TY - JOUR A1 - Wilhelm, Oliver A1 - Oberauer, Klaus T1 - Why are reasoning ability and working memory capacity related to mental speed? An investigation of stimulus- response compatibility in choice reaction time tasks N2 - A study with 114 young adults investigated the correlations of intelligence factors and working-memory capacity with reaction time (RT) tasks. Within two sets of four-choice RT tasks, stimulus-response compatibility was varied over three levels: compatible, incompatible, and arbitrary mappings. Two satisfactory measurement models for the RTs could be established: A general factor model without constraints on the loadings and a nested model with two correlated factors, distinguishing compatible from arbitrary mappings, with constraints on the loadings. Structural models additionally including factors for working memory and intelligence showed that the nested model with correlated factors is superior in fit. Working-memory capacity and fluid intelligence were correlated strongly with the nested factor for the RT tasks with arbitrary mappings, and less with the general RT factor. The results support the hypothesis that working memory is needed to maintain arbitrary bindings between stimulus representations and response representations, and this could explain the correlation of working-memory capacity with speed in choice RT tasks Y1 - 2006 U6 - https://doi.org/10.1080/09541440500215921 ER - TY - JOUR A1 - Oberauer, Klaus A1 - Hornig, R. A1 - Weidenfeld, Andrea A1 - Wilhelm, Oliver T1 - Effects of directionality in deductive reasoning : II. Premise integration and conclusion evaluation N2 - Previous research (Oberauer & Wilhelm, 2000) has shown an inherent directionality between the two terms linked in premises of typical deductive reasoning tasks. With three experiments we investigated the effect of inherent directionality on the time to integrate two premises and for the derivation of a conclusion. We varied figure (i.e., order of terms in the premises) and direction of inference (i.e., order of terms in the conclusion) in deduction tasks from various domains (propositional reasoning, syllogisms, spatial, temporal, and linear order reasoning). Effects of figure on premise reading times varied with the directionality of the relations. Effects of direction of inference reflected the same directionality for a subset of relations. We propose that two factors are jointly responsible for a large part of observed directionality effects in premise integration: the inherent directionality of relational statements and a general advantage for a given-new order of terms in the second premise. Difficulty of deriving a conclusion is affected by the directionality or relations if and only if the relation is semantically asymmetric, so that the directionality must be preserved in the integrated mental model Y1 - 2005 SN - 0272-4987 ER - TY - JOUR A1 - Oberauer, Klaus A1 - Schulze, Ralf A1 - Wilhelm, Oliver A1 - Süss, Heinz-Martin T1 - Working memory and intelligence : their correlation and their relation ; Comment on Ackerman, Beier, and Boyle (2005) N2 - On the basis of a mete-analysis of pairwise correlations between working memory tasks and cognitive ability measures, P. L. Ackerman. M. E. Beier, and M. O. Boyle (2005) claimed that working memory capacity (WMC) shares less than 25% of its variance with general intelligence (,;) and with reasoning ability. In this comment, the authors argue that this is an underestimation because of several methodological shortcomings and biases. A reanalysis of the data reported in Ackerman et al. using the correct statistical procedures demonstrates that g and WMC are very highly correlated. On a conceptual level. the authors point out that WMC should be regarded as an explanatory construct for intellectual abilities. Theories of working memory do not claim that WMC is isomorphic with intelligence factors but that it is a very strong predictor of reasoning ability and also predicts general fluid intelligence and g. Y1 - 2005 SN - 0033-2909 ER - TY - JOUR A1 - Oberauer, Klaus A1 - Suss, H. M. A1 - Wilhelm, Oliver A1 - Wittman, W. W. T1 - The multiple faces of working memory : storage, processing, supervision, and coordination Y1 - 2004 SN - 0160-2896 ER - TY - JOUR