Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
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New approaches to a homotopical problem in representation theory
Get PDFLet K be a field. The central object of this thesis is the τ-cluster morphism category W(A) of a finite-dimensional K-algebra A. This category encodes the information of all possible τ-tilting reductions in mod(A) and encompasses many objects considered in representation theory, for example (semi-)bricks, (τ-)tilting modules and (τ-)exceptional sequences. When A is a hereditary algebra, the category W(A) is well-understood and its classifying space BW(A) is a K(π,1) space in all representation finite and some tame cases. By definition, this means that the fundamental group is the only nontrivial homotopy group. This is insightful, because the fundamental group of this space, known as the picture group, is closely connected to maximal green sequences, a central object in the theory of cluster algebras.
The guiding question of this thesis is based on the conjecture that the classifying space of the τ-cluster morphism category is a K(π,1) space for all τ-tilting finite algebras. It is known that the classifying space of W(A) is a cube complex. Thus, the conditions developed by Gromov for cube complexes to be nonpositively curved may be lifted to three conditions which together imply that BW(A) is a K(π,1) space. The focus of this thesis lies on one of these conditions: the existence of a faithful functor from W(A) to a group considered as a groupoid with one object. In fact, given this condition BW(A) is nonpositively curved if and only if it satisfies the other two conditions.
Such a faithful functor to a group is conjectured to exist for all finite-dimensional algebras which are τ-tilting finite. However, few families of algebras satisfying this condition have been found so far. The first part of this thesis builds on a recently introduced geometric viewpoint of W(A) by Schroll-Tattar-Treffinger-Williams. This geometric approach is developed further to obtain a new family of algebras admitting faithful functors to groups. This is achieved by relaxing a condition in the geometric definition. In this way, a category is defined for any simplicial polyhedral fan with an admissible partition, so that the collection of these categories, for a given fan, forms a lattice. For the g-vector fan of an algebra A, the category W(A) is an element of this lattice. If the g-vector fan of A is a finite hyperplane arrangement, it is shown that W(A) admits a faithful functor to a group by using the theory of hyperplane arrangements in convex geometry.
In the second part of this thesis, a lattice theoretic approach to W(A) is introduced. As a first step, the τ-cluster morphism category is defined using the lattice of torsion classes of mod(A). Whenever A is τ-tilting finite, this definition is purely combinatorial, so that the lattice of torsion classes determines W(A) up to equivalence. Moreover, the lattice of torsion classes of a τ-tilting finite algebra is isomorphic to that of infinitely many others. Thus, this result extends the families of algebras whose τ-cluster morphism categories admit faithful functors to groups. Let I be an ideal of A. The lattice theoretic approach provides a framework for constructing a functor F from W(A) to W(A/I) and various properties of this functor are investigated. In particular, if A is τ-tilting finite, the functor is a regular epimorphism in the category of small categories.
The final chapter contains another application of the lattice theoretic approach. Let L:K be a MacLane separable field extension. After further developing the behaviour of τ-tilting theory under base field extension, a faithful functor G from W(A) to the τ-cluster morphism of the algebra A_L, obtained from A by tensoring by L over K, is constructed using lattice theory. The existence of G leads to the discovery of new families of algebras whose τ-cluster morphism categories admit faithful functors to groups. Thus, this thesis contributes substantially to understanding the relationship between τ-cluster morphism categories of different algebras as well as to answering the question of when their classifying spaces are K(π,1) spaces
Die Auswirkungen eines sporttherapeutischen Kraft- und Ausdauertrainings auf ausgewählte Stoffwechselparameter in Abhängigkeit des Ernährungszustandes bei Menschen mit nicht insulinpflichtigem Typ 2 Diabetes mellitus
Get PDF1. Zusammenfassung
Diese Studie untersucht, ob Training vor dem Frühstück in einem seit dem Vorabend
nüchternen Zustand wirksamer ist bei der Verbesserung der Gesundheit von Menschen mit
Typ-2-Diabetes mellitus (T2DM) als ein Training in einem postprandialen Zustand. Ein
prospektives Studiendesign wird genutzt, um die Auswirkungen von Nüchtern- und
postprandialem Training auf verschiedene metabolische Parameter zu analysieren.
