Accuracy of Intravenous and Enteral Preparations Involving Small Volumes for Paediatric Use: A Review

Background: Children often need to be administered very small volumes of medicines that are authorised for use in adults. Neonatal drug delivery is particularly challenging and doses are often immeasurable with the equipment currently available. Aim: To summarise research to date on the accuracy of intravenous and enteral medicine preparation requiring small volumes (<0.1mL), with a focus on paediatric use and to identify areas for further work. Method: Twenty-three publications were identified for the narrative review via: Web of Science (1950-2016), Cumulative Index to Nursing and Allied Health Literature (1976-2016), Excerpta Medica Database (1974-2016) and International Pharmaceutical Abstracts (1970-2016) searches. Nine additional papers were identified through backward citation tracking and a further 17 were included from the personal knowledge of the review team. Results: Measurement of volumes (<0.1mL), for enteral and intravenous dosing, account for 25% of medicine manipulations within paediatric hospitals. Inaccuracies are described throughout the literature with dose administration errors attributed to technique, calculation, dilution and problems associated with equipment. Whilst standardised concentrations for intravenous infusion and drug concentrations which avoid measurement of small volumes would ameliorate problems, further work is needed to establish accurate methods for handling small volumes during the administration of medicines to children and risk minimisation strategies to support staff involved are also necessary. Conclusion: This review has revealed a paucity of information on the clinical outcomes from problems in measuring small volumes for children and highlighted the need for further work to eliminate this source of inaccurate dosing and potential for medication error

How liquid are banks : some evidence from the United Kingdom

This paper uses quantitative balance sheet liquidity analysis, based upon modified versions of the BCBS 1 and Moody’s 2 models, to provide indicators which would alarm the UK banks’ short and long-term liquidity positions respectively. These information will also underpin other research related liquidity risk to banks’ lending and performance. Our framework accurately reflect UK banks’ liquidity positions under both normal and stress scenarios based on the consistent accounting information under IFRS. It has significant contribution on Basel III liquidity ratios calculation. The study also presents fundamental financial information to facilitate analysis of banks’ business models and funding strategies. Using data for the period 2005-2010, we provide evidence that there have been variable liquidity strains across the UK banks in our sample. The estimated results show that Barclays Bank was the only bank to maintain a healthy short-term liquidity position throughout the sample period; while HSBC remained liquid in the short term, in both normal and stress conditions, except in 2008 and 2010. RBS, meanwhile, maintained healthy long-term liquidity positions from 2008 after receiving government injections of capital. And Santander UK was also able to post healthy long-term liquidity positions, except in 2009. However, the other four banks, the Bank of Scotland, Lloyds TSB, Natwest, and Standard Chartered, proved illiquid, on both a short-term and long-term basis, throughout the six-year period, with Natwest being by far the worst performer

Complexity, Development, and Evolution in Morphogenetic Collective Systems

Many living and non-living complex systems can be modeled and understood as collective systems made of heterogeneous components that self-organize and generate nontrivial morphological structures and behaviors. This chapter presents a brief overview of our recent effort that investigated various aspects of such morphogenetic collective systems. We first propose a theoretical classification scheme that distinguishes four complexity levels of morphogenetic collective systems based on the nature of their components and interactions. We conducted a series of computational experiments using a self-propelled particle swarm model to investigate the effects of (1) heterogeneity of components, (2) differentiation/re-differentiation of components, and (3) local information sharing among components, on the self-organization of a collective system. Results showed that (a) heterogeneity of components had a strong impact on the system's structure and behavior, (b) dynamic differentiation/re-differentiation of components and local information sharing helped the system maintain spatially adjacent, coherent organization, (c) dynamic differentiation/re-differentiation contributed to the development of more diverse structures and behaviors, and (d) stochastic re-differentiation of components naturally realized a self-repair capability of self-organizing morphologies. We also explored evolutionary methods to design novel self-organizing patterns, using interactive evolutionary computation and spontaneous evolution within an artificial ecosystem. These self-organizing patterns were found to be remarkably robust against dimensional changes from 2D to 3D, although evolution worked efficiently only in 2D settings.Comment: 13 pages, 8 figures, 1 table; submitted to "Evolution, Development, and Complexity: Multiscale Models in Complex Adaptive Systems" (Springer Proceedings in Complexity Series

Higher-order mode substrate integrated waveguide cavity excitation for microstrip patch antenna arrays at 30 GHz

This paper presents a novel approach to the design and fabrication of low-cost and high-gain aperture-coupled microstrip patch antenna (AC-MPA) arrays with improved radiation pattern for millimetre-wave applications such as simultaneous wireless information and power transfer (SWIPT) and Internet-of-Things (IoT) device connectivity. A higher-order mode substrate integrated waveguide (SIW) cavity is used to feed the MPA arrays through aperture coupling. The improved design approach is introduced and discussed in detail. Simulation and experimental results for 2x2 and 4x4 arrays are presented, demonstrating excellent agreement. Key performance metrics are side-lobe levels of less than -24 dB and -29 dB in the E-plane and -22 dB and -26 dB in the H-plane and realized gain of 11 dBi and 15 dBi for the 2x2 and 4x4 arrays respectively, at a design frequency of 30 GHz

Denitrification and nitrous oxide emissions from riparian forests soils exposed to prolonged nitrogen runoff