A1 - Oberauer, Klaus A1 - Suss, H. M. A1 - Wilhelm, Oliver A1 - Wittman, W. W. T1 - The multiple faces of working memory : Storage, processing, supervision, and coordination Y1 - 2004 SN - 0160-2896 ER - TY - JOUR A1 - Oberauer, Klaus A1 - Wilhelm, Oliver T1 - Effects of directionality in deductive reasoning : I. The comprehension of single relational premises Y1 - 2000 SN - 0278-7393 ER - TY - JOUR A1 - Oberauer, Klaus A1 - Wilhelm, Oliver A1 - Rosas, D. R. T1 - Bayesian rationality for the selection task? : a test of optimal data selection theory Y1 - 1999 ER - TY - JOUR A1 - Chung, Oliver A1 - Vongpatanasin, Wanpen A1 - Bonaventura, Klaus A1 - Lotan, Yair A1 - Sohns, Christian A1 - Haverkamp, Wilhelm A1 - Dorenkamp, Marc T1 - Potential cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension JF - Journal of hypertension N2 - Background: Nonadherence to drug therapy poses a significant problem in the treatment of patients with presumed resistant hypertension. It has been shown that therapeutic drug monitoring (TDM) is a useful tool for detecting nonadherence and identifying barriers to treatment adherence, leading to effective blood pressure (BP) control. However, the cost-effectiveness of TDM in the management of resistant hypertension has not been investigated. Results: In the age group of 60-year olds, TDM gained 1.07 QALYs in men and 0.97 QALYs in women at additional costs of (sic)3854 and (sic)3922, respectively. Given a willingness-to-pay threshold of (sic)35 000 per QALY gained, the probability of TDM being cost-effective was 95% or more in all age groups from 30 to 90 years. Results were influenced mostly by the frequency of TDM testing, the rate of nonresponders to TDM, and the magnitude of effect of TDM on BP. Conclusion: Therapeutic drug monitoring presents a potential cost-effective healthcare intervention in patients diagnosed with resistant hypertension. Importantly, this finding is valid for a wide range of patients, independent of sex and age. KW - cardiovascular diseases KW - cost and cost analysis KW - cost-benefit analysis KW - drug monitoring KW - hypertension KW - medication adherence KW - probability KW - risk assessment Y1 - 2014 U6 - https://doi.org/10.1097/HJH.0000000000000346 SN - 0263-6352 SN - 1473-5598 VL - 32 IS - 12 SP - 2411 EP - 2421 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Abeysekara, A. U. A1 - Archer, A. A1 - Benbow, Wystan A1 - Bird, Ralph A1 - Brill, A. A1 - Brose, Robert A1 - Buchovecky, M. A1 - Calderon-Madera, D. A1 - Christiansen, J. L. A1 - Cui, W. A1 - Daniel, M. K. A1 - Falcone, A. A1 - Feng, Q. A1 - Fernandez-Alonso, M. A1 - Finley, J. P. A1 - Fortson, Lucy A1 - Furniss, Amy A1 - Gent, A. A1 - Giuri, C. A1 - Gueta, O. A1 - Hanna, David A1 - Hassan, T. A1 - Hervet, Oliver A1 - Holder, J. A1 - Hughes, G. A1 - Humensky, T. B. A1 - Johnson, Caitlin A. A1 - Kaaret, P. A1 - Kertzman, M. A1 - Kieda, David A1 - Krause, Maria A1 - Krennrich, F. A1 - Kumar, S. A1 - Lang, M. J. A1 - Maier, Gernot A1 - Moriarty, P. A1 - Mukherjee, Reshmi A1 - Nievas-Rosillo, M. A1 - Ong, R. A. A1 - Pfrang, Konstantin Johannes A1 - Pohl, Martin A1 - Prado, R. R. A1 - Pueschel, Elisa A1 - Quinn, J. A1 - Ragan, K. A1 - Reynolds, P. T. A1 - Ribeiro, D. A1 - Richards, G. T. A1 - Roache, E. A1 - Rovero, A. C. A1 - Sadeh, Iftach A1 - Santander, M. A1 - Sembroski, G. H. A1 - Shahinyan, Karlen A1 - Sushch, Iurii A1 - Svraka, T. A1 - Weinstein, A. A1 - Wells, R. M. A1 - Wilcox, Patrick A1 - Wilhelm, Alina A1 - Williams, David Arnold A1 - Williamson, T. J. A1 - Zitzer, B. T1 - Measurement of the Extragalactic Background Light Spectral Energy Distribution with VERITAS JF - The astrophysical journal : an international review of spectroscopy and astronomical physics N2 - The extragalactic background light (EBL), a diffuse photon field in the optical and infrared range, is a record of radiative processes over the universe?s history. Spectral measurements of blazars at very high energies (>100 GeV) enable the reconstruction of the spectral energy distribution (SED) of the EBL, as the blazar spectra are modified by redshift- and energy-dependent interactions of the gamma-ray photons with the EBL. The spectra of 14 VERITAS-detected blazars are included in a new measurement of the EBL