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PURPOSE: In diabetic macular edema (DME), the correlation between visual acuity (VA) and central subfield thickness (CST) is weak. We hypothesize that fluid volume (FV) in inner nuclear layer (INL) may correlate more strongly with VA. DESIGN: Retrospective, cross-sectional study METHOD: One eye each of diabetic patients with DME were included. We measured intraretinal fluid volume that detected by automated fluid detection algorithm on 3×3-mm optical coherence tomography angiogram volume scans. The detected fluid was subdivided into inner FV, bounded by the inner nuclear layer (INL), and outer FV, the fluid between outer border of INL to ellipsoid zone. RESULT: We enrolled 125 patients with DME (60 women, mean 61-year-old). The mean detected inner FV was 0.013 mm(3) in 109 eyes (87%). The mean detected outer FV was 0.042 mm(3) in 124 eyes (99%). Univariate analysis demonstrated that the VA significantly correlated with the inner FV (P

To quantify the level of decision regret in women ≥42 years of age after autologous in vitro fertilization (IVF) and identify factors associated with moderate-to-severe regret.Cross-sectional survey.Academic center.Ninety-four women ≥42 years of age who underwent autologous IVF between 2012 and 2018.None.Decision regret score, with25 as threshold for moderate-to-severe regret.The overall response rate was 22%. Respondents had a median age of 43 years at the time of IVF. The median and mean decision regret scores were 10 and 17.1 (range, 0-75), respectively. Seventy-three percent (n = 69) had absent-to-mild regret (score, 0-25), and 27% (n = 25) had moderate-to-severe regret (score,25) after IVF. Having no live births was associated with increased regret (odds ratio [OR], 22 [95% confidence interval {CI}, 2.82-171.82]). Among those who were unsuccessful, 40% (n = 24) had moderate-to-severe regret. Predictors for moderate-to-severe regret in this group included the lack of insurance coverage (OR, 0.33 [95% CI, 0.12-0.99]). Conversely, the perceived adequacy of information/counseling (OR, 0.44 [95% CI, 0.2-0.77]) and the perceived adequacy of emotional support (OR, 0.29 [95% CI, 0.15-0.55]) were protective factors inversely correlated with regret.Autologous IVF carries a low success rate and a considerable risk of decision regret in women ≥42 years of age. In those who were unsuccessful, the perceived adequacy of information and that of emotional support were protective factors against increased regret. Although concluding from a small, selected pool, our results strongly suggest that ample counseling and psychological support should be particularly emphasized within this patient population.

Machine learning tools and techniques were utilised to create a Novel Change Detection Algorithm (NCDA) as a supplementary quality assurance tool to alert users to potential significant changes in linear accelerator output using daily measurements. A prototype model was developed and validated that provides a forecast for the daily dose and indicated when there is the potential for the output to change beyond what is considered normal daily drift. The model provided a good fit with the validation dataset used, meaning that trends in daily output were easy to identify.The NCDA can be used either daily whereby output data is manually entered from the QA3 user interface, or on a weekly basis allowing input of the other data which is not traditionally presented on the interface. The NCDA should serve as a tool to alert users when data is trending out of tolerance and inform of possible output adjustments, therefore enabling effective allocation of time and resources.

Aqueous nanoparticle (NP) dispersions are commonly used as model systems for spectro- scopic study of singlet exciton fission (SF) in acenes such as 6,13-(triisopropylsilylethynyl) pentacene (TIPS-Pn). However, the potential for particle size effects to complicate interpretation of results in such model systems is generally ignored. In this work, we study amorphous TIPS-Pn NP dispersions prepared by the re-precipitation method over a range of particle sizes. Time-resolved fluorescence and femtosecond transient absorption spectroscopy show that exciton dynamics in these systems depend significantly upon particle size. Kinetic analysis reveals that SF becomes slower at smaller NP sizes, while triplet exciton decay (through both correlated triplet pair relaxation and geminate triplet-triplet annihilation) accelerates. These significant size-dependent effects are ascribed to increased morphological disorder within smaller NPs, weakening the intermolecular couplings which control SF and triplet migration. A non-radiative singlet quenching channel separate from SF is also identified, which has not been previously reported for NPs of SF-capable chromophores. This non-radiative singlet decay becomes a significant relaxation pathway at small particle sizes, substantially reducing SF yields. Interestingly, exciton kinetics in 81-nm NPs approach those of bulk amorphous TIPS-Pn, suggesting that NPs of this size or larger are likely good models for bulk TIPS-Pn. This work demonstrates that particle-size effects are significant for small NPs of SF chromophores, and must be accounted for in order to accurately model bulk materials with such NP dispersions.

Zinc–air flow fuel cells utilizing zinc particles as fuel possess the potential to evolve as efficient distributed grid generators. In this research study, electrochemical impedance analysis was employed to determine the optimum design and operational parameters for the feasible maneuver and enhanced energy generation from zinc fuel cells. Polarization resistance (Rp), ohmic resistance (Rs), and mass transfer resistance (Rm) were used as the indicators for determination of the optimum parameters of fuel cell performance. Experimental conditions optimized from previous studies like potassium hydroxide electrolyte with temperature of 25 °C and concentration of 40 wt% zinc powder quantity of 20 g, electrode reaction surface area of 48 cm2 were followed in the fuel cells used in the present study. Parameters like collector plate material, air flow velocity and cell operating temperature were augmented and finally were all implemented in the fuel cell and operated. Plain nickel or nickel-plated copper were both advantageous as collector plate materials whereas an air flow velocity ranging from 1–3 m s−1 and a cell operating temperature of 25 °C to 45 °C were beneficial for the stability and performance of the zinc fuel cells. Finally, based on the optimized parameters obtained from the above experiments, performance tests of zinc fuel cells were investigated. The maximum power produced was 16.5 W, along with a corresponding voltage of 0.8 V, maximum current density of 430 mA cm−2 and peak power density of 364.6 mW cm−2. Thus it can be concluded that the fuel cells designed and operated in this study were capable for feasible and efficient future applications.

