The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): Study protocol for a randomized controlled trial

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care.EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care.

METHODS/DESIGN: EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible.The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events.A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate.

TRIAL REGISTRATION: ISRCTN44464607.

Cataract extraction and intraocular lens implantation in anterior megalophthalmos

This report describes the implantation of a standard posterior chamber intraocular lens (IOL) in a patient with bilateral cataract and anterior megalophthalmos. After extracapsular cataract extraction, the IOL was sutured to the posterior surface of the iris and anterior capsule. Different types of IOLs were used in each eye, and the surgical technique was adapted to the characteristics of the IOL. No complications were noted. Visual rehabilitation was successful. Extracapsular cataract extraction with a posterior chamber IOL sutured to the posterior surface of the iris and anterior capsule is a useful option in patients with anterior megalophthalmos and cataract.

Spatial autocorrelation in the response of soft-bottom marine benthos to gas extraction activities: The case of amphipods in the Ionian Sea

The spatial distributions of marine fauna and of pollution are both highly structured, and thus the resulting high levels of autocorrelation may invalidate conclusions based on classical statistical approaches. Here we analyse the close correlation observed between proxies for the disturbance associated with gas extraction activities and amphipod distribution patterns around four hydrocarbon platforms. We quantified the amount of variation independently accounted for by natural environmental variables, proxies for the disturbance caused by platforms, and spatial autocorrelation. This allowed us to demonstrate how each of these three factors significantly affects the community structure of amphipods. Sophisticated statistical techniques are required when taking into account spatial autocorrelation: nevertheless our data demonstrate that this approach not only enables the formulation of robust statistical inferences but also provides a much deeper understanding of the subtle interactions between human disturbance and natural factors affecting the structure of marine invertebrates communities. (C) 2012 Elsevier Ltd. All rights reserved.

Studies in the use of magnetic microspheres for immunoaffinity extraction of paralytic shellfish poisoning toxins from shellfish

Paralytic shellfish poisoning (PSP) is a potentially fatal human health condition caused by the consumption of shellfish containing high levels of PSP toxins. Toxin extraction from shellfish and from algal cultures for use as standards and analysis by alternative analytical monitoring methods to the mouse bioassay is extensive and laborious. This study investigated whether a selected MAb antibody could be coupled to a novel form of magnetic microsphere (hollow glass magnetic microspheres, brand name Ferrospheres-N) and whether these coated microspheres could be utilized in the extraction of low concentrations of the PSP toxin, STX, from potential extraction buffers and spiked mussel extracts. The feasibility of utilizing a mass of 25 mg of Ferrospheres-N, as a simple extraction procedure for STX from spiked sodium acetate buffer, spiked PBS buffer and spiked mussel extracts was determined. The effects of a range of toxin concentrations (20-300 ng/mL), incubation times and temperature on the capability of the immuno-capture of the STX from the spiked mussel extracts were investigated. Finally, the coated microspheres were tested to determine their efficiency at extracting PSP toxins from naturally contaminated mussel samples. Toxin recovery after each experiment was determined by HPLC analysis. This study on using a highly novel immunoaffinity based extraction procedure, using STX as a model, has indicated that it could be a convenient alternative to conventional extraction procedures used in toxin purification prior to sample analysis.

Modal Extraction for Wind Turbines using Moving Window Subspace Identification

This paper proposes a method for wind turbine mode identification using the multivariable output error statespace (MOESP) identification algorithm. The paper incorporates a fast moving window QR decomposition and propagator method from array signal processing, yielding a moving window subspace identification algorithm. The algorithm assumes that the system order is known as a priori and remains constant during identification. For the purpose of extracting modal information for turbines modelled as a linear parameter varying (LPV) system, the algorithm is applicable since a nonlinear system can be approximated as a piecewise time invariant system in consecutive data windows. The algorithm is exemplified using numerical simulations which show that the moving window algorithm can track the modal information. The paper also demonstrates that the low computational burden of the algorithm, compared to conventional batch subspace identification, has significant implications for online implementation.

