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Cell-shape is a conglomerate of mechanical, chemical, and biological mechanisms that reflects the cell biophysical state. In a specific application, we consider aortic valve interstitial cells (AVICs), which maintain the structure and function of aortic heart valve leaflets. Actomyosin stress fibers help determine AVIC shape and facilitate processes such as adhesion, contraction, and mechanosensing. However, detailed 3D assessment of stress fiber architecture and function is currently impractical. Herein, we assessed AVIC shape and contractile behaviors using hydrogel-based 3D traction force microscopy to intuit the orientation and behavior of AVIC stress fibers. We utilized spherical harmonics (SPHARM) to quantify AVIC geometries through three days of incubation, which demonstrated a shift from a spherical shape to forming substantial protrusions. Furthermore, we assessed changes in post-three day AVIC shape and contractile function within two testing regimes: (1) normal contractile level to relaxation (cytochalasin D), and (2) normal contractile level to hyper-contraction (endothelin-1). In both scenarios, AVICs underwent isovolumic shape changes and produced complex displacement fields within the hydrogel. AVICs were more elongated when relaxed and more spherical in hyper-contraction. Locally, AVIC protrusions contracted along their long axis and expanded in their circumferential direction, indicating predominately axially aligned stress fibers. Furthermore, the magnitude of protrusion displacements was correlated with protrusion length and approached a consistent displacement plateau at a similar critical length across all AVICs. This implied that stress fiber behavior is conserved, despite great variations in AVIC shapes. We anticipate our findings will bolster future investigations into AVIC stress fiber architecture and function. Within the aortic valve there exists a population of aortic valve interstitial cells, which orchestrate the turnover, secretion, and remodeling of its extracellular matrix, maintaining tissue integrity and ultimately sustaining the proper mechanical function. Alterations in these processes are thought to underlie diseases of the aortic valve, which affect hundreds of thousands domestically and world-wide. Yet, to date, there are no non-surgical treatments for aortic heart valve disease, in part due to our limited understanding of the underlying disease processes. In the present study, we built upon our previous study to include a full 3D analysis of aortic valve interstitial cell shapes at differing contractile levels. The resulting detailed shape and deformation analysis provided insight into the underlying stress-fiber structures and mechanical behaviors. [Display omitted] [ABSTRACT FROM AUTHOR]

Since the American Board of Radiology (ABR) instituted the new system of board certification, there has been much discussion as to the test's validity. We decided to evaluate if subjective evaluation of resident performance correlated with ABR Qualifying (Core) Examination performance at this single institution. Data regarding resident evaluation scores by attending physicians and passage of board examinations was gathered regarding residents who had taken the ABR Qualifying (Core) Examination from 2013 through 2019 for a total of 42 residents, eight of whom failed the ABR Qualifying (Core) Examination on their first attempt. A univariate analysis comparing scores with resident passage or failure of the ABR Qualifying (Core) Examination on the first attempt and analyses correcting for class year only and class year and number of evaluations was performed. The non-weighted average evaluation score of years 1, 2, and 3 was 80.24% for those who failed the ABR Qualifying (Core) Examination and 83.71 % for those who passed. On univariate analysis along with analyses correcting for class year only and class year along with number of evaluations, there was a statistically significant correlation with decreased evaluation scores averaged over the three years of residency and failure of the ABR Qualifying (Core) Examination (p = 0.0102, p = 0.003, and p = 0.0043). The statistical significance held for the average numerical score in each individual year of training in all analyses except for year 1 of the univariate analysis (p = 0.1264). At the studied institution, there was a statistically significant correlation between lower subjective faculty evaluation scores and failure of the ABR Qualifying (Core) Examination. [ABSTRACT FROM AUTHOR]