PURPOSE: To compare retinal vessel density in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD) to age-matched healthy eyes using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: Study participants underwent macular 3×3-mm OCTA scans with spectral domain OCTA. Reflectance-compensated retinal vessel densities were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Quantitative analysis using normalized deviation compared the retinal vessel density in GA regions, 500 μm GA rim regions, and non-GA regions to similar macular locations in control eyes. RESULTS: Ten eyes with GA and 10 control eyes were studied. Eyes with GA had significantly lower vessel density in the SVC (54.8±2.4% vs. 60.8±3.1%, P

In this work, a wireless remote-control function and fuzzy control function were added to the mini-loader of a hybrid gas-electricity powertrain. The loader uses a long-range (LoRa) protocol for communication, which is capable of long-distance signal transmissions and has a high level of sensitivity. A frequency-hopping mechanism based on received signal strength, center frequency, and sensitivity information was constructed for the LoRa system, which aids the transmission of information over long distances in a stable manner. This allows the loader to be utilized in remote regions or topographically complex areas. A fuzzy controller was incorporated to alleviate the fuel consumption problems of the hybrid powertrain and provided efficient and stable hybrid power by tuning the torque and rotation speed of the motor. The functionalized mini-loader has achieved data transfer success rates greater than 90% in wireless transmissions within a range of 100 m. The energy consumption of the functionalized powertrain was lowered by 8%.

To construct an optical coherence tomography (OCT) nerve fiber layer (NFL) parameter that has maximal correlation and agreement with visual field (VF) mean deviation (MD). The NFL_MD parameter in dB scale was calculated from the peripapillary NFL thickness profile nonlinear transformation and VF area-weighted averaging. From the Advanced Imaging for Glaucoma study, 245 normal, 420 pre-perimetric glaucoma (PPG), and 289 perimetric glaucoma (PG) eyes were selected. NFL_MD had significantly higher correlation (Pearson R: 0.68 vs 0.55, p

PURPOSE: To detect plexus-specific peripapillary retinal perfusion defects in glaucoma using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: One eye each of 45 perimetric glaucoma participants and 37 age-matched normal participants were scanned using 4.5-mm OCTA scans centered on the disc. The PR-OCTA algorithm removed flow projection artifacts in OCT angiograms. Five en face OCTA slabs were analyzed: nerve fiber layer plexus (NFLP), ganglion cell layer plexus (GCLP), superficial vascular complex (SVC = NFLP + GCLP), deep vascular complex (DVC), and all plexuses combined. Peripapillary retinal capillary density (CD) and vessel density (VD) were calculated using a reflectance-compensated algorithm. RESULTS: Focal capillary dropout could be visualized more clearly in the NFLP than the other slabs. The NFLP, SVC and all-plexus CD in the glaucoma group were significantly lower (P

Background Nationwide efforts seek to address the opioid epidemic by increasing access to medications for opioid use disorder (OUD), particularly with buprenorphine. A poorly understood challenge is that among individuals with OUD who do receive buprenorphine, many do not adhere to the pharmacotherapy long enough to achieve sustained benefits. We aimed to identify factors associated with buprenorphine treatment utilization over time. Methods We used random-intercept modeling to identify factors associated with buprenorphine treatment utilization over 2 years after first follow-up by 789 individuals with OUD who had participated in a multi-site randomized clinical trial of buprenorphine compared to methadone. Key predictors were participants' reports of buprenorphine treatment accessibility and acceptability (assessed at first follow-up) and their interaction effects, controlling for baseline randomization status, sociodemographics, and other covariates. Results Approximately 9.3–11.2% of participants utilized buprenorphine treatment over the 2 years of follow-up. Interaction effects indicated that individuals who perceived buprenorphine to be both accessible and acceptable were most likely to use buprenorphine during follow-up, controlling for other factors. In contrast, individuals who perceived buprenorphine to be unacceptable were least likely to use buprenorphine, regardless the level of perceived access to the medication. Buprenorphine treatment utilization was also negatively associated with Hispanic ethnicity, West coast context, and cumulative months receiving methadone treatment and incarceration during follow-up. Conclusions To engage more individuals with OUD in long-term treatment with buprenorphine, interventions should target buprenorphine treatment acceptability, in addition to increasing buprenorphine access, and tailor efforts to meet the needs of vulnerable populations. Trial registration The START Follow-up Study on ClinicalTrials.gov ( NCT01592461 ).

Evaluations are practiced in political contexts, posing ethical dilemmas to evaluators. It is important, therefore, to prepare evaluation students for ethical decision-making in their future evalua...

Zn-air fuel cells (ZAFC) with electrolyte flow are the widely acknowledged. In this study, the theoretical aspects of OH− groups reaction with the Zn cluster were proposed using ab initio calculations. The optimal flowrate was then determined as 100 ml/min. The performance was determined as production of open circuit voltage, power and current density values which were with 1.41 V, 427.7 mW/cm2 and 518.6 mA/cm2 respectively. The ZAFC with electrolyte flow exhibited better reduction in electrochemical impedance spectroscopy. Nyquist plots were exploited to justify the results. Thus, upgrading processes of the ZAFC will prominently provide immense opportunities for their applications.

In this paper, we propose a novel approach for 3-D rain field reconstruction using satellite signals. It uses the estimated signal-to-noise ratio (SNR) at the ground receivers for low-earth orbit (LEO) satellites and, thus, indirectly estimates the path-integrated rain attenuation of the microwave communication links. A least-squares algorithm is employed to perform the 3-D tomographic reconstruction of the rain field. The proposed system model consists of an LEO satellite with a realistic overpass trajectory and multiple ground receivers with SNR estimators. Two synthetic rain events near the Great Barrier Reef in Australia are used to test the reconstruction outcome. Simulation results suggest that the reconstructed rain field has close agreement with the synthetic rain field.

