@article{ClausnitzerKleefeld2024, author = {Clausnitzer, Julian and Kleefeld, Andreas}, title = {A spectral Galerkin exponential Euler time-stepping scheme for parabolic SPDEs on two-dimensional domains with a C² boundary}, series = {Discrete and Continuous Dynamical Systems - Series B}, volume = {29}, journal = {Discrete and Continuous Dynamical Systems - Series B}, number = {4}, publisher = {AIMS}, address = {Springfield}, issn = {1531-3492}, doi = {10.3934/dcdsb.2023148}, pages = {1624 -- 1651}, year = {2024}, abstract = {We consider the numerical approximation of second-order semi-linear parabolic stochastic partial differential equations interpreted in the mild sense which we solve on general two-dimensional domains with a C² boundary with homogeneous Dirichlet boundary conditions. The equations are driven by Gaussian additive noise, and several Lipschitz-like conditions are imposed on the nonlinear function. We discretize in space with a spectral Galerkin method and in time using an explicit Euler-like scheme. For irregular shapes, the necessary Dirichlet eigenvalues and eigenfunctions are obtained from a boundary integral equation method. This yields a nonlinear eigenvalue problem, which is discretized using a boundary element collocation method and is solved with the Beyn contour integral algorithm. We present an error analysis as well as numerical results on an exemplary asymmetric shape, and point out limitations of the approach.}, language = {en} } @article{SchierenKleinschmidtSchmutzetal.2019, author = {Schieren, Mark and Kleinschmidt, Joris and Schmutz, Axel and Loop, Torsten and Gatzweiler, Karl-Heinz and Staat, Manfred and Wappler, Frank and Defosse, Jerome}, title = {Comparison of forces acting on maxillary incisors during tracheal intubation with different laryngoscopy techniques: a blinded manikin study}, series = {Anaesthesia}, volume = {74}, journal = {Anaesthesia}, number = {12}, publisher = {Wiley-Blackwell}, address = {Oxford}, isbn = {1365-2044}, doi = {10.1111/anae.14815}, year = {2019}, language = {en} } @incollection{Laack2020, author = {Laack, Walter van}, title = {Twee Kanten van {\´e}{\´e}n Medaille}, series = {Het Geheim van Elysion : 45 Jaar Studies naar Nabij-de-Dood-Ervaringen over Bewustzijn in Liefde zonder Waarheen}, booktitle = {Het Geheim van Elysion : 45 Jaar Studies naar Nabij-de-Dood-Ervaringen over Bewustzijn in Liefde zonder Waarheen}, publisher = {Van Warven}, address = {Kampen}, isbn = {978-94-93175-44-0}, pages = {97 -- 105}, year = {2020}, language = {nl} } @incollection{EngelmannShashaSlabu2021, author = {Engelmann, Ulrich M. and Shasha, Carolyn and Slabu, Ioana}, title = {Magnetic nanoparticle relaxation in biomedical application: focus on simulating nanoparticle heating}, series = {Magnetic nanoparticles in human health and medicine}, booktitle = {Magnetic nanoparticles in human health and medicine}, publisher = {Wiley-Blackwell}, address = {Hoboken, New Jeersey}, isbn = {978-1-119-75467-1}, pages = {327 -- 354}, year = {2021}, language = {en} } @unpublished{BornheimGriegerBlanecketal.2023, author = {Bornheim, Tobias and Grieger, Niklas and Blaneck, Patrick Gustav and Bialonski, Stephan}, title = {Preprint: Speaker attribution in German parliamentary debates with QLoRA-adapted large language models}, series = {Journal for Language Technology and Computational Linguistics}, journal = {Journal for Language Technology and Computational Linguistics}, doi = {10.48550/arXiv.2309.09902}, pages = {8 Seiten}, year = {2023}, abstract = {The growing body of political texts opens up new opportunities for rich insights into political dynamics and ideologies but also increases the workload for manual analysis. Automated speaker attribution, which detects who said what to whom in a speech event and is closely related to semantic role labeling, is an important processing step for computational text analysis. We study the potential of the large language model family Llama 2 to automate speaker attribution in German parliamentary debates from 2017-2021. We fine-tune Llama 2 with QLoRA, an efficient training strategy, and observe our approach to achieve competitive performance in the GermEval 2023 Shared Task On Speaker Attribution in German News Articles and Parliamentary Debates. Our results shed light on the capabilities of large language models in automating speaker attribution, revealing a promising avenue for computational analysis of political discourse and the development of semantic role labeling systems.