The application of local hypobaric pressure — A novel means to enhance macromolecule entry into the skin

AbstractThe local application of controlled hypobaric stress represents a novel means to facilitate drug delivery into the skin. The aims of this work were to understand how hypobaric stress modified the properties of the skin and assess if this penetration enhancement strategy could improve the percutaneous penetration of a macromolecule. Measurements of skin thickness demonstrated that the topical application of hypobaric stress thinned the tissue (p<0.05), atomic force microscopy showed that it shrunk the corneocytes in the stratum corneum (p<0.001) and the imaging of the skin hair follicles using multiphoton microscopy showed that it opened the follicular infundibula (p<0.001). Together, these changes contributed to a 19.6-fold increase in in vitro percutaneous penetration of a 10,000 molecular weight dextran molecule, which was shown using fluorescence microscopy to be localized around the hair follicles, when applied to the skin using hypobaric stress. In vivo, in the rat, a local hemodynamic response (i.e. a significant increase in blood flow, p<0.001) was shown to contribute to the increase in follicular transport of the dextran to produce a systemic absorption of 7.2±2.81fg·mL−1. When hypobaric stress was not applied to the rat there was no detectable absorption of dextran and this provided evidence that this novel penetration enhancement technique can improve the percutaneous penetration of macromolecules after topical application to the skin

Insights into the electrochemical reduction products and processes in silica anodes for next-generation lithium-ion batteries

The use of silica as a lithium‐ion battery anode material requires a pretreatment step to induce electrochemical activity. The partially reversible electrochemical reduction reaction between silica and lithium has been postulated to produce silicon, which can subsequently reversibly react with lithium, providing stable capacities higher than graphite materials. Up to now, the electrochemical reduction pathway and the nature of the products were unknown, thereby hampering the design, optimization, and wider uptake of silica‐based anodes. Here, the electrochemical reduction pathway is uncovered and, for the first time, elemental silicon is identified as a reduction product. These insights, gleaned from analysis of the current response and capacity increase during reduction, conclusively demonstrated that silica must be reduced to introduce reversible capacity and the highest capacities of 600 mAh g−1 are achieved by using a constant load discharge at elevated temperature. Characterization via total scattering X‐ray pair distribution function analysis reveal the reduction products are amorphous in nature, highlighting the need for local structural methods to uncover vital information often inaccessible by traditional diffraction. These insights contribute toward understanding the electrochemical reduction of silica and can inform the development of pretreatment processes to enable their incorporation into next‐generation lithium‐ion batteries

Assessing the Impact of Prolonged Averaging of Coronary Continuous Thermodilution Traces.

Continuous Thermodilution is a novel method of quantifying coronary flow (Q) in mL/min. To account for variability of Q within the cardiac cycle, the trace is smoothened with a 2 s moving average filter. This can sometimes be ineffective due to significant heart rate variability, ventricular extrasystoles, and deep inspiration, resulting in a fluctuating temperature trace and ambiguity in the location of the "steady state". This study aims to assess whether a longer moving average filter would smoothen any fluctuations within the continuous thermodilution traces resulting in improved interpretability and reproducibility on a test-retest basis. Patients with ANOCA underwent repeat continuous thermodilution measurements. Analysis of traces were performed at averages of 10, 15, and 20 s to determine the maximum acceptable average. The maximum acceptable average was subsequently applied as a moving average filter and the traces were re-analysed to assess the practical consequences of a longer moving average. Reproducibility was then assessed and compared to a 2 s moving average. Of the averages tested, only 10 s met the criteria for acceptance. When the data was reanalysed with a 10 s moving average filter, there was no significant improvement in reproducibility, however, it resulted in a 12% diagnostic mismatch. Applying a longer moving average filter to continuous thermodilution data does not improve reproducibility. Furthermore, it results in a loss of fidelity on the traces, and a 12% diagnostic mismatch. Overall, current practice should be maintained

The Development of International Industry Clusters: A Complexity Theory Approach

Recent research on networks and clusters as distributive systems of knowledge is drawing on complexity theory as a way of explaining the knowledge processes involved in these organizational forms. It appears that complexity theory and its component concepts, such as coevolution and self-organization, can offer some meaningful insights into, and possible explanations for, knowledge phenomena associated with networks and clusters. Using a case study approach, this paper explores the development of a New Zealand based industry cluster from early formation to international expansion, with a particular focus on the creation and dissemination of knowledge within the cluster. The observations are reported and discussed in the context of complexity theory, drawing particularly on coevolutionary principles. It is suggested that these approaches provide a useful way of understanding the process of industry cluster development and the dynamics associated with international expansion. Copyright Springer Science + Business Media, Inc. 2005clusters, evolution, complexity theory, knowledge,