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Ultra-high-resolution (UHR) optical coherence tomography (OCT) imaging technique is using adaptive optics, to perform better better treatment and monitoring of retinal diseases. Researchers have developed a new generation of adaptive optics (AO) UHR OCT (AO-UHR-OCT) instrument that combines an ultrabroadband spectral light source and an achromatizing element, to increase measured axial resolution to around 3.5 μm. The measured axial resolution is increased without reducing lateral resolution and image quality. The new instrument uses an AO system in the spectral/Fourier domain OCT sample arm, to facilitate correction of a patient's ocular aberrations. The detection channel of the OCT spectrometer acquires spectral fringes of light, back-scattered from the retina, along with light from the reference arm.

Ultra-high isotropic resolution imaging of retinal structures was made possible with an adaptive optics system using dual deformable mirrors and a Fourier-domain optical coherence tomography (Fd-OCT) system with correction for longitudinal chromatic aberration. This system was used to image microscopic retinal structures of healthy as well as diseased retinas in vivo. The improved resolution and contrast enhanced visualization of morphological structures in the retina can be clearly seen. The benefits of this instrument are apparent from comparison of new images with those acquired using a previous generation AO-OCT instrument. Big change in the appearance of speckle field (reduction in speckle size) can be observed as well. Additionally, further improvements in volumetric data acquisition and image representation will be discussed. This includes creation of large Field of View (FOV) AO-OCT volume from multiple sub-volumes and its visualization. Also techniques and results of reducing speckle contrast by averaging multiple B-scans will be presented.

We report first observations of the three-dimensional morphology of cone photoreceptors in the living human retina. Images were acquired with a high-speed adaptive optics (AO) spectral domain optical coherence tomography (SD-OCT) camera. The AO system consists of a Shack-Hartmann wavefront sensor and bimorph deformable mirror (AOptix) that measure and correct the ocular and system aberrations at a closed-loop rate of 12 Hz. Unlike previous AO-OCT and AO-SLO instruments, the bimorph mirror was strategically positioned between the XY mechanical scanners and the subject's eye so as to avoid beam distortion at the pupil plane, which is created when the mirror compensates for the refractive error of the eye. This new configuration is evaluated empirically and with commercial ray tracing software. The SD-OCT system consists of a superluminescent diode and a 512 pixel line scan charge-coupled device (CCD) that acquires 75,000 A-scans/sec. This rate is more than two times faster than that previously reported. Retina motion artifiacts were minimized by quickly acquiring small volume images of the retina with and without AO compensation. Camera sensitivity was sufficient to detect reflections from all major retinal layers. The distribution of bright spots observed within C-scans at the inner segment / outer segment (IS/OS) junction and at the posterior tips of the OS were found to be highly correlated with one another and with the expected cone spacing. No correlation was found between the IS/OS junction and either the plexiform layers or the layers immediately behind the OS posterior tips.

Purpose: The purpose of this study was to investigate the large somas presumed to be displaced retinal ganglion cells (dRGCs) located in the inner nuclear layer (INL) of the living human retina. Whereas dRGCs have previously been studied in mammals and human donor tissue, they have never been investigated in the living human retina., Methods: Five young, healthy subjects and three subjects with varying types of glaucoma were imaged at multiple locations in the macula using adaptive optics optical coherence tomography. In the acquired volumes, bright large somas at the INL border with the inner plexiform layer were identified, and the morphometric biomarkers of soma density, en face diameter, and spatial distribution were measured at up to 13 degrees retinal eccentricity. Susceptibility to glaucoma was assessed., Results: In the young, healthy individuals, mean density of the bright, large somas was greatest foveally (550 and 543 cells/mm2 at 2 degrees temporal and nasal, respectively) and decreased with increasing retinal eccentricity (38 cells/mm2 at 13 degrees temporal, the farthest we measured). Soma size distribution showed the opposite trend with diameters and size variation increasing with retinal eccentricity, from 12.7 ± 1.8 µm at 2 degrees to 15.7 ± 3.5 µm at 13 degrees temporal, and showed evidence of a bimodal distribution in more peripheral locations. Within and adjacent to the arcuate defects of the subjects with glaucoma, density of the bright large somas was significantly lower than found in the young, healthy individuals., Conclusions: Our results suggest that the bright, large somas at the INL border are likely comprised of dRGCs but amacrine cells may contribute too. These somas appear highly susceptible to glaucomatous damage.

