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- Benterud, T, et al.
(author)
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N-Acetylcysteine Amide Exerts Possible Neuroprotective Effects in Newborn Pigs after Perinatal Asphyxia
- 2017
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In: Neonatology. - : S. Karger AG. - 1661-7819 .- 1661-7800. ; 111:1, s. 12-21
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Journal article (peer-reviewed)abstract
- <b><i>Background:</i></b> Perinatal asphyxia and ensuing reoxygenation change the antioxidant capacity of cells and organs. <b><i>Objectives:</i></b> To analyze the neuroprotective effect of the antioxidant N-acetylcysteine amide (NACA) after perinatal hypoxia-reoxygenation with an emphasis on proinflammatory cytokines and the transcription factor NF-κB in the prefrontal cortex of neonatal pigs. <b><i>Methods:</i></b> Twenty-nine newborn pigs, aged 12-36 h, were subjected to global hypoxia and hypercapnia. One sham-operated group (n = 5) and 2 experimental groups (n = 12) were exposed to 8% oxygen, until the base excess was -20 mmol/l or the mean arterial blood pressure fell to <20 mm Hg (asphyxia with NACA or saline). The pigs were observed for 9.5 h after hypoxia. Samples of prefrontal cortex and plasma were analyzed. <b><i>Results:</i></b> Cortex: there was no significant difference in mRNA expression between the intervention groups regarding IL-1β, IL6, TNFα, MMP2, MMP9 or IL18. Pigs exposed to hypoxia-reoxygenation and treatment with NACA (NACA-pigs) had a significantly lower protein concentration of IL-1β than pigs treated with saline (placebo controls), i.e. 8.8 ± 3.9 versus 16.8 ± 10.5 pg/mg protein (p = 0.02). The activation of the transcription factor NF-κB (measured as the fold-change of phosphorylated p65<sup>Ser 536</sup>), was reduced in the NACA-pigs when compared to the placebo controls (5.2 ± 4.3 vs. 16.0 ± 13.5; p = 0.02). No difference between the intervention groups regarding brain histopathology or in the levels of 8-oxoguanine measured in the prefrontal cortex were observed. Plasma: the NACA-pigs had a stronger reduction of TNFα in the first 30 min following asphyxia compared with the placebo controls, i.e. 36 (30-44) versus 24 (14-32)% (p = 0.01). <b><i>Conclusion:</i></b> The reduced levels of the pivotal inflammatory markers IL-1β and TNFα and the transcription factor NF-κB may indicate that NACA has possible neuroprotective effects after perinatal asphyxia.
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- Di Bona, Gabriele, et al.
(author)
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Maximal dispersion of adaptive random walks
- 2022
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In: Physical Review Research. - : American Physical Society (APS). - 2643-1564. ; 4:4
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Journal article (peer-reviewed)abstract
- Maximum entropy random walks (MERWs) are maximally dispersing and play a key role in optimizing information spreading in various contexts. However, building MERWs comes at the cost of knowing beforehand the global structure of the network, a requirement that makes them totally inadequate in real-case scenarios. Here, we propose an adaptive random walk (ARW), which instead maximizes dispersion by updating its transition rule on the local information collected while exploring the network. We show how to derive ARW via a large-deviation representation of MERW and study its dynamics on synthetic and real-world networks.
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- Fall, Magnus, 1941, et al.
(author)
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Peripheral Electrical Stimulation.
- 2004
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In: Textbook of the neurogenic bladder : adults and children. - : Martin Dunitz. - 9781841842066 ; , s. 529-534
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Book chapter (other academic/artistic)
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- Hooker, Andrew C, et al.
(author)
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An evaluation of population D-optimal designs via pharmacokinetic simulations.
- 2003
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In: Annals of Biomedical Engineering. - 0090-6964 .- 1573-9686. ; 31:1, s. 98-111
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Journal article (peer-reviewed)abstract
- One goal of large scale clinical trials is to determine how a drug is processed by, and cleared from, the human body [i.e., its pharmacokinetic (PK) properties] and how these PK properties differ between individuals in a population (i.e., its population PK properties). Due to the high cost of these studies and the limited amount of data (e.g., blood samples) available from each study subject, it would be useful to know how many measurements are needed and when those measurements should be taken to accurately quantify population PK model parameters means and variances. Previous studies have looked at optimal design strategies of population PK experiments by developing an optimal design for an individual study (i.e., no interindividual variability was considered in the design), and then applying that design to each individual in a population study (where interindividual variability is present). A more algorithmically and informationally intensive approach is to develop a population optimal design, which inherently includes the assessment of interindividual variability. We present a simulation-based evaluation of these two design methods based on nonlinear Gaussian population PK models. Specifically, we compute standard individual and population D-optimal designs and compare population PK model parameter estimates based on simulated optimal design measurements. Our results show that population and standard D-optimal designs are not significantly different when both designs have the same number of samples per individual. However, population optimal designs allow for sampling schedules where the number of samples per individual is less than the number of model parameters, the theoretical limit allowed in standard optimal design. These designs with a low number of samples per individual are shown to be nearly as robust in parameter estimation as standard D-optimal designs. In the limit of just one sample per individual, however, population D-optimal designs are shown to be inadequate.
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