Background and Purpose— Many patients with acute ischemic stroke are not eligible for thrombolysis or mechanical reperfusion therapies due to contraindications, inaccessible vascular occlusions, late presentation, or large infarct core. Sphenopalatine ganglion (SPG) stimulation to enhance collateral flow and stabilize the blood-brain barrier offers an alternative, potentially more widely deliverable, therapy. Methods— In a randomized, sham-controlled, double-masked trial at 41 centers in 7 countries, patients with anterior circulation ischemic stroke not treated with reperfusion therapies within 24 hours of onset were randomly allocated to active SPG stimulation or sham control. The primary efficacy outcome was improvement beyond expectations on the modified Rankin Scale of global disability at 90 days (sliding dichotomy), assessed in the modified intention-to-treat population. The initial planned sample size was 660 patients, but the trial was stopped early when technical improvements in device placement occurred, so that analysis of accumulated experience could be conducted to inform a successor trial. Results— Among 303 enrolled patients, 253 received at least one active SPG or sham stimulation, constituting the modified intention-to-treat population (153 SPG stimulation and 100 sham control). Age was median 73 years (interquartile range, 64–79), 52.6% were female, deficit severity on the National Institutes of Health Stroke Scale was median 11 (interquartile range, 9–15), and time from last known well median 18.6 hours (interquartile range, 14.5–22.5). For the primary outcome, improved 3-month disability beyond expectations, rates in the SPG versus sham treatment groups were 49.7% versus 40.0%; odds ratio, 1.48 (95% CI, 0.89–2.47); P =0.13. A significant treatment interaction with stroke location (cortical versus noncortical) was noted, P =0.04. In the 87 patients with confirmed cortical involvement, rates of improvement beyond expectations were 50.0% versus 27.0%; odds ratio, 2.70 (95% CI, 1.08–6.73); P =0.03. Similar response patterns were observed for all prespecified secondary efficacy outcomes. No differences in mortality or serious adverse event safety end points were observed. Conclusions— SPG stimulation within 24 hours of onset is safe in acute ischemic stroke. SPG stimulation was not shown to statistically significantly improve 3-month disability above expectations, though favorable outcomes were nominally higher with SPG stimulation. Beneficial effects may distinctively be conferred in patients with confirmed cortical involvement. The results of this study need to be confirmed in a larger pivotal study. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT03767192.

Purpose To detect nonexudative choroidal neovascularization (CNV) in age-related macular degeneration (AMD) with OCT angiography (OCTA) and determine the risk of exudative CNV developing compared with eyes without nonexudative CNV. Design Prospective, longitudinal, observational study. Participants Consecutive patients with drusen and pigmentary changes in the study eye and exudative neovascular AMD in the fellow eye. Methods In this prospective observational study, participants underwent spectral-domain OCTA (AngioVue; Optovue, Inc, Fremont, CA), clinical examination, and structural OCT at baseline and 6-month intervals for 2 years. OCT angiography images were exported for custom processing to remove projection artifact and calculate CNV vessel area. Main Outcome Measures Rate of developing exudation in eyes with and without nonexudative CNV as detected by OCTA on regular follow-up. Results Sixty-three study participants were followed up every 6 months and 48 completed the 2-year study. Mean age was 78 years and 60.3% were female. On the baseline visit, 5 eyes (7.9%) were found to have nonexudative CNV by OCTA, and 3 of them demonstrated exudation. Of 58 eyes with a normal OCTA on baseline visit, 5 eyes developed nonexudative CNV during a follow-up visit. All 5 of these nonexudative CNV went on to develop exudation in subsequent visits. Overall, 8 of the 10 eyes with nonexudative CNV developed exudation with a mean time of 8 months and mean CNV area growth rate of 20% per month (P = 0.014, exponential model). Initiation of antiangiogenic treatment halted their growth. In comparison, exudation occurred in only 6 of the 53 eyes (11%) that lacked a precursor nonexudative CNV. Cox proportional hazard analysis showed that having nonexudative CNV detected was associated with an 18.1-fold increase in the rate of exudation subsequently developing (P Conclusions Nonexudative CNV frequently is detected by OCTA in the fellow eyes of those with exudative CNV. These lesions carry a high risk of exudation developing within the first year after detection and could benefit from close monitoring. The high risk of progression may justify prophylactic treatment; further studies are needed.

Author(s): Fung, Constance H; Martin, Jennifer L; Hays, Ron D; Col, Nananda; Patterson, Emily S; Josephson, Karen; Mitchell, Michael N; Grinberg, Austin; Aysola, Ravi; Song, Yeonsu; Dzierzewski, Joseph M; Liang, Li-Jung; Huang, David; Zeidler, Michelle; Alessi, Cathy

Virtual reality (VR) and game-based learning strategies have rarely been investigated together with a keen focus on motivational processing. This lack of understanding on motivational support of VR...

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.

Corneal imaging is important for the diagnostic and therapeutic evaluation of many eye diseases. Optical coherence tomography (OCT) is extensively used in ocular imaging due to its non-invasive and high-resolution volumetric imaging characteristics. Optical coherence microscopy (OCM) is a technical variation of OCT that can image the cornea with cellular resolution. Here, we demonstrate a blue-light OCM as a low-cost and easily reproducible system to visualize corneal cellular structures such as epithelial cells, endothelial cells, keratocytes, and collagen bundles within stromal lamellae. Our blue-light OCM system achieved an axial resolution of 12 µm in tissue over a 1.2 mm imaging depth, and a lateral resolution of 1.6 µm over a field of view of 750 µm × 750 µm.

