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To develop deep learning models for annualized geographic atrophy (GA) growth rate prediction using fundus autofluorescence (FAF) images and spectral-domain OCT volumes from baseline visits, which can be used for prognostic covariate adjustment to increase power of clinical trials.This retrospective analysis estimated GA growth rate as the slope of a linear fit on all available measurements of lesion area over a 2-year period. Three multitask deep learning models-FAF-only, OCT-only, and multimodal (FAF and OCT)-were developed to predict concurrent GA area and annualized growth rate.Patients were from prospective and observational lampalizumab clinical trials.The 3 models were trained on the development data set, tested on the holdout set, and further evaluated on the independent test sets. Baseline FAF images and OCT volumes from study eyes of patients with bilateral GA (NCT02247479; NCT02247531; and NCT02479386) were split into development (1279 patients/eyes) and holdout (443 patients/eyes) sets. Baseline FAF images from study eyes of NCT01229215 (106 patients/eyes) and NCT02399072 (169 patients/eyes) were used as independent test sets.Model performance was evaluated using squared Pearson correlation coefficient (rOn the holdout data set, rWe show the feasibility of using baseline FAF images and OCT volumes to predict individual GA area and growth rates using a multitask deep learning approach. The deep learning-based growth rate predictions could be used for covariate adjustment to increase power of clinical trials.

GDC‐0334 is a novel small molecule inhibitor of transient receptor potential cation channel member A1 (TRPA1), a promising therapeutic target for many nervous system and respiratory diseases. The pharmacokinetic (PK) profile and pharmacodynamic (PD) effects of GDC‐0334 were evaluated in this first‐in‐human (FIH) study. A starting single dose of 25 mg was selected based on integrated preclinical PK, PD, and toxicology data following oral administration of GDC‐0334 in guinea pigs, rats, dogs, and monkeys. Human PK and PK‐PD of GDC‐0334 were characterized after single and multiple oral dosing using a population modeling approach. The ability of GDC‐0334 to inhibit dermal blood flow (DBF) induced by topical administration of allyl isothiocyanate (AITC) was evaluated as a target‐engagement biomarker. Quantitative models were developed iteratively to refine the parameter estimates of the dose‐concentration‐effect relationships through stepwise estimation and extrapolation. Human PK analyses revealed that bioavailability, absorption rate constant, and lag time increase when GDC‐0334 was administered with food. The inhibitory effect of GDC‐0334 on the AITC‐induced DBF biomarker exhibited a clear sigmoid‐Emax relationship with GDC‐0334 plasma concentrations in humans. This study leveraged emerging preclinical and clinical data to enable iterative refinement of GDC‐0334 mathematical models throughout the FIH study for dose selection in subsequent cohorts throughout the study. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? GDC‐0334 is a novel, small molecule TRPA1 inhibitor and a pharmacokinetic‐pharmacodynamic (PK‐PD) modeling strategy could be implemented in a systematic and step‐wise manner to build and learn from emerging data for early clinical development. WHAT QUESTION DID THIS STUDY ADDRESS? Can noncompartmental and population‐based analyses be used to describe the PK and PD characteristics of GDC‐0334 in preclinical and clinical studies? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? GDC‐0334 exposure generally increased with dose in rats, dogs, and monkeys. The starting dose (25 mg) in the clinical study was determined based on the preclinical data. GDC‐0334 exhibited linear PK in humans and the bioavailability was increased with food. The inhibitory effect of GDC‐0334 on dermal blood flow induced by the TRPA1 agonist allyl isothiocyanate in humans indicates a clear PK‐PD relationship. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? The models developed based on TRPA1 agonist‐induced dermal blood flow inhibition data can be used to predict PK‐PD relationships in future preclinical and clinical studies evaluating new drug entities that target TRPA1.

Introduction: This retrospective analysis assessed geographic atrophy (GA) progression in fellow eyes from the Proxima B trial intermediate age-related macular degeneration (iAMD) subcohort using high-resolution multimodal imaging anchored on optical coherence tomography (OCT). Methods: Thirty-two patients from the Proxima B iAMD subcohort were assessed; all had GA with no macular neovascularization (MNV) in the contralateral eye. Imaging data, including color fundus photography, fluorescein angiography, near-infrared reflectance, fundus autofluorescence (FAF), and spectral-domain OCT, were obtained. Features preceding progression/conversion to advanced AMD (drusen, reticular pseudodrusen [RPD], MNV, incomplete/complete retinal pigment epithelium and outer retinal atrophy [iRORA/cRORA]) were assessed. Results: Of 30 fellow eyes with available follow-up images, 12 converted to GA (FAF), 2 converted to MNV, and 16 were nonconverters during the review period (median: 17.8 months). iRORA/cRORA features (present in all converters at baseline) were identified on OCT in eyes that progressed to GA. Median time interval from iRORA to cRORA and from cRORA to GA was 7 months each. GA development/progression was either drusen- or RPD-associated (n = 6 each). Eyes with baseline RPD showed faster GA progression versus eyes with drusen (1.49 vs. 0.38 mm2/year). Conclusions: RPD presence was associated with rapid GA lesion enlargement and may provide an early indication of faster GA progression.

