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A chromosome 14 inversion was found in a patient who developed bone marrow aplasia following treatment with allogeneic chimeric antigen receptor (CAR) Tcells containing gene edits made with transcription activator-like effector nucleases (TALEN). TALEN editing sites were not involved at either breakpoint. Recombination signal sequences (RSSs) were found suggesting recombination-activating gene (RAG)-mediated activity. The inversion represented a dominant clone detected in the context of decreasing absolute CAR Tcell and overall lymphocyte counts. The inversion was not associated with clinical consequences and wasnot detected in the drug product administered to this patient or in any drug product used in this or other trials using the same manufacturing processes. Neither was the inversion detected in this patient at earlier time points or in any other patient enrolled in this or other trials treated with this or other product lots. This case illustrates that spontaneous, possibly RAG-mediated, recombination events unrelated to gene editing can occur in adoptive cell therapy studies, emphasizes the need for ruling out off-target gene editing sites, and illustrates that other processes, such as spontaneous V(D)J recombination, can lead to chromosomal alterations in infused cells independent of gene editing.

To evaluate intraretinal cystoid spaces in patients with idiopathic macular hole (MH).Retrospective cohort study included consecutive patients with full-thickness MH who underwent successful MH surgery and 12 months of follow-up. Custom software was applied to preoperative optical coherence tomography scans to generate fluid volume. Inner fluid volume was defined as cystoid spaces in the inner nuclear layer, and outer fluid volume was defined as cystoid spaces in Henle fiber layer of the outer nuclear layer.Thirty-nine eyes from 39 participants were included. Postoperative 12-month visual acuity correlated with both inner fluid volume and minimum MH size (both P0.05) but not outer fluid volume. Inner fluid volume positively correlated with minimum MH size ( P = 0.0003). After accounting for minimum MH size with multivariable analysis, inner fluid volume effect on VA remained significant ( P = 0.025). After dividing inner fluid volume into tertiles, mean baseline visual acuity was 20/50 in eyes with small inner fluid volume, and was 20/125 in eyes with large inner fluid volume ( P = 0.0039). Mean postoperative 12-month visual acuity was 20/20 in eyes with small inner fluid volume compared with 20/32 in eyes with large inner fluid volume ( P = 0.019).Increased inner fluid volume was associated with worse postoperative VA.

As a vector of human health concern, blacklegged ticks ( Ixodes scapularis ) transmit pathogens that cause tick-borne diseases (TBDs), including Lyme disease (LD). Several hot spots of elevated LD risk have emerged across Canada as I. scapularis expands its range.

Background and ObjectivesPatients with multiple sclerosis (MS) may seek fertility treatment (FT)—including in vitro fertilization (IVF). Variable relapse risk after IVF has been reported in small historical cohorts, with more recent studies suggesting no change in annualized relapse rate (ARR). The objective of this study was to evaluate ARR 12 months pre-FT and 3 months post-FT in a multicenter cohort and identify factors associated with an increased risk of relapse.MethodsPatients with clinically isolated syndrome (CIS) or MS aged 18–45 years with at least 1 FT from January 1, 2010, to October 14, 2021, were retrospectively identified at 4 large academic MS centers. The exposed period of 3 months after FT was compared with the unexposed period of 12 months before FT. FTs included controlled ovarian stimulation followed by fresh embryo transfer (COS-ET), COS alone, embryo transfer (ET) alone, and oral ovulation induction (OI). The Wilcoxon signed rank test and mixed Poisson regression models with random effects were used to compare ARR pre-FT vs post-FT, with the incidence rate ratio (IRR) and 95% CI reported.ResultsOne hundred twenty-four FT cycles among 65 patients with MS (n = 56) or CIS (n = 9) were included: 61 COS-ET, 19 COS alone, 30 ET alone, and 14 OI. The mean age at FT was 36.5 ± 3.8 years, and the mean disease duration was 8.2 ± 5.0 years. Across 80 cycles with COS, only 5 relapses occurred among 4 unique patients within 3 months of treatment. The mean ARR after COS and before was not different (0.26 vs 0.25,p= 0.37), and the IRR was 0.95 (95% CI: 0.52–1.76,p= 0.88). No cycles with therapeutic disease-modifying therapies (DMTs) during COS had 3 months relapse (ARR 0 post-COS vs 0.18 pre-COS,p= 0.02, n = 34). Relapse rates did not vary by COS protocol. Among COS-ET cycles that achieved pregnancy (n = 43), ARR decreased from 0.26 to 0.09 (p= 0.04) within the first trimester of pregnancy. There were no relapses 3 months after ET alone and 1 relapse after OI.DiscussionIn this modern multicenter cohort of patients with MS undergoing diverse FTs, which included 43% on DMTs, we did not observe an elevated relapse risk after FT.

