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Result diversification is an important aspect in query events, web-based search, facility location and other applications. To satisfy more users in event-based social networks (EBSNs), search result diversification in an event that covers as many user intents as possible. Most existing result diversification algorithms recognize an user may search for information by issuing the different query as much as possible. In this paper, we leverage many different users in a same event such that satisfy the maximum benefit of users, where users want to participate in an event that s/he did not know any users, for example, blind date, Greek and other activities. To solve this problem, we devise an effective greedy heuristic method and integrate simulated annealing techniques to optimize the algorithm performance. In particular, the Greedy algorithm is more effective but less efficient than Integrate Simulated Annealing in most cases. Finally, we conduct extensive experiments on real and synthetic datasets which verify the efficiency and effectiveness of our proposed algorithms.

Spatial crowdsourcing is an activity consisting in outsourcing spatial tasks to a community of online, yet on-ground and mobile, workers. Presently an increasing number of spatial crowdsourcing applications emerges due to the related technologies tends to maturity. Distinct from traditional crowdsourcing dualistic entities, task and worker, a special kind of applications imports the third one of skill. Consequently, a novel assignment problem called multiple skills assignment problem (MSAP) is generated which extends the entity relationship from 2 to 3 dimensions. Inspired by group strategy we first propose a lightweight algorithm GMA that could achieve approximate optimal solution quickly. However, GMA exists a defect of ignoring that workers with multiple skills can decrease total travel distance significantly. Thus we propose a revised algorithm RGMA to cut down distance cost. With synthetic datasets, we empirically and comparatively evaluate the performance of the baseline and two proposed algorithms.

Investigating multiple research questions, or hypotheses, within one study is a common scenario in biomedical research with many examples in ophthalmology. As the number of statistical tests increases, the overall chance that we draw an erroneous conclusion in our study gets higher in a predictable manner. Each statistical test conducted at the conventional 5% significance level (α) has a one in 20 chance (or 0.05 probability) of appearing significant simply due to chance (a type I error) and a 1−0.05=0.95 probability of being non-significant. If we test two independent true null hypotheses, the probability that neither test will be significant is 0.95×0.95=0.90. Likewise, if we test 14 independent hypotheses, the probability that none will be significant is 0.9514=0.49, and the probability that at least one will be significant is 1−0.49=0.51, that is, we are more likely than not to find at least one test significant. In other words, if we go on carrying out tests of significance we are very likely to find a spurious significant result. In the field of statistics, this phenomenon is known as the problem of multiple testing or the multiplicity problem .1 Consider the ABC study which compared bevacizumab for neovascular age-related macular degeneration (nAMD) with standard National Health Service (NHS) care.2 This study was conducted on 131 patients and found that 21 (32%) of patients treated with bevacizumab gained ≥15 letters compared with two (3%) of those in the standard care group with an OR of 18.1 (95% CI 3.6 to 91.2; p

To derive macular thickness measures and their associations by performing rapid, automated segmentation of spectral-domain optical coherence tomography (SD OCT) images collected and stored as part of the UK Biobank (UKBB) study.Large, multisite cohort study in the United Kingdom. Analysis of cross-sectional data.Adults from the United Kingdom aged 40 to 69 years.Participants had nonmydriatic SD OCT (Topcon 3D OCT-1000 Mark II; Topcon GB, Newberry, Berkshire, UK) performed as part of the ocular assessment module. Rapid, remote, automated segmentation of the images was performed using custom optical coherence tomography (OCT) image analysis software (Topcon Advanced Boundary Segmentation [TABS]; Topcon GB) to generate macular thickness values. We excluded people with a history of ocular or systemic disease (diabetes or neurodegenerative diseases) and eyes with reduced vision (0.1 logarithm of the minimum angle of resolution) or with low SD OCT signal-to-noise ratio and low segmentation success certainty.Macular thickness values across 9 Early Treatment of Diabetic Retinopathy Study (ETDRS) subfields.The SD OCT scans of 67 321 subjects were available for analysis, with 32 062 people with at least 1 eye meeting the inclusion criteria. There were 17 274 women and 14 788 men, with a mean (standard deviation [SD]) age of 55.2 (8.2) years. The mean (SD) logarithm of the minimum angle of resolution visual acuity was -0.075 (0.087), and the refractive error was -0.071 (+1.91) diopters (D). The mean (SD) central macular thickness (CMT) in the central 1-mm ETDRS subfield was 264.5 (22.9) μm, with 95% confidence limits of 220.8 and 311.5 μm. After adjusting for covariates, CMT was positively correlated with older age, female gender, greater myopia, smoking, body mass index (BMI), and white ethnicity (all P0.001). Of note, macular thickness in other subfields was negatively correlated with older age and greater myopia.We report macular thickness data derived from SD OCT images collected as part of the UKBB study and found novel associations among older age, ethnicity, BMI, smoking, and macular thickness.