Background and purpose Develop a translational assay of Transient Receptor Potential Ankyrin 1 (TRPA1) activity for use as a preclinical and clinical biomarker. Experimental approach Allyl isothiocyanate (AITC), capsaicin or citric acid were applied to ears of wildtype and Trpa1-knock out (Trpa1 KO) rats, and changes in dermal blood flow (DBF) were measured by laser speckle contrast imaging. In humans, the DBF, pain and itch responses to 5-20% AITC applied to the forearm were measured and safety was evaluated. Reproducibility of the DBF, pain and itch responses to topically applied 10% and 15% AITC were assessed at two visits separated by 13-15 days. DBF changes were summarized at 5-minute intervals as areas under the curve (AUC) and maxima. Intraclass correlation coefficient (ICC) was calculated to assess arm-arm and period-period reproducibility. Key results AITC- and citric acid-induced DBF were significantly reduced in Trpa1 KO rats compared to wildtype (90 ± 2% and 65 ± 11% reduction, respectively), whereas capsaicin response did not differ. In humans, each AITC concentration significantly increased DBF compared to vehicle with the maximal increase occurring 5 minutes post application. Ten percent and 15% AITC were selected as safe and effective stimuli. AUC from 0 to 5 minutes was the most reproducible metric of AITC-induced DBF across arms (ICC = 0.92) and periods (ICC = 0.85). Subject-reported pain was more reproducible than itch across visits (ICC = 0.76 vs 0.17, respectively). Conclusion and implications AITC-induced DBF is a suitable target engagement biomarker of TRPA1 activity for preclinical and clinical studies of TRPA1 antagonists.

Purpose This study measured and correlated degeneration of the junction between the inner and outer segments (IS/OS), the retinal pigment epithelium (RPE), and the choriocapillaris (CC) in Stargardt disease (STGD). Design Prospective cross-sectional study. Methods This study was conducted at the Casey Eye Institute. A total of 23 patients with STGD were enrolled and underwent optical coherence tomography angiography (OCTA). Scans were centered on the fovea. OCT slab projections and en face boundary maps were used to create masks to measure total IS/OS loss or RPE atrophy as well as regions of isolated IS/OS loss, isolated RPE atrophy, and matched IS/OS and RPE degeneration or intact IS/OS junction and RPE. CC vascular density (CCVD) was quantified from the CC angiogram. Outcomes included the area of loss, and the CCVD of degeneration in different areas was quantified and correlated. Results The total area of IS/OS loss was strongly correlated with the total area of RPE atrophy (r = 0.96; P Conclusions Photoreceptor and RPE degeneration exhibited a strong relationship wherein the IS/OS loss was 1.6-fold greater than that of RPE atrophy, supporting the theory that photoreceptor degeneration precedes RPE in STGD. Both the photoreceptors and the RPE degeneration contributed synergistically to CCVD attenuation, but extralesional CCVD also tended to be abnormal. The findings and techniques in this study may be of utility in developing endpoints for clinical trials.

This study investigates the determinants of initial public offering (IPO) underpricing by focusing on variables relating to information asymmetry, investor sentiment and corporate governance and examines whether the determinants of IPO underpricing in high-technology and non-high-technology IPOs differ. With data from Taiwan for 2009–2011, this study finds that overallotment is negatively related to underpricing, whereas market momentum, first-day trading volume and managers’ ownership retention rates are positively related to underpricing, particularly for high-technology IPOs. Our results support the signalling hypothesis in high-technology IPOs. JEL Classification: G12, G14, G24, G32

This study set out to evaluate the financing efficiency of low‐carbon companies. Applying a three‐stage data envelopment analysis with the data from 85 listed companies in China's low‐carbon industries over the period 2011 to 2017, this study has found that the overall financing efficiency of low‐carbon companies was relatively high, and the pure technical efficiency was quite steady over the period. The overall financing efficiency of these low‐carbon companies on average tended to change with the scale efficiency. This study has also shown that the scale efficiency was the main constraint influencing the financing efficiency of low‐carbon companies in China over the period. Our results are robust and have significant implications for policy makers and corporate managers.

Despite the development of effective therapies, a substantial proportion of asthmatics continue to have uncontrolled symptoms, airflow limitation, and exacerbations. Transient receptor potential cation channel member A1 (TRPA1) agonists are elevated in human asthmatic airways, and in rodents, TRPA1 is involved in the induction of airway inflammation and hyperreactivity. Here, the discovery and early clinical development of GDC-0334, a highly potent, selective, and orally bioavailable TRPA1 antagonist, is described. GDC-0334 inhibited TRPA1 function on airway smooth muscle and sensory neurons, decreasing edema, dermal blood flow (DBF), cough, and allergic airway inflammation in several preclinical species. In a healthy volunteer Phase 1 study, treatment with GDC-0334 reduced TRPA1 agonist-induced DBF, pain, and itch, demonstrating GDC-0334 target engagement in humans. These data provide therapeutic rationale for evaluating TRPA1 inhibition as a clinical therapy for asthma.

This study investigates the role of gender diversity in fraud commission and detection with a view to identifying whether companies with more female corporate leaders are less likely to be involved in financial statement fraud. Using a bivariate probit model, the role of female corporate leaders in financial statement fraud commission and detection is examined for Chinese listed companies from 2007 to 2018. The representation of female corporate leaders increases the likelihood of fraud detection, thus reducing firms’ propensity to engage in fraud. The finding confirms that women are risk averse and more committed to ethical practices than men in corporate leadership positions. Moreover, this impact of gender diversity is contingent upon the nature of ultimate controllers of listed companies: more female representation in top leadership roles can mitigate fraud commission or detect fraud effectively in non-state-owned enterprises, but not in state-owned enterprises. In addition, the recent anti-corruption campaign initiated by Chinese President Jinping Xi is a powerful form of public governance . Female corporate leaders play a more positive role in mitigating fraud commission and detecting fraud commission in the post-campaign period than in the pre-campaign period.

