0,632). Für alle drei Scores war eine hohe Belastung signifikant mit dem Auftreten eines postoperativen Delirs in einer multivariablen Analyse assoziiert (adjustiert für Alter, Anzahl Arzneimittel in der Aufnahmemedikation, Demenz und American Society of Anesthesiologists Status). Bei der Verwendung als Screeninginstrument erzielten die Scores eine niedrige Sensitivität (GerACB 24 %, extMARANTE 42 %, GerDBI 41 %), eine hohe Spezifität (GerACB 94 %, extMARANTE 85 %, GerDBI 88 %), einen niedrigen PPV (GerACB 49 %, extMARANTE 39 %, GerDBI 43 %) und einen hohen NPV (GerACB 85 %, extMARANTE 87 %, GerDBI 87 %).
Die drei ACB-Scores sind aufgrund ihrer niedrigen Sensitivität und ihres geringen PPV als alleinige Screeninginstrumente für postoperatives Delir nicht geeignet, obwohl eine hohe Belastung signifikant mit postoperativem Delir assoziiert war. Dies unterstreicht die Notwendigkeit, die anticholinerge Belastung in Kombination mit weiteren Risikofaktoren für das postoperative Delir zu bewerten, wie beispielsweise durch den DRD-Score. Die zusätzliche Berücksichtigung der Dosis geht mit einer aufwändigeren Scoreberechnung einher, während sich die Bewertung der anticholinergen Belastung dadurch nur geringfügig ändert. Der einfache GerACB erzielte zwar die geringste Sensitivität, aber auch die höchste Spezifität und den höchsten PPV. Für eine einfache und pragmatische Überprüfung der anticholinergen Belastung der Aufnahmemedikation bleibt der GerACB somit ausreichend. Bei Patienten > 65 Jahre mit hoher anticholinerger Belastung sollten potenzielle Austauschmöglichkeiten, insbesondere von zentral wirksamen anticholinergen Wirkstoffen, evaluiert werden. Auch wenn in dieser Studie eine Dosisberücksichtigung bei Berechnung der anticholinergen Belastung als nicht notwendig bewertet wurde, sollte bei der Medikationsanalyse eine alters- und nierenfunktionsadaptierte Dosis überprüft werden.
Zusammenfassend wurden in dieser Doktorarbeit Möglichkeiten zur Identifizierung von Risikopatienten für postoperatives Delir bei stationärer Aufnahme anhand ihrer Medikation evaluiert. Delirrisiko-erhöhende und anticholinerge Arzneimittel in der Aufnahmemedikation sind für Patienten > 65 Jahre, insbesondere mit einer eingeschränkten Nierenfunktion, prädiktive und potenziell modifizierbare Risikofaktoren für postoperatives Delir. Die Berücksichtigung der Dosis anticholinerger Arzneimittel durch dosisbezogene ACB-Scores ist nicht erforderlich, die Verwendung eines einfachen potenzbasierten ACB-Scores ist ausreichend. Arzneimittel als prädiktive Risikofaktoren und die Anwendung des DRD-Scores und der ACB-Scores müssen im Kontext des multifaktoriellen Geschehens beim postoperativen Delir mit weiteren prädiktiven und auslösenden Risikofaktoren betrachtet werden. Damit ist eine moderate Sensitivität der Scores akzeptabel und mögliche pharmazeutische sowie nicht-pharmakologische Präventionsmaßnahmen sollten für Risikopatienten abgeleitet und umgesetzt werden. Sowohl der DRD- als auch die ACB-Scores erreichten eine hohe Spezifität, so dass bei Fehlen der medikationsbezogenen Risikofaktoren ein postoperatives Delir nur selten auftrat und pharmazeutischer Interventionsbedarf bei der Aufnahmemedikation nicht häufig erforderlich sein sollte. Als Ausblick zu dieser Arbeit sollte untersucht werden, ob Risikopatienten laut des DRD-Scores einen erhöhten Interventionsbedarf in ihrer Medikation aufweisen, welche pharmazeutischen Interventionen erforderlich sind und ob es möglich und sinnvoll ist, diese Interventionen im präoperativen Setting umzusetzen.Postoperative delirium is the most common complication following surgical procedures in older adult patients and is associated with adverse outcomes such as functional and cognitive decline and increased mortality and morbidity. With demographic changes and an aging society, there is a need to develop practical strategies that take limited healthcare resources into account to reduce postoperative complications in older patients. Early identification of patients at risk upon hospital admission is necessary for timely initiation of preventive measures, which is made possible by the use of risk scores. The development of postoperative delirium is influenced by numerous predisposing and precipitating factors, including drugs. Delirium risk-increasing and anticholinergic drugs in the admission medication are examples of predisposing risk factors. Following this, this dissertation investigates the identification of patients at risk for postoperative delirium at the time of medication reconciliation using a newly developed predictive risk score and compares different scores for assessing anticholinergic burden.
