Quantitative Preterm EEG Analysis: The Need for Caution in Using Modern Data Science Techniques

Hemodynamic changes during neonatal transition increase the vulnerability of the preterm brain to injury. Real-time monitoring of brain function during this period would help identify the immediate impact of these changes on the brain. Neonatal EEG provides detailed real-time information about newborn brain function but can be difficult to interpret for non-experts; preterm neonatal EEG poses even greater challenges. An objective quantitative measure of preterm brain health would be invaluable during neonatal transition to help guide supportive care and ultimately protect the brain. Appropriate quantitative measures of preterm EEG must be calculated and care needs to be taken when applying the many techniques available for this task in the era of modern data science. This review provides valuable information about the factors that influence quantitative EEG analysis and describes the common pitfalls. Careful feature selection is required and attention must be paid to behavioral state given the variations encountered in newborn EEG during different states. Finally, the detrimental influence of artifacts on quantitative EEG analysis is illustrated

Coupling between mean blood pressure and EEG in preterm neonates is associated with reduced illness severity scores

Hypotension or low blood pressure (BP) is a common problem in preterm neonates and has been associated with adverse short and long-term neurological outcomes. Deciding when and whether to treat hypotension relies on an understanding of the relationship between BP and brain functioning. This study aims to investigate the interaction (coupling) between BP and continuous multichannel unedited EEG recordings in preterm infants less than 32 weeks of gestational age. The EEG was represented by spectral power in four frequency sub-bands: 0.3 +/- 3 Hz, 3 +/- 8 Hz, 8 +/- 15 Hz and 15 +/- 30 Hz. BP was represented as mean arterial pressure (MAP). The level of coupling between the two physiological systems was estimated using linear and nonlinear methods such as correlation, coherence and mutual information. Causality of interaction was measured using transfer entropy. The illness severity was represented by the clinical risk index for babies (CRIB II score) and contrasted to the computed level of interaction. It is shown here that correlation and coherence, which are linear measures of the coupling between EEG and MAP, do not correlate with CRIB values, whereas adjusted mutual information, a nonlinear measure, is associated with CRIB scores (r = -0.57, p = 0.003). Mutual information is independent of the absolute values of MAP and EEG powers and quantifies the level of coupling between the short-term dynamics in both signals. The analysis indicated that the dominant causality is from changes in EEG producing changes in MAP. Transfer entropy (EEG to MAP) is associated with the CRIB score (0.3 +/- 3 Hz: r = 0.428, p = 0.033, 3 +/- 8 Hz: r = 0.44, p = 0.028, 8 +/- 15 Hz: r = 0.416, p = 0.038) and indicates that a higher level of directed coupling from brain activity to blood pressure is associated with increased illness in preterm infants. This is the first study to present the nonlinear measure of interaction between brain activity and blood pressure and to demonstrate its relation to the initial illness severity in the preterm infant. The obtained results allow us to hypothesise that the normal wellbeing of a preterm neonate can be characterised by a nonlinear coupling between brain activity and MAP, whereas the presence of weak coupling with distinctive directionality of information flow is associated with an increased mortality rate in preterms

Temporal evolution of quantitative EEG within 3 days of birth in early preterm infants

For the premature newborn, little is known about changes in brain activity during transition to extra-uterine life. We aim to quantify these changes in relation to the longer-term maturation of the developing brain. We analysed EEG for up to 72 hours after birth from 28 infants bornPeer reviewe

Bifidobacterium breve with α-Linolenic Acid and Linoleic Acid Alters Fatty Acid Metabolism in the Maternal Separation Model of Irritable Bowel Syndrome

peer-reviewedThe aim of this study was to compare the impact of dietary supplementation with a Bifidobacterium breve strain together with linoleic acid & α-linolenic acid, for 7 weeks, on colonic sensitivity and fatty acid metabolism in rats. Maternally separated and non-maternally separated Sprague Dawley rats (n = 15) were orally gavaged with either B. breve DPC6330 (109 microorganisms/day) alone or in combination with 0.5% (w/w) linoleic acid & 0.5% (w/w) α-linolenic acid, daily for 7 weeks and compared with trehalose and bovine serum albumin. Tissue fatty acid composition was assessed by gas-liquid chromatography and visceral hypersensitivity was assessed by colorectal distension. Significant differences in the fatty acid profiles of the non-separated controls and maternally separated controls were observed for α-linolenic acid and arachidonic acid in the liver, oleic acid and eicosenoic acid (c11) in adipose tissue, and for palmitoleic acid and docosahexaenoic acid in serum (p<0.05). Administration of B. breve DPC6330 to MS rats significantly increased palmitoleic acid, arachidonic acid and docosahexaenoic acid in the liver, eicosenoic acid (c11) in adipose tissue and palmitoleic acid in the prefrontal cortex (p<0.05), whereas feeding B. breve DPC6330 to non separated rats significantly increased eicosapentaenoic acid and docosapentaenoic acid in serum (p<0.05) compared with the NS un-supplemented controls. Administration of B. breve DPC6330 in combination with linoleic acid and α-linolenic acid to maternally separated rats significantly increased docosapentaenoic acid in the serum (p<0.01) and α-linolenic acid in adipose tissue (p<0.001), whereas feeding B. breve DPC6330 with fatty acid supplementation to non-separated rats significantly increased liver and serum docosapentaenoic acid (p<0.05), and α-linolenic acid in adipose tissue (p<0.001). B. breve DPC6330 influenced host fatty acid metabolism. Administration of B. breve DPC6330 to maternally separated rats significantly modified the palmitoleic acid, arachidonic acid and docosahexaenoic acid contents in tissues. The effect was not observed in non-separated animals.This work was supported by the Science Foundation of Ireland – funded Centre for Science, Engineering and Technology, the Alimentary Pharmabiotic Centre