Purpose To use OCT angiography (OCTA)-derived quantitative metrics to assess the response of choroidal neovascularization (CNV) to pro re nata (PRN) anti–vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (AMD). Design Prospective, longitudinal cohort study. Participants Fourteen eyes from 14 study participants with treatment-naive neovascular AMD were enrolled. Methods Participants were evaluated monthly and treated with intravitreal anti-VEGF agents under a PRN protocol for 1 year. At each visit, two 3 × 3-mm2 OCTA scans were obtained. Custom image processing was applied to segment the outer retinal slab, suppress projection artifact, and automatically detect CNV. Choroidal neovascularization membrane area and CNV vessel area were calculated. Main Outcome Measures Individual and mean CNV membrane area and CNV vessel area at each visit; within-visit repeatability determined by coefficient of variation. Results Eight eyes showed the entire CNV to be within the 3 × 3-mm2 scanning area and had adequate image quality for CNV quantification. One patient (patient 2) was excluded from analysis because of the presence of a large subretinal hemorrhage overlying the CNV membrane. In the remaining patients, CNV vessel area was reduced by 39%, 50%, 43%, and 41% at months 1, 3, 6, and 12, respectively. Choroidal neovascularization membrane area was reduced by 39%, 51%, 54%, and 45% at months 1, 3, 6, and 12. At month 6, mean change from baseline was not statistically significant for CNV vessel area, whereas it was statistically significant for CNV membrane area. Neither metric was significantly different compared with baseline at month 12. Individual analyses revealed each CNV had a unique response under PRN treatment. Within-visit repeatability was 7.96% (coefficient of variation) for CNV vessel area and 7.37% for CNV membrane area. Conclusions In this small exploratory study of CNV response to PRN anti-VEGF treatment, both CNV vessel area and membrane area were reduced compared with baseline after 3 months. After 1 year of follow-up, these reductions were no longer statistically significant. When anti-VEGF treatment was withheld, increasing CNV vessel area over time often resulted in exudation, but it was not possible to determine exactly when exudation occurs.

This study investigates the impact of economic freedom (EcF) on analysts’ earnings forecast (AEF) accuracy. EcF is measured from five aspects: Government, Protection, Money, Trade, and Regulation. With the sample of 7,014 firms from 12 economies in the Asia-Pacific region over the 18-year period, this study finds an optimistic bias in AEFs. The optimistic bias is stronger for large firms, value firms, stock with high analyst coverage, and low dispersion in AEFs. Also, the optimistic bias is stronger from analysts in economies with less EcF than in more freedom ones. Analysts are making more accurate earnings forecasts for firms in economies with more EcF. In addition, the study finds the optimism bias reduced the earnings forecast accuracy. These findings may suggest that an increase of EcF would lead to more transparent financial statements, which further reduces the analysts’ forecast bias.

Purpose To determine the sensitivity and specificity of OCT angiography (OCTA) in the detection of choroidal neovascularization (CNV) in age-related macular degeneration (AMD). Design Prospective case series. Subjects A prospective series of 72 eyes were studied, which included eyes with treatment-naive CNV due to AMD, non-neovascular AMD, and normal controls. Methods All eyes underwent OCTA with a spectral domain OCT. The 3-dimensional angiogram was segmented into separate en face views including the inner retinal angiogram, outer retinal angiogram, and choriocapillaris angiogram. Detection of abnormal flow in the outer retina served as candidate CNV with OCTA. Masked graders reviewed structural OCT alone, en face OCTA alone, and en face OCTA combined with cross-sectional OCTA for the presence of CNV. Main Outcome Measure The sensitivity and specificity of CNV detection compared to the gold standard of fluorescein angiography and OCT was determined for structural spectral domain OCT alone, en face OCTA alone, and with en face OCTA combined with cross-sectional OCTA. Results Of 32 eyes with CNV, both graders identified 26 true positives with en face OCTA alone, resulting in a sensitivity of 81.3%. Four of the 6 false negatives had large subretinal hemorrhage and sensitivity improved to 94% for both graders if eyes with subretinal hemorrhage were excluded. The addition of cross-sectional OCTA along with en face OCTA improved the sensitivity to 100% for both graders. Structural OCT alone also had a sensitivity of 100%. The specificity of en face OCTA alone was 92.5% for grader A and 97.5% for grader B. The specificity of structural OCT alone was 97.5% for grader A and 85% for grader B. Cross-sectional OCTA combined with en face OCTA had a specificity of 97.5% for grader A and 100% for grader B. Conclusions Sensitivity and specificity for CNV detection with en face OCTA combined with cross-sectional OCTA approaches that of the gold standard of fluorescein angiography with OCT, and it is better than en face OCTA alone. Structural OCT alone has excellent sensitivity for CNV detection. False positives from structural OCT can be mitigated with the addition of flow information with OCTA.

Purpose To develop deep learning (DL) models to predict best-corrected visual acuity (BCVA) from optical coherence tomography (OCT) images from patients with neovascular age-related macular degeneration (nAMD). Methods Retrospective analysis of OCT images and associated BCVA measurements from the phase 3 HARBOR trial (NCT00891735). DL regression models were developed to predict BCVA at the concurrent visit and 12 months from baseline using OCT images. Binary classification models were developed to predict BCVA of Snellen equivalent of

Purpose To evaluate the morphological structure of ill-defined choroidal neovascularisation (CNV) with traditional fluorescein angiography (FA) compared with optical coherence tomographic angiography (OCTA). Methods A retrospective case series study of 11 eyes with ill-defined CNV on FA was performed. Eyes were scanned with commercially available spectral-domain optical coherence tomography (OCT) (70 000 A-scans/s). The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to distinguish blood flow from static tissue. En face OCT angiograms were compared with FA. Results Eleven cases of ill-defined CNV on FA were identified from 10 study participants. Mean age of the participants was 74.5±6.8 years. Six cases had late leakage from undetermined source (LLUS) and five had fibrovascular pigment epithelial detachment (FVPED). Combining cross-sectional structural OCT with OCT angiograms, all cases were found to have type 1 CNV that corresponded to occult CNV with FA. In all cases of occult CNV on FA, distinct vascular structures were visible with OCTA in the outer retinal/retinal pigment epithelium slab. The mean CNV vessel area was 2.61±3.65 mm 2 . The mean CNV vessel area in cases with FVPED was larger than that in cases with LLUS (4.69±4.72 mm 2 compared with 0.85±0.90 mm 2 , Mann-Whitney p value=0.04). Conclusions Although the sample size is small to draw conclusions and the nature of work is retrospective and descriptive, OCTA has the potential to improve visualisation of ill-defined CNV with dye-based angiography, including occult CNV.

