Multi-scale Peak and Trough Detection Optimised for Periodic and Quasi-Periodic Neuroscience Data

Objectives The reliable detection of peaks and troughs in physiological signals is essential to many investigative techniques in medicine and computational biology. Analysis of the intracranial pressure (ICP) waveform is a particular challenge due to multi-scale features, a changing morphology over time and signal-to-noise limitations. Here we present an efficient peak and trough detection algorithm that extends the scalogram approach of Scholkmann et al, and results in greatly improved algorithm runtime performance. Materials and Methods Our improved algorithm (Modified-Scholkmann) was developed and analysed in Matlab R2015b (MathWorks Inc., Massachusetts, USA). Synthesised waveforms (periodic, quasi- periodic and chirp sinusoids) were degraded with white Gaussian noise to achieve signal-to- noise ratios down to 5dB and were used to compare the performance of the Original- Scholkmann and Modified-Scholkmann algorithms. Results Modified-Scholkmann has false positive (0%) and false negative (0%) detection rates identical to Original-Scholkmann when applied to our test suite. Actual compute time for a 200-run Monte Carlo simulation over a multicomponent noisy test signal was 40.96 ± 0.020 seconds (mean ± 95%CI) for Original-Scholkmann and 1.81 ± 0.003 seconds (mean ± 95%CI) for Modified-Scholkmann, demonstrating the expected improvement in run time complexity from ! to . Conclusions The accurate interpretation of waveform data to identify peaks and troughs is crucial in signal parameterization, feature extraction and waveform identification tasks. Modification of a standard scalogram technique has produced a robust algorithm with linear computational complexity that is particularly suited to the challenges presented by large, noisy physiological datasets. The algorithm is optimised through a single parameter and can identify sub- waveform features with minimal additional overhead, and is easily adapted to run in real-time on commodity hardware

Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution

Purpose Dynamic in-situ proton (1H) magnetic resonance imaging (MRI) and 1H T2-relaxometry experiments are described in an attempt to: (i) understand the physical processes, that occur during the reconstitution of lyophilized bovine serum albumen (BSA) and monoclonal antibody (mAb) proteins; and (ii) objectify the reconstitution time. Methods Rapid two-dimensional 1H MRI and diffusion weighted MRI were used to study the temporal changes in solids dissolution and characterise water mass transport characteristics. One-shot T2 relaxation time measurements were also acquired in an attempt to quantify the reconstitution time. Both MRI data and T2-relaxation data were compared to standard visual observations currently adopted by industry. The 1H images were further referenced to MRI calibration data to give quantitative values of protein concentration and, percentage of remaining undissolved solids. Results An algorithmic analysis the 1H T2-relaxation data shows it is possible to classify the reconstitution event into three regimes (undissolved, transitional and dissolved). Moreover, a combined analysis of the 2D 1H MRI and 1H T2-relaxation data gives a unique time point that characterises the onset of a reconstituted protein solution within well-defined error bars. These values compared favourably with those from visual observations. Diffusion weighted MRI showed that low concentration BSA and mAb samples showed distinct liquid-liquid phase separation attributed to two liquid layers with significant density gradients. Conclusions T2 relaxation time distributions (whose interpretation is validated from the 2D 1H MR images) provides a quick and effective framework to build objective, quantitative descriptors of the reconstitution process that facilitate the interpretation of subjective visual observations currently adopted as the standard practice industry.Medimmune PL

Statistical Signal Properties of the Pressure-Reactivity Index (PRx)

Objectives: The pressure-reactivity index (PRx) is defined in terms of the moving correlation coefficient between intracranial pressure (ICP) and mean arterial pressure (MAP) and is a measure of cerebral autoregulation ability. Histograms of PRx against cerebral perfusion pressure (CPP) show U-shaped behaviour- the minimum reflecting optimal cerebral autoregulation (CPPopt). However U-shaped behavior may also occur by chance. To date there has been no evaluation of the statistical properties of these signals. Materials and Methods: We simulated PRx/CPP distributions using synthetic ICP and MAP signals from Gaussian noise with known cross-correlation. We calculated the statistical distribution of extrema in the PRx/CPP relationship. Results: The calculation of PRx on random data is statistically biased to show a U-shaped behavior when the signals are positively cross-correlated (equivalent to PRx>0). For PR<0, the bias is towards inverse U-shaped behavior. We demonstrate that this bias is eliminated by Fisher transforming the PRx data before CPPopt analysis. Conclusions: Cross-correlated signals are biased to show a U-shaped distribution. A “CPPopt-like” behavior will be observed more often than not even from random ICP and MAP signals that do not exhibit autoregulation unless PRx is Fisher transformed. Care must be taken in interpreting CPPopt in terms of physiology calculated from untransformed dat