Allergic conjunctivitis (AC) is an ocular inflammatory disease with symptoms driven by eosinophils and mast cells. Allergic comorbidities are common. Current treatments are often ineffective in severe AC and limited by potential side effects. Lirentelimab is an anti–sialic acid–binding immunoglobulin-like lectin-8 mAb that depletes eosinophils and inhibits mast cells. We sought to determine safety and preliminary efficacy of lirentelimab in an open-label, phase 1b study. Patients with chronic, severely symptomatic atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC, and who had history of topical or systemic corticosteroid use, were enrolled to receive up to 6 monthly lirentelimab infusions (dose 1: 0.3 mg/kg, dose 2: 1 mg/kg, subsequent doses: 1 or 3 mg/kg). Changes from baseline in peripheral blood eosinophils, changes in patient-reported symptoms (measured by daily Allergic Conjunctivitis Symptom Questionnaire, including atopic comorbidities), changes in investigator-reported ocular signs and symptoms (Ocular Symptom Scores), changes in quality of life, and changes in tear cytokine and chemokine levels were assessed. Thirty patients were enrolled (atopic keratoconjunctivitis n = 13, vernal keratoconjunctivitis n = 1, perennial AC n = 16), 87% of whom had atopic comorbidities. After lirentelimab treatment, mean improvement was observed in Allergic Conjunctivitis Symptom Questionnaire score (−61%; 95% CI, −75% to −48%) and Ocular Symptom Scores (−53%; 95% CI, −76% to −31%), consistent across atopic keratoconjunctivitis, vernal keratoconjunctivitis, and perennial AC groups. There was substantial improvement in atopic comorbidities, with −55% (95% CI, −78% to −31%), −50% (95% CI, −82% to −19%), and −63% (95% CI, −87% and −38%) reduction in symptoms of atopic dermatitis, asthma, and rhinitis, respectively. Levels of key mediators of inflammation were reduced in patient tears after lirentelimab treatment. The most common adverse effects were mild to moderate infusion-related reactions. Lirentelimab was well tolerated, improved severe AC and concomitant atopic symptoms, and reduced inflammatory mediators in patient tears. [ABSTRACT FROM AUTHOR]

• We investigate the relationship between political risk and U.S. mutual fund performance. • We construct the weighted portfolio's political risk at both macro- and stock level. • We find a negative impact of the portfolio's political risk on fund performance at stock level. • Mutual funds are immune from the political risk at the macro level. • We also demonstrate that partisanship matters to mutual fund performance. Using text-based measures of firm-level political risk, we find a negative impact of the portfolio's weighted political risk on U.S. mutual fund performance. This relationship is robust to a wide range of topic-specific political risks at the firm level. We, however, find that national geopolitical risk, the U.S. state-level economic policy uncertainty, and Brexit-induced risk do not affect mutual fund performance. Our results suggest that even though mutual funds are immune from political risk at the macro level, they are significantly exposed to idiosyncratic political risk. We also demonstrate that partisanship matters to mutual fund performance. [ABSTRACT FROM AUTHOR]

Soil is contaminated with salinity, which inhibits plant growth and development and reduces crop yields. The DREB (dehydration responsive element binding protein) gene responds to salt stresses through enhanced transcriptional expression and activation of genes involved in plant salinity resistance. In this study, we present the results of the analysis of the expression of the GmDREB6 transgene, a gene that encodes the soybean DREB6 transcription factor, regulating the transcription of the NtP5CS and NtCLC genes in transgenic tobacco under salt stress conditions. The transcription of GmDREB6, NtP5CS , and NtCLC in transgenic tobacco lines was confirmed by qRT-PCR. Under salt stress conditions, the GmDREB6 gene transcription levels in the transgenic tobacco lines L1 and L9 had increased from 2.40- to 3.22- fold compared with the condition without salinity treatment. Two transgenic lines, L1 and L9, had transcription levels of the P5CS gene that had increased from 1.24- to 3.60- fold compared with WT plants. For the NtCLC gene, under salt stress conditions, the transgenic lines had transcription levels that had increased by 3.65–4.54 (fold) compared with WT plants (P < 0.05). The L1-transgenic tobacco line showed simultaneous expression of both the GmDREB6 transgene and two intrinsic genes, the NtP5CS and NtCLC genes. This study demonstrated that expression of the GmDREB6 gene from soybean increases the transcription levels of the NtP5CS and NtCLC genes in transgenic tobacco plants under salt stress conditions. The analysis results have suggested that the GmDREB6 gene is a potential candidate for improving the salt tolerance of plants, opening up research and development opportunities for salt stress-tolerant crops to respond to climate change and the rise in sea levels. [ABSTRACT FROM AUTHOR]

