A Novel, Fast, Reliable, and Data-Driven Method for Simultaneous Single-Trial Mining and Amplitude—Latency Estimation Based on Proximity Graphs and Network Analysis

Both amplitude and latency of single-trial EEG/MEG recordings provide valuable information regarding functionality of the human brain. In this article, we provided a data-driven graph and network-based framework for mining information from multi-trial event-related brain recordings. In the first part, we provide the general outline of the proposed methodological approach. In the second part, we provide a more detailed illustration, and present the obtained results on every step of the algorithmic procedure. To justify the proposed framework instead of presenting the analytic data mining and graph-based steps, we address the problem of response variability, a prerequisite to reliable estimates for both the amplitude and latency on specific N/P components linked to the nature of the stimuli. The major question addressed in this study is the selection of representative single-trials with the aim of uncovering a less noisey averaged waveform elicited from the stimuli. This graph and network-based algorithmic procedure increases the signal-to-noise (SNR) of the brain response, a key pre-processing step to reveal significant and reliable amplitude and latency at a specific time after the onset of the stimulus and with the right polarity (N or P). We demonstrated the whole approach using electroencephalography (EEG) auditory mismatch negativity (MMN) recordings from 42 young healthy controls. The method is novel, fast and data-driven succeeding first to reveal the true waveform elicited by MMN on different conditions (frequency, intensity, duration, etc.). The proposed graph-oriented algorithmic pipeline increased the SNR of the characteristic waveforms and the reliability of amplitude and latency within the adopted cohort. We also demonstrated how different EEG reference schemes (REST vs. average) can influence amplitude-latency estimation. Simulation results revealed robust amplitude-latency estimations under different SNR and amplitude-latency variations with the proposed algorithm

Gestational age and hospital utilization : three-years follow-up of an area-based birth cohort

OBJECTIVE: To investigate differences by gestational age in emergency department visits and re-hospitalizations during the three years following childbirth discharge. METHODS: We performed a historical cohort study in Lazio Region, Italy, for infants born in 2007-2008 to resident mothers. Health administrative data were used. Analysis was performed by multinomial logistic regression. RESULTS: Of 90 545 infants, more than 50% had at least one emergency department visit, and 18.8% at least one re-hospitalization. After the exclusion of infants with congenital anomalies, relative risk ratios of re-hospitalization and, to a lesser extent, of emergency department visits increased by decreasing gestational age; the two events were also higher for mothers ≤35 years of age, with low education and of Italian nationality. Residency outside the metropolitan area was associated with an increased risk of re-hospitalization and a decreased risk of emergency department visits. CONCLUSION: During the three years following childbirth discharge, re-hospitalizations and, to a lesser extent, emergency department use are inversely related to gestational age at birth; socio-demographic factors have an effect on the risk of infant use of hospital resources independent of gestational age

Thermodynamic calculations of oxygen self-diffusion in mixed-oxide nuclear fuels

Molecular dynamics calculations are used to provide a self-consistent prediction of the elastic, thermal expansion and oxygen self-diffusion properties of mixed oxide nuclear fuels at arbitrary compositions.</p

Bridging the gap between the gas and solution phase : solvent specific photochemistry in 4-tert-butylcatechol