Modified crack closure integral technique for extraction of SIFs in meshfee methods

A new approach for extracting stress intensity factors (SIFs) by the element-free Galerkin (EFG) class of methods through a modified crack closure integral (MCCI) scheme is proposed. Its primary feature is that it allows accurate calculation of mode I and mode II SIFs with a relatively simple and straightforward analysis even when a coarser nodal density is employed. The details of the adoption of the MCCI technique in the EFG method are described. Its performance is demonstrated through a number of case studies including mixed-mode and thermal problems in linear elastic fracture mechanics (LEFM). The results are compared with published theoretical solutions and those based on the displacement method, stress method, crack closure integral in conjunction with local smoothing (CCI–LS) technique, as well as the M-integral method. Its advantages are discussed.

Optimised extraction of heterocyclic aromatic amines from blood using hollow fibre membrane liquid-phase microextraction and triple quadrupole mass spectrometry

Heterocyclic aromatic amines (HCA) are carcinogenic mutagens formed during cooking of proteinaceous foods, particularly meat. To assist in the ongoing search for biomarkers of HCA exposure in blood, a method is described for the extraction from human plasma of the most abundant HCAs: 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMeIQx) (and its isomer 7,8-DiMeIQx), using Hollow Fibre Membrane Liquid-Phase Microextraction. This technique employs 2.5 cm lengths of porous polypropylene fibres impregnated with organic solvent to facilitate simultaneous extraction from an alkaline aqueous sample into a low volume acidic acceptor phase. This low cost protocol is extensively optimised for fibre length, extraction time, sample pH and volume. Detection is by UPLC-MS/MS using positive mode electrospray ionisation with a 3.4 min runtime, with optimum peak shape, sensitivity and baseline separation being achieved at pH 9.5. To our knowledge this is the first description of HCA chromatography under alkaline conditions. Application of fixed ion ratio tolerances for confirmation of analyte identity is discussed. Assay precision is between 4.5 and 8.8% while lower limits of detection between 2 and 5 pg/mL are below the concentrations postulated for acid-labile HCA-protein adducts in blood.

Artificial receptors for the extraction of nucleoside metabolite 7-methylguanosine from aqueous media made by molecular imprinting

A series of imprinted polymers targeting nucleoside metabolites, prepared using a template analogue approach, are presented. These were prepared following selection of the optimum functional monomer by solution association studies using 1H-NMR titrations whereby methacrylic acid was shown to be the strongest receptor with and affinity constant of 621 ± 51 L mol-1 vs. 110 ± 16 L mol-1 for acrylamide. The best performing polymers were prepared using methanol as porogenic co-solvent and although average binding site affinities were marginally reduced, 2.3×104 L mol-1 vs. 2.7×104 L mol-1 measured for a polymer prepared in acetonitrile, these polymers contained the highest number of binding sites, 5.27 μmol g-1¬¬ vs. 1.64 μmol g-1, while they also exhibited enhanced selectivity for methylated guanosine derivatives. When applied as sorbents in the extraction of nucleoside derivative cancer biomarkers from synthetic urine samples, significant sample clean-up and recoveries of up to 90% for 7-methylguanosine were achieved.

Learning from time series:Supervised Aggregative Feature Extraction

Many modeling problems require to estimate a scalar output from one or more time series. Such problems are usually tackled by extracting a fixed number of features from the time series (like their statistical moments), with a consequent loss in information that leads to suboptimal predictive models. Moreover, feature extraction techniques usually make assumptions that are not met by real world settings (e.g. uniformly sampled time series of constant length), and fail to deliver a thorough methodology to deal with noisy data. In this paper a methodology based on functional learning is proposed to overcome the aforementioned problems; the proposed Supervised Aggregative Feature Extraction (SAFE) approach allows to derive continuous, smooth estimates of time series data (yielding aggregate local information), while simultaneously estimating a continuous shape function yielding optimal predictions. The SAFE paradigm enjoys several properties like closed form solution, incorporation of first and second order derivative information into the regressor matrix, interpretability of the generated functional predictor and the possibility to exploit Reproducing Kernel Hilbert Spaces setting to yield nonlinear predictive models. Simulation studies are provided to highlight the strengths of the new methodology w.r.t. standard unsupervised feature selection approaches. © 2012 IEEE.