Introduction and Objectives: Radical cystectomy readmission rates remain high, with around 25% of patients readmitted to index and nonindex hospitals in 30 days. Nonindex readmissions have been associated with poorer outcomes, including longer lengths of stay and higher mortality rates. This study aimed to examine the associations of social factors (e.g., sex, race, socioeconomic status, insurance type, and resident location) on readmission to index versus nonindex hospitals and discharge disposition., Methods: We conducted a population-based retrospective study using the Pennsylvania Cancer Registry (PCR) to identify patients diagnosed with nonmetastatic muscle-invasive bladder cancer who underwent radical cystectomy in Pennsylvania between 2010 and 2018. Readmitted patients were identified using the Pennsylvania Health Care Cost Containment Council data (PHC4). The primary outcome was readmission location (i.e., index or nonindex hospital) following radical cystectomy. We used chi-square tests for categorical variables, Wilcoxon rank sum test for continuous variables, multivariable logistic regression model to assess predictors of being readmitted to an index hospital and calculating the predicted probability of being admitted to an index hospital depending on discharge disposition., Results: A total of 517 patients were readmitted within 30-days after radical cystectomy. The majority of readmissions were index readmissions (83%). Median readmission hospital stay was 4 days (interquartile range [IQR] 4) for index and 5 days (IQR 7) for nonindex hospitals, P = 0.01. Patients readmitted to index hospitals had fewer comorbidities (median weighted Elixhauser Comorbidity Index 2 (IQR 2)) and lived in urban areas (89%). Discharge with home care was associated with a higher odds of index readmission (odds ratio, [OR] 2.40; 95% confidence interval, [CI] 1.25-4.52)., Conclusions: Patients residing in urban areas and with fewer comorbidities were more likely to be readmitted to index hospitals than nonindex hospitals. Socioeconomic status and insurance type did not correlate with the type of readmission. Finally, being discharged with home health care was found to be a predictor of readmission to an index hospital., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of Interest Funding and support listed here did not support development of this document unless included in the acknowledgments section. Noura S. Abul-Husn is an equity holder of 23andMe; serves as a scientific advisory board member for Allelica; received personal fees from Genentech, Allelica, and 23andMe; received research funding from Akcea; and was previously employed by Regeneron Pharmaceuticals. Laura M. Amendola is a shareholder of Illumina, Inc. Wendy K. Chung is a member of the scientific advisory board of Regeneron Genetics Center and on the Board of Directors of Prime Medicine and Rallybio. Douglas R. Stewart is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, Rockville, MD and also performs contract clinical telehealth services for Genome Medical, Inc in accordance with relevant NCI ethics policies. All other authors have no conflicts to disclose.

Purpose: Assessment in medical education has changed over time to measure the evolving skills required of current medical practice. Physical and biophysical markers of assessment attempt to use technology to gain insight into medical trainees' knowledge, skills, and attitudes. The authors conducted a scoping review to map the literature on the use of physical and biophysical markers of assessment in medical training., Materials and Methods: The authors searched seven databases on 1 August 2022, for publications that utilized physical or biophysical markers in the assessment of medical trainees (medical students, residents, fellows, and synonymous terms used in other countries). Physical or biophysical markers included: heart rate and heart rate variability, visual tracking and attention, pupillometry, hand motion analysis, skin conductivity, salivary cortisol, functional magnetic resonance imaging (fMRI), and functional near-infrared spectroscopy (fNIRS). The authors mapped the relevant literature using Bloom's taxonomy of knowledge, skills, and attitudes and extracted additional data including study design, study environment, and novice vs. expert differentiation from February to June 2023., Results: Of 6,069 unique articles, 443 met inclusion criteria. The majority of studies assessed trainees using heart rate variability ( n  = 160, 36%) followed by visual attention ( n  = 143, 32%), hand motion analysis ( n  = 67, 15%), salivary cortisol ( n  = 67, 15%), fMRI ( n  = 29, 7%), skin conductivity ( n  = 26, 6%), fNIRs ( n  = 19, 4%), and pupillometry ( n  = 16, 4%). The majority of studies ( n  = 167, 38%) analyzed non-technical skills, followed by studies that analyzed technical skills ( n  = 155, 35%), knowledge ( n  = 114, 26%), and attitudinal skills ( n  = 61, 14%). 169 studies (38%) attempted to use physical or biophysical markers to differentiate between novice and expert., Conclusion: This review provides a comprehensive description of the current use of physical and biophysical markers in medical education training, including the current technology and skills assessed. Additionally, while physical and biophysical markers have the potential to augment current assessment in medical education, there remains significant gaps in research surrounding reliability, validity, cost, practicality, and educational impact of implementing these markers of assessment.

