University of Wuerzburg

We consider the sparse optimization problem with nonlinear constraints and an objective function, which is given by the sum of a general smooth mapping and an additional term defined by the $\ell _0$-quasi-norm. This term is used to obtain sparse solutions, but difficult to handle due to its nonconvexity and nonsmoothness (the sparsity-improving term is even discontinuous). The aim of this paper is to present two reformulations of this program as a smooth nonlinear program with complementarity-type constraints. We show that these programs are equivalent in terms of local and global minima and introduce a problem-tailored stationarity concept, which turns out to coincide with the standard KKT conditions of the two reformulated problems. In addition, a suitable constraint qualification as well as second-order conditions for the sparse optimization problem are investigated. These are then used to show that three Lagrange–Newton-type methods are locally fast convergent. Numerical results on different classes of test problems indicate that these methods can be used to drastically improve sparse solutions obtained by some other (globally convergent) methods for sparse optimization problems.

This study investigated the impact of various process conditions on the aqueous, direct recycling of LiNi0.8Mn0.1Co0.1O2 (NMC811) cathodes. Three model systems were used. The first system assumes that the current collector delamination is performed in a dry environment without the use of water as a process medium. Consequently, the NMC811 is only exposed to water during classification, where no aluminum foil is present. The second model system assumes that the current collector delamination occurs in water. Therefore, the NMC811 is exposed to water in the presence of aluminum foil. Due to the pH increase caused by the Li⁺/H⁺ exchange reaction, the pH value surpasses the stability window of the aluminum‐oxide passivation layer (pH 4.5–8.5), resulting in the deposition of aluminum‐containing species on the NMC811 surface. The third model system is identical to the second, with the exception that H3PO4 is added. This causes the pH to decrease and prevents corrosion of the aluminum foil. The findings reveal that process conditions significantly affect the surface chemistry on NMC811, influencing electrochemical performance. Notably, aluminum‐containing species increase polarization. Heat treatment simulating regeneration led to cation mixing as surface species diffused into the NMC811 bulk structure, highlighting the need to control recycling process conditions.

This chapter presents kinematically aligned (KA) total knee arthroplasty (TKA), which sets the femoral and tibial components to resurface the patient’s pre-arthritic knee and refrains from releasing collateral ligaments and the posterior cruciate ligament (PCL). High long-term implant survival rates and superior clinical outcomes relative to mechanical aligned TKA make KA TKA an attractive alignment strategy. The surgeon first resurfaces the femur and measures each resection with a caliper to confirm the resection thickness matches the thickness of the femoral component. The tibial resection restores the patient’s pre-arthritic articular surface, verified by four caliper measurements and a rectangular extension space. Using components that restore the articular surface geometry, which include an insert with a medial 1:1 ball-in-socket and lateral flat articulation, the surgeon selects the optimal insert thickness by using an insert goniometer that measures external tibial orientation in extension and internal tibial orientation at 90° flexion. KA TKA with a medial 1:1 ball-in-socket conformity confers anterior-posterior stability, replicating anterior cruciate ligament function. Combined with an intact PCL and a flat lateral articular surface, KA TKA restores a medial pivot with close-to-native knee kinematics.

Anxiety disorders are the most prevalent mental health conditions. Besides psycho-pharmacotherapy, cognitive behavioral therapy with an exposure-based approach is considered the gold standard. However, not all patients benefit from this approach. Here, we aimed to translate laboratory findings on enhanced fear extinction with repetitive transcranial magnetic stimulation (TMS) to the clinic. In this double-blind, randomized, placebo-controlled clinical trial, 76 participants with acrophobia received an activating intermittent theta burst stimulation (iTBS) targeting the left posterior prefrontal cortex immediately before two virtual reality exposure therapy sessions. Phobic symptoms were assessed at baseline, post-intervention, and a 6-month follow-up. Results revealed a significant reduction in phobic symptoms from baseline to post-assessment and follow-up and confirmed the efficacy of virtual reality exposure therapy as a treatment for specific phobias. Interestingly, no additional effect was observed for active iTBS compared to sham iTBS. Our post-hoc analyses argue for an individualized TMS application. Further research is needed to determine optimal TMS parameters and validate these results in clinical trials, accounting for methodological and inter- and intra-individual variability, as well as alternative therapeutic processes.