}, language = {en} } @inproceedings{BornheimGriegerBialonski2021, author = {Bornheim, Tobias and Grieger, Niklas and Bialonski, Stephan}, title = {FHAC at GermEval 2021: Identifying German toxic, engaging, and fact-claiming comments with ensemble learning}, series = {Proceedings of the GermEval 2021 Workshop on the Identification of Toxic, Engaging, and Fact-Claiming Comments : 17th Conference on Natural Language Processing KONVENS 2021}, booktitle = {Proceedings of the GermEval 2021 Workshop on the Identification of Toxic, Engaging, and Fact-Claiming Comments : 17th Conference on Natural Language Processing KONVENS 2021}, publisher = {Heinrich Heine University}, address = {D{\"u}sseldorf}, doi = {10.48415/2021/fhw5-x128}, pages = {105 -- 111}, year = {2021}, language = {en} } @article{AliaziziOezsoyluBakhshiSichanietal.2024, author = {Aliazizi, Fereshteh and {\"O}zsoylu, Dua and Bakhshi Sichani, Soroush and Khorshid, Mehran and Glorieux, Christ and Robbens, Johan and Sch{\"o}ning, Michael Josef and Wagner, Patrick}, title = {Development and Calibration of a Microfluidic, Chip-Based Sensor System for Monitoring the Physical Properties of Water Samples in Aquacultures}, series = {Micromachines}, volume = {15}, journal = {Micromachines}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {2072-666X}, doi = {10.3390/mi15060755}, year = {2024}, abstract = {In this work, we present a compact, bifunctional chip-based sensor setup that measures the temperature and electrical conductivity of water samples, including specimens from rivers and channels, aquaculture, and the Atlantic Ocean. For conductivity measurements, we utilize the impedance amplitude recorded via interdigitated electrode structures at a single triggering frequency. The results are well in line with data obtained using a calibrated reference instrument. The new setup holds for conductivity values spanning almost two orders of magnitude (river versus ocean water) without the need for equivalent circuit modelling. Temperature measurements were performed in four-point geometry with an on-chip platinum RTD (resistance temperature detector) in the temperature range between 2 °C and 40 °C, showing no hysteresis effects between warming and cooling cycles. Although the meander was not shielded against the liquid, the temperature calibration provided equivalent results to low conductive Milli-Q and highly conductive ocean water. The sensor is therefore suitable for inline and online monitoring purposes in recirculating aquaculture systems.}, language = {en} } @article{BayerTemizArtmannDigeletal.2020, author = {Bayer, Robin and Temiz Artmann, Ayseg{\"u}l and Digel, Ilya and Falkenstein, Julia and Artmann, Gerhard and Creutz, Till and Hescheler, J{\"u}rgen}, title = {Mechano-pharmacological testing of L-Type Ca²⁺ channel modulators via human vascular celldrum model}, series = {Cellular Physiology and Biochemistry}, volume = {54}, journal = {Cellular Physiology and Biochemistry}, publisher = {Cell Physiol Biochem Press}, address = {D{\"u}sseldorf}, issn = {1421-9778}, doi = {10.33594/000000225}, pages = {371 -- 383}, year = {2020}, abstract = {Background/Aims: This study aimed to establish a precise and well-defined working model, assessing pharmaceutical effects on vascular smooth muscle cell monolayer in-vitro. It describes various analysis techniques to determine the most suitable to measure the biomechanical impact of vasoactive agents by using CellDrum technology. Methods: The so-called CellDrum technology was applied to analyse the biomechanical properties of confluent human aorta muscle cells (haSMC) in monolayer. The cell generated tensions deviations in the range of a few N/m² are evaluated by the CellDrum technology. This study focuses on the dilative and contractive effects of L-type Ca²⁺ channel agonists and antagonists, respectively. We analyzed the effects of Bay K8644, nifedipine and verapamil. Three different measurement modes were developed and applied to determine the most appropriate analysis technique for the study purpose. These three operation modes are called, particular