The xCELLigence technology is a real-time cellular biosensor, which measures the net adhesion of cells to high-density gold electrode arrays printed on custom-designed E-plates. The strength of cellular adhesion is influenced by a myriad of factors that include cell type, cell viability, growth, migration, spreading and proliferation. We therefore hypothesised that xCELLigence biosensor technology would provide a valuable platform for the measurement of drug responses in a multitude of different experimental, clinical or pharmacological contexts. In this manuscript, we demonstrate how xCELLigence technology has been invaluable in the identification of (1) not only if cells respond to a particular drug, but (2) the window of drug responsiveness. The latter aspect is often left to educated guess work in classical end-point assays, whereas biosensor technology reveals the temporal profile of the response in real time, which enables both acute responses and longer term responses to be profiled within the same assay. In our experience, the xCELLigence biosensor technology is suitable for highly targeted drug assessment and also low to medium throughput drug screening, which produces high content temporal data in real time.
The observation of gravitational waves is hindered by the presence of transient noise (glitches). We study data from the third observing run of the Advanced LIGO detectors, and identify new glitch classes: fast scattering/crown and low-frequency blips. Using training sets assembled by monitoring of the state of the detector, and by citizen-science volunteers, we update the Gravity Spy machine-learning algorithm for glitch classification. We find that fast scattering/crown, linked to ground motion at the detector sites, is especially prevalent, and identify two subclasses linked to different types of ground motion. Reclassification of data based on the updated model finds that ∼27% of all transient noise at LIGO Livingston belongs to the fast scattering class, while ∼8% belongs to the low-frequency blip class, making them the most frequent and fourth most frequent sources of transient noise at that site. Our results demonstrate both how glitch classification can reveal potential improvements to gravitational-wave detectors, and how, given an appropriate framework, citizen-science volunteers may make discoveries in large data sets.
Hypoxic-ischemic (HI) studies in preterms lack reliable prognostic biomarkers for diagnostic tests of HI encephalopathy (HIE). Our group’s observations from in utero fetal sheep models suggest that potential biomarkers of HIE in the form of developing HI micro-scale epileptiform transients emerge along suppressed EEG/ECoG background during a latent phase of 6–7[Formula: see text]h post-insult. However, having to observe for the whole of the latent phase disqualifies any chance of clinical intervention. A precise automatic identification of these transients can help for a well-timed diagnosis of the HIE and to stop the spread of the injury before it becomes irreversible. This paper reports fusion of Reverse-Biorthogonal Wavelets with Type-1 Fuzzy classifiers, for the accurate real-time automatic identification and quantification of high-frequency HI spike transients in the latent phase, tested over seven in utero preterm sheep. Considerable high performance of 99.78 ± 0.10% was obtained from the Rbio-Wavelet Type-1 Fuzzy classifier for automatic identification of HI spikes tested over 42[Formula: see text]h of high-resolution recordings (sampling-freq:1024[Formula: see text]Hz). Data from post-insult automatic time-localization of high-frequency HI spikes reveals a promising trend in the average rate of the HI spikes, even in the animals with shorter occlusion periods, which highlights considerable higher number of transients within the first 2[Formula: see text]h post-insult.
Seizures are common in newborns after asphyxia at birth and are often refractory to anti-seizure agents. Magnesium sulphate (MgSO ) has anticonvulsant effects and is increasingly given to women in preterm labour for potential neuroprotection. There is limited information on its effects on perinatal seizures. We examined the hypothesis that MgSO infusion would reduce fetal seizures after asphyxia in utero. Preterm fetal sheep at 0.7 gestation (104 days, term = 147 days) were given intravenous infusions of either saline (n = 14) or MgSO (n = 12, 160 mg bolus + 48 mg h infusion over 48 h). Fetuses underwent umbilical cord occlusion (UCO) for 25 min, 24 h after the start of infusion. The start time for seizures did not differ between groups, but MgSO significantly reduced the total number of seizures (P < 0.001), peak seizure amplitude (P < 0.05) and seizure burden (P < 0.005). Within the saline-asphyxia group, male fetuses had significantly more seizures than females (P < 0.05). Within the MgSO -asphyxia group, although both sexes had fewer seizures than the saline-asphyxia group, the greatest effect of MgSO was on male fetuses, with reduced numbers of seizures (P < 0.001) and seizure burden (P < 0.005). Only 1 out of 6 MgSO males had seizures on the second day post-UCO compared to 5 out of 6 MgSO female fetuses (P = 0.08). Finally, seizures showed a circadian profile with peak seizures between 04.00 and 06.00 h on the first and second day post-UCO. Collectively, these results suggest that MgSO may have utility in treating perinatal seizures and has sexually dimorphic effects.
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