• Effects of nonlinear dissipation on optical beams and light bullets in cubic-quintic media are investigated. • A perturbative technique for the collision-induced dynamics of solitons in dimensions higher than 1 is proposed. • Theoretical expressions for the soliton collision-induced amplitude dynamics are derived. • Simulations of nonlinear Schrödinger models are demonstrated to validate the theoretical calculations. We derive the expressions for the collision-induced amplitude dynamics of two flat-top solitons in spatial dimensions of 1, 2, and 3 caused by the generic weak nonlinear loss under the framework of coupled cubic-quintic (n + 1)D nonlinear Schrödinger equations for n = 1 , 2 , 3. We develop a new perturbative technique which is mainly based on the calculations for the fast collision-induced changes in the soliton envelope and the use of the single perturbed soliton solution for the calculations. These results quantify the energy dropdown due to a fast collision of two pulses (n = 1) , or two optical beams (n = 2), or two light bullets (n = 3) in cubic-quintic nonlinear media with dissipation. The theoretical calculations are then confirmed by numerical simulations with the corresponding coupled nonlinear Schrödinger equations. Our approach can be used for studying the effects of dissipation on colliding solitons described by the coupled nonlinear Schrödinger models, where the unperturbed equation is nonintegrable. [ABSTRACT FROM AUTHOR]

We analyze a Crank–Nicolson finite difference discretization for the perturbed (2+1)D nonlinear Schrödinger equation with saturable nonlinearity and a perturbation of cubic loss. We show the boundedness, the existence and uniqueness of a numerical solution. We establish the error bound to prove the convergence of the numerical solution. Moreover, we find that the convergence rate is at the second order in both time step and spatial mesh size only under a mild and simple assumption. The numerical scheme is validated by the extensive simulations of the (2+1)D saturable nonlinear Schrödinger equation with cubic loss. The simulations for traveling 2D solitons are implemented by using an accelerated imaginary-time evolution scheme and the Crank–Nicolson finite difference method. • The (2+1)D NLS saturable equations can stabilize 2D solitons. • The rigorous analysis for the perturbed (2+1)D saturable NLS equation is demonstrated for the first time. • By appropriate settings, the existence and the uniqueness of a solution are proved. • An error analysis is established and validated by the simulations for traveling 2D solitons. [ABSTRACT FROM AUTHOR]

Improving or maintaining visual acuity is the main goal for the treatment of neovascular age-related macular degeneration (nAMD). Current nAMD standard of care dictates frequent intravitreal (IVT) anti–vascular endothelial growth factor (VEGF) injections, which places a substantial burden on patients, caregivers, and physicians. Brolucizumab, a newly developed anti-VEGF molecule for nAMD treatment, has demonstrated longer durability and improvement in visual and anatomic outcomes in clinical studies in a q12-week regimen, indicating its potential to reduce treatment burden as an important therapeutic tool in nAMD management. This review focuses on the development of brolucizumab and the preclinical and clinical studies evaluating its efficacy, tolerability, and safety. Brolucizumab (also known as "RTH258" and "ESBA1008") is a humanized, single-chain variable fragment (scFv) antibody with a molecular mass of approximately 26 kDa that inhibits VEGF-A. Preclinical studies show that brolucizumab readily penetrates the retina to reach the retinal pigment epithelium (RPE)/choroid with minimal subsequent systemic exposure. The safety, tolerability, and efficacy of a single IVT brolucizumab administration in patients with treatment-naïve nAMD were first demonstrated in the SEE Phase 1/2 study. The OSPREY Phase 2 study showed brolucizumab to be as efficacious as aflibercept in a q8-week regimen with regard to best-corrected visual acuity (BCVA) and brolucizumab achieving greater fluid resolution. Brolucizumab-treated patients in the OSPREY study were subsequently challenged with a q12-week dosing interval, and the outcomes provided key information for the study design and end points of the Phase 3 studies. In the HAWK and HARRIER Phase 3 studies, after 3 monthly loading injections, brolucizumab treatment regimen (q12-week or q8-week) was guided by individual disease activity assessment using functional and anatomic parameters (central subfield thickness [CST], intraretinal fluid [IRF], or subretinal fluid [SRF]) versus aflibercept (q8-week). Fewer brolucizumab 6-mg treated eyes had disease activity versus aflibercept, and anatomic outcome results at weeks 16 and 48 demonstrate brolucizumab as a potent drying agent. Moreover, of patients treated with 6 mg brolucizumab, 55.6% and 51.0% maintained a q12-week dosing interval immediately after the loading phase until week 48 in HAWK and HARRIER, respectively. These Phase 3 studies demonstrated that the brolucizumab q12-week regimen maintains efficacy and safety while reducing treatment burden associated with regular IVT injections for patients with nAMD. [ABSTRACT FROM AUTHOR]

