Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation

PURPOSE:There is a need for alternative analgosedatives such as dexmedetomidine in neonates. Given the ethical and practical difficulties, protocol design for clinical trials in neonates should be carefully considered before implementation. Our objective was to identify a protocol design suitable for subsequent evaluation of the dosing requirements for dexmedetomidine in mechanically ventilated neonates. METHODS: A published paediatric pharmacokinetic model was used to derive the dosing regimen for dexmedetomidine in a first-in-neonate study. Optimality criteria were applied to optimise the blood sampling schedule. The impact of sampling schedule optimisation on model parameter estimation was assessed by simulation and re-estimation procedures for different simulation scenarios. The optimised schedule was then implemented in a neonatal pilot study. RESULTS: Parameter estimates were more precise and similarly accurate in the optimised scenarios, as compared to empirical sampling (normalised root mean square error: 1673.1% vs. 13,229.4% and relative error: 46.4% vs. 9.1%). Most importantly, protocol deviations from the optimal design still allowed reasonable parameter estimation. Data analysis from the pilot group (n = 6) confirmed the adequacy of the optimised trial protocol. Dexmedetomidine pharmacokinetics in term neonates was scaled using allometry and maturation, but results showed a 20% higher clearance in this population compared to initial estimates obtained by extrapolation from a slightly older paediatric population. Clearance for a typical neonate, with a post-menstrual age (PMA) of 40 weeks and weight 3.4 kg, was 2.92 L/h. Extension of the study with 11 additional subjects showed a further increased clearance in pre-term subjects with lower PMA. CONCLUSIONS: The use of optimal design in conjunction with simulation scenarios improved the accuracy and precision of the estimates of the parameters of interest, taking into account protocol deviations, which are often unavoidable in this event-prone population

Fostering a sustainable community in batteries

As with nearly all facets of daily life, the COVID-19 pandemic has upended the traditional routines for science outreach and collaboration for battery researchers of all stripes. In-person conferences, meetings, lab visitations, and sabbaticals have largely been canceled or postponed, disrupting the typical avenues for communication between scientists, engineers, and researchers. Increasingly, researchers have developed creative ways to leverage electronic communication formats, harnessing growing online social media communities to create ad-hoc replacements for the essential functions served by these conventional in-person events. Concurrently, there has been a growing recognition of the fundamental tension between travel-intensive scientific networking and the stated goals of many research fields focused on mitigating anthropogenic climate change and environmental degradation. Recent analysis of a European economics conference estimated roughly 0.5 tonnes of CO2 emissions per participant, while the University of California Santa Barbara recently estimated that conference travel accounts for roughly 30% of its carbon footprint. Within this context, an online battery modeling community has taken shape. Centered around weekly webinars and a free-flowing Slack workspace, the community fulfills a critical need for connection between battery researchers with diverse backgrounds and interests from all over the world. The community provides new avenues for information exchange, networking, and collaboration, which we hope will persist and provide a template for global, decentralized, democratic, and emissions-friendly community-building in a post-COVID science landscape. In this Energy Focus, we describe the formation of this community, clearly state its mission, discuss initial activities, and identify challenges and opportunities moving forward

Highly efficient solid state catalysis by reconstructed (001) Ceria surface

Substrate engineering is a key factor in the synthesis of new complex materials. The substrate surface has to be conditioned in order to minimize the energy threshold for the formation of the desired phase or to enhance the catalytic activity of the substrate. The mechanism of the substrate activity, especially of technologically relevant oxide surfaces, is poorly understood. Here we design and synthesize several distinct and stable CeO(2) (001) surface reconstructions which are used to grow epitaxial films of the high-temperature superconductor YBa(2)Cu(3)O(7). The film grown on the substrate having the longest, fourfold period, reconstruction exhibits a twofold increase in performance over surfaces with shorter period reconstructions. This is explained by the crossover between the nucleation site dimensions and the period of the surface reconstruction. This result opens a new avenue for catalysis mediated solid state synthesis

Using “Tender” X-ray Ambient Pressure X-Ray Photoelectron Spectroscopy as A Direct Probe of Solid-Liquid Interface

We report a new method to probe the solid-liquid interface through the use of a thin liquid layer on a solid surface. An ambient pressure XPS (AP-XPS) endstation that is capable of detecting high kinetic energy photoelectrons (7 keV) at a pressure up to 110 Torr has been constructed and commissioned. Additionally, we have deployed a “dip & pull” method to create a stable nanometers-thick aqueous electrolyte on platinum working electrode surface. Combining the newly constructed AP-XPS system, “dip & pull” approach, with a “tender” X-ray synchrotron source (2 keV–7 keV), we are able to access the interface between liquid and solid dense phases with photoelectrons and directly probe important phenomena occurring at the narrow solid-liquid interface region in an electrochemical system. Using this approach, we have performed electrochemical oxidation of the Pt electrode at an oxygen evolution reaction (OER) potential. Under this potential, we observe the formation of both Pt(2+) and Pt(4+) interfacial species on the Pt working electrode in situ. We believe this thin-film approach and the use of “tender” AP-XPS highlighted in this study is an innovative new approach to probe this key solid-liquid interface region of electrochemistry