Spatial distribution of metabolites in the retina and its relevance to studies of metabolic retinal disorders

Introduction: The primate retina has evolved regional specialisations for specific visual functions. The macula is specialised towards high acuity vision and is an area that contains an increased density of cone photoreceptors and signal processing neurons. Different regions in the retina display unique susceptibility to pathology, with many retinal diseases primarily affecting the macula. Objectives: To better understand the properties of different retinal areas we studied the differential distribution of metabolites across the retina. Methods: We conducted an untargeted metabolomics analysis on full-thickness punches from three different regions (macula, temporal peri-macula and periphery) of healthy primate retina. Results: Nearly half of all metabolites identified showed differential abundance in at least one comparison between the three regions. Furthermore, mapping metabolomics results from macula-specific eye diseases onto our region-specific metabolite distributions revealed differential abundance defining systemic metabolic dysregulations that were region specific. Conclusions: The unique metabolic phenotype of different retinal regions is likely due to the differential distribution of different cell types in these regions reflecting the specific metabolic requirements of each cell type. Our results may help to better understand the pathobiology of retinal diseases with region specificity

Order of same-day concurrent training influences some indices of power development, but not strength, lean mass, or aerobic fitness in healthy, moderately-active men after 9 weeks of training

Background: The importance of concurrent exercise order for improving endurance and resistance adaptations remains unclear, particularly when sessions are performed a few hours apart. We investigated the effects of concurrent training (in alternate orders, separated by ~3 hours) on endurance and resistance training adaptations, compared to resistance-only training. Materials and methods: Twenty-nine healthy, moderately-active men (mean ± SD; age 24.5 ± 4.7 y; body mass 74.9 ± 10.8 kg; height 179.7 ± 6.5 cm) performed either resistance-only training (RT, n = 9), or same-day concurrent training whereby high-intensity interval training was performed either 3 hours before (HIIT+RT, n = 10) or after resistance training (RT+HIIT, n = 10), for 3 d.wk-1 over 9 weeks. Training-induced changes in leg press 1-repetition maximal (1-RM) strength, countermovement jump (CMJ) performance, body composition, peak oxygen uptake (VO2 peak), aerobic power (W peak), and lactate threshold (W LT) were assessed before, and after both 5 and 9 weeks of training. Results: After 9 weeks, all training groups increased leg press 1-RM (~24–28%) and total lean mass (~3-4%), with no clear differences between groups. Both concurrent groups elicited similar small-to-moderate improvements in all markers of aerobic fitness (VO 2 peak ~8–9%; W LT ~16-20%; W peak ~14-15%). RT improved CMJ displacement (mean ± SD, 5.3 ± 6.3%), velocity (2.2 ± 2.7%), force (absolute: 10.1 ± 10.1%), and power (absolute: 9.8 ± 7.6%; relative: 6.0 ± 6.6%). HIIT+RT elicited comparable improvements in CMJ velocity only (2.2 ± 2.7%). Compared to RT, RT+HIIT attenuated CMJ displacement (mean difference ± 90%CI, -5.1 ± 4.3%), force (absolute: -8.2 ± 7.1%) and power (absolute: -6.0 ± 4.7%). Only RT+HIIT reduced absolute fat mass (mean ± SD, -11.0 ± 11.7%). Conclusions: In moderately-active males, concurrent training, regardless of the exercise order, presents a viable strategy to improve lower-body maximal strength and total lean mass comparably to resistance-only training, whilst also improving indices of aerobic fitness. However, improvements in CMJ displacement, force, and power were attenuated when RT was performed before HIIT, and as such, exercise order may be an important consideration when designing training programs in which the goal is to improve lower-body power. © 2020 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Auditory Deficit as a Consequence Rather than Endophenotype of Specific Language Impairment: Electrophysiological Evidence

Are developmental language disorders caused by poor auditory discrimination? This is a popular theory, but behavioural evidence has been inconclusive. Here we studied children with specific language impairment, measuring the brain's electrophysiological response to sounds in a passive paradigm. We focused on the T-complex, an event-related peak that has different origins and developmental course from the well-known vertex response.We analysed auditory event-related potentials to tones and syllables from 16 children and 16 adolescents with specific language impairment who were compared with 32 typically-developing controls, matched for gender, IQ and age.We replicated prior findings of significant reduction in Ta amplitude for both children and adolescents with specific language impairment, which was particularly marked for syllables. The topography of the T-complex to syllables indicated a less focal response in those with language impairments. To distinguish causal models, we considered correlations between size of the Ta response and measures of language and literacy in parents as well as children. The best-fitting model was one in which auditory deficit was a consequence rather than a cause of difficulties in phonological processing.The T-complex to syllables has abnormal size and topography in children with specific language impairment, but this is more likely to be a consequence rather than a cause of difficulties in phonological processing