PurposeThe purpose of this paper is to explore whether any discrepancy exists between the disclosed in SSB reports of Islamic banks and the disclosure index which was based on stakeholders’ expectation.Design/methodology/approachThis study uses contents analysis as the research method to explore Shariâ’ah audit reporting practices of Islamic Banks.FindingsThe study finds that the level of disclosures overall by IFIs in the sample is rather low compared to the stakeholder expectations.Practical implicationsThis paper has important implication for policy makers as it contribute to the debate on that uniform disclosure standards across the globe need to be implemented to ensure a uniform level of disclosure by Islamic banks.Originality/valueThis study is amongst the few studies that examine and explore the nature and extent ofShari’ahSupervisory Board in Islamic banks.

Purpose To elucidate the relationship between vessel density (VD) measurements and signal strength in OCT angiography (OCTA). Design Cross-sectional study. Participants Healthy volunteers. Methods OCT angiography images obtained from healthy volunteers were analyzed to demonstrate the relationship between signal strength index (SSI) and VD. Experiments were performed to determine the effects of signal strength reduction on VD measurements on the Optovue/AngioVue (Optovue, Inc, Fremont, CA) and Cirrus/AngioPlex OCTA (Carl Zeiss Meditec, Inc, Dublin, CA) systems. Signal strength reduction was generated by either neutral density filters (NDFs) or defocus. Main Outcome Measures Regression analysis of signal strength effects on VD. Results Vessel density decreased linearly with signal strength with high statistical significance on both OCTA systems tested and for all analyzed sources of variation in signal strength. The slope of VD versus SSI was greatest when signal strength was adjusted by NDFs, followed by defocus, interscan difference, interindividual variation, and left–right eye difference. Multivariate analysis revealed that both SSI and age had a significant effect on the interindividual variation in VD. Conclusions Vessel density measurements using OCTA were affected significantly by OCT signal strengths on 2 OCTA platforms. Investigators should exercise caution when interpreting VD data from OCTA scans. Quantification algorithms for OCTA should ideally remove the signal strength bias.

OBJECTIVE: To evaluate the projection-resolved (PR) optical coherence tomography angiography (OCTA) algorithm in detecting plexus-specific vascular abnormalities in retinal pathologies. DESIGN: Cross-sectional observational clinical study PARTICIPANTS: Patients diagnosed with retinal vascular diseases and healthy volunteers. METHODS: Eyes were imaged using an OCT system operating at 840 nm and employing the split-spectrum amplitude decorrelation algorithm. A novel algorithm suppressed projection artifacts inherent to OCTA. The volumetric scans were segmented and visualized on different plexuses. MAIN OUTCOME MEASURES: Qualitative observation of vascular abnormalities on both cross-sectional and en face PR-OCTA images. RESULTS: Eight illustrative cases are reported. In cases of diabetic retinopathy, retinal vessel occlusion, and retinitis pigmentosa, PR-OCTA detected retinal nonperfusion regions within deeper retinal plexuses not visualized by conventional OCTA. In age-related macular degeneration, cross-sectional PR-OCTA permitted the classification of choroidal neovascularization, and, in a case of retinal angiomatous proliferation, identified a vertical vessel contiguous with the deep capillary plexus. In macular telangiectasia, PR-OCTA detected a diving perifoveal vein and delineated subretinal neovascularization. CONCLUSIONS: Application of PR-OCTA promises to improve sensitive, accurate evaluation of individual vascular plexuses in multiple retinal diseases.

The use of stock options and credit default swaps (CDS) in banks is not uncommon. Stock options can induce risk-taking incentives, while CDS can be used to hedge against credit risk. Building on the existing literature on executive compensation and risk management, our study contributes novel empirical support for the role of stock options in restraining the use of CDS for hedging purposes. Based on data of CEO stock options and CDS held by 60 European banks during the period 2006–2011, we find a negative relationship between option-induced risk-taking incentives (vega) and the proportion of CDS held for hedging. However, the extent of CDS held for hedging is found to be positively related to default risk in the period leading to the financial crisis that erupted in 2007. The findings imply that restraining the use of stock options can incentivize hedging with CDS, but this risk management strategy will not necessarily produce lower default risk in times of systemic credit crisis.

Diabetic retinopathy is a microangiopathy that causes capillary occlusion, vascular hyperpermeability, and neovascularization in the retinal vasculature.1 Detailed clinical examination for grading disease severity for risk of progression and vision loss is the standard of care2, but ophthalmic angiography has played a critical role in understanding and care of the disease. Early Treatment of Diabetic Retinopathy Study (ETDRS) examined the fluorescein angiographic features of the posterior pole of patients with non-proliferative diabetic retinopathy and correlated the specific features with their risk of disease progression. 3,4 Fluorescein angiography (FA) is also used to identify retinal neovascularization (RNV) in situations where clinical examination cannot detect RNV or distinguish from other anomalous appearing vessels on the retinal surface. While angiography provides valuable additional information compared to clinical examination or fundus photography, it is not part of the routine diabetic eye examination. FA requires venipuncture and intravenous injection of a dye that has a moderate risk of nausea and a rare but well documented risk of anaphylaxis and death. 5 Also, a standard protocol FA acquires images over 10 minutes with repeated exposure to a very bright light source, 6 which can cause significant discomfort for patients. Optical coherence tomography (OCT) angiography, a novel imaging technique that uses decorrelation between resampled images to detect flow to construct 2- and 3-dimensional images of blood flow within the eye, offers an alternative angiographic technique without some of the drawbacks of FA. Our group has developed the split-spectrum amplitude decorrelation algorithm (SSADA) for efficiently detecting flow signals for angiography. 7 Applying this algorithm, an OCT angiogram in areas up to 6 × 6 mm area can be acquired in 3.5 seconds without intravenous injection. This study describes features of diabetic retinopathy as seen on OCT angiography.

