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Validation of a novel score for urgent bariatric and metabolic surgery
No full textDie quantitative Testtheorie beschreibt die Erfüllung der drei Hauptgütekriterien Objektivität, Reliabilität und Validität für die Validierung eines Scores. Gegenstand der vorliegenden Arbeit ist die evidenzbasierte Validierung eines neuartigen, von Stier et al. (2022) entwickelten Notfallscores für bariatrische Patienten auf Basis dieser Gütekriterien. Es ist nach aktuellem Stand der erste Score dieser Art. Der Score soll die Dringlichkeit zur unmittelbaren stationären Aufnahme mit anschließender “fast- track rescue weight reduction bridging therapy” und folgender bariatrischer Operation ermitteln. Der Score ist positiv (cut-off) ab einem Wert von 14 Punkten oder bei maximaler Punktzahl acht in den Kategorien „physical status“ oder „pulmonary status“. Der Score besteht aus den Kategorien “age”, “gender”, BMI, “functional status”, “physical status”, “pulmonary status” und “diabetes status”.
Es wurden Daten von n = 142 Patienten gesammelt. Anschließend wurde das Patientenkollektiv von n = 5 ärztlichen Ratern auf Basis des genannten Scores bewertet. Eine Reliabilitätsanalyse zeigte, dass für sechs von sieben Kategorien des Scores reliable Ergebnisse erzielt werden konnten. Der ICC der einzelnen Kategorien und Rater lag zwischen 0.58 und 0.98. Nach Koo & Li (2016) sind dies moderate bis sehr gute Ergebnisse. Der Gesamtscore hatte einen ICC von 0.84 und somit ein gutes Ergebnis erzielt.
Weiterhin wurde die Objektivität des Scores diskutiert. Für fast alle Kategorien konnte ausreichende Objektivität bescheinigt werden. Lediglich für die Kategorie „functional status“ konnte keine Objektivität der Items beschrieben werden.
Anschließend wurde die Validität auf Basis der Kriteriumsvalidität per Pearsonkorrelationanalyse bestimmt. Für sechs von sieben Kategorien des Scores konnten positive Korrelationen berechnet werden. Die Korrelationen in der schlechtesten Kategorie lagen bei r = 0.30 (“functional status”) und für die beste bei r = 0.95 (“gender”). Aufgrund fehlender Daten konnte für die Kategorie „physical status“ keine Korrelation ermittelt werden. Für den Gesamtscore konnte aufgrund mangelnder Datenerhebung keine Konstruktvalidität bestimmt werden.
Limitierungen dieser Arbeit bestanden darin das teilweise nicht ausreichend Daten der Patienten bereit standen um genauere Ergebnisse des Scores zu ermitteln. Nichtsdestotrotz bescheinigen die vorliegenden Ergebnisse dem Gesamtscore ausreichende Objektivität, Reliabilität und Validität. Weitere Validierung wird jedochempfohlen vor allem in Bezug auf andere Konstrukte oder Anwendung auf eine Nicht- Risikogruppe
Karl Heinz Witte, Johannes von Basel: Der Meister des Lehrgesprächs: Eine augustinische Theologie der Beziehung Gottes zum Menschen in Auseinandersetzung mit Meister Eckhart, Stuttgart(Kohlhammer) 2023 (Meister-Eckhart-Jahrbuch. Beihefte, 8)
No full textFrom Koopman-von Neumann to Cosmic Structure Formation - Path Integral Approach to Classical Many-Body Systems
No full textWe develop a functional integral formalism for classical many-body systems based
on the Klimontovich equation, which governs the exact evolution of the N-particle
phase-space density without loss of microscopic information. Since no assumptions
are made on the exact form of the initial state, this formalism is well suited to
describe out-of-equilibrium systems. The formalism is discussed in detail and compared to alternative approaches. Analytical solutions to the tree-level equations for homogeneous systems are presented. Importantly, a first application to cosmic large
scale structure formation is given, and numerical results are discussed. We present
one-loop results for the density fluctuation power spectrum which agree well with
results from numerical simulations and conventional approaches
Senescence Control in Normoxic and Hypoxic HPV-Positive Cancer Cells: The Interplay between B-MYB and A-MYB
No full textHypoxia is a hallmark of solid tumors, including HPV-positive cervical cancers, and it poses a
significant challenge to cancer treatment, as hypoxic tumor regions are often associated with
increased therapy resistance and poor patient prognosis. One possible contributing factor to
this resistance is the ability of hypoxic cancer cells to evade cellular senescence – a process
leading to an irreversible growth arrest. While the repression of the HPV E6/E7 oncogenes in
normoxic HPV-positive cells efficiently induces senescence, hypoxic HPV-positive cells,
despite efficiently shutting off E6/E7 expression, evade senescence and induce a reversible
growth arrest that can be overcome by reoxygenation.
