Designing a trial for neonatal seizure treatment

Neonatal seizures are widely considered a neurological emergency with a need for prompt treatment, yet they are known to present a highly elusive target for bedside clinicians. Recent studies have suggested that the design of a neonatal seizure treatment trial will profoundly influence the sample size, which may readily increase to hundreds or even thousands as the achieved effect size diminishes to clinical irrelevance. The self-limiting and rapidly resolving nature of neonatal seizures diminishes the measurable treatment effect every hour after seizure onset and any effect may potentially be confused with spontaneous resolution, precluding the value of many observational studies. The large individual variability in seizure occurrence over time and between etiologies challenges group comparisons, while the absence of clinical signs mandates quantification of seizure occurrence with continuous multi-channel EEG monitoring. A biologically sound approach that views neonatal seizures as a functional cot-side biomarker rather than an object to treat can overcome these challenges. (C) 2018 Elsevier Ltd. All rights reserved.Peer reviewe

Contralateral fatigue during severe-intensity single-leg exercise: influence of acute acetaminophen ingestion

Exhaustive single-leg exercise has been suggested to reduce time to task failure (Tlim) during subsequent exercise in the contralateral leg by exacerbating central fatigue development. We investigated the influence of acetaminophen (ACT), an analgesic that may blunt central fatigue development, on Tlim during single-leg exercise completed with and without prior fatiguing exercise of the contralateral leg. Fourteen recreationally active men performed single-leg severe-intensity knee-extensor exercise to Tlim on the left (Leg1) and right (Leg2) legs without prior contralateral fatigue and on Leg2 immediately following Leg1 (Leg2-CONTRA). The tests were completed following ingestion of 1-g ACT or maltodextrin [placebo (PL)] capsules. Intramuscular phosphorus-containing metabolites and substrates and muscle activation were assessed using 31P-MRS and electromyography, respectively. Tlim was not different between Leg1ACT and Leg1PL conditions (402 ± 101 vs. 390 ± 106 s, P = 0.11). There was also no difference in Tlim between Leg2ACT-CONTRA and Leg2PL-CONTRA (324 ± 85 vs. 311 ± 92 s, P = 0.10), but Tlim was shorter in Leg2ACT-CONTRA and Leg2PL-CONTRA than in Leg2CON (385 ± 104 s, both P 0.05). These findings suggest that levels of metabolic perturbation and muscle activation at Tlim are not different during single-leg severe-intensity knee-extensor exercise completed with or without prior fatiguing exercise of the contralateral leg. Despite contralateral fatigue, ACT ingestion did not alter neuromuscular responses, muscle metabolites, or exercise performance.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.This research was not sponsored by any funding body external to the University of Exeter. J. Fulford’s salary was supported via National Institute for Health Research Grant CRF/2016/10027 to the University of Exeter.Accepted version (12 month embargo

Detailed temperature mapping-Warming characterizes archipelago zones

Rapidly warming shallow archipelago areas have the best energetic options for high ecological production. We analyzed and visualized the spring and summer temperature development in the Finnish coastal areas of the Northern Baltic Sea. Typical for the Baltic is a high annual periodicity and variability in water temperatures. The maximum difference between a single day average temperatures across the study area was 28.3 °C. During wintertime the littoral water temperature can decrease below zero in outer archipelago or open water areas when the protective ice cover is not present and the lowest observed value was −0.5 °C. The depth and exposition are the most important variables explaining the coastal temperature gradients from the innermost to the outermost areas in springtime when water is heated by increasing solar radiation. Temperature differs more within coastal area than between the basins. Water temperature sum was highest in innermost areas, lowest in open water areas and the variation in daily averages was highest in the middle region. At the end of the warming period, the difference in surface water temperatures between the innermost and outermost areas had diminished at the time when the cooling began in August–September. These clear temperature gradients enabled us use the cumulative water temperature to classify the coastal zones in a biologically sensible manner into five regions. Our study shows a novel approach to study detailed spatial variations in water temperatures. The results can further be used, for example, to model and predict the spatial distribution of aquatic biota and to determine appropriate spatio-temporal designs for aquatic biota surveys. The new spatial knowledge of temperature regions will also help the evaluation of possible causes of larger scale climatological changes in a biological context including productivity.Peer reviewe

