TY - JOUR A1 - Angermann, Susanne A1 - Günthner, Roman A1 - Hanssen, Henner A1 - Lorenz, Georg A1 - Braunisch, Matthias C. A1 - Steubl, Dominik A1 - Matschkal, Julia A1 - Kemmner, Stephan A1 - Hausinger, Renate A1 - Block, Zenonas A1 - Haller, Bernhard A1 - Heemann, Uwe A1 - Kotliar, Konstantin A1 - Grimmer, Timo A1 - Schmaderer, Christoph T1 - Cognitive impairment and microvascular function in end-stage renal disease JF - International Journal of Methods in Psychiatric Research (MPR) N2 - 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. KW - cerebral small vessel disease KW - cognitive impairment KW - dialysis KW - retinal vessels Y1 - 2022 U6 - https://doi.org/10.1002/mpr.1909 SN - 1049-8931 (Print) SN - 1557-0657 (Online) VL - 31 IS - 2 SP - 1 EP - 10 PB - Wiley ER - TY - JOUR A1 - Anding, Ralf A1 - Tabaza, Ruth A1 - Staat, Manfred A1 - Trenz, Eva A1 - Lohmann, Philipp A1 - Klinge, Uwe A1 - Kirschner-Hermanns, Ruth T1 - Introducing a method of in vitro testing of different anchoring systems used for female incontinence and prolapse surgery JF - BioMed research international Y1 - 2013 SN - 1110-7251 (E-Journal); 2314-6141 (E-Journal); 1110-7243 (Print); 2314-6133 (Print) VL - Vol. 2013 SP - Article ID 401417 ER - TY - JOUR A1 - Amin, Rashid A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard A1 - Lazarovici, Philip A1 - Lelkes, Peter I. T1 - Permeability of an In Vitro Model of Blood Brain Barrier (BBB) JF - 13th International Conference on Biomedical Engineering / Lim, Chwee Teck [Ed.] Y1 - 2009 SN - 978-3-540-92841-6 N1 - IFMBE Proceedings ; 23, Track 1 ; ICBME 2008 3–6 December 2008 Singapore SP - 81 EP - 84 ER - TY - JOUR A1 - Altherr, Lena A1 - Leise, Philipp A1 - Pfetsch, Marc E. A1 - Schmitt, Andreas T1 - Algorithmic design and resilience assessment of energy efficient high-rise water supply systems JF - Applied Mechanics and Materials N2 - High-rise water supply systems provide water flow and suitable pressure in all levels of tall buildings. To design such state-of-the-art systems, the consideration of energy efficiency and the anticipation of component failures are mandatory. In this paper, we use Mixed-Integer Nonlinear Programming to compute an optimal placement of pipes and pumps, as well as an optimal control strategy.Moreover, we consider the resilience of the system to pump failures. A resilient system is able to fulfill a predefined minimum functionality even though components fail or are restricted in their normal usage. We present models to measure and optimize the resilience. To demonstrate our approach, we design and analyze an optimal resilient decentralized water supply system inspired by a real-life hotel building. KW - MINLP KW - Buffering Capacity KW - Uncertainty KW - Water Supply Networks KW - Booster Stations Y1 - 2018 U6 - https://doi.org/10.4028/www.scientific.net/AMM.885.211 SN - 1662-7482 VL - 885 SP - 211 EP - 223 PB - Trans Tech Publications CY - Bäch ER - TY - JOUR A1 - Altherr, Lena A1 - Joggerst, Laura A1 - Leise, Philipp A1 - Pfetsch, Marc E. A1 - Schmitt, Andreas A1 - Wendt, Janine T1 - On obligations in the development process of resilient systems with algorithmic design methods JF - Applied Mechanics and Materials N2 - Advanced computational methods are needed both for the design of large systems and to compute high accuracy solutions. Such methods are efficient in computation, but the validation of results is very complex, and highly skilled auditors are needed to verify them. We investigate legal questions concerning obligations in the development phase, especially for technical systems developed using advanced methods. In particular, we consider methods of resilient and robust optimization. With these techniques, high performance solutions can be found, despite a high variety of input parameters. However, given the novelty of these methods, it is uncertain whether legal obligations are being met. The aim of this paper is to discuss if and how the choice of a specific computational method affects the developer’s product liability. The review of legal obligations in this paper is based on German law and focuses on the requirements that must be met during the design and development process. KW - legal obligations KW - product liability KW - design of technical systems KW - optimization KW - resilience Y1 - 2018 SN - 1662-7482 U6 - https://doi.org/10.4028/www.scientific.net/AMM.885.240 VL - 885 IS - 885 SP - 240 EP - 252 PB - Trans Tech Publications CY - Bäch ER - TY - JOUR A1 - Altherr, Lena A1 - Ederer, Thorsten A1 - Pöttgen, Philipp A1 - Lorenz, Ulf A1 - Pelz, Peter F. ED - Pelz, Peter F. ED - Groche, Peter T1 - Multicriterial optimization of technical systems considering multiple load and availability scenarios JF - Applied Mechanics and Materials N2 - Cheap does not imply cost-effective -- this is rule number one of zeitgeisty system design. The initial investment accounts only for a small portion of the lifecycle costs of a technical system. In fluid systems, about ninety percent of the total costs are caused by other factors like power consumption and maintenance. With modern optimization methods, it is already possible to plan an optimal technical system considering multiple objectives. In this paper, we focus on an often neglected contribution to the lifecycle costs: downtime costs due to spontaneous failures. Consequently, availability becomes an issue. KW - sustainability KW - availability KW - energy efficiency KW - mixed-integer linear programming KW - system synthesis Y1 - 2015 SN - 1660-9336 U6 - https://doi.org/10.4028/www.scientific.net/AMM.807.247 VL - 807 SP - 247 EP - 256 ER - TY - JOUR A1 - Altherr, Lena A1 - Ederer, Thorsten A1 - Lorenz, Ulf A1 - Pelz, Peter F. A1 - Pöttgen, Philipp ED - Lübbecke, Marco ED - Koster, Arie ED - Letmathe, Peter ED - Madlener, Reihard ED - Peis, Britta ED - Walther, Grit T1 - Experimental validation of an enhanced system synthesis approach JF - Operations Research Proceedings 2014 N2 - Planning the layout and operation of a technical system is a common task for an engineer. Typically, the workflow is divided into consecutive stages: First, the engineer designs the layout of the system, with the help of his experience or of heuristic methods. Secondly, he finds a control strategy which is often optimized by simulation. This usually results in a good operating of an unquestioned sys- tem topology. In contrast, we apply Operations Research (OR) methods to find a cost-optimal solution for both stages simultaneously via mixed integer program- ming (MILP). Technical Operations Research (TOR) allows one to find a provable global optimal solution within the model formulation. However, the modeling error due to the abstraction of physical reality remains unknown. We address this ubiq- uitous problem of OR methods by comparing our computational results with mea- surements in a test rig. For a practical test case we compute a topology and control strategy via MILP and verify that the objectives are met up to a deviation of 8.7%. Y1 - 2014 SN - 978-3-319-28695-2 U6 - https://doi.org/10.1007/978-3-319-28697-6_1 PB - Springer CY - Basel ER - TY - JOUR A1 - Altherr, Lena A1 - Brötz, Nicolas A1 - Dietrich, Ingo A1 - Gally, Tristan A1 - Geßner, Felix A1 - Kloberdanz, Hermann A1 - Leise, Philipp A1 - Pelz, Peter Franz A1 - Schlemmer, Pia A1 - Schmitt, Andreas T1 - Resilience in mechanical engineering - a concept for controlling uncertainty during design, production and usage phase of load-carrying structures JF - Applied Mechanics and Materials N2 - Resilience as a concept has found its way into different disciplines to describe the ability of an individual or system to withstand and adapt to changes in its environment. In this paper, we provide an overview of the concept in different communities and extend it to the area of mechanical engineering. Furthermore, we present metrics to measure resilience in technical systems and illustrate them by applying them to load-carrying structures. By giving application examples from the Collaborative Research Centre (CRC) 805, we show how the concept of resilience can be used to control uncertainty during different stages of product life. Y1 - 2018 SN - 1662-7482 U6 - https://doi.org/10.4028/www.scientific.net/AMM.885.187 VL - 885 SP - 187 EP - 198 PB - Trans Tech Publications CY - Bäch ER - TY - JOUR A1 - Alnemer, Momin Sami Mohammad A1 - Kotliar, Konstantin A1 - Neuhaus, Valentin A1 - Pape, Hans-Christoph A1 - Ciritsis, Bernhard D. T1 - Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model JF - Cost Effectiveness and Resource Allocation N2 - 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. KW - Hip fractures KW - Prevention KW - Geriatric KW - Cost-effectiveness KW - Prophylaxis Y1 - 2023 U6 - https://doi.org/10.1186/s12962-023-00482-4 SN - 1478-7547 N1 - Corresponding author: Momin S. Alnemer IS - 21, Article number: 77 PB - Springer Nature ER - TY - JOUR A1 - Almajhdi, Fahad N. A1 - Senger, Tilo A1 - Amer, Haitham M. A1 - Gissmann, Lutz A1 - Öhlschläger, Peter T1 - Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (Shuffling) JF - PLOS one N2 - Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0113461 SN - 1932-6203 VL - 11 IS - 9 PB - PLOS CY - San Francisco ER -