TY - JOUR A1 - Kühne, Katharina A1 - Nenaschew, Kristina A1 - Miklashevsky, Alex T1 - Space-valence mapping of social concepts BT - Do we arrange negative and positive ethnic stereotypes from left to right? JF - Frontiers in Psychology N2 - Introduction: The body-specificity hypothesis states that in right-handers, positive concepts should be associated with the right side and negative concepts with the left side of the body. Following this hypothesis, our study postulated that negative out-group ethnic stereotypes would be associated with the left side, and positive in-group stereotypes would be associated with the right side. Methods: The experiment consisted of two parts. First, we measured the spatial mapping of ethnic stereotypes by using a sensibility judgment task, in which participants had to decide whether a sentence was sensible or not by pressing either a left or a right key. The sentences included German vs. Arabic proper names. Second, we measured implicit ethnic stereotypes in the same participants using the Go/No-go Association Task (GNAT), in which Arabic vs. German proper names were presented in combination with positive vs. negative adjectives. Right-handed German native speakers (N = 92) participated in an online study. Results: As predicted, in the GNAT, participants reacted faster to German names combined with positive adjectives and to Arabic names combined with negative adjectives, which is diagnostic of existing valenced in-and outgroup ethnic stereotypes. However, we failed to find any reliable effects in the sensibility judgment task, i.e., there was no evidence of spatial mapping of positive and negative ethnic stereotypes. There was no correlation between the results of the two tasks at the individual level. Further Bayesian analysis and exploratory analysis in the left-handed subsample (N = 9) corroborated the evidence in favor of null results. Discussion: Our study suggests that ethnic stereotypes are not automatically mapped in a body-specific manner. KW - body-specificity hypothesis KW - embodied cognition KW - ethnic stereotypes KW - in-group stereotypes KW - implicit associations KW - GNAT KW - out-group stereotypes Y1 - 2022 U6 - https://doi.org/10.3389/fpsyg.2022.1070177 SN - 1664-1078 VL - 13 PB - Frontiers CY - Lausanne, Schweiz ER - TY - JOUR A1 - Schaefer, Laura A1 - Dech, Silas A1 - Bittmann, Frank T1 - Adaptive force and emotionally related imaginations BT - Preliminary results suggest a reduction of the maximal holding capacity as reaction to disgusting food imagination JF - Heliyon N2 - The link between emotions and motor control has been discussed for years. The measurement of the Adaptive Force (AF) provides the possibility to get insights into the adaptive control of the neuromuscular system in reaction to external forces. It was hypothesized that the holding isometric AF is especially vulnerable to disturbing inputs. Here, the behavior of the AF under the influence of positive (tasty) vs. negative (disgusting) food imaginations was investigated. The AF was examined in n = 12 cases using an objectified manual muscle test of the hip flexors, elbow flexors or pectoralis major muscle, performed by one of two experienced testers while the participants imagined their most tasty or most disgusting food. The reaction force and the limb position were measured by a handheld device. While the slope of force rises and the maximal AF did not differ significantly between tasty and disgusting imaginations (p > 0.05), the maximal isometric AF was significantly lower and the AF at the onset of oscillations was significantly higher under disgusting vs. tasty imaginations (both p = 0.001). A proper length tension control of muscles seems to be a crucial functional parameter of the neuromuscular system which can be impaired instantaneously by emotionally related negative imaginations. This might be a potential approach to evaluate somatic reactions to emotions. KW - Adaptive Force KW - Isometric Adaptive Force KW - Holding capacity KW - Holding KW - isometric muscle action KW - Imaginations KW - Emotions KW - Motor control KW - Functional weakness KW - Manual muscle test Y1 - 2021 U6 - https://doi.org/10.1016/j.heliyon.2021.e07827 SN - 2405-8440 VL - 7 IS - 8 PB - Elsevier CY - London ER - TY - JOUR A1 - Kühne, Katharina A1 - Fischer, Martin H. A1 - Jeglinski-Mende, Melinda A. T1 - During the COVID-19 pandemic participants prefer