SED that is independent of EBL SED models. The resulting SED covers an EBL wavelength range of 0.56?56 ?m, and is in good agreement with lower limits obtained by assuming that the EBL is entirely due to radiation from cataloged galaxies. KW - Extragalactic astronomy KW - Active galactic nuclei KW - Diffuse radiation KW - Cosmology Y1 - 2019 U6 - https://doi.org/10.3847/1538-4357/ab4817 SN - 0004-637X SN - 1538-4357 VL - 885 IS - 2 PB - IOP Publ. Ltd. CY - Bristol ER - TY - BOOK A1 - Zhang, Shuhao A1 - Plauth, Max A1 - Eberhardt, Felix A1 - Polze, Andreas A1 - Lehmann, Jens A1 - Sejdiu, Gezim A1 - Jabeen, Hajira A1 - Servadei, Lorenzo A1 - Möstl, Christian A1 - Bär, Florian A1 - Netzeband, André A1 - Schmidt, Rainer A1 - Knigge, Marlene A1 - Hecht, Sonja A1 - Prifti, Loina A1 - Krcmar, Helmut A1 - Sapegin, Andrey A1 - Jaeger, David A1 - Cheng, Feng A1 - Meinel, Christoph A1 - Friedrich, Tobias A1 - Rothenberger, Ralf A1 - Sutton, Andrew M. A1 - Sidorova, Julia A. A1 - Lundberg, Lars A1 - Rosander, Oliver A1 - Sköld, Lars A1 - Di Varano, Igor A1 - van der Walt, Estée A1 - Eloff, Jan H. P. A1 - Fabian, Benjamin A1 - Baumann, Annika A1 - Ermakova, Tatiana A1 - Kelkel, Stefan A1 - Choudhary, Yash A1 - Cooray, Thilini A1 - Rodríguez, Jorge A1 - Medina-Pérez, Miguel Angel A1 - Trejo, Luis A. A1 - Barrera-Animas, Ari Yair A1 - Monroy-Borja, Raúl A1 - López-Cuevas, Armando A1 - Ramírez-Márquez, José Emmanuel A1 - Grohmann, Maria A1 - Niederleithinger, Ernst A1 - Podapati, Sasidhar A1 - Schmidt, Christopher A1 - Huegle, Johannes A1 - de Oliveira, Roberto C. L. A1 - Soares, Fábio Mendes A1 - van Hoorn, André A1 - Neumer, Tamas A1 - Willnecker, Felix A1 - Wilhelm, Mathias A1 - Kuster, Bernhard ED - Meinel, Christoph ED - Polze, Andreas ED - Beins, Karsten ED - Strotmann, Rolf ED - Seibold, Ulrich ED - Rödszus, Kurt ED - Müller, Jürgen T1 - HPI Future SOC Lab – Proceedings 2017 T1 - HPI Future SOC Lab – Proceedings 2017 N2 - The “HPI Future SOC Lab” is a cooperation of the Hasso Plattner Institute (HPI) and industry partners. Its mission is to enable and promote exchange and interaction between the research community and the industry partners. The HPI Future SOC Lab provides researchers with free of charge access to a complete infrastructure of state of the art hard and software. This infrastructure includes components, which might be too expensive for an ordinary research environment, such as servers with up to 64 cores and 2 TB main memory. The offerings address researchers particularly from but not limited to the areas of computer science and business information systems. Main areas of research include cloud computing, parallelization, and In-Memory technologies. This technical report presents results of research projects executed in 2017. Selected projects have presented their results on April 25th and November 15th 2017 at the Future SOC Lab Day events. N2 - Das Future SOC Lab am HPI ist eine Kooperation des Hasso-Plattner-Instituts mit verschiedenen Industriepartnern. Seine Aufgabe ist die Ermöglichung und Förderung des Austausches zwischen Forschungsgemeinschaft und Industrie. Am Lab wird interessierten Wissenschaftlern eine Infrastruktur von neuester Hard- und Software kostenfrei für Forschungszwecke zur Verfügung gestellt. Dazu zählen teilweise noch nicht am Markt verfügbare Technologien, die im normalen Hochschulbereich in der Regel nicht zu finanzieren wären, bspw. Server mit bis zu 64 Cores und 2 TB Hauptspeicher. Diese Angebote richten sich insbesondere an Wissenschaftler in den Gebieten Informatik und Wirtschaftsinformatik. Einige der Schwerpunkte sind Cloud Computing, Parallelisierung und In-Memory Technologien. In diesem Technischen Bericht werden die Ergebnisse der Forschungsprojekte des Jahres 2017 vorgestellt. Ausgewählte Projekte stellten ihre Ergebnisse am 25. April und 15. November 2017 im Rahmen der Future SOC Lab Tag Veranstaltungen vor. T3 - Technische Berichte des Hasso-Plattner-Instituts für Digital Engineering an der Universität Potsdam - 130 KW - Future SOC Lab KW - research projects KW - multicore architectures KW - In-Memory technology KW - cloud computing KW - machine learning KW - artifical intelligence KW - Future SOC Lab KW - Forschungsprojekte KW - Multicore Architekturen KW - In-Memory