Background: Physician clinical educators play important roles in teaching, providing feedback, and evaluating trainees, but they often have variable preparation and competing demands on their time that make universal participation in workshops, seminars, or short courses designed to foster these skillsets inefficient or impossible., Methods: We designed and implemented a 52-week synchronous curriculum designed to address faculty opportunities to improve teaching skills, feedback for residents and medical students, and evaluation skills, which were delivered using marketing automation tools, including text messaging and email. We evaluated the programmatic impact and feasibility of using the implementation science framework., Results: Over a 104-week evaluation period, there were at least 10,499 total content impressions and 4558 unique recipients, indicating the significant reach of this program to approximately 120 faculty members. Faculty engagement with continuing education materials remained stable or increased over the 2-year evaluation period, indicating that programs like ours can have sustainable impacts. Resident evaluations of faculty across the six key domains also improved after the implementation of the program., Conclusions: Our experience with digital marketing tools reflects that they can be used to deliver impactful curricular content to faculty for continuing educational purposes and that faculty can use these resources in a sustainable way. However, because of the incomplete reach with any single communication, this type of content delivery is not appropriate for isolation as a material of critical importance. More research is needed to identify the best practices and additional education-related uses of this technology., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Michael SH et al.)

Objective: To develop a multipronged, evidence-based protocol to reduce readmission risk and readmission intensity, as represented by the duration of the index readmission, after radical cystectomy., Materials and Methods: A per-protocol study was performed. The protocol included preoperative nutritional supplementation, early stent removal, and a follow-up phone call within 4-5days of discharge. The preprotocol period was from February 1, 2020 to July 31, 2021 and the postprotocol period was from December 1, 2020 to November 31, 2021. Using multivariate regression models, we compared outcomes among patients treated with radical cystectomy before and after protocol initiation., Results: We identified 70 preprotocol patients and 126 postprotocol patients. After adjusting for age, sex, BMI, and frailty score, there was a significant reduction in 90-day readmission intensity (7 vs 5days; P = .048) among postprotocol patients., Conclusion: After implementation of an evidence-based protocol for patients undergoing radical 90-day readmission intensity decreased significantly. This protocol may move the needle forward on reducing readmissions, but a larger randomized trial is needed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Competing Interests: Conflict of Interest Funding and support listed here did not support development of this document unless included in the Acknowledgments section. N.S.A.-H. is an equity holder of 23andMe; serves as a scientific advisory board member for Allelica; received personal fees from Genentech, Allelica, and 23andMe; received research funding from Akcea; and was previously employed by Regeneron Pharmaceuticals. W.K.C. is a member of the scientific advisory board of Regeneron Genetics Center. D.T.M. has received an honorarium from Ambry Genetics. D.R.S. is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics of the National Cancer Institute, Rockville, MD, and also performs contract clinical telehealth services for Genome Medical, Inc., in accordance with relevant National Cancer Institute ethics policies. All other authors declare no conflicts of interest.