settings with a face mask, no interaction and at a closer distance JF - Scientific Reports N2 - Peripersonal space is the space surrounding our body, where multisensory integration of stimuli and action execution take place. The size of peripersonal space is flexible and subject to change by various personal and situational factors. The dynamic representation of our peripersonal space modulates our spatial behaviors towards other individuals. During the COVID-19 pandemic, this spatial behavior was modified by two further factors: social distancing and wearing a face mask. Evidence from offline and online studies on the impact of a face mask on pro-social behavior is mixed. In an attempt to clarify the role of face masks as pro-social or anti-social signals, 235 observers participated in the present online study. They watched pictures of two models standing at three different distances from each other (50, 90 and 150 cm), who were either wearing a face mask or not and were either interacting by initiating a hand shake or just standing still. The observers’ task was to classify the model by gender. Our results show that observers react fastest, and therefore show least avoidance, for the shortest distances (50 and 90 cm) but only when models wear a face mask and do not interact. Thus, our results document both pro- and anti-social consequences of face masks as a result of the complex interplay between social distancing and interactive behavior. Practical implications of these findings are discussed. Y1 - 2022 U6 - https://doi.org/10.1038/s41598-022-16730-1 SN - 2045-2322 VL - 12 SP - 1 EP - 12 PB - Springer Nature CY - Berlin ER - TY - JOUR A1 - Schaefer, Laura A1 - Bittmann, Frank T1 - The adaptive force as a potential biomechanical parameter in the recovery process of patients with long COVID JF - Diagnostics N2 - Long COVID patients show symptoms, such as fatigue, muscle weakness and pain. Adequate diagnostics are still lacking. Investigating muscle function might be a beneficial approach. The holding capacity (maximal isometric Adaptive Force; AFisomax) was previously suggested to be especially sensitive for impairments. This longitudinal, non-clinical study aimed to investigate the AF in long COVID patients and their recovery process. AF parameters of elbow and hip flexors were assessed in 17 patients at three time points (pre: long COVID state, post: immediately after first treatment, end: recovery) by an objectified manual muscle test. The tester applied an increasing force on the limb of the patient, who had to resist isometrically for as long as possible. The intensity of 13 common symptoms were queried. At pre, patients started to lengthen their muscles at ~50% of the maximal AF (AFmax), which was then reached during eccentric motion, indicating unstable adaptation. At post and end, AFisomax increased significantly to ~99% and 100% of AFmax, respectively, reflecting stable adaptation. AFmax was statistically similar for all three time points. Symptom intensity decreased significantly from pre to end. The findings revealed a substantially impaired maximal holding capacity in long COVID patients, which returned to normal function with substantial health improvement. AFisomax might be a suitable sensitive functional parameter to assess long COVID patients and to support therapy process KW - Adaptive Force KW - maximal isometric Adaptive Force KW - holding capacity KW - muscle function KW - long COVID fatigue KW - post COVID syndrome KW - muscle weakness KW - neuromuscular control KW - biomechanical parameter Y1 - 2023 U6 - https://doi.org/10.3390/diagnostics13050882 SN - 2075-4418 VL - 13 IS - 5 PB - MDPI CY - Basel ER - TY - JOUR A1 - Bosch, Sina A1 - De Cesare, Ilaria A1 - Demske, Ulrike A1 - Felser, Claudia T1 - New empirical approaches to grammatical variation and change JF - Languages : open access journal Y1 - 2021 U6 - https://doi.org/10.3390/languages6030113 SN - 2226-471X VL - 6 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Maier, Corinna Sabrina A1 - Wiljes, Jana de A1 - Hartung, Niklas A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - A continued learning approach for model-informed precision dosing BT - Updating models in clinical practice JF - CPT: pharmacometrics & systems pharmacology N2 - Model-informed precision dosing (MIPD) is a quantitative dosing framework that combines prior knowledge on the drug-disease-patient