TY - CHAP A1 - Démaris, Alise A1 - Grišić, Ana-Marija A1 - Huisinga, Wilhelm A1 - Walter, Reinisch A1 - Kloft, Charlotte T1 - Evaluation of dosing strategies of anti-TNF alpha monoclonal antibodies using pharmacokinetic modelling and simulation T2 - Journal of Crohn's and Colitis N2 - Background: Anti-TNFα monoclonal antibodies (mAbs) are a well-established treatment for patients with Crohn’s disease (CD). However, subtherapeutic concentrations of mAbs have been related to a loss of response during the first year of therapy1. Therefore, an appropriate dosing strategy is crucial to prevent the underexposure of mAbs for those patients. The aim of our study was to assess the impact of different dosing strategies (fixed dose or body size descriptor adapted) on drug exposure and the target concentration attainment for two different anti-TNFα mAbs: infliximab (IFX, body weight (BW)-based dosing) and certolizumab pegol (CZP, fixed dosing). For this purpose, a comprehensive pharmacokinetic (PK) simulation study was performed. Methods: A virtual population of 1000 clinically representative CD patients was generated based on the distribution of CD patient characteristics from an in-house clinical database (n = 116). Seven dosing regimens were investigated: fixed dose and per BW, lean BW (LBW), body surface area, height, body mass index and fat-free mass. The individual body size-adjusted doses were calculated from patient generated body size descriptor values. Then, using published PK models for IFX and CZP in CD patients2,3, for each patient, 1000 concentration–time profiles were simulated to consider the typical profile of a specific patient as well as the range of possible individual profiles due to unexplained PK variability across patients. For each dosing strategy, the variability in maximum and minimum mAb concentrations (Cmax and Cmin, respectively), area under the concentration-time curve (AUC) and the per cent of patients reaching target concentration were assessed during maintenance therapy. Results: For IFX and CZP, Cmin showed the highest variability between patients (CV ≈110% and CV ≈80%, respectively) with a similar extent across all dosing strategies. For IFX, the per cent of patients reaching the target (Cmin = 5 µg/ml) was similar across all dosing strategies (~15%). For CZP, the per cent of patients reaching the target average concentration of 17 µg/ml ranged substantially (52–71%), being the highest for LBW-adjusted dosing. Conclusion: By using a PK simulation approach, different dosing regimen of IFX and CZP revealed the highest variability for Cmin, the most commonly used PK parameter guiding treatment decisions, independent upon dosing regimen. Our results demonstrate similar target attainment with fixed dosing of IFX compared with currently recommended BW-based dosing. For CZP, the current fixed dosing strategy leads to comparable percentage of patients reaching target as the best performing body size-adjusted dosing (66% vs. 71%, respectively). KW - linical databases KW - crohn's disease KW - regimen KW - monoclonal antibodies KW - body surface area KW - infliximab KW - fat-free mass KW - certolizumab pegol KW - body mass index procedure Y1 - 2020 U6 - https://doi.org/10.1093/ecco-jcc/jjz203.201 SN - 1873-9946 SN - 1876-4479 VL - 14 IS - Supp. 1 SP - S171 EP - S172 PB - Oxford Univ. Press CY - Oxford ER - TY - CHAP A1 - Haase, Jennifer A1 - Matthiesen, Julia A1 - Schüffler, Arnulf A1 - Kluge, Annette T1 - Retentivity beats prior knowledge as predictor for the acquisition and adaptation of new production processes T2 - Proceedings of the 53rd Hawaii International Conference on System Sciences N2 - In the time of digitalization the demand for organizational change is rising and demands ways to cope with fundamental changes on the organizational as well as individual level. As a basis, learning and forgetting mechanisms need to be understood in order to guide a change process efficiently and successfully. Our research aims to get a better understanding of individual differences and mechanisms in the change context by performing an experiment where individuals learn and later re-learn a complex production process using a simulation setting. The individual’s performance, as well as retentivity and prior knowledge is assessed. Our results show that higher retentivity goes along with better learning and forgetting performances. Prior knowledge did not reveal such relation to the learning and forgetting performances. The influence of age and gender is discussed in detail. KW - Innovation in Organizations: Learning KW - learning KW - Unlearning KW - Intentional Forgetting KW - experiment KW - forgetting KW - prior knowledge KW - production process KW - retentivity Y1 - 2020 U6 - https://doi.org/10125/64331 VL - 53 SP - 4797 EP - 4805 ER - TY - CHAP A1 - Abramova, Olga T1 - Does a smile open all doors? BT - understanding the impact of appearance disclosure on accommodation sharing platforms T2 - Proceedings of the 53rd Hawaii International Conference on System Sciences N2 - Online photographs govern an individual’s choices across a variety of contexts. In sharing arrangements, facial appearance has been shown to affect the desire to collaborate, interest to explore a listing, and even willingness to pay for a stay. Because of the ubiquity of online images and their influence on social attitudes, it seems crucial to be able to control these aspects. The present study examines the effect of different photographic self-disclosures on the provider’s perceptions and willingness to accept a potential co-sharer. The findings from our experiment in the accommodation-sharing context suggest social attraction mediates the effect of photographic self-disclosures on willingness to host. Implications of the results for IS research and practitioners are discussed. KW - The Sharing Economy KW - airbnb KW - online photographs KW - self-disclosure KW - sharing economy KW - social attraction Y1 - 2020 SN - 978-0-9981331-3-3 SP - 831 EP - 840 PB - HICSS Conference Office University of Hawaii at Manoa CY - Honolulu ER - TY - CHAP A1 - Risch, Lucie A1 - Bashford, Greg A1 - Kulig, Kornelia A1 - Kaplick, Hannes A1 - Mayer, Frank A1 - Cassel, Michael T1 - Spatial frequency analysis identifies altered local Micromorphology in adolescent athletes with Achilles tendinopathy T2 - Medicine and science in sports and exercise : MSSE ; official journal of the American College of Sports Medicine Y1 - 2020 U6 - https://doi.org/10.1249/01.mss.0000670932.99564.57 SN - 0195-9131 SN - 1530-0315 VL - 52 SP - 82 EP - 82 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - CHAP A1 - Botsch, Gideon T1 - Rechtsextremer Antisemitismus in Brandenburg T2 - Mit der Verfassung gegen Antisemitismus : Dokumentation des Fach-Symposiums an der Universität Potsdam Y1 - 2020 UR - https://www.stiftung-toleranz.de/wp-content/uploads/2020/11/Mit-der-Verfassung-gegen-den-AS_Kompendium-final.pdf SP - 14 EP - 19 PB - F. C. Flick Stiftung CY - Potsdam ER - TY - CHAP A1 - Schenke, Maren A1 - Schjeide, Brit-Maren A1 - Püschel, Gerhard A1 - Seeger, Bettina T1 - Human motor neurons diffentiated from plutipotent stem cells as superior traged cells for botulinum neuotoxin potency testing BT - In: German Pharm-Tox Summit 2020: abstracts of the 86th Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) T2 - Naunyn-Schmiedeberg's archives of pharmacology Y1 - 2020 U6 - https://doi.org/10.1007/s00210-020-01828-y SN - 0028-1298 SN - 1432-1912 VL - 393 IS - SUPPL 1 SP - S10 EP - S10 PB - Springer CY - Berlin ; Heidelberg ER -