@article{WilhelmOberauer2006, author = {Wilhelm, Oliver and Oberauer, Klaus}, title = {Why are reasoning ability and working memory capacity related to mental speed? An investigation of stimulus- response compatibility in choice reaction time tasks}, doi = {10.1080/09541440500215921}, year = {2006}, abstract = {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}, language = {en} } @article{OberauerHornigWeidenfeldetal.2005, author = {Oberauer, Klaus and Hornig, R. and Weidenfeld, Andrea and Wilhelm, Oliver}, title = {Effects of directionality in deductive reasoning : II. Premise integration and conclusion evaluation}, issn = {0272-4987}, year = {2005}, abstract = {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}, language = {en} } @article{OberauerSchulzeWilhelmetal.2005, author = {Oberauer, Klaus and Schulze, Ralf and Wilhelm, Oliver and S{\"u}ss, Heinz-Martin}, title = {Working memory and intelligence : their correlation and their relation ; Comment on Ackerman, Beier, and Boyle (2005)}, issn = {0033-2909}, year = {2005}, abstract = {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.}, language = {en} } @article{OberauerSussWilhelmetal.2004, author = {Oberauer, Klaus and Suss, H. M. and Wilhelm, Oliver and Wittman, W. W.}, title = {The multiple faces of working memory : storage, processing, supervision, and coordination}, issn = {0160-2896}, year = {2004}, language = {en} } @article{OberauerSussWilhelmetal.2004, author = {Oberauer, Klaus and Suss, H. M. and Wilhelm, Oliver and Wittman, W. W.}, title = {The multiple faces of working memory : Storage, processing, supervision, and coordination}, issn = {0160-2896}, year = {2004}, language = {en} } @article{OberauerWilhelm2000, author = {Oberauer, Klaus and Wilhelm, Oliver}, title = {Effects of directionality in deductive reasoning : I. The comprehension of single relational premises}, issn = {0278-7393}, year = {2000}, language = {en} } @article{OberauerWilhelmRosas1999, author = {Oberauer, Klaus and Wilhelm, Oliver and Rosas, D. R.}, title = {Bayesian rationality for the selection task? : a test of optimal data selection theory}, year = {1999}, language = {en} } @article{ChungVongpatanasinBonaventuraetal.2014, author = {Chung, Oliver and Vongpatanasin, Wanpen and Bonaventura, Klaus and Lotan, Yair and Sohns, Christian and Haverkamp, Wilhelm and Dorenkamp, Marc}, title = {Potential cost-effectiveness of therapeutic drug monitoring in patients with resistant hypertension}, series = {Journal of hypertension}, volume = {32}, journal = {Journal of hypertension}, number = {12}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0263-6352}, doi = {10.1097/HJH.0000000000000346}, pages = {2411 -- 2421}, year = {2014}, abstract = {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.}, language = {en} } @article{AbeysekaraArcherBenbowetal.2019, author = {Abeysekara, A. U. and Archer, A. and Benbow, Wystan and Bird, Ralph and Brill, A. and Brose, Robert and Buchovecky, M. and Calderon-Madera, D. and Christiansen, J. L. and Cui, W. and Daniel, M. K. and Falcone, A. and Feng, Q. and Fernandez-Alonso, M. and Finley, J. P. and Fortson, Lucy and Furniss, Amy and Gent, A. and Giuri, C. and Gueta, O. and Hanna, David and Hassan, T. and Hervet, Oliver and Holder, J. and Hughes, G. and Humensky, T. B. and Johnson, Caitlin A. and Kaaret, P. and Kertzman, M. and Kieda, David and Krause, Maria and Krennrich, F. and Kumar, S. and Lang, M. J. and Maier, Gernot and Moriarty, P. and Mukherjee, Reshmi and Nievas-Rosillo, M. and Ong, R. A. and Pfrang, Konstantin Johannes and Pohl, Martin and Prado, R. R. and Pueschel, Elisa and Quinn, J. and Ragan, K. and Reynolds, P. T. and Ribeiro, D. and Richards, G. T. and Roache, E. and Rovero, A. C. and Sadeh, Iftach and Santander, M. and Sembroski, G. H. and Shahinyan, Karlen and Sushch, Iurii and Svraka, T. and Weinstein, A. and Wells, R. M. and Wilcox, Patrick and Wilhelm, Alina and Williams, David Arnold and Williamson, T. J. and Zitzer, B.}, title = {Measurement of the Extragalactic Background Light Spectral Energy Distribution with VERITAS}, series = {The astrophysical journal : an international review of spectroscopy and astronomical physics}, volume = {885}, journal = {The astrophysical journal : an international review of spectroscopy and astronomical physics}, number = {2}, publisher = {IOP Publ. Ltd.