system with patient data from therapeutic drug/ biomarker monitoring (TDM) to support individualized dosing in ongoing treatment. Structural models and prior parameter distributions used in MIPD approaches typically build on prior clinical trials that involve only a limited number of patients selected according to some exclusion/inclusion criteria. Compared to the prior clinical trial population, the patient population in clinical practice can be expected to also include altered behavior and/or increased interindividual variability, the extent of which, however, is typically unknown. Here, we address the question of how to adapt and refine models on the level of the model parameters to better reflect this real-world diversity. We propose an approach for continued learning across patients during MIPD using a sequential hierarchical Bayesian framework. The approach builds on two stages to separate the update of the individual patient parameters from updating the population parameters. Consequently, it enables continued learning across hospitals or study centers, because only summary patient data (on the level of model parameters) need to be shared, but no individual TDM data. We illustrate this continued learning approach with neutrophil-guided dosing of paclitaxel. The present study constitutes an important step toward building confidence in MIPD and eventually establishing MIPD increasingly in everyday therapeutic use. Y1 - 2021 U6 - https://doi.org/10.1002/psp4.12745 SN - 2163-8306 VL - 11 IS - 2 SP - 185 EP - 198 PB - London CY - Nature Publ. Group ER - TY - JOUR A1 - Hartung, Niklas A1 - Wahl, Martin A1 - Rastogi, Abhishake A1 - Huisinga, Wilhelm T1 - Nonparametric goodness-of-fit testing for parametric covariate models in pharmacometric analyses JF - CPT: pharmacometrics & systems pharmacology N2 - The characterization of covariate effects on model parameters is a crucial step during pharmacokinetic/pharmacodynamic analyses. Although covariate selection criteria have been studied extensively, the choice of the functional relationship between covariates and parameters, however, has received much less attention. Often, a simple particular class of covariate-to-parameter relationships (linear, exponential, etc.) is chosen ad hoc or based on domain knowledge, and a statistical evaluation is limited to the comparison of a small number of such classes. Goodness-of-fit testing against a nonparametric alternative provides a more rigorous approach to covariate model evaluation, but no such test has been proposed so far. In this manuscript, we derive and evaluate nonparametric goodness-of-fit tests for parametric covariate models, the null hypothesis, against a kernelized Tikhonov regularized alternative, transferring concepts from statistical learning to the pharmacological setting. The approach is evaluated in a simulation study on the estimation of the age-dependent maturation effect on the clearance of a monoclonal antibody. Scenarios of varying data sparsity and residual error are considered. The goodness-of-fit test correctly identified misspecified parametric models with high power for relevant scenarios. The case study provides proof-of-concept of the feasibility of the proposed approach, which is envisioned to be beneficial for applications that lack well-founded covariate models. Y1 - 2021 U6 - https://doi.org/10.1002/psp4.12614 SN - 2163-8306 VL - 10 IS - 6 SP - 564 EP - 576 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Démaris, Alix A1 - Widigson, Ella S. K. A1 - Ilvemark, Johan F. K. F. A1 - Steenholdt, Casper A1 - Seidelin, Jakob B. A1 - Huisinga, Wilhelm A1 - Michelet, Robin A1 - Aulin, Linda B. S. A1 - Kloft, Charlotte T1 - Ulcerative colitis and acute severe ulcerative colitis patients are overlooked in infliximab population pharmacokinetic models BT - results from a comprehensive review JF - Pharmaceutics / Molecular Diversity Preservation International N2 - Ulcerative colitis (UC) is part of the inflammatory bowels diseases, and moderate to severe UC patients can be treated with anti-tumour necrosis alpha monoclonal antibodies, including infliximab (IFX). Even though treatment of UC patients by IFX has been in place for over a decade, many gaps in modelling of IFX PK in this population remain. This is even more true for acute severe UC (ASUC) patients for which early prediction of IFX pharmacokinetic (PK) could highly improve treatment