time mode" (PTM), "long term mode" (LTM) and "real-time mode" (RTM). Results: It was possible to quantify the biomechanical response of haSMCs to the addition of vasoactive agents using CellDrum technology. Due to the supplementation of 100nM Bay K8644, the tension increased approximately 10.6\% from initial tension maximum, whereas, the treatment with nifedipine and verapamil caused a significant decrease in cellular tension: 10nM nifedipine decreased the biomechanical stress around 6,5\% and 50nM verapamil by 2,8\%, compared to the initial tension maximum. Additionally, all tested measurement modes provide similar results while focusing on different analysis parameters. Conclusion: The CellDrum technology allows highly sensitive biomechanical stress measurements of cultured haSMC monolayers. The mechanical stress responses evoked by the application of vasoactive calcium channel modulators were quantified functionally (N/m²). All tested operation modes resulted in equal findings, whereas each mode features operation-related data analysis.}, language = {en} } @article{UysalCreutzFiratetal.2022, author = {Uysal, Karya and Creutz, Till and Firat, Ipek Seda and Artmann, Gerhard and Teusch, Nicole and Temiz Artmann, Ayseg{\"u}l}, title = {Bio-functionalized ultra-thin, large-area and waterproof silicone membranes for biomechanical cellular loading and compliance experiments}, series = {Polymers}, volume = {14}, journal = {Polymers}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {2073-4360}, pages = {2213}, year = {2022}, abstract = {Biocompatibility, flexibility and durability make polydimethylsiloxane (PDMS) membranes top candidates in biomedical applications. CellDrum technology uses large area, <10 µm thin membranes as mechanical stress sensors of thin cell layers. For this to be successful, the properties (thickness, temperature, dust, wrinkles, etc.) must be precisely controlled. The following parameters of membrane fabrication by means of the Floating-on-Water (FoW) method were investigated: (1) PDMS volume, (2) ambient temperature, (3) membrane deflection and (4) membrane mechanical compliance. Significant differences were found between all PDMS volumes and thicknesses tested (p < 0.01). They also differed from the calculated values. At room temperatures between 22 and 26 °C, significant differences in average thickness values were found, as well as a continuous decrease in thicknesses within a 4 °C temperature elevation. No correlation was found between the membrane thickness groups (between 3-4 µm) in terms of deflection and compliance. We successfully present a fabrication method for thin bio-functionalized membranes in conjunction with a four-step quality management system. The results highlight the importance of tight regulation of production parameters through quality control. The use of membranes described here could also become the basis for material testing on thin, viscous layers such as polymers, dyes and adhesives, which goes far beyond biological applications.}, language = {en} } @article{UysalFiratCreutzetal.2022, author = {Uysal, Karya and Firat, Ipek Serat and Creutz, Till and Aydin, Inci Cansu and Artmann, Gerhard and Teusch, Nicole and Temiz Artmann, Ayseg{\"u}l}, title = {A novel in vitro wound healing assay using free-standing, ultra-thin PDMS membranes}, series = {membranes}, volume = {2023}, journal = {membranes}, number = {13(1)}, publisher = {MDPI}, address = {Basel}, doi = {10.3390/membranes13010022}, pages = {Artikel 22}, year = {2022}, abstract = {Advances in polymer science have significantly increased polymer applications in life sciences. We report the use of free-standing, ultra-thin polydimethylsiloxane (PDMS) membranes, called CellDrum, as cell culture substrates for an in vitro wound model. Dermal fibroblast monolayers from 28- and 88-year-old donors were cultured on CellDrums. By using stainless steel balls, circular cell-free areas were created in the cell layer (wounding). Sinusoidal strain of 1 Hz, 5\% strain, was applied to membranes for 30 min in 4 sessions. The gap circumference and closure rate of un-stretched samples (controls) and stretched samples were monitored over 4 days to investigate the effects of donor age and mechanical strain on wound closure. A significant decrease in gap circumference and an increase in gap closure rate were observed in trained samples from younger donors and control samples from older donors. In contrast, a significant decrease in gap closure rate and an increase in wound circumference were observed in the trained samples from older donors. Through these results, we propose the model of a cell monolayer on stretchable CellDrums as a practical tool for wound healing research. The combination of biomechanical cell loading in conjunction with analyses such as gene/protein expression seems promising beyond the scope published here.