Purpose To report the methodology and findings of a large scale investigation of burden and distribution of refractive error, from a contemporary and ethnically diverse study of health and disease in adults, in the UK. Methods U K Biobank, a unique contemporary resource for the study of health and disease, recruited more than half a million people aged 40–69 years. A subsample of 107,452 subjects undertook an enhanced ophthalmic examination which provided autorefraction data (a measure of refractive error). Refractive error status was categorised using the mean spherical equivalent refraction measure. Information on socio-demographic factors (age, gender, ethnicity, educational qualifications and accommodation tenure) was reported at the time of recruitment by questionnaire and face-to-face interview. Results Fifty four percent of participants aged 40–69 years had refractive error. Specifically 27% had myopia (4% high myopia), which was more common amongst younger people, those of higher socio-economic status, higher educational attainment, or of White or Chinese ethnicity. The frequency of hypermetropia increased with age (7% at 40–44 years increasing to 46% at 65–69 years), was higher in women and its severity was associated with ethnicity (moderate or high hypermetropia at least 30% less likely in non-White ethnic groups compared to White). Conclusions Refractive error is a significant public health issue for the UK and this study provides contemporary data on adults for planning services, health economic modelling and monitoring of secular trends. Further investigation of risk factors is necessary to inform strategies for prevention. There is scope to do this through the planned longitudinal extension of the UK Biobank study.

Circular scan Spectral-Domain Optic Coherence Tomography imaging (SD-OCT) is one of the best tools for diagnosis of retinal diseases. This technique provides more comprehensive detail of the retinal morphology and layers around the optic disc nerve head (ONH). Since manual labelling of the retinal layers can be tedious and time consuming, accurate and robust automated segmentation methods are needed to provide the thickness evaluation of these layers in retinal disorder assessments such as glaucoma. The proposed method serves this purpose by performing the segmentation of retinal layers boundaries in circular SD-OCT scans acquired around the ONH. The layers are detected by adapting a graph cut segmentation technique that includes a kernel-induced space and a continuous multiplier based max-flow algorithm. Results from scan images acquired with Spectralis (Heidelberg Engineering, Germany) prove that the proposed method is robust and efficient in detecting the retinal layers boundaries in images. With a mean root-mean-square error (RMSE) of 0.0835 ± 0.0495 and an average Dice coefficient of 0.9468 ± 0.0705 pixels for the retinal nerve fibre layer thickness, the proposed method demonstrated effective agreement with manual annotations.

Spectral-Domain Optical Coherence Tomography (SD-OCT) is a non-invasive imaging modality, which provides retinal structures with unprecedented detail in 3D. In this paper, we propose an automated segmentation method to detect intra-retinal layers in SD-OCT images around optic nerve head acquired from a high resolution RTVue-100 SD-OCT (Optovue, Fremont, CA, USA). This method starts by removing all the OCT imaging artifacts including the speckle noise and enhancing the contrast between layers using the 3D nonlinear anisotropic. Afterwards, we combine the level set method, k-means and MRF method to segment three intra-retinal layers around optical nerve head. The segmentation results show that our method can effectively delineate the surfaces of the retinal tissues in the noisy 3D optic nerve head images. The signed and unsigned significant differences between the segmentation results and the ground truth over optic nerve head B-scans are 1.01 \(\pm \) 1.13 and 1.93 \(\pm \) 2.21.