outcome. Thus, this review aims to compile and analyse published population PK models of IFX in UC and ASUC patients, and to assess the current knowledge on disease activity impact on IFX PK. For this, a semi-systematic literature search was conducted, from which 26 publications including a population PK model analysis of UC patients receiving IFX therapy were selected. Amongst those, only four developed a model specifically for UC patients, and only three populations included severe UC patients. Investigations of disease activity impact on PK were reported in only 4 of the 14 models selected. In addition, the lack of reported model codes and assessment of predictive performance make the use of published models in a clinical setting challenging. Thus, more comprehensive investigation of PK in UC and ASUC is needed as well as more adequate reports on developed models and their evaluation in order to apply them in a clinical setting. KW - infliximab KW - inflammatory bowel disease KW - ulcerative colitis KW - acute severe KW - disease activity KW - pharmacokinetic KW - pharmacometrics Y1 - 2022 U6 - https://doi.org/10.3390/pharmaceutics14102095 SN - 1999-4923 VL - 14 IS - 10 PB - MDPI CY - Basel ER - TY - JOUR A1 - Moldenhawer, Ted A1 - Moreno, Eduardo A1 - Schindler, Daniel A1 - Flemming, Sven A1 - Holschneider, Matthias A1 - Huisinga, Wilhelm A1 - Alonso, Sergio A1 - Beta, Carsten T1 - Spontaneous transitions between amoeboid and keratocyte-like modes of migration JF - Frontiers in Cell and Developmental Biology N2 - The motility of adherent eukaryotic cells is driven by the dynamics of the actin cytoskeleton. Despite the common force-generating actin machinery, different cell types often show diverse modes of locomotion that differ in their shape dynamics, speed, and persistence of motion. Recently, experiments in Dictyostelium discoideum have revealed that different motility modes can be induced in this model organism, depending on genetic modifications, developmental conditions, and synthetic changes of intracellular signaling. Here, we report experimental evidence that in a mutated D. discoideum cell line with increased Ras activity, switches between two distinct migratory modes, the amoeboid and fan-shaped type of locomotion, can even spontaneously occur within the same cell. We observed and characterized repeated and reversible switchings between the two modes of locomotion, suggesting that they are distinct behavioral traits that coexist within the same cell. We adapted an established phenomenological motility model that combines a reaction-diffusion system for the intracellular dynamics with a dynamic phase field to account for our experimental findings. KW - cell migration KW - amoeboid motility KW - keratocytle-like motility KW - modes of KW - migration KW - D. discoideum KW - actin dynamics Y1 - 2022 U6 - https://doi.org/10.3389/fcell.2022.898351 SN - 2296-634X VL - 10 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Hafner, Verena A1 - Hommel, Bernhard A1 - Kayhan, Ezgi A1 - Lee, Dongheui A1 - Paulus, Markus A1 - Verschoor, Stephan T1 - Editorial: The mechanisms underlying the human minimal self JF - Frontiers in psychology KW - agents KW - self KW - minimal self KW - robotics KW - humanoids KW - cognition Y1 - 2022 U6 - https://doi.org/10.3389/fpsyg.2022.961480 SN - 1664-1078 VL - 13 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Havermann, Felix A1 - Ghirardo, Andrea A1 - Schnitzler, Jörg-Peter A1 - Nendel, Claas A1 - Hoffmann, Mathias A1 - Kraus, David A1 - Grote, Rüdiger T1 - Modeling intra- and interannual variability of BVOC emissions from maize, oil-seed rape, and ryegrass JF - Journal of advances in modeling earth systems N2 - Air chemistry is affected by the emission of biogenic volatile organic compounds (BVOCs), which originate from almost all plants in varying qualities and quantities. They also vary widely among different crops, an aspect that has been largely neglected in emission inventories. In particular, bioenergy-related species can emit mixtures of highly reactive compounds that have received little attention so far. For such species, long-term field observations of BVOC exchange from relevant crops covering different phenological phases are scarcely available. Therefore, we measured and modeled the emission of three prominent European bioenergy crops (maize, ryegrass, and oil-seed rape) for full rotations in north-eastern