Technologie KW - Cloud Computing KW - maschinelles Lernen KW - Künstliche Intelligenz Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-433100 SN - 978-3-86956-475-3 SN - 1613-5652 SN - 2191-1665 IS - 130 PB - Universitätsverlag Potsdam CY - Potsdam ER - TY - JOUR A1 - Mueller-Schoell, Anna A1 - Groenland, Stefanie L. A1 - Scherf-Clavel, Oliver A1 - van Dyk, Madele A1 - Huisinga, Wilhelm A1 - Michelet, Robin A1 - Jaehde, Ulrich A1 - Steeghs, Neeltje A1 - Huitema, Alwin D. R. A1 - Kloft, Charlotte T1 - Therapeutic drug monitoring of oral targeted antineoplastic drugs JF - European journal of clinical pharmacology N2 - Purpose This review provides an overview of the current challenges in oral targeted antineoplastic drug (OAD) dosing and outlines the unexploited value of therapeutic drug monitoring (TDM). Factors influencing the pharmacokinetic exposure in OAD therapy are depicted together with an overview of different TDM approaches. Finally, current evidence for TDM for all approved OADs is reviewed. Methods A comprehensive literature search (covering literature published until April 2020), including primary and secondary scientific literature on pharmacokinetics and dose individualisation strategies for OADs, together with US FDA Clinical Pharmacology and Biopharmaceutics Reviews and the Committee for Medicinal Products for Human Use European Public Assessment Reports was conducted. Results OADs are highly potent drugs, which have substantially changed treatment options for cancer patients. Nevertheless, high pharmacokinetic variability and low treatment adherence are risk factors for treatment failure. TDM is a powerful tool to individualise drug dosing, ensure drug concentrations within the therapeutic window and increase treatment success rates. After reviewing the literature for 71 approved OADs, we show that exposure-response and/or exposure-toxicity relationships have been established for the majority. Moreover, TDM has been proven to be feasible for individualised dosing of abiraterone, everolimus, imatinib, pazopanib, sunitinib and tamoxifen in prospective studies. There is a lack of experience in how to best implement TDM as part of clinical routine in OAD cancer therapy. Conclusion Sub-therapeutic concentrations and severe adverse events are current challenges in OAD treatment, which can both be addressed by the application of TDM-guided dosing, ensuring concentrations within the therapeutic window. KW - targeted antineoplastic drugs KW - tyrosine kinase inhibitors KW - therapeutic KW - drug monitoring KW - oral anticancer drugs KW - personalised medicine Y1 - 2020 U6 - https://doi.org/10.1007/s00228-020-03014-8 SN - 0031-6970 SN - 1432-1041 VL - 77 IS - 4 SP - 441 EP - 464 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Stachanow, Viktoria A1 - Neumann, Uta A1 - Blankenstein, Oliver A1 - Bindellini, Davide A1 - Melin, Johanna A1 - Ross, Richard A1 - Whitaker, Martin J. J. A1 - Huisinga, Wilhelm A1 - Michelet, Robin A1 - Kloft, Charlotte T1 - Exploring dried blood spot cortisol concentrations as an alternative for monitoring pediatric adrenal insufficiency patients BT - a model-based analysis JF - Frontiers in pharmacology N2 - Congenital adrenal hyperplasia (CAH) is the most common form of adrenal insufficiency in childhood; it requires cortisol replacement therapy with hydrocortisone (HC, synthetic cortisol) from birth and therapy monitoring for successful treatment. In children, the less invasive dried blood spot (DBS) sampling with whole blood including red blood cells (RBCs) provides an advantageous alternative to plasma sampling. Potential differences in binding/association processes between plasma and DBS however need to be considered to correctly interpret DBS measurements for therapy monitoring. While capillary DBS samples would be used in clinical practice, venous cortisol DBS samples from children with adrenal insufficiency were analyzed due to data availability and to directly compare and thus understand potential differences between venous DBS and plasma. A previously published HC plasma pharmacokinetic (PK) model was extended by leveraging these DBS concentrations. In addition to previously characterized binding of cortisol to albumin (linear process) and