Distributions of measured data are often well modelled by known probability distributions, which provide a useful description of their underlying properties such as location (average), spread (variation) and shape. Statisticians use probability distributions to interpret and attribute meaning, draw conclusions and answer research questions using the measurements or data that researchers gather during their studies. Different types of data follow different probability distributions, and these distributions are characterised by certain features called parameters. Even the most statistically averse of researchers is likely to have heard of the normal distribution, which is often used to approximate the distribution of continuous or measurement data such as intraocular pressure, central retinal thickness and degree of proptosis. The normal distribution follows a ‘bell-shaped curve’ (although with a rim stretching to ±infinity) the shape of which is specified by the mean and SD, with different values of each, giving rise to different bell-shaped curves (see figure 1). Figure 1 Examples of the normal N (µ, σ) distributions parameterised by different values of mean (µ) and SD (σ). Other distributions such as the binomial and Poisson probability distributions are less commonly reported in ophthalmic research and are characterised by different parameters. The binomial distribution is used for dichotomous data and is characterised by the probability of success, that is, the number of ‘successes’ out of a total number of observed events, for example, the proportion of graft transplants that fail within 6 months of transplantation. The Poisson distribution is used for counts data and is characterised by the mean number of events, for example, endophthalmitis rates. The assumption that the observed data follow such probability distributions allows a statistician to apply appropriate statistical tests, which are known as parametric tests. The normal distribution is a powerful tool provided the data plausibly arise from that distribution or can be …

Background Vigabatrin (VGB) is an anti-epileptic medication which has been linked to peripheral constriction of the visual field. Documenting the natural history associated with continued VGB exposure is important when making decisions about the risk and benefits associated with the treatment. Due to its speed the Swedish Interactive Threshold Algorithm (SITA) has become the algorithm of choice when carrying out Full Threshold automated static perimetry. SITA uses prior distributions of normal and glaucomatous visual field behaviour to estimate threshold sensitivity. As the abnormal model is based on glaucomatous behaviour this algorithm has not been validated for VGB recipients. We aim to assess the clinical utility of the SITA algorithm for accurately mapping VGB attributed field loss. Methods The sample comprised one randomly selected eye of 16 patients diagnosed with epilepsy, exposed to VGB therapy. A clinical diagnosis of VGB attributed visual field loss was documented in 44% of the group. The mean age was 39.3 years ± 14.5 years and the mean deviation was -4.76 dB ±4.34 dB. Each patient was examined with the Full Threshold, SITA Standard and SITA Fast algorithm. Results SITA Standard was on average approximately twice as fast (7.6 minutes) and SITA Fast approximately 3 times as fast (4.7 minutes) as examinations completed using the Full Threshold algorithm (15.8 minutes). In the clinical environment, the visual field outcome with both SITA algorithms was equivalent to visual field examination using the Full Threshold algorithm in terms of visual inspection of the grey scale plots , defect area and defect severity. Conclusions Our research shows that both SITA algorithms are able to accurately map visual field loss attributed to VGB. As patients diagnosed with epilepsy are often vulnerable to fatigue, the time saving offered by SITA Fast means that this algorithm has a significant advantage for use with VGB recipients. Electronic supplementary material The online version of this article (doi:10.1186/1471-2415-14-166) contains supplementary material, which is available to authorized users.

Purpose: We test the hypothesis that age-related neurodegenerative eye disease can be detected by examining patterns of eye movement recorded whilst a person naturally watches a movie.\ud \ud Methods: Thirty-two elderly people with healthy vision (median age: 70, interquartile range [IQR] 64–75 years) and 44 patients with a clinical diagnosis of glaucoma (median age: 69, IQR 63–77 years) had standard vision examinations including automated perimetry. Disease severity was measured using a standard clinical measure (visual field mean deviation; MD). All study participants viewed three unmodified TV and film clips on a computer set up incorporating the Eyelink 1000 eyetracker (SR Research, Ontario, Canada). Eye movement scanpaths were plotted using novel methods that first filtered the data and then generated saccade density maps. Maps were then subjected to a feature extraction analysis using kernel principal component analysis (KPCA). Features from the KPCA were then classified using a standard machine based classifier trained and tested by a 10-fold cross validation which was repeated 100 times to estimate the confidence interval (CI) of classification sensitivity and specificity. Results: Patients had a range of disease severity from early to advanced (median [IQR] right eye and left eye MD was −7 [−13 to −5] dB and −9 [−15 to −4] dB, respectively). Average sensitivity for correctly identifying a glaucoma patient at a fixed specificity of 90% was 79% (95% CI: 58–86%). The area under the Receiver Operating Characteristic curve was 0.84 (95% CI: 0.82–0.87).\ud \ud Conclusions: Huge data from scanpaths of eye movements recorded whilst people freely watch TV type films can be processed into maps that contain a signature of vision loss. In this proof of principle study we have demonstrated that a group of patients with age-related neurodegenerative eye disease can be reasonably well separated from a group of healthy peers by considering these eye movement signatures alone.