PURPOSE: To formulate an Epithelial Modulation index to differentiate between eyes with contact lens warpage and keratoconus. METHODS: Normal eyes and eyes with either contact lens warpage or keratoconus were scanned by a Fourier-domain optical coherence tomography (OCT) system. Maps of epithelial thickness and anterior surface mean curvature were generated and converted to deviation maps by subtracting the average maps from a healthy population. The Epithelial Modulation index was defined as the covariance between the two types of deviation maps. A logistic regression model was used to classify eyes as non-keratoconus (normal or warp-age) or keratoconus (manifest, subclinical, or forme fruste). RESULTS: The average Epithelial Modulation index value for normal eyes was −0.6 ± 1.0 µm/m. Eyes with keratoconus were characterized by coincident high anterior surface mean curvature and low epithelial thickness, resulting in a high Epithelial Modulation index (manifest: 103.0 ± 82.9 µm/m, subclinical: 37.0 ± 23.0 µm/m, forme fruste: 7.3 ± 13.2 µm/m). The Epithelial Modulation index was closer to normal for eyes with warpage (−1.9 ± 4.0 µm/m). The classification accuracy of the Epithelial Modulation index during five-fold cross-validation of the logistic regression model was 100 ± 0% for normal eyes and 99.0 ± 2.0% for eyes with warpage. The accuracy was 100 ± 0%, 100 ± 0%, and 53.1 ± 1.5% for the manifest, subclinical, and forme fruste keratoconus groups, respectively. CONCLUSIONS: The Epithelial Modulation index is useful in distinguishing eyes with secondary epithelial modulation (keratoconus) from those with primary epithelial deformation (contact lens–related warpage). [ J Refract Surg . 2022;38(2):112–119.]

Nuclear architecture underlies the transcriptional programs within the cell to establish cell identity. As previously demonstrated, long-range chromatin interactions of the Oct4 distal enhancer (DE) are correlated with active transcription in naïve state embryonic stem cells. Here, we identify and characterize extreme long-range interactions of the Oct4 DE through a novel CRISPR labeling technique we developed and chromosome conformation capture to identify lethal giant larvae 2 (Llgl2) and growth factor receptor-bound protein 7 (Grb7) as putative functional interacting target genes in different chromosomes. We show that the Oct4 DE directly regulates expression of Llgl2 and Grb7 in addition to Oct4. Expression of Llgl2 and Grb7 closely correlates with the pluripotent state, where knock down of either result in loss of pluripotency, and overexpression enhances somatic cell reprogramming. We demonstrated that biologically important interactions of the Oct4 DE can occur at extreme distances that are necessary for the maintenance of the pluripotent state.

As an alternative to traditional meteorological methods, rain attenuation in satellite-to-Earth microwave communication signals has been used for rainfall reconstruction in recent years. In this article, the existing 2-D rain field reconstruction problem is extended to a 3-D scenario by leveraging the low Earth orbit satellite system. A compressive sensing approach is further proposed to solve the 3-D rain field reconstruction problem. The Starlink system is used as a reference, and two synthetic rain events near the Great Barrier Reef in Australia, which are generated from the weather research and forecasting model, are used to evaluate the reconstruction performance. Simulation results show that the compressive sensing approach performs better than both the traditional least squares and the least absolute shrinkage and selection operator approaches.

Understanding the solution-phase behaviour of organic semiconducting polymers is important for systematically improving the performance of devices based on solution-processed thin films of these molecules. Conventional polymer theory predicts that polymer conformations become more compact as solvent quality decreases, but recent experiments have shown the high-performance organic-semiconducting polymer P(NDI2OD-T2) to form extended rod-like aggregates much larger than a single chain in poor solvents, with the formation of these extended aggregates correlated with enhanced electron mobility in films deposited from these solutions. We explain the unexpected formation of extended aggregates using a novel coarse-grained simulation model of P(NDI2OD-T2) that we have developed to study the effect of solvent quality on its solution-phase behaviour. In poor solvents, we find that aggregation through only a few monomers gives effectively inseparable chains, leading to the formation of extended structures of partially overlapping chains via non-equilibrium assembly. This behaviour requires that multi-chain aggregation occurs faster than chain folding, which we show is the case for the chain lengths and concentrations shown experimentally to form rod-like aggregates. This kinetically controlled process introduces a dependence of aggregate structure on concentration, chain length, and chain flexibility, which we show is able to reconcile experimental findings and is generalisable to the solution-phase assembly of other semiflexible polymers.

