Motor and executive function at 6 years of age after extremely preterm birth

BACKGROUND. Studies of very preterm infants have demonstrated impairments in multiple neurocognitive domains. We hypothesized that neuromotor and executive- function deficits may independently contribute to school failure. METHODS.We studied children who were born at 25 completed weeks’ gestation in the United Kingdom and Ireland in 1995 at early school age. Children underwent standardized cognitive and neuromotor assessments, including the Kaufman Assessment Battery for Children and NEPSY, and a teacher-based assessment of academic achievement. RESULTS. Of 308 surviving children, 241 (78%) were assessed at a median age of 6 years 4 months. Compared with 160 term classmates, 180 extremely preterm children without cerebral palsy and attending mainstream school performed less well on 3 simple motor tasks: posting coins, heel walking, and 1-leg standing. They more frequently had non–right-hand preferences (28% vs 10%) and more associated/ overflow movements during motor tasks. Standardized scores for visuospatial and sensorimotor function performance differed from classmates by 1.6 and 1.1 SDs of the classmates’ scores, respectively. These differences attenuated but remained significant after controlling for overall cognitive scores. Cognitive, visuospatial scores, and motor scores explained 54% of the variance in teachers’ ratings of performance in the whole set; in the extremely preterm group, additional variance was explained by attention-executive tasks and gender. CONCLUSIONS. Impairment of motor, visuospatial, and sensorimotor function, including planning, self-regulation, inhibition, and motor persistence, contributes excess morbidity over cognitive impairment in extremely preterm children and contributes independently to poor classroom performance at 6 years of age

The EPICure study : growth and blood pressure at 6 years of age following extremely preterm birth

Background: Preterm children are at risk for reduced growth in early childhood, which may predispose them to later changes in blood pressure. We studied growth and blood pressure (BP) in extremely preterm (EP) children at age 6 years. Methods: We evaluated children who were born at 25 completed weeks of gestation or less in the United Kingdom and Ireland in 1995 when they reached early school age. Children underwent standardized assessments, including auxology and sitting blood pressure. Results: Of 308 surviving children, 241 (78 percent) were assessed at a median age of 6 years 4 months; 160 full term classmates acted as a comparison group. Compared to classmates, EP children were 1.2 standard deviations (SD) lighter, 0.97SD shorter, BMI was 0.95SD lower and head circumference 1.3SD lower. Compared to 2.5 years of age, EP children showed catch up in terms of weight by 0.37SD, height by 0.42SD and head circumference by 0.13SD. Systolic and diastolic BP were lower by 2.3mmHg and 2.4mmHg respectively in EP children but these differences were accounted for by differences in height and BMI. Maternal smoking in pregnancy was associated with lower BP, children born before 24 weeks had higher systolic and children given postnatal steroids higher diastolic pressures. Conclusions: Poor postnatal growth seen after birth and at in the third year persists into school age. Catch up growth reduces some of the early deficit but is least for head growth. Despite serious postnatal growth restriction blood pressure appears similar in both EP and term classmates

Forward Stochastic Reachability Analysis for Uncontrolled Linear Systems using Fourier Transforms

We propose a scalable method for forward stochastic reachability analysis for uncontrolled linear systems with affine disturbance. Our method uses Fourier transforms to efficiently compute the forward stochastic reach probability measure (density) and the forward stochastic reach set. This method is applicable to systems with bounded or unbounded disturbance sets. We also examine the convexity properties of the forward stochastic reach set and its probability density. Motivated by the problem of a robot attempting to capture a stochastically moving, non-adversarial target, we demonstrate our method on two simple examples. Where traditional approaches provide approximations, our method provides exact analytical expressions for the densities and probability of capture.Comment: V3: HSCC 2017 (camera-ready copy), DOI updated, minor changes | V2: Review comments included | V1: 10 pages, 12 figure

An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials

This document is the Accepted Manuscript version of the following article: Reinoud Maex, ‘An Interneuron Circuit Reproducing Essential Spectral Features of Field Potentials’, Neural Computation, March 2018. Under embargo until 22 June 2018. The final, definitive version of this paper is available online at doi: https://doi.org/10.1162/NECO_a_01068. © 2018 Massachusetts Institute of Technology. Content in the UH Research Archive is made available for personal research, educational, and non-commercial purposes only. Unless otherwise stated, all content is protected by copyright, and in the absence of an open license, permissions for further re-use should be sought from the publisher, the author, or other copyright holder.Recent advances in engineering and signal processing have renewed the interest in invasive and surface brain recordings, yet many features of cortical field potentials remain incompletely understood. In the present computational study, we show that a model circuit of interneurons, coupled via both GABA(A) receptor synapses and electrical synapses, reproduces many essential features of the power spectrum of local field potential (LFP) recordings, such as 1/f power scaling at low frequency (< 10 Hz) , power accumulation in the γ-frequency band (30–100 Hz), and a robust α rhythm in the absence of stimulation. The low-frequency 1/f power scaling depends on strong reciprocal inhibition, whereas the α rhythm is generated by electrical coupling of intrinsically active neurons. As in previous studies, the γ power arises through the amplifica- tion of single-neuron spectral properties, owing to the refractory period, by parameters that favour neuronal synchrony, such as delayed inhibition. The present study also confirms that both synaptic and voltage-gated membrane currents substantially contribute to the LFP, and that high-frequency signals such as action potentials quickly taper off with distance. Given the ubiquity of electrically coupled interneuron circuits in the mammalian brain, they may be major determinants of the recorded potentials.Peer reviewe