Circular bio-based building materials are "materials wholly or partly derived from renewable biological origins, or by-products and biowaste of plant and/or animal biomass that can be used as raw building materials and decorating items in construction, in their original forms or after being reprocessed". Literature shows that using these materials can represent a coherent solution to mitigate the climate impacts of the building sector according to the circular economy model. However, previous studies are fragmented due to the heterogeneity in the studied material types, scales of case studies, and sustainability assessment methods applied. Therefore, this systematic and bibliometric literature review of 97 articles aims to categorise case studies, review the state-of-the-art of sustainability assessment of case studies and highlight the pros and cons of circular bio-based building materials. Results indicate that the material scale is the most researched compared to the other scales. Environmental analysis, primarily employing life cycle assessment, is the most frequently researched, followed by economic analysis, while social impact research is still in an early stage. Concerning the pros and cons, circular bio-based building materials outperform traditional materials in reducing initial production costs and mitigating environmental impacts, especially climate change and abiotic resource use. However, some materials perform worse in categories like eutrophication, land use, etc., and may not be economically viable from an entire life cycle perspective. [Display omitted] [ABSTRACT FROM AUTHOR]

• The theoretical procedures for shifting the frequency of solitons are proposed. • These procedures are confirmed by numerical simulations with the propagation model. • Stabilizing soliton propagation and controlling soliton collisions are presented. • The results open a way for controlling soliton frequency and soliton dynamics. We develop the theoretical procedures for shifting the frequency of a single soliton and of a sequence of solitons of the nonlinear Schrödinger equation. The procedures are based on simple transformations of the soliton pattern in the Fourier domain and on the shape-preserving property of solitons. These theoretical frequency shifting procedures are verified by numerical simulations with the nonlinear Schrödinger equation using the split-step Fourier method. In order to demonstrate the use of the frequency shifting procedures, two important applications are presented: (1) stabilization of the propagation of solitons in waveguides with frequency dependent linear gain-loss; (2) induction of repeated soliton collisions in waveguides with weak cubic loss. The results of numerical simulations with the nonlinear Schrödinger model are in very good agreement with the theoretical predictions. [ABSTRACT FROM AUTHOR]

Abstract Correlation of the fission product Cs-137, U, and Pu with burn-up has been used to develop a method for determining the U and Pu contents of items originating from 30 spent fuel assemblies (SFAs), which became unusable due to an event in 2003 at Paks Nuclear Power Plant (NPP), Hungary. A mixture of broken fuel rods, pellets, and parts of the cladding were repacked into 72 canisters, whose nuclear material content was to be determined. In this paper, the method has been updated for scanning Cs137 activity and the Cs134/Cs137 ratio along the canisters in 100 s real time intervals by an HPGe detector using a narrow collimator. The effect of mixed burn-up and the irregular fuel geometry was taken into account by using the so-called infinite energy method. The absorption correction factor seems to be constant for all canisters. This is probably due to the overwhelming effect of the thick absorbing water layer in front of canisters lowered down into the service pit, where the measurements were done. Highlights • Taking U, Pu inventory of broken spent fuel pieces repacked into 72 canisters. • Nuclear inventory was prepared for individual canisters as separate batches. • Correlations with burn-up used for Cs137, U, Pu contents, Cs134/Cs137. • Almost constant absorption due to the thick water layer in front of canisters. • Hence, results more accurate by pure gamma spectrometry than by neutron measurements. [ABSTRACT FROM AUTHOR]