Background PLG0206 is an investigational, engineered cationic antimicrobial peptide designed to overcome the shortcomings of other natural AMPs, such as toxicity and limited activity. PLG0206 has recently been shown to be well tolerated and safe when administered i.v. in a Phase 1 study. The initial proposed indication for this peptide is the treatment of periprosthetic joint infections via irrigation due to a broad spectrum of activity and anti-biofilm properties. This study evaluated the activity of PLG0206 and comparator antimicrobials against staphylococci and enterococci, causes of periprosthetic joint infections, from the IHMA repository of isolates collected from various world-wide locations in 2019. Methods Isolates tested included Enterococcus faecalis (77), E. faecium (75), methicillin-resistant Staphylococcus aureus (MRSA, 180), methicillin-susceptible S. aureus (MSSA, 121) and 152 coagulase-negative staphylococci (CoNS) comprised of S. epidermidis (113), S. haemolyticus (31), S. hominis (4), S. lugdunensis (1), S. saprophyticus (2) and S. simulans (1). Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution in cation-adjusted Mueller Hinton broth (CA-MHB), except for PLG0206 which was tested in RPMI medium due to plate-reading difficulties with CA-MHB. The susceptibility of comparators was determined using the 2022 CLSI breakpoints. MDR was defined as resistance to ≥ 3 antibacterial classes. Results When tested in RPMI, 18 E. faecalis, 29 E. faecium, 9 S. aureus and 7 CoNS were unable to grow. Summary MIC and susceptibility data for PLG0206 and comparators just including those isolates able to grow in RPMI are shown in the Table. Identical MIC50 and MIC90 values were obtained for PLG0206 when tested against MDR E. faecium (38), MDR CoNS (63) and MDR MRSA (67). Insufficient numbers of MDR MSSA (7) and MDR E. faecalis (4) were tested to accurately evaluate. Conclusion PLG0206 was the most potent antimicrobial overall (based on MIC50 and MIC90) against enterococci and CoNS and compared well with the comparators against MRSA and MSSA. These data support the evaluation of this novel antimicrobial peptide as a treatment option for periprosthetic joint infections, including those caused by MDR strains. Disclosures David Huang, MD, PhD, Peptilogics: Employee Jonathan Steckbeck, PhD, Peptilogics: I am CEO of Peptilogics.

Background PLG0206 is an investigational, engineered cationic antimicrobial peptide designed to overcome the shortcomings of other natural AMPs, such as toxicity and limited activity. PLG0206 has recently been shown to be well tolerated and safe in a phase 1 study. This study evaluated the activity of PLG0206 and comparator antimicrobials against Enterobacterales isolates from the IHMA repository collected from various world-wide locations in 2019. Methods Isolates tested included Citrobacter spp. (151), Enterobacter cloacae (152), Escherichia coli (300), Klebsiella pneumoniae (300), Morganella morganii (43), Proteus spp. (152), Providencia spp. (61) and Serratia marcescens (45). Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution in cation-adjusted Mueller Hinton broth (CA-MHB), except for PLG0206 which was tested in RPMI medium due to plate-reading difficulties with CA-MHB. The susceptibility of comparators was determined using the 2022 CLSI breakpoints. MDR was defined as resistance to ≥ 3 antibacterial classes. Results Summary MIC and susceptibility data against Citrobacter spp., E. coli, E. cloacae, and K. pneumoniae are shown in the Table. PLG0206 retained activity against MDR isolates of Citrobacter spp. (26), E. coli (92), E. cloacae (45), and K. pneumoniae (132) with MIC50/90 values of 1/2, 1/2, 1/16 and 8/16 μg/mL, respectively. PLG0206 was essentially inactive against the Morganellaceae and Yersiniaceae isolates tested with MIC50 and MIC90 values of > 32 μg/mL (data not shown). Conclusion PLG0206 was active against isolates from the family Enterobacteriaceae, including MDR strains. The spectrum of activity of PLG0206 ranged from being most active against Citrobacter spp. and least active against K. pneumoniae. These data suggest that the novel antimicrobial peptide PLG0206 could be a potential treatment option against infections caused by Enterobacteriaceae isolates. Disclosures David Huang, MD, PhD, Peptilogics: Employee Jonathan Steckbeck, PhD, Peptilogics: I am CEO of Peptilogics.

This report examines changes in health disparities over time by race and ethnicity for HP2020 objectives using three measures of disparity.

Ticks in the familyIxodidaeare important vectors of zoonoses including Lyme disease (LD), which is caused by spirochete bacteria from theBorreliella(Borrelia)burgdorferisensu lato (Bbsl) complex. The blacklegged tick (Ixodes scapularis) continues to expand across Canada, creating hotspots of elevated LD risk at the leading edge of its expansion range. Current efforts to understand the risk of pathogen transmission associated withI. scapularisin Canada focus primarily on targeted screens, while variation in the tick microbiome remains poorly understood. Using multi-omics consisting of 16S metabarcoding and ribosome-depleted, whole-shotgun RNA transcriptome sequencing, we examined the microbial communities associated with adultI. scapularis(N = 32), sampled from four tissue types (whole tick, salivary glands, midgut, and viscera) and three geographical locations within a LD hotspot near Kingston, Ontario, Canada. The communities consisted of both endosymbiotic and known or potentially pathogenic microbes, including RNA viruses, bacteria, and aBabesiasp. intracellular parasite. We show that β-diversity is significantly higher between individual tick salivary gland and midgut bacterial communities, compared to whole ticks; while linear discriminant analysis (LDA) effect size (LEfSe) determined that the three potentially pathogenic bacteria detected by V4 16S rDNA sequencing also differed among dissected tissues only, including aBorreliafrom theBbslcomplex,Borrelia miyamotoi, andAnaplasma phagocytophilum. Importantly, we find co-infection ofI. scapularisby multiple microbes, in contrast to diagnostic protocols for LD, which typically focus on infection from a single pathogen of interest (B. burgdorferisensu stricto).IMPORTANCEA vector of human health concern, blacklegged ticks,Ixodes scapularis, transmit pathogens that cause tick-borne diseases (TBDs), including Lyme disease (LD). Several hotspots of elevated LD risk have emerged across Canada asI. scapularisexpands its range. Focusing on a hotspot in southeastern Ontario, we used high-throughput sequencing on whole ticks and dissected salivary glands and midguts. Compared to whole ticks, analysis of salivary glands and midguts revealed greater β-diversity among microbiomes that are less dominated byRickettsiaendosymbiont bacteria and enriched for pathogenic bacteria including aBbsl-associatedBorrelia,Borrelia miyamotoi, andAnaplasma phagocytophilum. We also find evidence of co-infection ofI. scapularisin this region by multiple microbes. Overall, our study highlights the challenges and opportunities associated with the surveillance of the microbiome ofI. scapularisfor pathogen detection using metabarcoding and metatranscriptome approaches.

