Pharmacotherapy for neonatal seizures: current knowledge and future perspectives

Seizures are the most common neurological emergencies in the neonatal period and are associated with poor neurodevelopmental outcomes. Seizures affect up to five per 1000 term births and population-based studies suggest that they occur even more frequently in premature infants. Seizures are a sign of an underlying cerebral pathology, the most common of which is hypoxic-ischaemic encephalopathy in term infants. Due to a growing body of evidence that seizures exacerbate cerebral injury, effective diagnosis and treatment of neonatal seizures is of paramount importance to reduce long-term adverse outcomes. Electroencephalography is essential for the diagnosis of seizures in neonates due to their subtle clinical expression, non-specific neurological presentation and a high frequency of electro-clinical uncoupling in the neonatal period. Hypoxic-ischaemic encephalopathy may require neuroprotective therapeutic hypothermia, accompanying sedation with opioids, anticonvulsant drugs or a combination of all of these. The efficacy, safety, tolerability and pharmacokinetics of seven anticonvulsant drugs (phenobarbital, phenytoin, levetiracetam, lidocaine, midazolam, topiramate and bumetanide) are reviewed. This review is focused only on studies reporting electrographically confirmed seizures and highlights the knowledge gaps that exist in optimal treatment regimens for neonatal seizures. Randomised controlled trials are needed to establish a safe and effective treatment protocol for neonatal seizures

An evaluation of an after-school soccer program for at-risk sixth grade boys using the TPSR model

The Soccer Coaching Club program utilized the Teaching Personal and Social Responsibility (TPSR) model in an after-school soccer program for sixth grade boys between 11 and 12 in a local middle school. Soccer, as the featured physical activity, provided the "hook" for regular attendance. Desired outcomes included improved self-control, respect, and cooperation with others. Research efforts included formative program evaluation, focusing on fidelity to the TPSR model, and summative evaluations of immediate impacts on participant understanding of TPSR concepts and participant behavior, as part of the program evaluation. A mixed methods approach was utilized, and data was gathered through a validated survey instrument, a program narrative, and post-program interview with the participants' classroom teachers. Using the two factor model of analysis of the survey data (Li, et al, 2008), the program evaluation yielded statistically significant improvements in the factor of social responsibility, although no statistically significant change was measured in the second area, personal responsibility. The observational data including the program narrative and the data gathered through the validated observational instrument provided evidence of frequent use of the strategies associated with fidelity in implementing a TPSR program and participant behaviors consistent with TPSR learning. The post-program interview with the participants' classroom teachers yielded observations that indicated some element of transference of program principles to the classroom, and both the classroom teachers and the school's leadership expressed overwhelming support for the program's return next spring and a desire for similar programs in the fall, another indicator of a successful program

Time-resolved pump-probe spectroscopy with spectral domain ghost imaging

An atomic-level picture of molecular and bulk processes, such as chemical bonding and charge transfer, necessitates an understanding of the dynamical evolution of these systems. On the ultrafast timescales associated with nuclear and electronic motion, the temporal behaviour of a system is often interrogated in a 'pump-probe' scheme. Here, an initial 'pump' pulse triggers dynamics through photoexcitation, and after a carefully controlled delay a 'probe' pulse initiates projection of the instantaneous state of the evolving system onto an informative measurable quantity, such as electron binding energy. In this paper, we apply spectral ghost imaging to a pump-probe time-resolved experiment at an X-ray free-electron laser (XFEL) facility, where the observable is spectral absorption in the X-ray regime. By exploiting the correlation present in the shot-to-shot fluctuations in the incoming X-ray pulses and measured electron kinetic energies, we show that spectral ghost imaging can be applied to time-resolved pump-probe measurements. In the experiment presented, interpretation of the measurement is simplified because spectral ghost imaging separates the overlapping contributions to the photoelectron spectrum from the pump and probe pulse

