Screening tests for detecting open-angle glaucoma: systematic review and meta-analysis

PURPOSE: To assess the comparative accuracy of potential screening tests for open angle glaucoma (OAG).

METHODS: Medline, Embase, Biosis (to November 2005), Science Citation Index (to December 2005), and The Cochrane Library (Issue 4, 2005) were searched. Studies assessing candidate screening tests for detecting OAG in persons older than 40 years that reported true and false positives and negatives were included. Meta-analysis was undertaken using the hierarchical summary receiver operating characteristic model.

RESULTS: Forty studies enrolling over 48,000 people reported nine tests. Most tests were reported by only a few studies. Frequency-doubling technology (FDT; C-20-1) was significantly more sensitive than ophthalmoscopy (30, 95% credible interval [CrI] 0-62) and Goldmann applanation tonometry (GAT; 45, 95% CrI 17-68), whereas threshold standard automated perimetry (SAP) and Heidelberg Retinal Tomograph (HRT II) were both more sensitive than GAT (41, 95% CrI 14-64 and 39, 95% CrI 3-64, respectively). GAT was more specific than both FDT C-20-5 (19, 95% CrI 0-53) and threshold SAP (14, 95% CrI 1-37). Judging performance by diagnostic odds ratio, FDT, oculokinetic perimetry, and HRT II are promising tests. Ophthalmoscopy, SAP, retinal photography, and GAT had relatively poor performance as single tests. These findings are based on heterogeneous data of limited quality and as such are associated with considerable uncertainty.

CONCLUSIONS: No test or group of tests was clearly superior for glaucoma screening. Further research is needed to evaluate the comparative accuracy of the most promising tests.

Detection of pathogen based on the catalytic growth of gold nanocrystals

A homogenous detection of pathogen (Giardia lamblia cysts) based on the catalytic growth of gold nanoparticles (AuNPs) has been studied. In this study, centrifugal filters were employed as tools to concentrate and separate the pathogen cells, and moreover amplify the detection signal. The catalytic growth of gold nanoparticles was verified to be positively related to gold seeds concentration. On this basis, homogenous detection of the pathogenic bacteria in liquid phase was established by means of conjugating antibody to gold seeds. Under the given experimental condition, detection limit of G. lamblia cysts was determined as low as 1.088 × 103 cells ml-1. The additional nonspecific binding tests were also conducted to verify the detection specificity. This sensing platform has been proved to be a sensitive, reliable and simple method for large-scale pathogen detection, and provide valuable insight for the development of gold nanocrystals based colorimetric biosensors.

A new method for non-labeling attomolar detection of diseases based on an individual gold nanorod immunosensor

Herein, we present the use of a single gold nanorod sensor for detection of diseases on an antibody-functionalized surface, based on antibody–antigen interaction and the localized surface plasmon resonance (LSPR) ?max shifts of the resonant Rayleigh light scattering spectra. By replacing the cetyltrimethylammonium bromide (CTAB), a tightly packed self-assembled monolayer of HS(CH2)11(OCH2CH2)6OCH2COOH(OEG6) has been successfully formed on the gold nanorod surface prior to the LSPR sensing, leading to the successful fabrication of individual gold nanorod immunosensors. Using prostate specific antigen (PSA) as a protein biomarker, the lowest concentration experimentally detected was as low as 111 aM, corresponding to a 2.79 nm LSPR ?max shift. These results indicate that the detection platform is very sensitive and outperforms detection limits of commercial tests for PSA so far. Correlatively, its detection limit can be equally compared to the assays based on DNA biobarcodes. This study shows that a gold nanorod has been used as a single nanobiosensor to detect antigens for the first time; and the detection method based on the resonant Rayleigh scattering spectrum of individual gold nanorods enables a simple, label-free detection with ultrahigh sensitivity.

Association Study of 167 Candidate Genes for Schizophrenia Selected by a Multi-Domain Evidence-Based Prioritization Algorithm and Neurodevelopmental Hypothesis

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n = 3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this
ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.