Acquiring accurate channel state information and mitigating severe intersymbol interference are challenging for underwater acoustic communications with moving transceivers due to the rapid changes of the underwater acoustic channels. In this work, we address the issue using a superimposed training (ST) scheme with a powerful channel estimation method. Different from the conventional time-multiplexed training, training sequences with a small power are superimposed with symbol sequences. The training signals are transmitted over all time, leading to enhanced tracking capability to deal with time-varying channels at the cost of only a small power loss. To realize this, based on the belief propagation, we develop a message-passing-based bidirectional channel estimation (BCE) algorithm, where all messages are Gaussian, enabling efficient implementation. In particular, the channel correlations are fully exploited through a forward recursion and a backward recursion, thereby achieving accurate channel estimation. Moreover, the ST-based BCE is combined with channel equalization (in the frequency domain) and decoding, and they are performed jointly in an iterative manner to significantly enhance the overall system performance. Field experiments were carried out in Jiaozhou Bay in 2019, and the results verify the effectiveness of the proposed scheme and algorithm.

Screening for perinatal depression is a clinical approach to identifying women in need of mental health diagnoses, referral, and treatment. Many states mandate screening for perinatal depression, b...

This study was designed to evaluate iVue Spectral-domain optical coherence tomography (SD-OCT) effectiveness in screening for eye disease compared to clinical examination. Subjects were recruited from the Casey Eye Community Outreach Program Mobile Clinic during its routinely scheduled outreach clinics to indigent, underserved populations throughout Oregon. Macular optical coherence tomography interpretation and automated optical coherence tomography analysis were compared to the clinical examination, with specific attention to findings indicative of retinal abnormalities, risks for glaucoma, and narrow angles. As a result, a total of 114 subjects were included in this study. In diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.39), with 22% of eyes having abnormal findings on macular optical coherence tomography and 26% of eyes having diabetic retinopathy or diabetic macular edema on fundus exam. In non-diabetics, optical coherence tomography and clinical exam were in fair agreement (kappa = 0.28), with 11% of eyes having abnormal findings on macular optical coherence tomography and 9% on fundus exam. Using optical coherence tomography ganglion cell complex and retinal nerve fiber layer analysis, 18% of eyes were found to be glaucoma suspects, whereas clinical exam of cup-to-disc ratio detected 8% and intraocular pressure 5%. Agreements between optical coherence tomography and other methods were poor (kappa

Molecular property predictors form the core of any AI-enabled drug discovery strategy. In recent years, there has been significant research in this area, resulting in the development of powerful predictors and representations. However, these diverse predictors have different software interfaces, dependencies, and levels of documentation. Due to lack of a unified API for molecular property prediction, an AI-enabled drug discovery endeavor often necessitates a tangled web of scripts, notebooks, and configuration. This makes it is needlessly difficult to share, distribute, and manage predictors, to ensemble predictors together, and to provide universal AI explainability tools. To this end, we present Oloren ChemEngine (OCE), an open-source Python library with a unified API for molecular property predictors with simplified model management and reproducibility. Using OCE, we create models which achieve superior performance on ADME/Tox prediction tasks by ensembling and integrating many different molecular property prediction methods. We include model-agnostic uncertainty quantification using calibrated confidence intervals and probabilities as well as interpretability using counterfactual methods.