In publication I, a predictive risk score for postoperative delirium was developed for use during pharmacist-led medication reconciliation based on admission medication and other available risk factors. The risk score including delirium risk-increasing drugs (DRD score) considers four risk factors: age (> 65 years, 2 points; > 75 years, 3 points), reduced kidney function (< 60 ml/min/1.73 m2, 1 point), high anticholinergic burden (German Anticholinergic Burden [GerACB] score ≥ 3, 1 point), and use of delirium risk-increasing drugs (≥ 2, 2 points). Patients with a score ≥ 4 points were classified as risk patients. The potential risk factors male gender, smoking, and heavy alcohol consumption [45] were not significantly associated with postoperative delirium and were therefore not included in the final score. For pharmacists in particular, the DRD score provides a pragmatic approach for rapid risk assessment of patients upon hospital admission, based on available medication and laboratory data.
The score achieved good to moderate sensitivity (development cohort [DevC] 83%, validation cohort [ValC] 63%) and good specificity (DevC 80%, ValC 77%). Approximately one-third of identified risk patients developed postoperative delirium (positive predictive value [PPV] DevC 38%, ValC 31%), whereas non-risk patients were unlikely to develop postoperative delirium (negative predictive value [NPV] DevC 97%, ValC 93%). The required risk factors are routinely available during medication reconciliation and a trained pharmacist can easily evaluate medication-related factors. Online calculators may also assist in calculating the ACB score [46]. The aim of the screening is to identify patients with an increased need for pharmaceutical interventions. Consequently, pharmacists can focus on interventions for identified risk patients during medication reconciliation. Possible contributions by pharmacists include recommendations for replacing drugs with central anticholinergic effects, reviewing drug doses according to age and kidney function, and checking for potentially inadequate medication for older patients. In addition, general non-pharmacological preventive measures could be initiated through risk communication with doctors and nurses.
A limitation of the DRD score is that other important risk factors, such as underlying diseases and functional and cognitive impairment, were not included. This is due to the focus on assessment during medication reconciliation with the aim of identifying patients who might benefit the most from drug safety recommendations. As the DRD score has been developed and internally validated in an orthopaedic and trauma surgery cohort, external validation in other patient populations is needed to broadly assess its predictive accuracy.
Publication II addressed anticholinergic burden in admission medication as a predictive risk factor for postoperative delirium and investigated whether the drug dose should be taken into account. Three anticholinergic burden (ACB) scores were compared: the GerACB (potency-related), the extended Muscarinic Acetylcholinergic Receptor ANTagonist Exposure (extMARANTE) scale (potency- and dose-related) and the German Drug Burden Index (GerDBI) (dose-related). Overall, there was substantial agreement in the assessment of admission medication by the scores (interrater reliability for patients with and without postoperative delirium κ = 0.645 and κ = 0.632). For all three scores, a high burden was significantly associated with postoperative delirium in a multivariable analysis (adjusted for age, number of drugs in the admission medication, dementia, and American Society of Anesthesiologists status). When used as a screening tool, the scores achieved low sensitivity (GerACB 24%, extMARANTE 42%, GerDBI 41%), high specificity (GerACB 94%, extMARANTE 85%, GerDBI 88%), low PPV (GerACB 49%, extMARANTE 39%, GerDBI 43%) and high NPV (GerACB 85%, extMARANTE 87%, GerDBI 87%).