DSPSR: Digital Signal Processing Software for Pulsar Astronomy

DSPSR is a high-performance, open-source, object-oriented, digital signal processing software library and application suite for use in radio pulsar astronomy. Written primarily in C++, the library implements an extensive range of modular algorithms that can optionally exploit both multiple-core processors and general-purpose graphics processing units. After over a decade of research and development, DSPSR is now stable and in widespread use in the community. This paper presents a detailed description of its functionality, justification of major design decisions, analysis of phase-coherent dispersion removal algorithms, and demonstration of performance on some contemporary microprocessor architectures.Comment: 15 pages, 10 figures, to be published in PAS

Drying techniques for the visualisation of agarose-based chromatography media by scanning electron microscopy

The drying of chromatography resins prior to scanning electron microscopy is critical to image resolution and hence understanding of the bead structure at sub-micron level. Achieving suitable drying conditions is especially important with agarose-based chromatography resins, as over-drying may cause artefact formation, bead damage and alterations to ultrastructural properties; and under-drying does not provide sufficient resolution for visualisation under SEM. This paper compares and contrasts the effects of two drying techniques, critical point drying and freeze drying, on the morphology of two agarose based resins (MabSelect(TM) : dw ~ 85 µm and Capto(TM) Adhere: dw ~75 µm) and provides a complete method for both. The results show that critical point drying provides better drying and subsequently clearer ultrastructural visualisation of both resins under SEM. Under this protocol both the polymer fibres (thickness ~20 nm) and the pore sizes (diameter ~100 nm) are clearly visible. Freeze drying is shown to cause bead damage to both resins, but to different extents. MabSelect resin encounters extensive bead fragmentation, whilst Capto Adhere resin undergoes partial bead disintegration, corresponding with the greater extent of agarose crosslinking and strength of this resin. While freeze drying appears to be the less favourable option for ultrastructural visualisation of chromatography resin, it should be noted that the extent of fracturing caused by the freeze drying process may provide some insight into the mechanical properties of agarose-based chromatography media

Analysis of fouling and breakthrough of process related impurities during depth filtration using confocal microscopy

Titer improvement has driven process intensification in mAb manufacture. However, this has come with the drawback of high cell densities and associated process related impurities such as cell debris, host cell protein (HCP), and DNA. This affects the capacity of depth filters and can lead to carryover of impurities to protein A chromatography leading to early resin fouling. New depth filter materials provide the opportunity to remove more process related impurities at this early stage in the process. Hence, there is a need to understand the mechanism of impurity removal within these filters. In this work, the secondary depth filter Millistak+ X0HC (cellulose and diatomaceous earth) is compared with the X0SP (synthetic), by examining the breakthrough of DNA and HCP. Additionally, a novel method was developed to image the location of key impurities within the depth filter structure under a confocal microscope. Flux, tested at 75, 100, and 250 LMH was found to affect the maximal throughput based on the max pressure of 30 psi, but no significant changes were seen in the HCP and DNA breakthrough. However, a drop in cell culture viability, from 87% to 37%, lead to the DNA breakthrough at 10% decreasing from 81 to 55 L/m2 for X0HC and from 105 to 47 L/m2 for X0SP. The HCP breakthrough was not affected by cell culture viability or filter type. The X0SP filter has a 30%–50% higher max throughput depending on viability, which can be explained by the confocal imaging where the debris and DNA are distributed differently in the layers of the filter pods, with more of the second tighter layer being utilized in the X0SP

Reactor Design for Continuous Monoclonal Antibody Precipitation Based Upon Micro‐mixing

BACKGROUND: Precipitation has been applied for the processing of important therapeutics, including monoclonal antibodies (mAbs). The scale‐up has proven to be a challenging task due to the complexity of the reactions and transport processes involved. This requires a good understanding of the molecular processes underpinning precipitate formation. The aim of this study was to build a micro‐mixing model for the precipitation of a mAb in continuous tubular reactors using ammonium sulphate. The effect of micro‐mixing on precipitate formation (with respect to size, strength, and nature) was evaluated. An ultra scale‐down (USD) centrifugation methodology was applied to determine the ease of precipitate clarification. RESULTS: The results demonstrated that the final mean particle size decreased with increased micro‐mixing, and was obtained with short residence times. Antibody yields in the tubular reactors were consistently above 90% and were shown to be independent of the mixing. Similar particle sizes between a lab and pilot‐scale reactor were correlated with the average energy dissipation rate. The smaller particles obtained from improved micro‐mixing had higher fractal dimensions that correlated with minimal breakage upon exposure to turbulent shear. Precipitates were easily clarified at the USD scale (> 95% clarification), but less so at pilot‐scale (< 80% clarification). CONCLUSION: Precipitation is a rapid process where the final precipitate properties are controlled by the flow conditions. Therefore, the process can be manipulated to acquire a certain particle size range. A high‐throughput precipitation process is also possible. However, further investigation into large‐scale precipitate recovery is required. © 2020 Society of Chemical Industr

Green's function of a finite chain and the discrete Fourier transform

A new expression for the Green's function of a finite one-dimensional lattice with nearest neighbor interaction is derived via discrete Fourier transform. Solution of the Heisenberg spin chain with periodic and open boundary conditions is considered as an example. Comparison to Bethe ansatz clarifies the relation between the two approaches.Comment: preprint of the paper published in Int. J. Modern Physics B Vol. 20, No. 5 (2006) 593-60

Observation of Phase Separation in a Strongly-Interacting Imbalanced Fermi Gas

We have observed phase separation between the superfluid and the normal component in a strongly interacting Fermi gas with imbalanced spin populations. The in situ distribution of the density difference between two trapped spin components is obtained using phase-contrast imaging and 3D image reconstruction. A shell structure is clearly identified where the superfluid region of equal densities is surrounded by a normal gas of unequal densities. The phase transition induces a dramatic change in the density profiles as excess fermions are expelled from the superfluid.Comment: 5 pages, 7 figure