In the project I’m currently working on the aim is to understand human experience in close relation to larger planetary systems. More precisely: developing a (sportive) relation with and within a specific bioregion. Not only can this take us closer to localized traditional sports from pre industrial society, more importantly it can give us the possibility to make a shift from anthropocentrism to ecocentrism through sport. A new understanding considering our existence and to ‘planetary health’ is what is desperately needed in the unfolding process of ecological crisis (Gammelsaeter & Loland 2022) (Goldblatt, 2023).
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Development of novel testing strategies to detect adverse human health effects is of interest to replace in vivo-based drug and chemical safety testing. The aim of the present study was to investigate whether physiologically based kinetic (PBK) modeling-facilitated conversion of in vitro toxicity data is an adequate approach to predict in vivo cardiotoxicity in humans. To enable evaluation of predictions made, methadone was selected as the model compound, being a compound for which data on both kinetics and cardiotoxicity in humans are available. A PBK model for methadone in humans was developed and evaluated against available kinetic data presenting an adequate match. Use of the developed PBK model to convert concentration–response curves for the effect of methadone on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) in the so-called multi electrode array (MEA) assay resulted in predictions for in vivo dose–response curves for methadone-induced cardiotoxicity that matched the available in vivo data. The results also revealed differences in protein plasma binding of methadone to be a potential factor underlying variation between individuals with respect to sensitivity towards the cardiotoxic effects of methadone. The present study provides a proof-of-principle of using PBK modeling-based reverse dosimetry of in vitro data for the prediction of cardiotoxicity in humans, providing a novel testing strategy in cardiac safety studies.
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New approach methodologies predicting human cardiotoxicity are of interest to support or even replace in vivo-based drug safety testing. The present study presents an in vitro–in silico approach to predict the effect of inter-individual and inter-ethnic kinetic variations in the cardiotoxicity of R- and S-methadone in the Caucasian and the Chinese population. In vitro cardiotoxicity data, and metabolic data obtained from two approaches, using either individual human liver microsomes or recombinant cytochrome P450 enzymes (rCYPs), were integrated with physiologically based kinetic (PBK) models and Monte Carlo simulations to predict inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. Chemical specific adjustment factors were defined and used to derive dose–response curves for the sensitive individuals. Our simulations indicated that Chinese are more sensitive towards methadone-induced cardiotoxicity with Margin of Safety values being generally two-fold lower than those for Caucasians for both methadone enantiomers. Individual PBK models using microsomes and PBK models using rCYPs combined with Monte Carlo simulations predicted similar inter-individual and inter-ethnic variations in methadone-induced cardiotoxicity. The present study illustrates how inter-individual and inter-ethnic variations in cardiotoxicity can be predicted by combining in vitro toxicity and metabolic data, PBK modelling and Monte Carlo simulations. The novel methodology can be used to enhance cardiac safety evaluations and risk assessment of chemicals.
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For almost fifteen years, the availability and regulatory acceptance of new approach methodologies (NAMs) to assess the absorption, distribution, metabolism and excretion (ADME/biokinetics) in chemical risk evaluations are a bottleneck. To enhance the field, a team of 24 experts from science, industry, and regulatory bodies, including new generation toxicologists, met at the Lorentz Centre in Leiden, The Netherlands. A range of possibilities for the use of NAMs for biokinetics in risk evaluations were formulated (for example to define species differences and human variation or to perform quantitative in vitro-in vivo extrapolations). To increase the regulatory use and acceptance of NAMs for biokinetics for these ADME considerations within risk evaluations, the development of test guidelines (protocols) and of overarching guidance documents is considered a critical step. To this end, a need for an expert group on biokinetics within the Organisation of Economic Cooperation and Development (OECD) to supervise this process was formulated. The workshop discussions revealed that method development is still required, particularly to adequately capture transporter mediated processes as well as to obtain cell models that reflect the physiology and kinetic characteristics of relevant organs. Developments in the fields of stem cells, organoids and organ-on-a-chip models provide promising tools to meet these research needs in the future.
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Locally produced methane, - either as biomethane or power-to-gas product, has to be stored to provide a reliable gas source for the fluctuating demand of any local gas distribution network. Additionally, methane is a prominent transportation fuel but its suitability for vehicular application depends on the ability to store an adequate amount in the onboard fuel tank. Adsorption in porous materials could enable a simple, safe and cost-effective method for storing methane at ambient temperature and at reasonably low pressure. In this project we study and test the main thermodynamic and kinetic characteristics of methane adsorption and desorption on activated carbon. Both calculations and measurements are performed to enhance our knowledge about the general performance and the cyclic behavior of the adsorption and desorption processes.