The results indicate that due to their low sensitivity and PPV, none of the three ACB scores are suitable as stand-alone screening tools for postoperative delirium, although there was a significant association between a high burden and postoperative delirium. This emphasises the need to evaluate the anticholinergic burden alongside other risk factors for delirium, as with the DRD score. Additional dose consideration requires a more complex calculation, whereas medication assessment changes only slightly. The simple GerACB score had the lowest sensitivity but the highest specificity and PPV, making it sufficient for pragmatic screening of admission medication. In patients aged > 65 years with a high anticholinergic burden, potential substitution of drugs should be evaluated, especially for drugs with central anticholinergic effects. Although dose consideration using dose-related ACB scores was not deemed necessary in this study, age- and renal function-adjusted dosing should be checked during medication analysis.
In summary, this dissertation evaluated methods to identify patients at risk for postoperative delirium at hospital admission based on their admission medication. Delirium risk-increasing and anticholinergic drugs in admission medication are predictive and potentially modifiable risk factors for postoperative delirium in patients aged > 65 years, especially in those with impaired renal function. The use of dose-related ACB scores is not necessary, and a simple potency-based ACB score remains sufficient for screening a patient’s medication. The impact of drugs as predictive risk factors and the use of the DRD and ACB scores must be evaluated in the context of the multifactorial aetiology of delirium, along with other predictive and precipitating risk factors. Therefore, a moderate sensitivity of the scores is acceptable, and potential pharmaceutical and non-pharmacological preventive measures should be derived and implemented for patients at risk. Both the DRD and ACB scores achieved high specificity, meaning that in the absence of medication-related risk factors, postoperative delirium is rare and pharmaceutical interventions regarding the admission medication should not be required frequently. Further investigations should determine whether risk patients according to the DRD score have an increased need for interventions in their medication, which pharmaceutical interventions are necessary, and whether it is possible and feasible to implement these interventions in the preoperative setting
Untersuchungen zum Futterwert und Einsatz von Produkten der Luzernepflanze (Medicago sativa) in der ökologischen Schweinefütterung
Get PDFDraw anatomy - an investigation of the learning method drawing on a tablet to learn gross anatomy
Get PDFMedical students can learn anatomy in many ways. Traditional methods of learning anatomy are increasingly being supplemented by new technology-based methods as mobile devices are used more frequently. Therefore, this thesis aimed to investigate one learning method, namely drawing anatomical content on a tablet. The central questions were whether drawing on a tablet leads to better learning outcome than paper-based methods and whether there is a difference in the sustainability of this learning outcome. Furthermore, it was investigated whether there is a correlation between the quality of strategy implementation and the learning outcome.
To answer these questions, a study was conducted with a total of 105 medical students who learned anatomical content using three different learning methods. These three learning methods were drawing on a tablet, drawing on paper, and making summaries on paper. The learning phase consisted of all participants reading the same learning text with the corresponding pictures and making drawings and summaries in sections about the anatomical content of this learning text. The group with the tablet used a drawing app, developed by our workgroup, on the tablet with a digital pen. To measure the learning outcome, an anatomy knowledge test was administered directly after the learning phase and at intervals of 4-6 weeks, and the quality of the drawings and summaries was assessed with a scoring sheet.
The results of this study showed that there was no significant difference between the three learning methods in terms of learning outcome and its sustainability. It was also found that there was a positive relationship between the quality of strategy implementation and the learning outcome and that the quality of the drawings and summaries produced moderated the effect of the learning method on the learning outcome. At low quality, writing on paper compared to drawing on paper, as well as drawing on a tablet compared to drawing on paper, led to lower learning outcome. At high quality, writing on paper compared to drawing on paper as well as drawing on the tablet compared to drawing on paper led to higher learning outcome.