}, language = {en} } @article{TemizArtmannKurulgandemirciFıratetal.2021, author = {Temiz Artmann, Ayseg{\"u}l and Kurulgan demirci, Eylem and F{\i}rat, Ipek Seda and Oflaz, Hakan and Artmann, Gerhard}, title = {Recombinant activated protein C (rhAPC) affects lipopolysaccharide-induced mechanical compliance changes and beat frequency of mESC-derived cardiomyocyte monolayers}, series = {SHOCK}, journal = {SHOCK}, publisher = {Wolters Kluwer}, address = {K{\"o}ln}, issn = {1540-0514}, doi = {10.1097/SHK.0000000000001845}, year = {2021}, language = {en} } @article{GossmannFrotscherLinderetal.2016, author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Bayer, Robin and Epple, U. and Staat, Manfred and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}, series = {Cellular physiology and biochemistry}, volume = {38}, journal = {Cellular physiology and biochemistry}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {1421-9778 (Online)}, doi = {10.1159/000443124}, pages = {1182 -- 1198}, year = {2016}, abstract = {Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.}, language = {en} } @article{ArinkinDigelPorstetal.2014, author = {Arinkin, Vladimir and Digel, Ilya and Porst, Dariusz and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Phenotyping date palm varieties via leaflet cross-sectional imaging and artificial neural network application}, series = {BMC bioinformatics}, volume = {15}, journal = {BMC bioinformatics}, number = {55}, issn = {1471-2105}, doi = {10.1186/1471-2105-15-55}, pages = {1 -- 8}, year = {2014}, abstract = {Background True date palms (Phoenix dactylifera L.) are impressive trees and have served as an indispensable source of food for mankind in tropical and subtropical countries for centuries. The aim of this study is to differentiate date palm tree varieties by analysing leaflet cross sections with technical/optical methods and artificial neural networks (ANN). Results Fluorescence microscopy images of leaflet cross sections have been taken from a set of five date palm tree cultivars (Hewlat al Jouf, Khlas, Nabot Soltan, Shishi, Um Raheem). After features extraction from images, the obtained data have been fed in a multilayer perceptron ANN with backpropagation learning algorithm. Conclusions Overall, an accurate result in prediction and differentiation of date palm tree cultivars was achieved with average prediction in tenfold cross-validation is 89.1\% and reached 100\% in one of the best ANN.}, language = {en} } @article{MiciliValterOflazetal.2013, author = {Micili, Serap C. and Valter, Markus and Oflaz, Hakan and Ozogul, Candan and Linder, Peter and F{\"o}ckler, Nicole and Artmann, Gerhard and Digel, Ilya and Temiz Artmann, Ayseg{\"u}l}, title = {Optical coherence tomography : a potential tool to predict premature rupture of fetal membranes}, series = {Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine}, volume = {Vol. 227}, journal = {Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine}, number = {No. 4}, publisher = {Sage}, address = {London}, issn = {0046-2039 (Print) ; 2041-3033 (E-Journal)}, pages = {393 -- 401}, year = {2013}, language = {en} } @article{KurulganDemirciDemirciLinderetal.2012, author = {Kurulgan Demirci, Eylem and Demirci, Taylan and Linder, Peter and Trzewik, J{\"u}rgen and Gierkowski, Jessica Ricarda and Gossmann, Matthias and Kayser, Peter and Porst, Dariusz and Digel, Ilya and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {rhAPC reduces the endothelial cell permeability via a decrease of contractile tensions induced by endothelial cells}, series = {Journal of Bioscience and Bioengineering}, volume = {113}, journal = {Journal of Bioscience and Bioengineering}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1347-4421}, doi = {10.1016/j.jbiosc.2012.03.019}, pages = {212 -- 219}, year = {2012}, abstract = {All cells generate contractile tension. This strain is crucial for mechanically controlling the cell shape, function and survival. In this study, the CellDrum technology quantifying cell's (the cellular) mechanical tension on a pico-scale was used to investigate the effect of lipopolysaccharide (LPS) on human aortic endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on endothelial cells is cell contraction causing endothelium permeability increase. The aim was to finding out whether recombinant activated protein C (rhAPC) would reverse the endothelial cell response in an in-vitro sepsis model. In this study, the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6) levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive oxygen species (ROS) activation by florescence staining. The thrombin cellular contraction effect on endothelial cells was used as a positive control when the CellDrum technology was applied. Additionally, the Ras homolog gene family, member A (RhoA) mRNA expression level was checked by real time-PCR to support contractile tension results. According to contractile tension results, the mechanical predominance of actin stress fibers was a reason of the increased endothelial contractile tension leading to enhanced endothelium contractility and thus permeability enhancement. The originality of this data supports firstly the basic measurement principles of the CellDrum technology and secondly that rhAPC has a beneficial effect on sepsis influenced cellular tension. The technology presented here is promising for future high-throughput cellular tension analysis that will help identify pathological contractile tension responses of cells and prove further cell in-vitro models.}, language = {en} } @book{ArtmannTemizArtmannZhubanovaetal.2018, author = {Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l and Zhubanova, Azhar A. and Digel, Ilya}, title = {Biological, physical and technical basics of cell engineering}, editor = {Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l and Zhubanova, Azhar A. and Digel, Ilya}, publisher = {Springer}, address = {Singapore}, isbn = {978-981-10-7903-0}, pages = {xxiv, 481 Seiten ; Illustrationen, Diagramme}, year = {2018}, language = {en} } @article{AngermannGuenthnerHanssenetal.2022, author = {Angermann, Susanne and G{\"u}nthner, Roman and Hanssen, Henner and Lorenz, Georg and Braunisch, Matthias C. and Steubl, Dominik and Matschkal, Julia and Kemmner, Stephan and Hausinger, Renate and Block, Zenonas and Haller, Bernhard and Heemann, Uwe and Kotliar, Konstantin and Grimmer, Timo and Schmaderer, Christoph}, title = {Cognitive impairment and microvascular function in end-stage renal disease}, series = {International Journal of Methods in Psychiatric Research (MPR)}, volume = {31}, journal = {International Journal of Methods in Psychiatric Research (MPR)}, number = {2}, publisher = {Wiley}, issn = {1049-8931 (Print)}, doi = {10.1002/mpr.1909}, pages = {1 -- 10}, year = {2022}, abstract = {Objective Hemodialysis patients show an approximately threefold higher prevalence of cognitive impairment compared to the age-matched general population. Impaired microcirculatory function is one of the assumed causes. Dynamic retinal vessel analysis is a quantitative method for measuring neurovascular coupling and microvascular endothelial function. We hypothesize that cognitive impairment is associated with altered microcirculation of retinal vessels. Methods 152 chronic hemodialysis patients underwent cognitive testing using the Montreal Cognitive Assessment. Retinal microcirculation was assessed by Dynamic Retinal Vessel Analysis, which carries out an examination recording retinal vessels' reaction to a flicker light stimulus under standardized conditions. Results In unadjusted as well as in adjusted linear regression analyses a significant association between the visuospatial executive function domain score of the Montreal Cognitive Assessment and the maximum arteriolar dilation as response of retinal arterioles to the flicker light stimulation was obtained. Conclusion This is the first study determining retinal microvascular function as surrogate for cerebral microvascular function and cognition in hemodialysis patients. The relationship between impairment in executive function and reduced arteriolar reaction to flicker light stimulation supports the involvement of cerebral small vessel disease as contributing factor for the development of cognitive impairment in this patient population and might be a target for noninvasive disease monitoring and therapeutic intervention.