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There are three volumes in this body of work. In volume one, we lay the foundation for a general theory of organizing. We propose that organizing is a continuous process of ongoing mutual or reciprocal influence between objects (e.g., human actors) in a field, whereby a field is infinite and connects all the objects in it much like electromagnetic fields influence atomic and molecular charged objects or gravity fields influence inanimate objects with mass such as planets and stars. We use field theory to build what we now call the Network Field Model. In this model, human actors are modeled as pointlike objects in the field. Influence between and investments in these point-like human objects are explained as energy exchanges (potential and kinetic) which can be described in terms of three different types of capital: financial (assets), human capital (the individual) and social (two or more humans in a network). This model is predicated on a field theoretical understanding about the world we live in. We use historical and contemporaneous examples of human activity and describe them in terms of the model. In volume two, we demonstrate how to apply the model. In volume 3, we use experimental data to prove the reliability of the model. These three volumes will persistently challenge the reader’s understanding of time, position and what it means to be part of an infinite field. http://dx.doi.org/10.5772/intechopen.99709
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Introduction: Strenuous physical stress induces a range of physiological responses, the extent depending, among others, on the nature and severity of the exercise, a person’s training level and overall physical resilience. This principle can also be used in an experimental set-up by measuring time-dependent changes in biomarkers for physiological processes. In a previous report, we described the effects of workload delivered on a bicycle ergometer on intestinal functionality. As a follow-up, we here describe an analysis of the kinetics of various other biomarkers. Aim: To analyse the time-dependent changes of 34 markers for different metabolic and immunological processes, comparing four different exercise protocols and a rest protocol. Methods: After determining individual maximum workloads, 15 healthy male participants (20–35 years) started with a rest protocol and subsequently performed (in a cross-over design with 1-week wash-out) four exercise protocols of 1-h duration at different intensities: 70% Wmax in a hydrated and a mildly dehydrated state, 50% Wmax and intermittent 85/55% Wmax in blocks of 2 min. Perceived exertion was monitored using the Borg’ Rating of Perceived Exertion scale. Blood samples were collected both before and during exercise, and at various timepoints up to 24 h afterward. Data was analyzed using a multilevel mixed linear model with multiple test correction. Results: Kinetic changes of various biomarkers were exercise-intensity-dependent. Biomarkers included parameters indicative of metabolic activity (e.g., creatinine, bicarbonate), immunological and hematological functionality (e.g., leukocytes, hemoglobin) and intestinal physiology (citrulline, intestinal fatty acid-binding protein, and zonulin). In general, responses to high intensity exercise of 70% Wmax and intermittent exercise i.e., 55/85% Wmax were more pronounced compared to exercise at 50% Wmax. Conclusion: High (70 and 55/85% Wmax) and moderate (50% Wmax) intensity exercise in a bicycle ergometer test produce different time-dependent changes in a broad range of parameters indicative of metabolic activity, immunological and hematological functionality and intestinal physiology. These parameters may be considered biomarkers of homeostatic resilience. Mild dehydration intensifies these time-related changes. Moderate intensity exercise of 50% Wmax shows sufficient physiological and immunological responses and can be employed to test the health condition of less fit individuals.
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An important performance determinant in wheelchair sports is the power exchanged between the athletewheelchair combination and the environment, in short, mechanical power. Inertial measurement units (IMUs) might be used to estimate the exchanged mechanical power during wheelchair sports practice. However, to validly apply IMUs for mechanical power assessment in wheelchair sports, a well-founded and unambiguous theoretical framework is required that follows the dynamics of manual wheelchair propulsion. Therefore, this research has two goals. First, to present a theoretical framework that supports the use of IMUs to estimate power output via power balance equations. Second, to demonstrate the use of the IMU-based power estimates during wheelchair propulsion based on experimental data. Mechanical power during straight-line wheelchair propulsion on a treadmill was estimated using a wheel mounted IMU and was subsequently compared to optical motion capture data serving as a reference. IMU-based power was calculated from rolling resistance (estimated from drag tests) and change in kinetic energy (estimated using wheelchair velocity and wheelchair acceleration). The results reveal no significant difference between reference power values and the proposed IMU-based power (1.8% mean difference, N.S.). As the estimated rolling resistance shows a 0.9–1.7% underestimation, over time, IMU-based power will be slightly underestimated as well. To conclude, the theoretical framework and the resulting IMU model seems to provide acceptable estimates of mechanical power during straight-line wheelchair propulsion in wheelchair (sports) practice, and it is an important first step towards feasible power estimations in all wheelchair sports situations.
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(This is part III of a series of essays on meme theory, all published on this site. Part I is called They Say That We Can’t Meme: Politics of Idea Compression. Part II is entitled Rude Awakening: Memes as Dialectical Images)
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(This is part I of a series of essays on meme theory. Part II is entitled Rude Awakening: Memes as Dialectical Images). Part III is called Memes and the Reactionary Totemism of the Theft of Joy)
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