These results show that drawing on a tablet can be used as an equivalent learning method for learning gross anatomy by medical students and that it is especially beneficial when the quality of the drawings is high. It must be kept in mind that the app we developed is still in its early stages and still has room for improvement. In addition, the students in this study have just had the opportunity to get to know the app and had to get used to the new
learning method. Future research could conduct further studies on drawing on the tablet
and investigate how learning outcomes change when the tablet and a drawing app are
integrated into the gross anatomy course and used regularly by the students. This work
contributes insights to this new learning method and thus enables further support of medical students in their learning
Statistische Auswertung zur Wirksamkeit von Pyrantel bei Strongyliden des Pferdes in Deutschland
Get PDFFacing the dilemma of trauma-focused therapy
Get PDFTrauma survivors often face a challenging dilemma: While clinical guidelines recommend early trauma-focused treatment to prevent chronic symptoms, legal actors frequently express concerns that such interventions – particularly imagery-based techniques like imagery rescripting (ImRs) and imaginal exposure (ImE) – could compromise the reliability of memory in legal contexts. This fear has led to widespread delays in clinical treatments until after judicial processes conclude, although empirical evidence from psychotherapy research supporting this cautious approach is lacking. The current dissertation systematically investigates whether and under which conditions imagery-based trauma-focused interventions impact voluntary, legally relevant memory of aversive events. To address this, three progressively building studies were conducted: two experimental analogue studies and one preregistered systematic review. Together, these studies aim to clarify potential memory effects of ImRs and ImE, compare their impact on memory accuracy, and integrate the findings into the broader memory distortion literature. This research offers essential insights for aligning clinical needs and forensic expectations in the treatment of trauma survivors.
Study I examined whether ImRs influences memory accuracy following real-life stress exposure. A total of 100 students were exposed to the Trier Social Stress Test (TSST), which reliably induces a personally experienced, psychosocially aversive event. Two days later, participants were randomly assigned to either a single ImRs session or a no-intervention control condition. Voluntary memory was assessed through free recall (before the intervention and one week later) and cued recall (one week later and after three months). The findings revealed that participants in the ImRs condition recalled significantly more correct details in free recall one week after the intervention compared to the control condition, without an increase in incorrect details. No differences between conditions emerged in cued recall after one week and after three months, however, voluntary memory tended to deteriorate over time. Contrary to expectations, this effect was not associated with ImRs.
Study II tested the effects of ImRs and ImE on memory accuracy following analogue trauma exposure. In a controlled laboratory setting, 120 highly anxious female participants watched a distressing scene involving sexual violence as part of the trauma-film paradigm. Twenty-four hours later, participants were randomly allocated to one of three conditions: ImRs, ImE, or a no-intervention control. Voluntary memory was measured through free recall (pre-intervention and six days post-intervention), cued recall, and recognition tasks (six days and two weeks post-intervention). The results showed that ImE significantly increased the number of correctly recalled details in free recall compared to both ImRs and control conditions, without increasing memory distortions. ImRs did not affect memory performance relative to the control condition. Across all condition, incorrect details decreased over time, and no evidence of false memory inflation was observed.
Study III presents a preregistered systematic review synthesizing evidence from 95 studies examining the effects of imagery tasks and imagery-based interventions on voluntary memory. This review included basic memory studies and experimental analogue applications of ImRs, ImE, and hypnosis. Isolated eye movement tasks, often used as components of EMDR but not full EMDR protocols, were also analyzed in non-clinical contexts. The analysis revealed that experimental imagery tasks and hypnosis were frequently associated with belief inflation, source confusion, and memory distortion. In contrast, structured clinical interventions, particularly ImRs and ImE, showed no evidence of memory impairment and, in some cases, even improved recall accuracy or narrative coherence. Effects of isolated eye movement tasks in non-clinical settings were mixed. Across studies, the risk of memory distortion appeared to be more strongly linked to suggestive procedures and a lack of autobiographical grounding than to the use of imagery per se. Overall, the findings suggest that imagery-based intervention, when applied in structured clinical contexts, do not compromise memory accuracy.