}, language = {en} } @article{KotliarOrtnerConradietal.2022, author = {Kotliar, Konstantin and Ortner, Marion and Conradi, Anna and Hacker, Patricia and Hauser, Christine and G{\"u}nthner, Roman and Moser, Michaela and Muggenthaler, Claudia and Diehl-Schmid, Janine and Priller, Josef and Schmaderer, Christoph and Grimmer, Timo}, title = {Altered retinal cerebral vessel oscillation frequencies in Alzheimer's disease compatible with impaired amyloid clearance}, series = {Neurobiology of Aging}, volume = {120}, journal = {Neurobiology of Aging}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0197-4580}, doi = {10.1016/j.neurobiolaging.2022.08.012}, pages = {117 -- 127}, year = {2022}, abstract = {Retinal vessels are similar to cerebral vessels in their structure and function. Moderately low oscillation frequencies of around 0.1 Hz have been reported as the driving force for paravascular drainage in gray matter in mice and are known as the frequencies of lymphatic vessels in humans. We aimed to elucidate whether retinal vessel oscillations are altered in Alzheimer's disease (AD) at the stage of dementia or mild cognitive impairment (MCI). Seventeen patients with mild-to-moderate dementia due to AD (ADD); 23 patients with MCI due to AD, and 18 cognitively healthy controls (HC) were examined using Dynamic Retinal Vessel Analyzer. Oscillatory temporal changes of retinal vessel diameters were evaluated using mathematical signal analysis. Especially at moderately low frequencies around 0.1 Hz, arterial oscillations in ADD and MCI significantly prevailed over HC oscillations and correlated with disease severity. The pronounced retinal arterial vasomotion at moderately low frequencies in the ADD and MCI groups would be compatible with the view of a compensatory upregulation of paravascular drainage in AD and strengthen the amyloid clearance hypothesis.}, language = {en} } @article{NeumaierWeissVeldemanetal.2021, author = {Neumaier, Felix and Weiss, Miriam and Veldeman, Michael and Kotliar, Konstantin and Wiesmann, Martin and Schulze-Steinen, Henna and H{\"o}llig, Anke and Clusmann, Hans and Schubert, Gerrit Alexander and Albanna, Walid}, title = {Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage - preliminary findings from an observational cohort study}, series = {Clinical Neurology and Neurosurgery}, volume = {208}, journal = {Clinical Neurology and Neurosurgery}, number = {Article No.: 106870}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0303-8467}, doi = {10.1016/j.clineuro.2021.106870}, year = {2021}, abstract = {Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH.}, language = {en} } @article{AlnemerKotliarNeuhausetal.2023, author = {Alnemer, Momin Sami Mohammad and Kotliar, Konstantin and Neuhaus, Valentin and Pape, Hans-Christoph and Ciritsis, Bernhard D.}, title = {Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model}, series = {Cost Effectiveness and Resource Allocation}, journal = {Cost Effectiveness and Resource Allocation}, number = {21, Article number: 77}, publisher = {Springer Nature}, issn = {1478-7547}, doi = {10.1186/s12962-023-00482-4}, pages = {12 Seiten}, year = {2023}, abstract = {Background Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices. Methods This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare \& Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10\% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results. Results With a 10\% fracture risk reduction, model A costs between \$8,850 and \$46,940 per quality-adjusted life-year (\$/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8\% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side's prophylaxis, the patient's age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between \$11,000/QALY and \$74,000/QALY, which is below the defined willingness to pay threshold. Conclusion Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks.}, language = {en} }