In recent decades, the treatment paradigm for noninfectious intermediate uveitis, posterior uveitis, and panuveitis, a group of intraocular inflammatory diseases, has included systemic and local (periocular or intraocular) corticosteroids, biologics, and other steroid-sparing immunomodulatory therapy agents. Recently, an intravitreal formulation of sirolimus, an immunosuppressant that inhibits the mammalian target of rapamycin, a key regulator of cell growth in the immune system, was developed. On the basis of this mechanism and the local method of delivery, it was hypothesized that intravitreal sirolimus can improve ocular inflammation in patients with noninfectious intermediate uveitis, posterior uveitis, and panuveitis, with minimal systemic exposure and systemic adverse events (AEs). This review summarizes the pharmacokinetics, efficacy, and safety results of intravitreal sirolimus from 3 preclinical studies and 4 phase 1–3 clinical studies. Preclinical studies in rabbits showed that 22 to 220 μg intravitreal sirolimus results in sustained release of sirolimus in the vitreous for 2 months or more, with systemic concentrations below the threshold for systemic immunosuppression (approximately 8 ng/ml). Subsequently, 2 phase 1 studies (n = 50 and n = 30) established that intravitreal sirolimus improves ocular inflammation in humans. Further investigation in phase 2 and 3 studies (n = 24 and n = 347, respectively) suggested that 440 μg has the best benefit-to-risk profile. In the phase 3 study, the proportion of patients who showed complete resolution of ocular inflammation at month 5 was significantly higher in the 440-μg group than in the 44-μg group (22.8% vs. 10.3%; P = 0.025, Fisher exact test). In addition, 47 of 69 patients (68.1%) who were treated with systemic corticosteroids at baseline discontinued corticosteroid use at month 5. No sirolimus-related systemic AEs were reported in phase 1–3 studies. Collectively, these preclinical and clinical study data of intravitreal sirolimus support the therapeutic rationale of treating noninfectious uveitis with a local mammalian target of rapamycin inhibitor and suggest that 440 μg intravitreal sirolimus has the potential to be an effective and well-tolerated anti-inflammatory and corticosteroid-sparing treatment for noninfectious intermediate uveitis, posterior uveitis, and panuveitis. [ABSTRACT FROM AUTHOR]

Many researchers who study the impact of computer-based assessment (CBA) focus on the affordances or complexities of CBA approaches in comparison to traditional assessment methods. This study examines how CBA approaches were configured within and between modules, and the impact of assessment design on students' engagement, satisfaction, and pass rates. The analysis was conducted using a combination of longitudinal visualisations, correlational analysis, and fixed-effect models on 74 undergraduate modules and their 72,377 students. Our findings indicate that educators designed very different assessment strategies, which significantly influenced student engagement as measured by time spent in the virtual learning environment (VLE). Weekly analyses indicated that assessment activities were balanced with other learning activities, which suggests that educators tended to aim for a consistent workload when designing assessment strategies. Since most of the assessments were computer-based, students spent more time on the VLE during assessment weeks. By controlling for heterogeneity within and between modules, learning design could explain up to 69% of the variability in students' time spent on the VLE. Furthermore, assessment activities were significantly related to pass rates, but no clear relation with satisfaction was found. Our findings highlight the importance of CBA and learning design to how students learn online. [ABSTRACT FROM AUTHOR]