On Cherry-Picking ... or Trying to Have One’s Cake and Eating It: past principles and practice in the pursuit of an alternative to [full] EU membership

With the United Kingdom’s continued membership of the EU being increasingly questioned and the Prime Minister, David Cameron, committed to 're-negotiate’ the terms of membership, consideration is being given to what forms alternatives to [full] membership may take. While much current discussion focuses on the advantages and disadvantages of particular existing arrangements (e.g. European Economic Area, Swiss bilateralism), this paper examines the broader principles and practices that have to date underpinned – and undermined – EU’s attempts to develop alternatives to [full] EU membership. Drawing on an analysis of the evolution of association as an alternative to membership, the paper assesses the principled, practical and political limitations the EU faces – and imposes on itself – in offering an acceptable balance of rights and obligations to states not wishing to assume the mantle of full membership. In its assessment the paper considers various proposed models of affiliate and associate membership. It also situates consideration of the UK case in the broader context of the EU’s relations with other European non-member states for which membership may not be achievable and for which alternatives to membership (e.g. a form of privileged partnership) have been proposed. In doing so, the paper reflects on the precedent-setting consequences of any arrangement that the EU might reach with any state re-negotiating membership or withdrawing.

Use of water in aiding olefin/paraffin (liquid + liquid) extraction via complexation with a silver bis(trifluoromethylsulfonyl)imide salt

This paper describes the extraction of C₅–C₈ linear α-olefins from olefin/paraffin mixtures of the same carbon number via a reversible complexation with a silver salt (silver bis(trifluoromethylsulfonyl)imide, Ag[Tf₂N]) to form room temperature ionic liquids [Ag(olefin)_x][Tf₂N]. From the experimental (liquid + liquid) equilibrium data for the olefin/paraffin mixtures and Ag[Tf₂N], 1-pentene showed the best separation performance while C₇ and C₈ olefins could only be separated from the corresponding mixtures on addition of water which also improves the selectivity at lower carbon numbers like the C₅ and C₆, for example. Using infrared and Raman spectroscopy of the complex and Ag[Tf₂N] saturated by olefin, the mechanism of the extraction was found to be based on both chemical complexation and the physical solubility of the olefin in the ionic liquid ([Ag(olefin)_x][Tf₂N]). These experiments further support the use of such extraction techniques for the separation of olefins from paraffins.

Insight Extraction for Semiconductor Manufacturing Processes

In the semiconductor manufacturing environment it is very important to understand which factors have the most impact on process outcomes and to control them accordingly. This is usually achieved through design of experiments at process start-up and long term observation of production. As such it relies heavily on the expertise of the process engineer. In this work, we present an automatic approach to extracting useful insights about production processes and equipment based on state-of-the-art Machine Learning techniques. The main goal of this activity is to provide tools to process engineers to accelerate the learning-by-observation phase of process analysis. Using a Metal Deposition process as an example, we highlight various ways in which the extracted information can be employed.

Automatic extraction of Reduced order models from CFD simulations for building energy modeling

Thermal comfort is defined as “that condition of mind which expresses satisfaction with the thermal environment’ [1] [2]. Field studies have been completed in order to establish the governing conditions for thermal comfort [3]. These studies showed that the internal climate of a room was the strongest factor in establishing thermal comfort. Direct manipulation of the internal climate is necessary to retain an acceptable level of thermal comfort. In order for Building Energy Management Systems (BEMS) strategies to be efficiently utilised it is necessary to have the ability to predict the effect that activating a heating/cooling source (radiators, windows and doors) will have on the room. The numerical modelling of the domain can be challenging due to necessity to capture temperature stratification and/or different heat sources (radiators, computers and human beings). Computational Fluid Dynamic (CFD) models are usually utilised for this function because they provide the level of details required. Although they provide the necessary level of accuracy these models tend to be highly computationally expensive especially when transient behaviour needs to be analysed. Consequently they cannot be integrated in BEMS. This paper presents and describes validation of a CFD-ROM method for real-time simulations of building thermal performance. The CFD-ROM method involves the automatic extraction and solution of reduced order models (ROMs) from validated CFD simulations. The test case used in this work is a room of the Environmental Research Institute (ERI) Building at the University College Cork (UCC). ROMs have shown that they are sufficiently accurate with a total error of less than 1% and successfully retain a satisfactory representation of the phenomena modelled. The number of zones in a ROM defines the size and complexity of that ROM. It has been observed that ROMs with a higher number of zones produce more accurate results. As each ROM has a time to solution of less than 20 seconds they can be integrated into the BEMS of a building which opens the potential to real time physics based building energy modelling.