Optical coherence tomography (OCT) is widely used in ophthalmic practice because it can visualize retinal structure and vasculature in vivo and 3-dimensionally (3D). Even though OCT procedures yield data volumes, clinicians typically interpret the 3D images using two-dimensional (2D) data subsets, such as cross-sectional scans or en face projections. Since a single OCT volume can contain hundreds of cross-sections (each of which must be processed with retinal layer segmentation to produce en face images), a thorough manual analysis of the complete OCT volume can be prohibitively time-consuming. Furthermore, 2D reductions of the full OCT volume may obscure relationships between disease progression and the (volumetric) location of pathology within the retina and can be prone to mis-segmentation artifacts. In this work, we propose a novel framework that can detect several retinal pathologies in three dimensions using structural and angiographic OCT. Our framework operates by detecting deviations in reflectance, angiography, and simulated perfusion from a percent depth normalized standard retina created by merging and averaging scans from healthy subjects. We show that these deviations from the standard retina can highlight multiple key features, while the depth normalization obviates the need to segment several retinal layers. We also construct a composite pathology index that measures average deviation from the standard retina in several categories (hypo- and hyper-reflectance, nonperfusion, presence of choroidal neovascularization, and thickness change) and show that this index correlates with DR severity. Requiring minimal retinal layer segmentation and being fully automated, this 3D framework has a strong potential to be integrated into commercial OCT systems and to benefit ophthalmology research and clinical care.

Parliamentary diplomacy has provided a crucial, promising outlet in Taiwan's challenging pursuit of its own interests in the international arena. This book assesses both the potentials and the constraints of parliamentary diplomacy for Taiwan. Through a comparative perspective, and using evidence from the relations of the Legislative Yuan in Taiwan with the US Congress and the European Parliament, the book investigates the implementation of parliamentary diplomacy in Taiwan and its impact in Taiwan's foreign policy. In the book's analysis, it draws vital lessons that will have important implications for other entities which have similar challenges and aspirations.

Importance Diabetic macular edema (DME) is the predominant cause of visual impairment in patients with type 1 or 2 diabetes. Automated fluid volume measurements using optical coherence tomography (OCT) may improve the diagnostic accuracy of DME screening. Objective To assess the diagnostic accuracy of an automated central macular fluid volume (CMFV) quantification using OCT for DME. Design, Setting, and Participants A cross-sectional observational study was conducted at a tertiary academic center among 215 patients with diabetes (1 eye each) enrolled from January 26, 2015, to December 23, 2019. All participants underwent comprehensive examinations, 6 × 6-mm macular structural OCT horizontal raster scans, and 6 × 6-mm macular OCT angiography volumetric scans. From January 1 to March 30, 2020, 2 retinal specialists reviewed the structural OCT scans independently and diagnosed DME if intraretinal or subretinal fluid was present. Diabetic macular edema was considered center involved if fluid was present within the central fovea (central 1-mm circle). A third retinal specialist arbitrated any discrepancy. The mean central subfield thickness (CST) within the central fovea was measured on structural OCT horizontal raster scans. A deep learning algorithm automatically quantified fluid volumes on 6 × 6-mm OCT angiography volumetric scans and within the central foveas (CMFV). Main Outcomes and Measures The area under the receiver operating characteristic curve (AUROC) and the sensitivity and specificity of CST and CMFV for DME diagnosis. Results We enrolled 1 eye each of 215 patients with diabetes (117 women [54.4%]; mean [SD] age, 59.6 [12.4] years). Diabetic macular edema was present in 136 eyes; 93 cases of DME were center involved. The AUROC of CMFV for diagnosis of center-involved DME (0.907 [95% CI, 0.861-0.954]) was greater than the AUROC of CST (0.832 [95% CI, 0.775-0.889]; P = .02). With the specificity set at 95%, the sensitivity of CMFV for detection of center-involved DME (78.5% [95% CI, 68.8%-86.3%]) was higher than that of CST (53.8% [95% CI, 43.1%-64.2%]; P = .002). Center-involved DME cases not detected by CST but detected by CMFV were associated with a thinner CST (290.8 μm [95% CI, 282.3-299.3 μm] vs 369.4 μm [95% CI, 347.1-391.7 μm]; P

BackgroundBiological tissues consist of heterogenous populations of cells. Because gene expression patterns from bulk tissue samples reflect the contributions from all cells in the tissue, understanding the contribution of individual cell types to the overall gene expression in the tissue is fundamentally important. We recently developed a computational method, CDSeq, that can simultaneously estimate both sample-specific cell-type proportions and cell-type-specific gene expression profiles using only bulk RNA-Seq counts from multiple samples. Here we present an R implementation of CDSeq (CDSeqR) with significant performance improvement over the original implementation in MATLAB and an added new function to aid cell type annotation. The R package would be of interest for the broader R community.ResultWe developed a novel strategy to substantially improve computational efficiency in both speed and memory usage. In addition, we designed and implemented a new function for annotating the CDSeq estimated cell types using single-cell RNA sequencing (scRNA-seq) data. This function allows users to readily interpret and visualize the CDSeq estimated cell types. In addition, this new function further allows the users to annotate CDSeq-estimated cell types using marker genes. We carried out additional validations of the CDSeqR software using synthetic, real cell mixtures, and real bulk RNA-seq data from the Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) project.ConclusionsThe existing bulk RNA-seq repositories, such as TCGA and GTEx, provide enormous resources for better understanding changes in transcriptomics and human diseases. They are also potentially useful for studying cell-cell interactions in the tissue microenvironment. Bulk level analyses neglect tissue heterogeneity, however, and hinder investigation of a cell-type-specific expression. The CDSeqR package may aid in silico dissection of bulk expression data, enabling researchers to recover cell-type-specific information.