Previous studies that have attempted to relate corporate environmental performance to financial performance have generated conflicting results. This paper presents the findings of a study on the relationship between greenhouse gas (GHG) emissions and the financial performance of Australian corporations. Using multiple regression models and data from a sample of 69 Australian public companies, this paper finds a positive correlation between GHG emissions and corporate financial performance. By testing the statistical significance of GHG emission factors in determining company Tobin's q, this study finds that a stronger Tobin's q often correlates with higher GHG emissions across all industry sectors. This finding is contrary to evidence found in previous studies conducted in other countries. The positive correlation found in this study could be explained with reference to the unique economic structure and development of Australia, particularly its dominant mining industry.

To detect macular perfusion defects in glaucoma using projection-resolved optical coherence tomography (OCT) angiography.Prospective observation study.A total of 30 perimetric glaucoma and 30 age-matched normal participants were included.One eye of each participant was imaged using 6×6-mm macular OCT angiography (OCTA) scan pattern by 70-kHz 840-nm spectral-domain OCT. Flow signal was calculated by the split-spectrum amplitude-decorrelation angiography algorithm. A projection-resolved OCTA (PR-OCTA) algorithm was used to remove flow projection artifacts. Four en face OCTA slabs were analyzed: the superficial vascular complex (SVC), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and all-plexus retina (SVC + ICP + DCP). The vessel density (VD), defined as the percentage area occupied by flow pixels, was calculated from en face OCTA. A novel algorithm was used to adjust the vessel density to compensate for local variations in OCT signal strength.Macular retinal VD, ganglion cell complex (GCC) thickness, and visual field (VF) sensitivity.Focal capillary dropout could be visualized in the SVC, but not the ICP and DVP, in glaucomatous eyes. In the glaucoma group, the SVC and all-plexus retinal VD (mean ± standard deviation: 47.2%±7.1% and 73.5%±6.6%) were lower than in the normal group (60.5%±4.0% and 83.2%±4.2%, both P0.001, t test). The ICP and DCP VD were not significantly lower in the glaucoma group. Among the overall macular VD parameters, the SVC VD had the best diagnostic accuracy as measured by the area under the receiver operating characteristic curve (AROC). The accuracy was even better when the worse hemisphere (inferior or superior) was used, achieving an AROC of 0.983 and a sensitivity of 96.7% at a specificity of 95%. Among the glaucoma participants, the hemispheric SVC VD values were highly correlated with the corresponding GCC thickness and VF sensitivity (P0.003). The reflectance compensation step in VD calculation significantly improved repeatability, normal population variation, and correlation with VF and GCC thickness.On the basis of PR-OCTA, glaucoma preferentially affects perfusion in the SVC in the macula more than the deeper plexuses. Reflectance-compensated SVC VD measurement by PR-OCTA detected glaucoma with high accuracy and could be useful in the clinical evaluation of glaucoma.

A microfluidic chip with microchannels ranging from 8 to 96 μm was used to mimic blood vessels down to the capillary level. Blood flow within the microfluidic channels was analyzed with split-spectrum amplitude-decorrelation angiography (SSADA)-based optical coherence tomography (OCT) angiography. It was found that the SSADA decorrelation value was related to both blood flow speed and channel width. SSADA could differentiate nonflowing blood inside the microfluidic channels from static paper. The SSADA decorrelation value was approximately linear with blood flow velocity up to a threshold Vsat of 5.83±1.33 mm/s (mean±standard deviation over the range of channel widths). Beyond this threshold, it approached a saturation value Dsat. Dsat was higher for wider channels, and approached a maximum value Dsm as the channel width became much larger than the beam focal spot diameter. These results indicate that decorrelation values (flow signal) in capillary networks would be proportional to both flow velocity and vessel caliber but would be capped at a saturation value in larger blood vessels. These findings are useful for interpretation and quantification of clinical OCT angiography results.

Purpose We observed and analyzed the morphologic characteristics of polypoidal lesions and abnormal branching vascular network (BVN) in patients with polypoidal choroidal vasculopathy (PCV) by optical coherence tomography angiography (OCTA). Methods A retrospective observational case series was done of patients with PCV. All patients were scanned with a 70-kHz spectral-domain OCT system using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm to distinguish blood flow from static tissue. The OCTA images of these patients were compared to those from indocyanine green angiography (ICGA). Semiautomated segmentation was used to further analyze the polypoidal lesion and the BVN. Results We studied 13 eyes of 13 patients 51 to 69 years old. A total of 11 patients were treatment-naive. Two patients had multiple anti-VEGF injections and one underwent photodynamic therapy (PDT). Optical coherence tomography angiography was able to detect the BVN in all cases. Using cross-sectional OCTA, BVN locations were shown to be in the space between the RPE and Bruch's membrane. Using en face OCTA, the BVN vascular pattern could be shown more clearly than by ICGA. Polypoidal lesions showed high flow signals in different patterns in 12 cases in the outer retina slab. Using cross-sectional OCTA, the polyps were shown to be just below the top of the pigment epithelial detachment (PED). In one case, the polypoidal lesion was not detectable at the outer retina slab. Conclusions Optical coherence tomography angiography is a noninvasive imaging tool for detecting vascular changes in PCV. Branching vascular networks showed more clearly on OCTA than on ICGA. Polypoidal lesions had variable patterns on OCTA and were not always detected. The OCTA patterns of the polypoidal lesions and the BVN are helpful in understanding the pathology of PCV.