The purpose of this study was to correct refractive error-associated bias in optical coherence tomography (OCT) and OCT angiography (OCTA) glaucoma diagnostic parameters.OCT and OCTA imaging were obtained from participants in the Hong Kong FAMILY cohort. The Avanti/AngioVue OCT/OCTA system was used to measure the peripapillary nerve fiber layer thickness (NFLT), peripapillary nerve fiber layer plexus capillary density (NFLP-CD), macular ganglion cell complex thickness (GCCT), and macular superficial vascular complex vascular density (SVC-VD). Healthy eyes, including ones with axial ametropia, were enrolled for analysis.A total of 1346 eyes from 792 participants were divided into 4 subgroups: high myopia (-6D), low myopia (-6D to -1D), emmetropia (-1D to 1D), and hyperopia (1D). After accounting for age, sex, and signal strength, multivariable regression showed strong dependence in most models for NFLT, GCCT, and NFLP-CD on axial eye length (AL), spherical equivalent (SE) refraction, and apparent optic disc diameter (DD). Optical analysis indicated that AL-related transverse optical magnification variations predominated over anatomic variations and were responsible for these trends. Compared to the emmetropic group, the false positive rates were significantly (Chi-square test P0.003) elevated in both myopia groups for NFLT, NFLP-CD, and GCCT. Regression-based adjustment of these diagnostic parameters with AL or SE significantly (McNemar test P0.03) reduced the elevated false positive rates.Myopic eyes are biased to have lower NFLT, GCCT, and NFLP-CD measurements. AL- and SE-based adjustments were effective in mitigating this bias.Adoption of these adjustments into commercial OCT systems may reduce false positive rates related to refractive error.

BackgroundPerinatal (during pregnancy and up until one year after birth) depression is one of the most common medical complications of pregnancy and is a major public health issue. The common early detection method to identify depression is to systematically administer depression screens to patients during their usual care clinic encounters. This study investigates how prenatal patients perceive depression screening and how screening informs their treatment to meet the specific needs of different racial and ethnic groups within both community and health care settings.MethodsBetween June 2019 and August 2019, semi-structured in-depth interviews were conducted to explore participants' experiences of depression screening with the Edinburgh Postnatal Depression Scale (EPDS). Perinatal women (N = 29) consented to participate in-depth, one-on-one qualitative interviews. Trained patient-researchers (n = 6), women who had previously experienced a perinatal mental health problem, were trained as research team members and facilitated the interviews alongside a research assistant. All interviews were recorded and transcribed verbatim. Data was analyzed with the use of Nvivo12. Thematic network analysis was used to analyze the data.ResultsThrough the in-depth patient engaged qualitative interviews this study uncovered several specific motivators and behaviors related to perinatal depression screening. Using directed content analysis, several themes within a COM-B frame emerged and could be reduced to themes and further divided into two different stages: the depression screening stage and the post-screening stage.ConclusionsThe results of this qualitative study provide information for health care providers to improve, adjust, and assess the process of conducting perinatal depression screening among women. The data also provide information for health care facilities to identify a better screening tool and develop and measure their screening process. These findings are essential to design comprehensive patient-centered screening protocols given the increase in state and federal policies urging universal depression screening.

Singlet fission (SF), a process that produces two triplet excitons from one singlet exciton, has attracted recent interest for its potential to circumvent the detailed-balance efficiency limit of single-junction solar cells. For the potential of SF to be fully realized, accurate assignment and quantification of SF is necessary. Intersystem crossing (ISC) is another process of singlet to triplet conversion that is important to distinguish from SF to avoid either over- or under-estimation of SF triplet production. Here, we quantify an upper bound on the rate of ISC in two commonly studied SF chromophores, TIPS–pentacene and TIPS–tetracene, by using transient absorption spectroscopy of solutions of varying concentrations in toluene. We show that SF in solutions of these acenes has previously been misidentified as ISC, and vice versa. By determining a bimolecular SF rate constant in concentrated solutions in which SF dominates over ISC, we distinguish triplet formation due to SF from triplet formation due to ISC and show that the characteristic time scale of ISC must be longer than 325 ns in TIPS–pentacene, while it must be longer than 118 ns in TIPS–tetracene. We additionally note that no excimer formation is observed in the relatively dilute (up to 8 mM) solutions studied here, indicating that previous excimer formation observed at much higher concentrations may be partially due to aggregate formation. This work highlights that an accurate quantification of ISC is crucial as it leads to accurate determination of SF rate constants and yields.

PURPOSE: To quantify the abnormal corneal thinning and posterior surface steepening that is observed in keratoconus with an Ectasia Index. METHODS: Optical coherence tomography (OCT) was used to image the corneas of normal individuals and patients with varying stages of keratoconus (manifest, subclinical, and forme fruste). Maps of corneal pachymetry and posterior surface mean curvature were generated, and an Ectasia Index was calculated by multiplying Gaussian fits obtained from the two types of maps. Repeated five-fold cross-validation was used to evaluate the ability of the Ectasia Index to differentiate between normal and keratoconic eyes. The classification performance of the Ectasia Index was compared to minimum pachymetry and maximum posterior mean curvature. RESULTS: Thirty-two eyes from 16 normal individuals, 89 eyes from 63 patients with manifest keratoconus, 16 eyes from 15 patients with subclinical keratoconus, and 26 eyes from 26 patients with forme fruste keratoconus were included in the study. During cross-validation, 100% of the eyes with manifest (89 of 89) and subclinical (16 of 16) keratoconus were correctly classified by the Ectasia Index. The average classification accuracy for the forme fruste keratoconus group was 63 ± 21% (16.4 of 26). The specificity for the normal group was 91 ± 10% (29.1 of 32). The Ectasia Index had a higher sensitivity for keratoconus detection and similar specificity in comparison to minimum pachymetry and maximum posterior mean curvature. CONCLUSIONS: The Ectasia Index could be a valuable additional metric for clinicians to consider when screening for keratoconus. [ J Refract Surg . 2022;38(8):502–510.]