The overall aim of this thesis was to uncover mechanisms that enable hypoxic HPV-positive
cancer cells to evade senescence. Through comparative gene and protein expression
analyses following E6/E7 repression under normoxic and hypoxic conditions, I identified
distinct regulatory patterns of key cell cycle regulatory factors. Notably, B-MYB emerged as a
critical factor differentially regulated under these conditions. Its strong downregulation in
normoxic cells following E6/E7 knockdown was associated with the onset of senescence, while
its sustained expression under hypoxia correlated with senescence evasion, suggesting a role
for B-MYB in controlling this process. To further investigate the functional role of B-MYB, I
performed knockdown experiments and assessed the phenotypic consequences using various
cellular assays. Interestingly, B-MYB depletion led to a partial senescence induction under
normoxia. I further showed that this limited senescence response was due to the compensatory
induction of a B-MYB paralog, A-MYB, which could counteract the pro-senescent effects of
B-MYB loss. Consequently, the combined repression of both B-MYB and A-MYB was needed
for efficient senescence induction under normoxia. Strikingly, I found that this compensatory
mechanism is disrupted under hypoxia, rendering hypoxic cancer cells particularly susceptible
to the pro-senescent effects of B-MYB loss. This increased vulnerability of hypoxic cells could
be reversed by ectopic A-MYB overexpression. Further, my studies revealed that the
B-MYB/A-MYB axis also plays a key role for the senescence response of normoxic and hypoxic
HPV-negative cancer cells of various histological backgrounds, indicating that this newly
discovered mechanism could be broadly conserved across different tumor types.
Collectively, my findings provide novel insights into the regulation of senescence in normoxic
and hypoxic cancer cells and identify B-MYB and A-MYB as central factors in these processes.
Further, they reveal a particular vulnerability of hypoxic cancer cells to B-MYB inhibition that
could be exploited to develop new strategies to target this therapeutically challenging tumor
cell population
Non-rigid registration of wind-affected terrestrial laser scanning point clouds of trees using deep learning
No full textMulti-station terrestrial laser scanning (TLS) is widely used to measure important forest variables. Wind effects like branch duplication remain a significant data quality issue in TLS point clouds and can lead to substantial errors in subsequent processing steps. Although scanning in windless conditions is recommended, it is not always practical.
The objective of this study is to present a method to transform wind-affected TLS point clouds into possible windless point cloud versions. Our method integrates recent deep learning (DL) models for the task of non-rigid registration, i.e., estimation of a displacement field.
To generate test data, we use virtual laser scanning (VLS) of dynamic scenes (VLS-4D): We simulate multi-station TLS acquisitions in HELIOS++ with each station capturing a dynamic tree model at a different timestamp. Knowing the exact movements of the virtual trees, we compute reference correspondences and respective displacement fields. We evaluate two pre-trained DL methods and a non-learned model-based method on the multi-view VLS-4D dataset. Performance is assessed by comparing estimated and reference displacement fields. In addition, we compare registered windless point clouds to truly windless VLS point clouds and evaluate the method on a real-world tree point cloud.
The strength of our approach is the validation using VLS. The manual generation of reference displacements in real-world data is error-prone, time-consuming and therefore not feasible for larger datasets. Our validation method takes procedurally generated and animated tree models as input, from which we compute error-free reference automatically. Preliminary results are promising and suggest that non-rigid registration enhances state-of-the-art registration and filtering workflows. This will improve the accuracy of subsequent processing tasks such as leaf-wood separation, quantitative structure modelling, and leaf area estimation
Modified treatment in cerebral ischemia 1 versus modified treatment in cerebral ischemia 0 before endovascular stroke treatment in middle cerebral artery’s M1-occlusion: Predictor for revascularization success and outcome?