Zusammenfassung In Deutschland besteht seit dem Inkrafttreten des Digitale-Versorgung-Gesetzes (DVG) von 2019 erstmals die Möglichkeit, medizinische Apps per Rezept zu verordnen. Bis August 2024 existiert jedoch noch keine zugelassene Digitale Gesundheitsanwendung (DiGA) für die axiale Spondyloarthritis (axSpA). Denkbar wäre, dass axSpA-Betroffene besonders von einer DiGA profitieren könnten, welche bewegungs- und verhaltenstherapeutische Interventionen per App vermittelt, da deren Wirksamkeit in der Vergangenheit vielfach im nicht-digitalen Setting nachgewiesen werden konnte. Es konnte zudem kürzlich gezeigt werden, dass axSpA-Betroffene selbst einen hohen Bedarf für eine krankheitsspezifische App sehen. In dieser Arbeit soll daher ein Überblick über bisher verfügbare, deutschsprachige Medizin-Apps gegeben werden, welche die axiale Spondyloarthritis direkt adressieren. Es wurden primär fünf deutschsprachige Medizin-Apps identifiziert, die auch oder ausschließlich auf die Indikation axSpA ausgerichtet sind. Im Detail handelt es sich um die App „Axia“, die „Mida Rheuma App“, die „RheCORD PLUS“ App, „Rheuma-Auszeit“ und die Yoga App „YogiTherapy“. Die bisher publizierte Evidenz zu den Anwendungen stammt vor allem aus Kurzzeit-Nutzertests, welche trotz einiger Hinweise zu möglichen positiven Effekten der Anwendungen noch keine abschließende Bewertung zulassen. Daneben existieren auch erste Daten zur Off-Label-Anwendung bereits für andere Indikationen zugelassener DiGAs bei axSpA Patient*innen. Die aktuelle Entwicklung lässt hoffen, dass vielleicht schon ab 2025 eine erste DiGA auch für die axSpA zur Verfügung stehen könnten.

We study some compactness properties of the set of conformally flat singular metrics with constant, positive sixth order Q-curvature on a finitely punctured sphere. Based on a recent classification of the local asymptotic behavior near isolated singularities, we introduce a notion of necksize for these metrics in our moduli space, which we use to characterize compactness. More precisely, we prove that if the punctures remain separated and the necksize at each puncture is bounded away from zero along a sequence of metrics, then a subsequence converges with respect to the Gromov–Hausdorff metric. Our proof relies on an upper bound estimate which is proved using moving planes and a blow-up argument. This is combined with a lower bound estimate which is a consequence of a removable singularity theorem. We also introduce a homological invariant which may be of independent interest for upcoming research.

Metal–Organic frameworks (MOFs) are promising candidates for advanced photocatalytically active materials. These porous crystalline compounds have large active surface areas and structural tunability and are thus highly competitive with oxides, the well‐established material class for photocatalysis. However, due to their complex organic and coordination chemistry composition, photophysical mechanisms involved in the photocatalytic processes in MOFs are still not well understood. Employing electron paramagnetic resonance (EPR) spectroscopy and time‐resolved photoluminescence spectroscopy (trPL), the fundamental processes of electron and hole generation are investigated, as well as capture events that lead to the formation of various radical species in UiO‐66, an archetypical MOF photocatalyst. A manifold of photoinduced electron spin centers is detected, which is subsequently analyzed and identified with the help of density‐functional theory (DFT) calculations. Under UV illumination, the symmetry, g‐tensors, and lifetimes of three distinct contributions are revealed: a surface O2‐radical, a light‐induced electron‐hole pair, and a triplet exciton. Notably, the latter is found to emit (delayed) fluorescence. The findings provide new insights into the photoinduced charge transfer processes, which are the basis of photocatalytic activity in UiO‐66. This sets the stage for further studies on photogenerated spin centers in this and similar MOF materials.