Glaucomatous optic neuropathy, an important neurodegenerative condition and the commonest optic neuropathy in humans, is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with ageing and raised intraocular pressure (IOP). Using glaucomatous optic neuropathy as an exemplar for neurodegeneration, this study investigates putative factors imparting resistance to neurodegeneration. Systemic mitochondrial function, oxidative stress and vascular parameters were compared from isolated lymphocytes, whole blood and urine samples between 30 patients who have not developed the neuropathy despite being exposed for many years to very high IOP ('resistant'), 30 fast deteriorating glaucoma patients despite having low IOP ('susceptible'), and 30 age-similar controls. We found that 'resistant' individuals showed significantly higher rates of ADP phosphorylation by mitochondrial respiratory complexes I, II and IV, hyperpolarised mitochondrial membrane potential, higher levels of mitochondrial DNA, and enhanced capacity to deal with cytosolic calcium overload and exogenous oxidative stress, as compared to both controls and glaucoma patients. While it has been known for some years that mitochondrial dysfunction is implicated in neurodegeneration, this study provides a fresh perspective to the field of neurodegeneration by providing, for the first time, evidence that systemic mitochondrial efficiency above normal healthy levels is associated with an enhanced ability to withstand optic nerve injury. These results demonstrate the importance of cellular bioenergetics in glaucomatous disease progression, with potential relevance for other neurodegenerative disorders, and raise the possibility for new therapeutic targets in the field of neurodegeneration.

Photoplethysmogram (PPG) is an important physiological signal for evaluating the status of arterial wall, such as calculating markers like pulse wave velocity and pulse arrival time to reflect arterial stiffness. Detecting the onset points is an important prerequisite for analyses of PPG. In this paper, we proposed a novel algorithm using trend change of PPG waveform to detect its pulse onset points. This idea raised from the physiological phenomenon that due to the arrival of arterial pulse, the trend of PPG waveform changes sharply on both sides of PPG onset points from a decreasing trend in the previous end-diastolic phase to a sharp rising trend in the coming early systolic phase. In our algorithm, a published method was adopted to detect the peaks of 1st derivative wave of PPG. And then, in the neighborhood of each 1st derivative PPG peak point, the waveform trend changes between two sides of each point in this neighborhood was calculated, and the onset point was defined as the one with biggest positive trend change. The trend on one side of a target point was calculated from the arc tangent angles between the target point and its nearby points on this side. To evaluate the performance of the proposed algorithm, data collected on 15 healthy elderly subjects in a previous exercise study was analyzed. The results showed that the proposed algorithm achieved at a sensitivity of 99.69%, a positive predictivity of 99.24% and a failed detection rate of 1.07%. Our results demonstrated that the proposed method was robust to noises during exercise and was able to detect PPG onset points of these subjects at a satisfactory accuracy. Since the algorithm is also low in computing cost, it is promising to be used real time in ambulatory/wearable systems in the future.

Visual fields measured with standard automated perimetry are a benchmark test for determining retinal function in ocular pathologies such as glaucoma. Their monitoring over time is crucial in detecting change in disease course and, therefore, in prompting clinical intervention and defining endpoints in clinical trials of new therapies. However, conventional change detection methods do not take into account non-stationary measurement variability or spatial correlation present in these measures. An inferential statistical model, denoted ‘Analysis with Non-Stationary Weibull Error Regression and Spatial enhancement’ (ANSWERS), was proposed. In contrast to commonly used ordinary linear regression models, which assume normally distributed errors, ANSWERS incorporates non-stationary variability modelled as a mixture of Weibull distributions. Spatial correlation of measurements was also included into the model using a Bayesian framework. It was evaluated using a large dataset of visual field measurements acquired from electronic health records, and was compared with other widely used methods for detecting deterioration in retinal function. ANSWERS was able to detect deterioration significantly earlier than conventional methods, at matched false positive rates. Statistical sensitivity in detecting deterioration was also significantly better, especially in short time series. Furthermore, the spatial correlation utilised in ANSWERS was shown to improve the ability to detect deterioration, compared to equivalent models without spatial correlation, especially in short follow-up series. ANSWERS is a new efficient method for detecting changes in retinal function. It allows for better detection of change, more efficient endpoints and can potentially shorten the time in clinical trials for new therapies.