Untersucht werden dreißig Menschen mit nicht-insulinpflichtigem Typ 2 Diabetes mellitus in
einem Alter von 60 ± 8 Jahren und einem BMI von 33,7 ± 4,6 kg/m². Diese Probandinnen und
Probanden wurden nach dem Zufallsprinzip der F-Gruppe (Training im über Nacht nüchternen
Zustand (n = 15) und in der C-Gruppe (Training im postprandialen Zustand (Kontrollgruppe, n
= 15) eingeteilt. Alle Personen absolvieren ein 8-wöchiges kombiniertes Ausdauer- /
Krafttrainingsprogramm.
Das körperliche Training verlängerte im Mittel für alle Probandinnen und Probanden die Zeit
bis zur körperlichen Erschöpfung im Ausdauertest (+10,4 %), die Leistung im Krafttest wurde
ebenso gesteigert (Brustpresse: +36,7 % und Ruderzug: +37,8 %). Die fettfreie Masse wurde
im Mittel für alle Probandinnen und Probanden gesteigert (+1,7 kg), die Körper Fettmasse
verringert (-1,9 kg), die glykierten Hämoglobinwerte (HbA1c) verringert (absolute Veränderung:
-0,3%), die Seruminsulinwerte verringert (-2,5 μU/ml), die homöostatische Modellbewertung
für die Insulinresistenz (HOMA-IR) verringert (-1,1) und der Triglyceridspiegel verringert (-31
mg/dl).
Das Training hatte keine Auswirkungen auf den Body-Mass-Index, Serum-Nüchternglukose,
Gesamtcholesterin, Low-Density-Lipoprotein / High-Density-Lipoprotein-Verhältnis bzw.
Interleukin (IL)-6, IL-10 und den Tumornekrosefaktor (TNF)αLevel. Die Varianzanalysen
ergaben keine Zeit × Gruppeninteraktion für irgendeinen der genannten Parameter (P > .05).
Die erhobenen Daten liefern keinen Beweis dafür, dass der Ernährungszustand (über Nacht
nüchtern oder postprandial) bei regelmäßigem körperlichem Training eine wichtige Rolle für
trainingsinduzierte Anpassungen bei T2DM-Patientinnen und Patienten spielt. Das Training
war insgesamt in beiden Gruppen effektiv in Bezug auf die Verbesserung der glykämischen
Kontrolle, des Triglyceridstoffwechsels, der körperlichen Leistungsfähigkeit und damit der
Gesundheit bei Menschen mit nicht-insulinpflichtigem Typ-2-Diabetes mellitus.
Die Arbeit ist insofern bedeutend, da sie neue Erkenntnisse über die Rolle von
Nüchterntraining bei der Behandlung von Typ-2-Diabetes liefert. Weitere Studien, auch mit
anderen Trainingsprotokollen, sollten durchgeführt werden, um weitere Kenntnisse über die
Relevanz der Einnahme eines Frühstücks vor oder nach dem Training zu untersuche
Regulation of Vascular Endothelial Cells and Cytokines in the Tumor Microenvironment by Radiotherapy
Get PDFCancer is still an essential threat to human health. In recent decades, research on the
treatment of tumors has made great progress. Surgery, radiotherapy (RT) and chemotherapy
(CT) are traditional cancer treatments. In addition, with the development of scientific research
and the deepening of the understanding of the molecular level, research on cancer treatment
at the molecular level is becoming one of the most important directions, and immunotherapy
has become a milestone in cancer treatment. Surgery, RT and CT are aimed at directly
killing malignant cells, while immunotherapy mainly achieves the purpose of destroying
cancer cells by eliminating the tumor's immune escape and activating the host's immune
response. Although great breakthroughs and progress have been made in cancer treatments
over the years, cancer remains one of the biggest threats to people's health. Since rays were
discovered to damage the deoxyribonucleic acid (DNA) of cells and were used to kill cancer
cells and control the growth of tumors, RT technology has been constantly innovating with
the development of science and technology. From conventional radiotherapy to intensity
modulated radiotherapy (IMRT), and from external radiotherapy to brachytherapy and particle implantation, the accuracy, safety and effectiveness of radiotherapy are constantly
improving. However, due to the unlimited proliferation nature of cancer cells, cancer always
becomes resistant to treatments and cancer cells continue to grow. Since immunotherapy
was applied to clinical treatment, a milestone breakthrough was made in tumor treatment.