Collectively, the three studies provide converging evidence that manualized, structured imagery interventions such as ImRs and ImE do not compromise the factual accuracy of voluntary memory. They may facilitate access to correct details under certain conditions and with appropriate safeguards. Crucial protective factors include a clear session structure, sufficient time for memory consolidation, strong patient authorship, and transparent separation between original and rescripted memory elements. In contrast, suggestive, externally controlled, or hypnotic interventions remain problematic and can indeed pose a risk to memory credibility. The findings challenge the common practice of delaying trauma-focused therapy during legal proceedings out of fear of contaminating memory evidence. Instead, legal and clinical professionals should collaborate to ensure that psychological treatments is conducted under scientifically validated conditions that protect both the well-being of survivors and the integrity of their testimony. Ultimately, this dissertation offers a valuable framework for balancing therapeutic urgency with forensic reliability
Effective learning mechanisms of external representations in quantum technology
Get PDFResearch into how learners visualize and learn quantum phenomena has been conducted in various ways for several decades (Küblbeck & Müller, 2002; Lichtfeldt, 1992; Müller & Wiesner, 1999; Wiesner, 1996). With the emergence of potential applications such as quantum computers, quantum cryptography and quantum sensor technology, interest in conveying quantum physics in an accessible, audience-appropriate way has grown markedly, corresponding competence frameworks for professional requirements in quantum technologies have been developed (European Commission et al., 2025; Greinert et al., 2022), and many representations have been developed or refined (e.g., Bley et al., 2024; Donhauser et al., 2024; Dür & Heusler, 2012, 2014; Huber & Glaser, 2024; Johnston et al., 2019; Yeung, 2020). Learners without a strong mathematical background—whether in schools or in professional settings (e.g., Kelly et al., 2024; Piña et al., 2025)—need approaches that make the field’s central element, the qubit, tangible. As an instructional strategy, the so-called “spin first approach” is recommended (Dür & Heusler, 2012; Sadaghiani, 2016; Sadaghiani & Munteanu, 2015); it introduces a two-state system early on, thereby enabling an early representation of the qubit.
This dissertation investigates which aspects of visual qubit representations differ in terms of effectiveness in learning quantum physics, without completely ignoring the underlying mathematics. To that end, it introduces a category system grounded in representation research, physics education, and quantum science, which was evaluated by experts using four exemplary visual qubit representations (Bloch sphere, Quantum Bead (Huber & Glaser, 2024), Pie-chart Model (Qake) (Donhauser et al., 2024; Yeung, 2020) and the circle notation (Bley et al., 2024; Johnston et al., 2019)).
Key objective was to find out how the features of visual qubit representations differ in terms of effectiveness in learning quantum physics concepts. First from an expert perspective (1) then from learners’ perspective (2, 3). This led to research focusing on multiple external representations, asking: (2) Do informational redundant qubit representations influence cognitive load and learning behavior? It also led to research in the context of direct application, asking: (3) Are the features identified by experts also beneficial for students’ learning?
Experts highlighted, in particular, the features for visualizing phase and amplitude, the combination of different representations, and the avoidance of learning difficulties or misconceptions. They also agreed that no single representation could meet all requirements equally well—making a repertoire of multiple representations essential.
To verify these evaluations and to examine the use of multiple representations in more detail, two additional studies were conducted. One focused on variations of informational redundant representations in the context of the Mach–Zehnder interferometer with single photons and compared four groups: (1) Text only (control), (2) Text + formula, (3) Text + Bloch sphere, (4) Text + formula + Bloch sphere.