Purpose To investigate the influence of intersubject variation in ocular parameters on the mapping of retinal locations to the retinal nerve fiber layer and optic nerve head. Methods One hundred retinal nerve fiber layer (RNFL) bundle photographs from 100 subjects were optimized digitally and single RNFL bundles manually traced back to the ONH where their entry point was noted. A 24-2 visual field (VF) grid pattern was superimposed onto the photographs in order to relate VF test points to intersecting RNFL bundles and their entry angles into the ONH. Axial length, spherical equivalent, the position of the ONH in relation to the fovea, size, orientation, tilt, and shape of the ONH were assessed. Multilevel linear models were generated for predicting the entry angle of RNFL bundles, based on ocular parameters. Results A total of 6388 RNFL bundles were traced. The influence of ocular parameters could be evaluated for 33 out of 52 VF locations. The position of the ONH in relation to the fovea was the most prominent predictor for variations in the mapping of retinal locations to the ONH, followed by disc area, axial length, spherical equivalent, disc shape, disc orientation, and disc tilt. Conclusions Mapping of retinal locations to the optic nerve head varies between patients according to a given patient's ocular parameters. By considering these parameters, patient-tailored, structure-function maps can be built and structural and functional measurements can be correlated more accurately. Individualized maps may assist clinicians detecting glaucoma and monitoring glaucomatous progression.

Measurement of retinal nerve fiber layer (RNFL) thickness using optical coherence tomography (OCT) is commonly used in the detection and management of glaucoma. The Stratus OCT (Carl Zeiss Meditec, Inc., Dublin, CA) is widely used, but image acquisition is subject to artifacts, such as those caused by normal fixational eye movements, and this leads to unreliable measurements. Novel analytical methods have been developed to estimate the amount of misalignment of the circular scanning protocol used by the Stratus OCT. A computer program with a graphical user interface implementing these methods has been written by some of the authors. A case example is presented in this report that shows the effect that vertical displacements of the OCT scan have on measured RNFL thickness. The example is used to demonstrate how the software can be used for estimating the positional alignment of the scan circle. This software can potentially improve the identification of unreliable RNFL thickness measurements and is freely available from the authors.

Optical coherence tomography (OCT) is widely used in the assessment of retinal nerve fibre layer thickness (RNFLT) in glaucoma. Images are typically acquired with a circular scan around the optic nerve head. Accurate registration of OCT scans is essential for measurement reproducibility and longitudinal examination. This study developed and evaluated a special image registration algorithm to align the location of the OCT scan circles to the vessel features in the retina using probabilistic modelling that was optimised by an expectation-maximization algorithm. Evaluation of the method on 18 patients undergoing large numbers of scans indicated improved data acquisition and better reproducibility of measured RNFLT when scanning circles were closely matched. The proposed method enables clinicians to consider the RNFLT measurement and its scan circle location on the retina in tandem, reducing RNFLT measurement variability and assisting detection of real change of RNFLT in the longitudinal assessment of glaucoma.