However, what is confusing is that many patients still cannot benefit from immunotherapy. It
is worth noting that clinical studies have found that the therapeutic effect of combined RT and
immunotherapy is better than that of immunotherapy alone, and even some patients who do
not respond to immunotherapy can benefit from immunotherapy after receiving combined RT
and immunotherapy. Compared with single treatment, combination therapy often achieves
better results, and RT, CT and surgery are often used in combination treatment. However,
the difference is that the combination of RT, CT and surgery mainly depends on the
superposition effect of different treatment methods on the killing of malignant cells, while the
promotion of RT and immunotherapy combined therapy may affect the immune response
system, which is a direction worthy of exploration. Activation of anti-tumor immune response
requires activation of the immune system to recognize tumor antigens and activated immune
cells to migrate across the endothelium to the location of cancer cells to exert immune
effects. Immunotherapy, such as checkpoint inhibitors, can prevent cancer from escaping the
immune system and reactivate the immune system's response to malignant cells. Some
patients do not respond to immunotherapy alone, but benefit from the combination of
immunotherapy and RT. We speculate that one reason for this phenomenon may be that RT
can change the tumor microenvironment (TME) and promote the transendothelial migration
(TEM) of immune cells. The TME is one of the most important areas of tumor treatment
research, including the aggregation and migration of immune cells, the dysfunction and
activation of vascular endothelial cells, and various cytokines such as TNF-α, IFN-γ, IL-6, etc.
Therefore, the activation of vascular endothelial cells (ECs) is very important for cancer
immunotherapy, and the adhesion molecules such as P-selectin, E-selectin, ICAM1 and
VCAM1 on the surface of vascular endothelium play a critical role in the process of TEM of
immune cells. In this thesis, I investigated the influence of RT on the TME especially on the
regulation of adhesion molecules expressed on the surface of vascular ECs through in vivo
and in vitro experiments. The results showed that RT upregulated the expression levels of
E-selectin, P-selectin, ICAM1 and VCAM1 on ECs, and also upregulated the levels of some
inflammatory cytokines GM-CSF, IL-1α and IL-1β. The upregulation of vascular endothelial
adhesion receptors and inflammatory cytokines may be the targets and new points for the
study of combination therapy with RT and immunotherapy
Computer Tomographie mit Pulmonalisangiographie in der Diagnostik pulmonaler Mykosen
No full textInvasive Mykosen sind eine seltene, aber sehr gefährliche Erkrankung mit zunehmender Inzidenz (von Lilienfeld-Toal et al., 2019). Sie weisen eine hohe Letalität auf und sind
eine Haupttodesursache immunsupprimierter Patient*innen (Ruhnke et al., 2018). Aufgrund einer sehr variablen Symptomatik verbunden mit einem schnell progredienten
Verlauf ist eine frühzeitige Diagnostik schwierig (Guberina et al., 2016, Lum et al., 2019). Die hohe Letalität verbunden mit der zunehmenden Inzidenz pulmonaler Mykosen
begründet die Motivation, die Diagnostik zu optimieren.
Aufgrund von Hinweisen darauf, dass die Computer Tomographie mit Pulmonalisangiographie (CTPA) wesentlich zur Verbesserung der Diagnostik beitragen könnte (Sonnet et al., 2005, Stanzani et al., 2015, Stanzani et al., 2012, Henzler et al., 2017), wurde an der Universität zu Köln eine neue Leitlinie eingeführt. Diese empfahl bei Patient*innen in Neutropenie mit einer Temperatur von über 37,5 °C die Durchführung einer Lowdose-CT Untersuchung. Wenn diese CT-Aufnahme einen Herd mit einem Durchmesser von über 1,5 cm aufwies, sollte eine CTPA angeschlossen werden. Bei der Auswertung der Ergebnisse fällt auf, dass insbesondere die Sensitivität der CTPA in der untersuchten Fallgruppe mit 22,2 % sehr viel niedriger als Vergleichswerte der Literatur (78 – 100 %) war. Die Number Needed to Diagnose lag bei 14. Betrachtet man auf der anderen Seite die schädigende Wirkung der CTPA, lag die Number Needed to Harm bei 11, wobei ausschließlich kontrastmittel-induzierte Nierenschädigungen berücksichtigt wurden. Auch die Sensitivität für das Vorliegen eines Herdes mit einem Durchmesser von über 1,5 cm in der nativen CT war mit 28,9 % sehr niedrig.