Germany. Using a proton transfer reaction-mass spectrometer combined with automatically moving large canopy chambers, we were able to quantify the characteristic seasonal BVOC flux dynamics of each crop species. The measured BVOC fluxes were used to parameterize and evaluate the BVOC emission module (JJv) of the physiology-oriented LandscapeDNDC model, which was enhanced to cover de novo emissions as well as those from plant storage pools. Parameters are defined for each compound individually. The model is used for simulating total compound-specific reactivity over several years and also to evaluate the importance of these emissions for air chemistry. We can demonstrate substantial differences between the investigated crops with oil-seed rape having 37-fold higher total annual emissions than maize. However, due to a higher chemical reactivity of the emitted blend in maize, potential impacts on atmospheric OH-chemistry are only 6-fold higher. KW - biogenic volatile organic compounds KW - process-based modeling KW - Zea mays KW - Brassica napus KW - Lolium multiflorum KW - plant ontogenetic stage Y1 - 2022 U6 - https://doi.org/10.1029/2021MS002683 SN - 1942-2466 VL - 14 IS - 3 PB - American Geophysical Union CY - Washington ER - TY - JOUR A1 - Wicha, Sebastian G. A1 - Huisinga, Wilhelm A1 - Kloft, Charlotte T1 - Translational pharmacometric evaluation of typical antibiotic broad-spectrum combination therapies against staphylococcus aureus exploiting in vitro information JF - CPT: pharmacometrics & systems pharmacology N2 - Broad-spectrum antibiotic combination therapy is frequently applied due to increasing resistance development of infective pathogens. The objective of the present study was to evaluate two common empiric broad-spectrum combination therapies consisting of either linezolid (LZD) or vancomycin (VAN) combined with meropenem (MER) against Staphylococcus aureus (S. aureus) as the most frequent causative pathogen of severe infections. A semimechanistic pharmacokinetic-pharmacodynamic (PK-PD) model mimicking a simplified bacterial life-cycle of S. aureus was developed upon time-kill curve data to describe the effects of LZD, VAN, and MER alone and in dual combinations. The PK-PD model was successfully (i) evaluated with external data from two clinical S. aureus isolates and further drug combinations and (ii) challenged to predict common clinical PK-PD indices and breakpoints. Finally, clinical trial simulations were performed that revealed that the combination of VAN-MER might be favorable over LZD-MER due to an unfavorable antagonistic interaction between LZD and MER. Y1 - 2017 U6 - https://doi.org/10.1002/psp4.12197 SN - 2163-8306 VL - 6 SP - 512 EP - 522 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Hülscher, Julian A1 - Sobel, Edward A1 - Kallnik, Niklas A1 - Hoffmann, J. Elis A1 - Millar, Ian L. A1 - Hartmann, Kai A1 - Bernhardt, Anne T1 - Apatites record sedimentary provenance change 4-5 myrs before clay in the Oligocene/Miocene Alpine molasse JF - Frontiers in Earth Science N2 - Extracting information about past tectonic or climatic environmental changes from sedimentary records is a key objective of provenance research. Interpreting the imprint of such changes remains challenging as signals might be altered in the sediment-routing system. We investigate the sedimentary provenance of the Oligocene/Miocene Upper Austrian Northern Alpine Foreland Basin and its response to the tectonically driven exhumation of the Tauern Window metamorphic dome (28 +/- 1 Ma) in the Eastern European Alps by using the unprecedented combination of Nd isotopic composition of bulk-rock clay-sized samples and partly previously published multi-proxy (Nd isotopic composition, trace-element geochemistry, U-Pb dating) sand-sized apatite single-grain analysis. The basin offers an excellent opportunity to investigate environmental signal propagation into the sedimentary record because comprehensive stratigraphic and seismic datasets can be combined with present research results. The bulk-rock clay-sized fraction epsilon Nd values of well-cutting samples from one well on the northern basin slope remained stable at similar to-9.7 from 27 to 19 Ma but increased after 19 Ma to similar to-9.1. In contrast, apatite single-grain distributions, which were extracted from 22 drill-core samples, changed significantly around 23.3 Ma from apatites dominantly from low-grade (