PurposeTo assess the effects of algorithms and covariates in glaucoma diagnosis with optical coherence tomography angiography (OCTA).MethodsIn this prospective cross-sectional study, one eye each of 36 normal controls and 64 patients with glaucoma underwent 4.5 mm disc-centred and 6 mm macula-centred OCTA scans. The peripapillary nerve fibre layer plexus capillary density (NFLP-CD) and macular superficial vascular complex vessel density (SVC-VD) were measured using both a commercial algorithm (AngioAnalytics) and a custom algorithm (Center for Ophthalmic Optics & Lasers Angiography Reading Toolkit (COOL-ART)). The nerve fibre layer and ganglion cell complex thicknesses were measured on structural OCT.ResultsThe overall peripapillary NFLP-CD and macular SVC-VD measured with the two algorithms were highly correlated but poorly agreed. Among the normal controls, the perfusion measurements made by both algorithms were significantly correlated with age. AngioAnalytics measurements were also correlated with signal strength index, while COOL-ART measurements were not. These covariates were adjusted. The diagnostic accuracy, measured as the area under the receiver operating characteristic curve for glaucoma detection, was not significantly different between algorithms, between structural and perfusion parameters and between the peripapillary and macular regions (All p>0.05). The macular SVC-VD in the 6 mm square had a significantly higher diagnostic accuracy than that of the central 3 mm square area (p=0.005).ConclusionsAngioAnalytics and COOL-ART vessel density measurements are not interchangeable but potentially interconvertible. Age and signal strength are significant covariates that need to be considered. Both algorithms and both peripapillary and macular perfusion parameters have similarly good diagnostic accuracy comparable to structural OCT. A larger macular analytic area provides higher diagnostic accuracy.

This research examined the operation of zinc–air fuel cell (ZAFC) with two different anode fuel types, namely zinc plate and zinc particle. The cell operation with zinc particle fuel also included ...

ImportanceFibroids are benign uterine tumors that can cause significant morbidity. Knowledge on fibroid prevalence, especially in the asymptomatic population and in Asian and Hispanic or Latina individuals, is limited, and a better understanding of affected groups will improve timely diagnosis and motivate appropriate recruitment in clinical trials to reduce health disparities.ObjectiveTo estimate the prevalence of fibroids in a diverse cohort of female individuals.Design, Setting, and ParticipantsThis cross-sectional study included female individuals not seeking treatment for fertility or other conditions who were prospectively recruited in an academic medical center in San Francisco, California. Effort was made to recruit an equal proportion of participants from 4 large racial and ethnic groups in the United States (Asian-Chinese, Black or African American, Hispanic or Latina, and White) and across 4 equal age groups between 25 and 45 years. All participants reported regular menses (21-35 days), had not used estrogen- or progestin-containing medications in the 3 months prior to enrollment, and denied history of pelvic surgery. The assessment of ultrasonography results was part of an ongoing longitudinal cohort, with initial recruitment from October 2006 to September 2012. Data analysis was performed in April to September 2022.Main Outcomes and MeasuresFibroid presence and burden as assessed by transvaginal ultrasonography.ResultsA total of 996 female participants were included in the analysis, including 229 (23.0%) Asian-Chinese, 249 (25.0%) Black or African American, 237 (23.8%) Hispanic or Latina, and 281 (28.2%) White individuals. Mean (SD) age was 34.8 (5.7) years in Asian-Chinese participants, 35.4 (6.1) years in Black or African American participants, 34.8 (5.3) years in Hispanic or Latina participants, and 35.3 (5.0) years in White participants. Fibroids were present in 21.8% (95% CI, 16.7%-27.8%) of Asian-Chinese participants, 35.7% (95% CI, 29.8%-42.0%) of Black or African American participants, 12.7% (95% CI, 8.7%-17.6%) of Hispanic or Latina participants, and 10.7% (95% CI, 7.3%-14.9%) of White participants. Black or African American and Asian-Chinese participants were more likely to have fibroids than White participants (Black or African American: adjusted odds ratio [OR], 4.72 [95% CI, 2.72-8.18]; P P P = .06). The largest mean (SD) fibroid diameter was 3.9 (1.9) cm in Black or African American participants, 3.2 (1.6) cm in Asian-Chinese participants, 3.2 (1.6) cm in White participants, and 3.0 (1.4) cm in Hispanic or Latina participants (P = .03).Conclusions and RelevanceIn this study of female participants in a nonclinical setting, Black or African American and Asian-Chinese participants were disproportionately affected by uterine fibroids. Hispanic or Latina participants had similar fibroid burden to White participants.

