Early prediction of hypoxic ischaemic encephalopathy in newborn infants in a resource-limited setting

Includes bibliographical references.Hypoxic ischaemic encephalopathy (HIE) after birth is an important cause of neonatal morbidity and mortality, particularly in resource-limited regions. Therapeutic hypothermia initiated within the first 6 hours of life, in settings that can offer neonatal intensive care, is a therapy that can reduce death or severe disability in newborn infants with moderate or severe HIE. Therapeutic hypothermia has not been shown to be safe or effective in low-resource settings where neonatal intensive care is not available; however, there are situations such as in some centres in South Africa, where limited neonatal intensive care (NICU) is available against a background of moderate neonatal mortality rates, relatively low socio-economic conditions and limited capacity for long-term follow-up. In such settings, accurate case definition and early prediction of HIE and outcome may assist with the appropriate allocation of resources. The amplitude-integrated electro-encephalogram (aEEG) is an ideal tool to use for prediction of outcome and the need for cooling, but it’s availability is limited, particularly at primary and secondary hospitals

Electrostatic Contributions of Aromatic Residues in the Local Anesthetic Receptor of Voltage-Gated Sodium Channels

Antiarrhythmics, anticonvulsants, and local anesthetics target voltage-gated sodium channels, decreasing excitability of nerve and muscle cells. Channel inhibition by members of this family of cationic, hydrophobic drugs relies on the presence of highly conserved aromatic residues in the pore-lining S6 segment of the fourth homologous domain of the channel. We tested whether channel inhibition was facilitated by an electrostatic attraction between lidocaine and {pi} electrons of the aromatic rings of these residues, namely a cation-{pi} interaction. To this end, we used the in vivo nonsense suppression method to incorporate a series of unnatural phenylalanine derivatives designed to systematically reduce the negative electrostatic potential on the face of the aromatic ring. In contrast to standard point mutations at the same sites, these subtly altered amino acids preserve the wild-type voltage dependence of channel activation and inactivation. Although these phenylalanine derivatives have no effect on low-affinity tonic inhibition by lidocaine or its permanently charged derivative QX-314 at any of the substituted sites, high-affinity use-dependent inhibition displays substantial cation-{pi} energetics for 1 residue only: Phe1579 in rNaV1.4. Replacement of the aromatic ring of Phe1579 by cyclohexane, for example, strongly reduces use-dependent inhibition and speeds recovery of lidocaine-engaged channels. Channel block by the neutral local anesthetic benzocaine is unaffected by the distribution of {pi} electrons at Phe1579, indicating that our aromatic manipulations expose electrostatic contributions to channel inhibition. These results fine tune our understanding of local anesthetic inhibition of voltage-gated sodium channels and will help the design of safer and more salutary therapeutic agents

Robust exact differentiators with predefined convergence time

The problem of exactly differentiating a signal with bounded second derivative is considered. A class of differentiators is proposed, which converge to the derivative of such a signal within a fixed, i.e., a finite and uniformly bounded convergence time. A tuning procedure is derived that allows to assign an arbitrary, predefined upper bound for this convergence time. It is furthermore shown that this bound can be made arbitrarily tight by appropriate tuning. The usefulness of the procedure is demonstrated by applying it to the well-known uniform robust exact differentiator, which the considered class of differentiators includes as a special case

Evidence for voltage-dependent S4 movement in sodium channels

AbstractThe mutation R1448C substitutes a cysteine for the outermost arginine in the fourth transmembrane segment (S4) of domain 4 in skeletal muscle sodium channels. We tested the accessibility of this cysteine residue to hydrophilic methanethiosulfonate reagents applied to the extracellular surface of cells expressing these mutant channels. The reagents irreversibly increase the rate of inactivation of R1 448C, but not wild-type, channels. Cysteine modification is voltage dependent, as if depolarization extends this residue into the extracellular space. The rate of cysteine modification increases with depolarization and has the voltage dependence and kinetics expected for the movement of a voltage sensor controlling channel gating

Application of Process Mining Techniques to Support Maintenance-Related Objectives

The variety of data types generated in manufacturing environments leads to a situation where data-driven approaches for analytical maintenance support no longer have to be limited to the equipment level, but rather can be extended to further perspectives. To this end, this paper examines how process mining(PM) as an approach to extract knowledge about process-related relationships can be applied to support maintenance-related objectives. Our research is carried out by using exemplary data from a manufacturing company, where we successively take different data attributes from various source systems into account and apply selected PM techniques to demonstrate their applicability. As a result, we showcase how different insights can be provided, such as the analysis of a machine\u27s internal behavior, examination of error dependencies across multiple production steps, determination of a machine’s relevance within the equipment network or the discovery of bottlenecks regarding frequencies, cycle times and costs

Breaking waves on a dynamic Hele-Shaw beach

We report the formation of quasi-steady beaches and dunes via breaking waves in our tabletop ‘Hele-Shaw’ beach experiment. Breaking waves are generated by a wave maker, and zeolite particles act as sand. The tank is narrow, just over one-particle diameter wide, creating a quasi-2D set-up. Classical breaker types are observed on a time-scale of about a second. Beach formation under breakers occurs on a longer time-scale, and is a matter of minutes for a range of mono-chromatic wave frequencies. Alternating the wave maker motion between two frequencies generally leads to beach formation but occasionally to formation of a stable dune with water on either side. Finally, the Hele-Shaw configuration explored here experimentally lends itself to multi-scale modeling of beach dynamics

Revisiting Hele-Shaw dynamics to better understand beach evolution

Wave action, particularly during storms, drives the evo lution of beaches. Beach evolution by non-linear break ing waves is poorly understood due to its three-dimensional character, the range of scales involved, and our limited understanding of particle-wave interactions. We show how a novel, three-phase extension to the classic “Hele-Shaw” laboratory experiment can be designed that creates beach morphologies with breaking waves in a quasi-two-dimensional setting. Our thin Hele-Shaw cell simplifies the inherent complexity of three-phase dynamics: all dynamics become clearly visible and measurable. We show that beaches can be created in tens of minutes by several types of breaking waves, with about one-second periods. Quasi-steady beach morphologies emerge as function of initial water depth, at-rest bed level and wave-maker frequency. These are classified mathematically and lead to beaches, berms and sand bars