No full textBackground
Little is known about the implications for revascularization success of target vessel occlusions (TVOs) with persisting antegrade perfusion before initiation of endovascular stroke treatment (EST) (modified treatment in cerebral ischemia (mTICI 1)) compared to a complete occlusion (mTICI 0). Here, we compared these two states of TVO.
Methods
Retrospective, single-center analysis of patients treated for M1-segment middle cerebral artery (MCA) occlusion with EST from January 2015 until May 2020 in a tertiary stroke center. Primary study endpoint was successful recanalization (mTICI 2c-3) after one thrombectomy attempt. Secondary endpoints were clinical outcome (modified Rankin Scale (mRS) 90 days after stroke onset), complication rate, and rate of underlying atherosclerotic disease. The two study groups were compared in univariate analysis including patient characteristics and procedural details.
Results
In this study, 422/581 patients (72.6%) presented with complete M1-occlusion compared to 159/581 (27.4%) with incomplete M1-occlusion. Neither did the recanalization success rate differ between the study groups nor the rate of complications (mTICI 0: 2.4%, mTICI 1: 0.6%, p = 0.304) or underlying atherosclerotic disease. Patients with incomplete initial occlusion showed a lower mRS at discharge (median interquartile range (IQR) mTICI 0: 4 (3–5) vs. mTICI 1: 3 (2–6), p = 0.014), but a comparable mRS 90 days after stroke onset (mTICI 0: 3 (2–6) vs. mTICI 1: 4 (2–6), p = 0.479).
Conclusion
Complete M1-occlusions (mTICI 0) and incomplete occlusions (mTICI 1) show the same recanalization success, comparable complication rate, and clinical outcome as well as the same rate of underlying atherosclerotic disease. Thus, incomplete M1-occlusions do not allow for an individualized interventional approach
Assessing fossil CO2 emissions in Europe: how reliably do ICOS 14CO2 and CO observations constrain atmospheric inversions?
No full textAccurate quantification of country-scale fossil fuel CO2 (ffCO2) emissions is essential for monitoring efforts to mitigate climate change. This thesis employs the regional isotope budget approach (RIBA) to calculate ffCO2 observations based on flask, CO, and integral samples, and assesses their constraint on top-down fossil emission estimates within a Bayesian inversion framework. Flasks provide a limited number of precise hour-long observations, CO-based estimates are less precise but recorded every minute, and integral samples yield reliable two-week averages. The coverage of currently available 14CO2 data from the Integrated Carbon Observation System (ICOS) infrastructure mainly includes Germany and nearby regions. When comparing to the emission inventories by the Global Carbon Project (GCP) and the Emissions Database for Global Atmospheric Research (EDGAR), corresponding winter emissions estimated from the atmospheric data differ by 0–4% from GCP but by 10–14% from EDGAR, reducing the discrepancy between the GCP and EDGAR inventories from 21% to about half. Incorporating ffCO2 observations decreases the GCP inventory uncertainty by 30% in the Germany+ domain. Uncertainty analysis indicates that biases in 14CO2 background are critical for the RIBA. A background bias of 2‰ results in estimated flux variations of 20%. Since integral-based samples have lower requirements for hourly-specific model transport, they are found to be the most suitable proxy for constraining trends and seasonal fossil fuel emissions. They effectively track trends and align with realistic expectations derived from bottom-up inventories. Flask-based estimates perform equally well if sampled more frequently than weekly, but demand more analytical resources. CO-based estimates are found to be less suitable due to their additional dependence on CO background estimates and unmodeled air chemistry. The two main recommendations for ICOS to monitor country-scale fossil emissions and their trends are: (a) diversifying European 14CO2 background observations to reduce bias risk, and (b) prioritizing integral 14CO2 sampling
Experimental Studies on the Ligand Field Effects and Magnetic Interactions in 3d, 4f and 5d Mono- and Heterometallic Molecular Compounds