Objective To evaluate a new method of quantifying and visualizing discordance between structural and functional measurements in glaucomatous eyes by predicting the visual field (VF) from retinal nerve fiber layer thickness (RNFLT) using a bayesian radial basis function. Methods Five GDx VCC RNFLT scans and 5 Humphrey 24-2 Swedish Interactive Thresholding Algorithm VF tests were performed for 50 glaucomatous eyes from 50 patients. A best-available estimate (BAE) of the true VF was calculated as the pointwise median of these 5 replications. This BAE VF was compared with every RNFLT-predicted VF from the bayesian radial basis function and every measured VF. Predictability of VFs from RNFLT was established from previous data. A structure-function pattern discordance map and a structure-function discordance index (scores of 0-1) were established from the predictability limits for each structure-function measurement pair to quantify and visualize the discordance between the structure-predicted and measured VFs. Results The mean absolute difference between the structure-predicted and BAE VFs was 3.9 dB. The mean absolute difference between measured and BAE VFs was 2.6 dB. The mean (SD) structure-function discordance index score was 0.34 (0.11). Ninety-seven (39%) of the structure-predicted VFs showed significant discordance (structure-function discordance index score >0.3) from measured VFs. Conclusions On average, the bayesian radial basis function predicts the BAE VF from RNFLT slightly less well than a measured VF from the 5 VFs composing the BAE VF. The pattern discordance map highlights locations with structure-function discordance, with the structure-function discordance index providing a summary index. These tools may help clinicians trust the mutually confirmatory structure-function measurements with good concordance or identify unreliable ones with poor concordance.

Spectral-domain optical coherence tomography (SD-OCT) provides volumetric images of retinal structures with unprecedented detail. Accurate segmentation algorithms and feature quantification in these images, however, are needed to realize the full potential of SD-OCT. The fully automated segmentation algorithm, FloatingCanvas, serves this purpose and performs a volumetric segmentation of retinal tissue layers in three-dimensional image volume acquired around the optic nerve head without requiring any pre-processing. The reconstructed layers are analyzed to extract features such as blood vessels and retinal nerve fibre layer thickness. Findings from images obtained with the RTVue-100 SD-OCT (Optovue, Fremont, CA, USA) indicate that FloatingCanvas is computationally efficient and is robust to the noise and low contrast in the images. The FloatingCanvas segmentation demonstrated good agreement with the human manual grading. The retinal nerve fibre layer thickness maps obtained with this method are clinically realistic and highly reproducible compared with time-domain StratusOCT(TM).

Purpose: To develop and validate a method for predicting visual function from retinal nerve fibre layer (RNFL) structure in glaucoma.\ud \ud Methods: RNFL thickness (RNFLT) measurements from GDxVCC scanning laser polarimetry (SLP) and visual field (VF) sensitivity from standard automated perimetry were made available from 535 eyes from three centres. In a training dataset, structure-function relationships were characterized using linear regression and a type of neural network: Radial Basis Function customised under a Bayesian framework (BRBF). These two models were used in a test dataset to 1) predict sensitivity values at individual VF locations from RNFLT measurements and 2) predict the spatial relationship between VF locations and positions at a peripapillary RNFLT measurement annulus. Predicted spatial relationships were compared with a published anatomical structure-function map.\ud \ud Results: Compared with linear regression, BRBF yielded a nearly two-fold improvement (P

Background and Objective: The purpose of this study was to examine the hypothesis that retinal nerve fiber layer (RNFL) birefringence increases following surgical reduction of intraocular pressure (IOP). Patients and Methods: Twenty-six glaucomatous eyes requiring trabeculectomy or drainage implant were enrolled. Optical coherence tomography (OCT), scanning laser polarimetry (SLP), and IOP measurements were performed preoperatively and 3 months postoperatively. The OCT and SLP images were aligned using a new algorithm that aligns the vessels in an OCT image to those in the corresponding SLP reflectance image. The SLP retardance values at the location of the OCT scan circle were then extracted using the OCT scan circle position inferred by the algorithm. Sixty-four corresponding RNFL segments were extracted from SLP and OCT to calculate RNFL birefringence. A significant birefringence change was defined as 1.96 times the weighted test–retest standard deviation in four contiguous segments. Results: Preoperative IOP (19.3 ± 6.1 mm Hg) was significantly ( P < .001) lower than postoperative IOP (10.4 ± 3.7 mm Hg). Average birefringence magnitude did not change ( P = .19) postoperatively. Localized birefringence magnitude increased significantly in 6 (23%) eyes and decreased significantly in 7 (27%) eyes. Conclusion: In this cohort, variable changes in localized birefringence were observed following surgical reduction of IOP.