No significant differences emerged in learning outcome or cognitive load. However, eye-tracking observations showed that groups working with the Bloch sphere exhibited a significant increase in transitions between text and representation.
The other study was carried out to verify the experts’ evaluations at the learner level. Conceptual understanding, cognitive load, and application-oriented tasks on phase, amplitude, quantum state, superposition, and quantum measurement for each representation (Bloch sphere and Quantum Bead) were examined. The results showed that students completed the application-oriented tasks significantly more efficiently when using the Bloch sphere, even though no group differences appeared in conceptual understanding or cognitive load. These findings partially confirm the expert ratings and demonstrate how the category system can guide the use of other representations that share characteristics with the four examples investigated.
The results indicate that our category system with representations can be applied in various settings—for instance, to experimental setups or practice-oriented scenarios in quantum technology. While neither study revealed group differences in conceptual understanding or cognitive load, the process data from eye tracking and timing measurements uncovered subtle distinctions in how learners interacted with the representations.
These findings partially validate the category system: it is useful both for selecting suitable representations and for guiding the design of new ones.
Research into learning with representations is far from complete, yet the feature structure presented here offers a solid starting point for future work—whether on different variations of multiple external representations or on specific concepts such as entanglement. Overall, this dissertation provides an insight into the broad, complex landscape of representations in quantum physics
Modeling Earth as an exoplanet in reflected and polarized light
Get PDFThe next generation of ground- and space-based observatories will enable the detailed characterization of rocky exoplanets within the habitable zones of their host stars. With improved sensitivity, these facilities allow us to observe Earth-like planets and study their reflected light, which provides valuable information about planetary albedo, a result of the interplay between surface and atmospheric properties. For the first time, we will be able to assess the habitability of nearby non-transiting rocky exoplanets, such as Proxima b, and explore whether they might retain liquid water on their surfaces.
Observing Earth as if it were an exoplanet offers crucial insights into how we assess exoplanetary habitability. Earthshine, the sunlight reflected from Earth onto the darker portion of the visible Moon, provides an opportunity to study Earth in a way that closely mirrors how exoplanets are observed in reflected light. Unlike satellite observations, Earthshine captures the complex scattering and reflection geometries encountered when observing exoplanets.
In this thesis, I model Earth as an exoplanet using advanced 3D Monte Carlo radiative transfer codes in the visible and near-infrared spectral ranges. My approach builds on codes originally developed for Earth’s remote sensing, using 3D atmospheres and 2D surface albedo maps. By combining state-of-the-art knowledge from Earth observations and reanalysis product, I generate spatially unresolved spectra and phase curves of Earth. I address two notorious challenges: the accurate representation of surface properties and the complex behavior of clouds.
Earth’s surface albedo is highly variable across space and time, with also wavelength-dependent features like the Vegetation Red Edge (VRE), a peak in vegetation reflectivity around 700 nm caused by chlorophyll absorption. Satellite data provides detailed albedo maps at only a few wavelengths in the visible and near-infrared, limiting our ability to fully simulate these features. To extend this data, I employ a Principal Component Analysis (PCA) algorithm to generate hyperspectral albedo maps, greatly improving surface representation.
Clouds pose an even greater challenge due to their complexity. Standard models using cloud properties from satellite observations and weather forecasts significantly overestimate the planet’s global reflectivity, an issue also seen in climate models. To address this, I develop a 3D cloud generator algorithm that creates finer-grid cloud patterns, representing their patchy nature. This approach allows for a more precise representation of Earth's clouds and their influence on reflectivity, enhancing our ability to model Earth as an exoplanet.
I validate my model, particularly its treatment of clouds and surface albedo, using a decade-long dataset of Earthshine observations that encompass a variety of planetary geometries and cloud conditions, for both intensity and polarization. Polarization offers deeper insights into the planet’s physical properties and has the advantage of not requiring atmospheric correction. I successfully validate the surface and clouds models in both intensity and polarized light, creating a robust framework capable of accurately representing Earth as an exoplanet. My model is far superior to previous descriptions in the literature because it matches both the continuum features and the absorption lines of Earthshine observations in a way that has never been achieved by earlier attempts.