Accurate classification of cells in bronchoalveolar lavage (BAL) fluid is essential for the assessment of lung disease in pneumology and critical care medicine. However, the effectiveness of BAL fluid analysis is highly dependent on individual expertise. Our research is focused on improving the accuracy and efficiency of BAL cell classification using the “You Only Look Once” (YOLO) algorithm to reduce variability and increase the accuracy of cell detection in BALF analysis. We assess various YOLOv7 iterations, including YOLOv7, YOLOv7 with Adam and label smoothing, YOLOv7-E6E, and YOLOv7-E6E with Adam and label smoothing focusing on the detection of four key cell types of diagnostic importance in BAL fluid: macrophages, lymphocytes, neutrophils, and eosinophils. This study utilised cytospin preparations of BAL fluid, employing May-Grunwald-Giemsa staining, and analysed a dataset comprising 2032 images with 42,221 annotations. Classification performance was evaluated using recall, precision, F1 score, mAP@.5, and mAP@.5;.95 along with a confusion matrix. The comparison of four algorithmic approaches revealed minor distinctions in mean results, falling short of statistical significance (p < 0.01; p < 0.05). YOLOv7, with an inference time of 13.5 ms for 640 × 640 px images, achieved commendable performance across all cell types, boasting an average F1 metric of 0.922, precision of 0.916, recall of 0.928, and mAP@.5 of 0.966. Remarkably, all four cell types were classified consistently with high-performance metrics. Notably, YOLOv7 demonstrated marginally superior class value dispersion when compared to YOLOv7-adam-label-smoothing, YOLOv7-E6E, and YOLOv7-E6E-adam-label-smoothing, albeit without statistical significance. Consequently, there is limited justification for deploying the more computationally intensive YOLOv7-E6E and YOLOv7-E6E-adam-label-smoothing models. This investigation indicates that the default YOLOv7 variant is the preferred choice for differential cytology due to its accessibility, lower computational demands, and overall more consistent results than more complex models.

The physics of complex systems stands to greatly benefit from the qualitative changes in data availability and advances in data-driven computational methods. Many of these systems can be represented by interacting degrees of freedom on inhomogeneous graphs. However, the lack of translational invariance presents a fundamental challenge to theoretical tools, such as the renormalization group, which were so successful in characterizing the universal physical behaviour in critical phenomena. Here we show that compression theory allows the extraction of relevant degrees of freedom in arbitrary geometries, and the development of efficient numerical tools to build an effective theory from data. We demonstrate our method by applying it to a strongly correlated system on an Ammann-Beenker quasicrystal, where it discovers an exotic critical point with broken conformal symmetry. We also apply it to an antiferromagnetic system on non-bipartite random graphs, where any periodicity is absent.

Intercalating two-dimensional quantum materials beneath a sheet of graphene provides effective environmental protection and facilitates ex situ device fabrication. However, developing a functional device requires rapid, large-scale screening methods to evaluate the quality of the intercalant, which to date can be monitored only by slow, ultra-high vacuum-based surface science techniques. In this study, we utilize ex situ Raman micro-spectroscopy to optically and nondestructively identify the quantum spin Hall insulator indenene, a monolayer of indium sandwiched between a SiC(0001) substrate and a single sheet of graphene. Color modulation combined with indenene's distinctive low-frequency Raman fingerprint enables rapid assessment of its homogeneity and crystalline quality. Density functional perturbation theory indicates that this Raman signature originates mainly from indenene's shear and breathing modes, while additional higher order modes are tentatively attributed to defect-assisted and two-phonon Raman processes.

Background Whether carriers of BRCA1 or BRCA2 (BRCA1/2) pathogenic variants (PVs) have increased risks of childhood, adolescent, and young adult (CAYA) cancers is controversial. We aimed to evaluate this risk and to inform clinical care of young BRCA1/2 PV carriers and genetic testing for CAYA cancer patients. Methods Using data from 47,117 individuals from 3,086 BRCA1/2 families, we conducted pedigree analysis to estimate relative risks (RRs) for cancers diagnosed before age 30. Results Our data included 274 cancers diagnosed before age 30: 139 breast cancers, 10 ovarian cancers, and 125 non-breast non-ovarian cancers. Associations for breast cancer in young adulthood (20-29 years) were found with RRs of 11.4 (95% CI: 5.5, 23.7) and 5.2 (95% CI: 1.6, 17.7) for BRCA1 and BRCA2 PV carriers, respectively. No association was found for any other investigated CAYA cancer, nor for all non-breast non-ovarian cancers combined: the RRs were 0.4 (95% CI: 0.1, 1.4) and 1.4 (95% CI: 0.7, 3.0) in BRCA1 or BRCA2 PV carriers, respectively. Conclusion We found no evidence that BRCA1/2 PV carriers have an increased CAYA cancer risk aside from breast cancer in women in their 20’s. Our results, along with a critical evaluation of previous germline sequencing studies, suggest that the childhood and adolescent cancer risk conferred by BRCA1/2 PV would be low (ie, RR < 2) if it existed. Our findings do not support PV testing for offspring of BRCA1/2 PV carriers at ages <18 years, nor for conducting BRCA1/2 PV testing for childhood and adolescent cancer patients.

