The Use of High Surface Area Silica and Supercritical Carbon Dioxide to Enhance Solubility of Poorly Water-Soluble Drugs

Purpose Poor water-solubility of BCS class II drugs can limit their commercialization because of reduced oral bioavailability. It has been reported that loading of drug by adsorption onto porous silica would enhance drug solubility due to the increased surface area available for solvent diffusion. In this work, solid dispersions are formed using supercritical carbon dioxide (scCO2). The aim of this research was to characterise the solid-state properties of scCO2 dispersion and to investigate the impact of altering scCO2 processing conditions on final amorphous product performance that could lead to enhancement of drug dissolution rate for BCS class II drugs. Methods Indomethacin (IND) was purchased from Sigma-Aldrich (Dorset, UK) and was used as a model drug with two grades of high surface area silica (average particle sizes 3&[micro] and 7&[micro]), which were obtained directly from Grace-Davison (Germany). Material crystallinity was evaluated using powder X-ray diffraction (PXRD, Rigaku™, miniflex II, Japan) and high-speed differential scanning calorimetry (Hyper-DSC 8000, Perkin Elmer, USA). Materials were placed in a high-pressure vessel consisting of a CO2 cylinder, a Thar™ Technologies P50 high-pressure pump and a 750 ml high-pressure vessel (Thar, USA). Physical mixtures were exposed to CO2 gas above its critical conditions. SEM imaging and elemental analysis were conducted using a Jeol 6500 FEGSEM (Advanced MicroBeam Inc., Austria). Drug release was examined using USP type II dissolution tester (Caleva™, UK). Results The two grades of silica were found to be amorphous using PXRD and Hyper-DSC. Using PXRD, it was shown that an increase in incubation time and pressure resulted in a decrease in the crystalline content. Drug release profiles from the two different silica formulations prepared under the same conditions are shown in Figure 1. It was found that there was a significant enhancement in drug release, which was influenced, by silica type and other experiment conditions such as temperature, pressure and exposure time. SEM imaging and elemental analysis showed drug deposited inside silica pores as well as on the outer surface. Conclusion This project has shown that silica carrier platforms may be used as an alternative approach to generating polymeric solid dispersions of amorphous drugs exhibiting enhanced solubility.

Review of the area planning process (a)

The area planning process continues and formal recommendations arising from it are now being brought forward as development proposals to amalgamate or close schools. At this point in the process the Education Committee requested some comment on five different aspects of the process: the impact of Area Planning to date; the validity of the surplus school vacancy calculation methodology; the Annual Area Profile information; the Needs Model (including as appropriate the implications of the Drumragh judgement); possible enhancements to the consultation and communication process;the facilitation of alternative cross-sectoral or cross-border solutions. This paper offers high level comment on each of these issues. In addition, the Education Committee facilitated a stakeholder consultation meeting in Parliament Buildings on 4 February, 2015. The broad themes that emerged in that discussion will also be mentioned in this paper.

Review of the area planning process (b)

This paper offers a commentary on the area planning reports form primary schools published by each of the Education and Library Boards (ELB) in June 2014. The format of the reports are broadly similar for each ELB, although there are some differences amongst them. All provide an overview on the policy context for the area planning process, a statistical picture of the schools in the ELB and detail on the issues considered for sets of schools within the ELB.

The influence of area level social deprivation on preoperative disease severity and postoperative outcomes following unicompartmental knee joint replacement

BACKGROUND: This study investigated the effect of socioeconomic deprivation on preoperative disease and outcome following unicompartmental knee replacement (UKR).

METHODS: 307 Oxford UKRs implanted between 2008 and 2013 under the care of one surgeon using the same surgical technique were analysed. Deprivation was quantified using the Northern Ireland Multiple Deprivation Measure. Preoperative disease severity and postoperative outcome were measured using the Oxford Knee Score (OKS).

RESULTS: There was no difference in preoperative OKS between deprivation groups. Preoperative knee range of motion (ROM) was significantly reduced in more deprived patients with 10° less ROM than least deprived patients. Postoperatively there was no difference in OKS improvement between deprivation groups (p=0.46), with improvements of 19.5 and 21.0 units in the most and least deprived groups respectively. There was no significant association between deprivation and OKS improvement on unadjusted or adjusted analysis. Preoperative OKS, Short Form 12 mental component score and length of stay were significant independent predictors of OKS improvement. A significantly lower proportion of the most deprived group (15%) reported being able to walk an unlimited distance compared to the least deprived group (41%) one year postoperatively.

CONCLUSION: More deprived patients can achieve similar improvements in OKS to less deprived patients following UKR.