Artifacts introduced by eye motion in optical coherence tomography angiography (OCTA) affect the interpretation of images and the quantification of parameters with clinical value. Eradication of such artifacts in OCTA remains a technical challenge. We developed an algorithm that recognizes five different types of motion artifacts and used it to evaluate the performance of three motion removal technologies. On en face maximum projection of flow images, the summed flow signal in each row and column and the correlation between neighboring rows and columns were calculated. Bright line artifacts were recognized by large summed flow signal. Drifts, distorted lines, and stretch artifacts exhibited abnormal correlation values. Residual lines were simultaneously a local maximum of summed flow and a local minimum of correlation. Tracking-assisted scanning integrated with motion correction technology (MCT) demonstrated higher performance than tracking or MCT alone in healthy and diabetic eyes.

Novel therapies for choroideremia, an X-linked recessive chorioretinal degeneration, demand a better understanding of the primary site(s) of cellular degeneration. Optical coherence tomography angiography allows for choriocapillaris (CC) imaging. We compared the extent of structural alterations of the CC, retinal pigment epithelium, and photoreceptors with multimodal imaging.In a clinical case series conducted from September 15, 2014, through February 5, 2015, 14 eyes of 7 male patients with choroideremia (median age, 34 years [interquartile range, 15-46 years]; age range, 13-48 years), 4 eyes of 2 women with choroideremia carrier state (both in mid-50s), and 6 eyes of 6 controls (median age, 42.5 years [interquartile range, 33-55 years]; age range, 24-55 years) underwent multimodal imaging with optical coherence tomography angiography and electroretinography. The mean (SD) macular CC density was 82.9% (13.4%) in patients with choroideremia, 93.0% (3.8%) in female carriers, and 98.2% (1.3%) in controls. The mean (SD) CC density in affected eyes was higher in regions with preserved (92.6% [5.8%]) vs absent (75.9% [12.6%]) ellipsoid zone (mean difference, 16.7%; 95% CI, 12.1% to 21.3%; P .001). Seventeen of 18 eyes of the patients and carriers had outer retinal tubulations forming pseudopod-like extensions from islands of preserved ellipsoid zone. Outer retinal tubulations were associated with absence of underlying retinal pigment epithelium and were longer (r = -0.62; 95% CI, -0.84 to -0.19; P .001) and more numerous (r = -0.71; 95% CI, -0.91 to -0.27; P .001) in more severely affected eyes.These findings suggest that regional changes in CC density correlate with photoreceptor structural alterations in choroideremia. Although closely coupled, the results suggest that retinal pigment epithelium loss is more extensive than photoreceptor loss.

Quantification of choroidal neovascularization (CNV) as visualized by optical coherence tomography angiography (OCTA) may have importance clinically when diagnosing or tracking disease. Here, we present an automated algorithm to quantify the vessel skeleton of CNV as vessel length. Initial segmentation of the CNV on en face angiograms was achieved using saliency-based detection and thresholding. A level set method was then used to refine vessel edges. Finally, a skeleton algorithm was applied to identify vessel centerlines. The algorithm was tested on nine OCTA scans from participants with CNV and comparisons of the algorithm’s output to manual delineation showed good agreement.

To assess long-term effects of genotype on chorioretinopathy severity in patients with mitochondrial trifunctional protein (MTP) disorders.Retrospective case series.Consecutive patients with MTP disorders evaluated at a single center from 1994 through 2015, including 18 patients with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and 3 patients with trifunctional protein deficiency (TFPD).Local records from all visits were reviewed. Every participant underwent a complete ophthalmic examination and was evaluated by a metabolic physician and dietitian. Nine patients underwent ancillary funduscopic imaging including optical coherence tomography (OCT) and OCT angiography.The primary outcome measure was best-corrected visual acuity at the final visit. Secondary outcome measures included spherical equivalent refraction, visual fields, electroretinography B-wave amplitudes, and qualitative imaging findings.Participants were followed up for a median of 5.6 years (range 0.3-20.2 years). The median age of LCHADD participants at initial and final visits was 2.3 and 11.9 years, whereas that for TFPD participants at initial and final visits was 4.7 and 15.5 years, respectively. Four long-term survivors older than 16 years were included (3 with LCHADD and 1 with TFPD). The LCHADD participants demonstrated a steady decline in visual acuity from an average of 0.23 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/34) at baseline to 0.42 logMAR (Snellen equivalent, 20/53) at the final visit, whereas TFPD patients maintained excellent acuity throughout follow-up. Participants with LCHADD, but not TFPD, showed an increasing myopia with a mean decrease in spherical equivalent refraction of 0.24 diopters per year. Visual fields showed sensitivity losses centrally associated with defects on OCT. Multimodal imaging demonstrated progressive atrophy of the outer retina in LCHADD, often preceded by the formation of outer retinal tubulations and choriocapillaris dropout. Electroretinography findings support the more severe clinical profile of LCHADD patients compared with TFPD patients; the function of both rods and cones are attenuated diffusely in LCHADD patients, but are within normal limits for TFPD patients.Despite improved survival with early diagnosis, medical management, and dietary treatment, participants with the LCHADD subtype of MTP disorder continue to demonstrate visually disabling chorioretinopathy. Multimodal imaging is most consistent with choriocapillaris loss exceeding photoreceptor loss.