To test the ability of the corneal epithelial pattern standard deviation to distinguish between normal and cases with corneal ectatic condition.Instituto de Olhos Renato Ambrósio, Rio de janeiro, Brazil.Cross-sectional retrospective study.Patients were stratified into four groups based on clinical data and.(Groups 1 and 2 comprised one eye randomly selected from 105 patients with normal corneas (N) and 86 patients with bilateral keratoconus (KC). Groups 3 and 4, respectively comprised 11 ectatic eyes with no surgical treatment for keratoconus (VAE-E) from patients whose fellow eyes (61) presented with normal topographic patterns (VAE-NT). Corneas were scanned using an OCT system (RT Vue) and Scheimpflug corneal tomography (Pentacam), and also had biomechanical assessment through the Corvis ST. Corneal epithelial thickness maps were analyzed and the pattern standard deviation (PSD) value was calculated. The area under the ROC curve analysis was used to evaluate the diagnostic accuracy of the indices.Epithelial PSD was significantly different across the four groups (p0.0001). The pairwise comparison revealed that the normal group presented significantly lower values than both ectasia groups (KC and VAE-E, p0.0001) and the VAE-NT group (p=0.0008). There was no significant difference between KC and VAE-E (p=0.4284), while they were significantly higher than the VAE-NT group (p0.0001 and p=0.0004).Epithelial PSD can be used to detect abnormal epithelial thickness patterns. Corneal epithelial thickness changes could be detected accurately in keratoconus patients, even in the form fruste of the disease.

Organic donor:acceptor semiconductor nanoparticles (NPs) formed through the miniemul- sion method have been shown to be active photocatalysts. Here we report photocatalytic hydrogen (H2) evolution under sacrificial conditions with Pt as a co-catalyst by NPs comprising only the non-fullerene acceptor Y6, stabilized by either sodium dodecyl sulfate (SDS) or the thiophene-containing surfactant 2-(3-thienyl)ethyloxybutylsulfonate sodium salt (TEBS). Typically, changes in the photocatalytic activity of donor:acceptor NPs are associated with differences in morphology due to the use of surfactants. However, as these NPs are single-component, their photocatalytic activity has a significantly lower dependence on morphology than two-component donor:acceptor NPs. Results from ultrafast transient absorption spectroscopy show a minor difference between the photophysics of the TEBS- and SDS-stabilized Y6 NPs, with free charges present with either surfactant. The similar photophysics suggest that both TEBS- and SDS-stabilized Y6 NPs would be expected to have similar rates of H2 evolution. However, the results from photocatalysis show that Y6 NPs stabilized by TEBS have a H2 evolution rate 21 times higher than that of the SDS- stabilized NPs under broadband solar-like illumination (400–900 nm). Transmission electron microscopy images of the Y6 NPs show effective photodeposition of Pt on the surface of the TEBS-stabilized NPs. In contrast, photodeposition of Pt is inhibited when SDS is used. Furthermore, the zeta potential of the NPs is higher in magnitude when SDS is present. Hence, we hypothesize that SDS forms a dense, insulating layer on the NP surface which hinders the photodeposition of Pt and reduces the rate of H2 evolution. This insulating effect is absent for TEBS-stabilized Y6 NPs, allowing a high rate of H2 evolution. The TEBS-stabilized Y6 NPs have a H2 evolution rate higher than most single-component organic photocatalysts, signaling the potential use of the Y-series acceptors for H2 evolution in Z-scheme photocatalysis.

Singlet fission (SF), a process that produces two triplet excitons from one singlet exciton, has attracted recent interest for its potential to circumvent the detailed-balance efficiency limit of single-junction solar cells. For the potential of SF to be fully realized, accurate assignment and quantification of SF is necessary. Intersystem crossing (ISC) is another process of singlet to triplet conversion that is important to distinguish from SF to avoid either over- or under-estimation of SF triplet production. Here, we quantify an upper bound on the rate of ISC in two commonly studied SF chromophores, TIPS-pentacene and TIPS-tetracene, by using transient absorption spectroscopy of solutions of varying concentrations in toluene. We show that SF in solutions of these acenes has previously been misidentified as ISC, and vice versa. By determining a bimolecular SF rate constant in concentrated solutions in which SF dominates over ISC, we distinguish triplet formation due to SF from triplet formation due to ISC, and show that the characteristic time scale of ISC must be longer than 325 ns in TIPS-pentacene, while it must be longer than 118 ns in TIPS- tetracene. We additionally note that no excimer formation is observed in the relatively dilute (up to 8 mM) solutions studied here, indicating that previous excimer formation observed at much higher concentrations may be partially due to aggregate formation. This work highlights that an accurate quantification of ISC is crucial as it leads to accurate determination of SF rate constants and yields.

