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Dataset for The influence of placental metabolism on fatty acid transfer to the fetus
No full textDataset supporting:
Perazzolo, Simone, Sengers, Bram and Lewis, Rohan (2016) The influence of placental metabolism on fatty acid transfer to the fetus. The Journal of Lipid Research.</span
Modelling nutrient transfer across the placenta
No full textThe placenta is a fetal organ that separates the maternal from the fetal circulation and mediates the transfer of nutrients between the mother and the fetus. Placental transfer of nutrients occurs across the placental villi, which are finely branched tree-like structures. Nutrients from the maternal blood in the intervillous space cross the villous barrier and then enter the fetal capillaries. A healthy pregnancy outcome is dependent on adequate placental transfer of gases and nutrients from the maternal to the fetal circulation. Impairments in nutrient transfer lead to altered fetal growth, which also has health implications in later life. While the transport mechanisms that mediate this transfer are known, the ways in which these interact as a system are not well understood.Mathematical modelling provides a tool to enhance the interpretation of placental transfer experiments. In this thesis, physiologically based compartmental models were employed for the study of nutrient transfer between the mother and the fetus and validated with data from ex vivo placental perfusion and in vivo clinical experiments. With respect to previous models, a more extensive range of modelling applications is presented in this thesis including several different transport mechanisms. Model implementation was carried out for fatty acids, amino acids and cortisol. In particular, fatty acids were studied extensively in vivo and in vitro. In addition, a 3D image based modelling approach of the placental microstructures was carried out. The main novelty compared to previous approaches was that the transport of nutrients in the maternal blood was modelled explicitly and a study of nutrient uptake with respect to different maternal blood flow rates was performed.The main objectives of this thesis were to increase the biological understanding of placental transfer and to provide a platform for quantification, prediction and evaluation of nutrient transfer across the placenta. This may ultimately form the basis for clinical tools to help physicians to prevent, recognise, intervene and cure problematic pregnancies.The main results of the thesis were that placental metabolism was found to play a rate-limiting role in fatty acid and amino acid transfer and that the flow environment in the placental microstructure had a significant effect on limiting transfer. Examples of application of the proposed models to experimental data from external collaborators was successful and enhanced their interpretation and value.Future work needs to focus on the further investigation of placental metabolism, such as the localisation and characterisation of metabolic sub compartments. Moreover, future modelling investigation of the 3D microstructure of the placenta should focus on the inclusion of both maternal and fetal capillary flow and the implememntation of more complex transport mechanisms. The models developed in this thesis could equally be used to study the transfer of other substances, e.g. drugs or toxins, in normal and altered pregnancies. In this respect, the models presented should be integrated as part of the realisation of a “virtual” placenta
Dataset for Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure
No full textComsol files used for the simulations presented in the following paper:
Simone Perazzolo, Rohan Lewis, Bram Sengers, Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure. Placenta 2017.</span
Modelling nutrient transfer based on 3D imaging of the human placental microstructure
No full textImpaired transfer of nutrients from mother to fetus can affect pregnancy outcomes. The placenta has a complex microstructure, including the maternal intervillous space and fetal capillaries. Previous computational models of placental transfer either assumed a simplified idealized local geometry or were based on 2D imaging. In this study, we present a novel 3D computational model to assess the placental transfer of nutrients at the microscale in interaction with the maternal flow environment. A stack of confocal microscopy images of the placental terminal villi was collected and reconstructed. The 3D simulation framework was tested for the transport of oxygen. Preliminary results identified local stagnant zones, as well as areas of high nutrient transfer into the fetal capillaries in the most exposed branches of the villi as a result of better perfusion, combined with a smaller thickness of the tissue barrier. Overall, the current model may serve as a tool for assessing pregnancy conditions affected by inefficient nutrient transfer due to altered microscale placental morphology
Modelling the effect of intervillous flow on solute transfer based on 3D imaging of the human placental microstructure
No full textIntroduction: A healthy pregnancy depends on placental transfer from mother to fetus. Placental transfer takes place at the micro scale across the placental villi. Solutes from the maternal blood are taken up by placental villi and enter the fetal capillaries. This study investigated the effect of maternal blood flow on solute uptake at the micro scale. Methods: A 3D image based modelling approach of the placental microstructures was undertaken. Solute transport in the intervillous space was modelled explicitly and solute uptake with respect to different maternal blood flow rates was estimated. Fetal capillary flow was not modelled and treated as a perfect sink. Results: For a freely diffusing small solute, the flow of maternal blood through the intervillous space was found to be limiting the transfer. Ignoring the effects of maternal flow resulted in a 2.4 ± 0.4 fold over-prediction of transfer by simple diffusion, in absence of binding. Villous morphology affected the efficiency of solute transfer due to concentration depleted zones. Interestingly, less dense microvilli had lower surface area available for uptake which was compensated by increased flow due to their higher permeability. At super-physiological pressures, maternal flow was not limiting, however the efficiency of uptake decreased. Conclusions: This study suggests that the interplay between maternal flow and villous structure affects the efficiency of placental transfer but predicted that flow rate will be the major determinant of transfer
The influence of placental metabolism on fatty acid transfer to the fetus
No full textThe factors determining fatty acid transfer across the placenta are not fully understood. This study used a combined experimental and computational modeling approach to explore placental transfer of nonesterified fatty acids and identify the rate-determining processes. Isolated perfused human placenta was used to study the uptake and transfer of 13C-fatty acids and the release of endogenous fatty acids. Only 6.2 ± 0.8% of the maternal 13C-fatty acids taken up by the placenta was delivered to the fetal circulation. Of the unlabeled fatty acids released from endogenous lipid pools, 78 ± 5% was recovered in the maternal circulation and 22 ± 5% in the fetal circulation. Computational modeling indicated that fatty acid metabolism was necessary to explain the discrepancy between uptake and delivery of 13C-fatty acids. Without metabolism, the model overpredicts the fetal delivery of 13C-fatty acids 15-fold. Metabolic rate was predicted to be the main determinant of uptake from the maternal circulation. The microvillous membrane had a greater fatty acid transport capacity than the basal membrane. This study suggests that incorporation of fatty acids into placental lipid pools may modulate their transfer to the fetus. Future work needs to focus on the factors regulating fatty acid incorporation into lipid pools
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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