Inner Valence Hole Migration in Isopropanol

Even within the sudden approximation, the removal of one neutral Hartree-Fock orbital does not leave the molecule in a pure one-hole state of the cation; coupling to virtual orbitals leads to a breakdown in the molecular orbital picture. This can be understood as interaction with two-hole one-particle states (singly excited cations) and becomes significant when those states are energetically similar to the one-hole states. This splitting of states is most relevant for inner valence holes which lie above the double ionisation potential. As such, impulsive creation of an inner valence hole (IVH) wavepacket results in a time dependent charge density which is purely electronic in nature (charge migration) [1] , [2] , though it depends on the nuclear geometry at the time of excitation, and subsequent nuclear motion will result in decoherence [3]

Integronlike Structures in Campylobacter spp. of Human and Animal Origin

Resistance to antimicrobial agents used to treat severe Campylobacter spp. gastroenteritis is increasing worldwide. We assessed the antimicrobial resistance patterns of Campylobacter spp. isolates of human and animal origin. More than half (n = 32) were resistant to sulphonamide, a feature known to be associated with the presence of integrons. Analysis of these integrons will further our understanding of Campylobacter spp. epidemiology

Poly(ethylene glycol)-Based Peptidomimetic “PEGtide” of Oligo-Arginine allows for efficient siRNA Transfection and gene inhibition

While a wide range of experimental and commercial transfection reagents are currently available, persistent problems remain regarding their suitability for continued development. These include the transfection efficiency for difficult-to-transfect cell types and the risks of decreased cell viability that may arise from any transfection that does occur. Therefore, research is now turning toward alternative molecules that improve the toxicity profile of the gene delivery vector (GDV), while maintaining the transfection efficiency. Among them, cell-penetrating peptides, such as octa-arginine, have shown significant potential as GDVs. Their pharmacokinetic and pharmacodynamic properties can be enhanced through peptidomimetic conversion, whereby a peptide is modified into a synthetic analogue that mimics its structure and/or function, but whose backbone is not solely based on α-amino acids. Using this technology, novel peptidomimetics were developed by co- and postpolymerization functionalization of substituted ethylene oxides, producing poly(ethylene glycol) (PEG)-based peptidomimetics termed “PEGtides”. Specifically, a PEGtide of the poly(α-amino acid) oligo-arginine [poly(glycidylguanidine)] was assessed for its ability to complex and deliver a small interfering ribonucleic acid (siRNA) using a range of cell assays and high-content analysis. PEGtide–siRNA demonstrated significantly increased internalization and gene inhibition over 24 h in Calu-3 pulmonary epithelial cells compared to commercial controls and octa-arginine-treated samples, with no evidence of toxicity. Furthermore, PEGtide–siRNA nanocomplexes can provide significant levels of gene inhibition in “difficult-to-transfect” mouse embryonic hypothalamic (mHypo N41) cells. Overall, the usefulness of this novel PEGtide for gene delivery was clearly demonstrated, establishing it as a promising candidate for continued translational research

Single Lateral Mode Mid-Infrared Laser Diode using Sub-Wavelength Modulation of the Facet Reflectivity

The characteristics of mid-infrared laser diodes have been investigated before and after the patterning of sub-wavelength metallic apertures on the emitting facet. Before modification of the facet the emitted spectrum consisted of a large number of peaks associated with different spatial modes, whereas afterwards the spectrum was dominated by a single peak. Simulations showed that the patterning of the facet caused the effective reflectivity to be different for each lateral mode, suggesting that the peak in the measured spectra is associated with the single lateral mode which is most strongly reflected from the modified facet.Comment: 12 pages, 3 figure

A selective metasurface absorber with an amorphous carbon interlayer for solar thermal applications

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordData availability: Data shown in this paper is accessible via the University of Bristol data repository: 10.5523/bris.11twobtdyxfs1ib2fxhlvn107This paper presents fabrication, measurement and modelling results for a metal-dielectric-metal metasurface absorber for solar thermal applications. The structure uses amorphous carbon as an inter-layer between thin gold films with the upper film patterned with a 2D periodic array using focused ion beam etching. The patterned has been optimised to give high absorptance from 400-1200nm and low absorptance above this wavelength range to minimise thermal radiation and hence obtain higher temperature performance. Wide angle absorptance results are shown and detailed modelling of a realistic nanostructured upper layer results in excellent agreement between measured and modelled results. The use of gold in this paper is a first step towards a high temperature metasurface where gold can be replaced by other refractory metals such as tungsten or chrome.Engineering and Physical Sciences Research Council (EPSRC