Application of cattle slurry to grassland soil has environmental impacts such as ammonia volatilization and greenhouse gas emissions. The extent, however, depends on application method and soil conditions through their effects on infiltration and oxygen (O 2 ) availability during subsequent decomposition. Here, we applied O 2 planar optode and N 2 O isotopomer techniques to investigate the linkage between soil O 2 dynamics and N 2 O production pathways in soils treated with cattle slurry (treatment CS) and tested the effect of the nitrification inhibitor 3,4-dimethyl pyrazole phosphate, DMPP (treatment CSD). Two-dimensional planar optode images of soil O 2 over time revealed that O 2 depletion ultimately extended to 1.5 cm depth in CS, as opposed to 1.0 cm in CSD. The 15 N site preference (SP) and δ 18 O of emitted N 2 O varied between 11-25‰ and 35–47‰, respectively, indicating a mixture of production sources during the incubation. An early peak of N 2 O emission occurred in both manure treated soils by day 1, with the highest SP values and δ 18 O-N 2 O indicating that fungal denitrification of nitrate in the soil was the main contributor to the early peak. During the first five days, N 2 O fluxes in CS and CSD treatments were similar, and hence nitrification did not influence N 2 O emissions for several days under the experimental conditions of this study. The second peak of N 2 O emission occurring only in CS peaking around day 14, could be due to both nitrification and bacterial denitrification of nitrate produced during incubation. Over 18 days, the application of DMPP substantially mitigated N 2 O emissions by 60% compared to untreated CS in the investigated system which in terms of aeration status corresponded to wet or compacted grassland soil. Using this novel combination of O 2 planar optode imaging and N 2 O isotopomer analysis, our results provide a better understanding of the coupled O 2 and N 2 O dynamics in manure-amended soils, and they illustrate the roles of bacterial and fungal denitrification in N 2 O production in grassland soil under high soil water content. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the efficacy and safety of intravitreal sirolimus in the treatment of noninfectious uveitis (NIU) of the posterior segment (i.e., posterior, intermediate, or panuveitis). Design Phase III, randomized, double-masked, active-controlled, 6-month study with intravitreal sirolimus. Participants Adults with active NIU of the posterior segment (intermediate, posterior, or panuveitis), defined as a vitreous haze (VH) score >1+. Subjects discontinued NIU medications before baseline, except for systemic corticosteroids, which were allowed only for those already receiving them at baseline and were rapidly tapered after baseline per protocol. Methods Intravitreal sirolimus assigned 1:1:1 at doses of 44 (active control), 440, or 880 μg, administered on Days 1, 60, and 120. Main Outcome Measures The primary efficacy outcome was the percentage of subjects with VH 0 response at Month 5 (study eye) without use of rescue therapy. Secondary outcomes at Month 5 were VH 0 or 0.5+ response rate, corticosteroid tapering success rate (i.e., tapering to a prednisone-equivalent dosage of ≤5 mg/day), and changes in best-corrected visual acuity (BCVA). Adverse events during the double-masked treatment period are presented. Results A total of 347 subjects were randomized. Higher proportions of subjects in the intravitreal sirolimus 440 μg (22.8%; P = 0.025) and 880 μg (16.4%; P = 0.182) groups met the primary end point than in the 44 μg group (10.3%). Likewise, higher proportions of subjects in the 440 μg (52.6%; P = 0.008) and 880 μg (43.1%; P = 0.228) groups achieved a VH score of 0 or 0.5+ than in the 44 μg group (35.0%). Mean BCVA was maintained throughout the study in each dose group, and the majority of subjects receiving corticosteroids at baseline successfully tapered off corticosteroids (44 μg [63.6%], 440 μg [76.9%], and 880 μg [66.7%]). Adverse events in the treatment and active control groups were similar in incidence, and all doses were well tolerated. Conclusions Intravitreal sirolimus 440 μg demonstrated a significant improvement in ocular inflammation with preservation of BCVA in subjects with active NIU of the posterior segment. [ABSTRACT FROM AUTHOR]

Estimation of the temperature-dependent absorption coefficient in laser welding process is known as high non-linear inverse problem. Thus, it is necessary to propose a robust and efficiency method to estimate this coefficient. In this paper, a modified Newton–Raphson method combined with the concept of future time is presented to estimate the absorption coefficient in the laser welding process. The special characteristics of this method are that no preselected functional form for the unknown absorption coefficient is necessary and non-linear least-squares is not needed in the algorithm. Two examples have been fulfilled to demonstrate the proposed method. The results show that the proposed method is an accurate, stable, and efficient method to estimate the absorption coefficient in the laser welding process. In addition, two kinds of future time description are considered in this work. One is a linear type and the other is a constant type. From the estimated results, it is evidenced that the accuracy of the estimated results for the linear type of future time description is higher than that for the constant one of future time description. [ABSTRACT FROM AUTHOR]

Purpose To evaluate visual and anatomic outcomes after intravitreal aflibercept injection (IAI) versus laser in diabetic macular edema (DME) patients with and without prior anti–vascular endothelial growth factor (VEGF) treatment for DME. Design Post hoc analysis of eyes from 2 similarly designed, phase 3 trials, VISTA and VIVID. Participants Patients (eyes) with DME with central involvement from VISTA (n = 461) and VIVID (n = 404). Methods Eyes received IAI 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 monthly doses (2q8), or macular laser photocoagulation. Main Outcome Measures This study reports exploratory outcomes through week 100. Analyses focused on VISTA because more patients received prior anti-VEGF therapy in VISTA (42.9%) versus VIVID (8.9%). Results Of 42.9% of patients in VISTA who received prior anti-VEGF treatment, 83.3% to 92.6% received ≥ 1 prior injections of bevacizumab, and 71.4% to 82.4% received bevacizumab only as prior anti-VEGF treatment for a duration ranging from 28 days to 3.9 years. In patients with prior anti-VEGF treatment, mean best-corrected visual acuity (BCVA) changes from baseline in the IAI 2q4, IAI 2q8, and laser groups were +10.4 letters, +10.5 letters, and −0.7 letters at week 52 and +10.9 letters, +10.8 letters, and −0.8 letters at week 100, respectively. Corresponding changes in patients without prior anti-VEGF treatment were +14.1 letters, +11.0 letters, and +0.9 letters at week 52 and +12.0 letters, +11.3 letters, and +2.1 letters at week 100. In patients with prior anti-VEGF treatment, mean reductions in central retinal thickness were 180.2 μm, 192.2 μm, and 90.9 μm at week 52 and 180.1 μm, 196.4 μm, and 94.1 μm at week 100. Corresponding reductions in patients without prior anti-VEGF treatment were 190.3 μm, 175.7 μm, and 61.0 μm at week 52 and 200.0 μm, 186.7 μm, and 76.9 μm at week 100. The most frequent serious ocular adverse event was vitreous hemorrhage (1.3%, 0.7%, and 1.9%, respectively). Conclusions Visual and anatomic improvements over laser with both IAI regimens were significant and similar through week 100 in subgroups of patients in VISTA with and without prior anti-VEGF treatment for DME. [ABSTRACT FROM AUTHOR]