No full textThis thesis presents detailed magnetic investigations on metal-organic compounds hosting 4f lanthanide ions, as well as 3d and 5d transition metal ions. Using combined magnetic susceptibility and tunable high-frequency/high-field electron paramagnetic resonance spectroscopy studies, the microscopic spin Hamiltonian parameters are determined with a high degree of precision. The triply-capped, slightly distorted trigonal-prismatic ligand field of a muffin-shaped, mononuclear Er(III) complex is found to stabilise the mJ = ±9/2 Kramers doublet (KD) as the magnetic ground state. Furthermore, significant transverse components of the effective g-tensor account for the observed fast quantum tunnelling of the magnetisation (QTM) in zero magnetic field and indicate that slow relaxation at B = 0.1 T occurs through a thermally-activated process including the first excited KD at Δ = 37.4(2) K. The experimental findings are in close agreement with the results of ab-initio CASOCI calculations. In a series of pentagonal-bipyramidal, mononuclear ErIII complexes with similar equatorial but differing apical ligands, thermally-assisted QTM governs the different in-field relaxation dynamics. While all complexes exhibit QTM in the predominantly mJ = ±11/2 ground state KD, due to non-axial effective g-tensors, the incorporation of two charged axial ligands results in considerably low-lying excited energy states, thereby increasing the relaxation rate. The spectroscopic data are used to assess the validity of numerical crystal field analysis and ab-initio CASSCF calculations. For anionic complexes, the latter are demonstrated to overestimate the energy splittings. An interplay of the single-ion anisotropy and the antiferromagnetic 3d-4f exchange coupling is revealed in a family of VIII2 LnIII 2 complexes with butterfly architecture. The observed correlation indicates that 3d→4f charge transfer is the dominant exchange process and strongly depends on the anisotropic electron distribution of the lanthanide 4f orbitals. The importance of the 4f anisotropy shape also manifests in the magnetic relaxation dynamics. Antiferromagnetic intermolecular interactions in a ReIV-based molecular complex are found to lead to the formation of spin chains. Analysis of the magnetic data shows that an isotropic Heisenberg-chain model with local single-ion anisotropy fails to describe the observed magnetic behaviour. Instead, the diffuse nature of the involved 5d orbitals gives rise to a more complex exchange mechanism
The Universe as a neutrino laboratory: Probing neutrino nature and interactions in cosmology and astrophysics
No full textUnderstanding neutrino properties remains a key open question in particle physics. This thesis explores how cosmology and astrophysics constrain or support a possible Dirac nature of neutrinos and probe neutrino interactions with dark matter (DM).
Explaining a Dirac mass for neutrinos requires new fields and symmetries. These lead to an experimentally constrained excess in from production of right-handed neutrinos in the early Universe.
We develop a Monte Carlo-based scheme for integrated Boltzmann equations and apply it to Dirac neutrino models. First, we study extensions, finding them subject to strong and generic constraints from that are only avoided if the thermal history of the Universe was non-standard or it reheated to .
We also introduce a Dirac-Type-I seesaw family as a unified framework of Dirac seesaws and a generalization of the Majorana Type-I seesaw family. We study two minimal UV completions with a spontaneously broken global symmetry yielding the Diracon as a Nambu-Goldstone boson. The production of light degrees of freedom is suppressed compared to gauged models, which leads to weaker bounds from \dneff in direct comparison. Astrophysical and laboratory-based flavor observables involving the Diracon and complementary to \dneff are identified. Minimal Dirac models with a global symmetry appear as a viable alternative to a gauge symmetry, due to the strong and generic constraints we find on the latter.
In a separate study, we turn to astrophysical tests of neutrino-DM interactions. We investigate the upscattering of MeV-scale DM by the diffuse supernova neutrino background (DSNB), focusing on model dependence and improved flux attenuation modeling.
The strength of neutrino-DM interactions preferred by cosmological data is below current experimental sensitivities. We discuss the role of DSNB upscattering in probing such interactions and its wider implications for DM direct detection. Unlike cosmological tests, upscattering offers a direct experimental window into neutrino-DM interactions