Die Ergebnisse dieser Untersuchung konnten keinen Vorteil der CTPA gegenüber der nativen CT nachweisen, während Hinweise auf eine mögliche Schädigung durch die Kontrastmittelgabe bestanden. Weitere Studien sollten erfolgen, um den Nutzen und die Schädigungen einer CTPA näher zu untersuchen. Sollten sich dabei Tendenzen dieser
Untersuchung bestätigen, würde eine Nutzen-Risiko-Abwägung verbunden mit einer Kosten-Nutzen-Analyse einen standardmäßigen Einsatz einer CTPA zur Diagnostik invasiver pulmonaler Mykosen nicht rechtfertigen
Cysteine in signaling and plant pathogen response
No full textBeyond their role as building blocks of proteins, amino acids serve a variety of additional functions in plants. Since plants are sessile organisms, they need to identify and properly deal with a plethora of adverse environmental circumstances. Amino acids are known to be implicated in plant stress responses in different ways. While some aspects are already well understood, many remain elusive to date. Here, we reviewed the recent research progress on amino acids in plant-microbe interactions (chapter 2). There, we explored how specialized metabolites and amino acid transporters shape the plant microbiome and elaborated on how amino acids impact plant immunity. Furthermore, we aimed to elucidate the role of cysteine in signaling and plant pathogen response (chapter 3). To that end, we set up a liquid culture approach in which Arabidopsis thaliana seedlings were incubated with 1 mM cysteine for 24 hours. Subsequent shotgun proteome analysis revealed that elevated cysteine levels are interpreted as a biotic threat by the plant. Consistent with this, cysteine both primed adult Arabidopsis plants against infection with the hemibiotrophic leaf pathogen Pseudomonas syringae (Pst) and its levels increased in response to Pst infection. Comparing proteome responses of cysteine-treated and Pst-infected plants revealed potential mediators of the cysteine-induced defense response. Unlike other amino acids, cysteine can be synthesized in multiple subcellular compartments by different O-acetylserine(thiol)lyase (OASTL) isoforms. Here, we found that the lack of mitochondrial OASTL-C renders Arabidopsis plants more susceptible to infection with Pst. Remarkably, mitochondria allow for the complete oxidation of cysteine facilitated by a four-step enzymatic process. This is the only pathway to degrade cysteine without producing sulfide, which becomes toxic in high concentrations. However, the first enzyme catalyzing the transamination of cysteine is unknown. Here, we aimed to identify the missing aminotransferase to complete the mitochondrial cysteine degradation pathway (chapter 4). Thus, we established mass spectrometry-based thermal proteome profiling (TPP) with mitochondrial fractions to find novel proteins binding or interacting with cysteine. Consequently, selected candidate proteins were produced in Escherichia coli and purified using immobilized metal affinity- and size exclusion chromatography. Strikingly, alanine aminotransferase 1 and aspartate aminotransferase 1 showed activity using cysteine as an amino donor. Moreover, both enzymes were able to complete the mitochondrial cysteine degradation pathway in vitro. The findings in this dissertation expand our understanding of cysteine as an infochemical in the plant pathogen response, highlight the importance of plant mitochondria for biotic stress adaptation and suggest potent targets for future research in plant immunity. Additionally, we present a powerful tool to identify novel protein metabolite interactions and, thereby, further our knowledge about the mitochondrial cysteine metabolism
Singularities of Closed Positive Currents
No full textThis thesis focuses on analyzing the singularities of closed positive currents on compact complex manifolds, consists of six chapters.
In the second chapter, some crucial background in pluripotential theory and complex geometry is reviewed. In the third chapter, we introduce the relative non-pluripolar products in Hermitian setting, which is a way defining the wedge products of closed positive (1,1)-currents and a closed positive (p,p)-current on Hermitian manifolds. We discuss the construction of this product, the monotonicity property, and its relation with density currents, which is a general way defining wedge products of higher bi-degree currents.
The fourth chapter focuses on estimating the size of the singular locus of a given closed positive current T, where the singular locus is the set of points at which T has positive Lelong numbers. Specifically, we established upper bounds for the volumes of arbitrary maximal irreducible analytic sets contained in the Lelong upper level sets of closed positive currents. Moreover, in the bi-degree (1,1) case, we proved that these bounds are optimal.