Objective: To examine the association of area-level socioeconomic status, rural-urban residence, and type of insurance with overall and cancer-specific mortality among patients with muscle-invasive bladder cancer., Methods: Using the Pennsylvania Cancer Registry, which collects demographic, insurance, and clinical information on every patient with cancer within the state, we identified all patients diagnosed with non-metastatic muscle-invasive bladder cancer between 2010 and 2016 based on clinical and pathologic staging. We used the Area Deprivation Index (ADI) as a surrogate for socioeconomic status and Rural-Urban Commuting Area codes to classify urban, large town, and rural communities. ADI was reported in quartiles, with 4 representing the lowest socioeconomic status. We fit multivariable logistic regression and Cox models to assess the relationship of these social determinants with overall and cancer-specific survival adjusting for age, sex, race, stage, treatment, rural-urban classification, insurance and ADI., Results: We identified 2597 patients with non-metastatic muscle-invasive bladder cancer. On multivariable analysis, Medicare (hazards ratio [HR] 1.15), Medicaid (HR 1.38), ADI 3 (HR 1.16) and ADI 4 (HR 1.21) were independent predictors of greater overall mortality (all P < 0.05). Female sex and receipt of non-standard treatment were associated with increased overall mortality and bladder cancer-specific mortality. There was no significant difference in both overall and cancer-specific survival between patients who were non-Hispanic White compared to non-White or between those from urban areas, large towns, or rural locations., Conclusion: Lower socioeconomic status and Medicare and Medicaid insurance were associated with a greater risk of overall mortality while rural residence was not a significant factor. Implementation of public health programs may help reduce the gap in mortality for low SES at-risk populations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction The use of androgenic anabolic steroids (AAS) negatively affects male fertility by disrupting hormone release and reducing testosterone levels. Despite this, many men using steroids are unaware of fertility-related consequences. We aimed to determine the factors associated with AAS resumption during fertility treatment, specifically focusing on the duration, age, and dosage of AAS use prior to treatment. Our study, the first of its kind, investigated risk factors for resuming AAS following fertility assessment. Methods We conducted a retrospective review of adult men diagnosed with infertility due to chronic AAS use between 2012 and 2022 at the University of Miami. The study included men with azoospermia or severe oligospermia who were instructed to stop using AAS. Excluded were those who underwent orchiectomy for benign or malignant conditions. We collected data on demographic characteristics, AAS route details, fertility treatments, and AAS resumption. We hypothesized that risk factors for restarting AAS would include duration of AAS use, type of AAS, pre-treatment testosterone levels, and increased age. Results We identified 94 men with infertility caused by AAS use. Among them, 31 (33.0%) resumed AAS therapy within eight months after cessation. The median age of men who restarted AAS was 40 years. Those who resumed AAS had used it for a longer duration prior to fertility assessment compared to those who did not (60 months vs. 17 months, respectively). However, we found no statistically significant differences in age, duration of AAS use, AAS administration details, or serum testosterone levels at the time of initial assessment. Conclusion In conclusion, most men seeking fertility assessment due to AAS abuse did not resume testosterone therapy. However, those who did restart AAS had a longer history of AAS use. Future high-quality prospective studies are needed to better understand the risk factors associated with resuming AAS in male infertility caused by anabolic steroids., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, White et al.)

Introduction To confirm the safety and examine outcomes of a day of surgery discharge following artificial urinary sphincter implantation in a population discharged without a catheter. Methods We retrospectively identified 110 patients, 31 of whom were discharged on the day of surgery, from a single surgeon following artificial urinary sphincter implantation. After institutional board review approval, patient charts were reviewed capturing demographics as well as three, thirty, and ninety-day outcomes. Further outcomes specific to urinary retention were obtained. Results Patients who were discharged the same day were older (71 vs. 68), had shorter operative times (92 minutes vs 109 minutes), and were less likely to have been smokers (6% vs 31%). There were no differences in the proportion of patients who underwent prior radiation or prior implant surgery. There was no significant difference in the number of patients who had emergency department visits, urinary retention, office calls, office visits, or unplanned office visits at all time points following surgery. There was no significant difference in overall urinary retention (15% vs 5%), retention presenting after the initial surgical event (6% vs 5%), or need for a suprapubic tube (0% vs 5%). Conclusions Day of surgery discharge is a safe discharge strategy for patients who have undergone artificial urinary sphincter placement. Furthermore, catheter-free days of discharge surgery did not have a significantly greater risk of urinary retention, office calls, emergency department (ED) visits, or office visits compared to our overnight observation population. This approach should be considered for all patients undergoing artificial urinary sphincter (AUS) implantation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Myrga et al.)

Malignant peripheral nerve sheath tumor (MPNST), an aggressive soft-tissue sarcoma, occurs in people with neurofibromatosis type 1 (NF1) and sporadically. Whole-genome and multiregional exome sequencing, transcriptomic, and methylation profiling of 95 tumor samples revealed the order of genomic events in tumor evolution. Following biallelic inactivation of NF1, loss of CDKN2A or TP53 with or without inactivation of polycomb repressive complex 2 (PRC2) leads to extensive somatic copy-number aberrations (SCNA). Distinct pathways of tumor evolution are associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumors with H3K27me3 loss evolve through extensive chromosomal losses followed by whole-genome doubling and chromosome 8 amplification, and show lower levels of immune cell infiltration. Retention of H3K27me3 leads to extensive genomic instability, but an immune cell-rich phenotype. Specific SCNAs detected in both tumor samples and cell-free DNA (cfDNA) act as a surrogate for H3K27me3 loss and immune infiltration, and predict prognosis., Significance: MPNST is the most common cause of death and morbidity for individuals with NF1, a relatively common tumor predisposition syndrome. Our results suggest that somatic copy-number and methylation profiling of tumor or cfDNA could serve as a biomarker for early diagnosis and to stratify patients into prognostic and treatment-related subgroups. This article is highlighted in the In This Issue feature, p. 517., (©2023 The Authors; Published by the American Association for Cancer Research.)