corticosteroid-binding globulin (CBG; saturable process), DBS data enabled the characterization of a linear cortisol association with RBCs, and thereby providing a quantitative link between DBS and plasma cortisol concentrations. The ratio between the observed cortisol plasma and DBS concentrations varies highly from 2 to 8. Deterministic simulations of the different cortisol binding/association fractions demonstrated that with higher blood cortisol concentrations, saturation of cortisol binding to CBG was observed, leading to an increase in all other cortisol binding fractions. In conclusion, a mathematical PK model was developed which links DBS measurements to plasma exposure and thus allows for quantitative interpretation of measurements of DBS samples. KW - adrenal insufficiency KW - cortisol KW - dried blood spots KW - pediatrics KW - pharmacokinetics KW - binding KW - association KW - red blood cells Y1 - 2022 U6 - https://doi.org/10.3389/fphar.2022.819590 SN - 1663-9812 VL - 13 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Michelet, Robin A1 - Bindellini, Davide A1 - Melin, Johanna A1 - Neumann, Uta A1 - Blankenstein, Oliver A1 - Huisinga, Wilhelm A1 - Johnson, Trevor N. A1 - Whitaker, Martin J. A1 - Ross, Richard A1 - Kloft, Charlotte T1 - Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach JF - Frontiers in Pharmacology N2 - Introduction: Hydrocortisone is the standard of care in cortisol replacement therapy for congenital adrenal hyperplasia patients. Challenges in mimicking cortisol circadian rhythm and dosing individualization can be overcome by the support of mathematical modelling. Previously, a non-linear mixed-effects (NLME) model was developed based on clinical hydrocortisone pharmacokinetic (PK) pediatric and adult data. Additionally, a physiologically-based pharmacokinetic (PBPK) model was developed for adults and a pediatric model was obtained using maturation functions for relevant processes. In this work, a middle-out approach was applied. The aim was to investigate whether PBPK-derived maturation functions could provide a better description of hydrocortisone PK inter-individual variability when implemented in the NLME framework, with the goal of providing better individual predictions towards precision dosing at the patient level. Methods: Hydrocortisone PK data from 24 adrenal insufficiency pediatric patients and 30 adult healthy volunteers were used for NLME model development, while the PBPK model and maturation functions of clearance and cortisol binding globulin (CBG) were developed based on previous studies published in the literature. Results: Clearance (CL) estimates from both approaches were similar for children older than 1 year (CL/F increasing from around 150 L/h to 500 L/h), while CBG concentrations differed across the whole age range (CBG(NLME) stable around 0.5 mu M vs. steady increase from 0.35 to 0.8 mu M for CBG (PBPK)). PBPK-derived maturation functions were subsequently included in the NLME model. After inclusion of the maturation functions, none, a part of, or all parameters were re-estimated. However, the inclusion of CL and/or CBG maturation functions in the NLME model did not result in improved model performance for the CL maturation function (& UDelta;OFV > -15.36) and the re-estimation of parameters using the CBG maturation function most often led to unstable models or individual CL prediction bias. Discussion: Three explanations for the observed discrepancies could be postulated, i) non-considered maturation of processes such as absorption or first-pass effect, ii) lack of patients between 1 and 12 months, iii) lack of correction of PBPK CL maturation functions derived from urinary concentration ratio data for the renal function relative to adults. These should be investigated in the future to determine how NLME and PBPK methods can work towards deriving insights into pediatric hydrocortisone PK. KW - hydrocortisone KW - congenital adrenal hyperplasia KW - population pharmacokinetics KW - middle-out approach KW - pediatrics KW - physiologically-based pharmacokinetics (PBPK) KW - non-linear mixed effects modelling (NLME); KW - maturation Y1 - 2023 U6 - https://doi.org/10.3389/fphar.2022.1090554 SN - 1663-9812 VL - 13 PB - Frontiers Media CY - Lausanne ER -