The effect of reducing EEG electrode number on the visual interpretation of the human expert for neonatal seizure detection

Objectives: To measure changes in the visual interpretation of the EEG by the human expert for neonatal seizure detection when reducing the number of recording electrodes. Methods: EEGs were recorded from 45 infants admitted to the neonatal intensive care unit (NICU). Three experts annotated seizures in EEG montages derived from 19, 8 and 4 electrodes. Differences between annotations were assessed by comparing intra-montage with inter-montage agreement (K). Results: Three experts annotated 4464 seizures across all infants and montages. The inter-expert agreement was not significantly altered by the number of electrodes in the montage (p = 0.685, n = 43). Reducing the number of EEG electrodes altered the seizure annotation for all experts. Agreement between the 19-electrode montage (K-19,K-19 = 0.832) was significantly higher than the agreement between 19 and 8-electrode montages (dK = 0.114; p <0.001, n = 42) or 19 and 4-electrode montages (dK = 0.113, p <0.001, n = 43). Seizure burden and number were significantly underestimated by the 4 and 8-electrode montage (p <0.001). No significant difference in agreement was found between 8 and 4-electrode montages (dK = 0.002; p = 0.07, n = 42). Conclusions: Reducing the number of EEG electrodes from 19 electrodes resulted in slight but significant changes in seizure detection. (C) 2017 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Analysis of infant cortical synchrony is constrained by the number of recording electrodes and the recording montage

Objective: To assess how the recording montage in the neonatal EEG influences the detection of cortical source signals and their phase interactions. Methods: Scalp EEG was simulated by forward modeling 20-200 simultaneously active sources covering the cortical surface of a realistic neonatal head model. We assessed systematically how the number of scalp electrodes (11-85), analysis montage, or the size of cortical sources affect the detection of cortical phase synchrony. Statistical metrics were developed for quantifying the resolution and reliability of the montages. Results: The findings converge to show that an increase in the number of recording electrodes leads to a systematic improvement in the detection of true cortical phase synchrony. While there is always a ceiling effect with respect to discernible cortical details, we show that the average and Laplacian montages exhibit superior specificity and sensitivity as compared to other conventional montages. Conclusions: Reliability in assessing true neonatal cortical synchrony is directly related to the choice of EEG recording and analysis configurations. Because of the high conductivity of the neonatal skull, the conventional neonatal EEG recordings are spatially far too sparse for pertinent studies, and this loss of information cannot be recovered by re-montaging during analysis. Significance: Future neonatal EEG studies will need prospective planning of recording configuration to allow analysis of spatial details required by each study question. Our findings also advice about the level of details in brain synchrony that can be studied with existing datasets or by using conventional EEG recordings. (C) 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Influence of hyperoxia on muscle metabolic responses and the power-duration relationship during severe-intensity exercise in humans: a 31P magnetic resonance spectroscopy study

addresses: School of Sport and Health Sciences, St Luke's Campus, University of Exeter, Exeter EX1 2LU, UK.types: Journal Article; Randomized Controlled TrialThis is the author's post-print version of an article published in Experimental Physiology, 2010, Vol. 95, Issue 4, pp. 528 – 540 Copyright © 2010 Wiley-Blackwell /The Physiological Society. The definitive version is available at www3.interscience.wiley.comSevere-intensity constant-work-rate exercise results in the attainment of maximal oxygen uptake, but the muscle metabolic milieu at the limit of tolerance (T(lim)) for such exercise remains to be elucidated. We hypothesized that T(lim) during severe-intensity exercise would be associated with the attainment of consistently low values of intramuscular phosphocreatine ([PCr]) and pH, as determined using (31)P magnetic resonance spectroscopy, irrespective of the work rate and the inspired O(2) fraction. We also hypothesized that hyperoxia would increase the asymptote of the hyperbolic power-duration relationship (the critical power, CP) without altering the curvature constant (W). Seven subjects (mean +/- s.d., age 30 +/- 9 years) completed four constant-work-rate knee-extension exercise bouts to the limit of tolerance (range, 3-10 min) both in normoxia (N) and in hyperoxia (H; 70% O(2)) inside the bore of 1.5 T superconducting magnet. The [PCr] (approximately 5-10% of resting baseline) and pH (approximately 6.65) at the limit of tolerance during each of the four trials was not significantly different either in normoxia or in hyperoxia. At the same fixed work rate, the overall rate at which [PCr] fell with time was attenuated in hyperoxia (mean response time: N, 59 +/- 20 versus H, 116 +/- 46 s; P < 0.05). The CP was higher (N, 16.1 +/- 2.6 versus H, 18.0 +/- 2.3 W; P < 0.05) and the W was lower (N, 1.92 +/- 0.70 versus H, 1.48 +/- 0.31 kJ; P < 0.05) in hyperoxia compared with normoxia. These data indicate that T(lim) during severe-intensity exercise is associated with the attainment of consistently low values of muscle [PCr] and pH. The CP and W parameters of the power-duration relationship were both sensitive to the inspiration of hyperoxic gas