This review describes the progress that has been achieved since adaptive optics (AO) was incorporated into the ophthalmoscope a quarter of a century ago, transforming our ability to image the retina at a cellular spatial scale inside the living eye. The review starts with a comprehensive tabulation of AO papers in the field and then describes the technological advances that have occurred, notably through combining AO with other imaging modalities including confocal, fluorescence, phase contrast, and optical coherence tomography. These advances have made possible many scientific discoveries from the first maps of the topography of the trichromatic cone mosaic to exquisitely sensitive measures of optical and structural changes in photoreceptors in response to light. The future evolution of this technology is poised to offer an increasing array of tools to measure and monitor in vivo retinal structure and function with improved resolution and control., Competing Interests: DRW: USPTO 6,199,986, 6,264,328, 6,338,559 (P), R: Canon, Inc., Bausch and Lomb, Inc., Boston Micromachines Corporation. (R); SAB: No conflicts of interest; DTM: USPTO 11,324,398 (P); AR: USPTO 7,118,216, 6,890,076, 10,130,253 (P), Boston Micromachines Corporation, Canon, Inc., C.Light Technologies (R), C. Light Technologies (I), (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Objective quantification of photoreceptor cell morphology, such as cell diameter and outer segment length, is crucial for early, accurate, and sensitive diagnosis and prognosis of retinal neurodegenerative diseases. Adaptive optics optical coherence tomography (AO-OCT) provides three-dimensional (3-D) visualization of photoreceptor cells in the living human eye. The current gold standard for extracting cell morphology from AO-OCT images involves the tedious process of 2-D manual marking. To automate this process and extend to 3-D analysis of the volumetric data, we propose a comprehensive deep learning framework to segment individual cone cells in AO-OCT scans. Our automated method achieved human-level performance in assessing cone photoreceptors of healthy and diseased participants captured with three different AO-OCT systems representing two different types of point scanning OCT: spectral domain and swept source., Competing Interests: The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the US Department of Health and Human Services., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Over five million cases of skin cancer are diagnosed each year in the United States with melanoma the third most common cancer in young adults. While publications have shown that sunburns increase the risk of developing melanoma throughout the lifetime including in adolescence and adulthood showing the importance of altering sun exposing behaviors throughout the lifetime, use of sun protection in college students remails low. In Fall 2019, an online survey of undergraduate students living on campus at a large southwestern university was conducted to determine the frequency of recent sunburns as well as sun protective behaviors and perceived knowledge of and barriers to sun protection. Associations between knowledge, behaviors, and barriers with self-reported sunburn were evaluated using logistic regression. Over 46% of 458 students reported at least one sunburn in the past three months and 21% reported having multiple sunburns in that period. Furthermore, 53% reported that they intentionally tanned their skin outdoors occasionally or more frequently, while 6.4% reported using an indoor tanning bed occasionally or more. Adjusted for skin sensitivity, recent sunburn history was associated with higher tanning activity scores and with high agreement that tanning was attractive ( p < 0.01). This information can inform a more targeted series of intervention programming on the university campus.