A sequential method is adopted to estimate the surface absorptivity in the process of laser surface hardening in this paper. The experimental temperature data given by Wang et al. [8] is used to verify the applicability of the proposed method. The results indicated that the proposed method is able to estimate the surface absorptivity accurately in the process of laser surface hardening. [ABSTRACT FROM AUTHOR]

We study dielectric and optical properties of perovskites ATiO 3 (A = Ca, Sr, Ba, Pb) in the cubic phase. The calculations are performed within the time-dependent density functional theory, including local field effects. The origin of absorption peaks is indicated based on the orbital-projected band structure. The theoretical calculations show that the perovskites have a plasmon mode at around 12 eV, which was not observed in experiments. • The dielectric functions of cubic perovskite titanates: CaTiO 3 , SrTiO 3 , BaTiO 3 , and PbTiO 3. • The physical original of optical absorption peaks. • The plasmon excitation at around 12 eV. [ABSTRACT FROM AUTHOR]

• We investigate the different behaviors between stablecoins and traditional cryptocurrencies in response to the US federal funds rate and Chinese interbank rate. • A higher federal funds rate and Chinese interbank rate compress the prices and price volatility of stablecoins but increase the prices and price volatility of traditional cryptocurrencies. • Both rates also increase the trading value of both types of coins. • The federal funds rate tends to have stronger impacts compared to the Chinese interbank rate on both types of coins, except for the price response of traditional cryptocurrencies. This study investigates the impacts of the United States (US) federal funds rate and Chinese interbank rate on the behaviors of stablecoins and traditional cryptocurrencies. We employ GARCH, EGARCH and Fixed Effects models for the daily sample of the top five stablecoins and the top five traditional cryptocurrencies in terms of market capitalization from December 2018 to December 2019. Our results show that a higher federal funds rate and Chinese interbank rate compress the prices and price volatility of stablecoins. In contrast, higher rates from both countries increase the prices and price volatility of traditional cryptocurrencies. Both rates also increase the trading value of both types of coins. The federal funds rate tends to have stronger impacts compared to the Chinese interbank rate on both types of coins, except for the price response of traditional cryptocurrencies. JEL: E43; E52; G10; F40 [ABSTRACT FROM AUTHOR]

• Inclusion of distributed PVs in distribution feeders in the sub-transmission planning. • A wide set of input scenarios with different magnitudes and locations of voltage violations. • An effective relaxation approach to handle a huge number of integer variables. • Conservative and machine-learning based methods for making final planning decision. • A realistic large-scale sub-transmission system for result analysis and performance evaluation. High penetration of grid-edge, inverter-based photovoltaic (PV) can cause significant voltage fluctuations not only at the distribution but also at the sub-transmission levels due to PV output intermittency. This paper proposes a reactive power planning tool for sub-transmission systems to mitigate voltage violations and fluctuations caused by high PV penetration and intermittency with a minimum investment cost. The planning tool considers all existing var assets in both sub-transmission and distribution systems to reduce the need of new equipment. It also closely coordinates with an optimization-based volt-var operational tool for selecting a set of scenarios with voltage violations due to PV intermittency and testing the final investment decision. The planning tool obtains an investment need for each scenario based on a proposed optimal power-flow framework. Because of a high number of discrete variables in this optimization problem, an efficient technique to recover the feasibility for the solution of the relaxed optimization problem is included. After obtaining separated solutions for all scenarios, two options are provided for making final planning decision: i) a conservative direct combination of investment need solutions and ii) a machine learning-based selection of representative investment needs at most time steps. The final investment decision options are verified using a realistic large-scale sub-transmission system and 5-min PV and load data. The results show a significant voltage performance improvement with a lower investment cost for additional var equipment compared to conventional approaches. [ABSTRACT FROM AUTHOR]