This study, set at the epicenter of the initial U.S. COVID-19 outbreak, shows that nearly 1/5 of cancer patients seeking radiotherapy during the initial surge experienced a COVID-related care change. Notably, advanced age, curative intent, and rectal cancer were predictors of experiencing a care change. Taken together with long-term outcomes data and changes implemented by other groups, we hope this study will help inform the development of treatment guidelines for this and potential future pandemics., Purpose To define how the coronavirus disease 2019 (COVID-19) pandemic impacted the role, timing, and delivery of radiotherapy in a high-prevalence region at the height of the initial U.S. outbreak. Methods We performed a retrospective review of all patients seen at three radiation oncology departments within the “XXXX” Health system in “XXXX” during the initial COVID-19 surge. Primary end points were to define and quantify COVID-related, radiation-specific care changes, and to identify predictive factors of experiencing COVID-related care changes. Results 545 cancer patients were seen during the study period, 99 of whom (18.1%) experienced >1 COVID-related care change. Radiation treatment (RT) delays were most common, accounting for 51.5% of all care changes. Physician-directed delays accounted for 41.2% of RT delays, while patient fears, COVID testing, and access barriers were responsible for 27.5%, 17.6%, and 13.7%, respectively. Patient age (p=0.040), intent of treatment (p=0.047), and cancer type (p

Optical coherence tomography (OCT) and OCT angiography (OCTA) enable noninvasive structural and angiographic imaging of the eye. Portable handheld OCT/OCTA systems are required for imaging patients in the supine position. Examples include infants in the neonatal intensive care unit (NICU) and operating room (OR). The speed of image acquisition plays a pivotal role in acquiring high quality OCT/OCTA images, particularly with the handheld system, since both the operator hand tremor and subject motion can cause significant motion artifacts. In addition, having a large field of view and the ability of real-time data visualization are critical elements in rapid disease screening, reducing imaging time, and detecting peripheral retinal pathologies. The arrangement of optical components is less flexible in the handheld system due to the limitation of size and weight. In this paper, we introduce a 400-kHz, 55-degree field of view handheld OCT/OCTA system that has overcome many technical challenges as a portable OCT system as well as a high-speed OCTA system. We demonstrate imaging premature infants with retinopathy of prematurity (ROP) in the NICU, and patients with incontinentia pigmenti (IP) in the OR using our handheld OCT system. Our design may have potential for improving the diagnosis of retinal diseases and help provide a practical guideline for designing a flexible and portable OCT system.

Optical coherence tomography (OCT) and OCT angiography (OCTA) enable noninvasive structural and angiographic imaging of the eye. Portable handheld OCT/OCTA systems are required for imaging patients in the supine position. Examples include infants in the neonatal intensive care unit (NICU) and operating room (OR). The speed of image acquisition plays a pivotal role in acquiring high-quality OCT/OCTA images, particularly with the handheld system, since both the operator hand tremor and subject motion can cause significant motion artifacts. In addition, having a large field of view and the ability of real-time data visualization are critical elements in rapid disease screening, reducing imaging time, and detecting peripheral retinal pathologies. The arrangement of optical components is less flexible in the handheld system due to the limitation of size and weight. In this paper, we introduce a 400-kHz, 55-degree field of view handheld OCT/OCTA system that has overcome many technical challenges as a portable OCT system as well as a high-speed OCTA system. We demonstrate imaging premature infants with retinopathy of prematurity (ROP) in the NICU, a patient with incontinentia pigmenti (IP), and a patient with X-linked retinoschisis (XLRS) in the OR using our handheld OCT system. Our design may have the potential for improving the diagnosis of retinal diseases and help provide a practical guideline for designing a flexible and portable OCT system.

MRSA endovascular infections are frequently recalcitrant to treatment with standard-of-care antibiotics. Anti-staphylococcal phage lysins represent important candidate adjunctive agents against invasive MRSA infections because of both their microbicidal and anti-biofilm properties. We utilized the rabbit model of aortic valve infective endocarditis (using the prototype MRSA strain, MW2) to examine the combined efficacy of the lysin, LSVT-1701, plus daptomycin. LSVT-1701 was given at two dose-regimens (32.5 mg/kg and 50 mg/kg) with different dose-durations (single dose vs daily dose for 2 d vs daily dose for 4 d); daptomycin was given at a sub-lethal daily dose of 4 mg/kg for 4 d to maximize potential synergistic interaction outcomes. The combination of LSVT-1701 plus daptomycin was highly effective at reducing target tissue MRSA counts (cardiac vegetations, kidneys, and spleen), especially when the lysin was given for multiple days and/or at higher daily doses. Of importance, when given for four daily doses, both lysin dose-regimens in combination with daptomycin sterilized all target tissues. These findings suggest that LSVT-1701 warrants further clinical evaluation as adjunctive therapy for the treatment of invasive MRSA infections.

The emergence and rapid global spread of SARS-CoV-2 demonstrates the importance of infectious disease surveillance, particularly during the early stages. Viral genomes can provide key insights into transmission chains and pathogenicity. Nasopharyngeal swabs were obtained from thirty-two of the first SARS-CoV-2 positive cases (March 18–30) in Kingston Ontario, Canada. Viral genomes were sequenced using Ion Torrent (n = 24) and MinION (n = 27) sequencing platforms. SARS-CoV-2 genomes carried forty-six polymorphic sites including two missense and three synonymous variants in the spike protein gene. The D614G point mutation was the predominate viral strain in our cohort (92.6%). A heterozygous variant (C9994A) was detected by both sequencing platforms but filtered by the ARTIC network bioinformatic pipeline suggesting that heterozygous variants may be underreported in the SARS-CoV-2 literature. Phylogenetic analysis with 87,738 genomes in the GISAID database identified global origins and transmission events including multiple, international introductions as well as community spread. Reported travel history validated viral introduction and transmission inferred by phylogenetic analysis. Molecular epidemiology and evolutionary phylogenetics may complement contact tracing and help reconstruct transmission chains of emerging diseases. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to limit future pandemics.