In the fifth chapter, we compare the Lelong numbers of closed positive (1,1)-currents in the same big class. More precisely, let T,T' be two closed positive (1,1)-currents in the same class such that T is less singular than T'. We provide an upper bound of the difference of the Lelong numbers of T and T', in terms of the difference of the non-pluripolar masses of T and T' respectively.
Finally, in the sixth chapter, we provide a method for defining the Lelong number of non-pluripolar cohomology (m,m)-classes on compact Kähler manifolds. We compare the cup products and the relative non-pluripolar products. It turns out that the Lelong number of non-pluripolar cohomology classes obstructs the equality of these two classes. As an application, we present a higher-dimensional version of the Zariski decomposition
Navigating What Is Not Known—Patients’ Experience of the Life Threat Connected to Allogeneic Stem Cell Transplantation
No full textBackground: Allogeneic stem cell transplantation (allo‐SCT) represents a firmly established therapeutic option for patients facing (non‐)malignant haematological diseases. Despite its curative potential, however, this treatment is associated with substantial morbidity and mortality rates as well as a decreased quality of life. Given this context, a scientific void needs to be addressed: How do patients deal with the existential situation of being exposed to a life threat despite the curative potential of their treatment? This study aims to explore the patients’ experiences considering their life threat in the context of the allo‐SCT. Methods: Qualitative semistructured, in‐depth interviews were conducted with patients treated by allo‐SCT over the course of transplantation (before, during or after hospitalization). Interview data were interpreted using category‐based qualitative content analysis. Results: Seventeen interviews were conducted. Results revealed a strong focus on hope and avoidance of dealing with the life threat. At the same time, challenges due to the lack of alternative treatments and the uncertain course were highlighted. The data revealed that patients wished to receive support by healthcare professionals, their carers and their social environment in general. Beyond that, patients desired to obtain honest information within an open discussion about a realistic prognosis and risk of treatment and course of disease. Conclusion: The findings emphasize an interplay between hope, avoidance and psychological distress in the face of the patients’ life threat. To assist allo‐SCT recipients in navigating their life threat during treatment, it is desirable to establish avenues that provide adequate support. Trial Registration: German Registry of Clinical Trials: DRKS0002729
Neue kristalline Verbindungen basierend auf Acetylid-Anionen der Hauptgruppenelemente
Get PDFIn Anlehnung an die ternären Hauptgruppenelement-Acetylide der Formel ASeC2H und A2Se2C2 mit A = Na–Cs lag der Fokus dieser Dissertation unter anderem auf der strukturellen Aufklärung dieser Verbindungen mittels Einkristallstrukturanalyse. Hierzu wurden Kristallisationsmethoden in organischen Lösungsmitteln etabliert, wodurch Einkristalle der Verbindungen RbSeC2H und CsSeC2H zugänglich wurden, und welche die Ergebnisse aus der Röntgenpulverdiffraktometrie bestätigten. Zur weiteren strukturellen Aufklärung des Dianions wurden Reaktionen von Interalkalimetall-Acetyliden mit Selen zur Darstellung von AA′Se2C2 mit A und A′ = Na–Cs (A ̸= A′) untersucht. Ebenfalls Teil dieser Arbeit war die Untersuchung des thermischen Verhaltens der Verbindungen ASeC2H, welche nicht nur untereinander, sondern des Weiteren mit dem thermischen Verhalten der Acetylide des Typs ASC2H verglichen wurden.
Basierend auf der Darstellung der Hydrogenacetylide AC2H wurden im Rahmen dieser Arbeit die Verbindungen Ca(C2H)2·4NH3 und EA(C2H)2 mit EA = Sr, Ba über die Synthese in flüssigem Ammoniak erstmals dargestellt. Die Kristallstruktur der Ca-Verbindung, welche in Ammoniak als farblose Nadeln auskristallisiert wurde, konnte mit Hilfe von Einkristalldiffraktometrie aufgeklärt werden. Ca(C2H)2·4NH3 kristallisiert in der orthorhombischen Raumgruppe Pnma (Nr. 62). Die Strukturen der Verbindungen Sr(C2H)2 und Ba(C2H)2 konnten mittels hochaufgelöster Röntgenpulverdiffraktionsdaten aufgeklärt werden. Die Acetylide kristallisieren isotyp zueinander in der trigonalen Raumgruppe P¯3m1 (Nr. 164). Zur Charakterisierung wurde auf die Methoden der IR- und Raman-Spektroskopie zurückgegriffen und das thermische Verhalten mit Hilfe der DSC/TG-Analyse untersucht. Dabei wurde das Vorliegen
des –C2H-Anions erneut bestätigt. Analog zu den Alkalimetall-Verbindungen AC2H mit A = K–Cs wurde Ba(C2H)2 unter Zugabe einer äquimolaren Menge elementaren Bariums thermisch zu dem Acetylid BaC2 umgesetzt.