This work also proposes an optimal strategy for detecting liquid water on exoplanets. Ocean glint, observable at high phase angles through phase curve variability or water lines, is best detected via polarization, which is highly sensitive to ocean surfaces. Polarization also reveals liquid water in clouds by identifying rainbows at smaller phase angles, offering detailed insights into cloud droplet properties. Combining polarization with traditional spectroscopy enhances the precision of exoplanet habitability assessments. This study paves the way for future instruments on observatories like the Extremely Large Telescope (ELT) and upcoming space missions such as the Habitable Worlds Observatory (HWO). Additionally, the advanced modeling developed here contributes to both exoplanet science and climate research
Marker zur Vorhersage der Pro- und Regressionswahrscheinlichkeit der zervikalen intraepithelialen Neoplasie
Get PDFPharmacodynamics of carfentanil and its neutralization by antagonists and antibodies in HEK293-µOR cells
Get PDFHighly potent synthetic opioids, such as carfentanil (CAR), pose significant challenges to the healthcare system due to their misuse as drugs and potential application as chemical weapons. The interactions between CAR and the µ-opioid receptor (µOR) remain poorly understood and current treatments with µOR antagonists, such as naloxone, are often insufficient. This study aims to elucidate the pharmacodynamics of CAR at µOR, assess its impact on antagonist effectiveness and evaluate anti-fentanyl antibodies for their potential to neutralize CAR´s µOR binding and activation.
Binding assays using HEK293 cells stably expressing the µOR and [³H]-naloxone as a tracer were performed to determine the binding affinities of CAR, fentanyl (FEN), remifentanil (REMI), morphine (MOR) and endomorphin-1 (ENDO). In combination with functional characterization through forskolin-stimulated cyclic adenosine monophosphate (cAMP) assays and Western Blot analysis of extracellular signal-regulated kinases 1 and 2 (ERK1/2) phosphorylation, this analyses demonstrated that CAR acts as a high-affinity ligand with exceptionally strong cAMP inhibition, yet induces comparatively weak ERK1/2 phosphorylation. µOR phosphorylation patterns, analyzed by ELISA at saturated opioid concentrations, showed that CAR promotes significantly increased phosphorylation at residues T370 and T379, distinguishing it from other tested opioids. A phospho-kinase array was used to screen for opioid-induced phosphorylation profile of cellular proteins; however, CAR exhibited phosphorylation patterns largely comparable to those of the other opioids tested. Antagonist potency against opioid concentrations of equal affinity was assessed in cAMP assays, revealing that both naloxone and nalmefene were significantly less effective at reversing CAR-induced µOR activation.
The potential of anti-fentanyl antibodies to interfere with opioid binding and signaling was evaluated through additional binding and cAMP assays. Of nine antibodies tested, three selectively blocked FEN binding, four inhibited both FEN and CAR and one uniquely targeted CAR, with no cross-reactivity toward REMI, MOR or ENDO. Selected antibodies also attenuated CAR- and FEN-induced cAMP signaling, although inhibition was generally more potent for FEN.