STUDY OBJECTIVES: Person-centered obstructive sleep apnea (OSA) care is a collaborative approach that is respectful of an individual’s health priorities. Informed decision-making is essential to person-centered care, especially as patients age. In a feasibility study, we evaluated the effects of a new decision aid (Decide2Rest) on OSA treatment decision-making in older adults. METHODS: Patients (aged ≥ 60 years) with newly diagnosed OSA were recruited from two health care systems and randomized either to Decide2Rest or to a control program. Postintervention outcomes included 1) Decisional Conflict Scale (0–100, where 0 = low and 100 = high conflict), which measures perceptions of uncertainty, whether decisions reflect what matters most to patients, and whether patients feel supported in decision-making; 2) Preparation for Decision-Making scale (0–100, where 0 = least and 100 most prepared); and 3) OSA knowledge (0–100, where 0 = poor and 100 = outstanding). Multivariable linear regression models examined relationships between Decide2Rest and outcomes (Decisional Conflict Scale, Preparation for Decision-Making, OSA knowledge). RESULTS: Seventy-three patients were randomized to Decide2Rest (n = 36; mean age, 69 years; 72% male) vs control (n = 37; mean age, 69 years; 70% male). Results from the regressions, controlling for study site, indicate that the Decide2Rest program resulted in less decisional conflict (20.5 vs 32.7 on the Decisional Conflict Scale; P = .014), more preparedness for decision-making (87.8 vs 66.2 on the Preparation for Decision-Making scale; P < .001), and greater OSA knowledge (75.1 vs 65.3 OSA knowledge score; P = .04) scores than in the control group. CONCLUSIONS: The Decide2Rest program promotes person-centered OSA decision-making for older patients with newly diagnosed OSA. Future studies are needed to optimize implementation of the program. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov, Name: Improving Older Adults’ Decision-Making for OSAT (eDecide2Rest); URL: https://clinicaltrials.gov/ct2/show/NCT03138993; Identifier: NCT03138993. CITATION: Fung CH, Martin JL, Liang LJ, et al. Efficacy of a patient decision aid for improving person-centered decision-making by older adults with obstructive sleep apnea. J Clin Sleep Med. 2021;17(2):121–128.

Reliable classification of referable and vision threatening diabetic retinopathy (DR) is essential for patients with diabetes to prevent blindness. Optical coherence tomography (OCT) and its angiography (OCTA) have several advantages over fundus photographs. We evaluated a deep-learning-aided DR classification framework using volumetric OCT and OCTA.Four hundred fifty-six OCT and OCTA volumes were scanned from eyes of 50 healthy participants and 305 patients with diabetes. Retina specialists labeled the eyes as non-referable (nrDR), referable (rDR), or vision threatening DR (vtDR). Each eye underwent a 3 × 3-mm scan using a commercial 70 kHz spectral-domain OCT system. We developed a DR classification framework and trained it using volumetric OCT and OCTA to classify eyes into rDR and vtDR. For the scans identified as rDR or vtDR, 3D class activation maps were generated to highlight the subregions which were considered important by the framework for DR classification.For rDR classification, the framework achieved a 0.96 ± 0.01 area under the receiver operating characteristic curve (AUC) and 0.83 ± 0.04 quadratic-weighted kappa. For vtDR classification, the framework achieved a 0.92 ± 0.02 AUC and 0.73 ± 0.04 quadratic-weighted kappa. In addition, the multiple DR classification (non-rDR, rDR but non-vtDR, or vtDR) achieved a 0.83 ± 0.03 quadratic-weighted kappa.A deep learning framework only based on OCT and OCTA can provide specialist-level DR classification using only a single imaging modality.The proposed framework can be used to develop clinically valuable automated DR diagnosis system because of the specialist-level performance showed in this study.

We derive a systematic and general method for parameterizing coarse-grained molecular models consisting of anisotropic particles from fine-grained (e.g., all-atom) models for condensed-phase molecular dynamics simulations. The method, which we call anisotropic force-matching coarse-graining (AFM-CG), is based on rigorous statistical mechanical principles, enforcing consistency between the coarse-grained and fine-grained phase-space distributions to derive equations for the coarse-grained forces, torques, masses, and moments of inertia in terms of properties of a condensed-phase fine-grained system. We verify the accuracy and efficiency of the method by coarse-graining liquid-state systems of two different anisotropic organic molecules, benzene and perylene, and show that the parameterized coarse-grained models more accurately describe properties of these systems than previous anisotropic coarse-grained models parameterized using other methods that do not account for finite-temperature and many-body effects on the condensed-phase coarse-grained interactions. The AFM-CG method will be useful for developing accurate and efficient dynamical simulation models of condensed-phase systems of molecules consisting of large, rigid, anisotropic fragments, such as liquid crystals, organic semiconductors, and nucleic acids.