The effect of sleep restriction, with or without high-intensity interval exercise, on myofibrillar protein synthesis in healthy young men

© 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. Key points: Sleep restriction has previously been associated with the loss of muscle mass in both human and animal models. The rate of myofibrillar protein synthesis (MyoPS) is a key variable in regulating skeletal muscle mass and can be increased by performing high-intensity interval exercise (HIIE), although the effect of sleep restriction on MyoPS is unknown. In the present study, we demonstrate that participants undergoing a sleep restriction protocol (five nights, with 4 h in bed each night) had lower rates of skeletal muscle MyoPS; however, rates of MyoPS were maintained at control levels by performing HIIE during this period. Our data suggest that the lower rates of MyoPS in the sleep restriction group may contribute to the detrimental effects of sleep loss on muscle mass and that HIIE may be used as an intervention to counteract these effects. Abstract: The present study aimed to investigate the effect of sleep restriction, with or without high-intensity interval exercise (HIIE), on the potential mechanisms underpinning previously-reported sleep-loss-induced reductions to muscle mass. Twenty-four healthy, young men underwent a protocol consisting of two nights of controlled baseline sleep and a five-night intervention period. Participants were allocated into one of three parallel groups, matched for age, (Formula presented.), body mass index and habitual sleep duration; a normal sleep (NS) group [8 h time in bed (TIB) each night], a sleep restriction (SR) group (4 h TIB each night), and a sleep restriction and exercise group (SR+EX, 4 h TIB each night, with three sessions of HIIE). Deuterium oxide was ingested prior to commencing the study and muscle biopsies obtained pre- and post-intervention were used to assess myofibrillar protein synthesis (MyoPS) and molecular markers of protein synthesis and degradation signalling pathways. MyoPS was lower in the SR group [fractional synthetic rate (% day–1), mean ± SD, 1.24 ± 0.21] compared to both the NS (1.53 ± 0.09) and SR+EX groups (1.61 ± 0.14) (P < 0.05). However, there were no changes in the purported regulators of protein synthesis (i.e. p-AKTser473 and p-mTORser2448) and degradation (i.e. Foxo1/3 mRNA and LC3 protein) in any group. These data suggest that MyoPS is acutely reduced by sleep restriction, although MyoPS can be maintained by performing HIIE. These findings may explain the sleep-loss-induced reductions in muscle mass previously reported and also highlight the potential therapeutic benefit of HIIE to maintain myofibrillar remodelling in this context

Gold nanoparticles improve metabolic profile of mice fed a high-fat diet

© 2018 The Author(s). Background: Obesity is a high risk for multiple metabolic disorders due to excessive influx of energy, glucose and lipid, often from a western based diet. Low-grade inflammation plays a key role in the progression of such metabolic disorders. The anti-inflammatory property of gold compounds has been used in treating rheumatoid arthritis in the clinic. Previously we found that pure gold nanoparticles (AuNPs, 21 nm) also possess anti-inflammatory effects on the retroperitoneal fat tissue following intraperitoneal injection, by downregulating tumor necrosis factor (TNF) α. However, whether such an effect can change the risk of metabolic disorders in the obese has not been well studied. The study employed C57BL/6 mice fed a pellet high fat diet (HFD, 43% as fat) that were treated daily with AuNPs [low (HFD-LAu) or high (HFD-HAu) dose] via intraperitoneal injection for 9 weeks. In the in vitro study, RAW264.7 macrophages and 3T3-L1 adipocytes were cultured with low and high concentrations of AuNPs alone or together. Results: The HFD-fed mice showed a significant increase in fat mass, glucose intolerance, dyslipidemia, and liver steatosis. The HFD-LAu group showed an 8% reduction in body weight, ameliorated hyperlipidemia, and normal glucose tolerance; while the HFD-HAu group had a 5% reduction in body weight with significant improvement in their glucose intolerance and hyperlipidemia. The underlying mechanism may be attributed to a reduction in adipose and hepatic local proinflammatory cytokine production, e.g. TNFα. In vitro studies of co-cultured murine RAW264.7 macrophage and 3T3-L1 adipocytes supported this proposed mechanism. Conclusion: AuNPs demonstrate a promising profile for potential management of obesity related glucose and lipid disorders and are useful as a research tool for the study of biological mechanisms

Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution

Dynamic in-situ proton (1H) magnetic resonance imaging (MRI) and 1H T2-relaxometry experiments are described in an attempt to: (i) understand the physical processes, that occur during the reconstitution of lyophilized bovine serum albumin (BSA) and monoclonal antibody (mAb) proteins; and (ii) objectify the reconstitution time