}, address = {Bristol}, issn = {0004-637X}, doi = {10.3847/1538-4357/ab4817}, pages = {8}, year = {2019}, abstract = {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.}, language = {en} } @book{ZhangPlauthEberhardtetal.2020, author = {Zhang, Shuhao and Plauth, Max and Eberhardt, Felix and Polze, Andreas and Lehmann, Jens and Sejdiu, Gezim and Jabeen, Hajira and Servadei, Lorenzo and M{\"o}stl, Christian and B{\"a}r, Florian and Netzeband, Andr{\´e} and Schmidt, Rainer and Knigge, Marlene and Hecht, Sonja and Prifti, Loina and Krcmar, Helmut and Sapegin, Andrey and Jaeger, David and Cheng, Feng and Meinel, Christoph and Friedrich, Tobias and Rothenberger, Ralf and Sutton, Andrew M. and Sidorova, Julia A. and Lundberg, Lars and Rosander, Oliver and Sk{\"o}ld, Lars and Di Varano, Igor and van der Walt, Est{\´e}e and Eloff, Jan H. P. and Fabian, Benjamin and Baumann, Annika and Ermakova, Tatiana and Kelkel, Stefan and Choudhary, Yash and Cooray, Thilini and Rodr{\´i}guez, Jorge and Medina-P{\´e}rez, Miguel Angel and Trejo, Luis A. and Barrera-Animas, Ari Yair and Monroy-Borja, Ra{\´u}l and L{\´o}pez-Cuevas, Armando and Ram{\´i}rez-M{\´a}rquez, Jos{\´e} Emmanuel and Grohmann, Maria and Niederleithinger, Ernst and Podapati, Sasidhar and Schmidt, Christopher and Huegle, Johannes and de Oliveira, Roberto C. L. and Soares, F{\´a}bio Mendes and van Hoorn, Andr{\´e} and Neumer, Tamas and Willnecker, Felix and Wilhelm, Mathias and Kuster, Bernhard}, title = {HPI Future SOC Lab - Proceedings 2017}, number = {130}, editor = {Meinel, Christoph and Polze, Andreas and Beins, Karsten and Strotmann, Rolf and Seibold, Ulrich and R{\"o}dszus, Kurt and M{\"u}ller, J{\"u}rgen}, publisher = {Universit{\"a}tsverlag Potsdam}, address = {Potsdam}, isbn = {978-3-86956-475-3}, issn = {1613-5652}, doi = {10.25932/publishup-43310}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-433100}, publisher = {Universit{\"a}t Potsdam}, pages = {ix, 235}, year = {2020}, abstract = {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.}, language = {en} } @article{MuellerSchoellGroenlandScherfClaveletal.2020, author = {Mueller-Schoell, Anna and Groenland, Stefanie L. and Scherf-Clavel, Oliver and van Dyk, Madele and Huisinga, Wilhelm and Michelet, Robin and Jaehde, Ulrich and Steeghs, Neeltje and Huitema, Alwin D. R. and Kloft, Charlotte}, title = {Therapeutic drug monitoring of oral targeted antineoplastic drugs}, series = {European journal of clinical pharmacology}, volume = {77}, journal = {European journal of clinical pharmacology}, number = {4}, publisher = {Springer}, address = {Heidelberg}, issn = {0031-6970}, doi = {10.1007/s00228-020-03014-8}, pages = {441 -- 464}, year = {2020}, abstract = {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.}, language = {en} } @article{StachanowNeumannBlankensteinetal.2022, author = {Stachanow, Viktoria and Neumann, Uta and Blankenstein, Oliver and Bindellini, Davide and Melin, Johanna and Ross, Richard and Whitaker, Martin J. J. and Huisinga, Wilhelm and Michelet, Robin and Kloft, Charlotte}, title = {Exploring dried blood spot cortisol concentrations as an alternative for monitoring pediatric adrenal insufficiency patients}, series = {Frontiers in pharmacology}, volume = {13}, journal = {Frontiers in pharmacology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1663-9812}, doi = {10.3389/fphar.2022.819590}, pages = {8}, year = {2022}, abstract = {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.}, language = {en} } @article{MicheletBindelliniMelinetal.2023, author = {Michelet, Robin and Bindellini, Davide and Melin, Johanna and Neumann, Uta and Blankenstein, Oliver and Huisinga, Wilhelm and Johnson, Trevor N. and Whitaker, Martin J. and Ross, Richard and Kloft, Charlotte}, title = {Insights in the maturational processes influencing hydrocortisone pharmacokinetics in congenital adrenal hyperplasia patients using a middle-out approach}, series = {Frontiers in Pharmacology}, volume = {13}, journal = {Frontiers in Pharmacology}, publisher = {Frontiers Media}, address = {Lausanne}, issn = {1663-9812}, doi = {10.3389/fphar.2022.1090554}, pages = {14}, year = {2023}, abstract = {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.}, language = {en} }