Time-Varying EEG Correlations Improve Automated Neonatal Seizure Detection

The aim of this study was to develop methods for detecting the nonstationary periodic characteristics of neonatal electroencephalographic (EEG) seizures by adapting estimates of the correlation both in the time (spike correlation; SC) and time-frequency domain (time-frequency correlation; TFC). These measures were incorporated into a seizure detection algorithm (SDA) based on a support vector machine to detect periods of seizure and nonseizure. The performance of these nonstationary correlation measures was evaluated using EEG recordings from 79 term neonates annotated by three human experts. The proposed measures were highly discriminative for seizure detection (median AUC(SC): 0.933 IQR: 0.821-0.975, median AUC(TFC): 0.883 IQR: 0.707-0.931). The resultant SDA applied to multi-channel recordings had a median AUC of 0.988 (IQR: 0.931-0.998) when compared to consensus annotations, outperformed two state-of-the-art SDAs (p <0.001) and was noninferior to the human expert for 73/79 of neonates.Peer reviewe

Species distribution modelling as basis for the ecosystem-based management: a case study for the Eastern Baltic Sea

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Dietary nitrate accelerates postexercise muscle metabolic recovery and O2 delivery in hypoxia.

We tested the hypothesis that the time constants (τ) of postexercise T2* MRI signal intensity (an index of O2 delivery) and muscle [PCr] (an index of metabolic perturbation, measured by (31)P-MRS) in hypoxia would be accelerated after dietary nitrate (NO3 (-)) supplementation. In a double-blind crossover design, eight moderately trained subjects underwent 5 days of NO3 (-) (beetroot juice, BR; 8.2 mmol/day NO3 (-)) and placebo (PL; 0.003 mmol/day NO3 (-)) supplementation in four conditions: normoxic PL (N-PL), hypoxic PL (H-PL; 13% O2), normoxic NO3 (-) (N-BR), and hypoxic NO3 (-) (H-BR). The single-leg knee-extension protocol consisted of 10 min of steady-state exercise and 24 s of high-intensity exercise. The [PCr] recovery τ was greater in H-PL (30 ± 4 s) than H-BR (22 ± 4 s), N-PL (24 ± 4 s) and N-BR (22 ± 4 s) (P 0.05). These findings suggest that the NO3 (-)-NO2 (-)-NO pathway is a significant modulator of muscle energetics and O2 delivery during hypoxic exercise and subsequent recovery.J. Fulford's salary was supported via National Institute of Health Research Grant 50112

A dataset of neonatal EEG recordings with seizure annotations

Neonatal seizures are a common emergency in the neonatal intensive care unit (NICU). There are many questions yet to be answered regarding the temporal/spatial characteristics of seizures from different pathologies, response to medication, effects on neurodevelopment and optimal detection. The dataset presented in this descriptor contains EEG recordings from human neonates, the visual interpretation of the EEG by the human experts, supporting clinical data and codes to assist access. Multi-channel EEG was recorded from 79 term neonates admitted to the NICU at the Helsinki University Hospital. The median recording duration was 74 min (IQR: 64 to 96 min). The presence of seizures in the EEGs was annotated independently by three experts. An average of 460 seizures were annotated per expert in the dataset; 39 neonates had seizures and 22 were seizure free, by consensus. The dataset can be used as a reference set of neonatal seizures, in studies of inter-observer agreement and for the development of automated methods of seizure detection and other EEG analyses.Peer reviewe