This article addresses the under-researched issue of risk management (RM) and risk management capability building in small and medium sized enterprise (SMEs). It draws upon theories of social capital to explain enablers and obstacles for RM capability building and practice sharing in a small and medium-sized construction enterprise in China. Two related propositions are made: first, RM capability is built by SMEs without formal structures and knowledge; and second, such firms are more likely to adopt informal processes to develop RM capability. The article concludes that the role of cognitive capital is the most important for the RM capability building of SMEs and that cognitive capital plays a crucial role in accumulating structural and relational capital. It proposes a model of cognitive capital-based RM capability building in which integrates communication, knowledge, relationship and learning.

Human hearing loss often occurs as a result of damage or malformations to the functional soft tissues within the cochlea, but these changes are not appreciable with current medical imaging modalities. We sought to determine whether optical coherence tomography (OCT) could assess the soft tissue structures relevant to hearing using mouse models. We imaged excised cochleae with an altered tectorial membrane and during normal development. The soft tissue structures and expected anatomical variations were visible using OCT, and quantitative measurements confirmed the ability to detect critical changes relevant to hearing.

The tectorial membrane (TM) connects to the stereociliary bundles of outer hair cells (OHCs). Humans with an autosomal dominant C1509G mutation in alpha-tectorin, a protein constituent of the TM, are born with a partial hearing loss that worsens over time. The Tecta(C1509/+) transgenic mouse with the same point mutation has partial hearing loss secondary to a shortened TM that only contacts the first row of OHCs. As well, Tecta(C1509G/+) mice have increased expression of the OHC electromotility protein, prestin. We sought to determine whether these changes impact OHC survival. Distortion product otoacoustic emission thresholds in a quiet environment did not change to 6 months of age. However, noise exposure produced acute threshold shifts that fully recovered in Tecta (+/+) mice but only partially recovered in Tecta(C1509G/+) mice. While Tecta(+/+) mice lost OHCs primarily at the base and within all three rows, Tecta(C1509G/+) mice lost most of their OHCs in a more apical region of the cochlea and nearly completely within the first row. In order to estimate the impact of a shorter TM on the forces faced by the stereocilia within the first OHC row, both the wild type and the heterozygous conditions were simulated in a computational model. These analyses predicted that the shear force on the stereocilia is ~50% higher in the heterozygous condition. We then measured electrically induced movements of the reticular lamina in situ and found that while they decreased to the noise floor in prestin null mice, they were increased by 4.58 dB in Tecta(C1509G/+) mice compared to Tecta(+/+) mice. The increased movements were associated with a fourfold increase in OHC death as measured by vital dye staining. Together, these findings indicate that uncoupling the TM from some OHCs leads to partial hearing loss and places the remaining coupled OHCs at higher risk. Both the mechanics of the malformed TM and the increased prestin-related movements of the organ of Corti contribute to this higher risk profile.

Purpose – The purpose of this paper is to investigate multinational corporations' (MNCs) voluntary practice of including corporate social and environmental disclosure (CSED) on their web sites and characteristics that inspire MNCs to be more accountable in this regard.Design/methodology/approach – This study adopts discrimination analysis to test six hypotheses to determine which variables influence the MNCs to post their CSED on the web sites. Data from a sample of 49 MNCs were analyzed with STATISTICA. The independent variables tested include log of total assets (size) and log of total equity (size), return on assets (profitability), debt ratio (risk), auditor (Big4 and non‐Big4), country effect (origin the USA or non‐USA) and industry effect (manufacturing versus services).Findings – The results show that companies with a strong equity base and in a good financial condition have a propensity to voluntarily disclose more environmental information. For social disclosure, company size and the profitabilit...

Optical coherence tomography angiography has recently been used to visualize choroidal neovascularization (CNV) in participants with age-related macular degeneration. Identification and quantification of CNV area is important clinically for disease assessment. An automated algorithm for CNV area detection is presented in this article. It relies on denoising and a saliency detection model to overcome issues such as projection artifacts and the heterogeneity of CNV. Qualitative and quantitative evaluations were performed on scans of 7 participants. Results from the algorithm agreed well with manual delineation of CNV area.

The split-spectrum amplitude-decorrelation angiography algorithm was optimized on a spectral optical coherence tomography system using a flow phantom. The number of times the spectrum was split and the bandwidth of each split were adjusted to maximize the flow phantom decorrelation signal-to-noise ratio. The improvement in flow detection was then demonstrated with en face retinal angiograms. The optimized algorithm increased the detectable retinal microvascular flow and decreased the variability of the quantified vessel density in OCT retinal angiograms of healthy human subjects.

Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.

We propose methods to align interferograms affected by trigger jitter to a reference interferogram based on the information (amplitude/phase) at a fixed-pattern noise location to reduce residual fixed-pattern noise and improve the phase stability of swept source optical coherence tomography (SS-OCT) systems. One proposed method achieved this by introducing a wavenumber shift (k-shift) in the interferograms of interest and searching for the k-shift that minimized the fixed-pattern noise amplitude. The other method calculated the relative k-shift using the phase information at the residual fixed-pattern noise location. Repeating this wavenumber alignment procedure for all A-lines of interest produced fixed-pattern noise free and phase stable OCT images. A system incorporating these correction routines was used for human retina OCT and Doppler OCT imaging. The results from the two methods were compared, and it was found that the intensity-based method provided better results.

We demonstrate the proof of concept of a novel Fourier-domain optical coherence tomography contrast mechanism using gold nanorod contrast agents and a spectral fractionation processing technique. The methodology detects the spectral shift of the backscattered light from the nanorods by comparing the ratio between the short and long wavelength halves of the optical coherence tomography signal intensity. Spectral fractionation further divides the halves into sub-bands to improve spectral contrast and suppress speckle noise. Herein, we show that this technique can detect gold nanorods in intralipid tissue phantoms. Furthermore, cellular labeling by gold nanorods was demonstrated using retinal pigment epithelial cells in vitro.