Aus den Reaktionen der Erdalkalimetallhydrogenacetylide mit den Chalkogenen Schwefel und Selen in flüssigem Ammoniak wurden die Acetylide EA(XC2H)2·xNH3 mit EA = Ca–Ba und X=S, Se zugänglich. Die Kristallstruktur der Sr-Verbindung der Formel Sr(SeC2H)2·2NH3 wurde mithilfe eines hochaufgelösten Röntgenpulverdiffraktogramms aufgeklärt. Das Acetylid kristallisiert in der orthorhombischen Raumgruppe Pnma (Nr. 62). Die Identität des –XC2H-Anions wurde auch hier spektroskopisch bestätigt. Im Vergleich zu ihren Alkalimetall-Analoga konnte bei den Verbindungen des Typs EA(SeC2H)2 ·x NH3 eine deutlich höhere Explosionsbereitschaft beobachtet werden, welche zu den schwereren Erdalkalimetallen hin zunimmt
Deciphering the role of cGAS/STING signaling in vivo using the short-lived turquoise killifish Nothobranchius furzeri
Get PDFThe cGAS/STING pathway is a central innate immune signaling pathway whose chronic activation has been implicated in multiple age-related pathologies, yet its impact on life span itself is unknown. Here we engineered knockouts of pathway components in the killifish Nothobranchius furzeri, and assessed their impact on physiology and aging. In vitro, loss of killifish cGAS and STING mitigated DNA damage-induced senescence in cultured primary fibroblasts, while cGAS loss uniquely triggered low levels of basal DNA damage. In vivo, cGAS knockout unexpectedly led to transcriptional signatures indicative of low-grade inflammation. It also attenuated changes in gene expression in response to DNA damage in young animals and age-related changes in the transcriptome of old animals, suggesting dampening of senescence and aging. Necroscopy indicated that STING KO appeared to have less infection rates and that tissue pathology tended to be milder overall in both mutants, though some tissues showed a trend for enhanced sterile macrophage infiltration. Our observation of cGAS-specific effects related to the DNA damage response and ageing transcriptome hint towards functions separate from canonical cGAS/STING pathway. Despite the attenuated aging signatures, however, longevity of cGAS or STING mutants was not significantly different from that of wild type. Our findings reveal a potential tradeoff, where inhibiting the cGAS/STING pathway alleviates age-related signatures, but increases sterile inflammation, offsetting potential beneficial effects on lifespan
Physician behaviour and quality of care in healthcare
Get PDFThe concept of quality of care is evolving, extending beyond traditional indicators such as health outcomes, safety, and effectiveness. Increasingly, factors such as the motivation of health care professionals, their communication and expertise, and the institutional quality culture are recognized as critical components in defining quality of care. At the center of this discourse are physicians, whose decisions and actions significantly influence both patient experiences and health outcomes. This work, structured across four independent studies, investigates how physicians’ actions and their preconditions affect the quality of health care in both outpatient and inpatient settings. It examines the multifaceted nature of health care quality, integrating individual physician actions with broader systemic factors. The findings demonstrate that physicians’ actions and performances are shaped not only by personal attitudes but also by environmental factors and institutional processes. In particular, the following research questions were addressed: How did physicians maintain and adapt their practice under challenging conditions such as the COVID-19 pandemic (Study I)? How did physicians' attitudes towards treatments such as COVID-19 vaccination affect medical practice (Study II)? What role did social and organizational factors play in shaping patient safety and quality of care in hospitals (Study III)? And how did patient volume and medical staffing levels impacted obstetric care (Study IV)? Together, the research reveals the complex interplay of personal, social, and systemic dimensions in determining quality of health care, offering valuable insights into the perception of quality