ELIMED:A new hadron therapy concept based on laser driven ion beams

Laser accelerated proton beams have been proposed to be used in different research fields. A great interest has risen for the potential replacement of conventional accelerating machines with laser-based accelerators, and in particular for the development of new concepts of more compact and cheaper hadrontherapy centers. In this context the ELIMED (ELI MEDical applications) research project has been launched by INFN-LNS and ASCR-FZU researchers within the pan-European ELI-Beamlines facility framework. The ELIMED project aims to demonstrate the potential clinical applicability of optically accelerated proton beams and to realize a laser-accelerated ion transport beamline for multi-disciplinary user applications. In this framework the eye melanoma, as for instance the uveal melanoma normally treated with 62 MeV proton beams produced by standard accelerators, will be considered as a model system to demonstrate the potential clinical use of laser-driven protons in hadrontherapy, especially because of the limited constraints in terms of proton energy and irradiation geometry for this particular tumour treatment. Several challenges, starting from laser-target interaction and beam transport development up to dosimetry and radiobiology, need to be overcome in order to reach the ELIMED final goals. A crucial role will be played by the final design and realization of a transport beamline capable to provide ion beams with proper characteristics in terms of energy spectrum and angular distribution which will allow performing dosimetric tests and biological cell irradiation. A first prototype of the transport beamline has been already designed and other transport elements are under construction in order to perform a first experimental test with the TARANIS laser system by the end of 2013. A wide international collaboration among specialists of different disciplines like Physics, Biology, Chemistry, Medicine and medical doctors coming from Europe, Japan, and the US is growing up around the ELIMED project with the aim to work on the conceptual design, technical and experimental realization of this core beamline of the ELI Beamlines facility. © 2013 SPIE.

A PCR-based method to distinguish fungi of the rice sheath-blight complex, Rhizoctonia solani, R. oryzae and R. oryzae-sativae

Identification of Rhizoctonia solani, R. oryzae and R. oryzae-sativae, components of the rice sheath disease complex, is extremely difficult and often inaccurate and as a result may hinder the success of extensive breeding programmes throughout Asia. In this study, primers designed from unique regions within the rDNA internal transcribed spacers have been used to develop a rapid PCR-based diagnostic test to provide an accurate identification of the species on rice. Tests on the specificity of the primers concerned showed that they provide the means for accurate identification of the Rhizoctonia species responsible for sheath diseases in rice.

Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms:a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

Examining the Neurocognitive Validity of Commercially Available, Smartphone-Based Puzzle Games

Cognitive assessment typically involves assessing a person’s cognitive performance in unfamiliar and ar-guably unnatural clinical surroundings. User-centred approaches to assessment and monitoring, driven by issues such as enjoyability and familiarity, are largely absent. Everyday technologies, for example, smartphones represent an opportunity to obtain an objective assessment of a person’s cognitive capabili-ties in a non-threatening, discreet and familiar way, e.g. by everyday puzzle games undertaken as a leisure activity at home. We examined the strength of relationships that exist between performance on common puzzle games and standard measures of neuropsychological performance. Twenty-nine participants, aged 50 - 65 years, completed a comprehensive neuropsychological test battery and played three smart-phone-based puzzle games in triplicate: a picture puzzle [Matches Plus], a word puzzle [Jumbline] and a number puzzle [Sudoku]. As anticipated, a priori, significant correlations were observed between scores on a picture puzzle and visual memory test (r = 0.49; p = 0.007); a word puzzle and estimated verbal IQ (r = 0.53; p = 0.003) and verbal learning (r = 0.30; p = 0.039) tests; and a number puzzle and reason-ing/problem solving test (r = 0.42; p = 0.023). Further analyses making allowance for multiple compari-sons identified a significant unanticipated correlation (r = 0.49; p = 0.007) between number puzzle scores and a measure of nonverbal working memory. Performance on these smartphone-based games was in-dicative of relative cognitive ability across several cognitive domains at a fixed time point. Smart-phone-based, everyday puzzle games may offer a valid, portable measure of assessing and monitoring cognition in older adults.