Steel is a commonly used material in the construction field but the steel's surface is easily corroded under natural conditions and especially in the environments containing a salt solution and continuous UV illumination. The fabrication and modification of polyurethane (PU) coatings toward a protection of the steel surface have been received much more special attention. The TiO 2 and carbon nanotubes (CNTs) composites are synthesized by a ball milling method toward the enhancing properties for the smart PU coating. The modified PU coatings, which are coated on the CT3 steel substrates (abbreviation: CNTs/TiO 2 /PU films), also express a highly effective antibacterial ability (over 95%) against Staphylococcus aureus (S. aureus) bacteria. By the electrochemical analysis of the CNTs/TiO 2 /PU films, we found that 1%wt CNTs/TiO 2 /PU film has the most excellent protection for the CT3 steel surface. In detail, the physical and the mechanical strength assessments demonstrate that the 1%wt CNTs/TiO 2 composite is 1.67 times, 1.48 times, and 1.70 times higher than that of the purity PU in a comparision of the adhesion, tensile strength, and impact strength, respectively. Moreover, the 1%wt CNTs/TiO 2 /PU film effectively protects against the corrosion of the steel surface up to 31 days under the environments containing 1 M Na 2 SO 4 solution and continuous UV illumination (λ = 285 nm). • 1%wt CNTs is the best content in CNTs/TiO 2 composite for enhancing properties of CNTs/TiO 2 /PU films. • CNTs/TiO 2 /PU films has a highly effective S. aureus antibacterial ability over 95%. • CNTs/TiO 2 /PU films protect CT3 steel up to 31 days under 1 M Na 2 SO 4 and UV illumination (λ = 285 nm). [ABSTRACT FROM AUTHOR]

In this paper, the inverse determination of the laser power in welding process with a given width penetration using the modified Newton–Raphson method (MRN) is presented. The advantage of this inverse method does not adopt the nonlinear least-squares error to formulate the inverse problem, but it is implemented a direct comparison between the known melting temperature and the computed melting temperature. The isothermal elliptic shape at the bottom surface is considered, and two “auxiliary” variables including a semi-major axis and an elliptic center are added into the formulation. Two examples are used to demonstrate the proposed method. The results shows that the proposed method is an accurate and robust method to inversely estimate the laser power for a given width penetration. [ABSTRACT FROM AUTHOR]

Discussion forums are the primary medium for supporting in-course student interactions in digital learning settings. Despite the significant uptake of discussion forums, questions remain as to how the tool can be used to initiate, maintain, and support interpersonal student connections. Large-scale patterns of student online interactions in forums derived from across the university are under-explored. Most studies have relied on data derived from a single course. This study presents a multi-site analysis of student interactions in online course forums at the university-level. Digital interactions of 14,643 students were analysed across several years in three universities located in the North American, South-East Asian, and Pacific regions. Descriptive results indicate that students with similar grades tend to co-participate in learning discussions. We applied exponential random graph modelling and regression analysis to further understand this observed similarity. Results suggest that this phenomenon can be explained by social processes of selection only to a small extent, and even less so by peer influence mechanisms. The study suggests that occurrence of similarity stems from other factors, such as course and forum designs. The implications of these results raise questions regarding learning designs and the benefits linked to the formation of student connections based on grade similarity. • This study is the first large-scale multi-site analysis of university online course forums. • The study describes grade-based similarity for students in online course forums at scale. • At the university level, students participate online with those in the same or neighbouring academic performance-bands. • Factors other than social processes appear to influence why students of similar performance co-participate online. • A change of academic grade based on peer connections in the online discussion is unlikely. [ABSTRACT FROM AUTHOR]

Purpose: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME). Design: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection–controlled for 2 years. Participants: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥275 μm on optical coherence tomography. Methods: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary. Main Outcome Measures: The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24. Results: Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group. Conclusions: The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references. [Copyright &y& Elsevier]