Population preference values for treatment outcomes in chronic lymphocytic leukaemia: a cross-sectional utility study

<p>Abstract</p> <p>Background</p> <p>Given that treatments for chronic lymphocytic leukaemia (CLL) are palliative rather than curative, evaluating the patient-perceived impacts of therapy is critical. To date, no utility (preference) studies from the general public or patient perspective have been conducted in CLL. The objective of this study was to measure preferences for health states associated with CLL treatment.</p> <p>Methods</p> <p>This was a cross-sectional study of 89 members of the general population in the UK (England and Scotland). Using standard gamble, each participant valued four health states describing response status, six describing treatment-related toxicities based on Common Toxicity Criteria, and two describing line of treatment. The health states incorporated standardized descriptions of treatment response (symptoms have "improved," "stabilized," or "gotten worse"), swollen glands, impact on daily activities, fatigue, appetite, and night sweats. Utility estimates ranged from 0.0, reflecting dead, to 1.0, reflecting full health.</p> <p>Results</p> <p>Complete response (CR) was the most preferred health state (mean utility, 0.91), followed by partial response (PR), 0.84; no change (NC), 0.78; and progressive disease (PD), 0.68. Among the toxicity states, grade I/II nausea and nausea/vomiting had the smallest utility decrements (both were -0.05), and grade III/IV pneumonia had the greatest decrement (-0.20). The utility decrements obtained for toxicity states can be subtracted from utilities for CR, PR, NC, and PD, as appropriate. The utilities for second- and third-line treatments, which are attempted when symptoms worsen, were 0.71 and 0.65, respectively. No significant differences in utilities were observed by age, sex, or knowledge/experience with leukaemia.</p> <p>Conclusions</p> <p>This study reports UK population utilities for a universal set of CLL health states that incorporate intended treatment response and unintended toxicities. These utilities can be applied in future cost-effectiveness analyses of CLL treatment.</p

Correlative super-resolution fluorescence and electron microscopy using conventional fluorescent proteins in vacuo

Super-resolution light microscopy, correlative light and electron microscopy, and volume electron microscopy are revolutionising the way in which biological samples are examined and understood. Here, we combine these approaches to deliver super-accurate correlation of fluorescent proteins to cellular structures. We show that YFP and GFP have enhanced blinking properties when embedded in acrylic resin and imaged under partial vacuum, enabling in vacuo single molecule localisation microscopy. In conventional section-based correlative microscopy experiments, the specimen must be moved between imaging systems and/or further manipulated for optimal viewing. These steps can introduce undesirable alterations in the specimen, and complicate correlation between imaging modalities. We avoided these issues by using a scanning electron microscope with integrated optical microscope to acquire both localisation and electron microscopy images, which could then be precisely correlated. Collecting data from ultrathin sections also improved the axial resolution and signal-to-noise ratio of the raw localisation microscopy data. Expanding data collection across an array of sections will allow 3-dimensional correlation over unprecedented volumes. The performance of this technique is demonstrated on vaccinia virus (with YFP) and diacylglycerol in cellular membranes (with GFP)

Neonatal EEG graded for severity of background abnormalities in hypoxic-ischaemic encephalopathy

This report describes a set of neonatal electroencephalogram (EEG) recordings graded according to the severity of abnormalities in the background pattern. The dataset consists of 169 hours of multichannel EEG from 53 neonates recorded in a neonatal intensive care unit. All neonates received a diagnosis of hypoxic-ischaemic encephalopathy (HIE), the most common cause of brain injury in full term infants. For each neonate, multiple 1-hour epochs of good quality EEG were selected and then graded for background abnormalities. The grading system assesses EEG attributes such as amplitude and frequency, continuity, sleep--wake cycling, symmetry and synchrony, and abnormal waveforms. Background severity was then categorised into 4 grades: normal or mildly abnormal EEG, moderately abnormal EEG, severely abnormal EEG, and inactive EEG. The data can be used as a reference set of multi-channel EEG for neonates with HIE, for EEG training purposes, or for developing and evaluating automated grading algorithms