The patterns and determinants of corporate social and environmental disclosure (CSED) in Hong Kong (HK) are examined by analysing 154 annual reports of 33 HK listed companies from 1993 to 1997. The research finds that industry difference has an impact on the amount, content theme and location of CSED. There is a positive correlation between company size and the level of CSED. Utility companies disclose more CSED than property and banking firms.

The tonotopic map of the mammalian cochlea is commonly thought to be determined by the passive mechanical properties of the basilar membrane. The other tissues and cells that make up the organ of Corti also have passive mechanical properties; however, their roles are less well understood. In addition, active forces produced by outer hair cells (OHCs) enhance the vibration of the basilar membrane, termed cochlear amplification. Here, we studied how these biomechanical components interact using optical coherence tomography, which permits vibratory measurements within tissue. We measured not only classical basilar membrane tuning curves, but also vibratory responses from the rest of the organ of Corti within the mouse cochlear apex in vivo. As expected, basilar membrane tuning was sharp in live mice and broad in dead mice. Interestingly, the vibratory response of the region lateral to the OHCs, the “lateral compartment,” demonstrated frequency-dependent phase differences relative to the basilar membrane. This was sharply tuned in both live and dead mice. We then measured basilar membrane and lateral compartment vibration in transgenic mice with targeted alterations in cochlear mechanics. Prestin499/499, Prestin−/−, and TectaC1509G/C1509G mice demonstrated no cochlear amplification but maintained the lateral compartment phase difference. In contrast, SfswapTg/Tg mice maintained cochlear amplification but did not demonstrate the lateral compartment phase difference. These data indicate that the organ of Corti has complex micromechanical vibratory characteristics, with passive, yet sharply tuned, vibratory characteristics associated with the supporting cells. These characteristics may tune OHC force generation to produce the sharp frequency selectivity of mammalian hearing.

The Notch signaling pathway is thought to regulate multiple stages of inner ear development. Mutations in the Notch signaling pathway cause disruptions in the number and arrangement of hair cells and supporting cells in sensory regions of the ear. In this study we identify an insertional mutation in the mouse Sfswap gene, a putative splicing factor, that results in mice with vestibular and cochlear defects that are consistent with disrupted Notch signaling. Homozygous Sfswap mutants display hyperactivity and circling behavior consistent with vestibular defects, and significantly impaired hearing. The cochlea of newborn Sfswap mutant mice shows a significant reduction in outer hair cells and supporting cells and ectopic inner hair cells. This phenotype most closely resembles that seen in hypomorphic alleles of the Notch ligand Jagged1 (Jag1). We show that Jag1; Sfswap compound mutants have inner ear defects that are more severe than expected from simple additive effects of the single mutants, indicating a genetic interaction between Sfswap and Jag1. In addition, expression of genes involved in Notch signaling in the inner ear are reduced in Sfswap mutants. There is increased interest in how splicing affects inner ear development and function. Our work is one of the first studies to suggest that a putative splicing factor has specific effects on Notch signaling pathway members and inner ear development., Author Summary The organ of Corti is a sensory structure in the cochlea that mediates our sense of hearing. It consists of one row of inner hair cells and three rows of outer hair cells, together with an array of neighboring supporting cells. The precise arrangement of these different cell types is regulated very tightly by a number of signaling pathways during embryonic development, and mutations in genes that regulate this pattern often lead to deafness. We have generated a mouse mutant containing a lentiviral insertion in a gene encoding a putative RNA splicing factor called Sfswap. Homozygous mutant mice have hearing and balance defects, and have an abnormal arrangement of hair cells in their cochlea. These defects are consistent with defects in the Notch signaling pathway. We show that Sfswap mutants interact genetically with a mutation in Jagged1, which encodes a Notch ligand. We show that expression of some genes involved in Notch signaling is disrupted in Sfswap mutant mice. Our work is one of the first studies to show that a putative splicing factor has specific effects on Notch signaling pathway members and on inner ear development.

Given the frequent use of improvised explosive devices (IEDs) around the world, the study of traumatic blast injuries is of increasing interest. The ear is the most common organ affected by blast injury because it is the body’s most sensitive pressure transducer. We fabricated a blast chamber to re-create blast profiles similar to that of IEDs and used it to develop a reproducible mouse model to study blast-induced hearing loss. The tympanic membrane was perforated in all mice after blast exposure and found to heal spontaneously. Micro-computed tomography demonstrated no evidence for middle ear or otic capsule injuries; however, the healed tympanic membrane was thickened. Auditory brainstem response and distortion product otoacoustic emission threshold shifts were found to be correlated with blast intensity. As well, these threshold shifts were larger than those found in control mice that underwent surgical perforation of their tympanic membranes, indicating cochlear trauma. Histological studies one week and three months after the blast demonstrated no disruption or damage to the intra-cochlear membranes. However, there was loss of outer hair cells (OHCs) within the basal turn of the cochlea and decreased spiral ganglion neurons (SGNs) and afferent nerve synapses. Using our mouse model that recapitulates human IED exposure, our results identify that the mechanisms underlying blast-induced hearing loss does not include gross membranous rupture as is commonly believed. Instead, there is both OHC and SGN loss that produce auditory dysfunction.

Automated detection and grading of angiographic high-risk features in diabetic retinopathy can potentially enhance screening and clinical care. We have previously identified capillary dilation in angiograms of the deep plexus in optical coherence tomography angiography as a feature associated with severe diabetic retinopathy. In this study, we present an automated algorithm that uses hybrid contrast to distinguish angiograms with dilated capillaries from healthy controls and then applies saliency measurement to map the extent of the dilated capillary networks. The proposed algorithm agreed well with human grading.