Glaucoma is a leading cause of irreversible blindness and requires precise measures for early detection and follow-up. However, individual clinical measures in glaucoma are highly variable. It is anticipated that this variability can be reduced by combining the independent measurements that test various as- pects of the glaucomatous damage. This study proposes a mathematical framework to link retinal nerve fibre layer (RNFL) structure and visual function using the data typically acquired in the clinical management of glaucoma. The model performed and generalized well over different populations from three clinical centres. The derived structure-function relationship accorded well with RNFL anatomy, and could be applied to reduce the variability that confounds the measurement of glaucoma damage.

Purpose: To investigate the effects of levocabastine hydrochloride on the profileration, Deoxyribonucleic acid (DNA) synthesis and induction of apoptosis, in human Tenon’s capsule fibroblasts. Methods: The maximum intoxicate concentration was determined by measuring the release of lactate dehydrogenase. Proliferation of fibroblasts was analyzed with a WST-1 method. DNA synthesis was examined by quantifying the incorporation of 5-bromo-2’-deoxyuridine into dividing cells, and apoptosis was analyzed using an Annexin-V-FLUOS Staining Kit. Results: Levocabastine hydrochloride (10−4 M), ketotifen fumarate (3 × 10−5 M) and tranilast (10−4 M) significantly inhibited proliferation of fibroblasts. Levocabastine hydrochloride (10−4 M), ketotifen fumarate (10−4 M) and tranilast (10−3 M) inhibited DNA synthesis and induced apoptosis. Conclusion: Levocabastine hydrochloride inhibited the proliferation of fibroblasts.

Purpose To validate a method for visual field (VF) progression analysis, called ANSWERS (Analysis with Non-Stationary Weibull Error Regression and Spatial Enhancement), which takes into account increasing measurement variability as glaucoma progresses and spatial correlation among test locations. Methods ANSWERS outputs both a global index of progression and a pointwise estimate of rate of change at each VF location. ANSWERS was compared with linear regression of mean deviation (MD) and permutation of pointwise linear regression (PoPLR). Visual field series of up to 2 years from the United Kingdom Glaucoma Treatment Study were used. This consists of 9104 Swedish Interactive Thresholding Algorithm Standard 24-2 VFs. ANSWERS and PoPLR rate of change were used to predict the VF at the next visit using subseries that were within 7, 13, 18, or 22 months from the baseline. The comparison was carried out on the statistical sensitivity, specificity, and accuracy of predicting future VF. Results Across all subseries, statistical sensitivity of ANSWERS in detecting VF deterioration was significantly better than the linear regression of MD and PoPLR, especially in short time series. Prediction accuracy of ANSWERS was better than PoPLR at all series lengths, and the improvement was particularly marked in shorter series. Seventy-five percent of VF series were better predicted by ANSWERS compared with PoPLR. The average prediction error of ANSWERS was 15% lower than that of PoPLR. Conclusions ANSWERS is more sensitive to detect VF progression and predicts future VF loss better than linear regression of MD and PoPLR, especially over short observation periods. (http://www.isrctn.com number, ISRCTN96423140.).