Fluorescence based fibre optic pH sensor for the pH 10–13 range suitable for corrosion monitoring in concrete structures

The design, development and evaluation of an optical fibre pH sensor for monitoring pH in the alkaline region are discussed in detail in this paper. The design of this specific pH sensor is based on the pH induced change in fluorescence intensity of a coumarin imidazole dye which is covalently attached to a polymer network and then fixed to the distal end of an optical fibre. The sensor provides a response over a pH range of 10.0–13.2 with an acceptable response rate of around 50 min, having shown a very good stability over a period of longer than 20 months thus far. The sensor has also demonstrated little cross-sensitivity to ionic strength (IS) and also excellent photostability through a series of laboratory tests. These features make this type of sensor potentially well suited for in situ long term monitoring of pH in concrete structures, to enhance structural monitoring in the civil engineering sector

Identification and Validation of an Anthracycline/Cyclophosphamide–Based Chemotherapy Response Assay in Breast Cancer

Background: There is no method routinely used to predict response to anthracycline and cyclophosphamide–based chemotherapy in the clinic; therefore patients often receive treatment for breast cancer with no benefit. Loss of the Fanconi anemia/BRCA (FA/BRCA) DNA damage response (DDR) pathway occurs in approximately 25% of breast cancer patients through several mechanisms and results in sensitization to DNA-damaging agents. The aim of this study was to develop an assay to detect DDR-deficient tumors associated with loss of the FA/BRCA pathway, for the purpose of treatment selection.

Methods: DNA microarray data from 21 FA patients and 11 control subjects were analyzed to identify genetic processes associated with a deficiency in DDR. Unsupervised hierarchical clustering was then performed using 60 BRCA1/2 mutant and 47 sporadic tumor samples, and a molecular subgroup was identified that was defined by the molecular processes represented within FA patients. A 44-gene microarray-based assay (the DDR deficiency assay) was developed to prospectively identify this subgroup from formalin-fixed, paraffin-embedded samples. All statistical tests were two-sided.

Results: In a publicly available independent cohort of 203 patients, the assay predicted complete pathologic response vs residual disease after neoadjuvant DNA-damaging chemotherapy (5-fluorouracil, anthracycline, and cyclophosphamide) with an odds ratio of 3.96 (95% confidence interval [Cl] =1.67 to 9.41; P = .002). In a new independent cohort of 191 breast cancer patients treated with adjuvant 5-fluorouracil, epirubicin, and cyclophosphamide, a positive assay result predicted 5-year relapse-free survival with a hazard ratio of 0.37 (95% Cl = 0.15 to 0.88; P = .03) compared with the assay negative population.

Conclusions: A formalin-fixed, paraffin-embedded tissue-based assay has been developed and independently validated as a predictor of response and prognosis after anthracycline/cyclophosphamide–based chemotherapy in the neoadjuvant and adjuvant settings. These findings warrant further validation in a prospective clinical study.

Vibration based seismic damage identification procedure for a steel concentrically braced frame structure

An approach for seismic damage identification of a single-storey steel concentrically braced frame (CBF) structure is presented through filtering and double integration of a recorded acceleration signal. A band-pass filter removes noise from the acceleration signal followed by baseline correction being used to reduce the drift in velocity and displacement during numerical integration. The pre-processing achieves reliable numerical integration that predicts the displacement response accurately when compared to the measured lateral in-plane displacement of the CBF structure. The lateral displacement of the CBF structure is used to infer buckling and yielding of bracing members through seismic tests. The level of interstorey drift of the CBF during a seismic excitation allows the yield and buckling of the bracing members to be identified and indirectly detects damage based on exceedance of calculated displacement limits. The calculated buckling and yielding displacement threshold limits used to identify damage are demonstrated to accurately identify initial buckling and yielding in the bracing members.