PRECIS An association between macular vessel density (VD) and total retinal blood flow (TRBF) was demonstrated in subjects with primary open-angle glaucoma (POAG) and visual field (VF) loss. PURPOSE The purpose of this study was to report relationships of macular VD metrics and TRBF in POAG. MATERIALS AND METHODS A total of 24 POAG and 19 healthy control subjects participated in the study. Subjects underwent optical coherence tomography and angiography for measurements of inner retinal thickness (IRT), VD, and spacing between large vessels (SLV) and small vessels (SSV). Doppler optical coherence tomography imaging was performed for TRBF measurement. In POAG subjects, automated perimetry was performed and VF loss expressed as mean deviation was measured. RESULTS Compared with the control group, POAG group had decreased VD, TRBF, IRT, and increased SLV (P

Background With the expansion of online patient portals linked to electronic health records in safety-net health care settings, we need more data on the use of these websites by patients with limited English proficiency (LEP) in order to guide their continued design, implementation, and evaluation as portals for the underserved. Methods Cross-sectional portal data for the Los Angeles County Department of Health Services, the second largest safety-net system in the nation. We examined differences in portal use across language (English vs. non-English/LEP), covering four years since implementation. Results Of 425,281 patients assigned to primary care as of March 2019, 55,190 (13%) unique portal enrollments were registered. Among 54,981 portal users, LEP users had lower adjusted odds of using an active portal function (e.g., medication refill) vs. English-speakers. Conclusions Even among those registered to access portals, these websites are underused, particularly by LEP patients. All systems must facilitate use for these populations, especially for time-saving active functions, which can improve outcomes. Health systems must prioritize design/usability as a factor to counter LEP underuse.

Significance Many environmental pollutants act as endocrine disruptors that interfere with normal endocrine regulation and promote adverse effects in humans. As a major target of xenobiotics, the pregnane X receptor (PXR) is known to play opposite roles by both facilitating their clearance and mediating their toxic effects. Here, we use structural and functional approaches to describe two converging mechanisms leading to a robust synergistic stimulation of the PXR pathway by mixtures of three chemicals exhibiting very low efficacy when administered separately. This “cocktail effect” relies on two cooperative binding processes that enhance both ligand binding affinity and recruitment of transcriptional coactivators. Our findings show how chemical mixtures may alter physiology and homeostasis at concentrations where individual components are considered safe., Humans are chronically exposed to mixtures of xenobiotics referred to as endocrine-disrupting chemicals (EDCs). A vast body of literature links exposure to these chemicals with increased incidences of reproductive, metabolic, or neurological disorders. Moreover, recent data demonstrate that, when used in combination, chemicals have outcomes that cannot be predicted from their individual behavior. In its heterodimeric form with the retinoid X receptor (RXR), the pregnane X receptor (PXR) plays an essential role in controlling the mammalian xenobiotic response and mediates both beneficial and detrimental effects. Our previous work shed light on a mechanism by which a binary mixture of xenobiotics activates PXR in a synergistic fashion. Structural analysis revealed that mutual stabilization of the compounds within the ligand-binding pocket of PXR accounts for the enhancement of their binding affinity. In order to identify and characterize additional active mixtures, we combined a set of cell-based, biophysical, structural, and in vivo approaches. Our study reveals features that confirm the binding promiscuity of this receptor and its ability to accommodate bipartite ligands. We reveal previously unidentified binding mechanisms involving dynamic structural transitions and covalent coupling and report four binary mixtures eliciting graded synergistic activities. Last, we demonstrate that the robust activity obtained with two synergizing PXR ligands can be enhanced further in the presence of RXR environmental ligands. Our study reveals insights as to how low-dose EDC mixtures may alter physiology through interaction with RXR–PXR and potentially several other nuclear receptor heterodimers.

Optical coherence tomographic angiography (OCTA) is a non-invasive imaging modality that provides three-dimensional, information-rich vascular images. With numerous studies demonstrating unique capabilities in biomarker quantification, diagnosis, and monitoring, OCTA technology has seen rapid adoption in research and clinical settings. The value of OCTA imaging is significantly enhanced by image analysis tools that provide rapid and accurate quantification of vascular features and pathology. Today, the most powerful image analysis methods are based on artificial intelligence (AI). While AI encompasses a large variety of techniques, machine learning-based, and especially deep-learning-based, image analysis provides accurate measurements from a variety of contexts, including different diseases and regions of the eye. Here, we discuss the principles of both OCTA and AI that make their combination capable of answering new questions. We also review contemporary applications of AI in OCTA, which include accurate detection of pathologies such as choroidal neovascularization, precise quantification of retinal perfusion, and reliable disease diagnosis.

Importance Data on the efficacy of hydroxychloroquine for the treatment of coronavirus disease 2019 (COVID-19) are needed. Objective To determine whether hydroxychloroquine is an efficacious treatment for adults hospitalized with COVID-19. Design, Setting, and Participants This was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled between April 2 and June 19, 2020, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients, with interim analyses planned after every 102 patients were enrolled. The trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients. Interventions Patients were randomly assigned to hydroxychloroquine (400 mg twice daily for 2 doses, then 200 mg twice daily for 8 doses) (n = 242) or placebo (n = 237). Main Outcomes and Measures The primary outcome was clinical status 14 days after randomization as assessed with a 7-category ordinal scale ranging from 1 (death) to 7 (discharged from the hospital and able to perform normal activities). The primary outcome was analyzed with a multivariable proportional odds model, with an adjusted odds ratio (aOR) greater than 1.0 indicating more favorable outcomes with hydroxychloroquine than placebo. The trial included 12 secondary outcomes, including 28-day mortality. Results Among 479 patients who were randomized (median age, 57 years; 44.3% female; 37.2% Hispanic/Latinx; 23.4% Black; 20.1% in the intensive care unit; 46.8% receiving supplemental oxygen without positive pressure; 11.5% receiving noninvasive ventilation or nasal high-flow oxygen; and 6.7% receiving invasive mechanical ventilation or extracorporeal membrane oxygenation), 433 (90.4%) completed the primary outcome assessment at 14 days and the remainder had clinical status imputed. The median duration of symptoms prior to randomization was 5 days (interquartile range [IQR], 3 to 7 days). Clinical status on the ordinal outcome scale at 14 days did not significantly differ between the hydroxychloroquine and placebo groups (median [IQR] score, 6 [4-7] vs 6 [4-7]; aOR, 1.02 [95% CI, 0.73 to 1.42]). None of the 12 secondary outcomes were significantly different between groups. At 28 days after randomization, 25 of 241 patients (10.4%) in the hydroxychloroquine group and 25 of 236 (10.6%) in the placebo group had died (absolute difference, −0.2% [95% CI, −5.7% to 5.3%]; aOR, 1.07 [95% CI, 0.54 to 2.09]). Conclusions and Relevance Among adults hospitalized with respiratory illness from COVID-19, treatment with hydroxychloroquine, compared with placebo, did not significantly improve clinical status at day 14. These findings do not support the use of hydroxychloroquine for treatment of COVID-19 among hospitalized adults. Trial Registration ClinicalTrials.gov:NCT04332991