LEVEL OF EVIDENCE: 2b - retrospective cohort study of prognosis.

Joint Optimization of Area Spectral Efficiency and Delay over PPP Interfered Ad-Hoc Networks

To evaluate the performance of the co-channel transmission based communication, we propose a new metric for area spectral efficiency (ASE) of interference limited ad-hoc network by assuming that the nodes are randomly distributed according to a Poisson point processes (PPP). We introduce a utility function, U = ASE/delay and derive the optimal ALOHA transmission probability p and the SIR threshold τ that jointly maximize the ASE and minimize the local delay. Finally, numerical results have been conducted to confirm that the joint optimization based on the U metric achieves a significant performance gain compared to conventional systems.

A Largest Matching Area Approach to Image Denoising

Given the success of patch-based approaches to image denoising,this paper addresses the ill-posed problem of patch size selection.Large patch sizes improve noise robustness in the presence of good matches, but can also lead to artefacts in textured regions due to the rare patch effect; smaller patch sizes reconstruct details more accurately but risk over-fitting to the noise in uniform regions. We propose to jointly optimize each matching patch’s identity and size for gray scale image denoising, and present several implementations.The new approach effectively selects the largest matching areas, subject to the constraints of the available data and noise level, to improve noise robustness. Experiments on standard test images demonstrate our approach’s ability to improve on fixed-size reconstruction, particularly at high noise levels, on smoother image regions.

Simultaneous Measurements of the Channel Response for Multiple Eavesdroppers Operating in the Vicinity of a Body Area Network at 2.45 GHz

Channel randomness can be exploited to generate secret keys. However, to ensure secrecy, it is necessary that the channel response of any eavesdropping party remain sufficiently de-correlated with that of the legitimate users'. In this paper, we investigate whether such de-correlation occurs for a body area network (BAN) operating in an indoor environment at 2.45 GHz. The hypothetical BAN configuration consisted of two legitimate transceivers, one situated on the user's left wrist and the other on the user's waist. The eavesdroppers were positioned in either a co-located or distributed manner in the area surrounding the BAN user. Using the simultaneous channel response measured at the legitimate BAN nodes and the eavesdropper positions for stationary and mobile scenarios, we analyze the localized correlation coefficient. This allows us to determine if it is possible to generate secret keys in the presence of multiple eavesdroppers in an indoor environment. Our experimental results show that although channel reciprocity was observed for both the stationary and the mobile scenarios, a higher de-correlation between the legitimate users' channels was observed for the stationary case. This indicates that mobile scenarios are better suited for secret key generation.

Economic Stability and Economic Governance in the Euro Area:What the European Crisis Can Teach on the Limits of Economic Integration

The recent European economic crisis has dramatically exposed the failures of
the various institutional mechanisms in place to maintain economic stability
in Europe, and has unveiled the difficulty in achieving international coordination
on fiscal and financial stability policies. Drawing on the European
experience, this article analyzes the concept of economic stability in international
law and highlights the peculiar problems connected to its maintenance
or promotion. First, we demonstrate that policies that safeguard and
protect economic stability are largely regulated and managed at the national
level, due to their inextricable relationship with the exercise of national political
power. Until recently, more limited levels of pan-European integration
did not make the coordination of economic stability policies seem necessary.
However, a much deeper level of economic integration makes it very difficult
to tackle an international economic crisis through national responses. If EU
Member states wish to maintain and deepen economic integration, they
must accept an erosion of sovereignty over their economic stability policies.
This will not only deprive states of a fundamental anchor of political power,
but also create a challenge for the maintenance of democratic control over
economic policies. Second, this article argues that soft law approaches are
likely ineffective in enforcing the regulatory disciplines required to ensure
economic stability.

Wide-Area Phase-Angle Measurements for Islanding Detection—An Adaptive Nonlinear Approach

The integration of an ever growing proportion of large scale distributed renewable generation has increased the probability of maloperation of the traditional RoCoF and vector shift relays. With reduced inertia due to non-synchronous penetration in a power grid, system wide disturbances have forced the utility industry to design advanced protection schemes to prevent system degradation and avoid cascading outages leading to widespread blackouts. This paper explores a novel adaptive nonlinear approach applied to islanding detection, based on wide area phase angle measurements. This is challenging, since the voltage phase angles from different locations exhibit not only strong nonlinear but also time-varying characteristics. The adaptive nonlinear technique, called moving window kernel principal component analysis is proposed to model the time-varying and nonlinear trends in the voltage phase angle data. The effectiveness of the technique is exemplified using both DigSilent simulated cases and real test cases recorded from the Great Britain and Ireland power systems by the OpenPMU project.