Eumelanin is a naturally synthesized ultraviolet light absorbing biomolecule, possessing both photoprotective and phototoxic properties. We infer insight into these properties of eumelanin using a bottom-up approach, by investigating a subunit analogue, 4-tert-butylcatechol. Utilizing a combination of femtosecond transient electronic absorption spectroscopy and time-re-solved velocity map ion imaging, our results suggest an environmental-dependent relaxation pathway, following irradiation at 267 nm to populate the S1 (1ππ*) state. Gas-phase and non-polar solution-phase measurements reveal that the S1 state decays through coupling onto the S2 (1πσ*) state that is dissociative along the non-intramolecular hydrogen bonded ‘free’ O–H bond. This process is mediated by tunneling beneath an S1/S2 conical intersection and occurs in 4.9 ± 0.6 ps in the gas-phase and 27 ± 7 ps in the non-polar cyclohexane solution. Comparative studies on the deuterated isotopologue of 4-tert-butylcatechol in both the gas- and solution-phase (cyclohexane) reveals an average kinetic isotope effect of ~19 and ~7, respectively, supportive of O–H dissociation mediated by a quantum tunneling mechanism. In contrast, in the polar acetonitrile, the S1 state decays on a much longer timescale of 1.7 ± 0.1 ns. We propose that the S1 decay is now multicomponent, likely driven by internal conversion, intersystem crossing and fluorescence, as well as O–H dissociation. The attribution of conformer driven excited state dynamics to explain how the S1 state decays in the gas- and non-polar solution-phase versus the polar solution-phase, elegantly demonstrates the influence the environment has on the ensuing excited state dynamics

Excited-state dynamics of a two-photon-activatable ruthenium prodrug

We present a new approach to investigate how the photodynamics of an octahedral ruthenium(II) complex activated through two-photon absorption (TPA) differ from the equivalent complex activated through one-photon absorption (OPA). We photoactivated a RuII polypyridyl complex containing bioactive monodentate ligands in the photodynamic therapy window (620–1000 nm) by using TPA and used transient UV/Vis absorption spectroscopy to elucidate its reaction pathways. Density functional calculations allowed us to identify the nature of the initially populated states and kinetic analysis recovers a photoactivation lifetime of approximately 100 ps. The dynamics displayed following TPA or OPA are identical, showing that TPA prodrug design may use knowledge gathered from the more numerous and easily conducted OPA studies

An RNA interference-based screen of transcription factor genes identifies pathways necessary for sensory regeneration in the avian inner ear

Sensory hair cells of the inner ear are the mechano-electric transducers of sound and head motion. In mammals, damage to sensory hair cells leads to hearing or balance deficits. Non-mammalian vertebrates such as birds can regenerate hair cells after injury. In a previous study, we characterized transcription factor gene expression during chicken hair cell regeneration. In those studies, a laser micro-beam or ototoxic antibiotics were used to damage the sensory epithelia (SE). The current study focused on 27 genes that were up-regulated in regenerating SE compared to untreated SE in the previous study. Those genes were knocked down by siRNA, to determine their requirement for supporting cell proliferation and to measure resulting changes in the larger network of gene expression. We identified 11 genes necessary for proliferation and also identified novel interactive relationships between many of them. Defined components of the WNT, PAX and AP1 pathways were shown to be required for supporting cell proliferation. These pathways intersect on WNT4, which is also necessary for proliferation. Among the required genes, the CCAAT enhancer binding protein, CEBPG, acts downstream of Jun Kinase and JUND in the AP1 pathway. The WNT co-receptor LRP5 acts downstream of CEBPG as does the transcription factor BTAF1. Both of these genes are also necessary for supporting cell proliferation. This is the first large scale screen of its type and suggests an important intersection between the AP1 pathway, the PAX pathway and WNT signaling in the regulation of supporting cell proliferation during inner ear hair cell regeneration

Protocolised non-invasive compared with invasive weaning from mechanical ventilation for adults in intensive care : the Breathe RCT

