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- Dahl, Svein G., et al.
(författare)
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Incorporating Physiological and Biochemical Mechanisms into Pharmacokinetic-Pharmacodynamic Models : A Conceptual Framework
- 2010
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 106:1, s. 2-12
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Forskningsöversikt (refereegranskat)abstract
- The aim of this conceptual framework paper is to contribute to the further development of the modelling of effects of drugs or toxic agents by an approach which is based on the underlying physiology and pathology of the biological processes. In general, modelling of data has the purpose (1) to describe experimental data, (2a) to reduce the amount of data resulting from an experiment, e.g. a clinical trial and (2b) to obtain the most relevant parameters, (3) to test hypotheses and (4) to make predictions within the boundaries of experimental conditions, e.g. range of doses tested (interpolation) and out of the boundaries of the experimental conditions, e.g. to extrapolate from animal data to the situation in man. Describing the drug/xenobiotic-target interaction and the chain of biological events following the interaction is the first step to build a biologically based model. This is an approach to represent the underlying biological mechanisms in qualitative and also quantitative terms thus being inherently connected in many aspects to systems biology. As the systems biology models may contain variables in the order of hundreds connected with differential equations, it is obvious that it is in most cases not possible to assign values to the variables resulting from experimental data. Reduction techniques may be used to create a manageable model which, however, captures the biologically meaningful events in qualitative and quantitative terms. Until now, some success has been obtained by applying empirical pharmacokinetic/pharmacodynamic models which describe direct and indirect relationships between the xenobiotic molecule and the effect, including tolerance. Some of the models may have physiological components built in the structure of the model and use parameter estimates from published data. In recent years, some progress toward semi-mechanistic models has been made, examples being chemotherapy-induced myelosuppression and glucose-endogenous insulin-antidiabetic drug interactions. We see a way forward by employing approaches to bridge the gap between systems biology and physiologically based kinetic and dynamic models. To be useful for decision making, the 'bridging' model should have a well founded mechanistic basis, but being reduced to the extent that its parameters can be deduced from experimental data, however capturing the biological/clinical essential details so that meaningful predictions and extrapolations can be made.
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| 2. |
- Krause-Jensen, D, et al.
(författare)
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Nordic Blue Carbon Ecosystems: Status and Outlook
- 2022
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Ingår i: Frontiers in Marine Science. - : Frontiers Media SA. - 2296-7745. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Vegetated coastal and marine habitats in the Nordic region include salt marshes, eelgrass meadows and, in particular, brown macroalgae (kelp forests and rockweed beds). Such habitats contribute to storage of organic carbon (Blue Carbon – BC) and support coastal protection, biodiversity and water quality. Protection and restoration of these habitats therefore have the potential to deliver climate change mitigation and co-benefits. Here we present the existing knowledge on Nordic BC habitats in terms of habitat area, C-stocks and sequestration rates, co-benefits, policies and management status to inspire a coherent Nordic BC roadmap. The area extent of BC habitats in the region is incompletely assessed, but available information sums up to 1,440 km2 salt marshes, 1,861 (potentially 2,735) km2 seagrass meadows, and 16,532 km2 (potentially 130,735 km2, including coarse Greenland estimates) brown macroalgae, yielding a total of 19,833 (potentially 134,910) km2. Saltmarshes and seagrass meadows have experienced major declines over the past century, while macroalgal trends are more diverse. Based on limited salt marsh data, sediment C-stocks average 3,311 g Corg m-2 (top 40-100 cm) and sequestration rates average 142 g Corg m-2 yr-1. Eelgrass C-stocks average 2,414 g Corg m-2 (top 25 cm) and initial data for sequestration rates range 5-33 g Corg m-2, quantified for one Greenland site and one short term restoration. For Nordic brown macroalgae, peer-reviewed estimates of sediment C-stock and sequestration are lacking. Overall, the review reveals substantial Nordic BC-stocks, but highlights that evidence is still insufficient to provide a robust estimate of all Nordic BC-stocks and sequestration rates. Needed are better quantification of habitat area, C-stocks and fluxes, particularly for macroalgae, as well as identification of target areas for BC management. The review also points to directives and regulations protecting Nordic marine vegetation, and local restoration initiatives with potential to increase C-sequestration but underlines that increased coordination at national and Nordic scales and across sectors is needed. We propose a Nordic BC roadmap for science and management to maximize the potential of BC habitats to mitigate climate change and support coastal protection, biodiversity and additional ecosystem functions.
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