A fuzzy control strategy is developed in this study to manage the parallel hybrid power system of internal combustion engine (ICE) and electric motor (EM) for hybrid vehicles. The rules established for the fuzzy logic are based on the conditions of vehicle pedal position, vehicle velocity, and the state of charge to control the throttle position of the ICE and the switch position of EM in low-, mid-, and high-power cruising. The optimization of the control strategy can make vehicles achieving ECE 40 driving pattern. In addition, the ICE can work in an optimal operation range, thus reducing carbon emission. The EM may provide power according to the demand, such that the torque output of the output shaft of the power split device is twice of the input of the two power sources separately.

ObjectiveTo detect the plexus-specific retinal capillary avascular area in exudative age-related macular degeneration (EAMD) with projection-resolved optical coherence tomography angiography (PR-OCTA).Methods and analysisIn this prospective cross-sectional single centre study, eyes with treatment-naïve EAMD underwent macular 3×3 mm OCTA with AngioVue system. OCTA scans were analysed and processed including three-dimensional projection artefact removal, retinal layer semi-automated segmentation and en face angiogram generation. Automated quantification of extrafoveal (excluding the central 1 mm circle) avascular area (EAA) were calculated on projection-resolved superficial vascular complex (SVC), intermediate capillary plexus (ICP) and deep capillary plexus (DCP), respectively.ResultsNineteen eyes with EAMD and 19 age-matched healthy control eyes were included. There was no significant difference between the EAMD and control eyes in terms of age, sex, axial length and mean ocular perfusion pressure (all p>0.05). Compared with control eyes, EAMD eyes had significantly larger EAA in SVC (median 0.125 vs 0.059 mm2, p=0.006), ICP (0.016 vs 0.000 mm2, p=0.004) and DCP (0.033 vs 0.000 mm2, p＜0.001).ConclusionPR-OCTA showed that EAMD is associated with focal avascular area in all the three retinal vascular plexuses.

The emergence and global spread of SARS-CoV-2 has had profound social and economic consequences and has shed light on the importance of continued and additional investment in global health and infectious disease surveillance. Identifying changes in viral genomes provides key insights into viral diversity, how viruses spread within populations, and viral strategies for evasion of host immune systems. Here we report twenty-five SARS-CoV-2 genome sequences collected from some of the first COVID-19 cases in eastern Ontario, Canada (March 18-30, 2020). The reported genomes belong to the S-clade (n=2) and G-clade (n=23) of SARS-CoV-2 and contain 45 polymorphic sites including one shared missense and three unique synonymous variants in the gene encoding the spike protein. A phylogenetic analysis enabled the tracing of viral origin and potential transmission into and within Canada. There may be as many as sixteen unique infection events represented in these samples, including at least three that were likely introduced from Europe and seven from the USA. In addition, four separate genomes are each shared by multiple patients, suggesting a common origin or community spread even during this early stage of infection. These results demonstrate how molecular epidemiology and evolutionary phylogenetics can help local health units track origins and vectors of spread for emerging diseases like SARS-CoV-2. Earlier detection and screening in this way could improve the effectiveness of regional public health interventions to prevent future pandemics.

Purpose: To evaluate nerve fiber layer (NFL) reflectance for glaucoma diagnosis. Methods: Participants were imaged with 4.5X4.5-mm volumetric disc scans using spectral-domain optical coherence tomography (OCT). The normalized NFL reflectance map was processed by an azimuthal filter to reduce directional reflectance bias due to variation of beam incidence angle. The peripapillary area of the map was divided into 160 superpixels. Average reflectance was the mean of superpixel reflectance. Low-reflectance superpixels were identified as those with NFL reflectance below the 5 percentile normative cutoff. Focal reflectance loss was measure by summing loss in low-reflectance superpixels. Results: Thirty-five normal, 30 pre-perimetric and 35 perimetric glaucoma participants were enrolled. Azimuthal filtering improved the repeatability of the normalized NFL reflectance, as measured by the pooled superpixel standard deviation (SD), from 0.73 to 0.57 dB (p, pages: 31; Tables: 6; Figures: 9

Regional specification is critical for skin development, regeneration, and evolution. The contribution of epigenetics in this process remains unknown. Here, using avian epidermis, we find two major strategies regulate β-keratin gene clusters. (1) Over the body, macro-regional specificities (scales, feathers, claws, etc.) established by typical enhancers control five subclusters located within the epidermal differentiation complex on chromosome 25; (2) within a feather, micro-regional specificities are orchestrated by temporospatial chromatin looping of the feather β-keratin gene cluster on chromosome 27. Analyses suggest a three-factor model for regional specification: competence factors (e.g., AP1) make chromatin accessible, regional specifiers (e.g., Zic1) target specific genome regions, and chromatin regulators (e.g., CTCF and SATBs) establish looping configurations. Gene perturbations disrupt morphogenesis and histo-differentiation. This chicken skin paradigm advances our understanding of how regulation of big gene clusters can set up a two-dimensional body surface map.