In 28 patients supported by an Impella pump (Impella CP, Abiomed Inc. ® , Danvers, MA), hemodynamic measurements by PiCCO (PULSION Medical Systems SE ® , Feldkirchen, Germany) and pulmonary artery catheter (PAC or Swan-Ganz Catheter; Edwards Lifescience ® , Unterschleissheim, Germany) were compared. There was a significant positive correlation of cardiac output (CO; r ² = 0.917, p < 0.001), systemic vascular resistance index (SVRI; r ² = 0.904, p < 0.001), stroke volume index (SI; r ² = 0.909, p < 0.001) and left ventricular work index (LCWI; r ² = 0.689, p < 0.001) in PiCCO and PAC measurements under Impella CP support. We conclude, that in patients with left-ventricular Impella support, hemodynamics may be assessentd by PiCCO or PAC.

Mechanistic or process‐based models offer great insights into the range dynamics of species facing non‐equilibrium conditions, such as climate and land‐use changes or invasive species. Their consideration of underlying mechanisms relaxes the species‐environment equilibrium assumed by correlative approaches, while also generating conservation‐relevant indicators, such as range‐wide abundance time series and migration rates if demographically explicit. However, the computational complexity of mechanistic models limits their development and applicability to large spatiotemporal extents. We present the R package “metaRange”: a modular framework to build population‐based and metabolically constrained range models. We also provide a catalogue of biological functions to calculate niche‐based suitability, metabolic scaling, population dynamics, biotic interactions and kernel‐based dispersal, which may include directed movement. The framework's modularity enables the user to combine, extend, or replace these functions, making it possible to customize the model to the ecology of the study system. The package supports an unlimited number of static or dynamic environmental factors as input, including climate and land use. As examples, we include one single‐species application to predict the range dynamics of the European wildcat (Felis silvestris) in Germany, and one theoretical study in which we simulated 100 virtual species in three scenarios: without competition, with competition, and with competition under a generalist‐specialist trade‐off. Due to the population‐level, the package can execute such extensive simulation experiments on regular end‐user hardware in a short amount of time. We provide detailed technical documentation, both for the individual functions in the package as well as instructions on how to set up different types of model structures and experimental designs. The metaRange framework enables process‐based simulations of range dynamic of multiple interacting species on a high resolution and low computational demand. We believe that it allows for theoretical insights and hypotheses testing about future range dynamics of real‐world species, which may better support conservation policies targeting biodiversity loss mitigation.

Pharmacokinetics and biodistribution profiles of active substances are crucial aspects for their safe and successful administration. Since many immunogenic compounds do not meet all requirements for safe and effective administration, well-defined drug nanocarrier systems are necessary with a stimuli-responsive drug-release profile. For this purpose, a novel pH-responsive aliphatic cyclic carbonate is introduced with benzyl ketal side chains and polymerized onto a poly(ethylene glycol) macroinitiator. The resulting block copolymers could be formulated via a solvent-evaporation method into well-defined polymeric micelles. The hydrophobic carbonate block was equipped with an acid degradable ketal side group that served as an acid-responsive functional group. Already subtle pH alternations led to micelle disassembly and the release of the active cargo. Furthermore, basic carbonate backbone degradation assured the pH responsiveness of the nanocarriers in both acidic and basic conditions. To investigate the delivery capacity of polymeric micelles, the model small molecule compound CL075, which serves as an immunotherapeutic TLR7/8 agonist, was encapsulated. Incubation studies with human blood plasma revealed the absence of undesirable protein adsorption on the drug-loaded nanoparticles. Furthermore, in vitro applications confirmed cell uptake of the nanodrug formulations by macrophages and the induction of payload-mediated immune stimulation. Altogether, these results underline the huge potential of the developed multi-pH-responsive polymeric nanocarrier for immunodrug delivery.

Chiral 3a,6a-dihydroborolo[3,2-b]boroles are obtained in one diastereoselective step from the reactions of ortho-(dihaloboryl)arenes with stannole derivatives via a complex rearrangement of 1-borolyl-2-(dihaloboryl)arene intermediates.

Computational investigations employing Density Functional Theory (SMD(benzene)-M06-2X-D3/6-311+G*) predict that stable metal-free mono (Lewis base)-stabilized borylenes could strongly bind with transition metal (Fe and Ni) complexes. The binding results in increase in the Lewis basicity of the metal centers thus facilitating the formation of metal only Lewis pairs (MOLPs) of the form [L(CO)4Fe → GaCl3] and [L(CO)3Ni → GaCl3] (L = electron donating ligands). Further, the binding of different ligands with the metals as well as bonding in the MOLPs have been further investigated with the help of QTAIM and EDA-NOCV analyses.