PURPOSE. The Ocular Response Analyzer (ORA) is a new instrument that measures the corneal biomechanical response (corneal hysteresis, CH) to rapid indentation by an air jet. CH is the difference in applanation pressures (P1, P2) between the rising and falling phases of the air jet. The investigation had two parts: a characterization study and a validation study. In the characterization study, the purposes were to investigate the intraocular pressure (IOP)– dependence of CH and to characterize the performance of the ORA. In the validation study, the purposes were to investigate the association between CH and both age and central corneal thickness (CCT) and the agreement between ORA and Goldmann applanation tonometer (GAT) IOP measurements. METHODS. For the characterization study, data were collected from 105 untreated subjects (45 ocular hypertensive patients and 60 normal subjects; mean age, 60 years, range, 26 – 82). GAT and ORA measurements were performed before and after IOP lowering of one randomly selected eye with apraclonidine drops. The change in P1 and P2 (arbitrary units) in relation to change in GAT IOP was analyzed to calibrate the instrument. The relation between P1, P2, and CCT was explored and ORA IOP was derived from the analyses. For the validation study, ORA and GAT IOP and CCT were measured in 144 eyes of 144 untreated subjects (mean age, 58 years; range, 19 – 83). The characterization calculations were applied to the dataset and values of CH and ORA IOP were calculated. The relationship between CH and both subject age and CCT was determined. The associations between CH and CCT and between ORA and GAT IOPs, were investigated by linear regression analysis. The agreement between measuring devices was calculated. RESULTS. In the characterization study, P1 changed by 6.41 arbitrary units for every 1-mm Hg change in GAT IOP. CH (P1 P2) changed by 1.60 arbitrary units for every 1-mm Hg change in GAT IOP. For each unit change in P2, P1 changed by 1.27 units. From this association a new IOP-independent corneal factor was derived [P1 (P2/1.27)] and is termed the corneal constant factor (CCF; mm Hg). ORA IOP normalized for CCF was defined as P2 – CCF (mm Hg). The CCF (mm Hg) was associated with CCT (micrometers) and with age: CCF [(0.036 CCT) (0.028 age)] 1.06 (adjusted r 2 0.34; P 0.0001 for CCT, P 0.007 for age). Normalized ORA IOP measurements were not associated with CCT. GAT IOP was associated with CCT and CCF—more strongly with the latter: GAT IOP (0.03 CCT)1.52 (r 2 0.06, P 0.002); GAT IOP (0.65 CCF) 4.5 (r 2 0.13, P 0.0001). The mean difference (95% limits of agreement) between GAT and normalized ORA IOP was 0.1 (6.6 to 6.8) mm Hg. CONCLUSIONS. The CCF describes an IOP-independent biomechanical property of the cornea that increases with thicker CCT and decreases with greater age. It is moderately strongly associated with CCT and yet explains more of the interindividual variation in GAT IOP than does CCT. Normalized ORA IOP measurements are not associated with CCT. (Invest Ophthalmol Vis Sci. 2006;47:5337–5347) DOI:10.1167/iovs.060557

Imaging and evaluation of the optic nerve head (ONH) plays an essential part in the detection and clinical management of glaucoma. The morphological characteristics of ONHs vary greatly from person to person and this variability means it is difficult to quantify them in a standardized way. We developed and evaluated a feature extraction approach using shift-invariant wavelet packet and kernel principal component analysis to quantify the shape features in ONH images acquired by scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT]). The methods were developed and tested on 1996 eyes from three different clinical centers. A shape abnormality score (SAS) was developed from extracted features using a Gaussian process to identify glaucomatous abnormality. SAS can be used as a diagnostic index to quantify the overall likelihood of ONH abnormality. Maps showing areas of likely abnormality within the ONH were also derived. Diagnostic performance of the technique, as estimated by ROC analysis, was significantly better than the classification tools currently used in the HRT software – the technique offers the additional advantage of working with all images and is fully automated.

Background: With the development and innovation of digital information technologies and new-generation Internet information platforms, new types of information exchange methods have been spawned. It has broken the restriction of the traditional internet boundary, and integrated all round connections between people and objects. Methods: Based on the above progresses, digital multimedia contents distributed or published much more convenient on the internet than before and most of them without any copyright protection. The dishonest owner can easily copy and distribute digital multimedia content without reducing any perceptual quality. According to the relative concerns, watermark protocol networks play a very important role in the usage tracking and copyrights infringement authentication, etc. However, most of the watermark protocols always require a “fully trusted third party”, which has a potential risk to suffer conspiracy attack. Results: Therefore, in this paper, we focus on designing a watermark protocol with trustless third party via blockchain for protecting copyrights of owners that they want to publish or distribute on the internet. The proposed watermark protocol includes three sub-protocols which covers the negotiation process, transaction process and identification processes. Conclusion: In addition, this paper also provides a fully detail analysis that describes the benefits and weaknesses of current solution.

Pragmatic trials of treatment pathways can require patient awareness of treatment allocation in order to better represent clinical reality, for example when concordance with a treatment has an important effect on outcome. Conversely, masking of treating clinicians to allocation group can be impossible when full clinical assessment requires knowledge of the current treatments, resources do not permit separate teams for treatment and assessment or when such duplication of clinician contact might affect an outcome such as patient experience. The LiGHT trial is a 718 subject multi-centre 6-year NIHR-funded study of two treatment pathways for glaucoma with outcome measures of health related quality of life and cost effectiveness. We aimed to minimise variation in aspects of clinical behaviour that might introduce bias by affecting either of these outcomes.