Compared to upland forests, riparian forest soils have greater potential to remove nitrate (NO3) from agricultural run-off through denitrification. It is unclear, however, whether prolonged exposure of riparian soils to nitrogen (N) loading will affect the rate of denitrification and its end products. This research assesses the rate of denitrification and nitrous oxide (N2O) emissions from riparian forest soils exposed to prolonged nutrient run-off from plant nurseries and compares these to similar forest soils not exposed to nutrient run-off. Nursery run-off also contains high levels of phosphate (PO4). Since there are conflicting reports on the impact of PO4 on the activity of denitrifying microbes, the impact of PO4 on such activity was also investigated. Bulk and intact soil cores were collected from N-exposed and non-exposed forests to determine denitrification and N2O emission rates, whereas denitrification potential was determined using soil slurries. Compared to the non-amended treatment, denitrification rate increased 2.7- and 3.4-fold when soil cores collected from both N-exposed and non-exposed sites were amended with 30 and 60 μg NO3-N g-1 soil, respectively. Net N2O emissions were 1.5 and 1.7 times higher from the N-exposed sites compared to the non-exposed sites at 30 and 60 μg NO3-N g-1 soil amendment rates, respectively. Similarly, denitrification potential increased 17 times in response to addition of 15 μg NO3-N g-1 in soil slurries. The addition of PO4 (5 μg PO4–P g-1) to soil slurries and intact cores did not affect denitrification rates. These observations suggest that prolonged N loading did not affect the denitrification potential of the riparian forest soils; however, it did result in higher N2O emissions compared to emission rates from non-exposed forests

Matrix metalloproteinase-9 activity and a downregulated Hedgehog pathway impair blood-brain barrier function in an <i>in vitro</i> model of CNS tuberculosis

Central nervous system tuberculosis (CNS TB) has a high mortality and morbidity associated with severe inflammation. The blood-brain barrier (BBB) protects the brain from inflammation but the mechanisms causing BBB damage in CNS TB are uncharacterized. We demonstrate that Mycobacterium tuberculosis (Mtb) causes breakdown of type IV collagen and decreases tight junction protein (TJP) expression in a co-culture model of the BBB. This increases permeability, surface expression of endothelial adhesion molecules and leukocyte transmigration. TJP breakdown was driven by Mtb-dependent secretion of matrix metalloproteinase (MMP)-9. TJP expression is regulated by Sonic hedgehog (Shh) through transcription factor Gli-1. In our model, the hedgehog pathway was downregulated by Mtb-stimulation, but Shh levels in astrocytes were unchanged. However, Scube2, a glycoprotein regulating astrocyte Shh release was decreased, inhibiting Shh delivery to brain endothelial cells. Activation of the hedgehog pathway by addition of a Smoothened agonist or by addition of exogenous Shh, or neutralizing MMP-9 activity, decreased permeability and increased TJP expression in the Mtb-stimulated BBB co-cultures. In summary, the BBB is disrupted by downregulation of the Shh pathway and breakdown of TJPs, secondary to increased MMP-9 activity which suggests that these pathways are potential novel targets for host directed therapy in CNS TB

A model for transition of 5 '-nuclease domain of DNA polymerase I from inert to active modes

Bacteria contain DNA polymerase I (PolI), a single polypeptide chain consisting of similar to 930 residues, possessing DNA-dependent DNA polymerase, 3'-5' proofreading and 5'-3' exonuclease (also known as flap endonuclease) activities. PolI is particularly important in the processing of Okazaki fragments generated during lagging strand replication and must ultimately produce a double-stranded substrate with a nick suitable for DNA ligase to seal. PolI's activities must be highly coordinated both temporally and spatially otherwise uncontrolled 5'-nuclease activity could attack a nick and produce extended gaps leading to potentially lethal double-strand breaks. To investigate the mechanism of how PolI efficiently produces these nicks, we present theoretical studies on the dynamics of two possible scenarios or models. In one the flap DNA substrate can transit from the polymerase active site to the 5'-nuclease active site, with the relative position of the two active sites being kept fixed; while the other is that the 5'-nuclease domain can transit from the inactive mode, with the 5'-nuclease active site distant from the cleavage site on the DNA substrate, to the active mode, where the active site and substrate cleavage site are juxtaposed. The theoretical results based on the former scenario are inconsistent with the available experimental data that indicated that the majority of 5'-nucleolytic processing events are carried out by the same PolI molecule that has just extended the upstream primer terminus. By contrast, the theoretical results on the latter model, which is constructed based on available structural studies, are consistent with the experimental data. We thus conclude that the latter model rather than the former one is reasonable to describe the cooperation of the PolI's polymerase and 5'-3' exonuclease activities. Moreover, predicted results for the latter model are presented

Moderate and heavy metabolic stress interval training improve arterial stiffness and heart rate dynamics in humans

Traditional continuous aerobic exercise training attenuates age-related increases of arterial stiffness, however, training studies have not determined whether metabolic stress impacts these favourable effects. Twenty untrained healthy participants (n = 11 heavy metabolic stress interval training, n = 9 moderate metabolic stress interval training) completed 6 weeks of moderate or heavy intensity interval training matched for total work and exercise duration. Carotid artery stiffness, blood pressure contour analysis, and linear and non-linear heart rate variability were assessed before and following training. Overall, carotid arterial stiffness was reduced (p  0.05). This study demonstrates the effectiveness of interval training at improving arterial stiffness and autonomic function, however, the metabolic stress was not a mediator of this effect. In addition, these changes were also independent of improvements in aerobic capacity, which were only induced by training that involved a high metabolic stress