One of the highest performing materials in organic photovoltaics is a blend of the polymer donor PM6 and non-fullerene acceptor (NFA) Y6. We report the use of 1:1 PM6:Y6 blend nanoparticles (NPs) prepared by the miniemulsion method for the photocatalytic production of hydrogen under sacrificial conditions, with a 2% mass loading of Pt co-catalyst. When pre- pared using TEBS, a thiophene-containing surfactant, these blend NPs have a desirable inter- mixed morphology. Under ≈1-sun illumination from 400 to 900 nm, hydrogen is produced at a rate of 8000 ± 400 μmol h−1 g−1, which is among the highest reported for organic photocata- lysts under similar conditions. Remarkably, this rate remains high at 5200 ± 300 μmol h−1 g−1 under 650 −900 nm excitation, where Y6 is exclusively excited, generating free charges by hole transfer from Y6 to PM6. The rate drops to 2400 ± 200 μmol h−1 g−1 at 400 −600 nm excitation, where PM6 is preferentially excited and free charges are generated from the conventional electron transfer mechanism. Additionally, external quantum efficiencies of 0.27 ± 0.08% at 405nm, 0.19 ± 0.04% at 565nm, and 0.22 ± 0.02% at 780nm were measured, indicating that this photocatalyst uses a broad region of solar spectrum to yield hydrogen from excitation of both the donor and the acceptor. Transient absorption spectroscopy results show that both hole transfer and electron transfer occur following the excitation of Y6 and PM6, respectively. This work is the first study to show that free charge generation via hole transfer is the dominant mechanism of hydrogen evolution in a donor:NFA blend. This work also highlights the potential that other donor:NFA blends may have for highly efficient green hydrogen production.

Background Approximately 3.8% of adults worldwide have used cannabis in the past year. Understanding how cannabis use is associated with other health conditions is crucial for healthcare providers seeking to understand the needs of their patients, and for health policymakers. This paper analyzes the relationship between documented cannabis use disorders (CUD), cannabis use (CU) and other health diagnoses among primary care patients during a time when medical use of marijuana was permitted by state law in California, United States of America. Methods The study utilized primary care electronic health record (EHR) data from an academic health system, using a case–control design to compare diagnoses among individuals with CUD/CU to those of matched controls, and those of individuals with CUD diagnoses with individuals who had CU otherwise documented. Associations of documented CU and CUD with general medical conditions and health conditions associated with cannabis use (both medical and behavioral) were analyzed using conditional logistic regression. Results Of 1,047,463 patients with ambulatory encounters from 2013–2017, 729 (0.06%) had CUD diagnoses and 3,731 (0.36%) had CU documented in their EHR. Patients with documented CUD and CU patients had significantly (p Conclusion The prevalence of CUD and CU notation in EHR data from an academic health system was low, highlighting the need for improved screening in primary care. CUD and CU documentation were associated with increased risk for many health conditions, with the most elevated risk for behavioral health disorders and HIV/AIDS (among CUD-documented, but not CU-documented patients). Given the strong associations of CUD and CU documentation with health problems, it is important for healthcare providers to be prepared to identify CU and CUD, discuss the pros and cons of cannabis use with patients thoughtfully and empathically, and address cannabis-related comorbidities among these patients.

Zinc-air fuel cells (ZAFCs) have great potential as next-generation green energy sources. However, a practical application remains a challenge, because to achieve continuity and automation the oper...

PURPOSE: To develop a coincident thinning (CTN) index to differentiate between keratoconic and healthy corneas using optical coherence tomography (OCT) measurements of pachymetry and epithelial thickness. METHODS: Pattern deviation maps of pachymetry and epithelial thickness were generated using Fourier-domain OCT images of the cornea. The co-localized thinning of the two maps was quantified using a novel CTN index, which was calculated from Gaussian fits of the regions of maximum relative thinning. The CTN index was validated using k-fold cross-validation, and its classification performance was compared to minimum pachymetry and maximum keratometry. RESULTS: A total of 82 normal eyes and 133 eyes within three groups of keratoconus severity were evaluated. The pattern deviation maps for the keratoconic eyes showed relative thinning that was larger in magnitude and more strongly correlated with the Gaussian function compared to normal eyes (all P < .01). The distance between the pachymetric and epithelial maximum relative thinning locations was significantly smaller for the keratoconic eyes than for the normal eyes (all P < .02). The CTN index was significantly larger for all three keratoconus groups compared to normal eyes (all P < .0001). The CTN index demonstrated a sensitivity of 100% in detecting manifest keratoconus, 100% for subclinical keratoconus, and 56% for forme fruste keratoconus. The overall classification accuracy was better for the CTN index (93%) than for minimum pachymetry (86%) and maximum keratometry (86%). CONCLUSIONS: The CTN index is a highly sensitive measure of coincident pachymetric and epithelial thinning. It provides valuable information for detecting and monitoring early to moderate keratoconus. [ J Refract Surg . 2020;36(11):757–765.]