The pharmadynamic analysis revealed a unique µOR conformation stabilized by CAR that elicits selectively ultra-active cAMP inhibition and increased µOR phosphorylation, while showing reduced sensitivity to antagonists. Neutralizing CAR with specific antibodies could inhibit µOR binding independently of its conformation. This study underscores the need for alternative countermeasures, highlighting the potential of antibodies in treating or preventing FEN and CAR intoxications.Abgesehen von ihren medizinischen Vorteilen stellen hochpotente synthetische Opioide wie Carfentanil (CAR) das Gesundheitssystem vor Herausforderungen, da sie missbräuchlich als Drogen oder potenzielle chemische Waffen verwendet werden können. Die Interaktionen zwischen CAR und µ-Opioidrezeptoren (µOR) sind nicht ausreichend verstanden und die aktuelle Standardtherapie mit µOR-Antagonisten (z. B. Naloxon) ist oft unzureichend. Alternative Gegenmaßnahmen sind dringend erforderlich. Diese Studie zielt darauf ab, die Pharmakodynamik von CAR am µOR zu untersuchen, um Mechanismen zu identifizieren, die CAR´s hoher Toxizität zugrunde liegen könnten. Darüber hinaus untersucht sie die Effektivität der Antagonisten Naloxon und Nalmefen gegen CAR und analysiert spezifische Anti-Fentanyl-Antikörper hinsichtlich ihrer neutralisierenden Wirkung auf die µOR-Bindung und -Aktivierung sowie hinsichtlich der Kreuzreaktivität zu anderen Opioiden in vitro.
Liganden-Bindungsassays mit stabil µOR-exprimierenden HEK293-Zellen und [³H]-Naloxon als Tracer dienten der Bestimmung der Bindungsaffinitäten von CAR, Fentanyl (FEN), Remifentanil (REMI), Morphin (MOR) und Endomorphin-1 (ENDO). Ergänzend dazu zeigten forskolin-stimulierte Assays zur Messung von zyklischem Adenosinmonophosphat (cAMP) sowie Western-Blot-Analysen der Phosphorylierung der extrazellulären signalregulierten Kinasen 1 und 2 (ERK1/2), dass CAR ein hochaffiner Ligand mit außergewöhnlich starker Aktivierung des cAMP-Signalwegs ist, jedoch nur eine vergleichsweise geringe ERK1/2-Phosphorylierung induziert. Die Untersuchung der µOR-Phosphorylierung mittels ELISA bei gesättigten Opioidkonzentrationen ergab, dass CAR eine deutlich stärkere Phosphorylierung an den Aminosäuren T370 und T379 bewirkt als andere getestete Opioide. Ein Phospho-kinase Array zur Analyse opioid-induzierter Phosphorylierungsmuster zellulärer Proteine zeigte, dass CAR weitgehend ähnliche Muster wie die anderen Opioide hervorrief. Die Wirksamkeit der Antagonisten Naloxon und Nalmefen gegen die Opioide wurde anhand von cAMP-Assays unter Berücksichtigung gleicher Rezeptorbelegung überprüft; dabei zeigte sich, dass beide Antagonisten deutlich weniger effektiv waren, die CAR-induzierte µOR-Aktivierung zu blockieren.
Das Potenzial von Anti-Fentanyl-Antikörpern, die Bindung und Signaltransduktion von Opioiden zu hemmen, wurde in weiteren Bindungs- und cAMP-Assays untersucht. Von neun getesteten Antikörpern blockierten drei selektiv die FEN-Bindung, vier hemmten sowohl FEN als auch CAR und ein Antikörper erkannte spezifisch CAR, ohne Kreuzreaktionen mit REMI, MOR oder ENDO zu zeigen. Zudem konnten ausgewählte Antikörper die cAMP-Inhibition durch CAR und FEN abschwächen - wobei die Potenz gegen FEN insgesamt stärker ausfiel.
Die Ergebnisse deuten darauf hin, dass CAR eine einzigartige µOR-Konformation stabilisiert, die durch eine außergewöhnlich hohe Effektivität im cAMP-Signalweg, verstärkte Rezeptor-Phosphorylierung und eine verminderte Empfindlichkeit gegenüber Antagonisten gekennzeichnet ist. Die Neutralisierung von CAR durch spezifische Antikörper könnte die µOR-Bindung unabhängig von seiner Konformation unterbinden. Damit verdeutlicht diese Arbeit die dringende Notwendigkeit alternativer therapeutischer Ansätze und unterstreicht das Potenzial spezifischer Antikörper bei der Behandlung oder Prävention von FEN- und CAR-Vergiftungen