Partial least squares model for dynamic rating of overhead line in wind intensive areas based on field measurements

This paper presents a statistical model for the thermal behaviour of the line model based on lab tests and field measurements. This model is based on Partial Least Squares (PLS) multi regression and is used for the Dynamic Line Rating (DLR) in a wind intensive area. DLR provides extra capacity to the line, over the traditional seasonal static rating, which makes it possible to defer the need for reinforcement the existing network or building new lines. The proposed PLS model has a number of appealing features; the model is linear, so it is straightforward to use for predicting the line rating for future periods using the available weather forecast. Unlike the available physical models, the proposed model does not require any physical parameters of the line, which avoids the inaccuracies resulting from the errors and/or variations in these parameters. The developed model is compared with physical model, the Cigre model, and has shown very good accuracy in predicting the conductor temperature as well as in determining the line rating for future time periods. 

Determination of Non-linear Damping Coefficients of bottom-hinged Oscillating Wave Surge Converters Using Numerical Free Decay Tests

Linear wave theory models are commonly applied to predict the performance of bottom-hinged oscillating wave surge converters (OWSC) in operational sea states. To account for non-linear effects, the additional input of coefficients not included in the model itself becomes necessary. In ocean engineering it is
common practice to obtain damping coefficients of floating structures from free decay tests. This paper presents results obtained from experimental tank tests and numerical computational fluid dynamics simulations of OWSC’s. Agreement between numerical and experimental methods is found to be very good, with CFD providing more data points at small amplitude rotations.
Analysis of the obtained data reveals that linear quadratic-damping, as commonly used in time domain models, is not able to accurately model the occurring damping over the whole regime of rotation amplitudes. The authors
conclude that a hyperbolic function is most suitable to express the instantaneous damping ratio over the rotation amplitude and would be the best choice to be used in coefficient based time domain models.

An indirect bridge inspection method incorporating a wavelet-based damage indicator and pattern recognition

In recent years, there has been a move towards the development of indirect structural health monitoring (SHM)techniques for bridges; the low-cost vibration-based method presented in this paper is such an approach. It consists of the use of a moving vehicle fitted with accelerometers on its axles and incorporates wavelet analysis and statistical pattern recognition. The aim of the approach is to both detect and locate damage in bridges while reducing the need for direct instrumentation of the bridge. In theoretical simulations, a simplified vehicle-bridge interaction model is used to investigate the effectiveness of the approach in detecting damage in a bridge from vehicle accelerations. For this purpose, the accelerations are processed using a continuous wavelet transform as when the axle passes over a damaged section, any discontinuity in the signal would affect the wavelet coefficients. Based on these coefficients, a damage indicator is formulated which can distinguish between different damage levels. However, it is found to be difficult to quantify damage of varying levels when the vehicle’s transverse position is varied between bridge crossings. In a real bridge field experiment, damage was applied artificially to a steel truss bridge to test the effectiveness of the indirect approach in practice; for this purpose a two-axle van was driven across the bridge at constant speed. Both bridge and vehicle acceleration measurements were recorded. The dynamic properties of the test vehicle were identified initially via free vibration tests. It was found that the resulting damage indicators for the bridge and vehicle showed similar patterns, however, it was difficult to distinguish between different artificial damage scenarios.

DFIG Machine Design for Maximizing Power Output Based on Surrogate Optimization Algorithm

This paper presents a surrogate-model based optimization of a doubly-fed induction generator (DFIG) machine winding design for maximizing power yield. Based on site-specific wind profile data and the machine’s previous operational performance, the DFIG’s stator and rotor windings are optimized to match the maximum efficiency with operating conditions for rewinding purposes. The particle swarm optimization (PSO)-based surrogate optimization techniques are used in conjunction with the finite element method (FEM) to optimize the machine design utilizing the limited available information for the site-specific wind profile and generator operating conditions. A response surface method in the surrogate model is developed to formulate the design objectives and constraints. Besides, the machine tests and efficiency calculations follow IEEE standard 112-B. Numerical and experimental results validate the effectiveness of the proposed technologies.