Background: Invasive mechanical ventilation (IMV) is a life-saving intervention. Following resolution of the condition that necessitated IMV, a spontaneous breathing trial (SBT) is used to determine patient readiness for IMV discontinuation. In patients who fail one or more SBTs, there is uncertainty as to the optimum management strategy. Objective: To evaluate the clinical effectiveness and cost-effectiveness of using non-invasive ventilation (NIV) as an intermediate step in the protocolised weaning of patients from IMV. Design: Pragmatic, open-label, parallel-group randomised controlled trial, with cost-effectiveness analysis. Setting: A total of 51 critical care units across the UK. Participants: Adult intensive care patients who had received IMV for at least 48 hours, who were categorised as ready to wean from ventilation, and who failed a SBT. Interventions: Control group (invasive weaning): patients continued to receive IMV with daily SBTs. A weaning protocol was used to wean pressure support based on the patient’s condition. Intervention group (non-invasive weaning): patients were extubated to NIV. A weaning protocol was used to wean inspiratory positive airway pressure, based on the patient’s condition. Main outcome measures: The primary outcome measure was time to liberation from ventilation. Secondary outcome measures included mortality, duration of IMV, proportion of patients receiving antibiotics for a presumed respiratory infection and health-related quality of life. Results: A total of 364 patients (invasive weaning, n = 182; non-invasive weaning, n = 182) were randomised. Groups were well matched at baseline. There was no difference between the invasive weaning and non-invasive weaning groups in median time to liberation from ventilation {invasive weaning 108 hours [interquartile range (IQR) 57–351 hours] vs. non-invasive weaning 104.3 hours [IQR 34.5–297 hours]; hazard ratio 1.1, 95% confidence interval [CI] 0.89 to 1.39; p = 0.352}. There was also no difference in mortality between groups at any time point. Patients in the non-invasive weaning group had fewer IMV days [invasive weaning 4 days (IQR 2–11 days) vs. non-invasive weaning 1 day (IQR 0–7 days); adjusted mean difference –3.1 days, 95% CI –5.75 to –0.51 days]. In addition, fewer non-invasive weaning patients required antibiotics for a respiratory infection [odds ratio (OR) 0.60, 95% CI 0.41 to 1.00; p = 0.048]. A higher proportion of non-invasive weaning patients required reintubation than those in the invasive weaning group (OR 2.00, 95% CI 1.27 to 3.24). The within-trial economic evaluation showed that NIV was associated with a lower net cost and a higher net effect, and was dominant in health economic terms. The probability that NIV was cost-effective was estimated at 0.58 at a cost-effectiveness threshold of £20,000 per quality-adjusted life-year. Conclusions: A protocolised non-invasive weaning strategy did not reduce time to liberation from ventilation. However, patients who underwent non-invasive weaning had fewer days requiring IMV and required fewer antibiotics for respiratory infections. Future work: In patients who fail a SBT, which factors predict an adverse outcome (reintubation, tracheostomy, death) if extubated and weaned using NIV? Trial registration: Current Controlled Trials ISRCTN15635197. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 48. See the NIHR Journals Library website for further project information

Architectural and biochemical adaptations in skeletal muscle and bone following rotator cuff injury in a rat model

BACKGROUND: Injury to the rotator cuff can cause irreversible changes to the structure and function of the associated muscles and bones. The temporal progression and pathomechanisms associated with these adaptations are unclear. The purpose of this study was to investigate the time course of structural muscle and osseous changes in a rat model of a massive rotator cuff tear. METHODS: Supraspinatus and infraspinatus muscle architecture and biochemistry and humeral and scapular morphological parameters were measured three days, eight weeks, and sixteen weeks after dual tenotomy with and without chemical paralysis via botulinum toxin A (BTX). RESULTS: Muscle mass and physiological cross-sectional area increased over time in the age-matched control animals, decreased over time in the tenotomy+BTX group, and remained nearly the same in the tenotomy-alone group. Tenotomy+BTX led to increased extracellular collagen in the muscle. Changes in scapular bone morphology were observed in both experimental groups, consistent with reductions in load transmission across the joint. CONCLUSIONS: These data suggest that tenotomy alone interferes with normal age-related muscle growth. The addition of chemical paralysis yielded profound structural changes to the muscle and bone, potentially leading to impaired muscle function, increased muscle stiffness, and decreased bone strength. CLINICAL RELEVANCE: Structural musculoskeletal changes occur after tendon injury, and these changes are severely exacerbated with the addition of neuromuscular compromise