Objective: To show that zero-opioid discharges after both open and robotic cystectomy are feasible and to examine the impact of zero-opioid discharges on patient interaction with the physician's office., Materials and Methods: One hundred seven patients who underwent either open or robotic radical cystectomy from March 1, 2020 to December 30, 2020 were identified. Patient demographics, perioperative data, and 30 day pain related outcomes including phone calls, office visits, requests for pain medication, emergency department visits, and readmissions were abstracted from the chart. We then examined variables associated with a zero-opioid discharge., Results: Thirty-two patients were discharged with an opioid prescription (Median Oral Morphine Equivalents Prescribed = 90) and 75 were discharged without an opioid prescription. On regression analysis, age (OR 1.07, 95% CI [1.02-1.12]) and pathology (OR 0.36, 95% CI[0.14-0.9]) remained significantly associated with post-operative opioid prescriptions. There were no differences in the percent of patients presenting to the emergency department, being readmitted, calling the office, calling the office regarding pain, or requesting opioid prescriptions within 30 days of discharge, or the number of post-operative office visits (P >.05 for all)., Conclusion: Patients can safely be discharged home without opioids following cystectomy, regardless of robotic or open approach. Age and pathology are predictors of the need for an opioid prescription on discharge. These patients did not have increased follow-up visits, phone calls, or requests for pain medication., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to develop and evaluate a novel curriculum and assessment tool for Core Entrustable Professional Activity (EPA) 10 competencies and entrustment scoring in a cohort of medical students in their emergency medicine (EM) clerkship using a framework of individualized, ad hoc, formative assessment. Core EPA 10 is an observable workplace-based activity for graduating medical students to recognize a patient requiring urgent or emergent care and initiate evaluation and management., Methods: This is a prospective, pretest-posttest study of medical students during their EM clerkship. Using the Thomas and Kern framework, we created a curriculum of simulation cases about chest pain/cardiac arrest and respiratory distress, which included novel assessment checklists, and instructional videos about recognizing and managing emergencies. Students were individually pretested on EPA 10 competencies using the simulation cases. Two raters scored students using standardized checklists. Students then watched instructional videos, underwent a posttest with the simulation cases, and were scored again by the two raters using the checklists. Differences between pretest and posttest scores were analyzed using paired t-tests and Wilcoxon signed-rank tests., Results: Seventy-three out of 85 (86%) students completed the curriculum. Mean scores from pretest to final posttest in the chest pain/cardiac arrest and respiratory distress cases significantly improved from 14.8/19 (SD 1.91), to 17.1/19 (SD = 1.00), t(68) = 10.56, p  < 0.001, and 8.5/13 (SD 1.79), to 11.1/13(SD 0.89), t(67) = 11.15, p  < 0.001, respectively. The kappa coefficients were 0.909 ( n  = 2698, p  < 0.001) and 0.931 ( n  = 1872, p  < 0.001). Median modified Chen entrustment scores improved from 1b (i.e., "Watch me do this") to 2b (i.e., "I'll watch you") for the chest pain/cardiac arrest case ( p  < 0.001) and 1b/2a (i.e., "Watch me do this"/ "Let's do this together") to 3a (i.e. "You go ahead, and I'll double-check all of your findings") for the respiratory distress case ( p  < 0.001)., Conclusion: A new directed curriculum of standardized simulation cases and asynchronous instructional videos improved medical student performance in EPA 10 competencies and entrustment scores. This study provides a curricular framework to support formative individualized assessments for EPA 10., Competing Interests: DTM reports grant money to the University of Colorado to conduct research conceived and written by DTM from the Society of Academic Emergency Medicine, Emergency Medicine Foundation. WG, HCW, KN, SSS, and MAG report no conflicts of interest., (© 2022 Society for Academic Emergency Medicine.)

Purpose: Postzygotic (somatic) variants in the mTOR pathway genes cause a spectrum of distinct developmental abnormalities. Accurate classification of somatic variants in this group of disorders is crucial for affected individuals and their families., Methods: The ClinGen Brain Malformation Variant Curation Expert Panel was formed to curate somatic variants associated with developmental brain malformations. We selected the genes AKT3, MTOR, PIK3CA, and PIK3R2 as the first set of genes to provide additional specifications to the 2015 American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) sequence variant interpretation guidelines, which currently focus solely on germline variants., Results: A total of 24 of the original 28 ACMG/AMP criteria required modification. Several modifications used could be applied to other genes and disorders in which somatic variants play a role: 1) using variant allele fraction differences as evidence that somatic mutagenesis occurred as a proxy for de novo variation, 2) incorporating both somatic and germline evidence, and 3) delineating phenotype on the basis of variable tissue expression., Conclusion: We have established a framework for rigorous interpretation of somatic mosaic variants, addressing issues unique to somatic variants that will be applicable to many genes and conditions., Competing Interests: Conflict of Interest D.T.M. has received honoraria from Ambry Genetics and PreventionGenetics. All other authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

Background: The Standardized Letter of Evaluation (SLOE) stratifies the assessment of emergency medicine (EM) bound medical applicants. However, bias in SLOE, particularly regarding race and ethnicity, is an underexplored area., Objective: This study aims to assess whether underrepresented in medicine (UIM) and non-UIM applicants are rated differently in SLOE components., Methods: This was a cross-section study of EM-bound applicants across 3 geographically distinct US training programs during the 2019-2020 application cycle. Using descriptive and regression analyses, we examine the differences between UIM applicants and non-UIM applicants for each of the SLOE components: 7 qualifications of an EM physician (7QEM), global assessment (GA) rating, and projected rank list (RL) position., Results: Out of a combined total of 3759, 2002 (53.3%) unique EM-bound applicants were included. UIM applicants had lower ratings for each of the 7QEM questions, GA, and RL positions. Compared to non-UIM applicants, only some of the 7QEM components: "Work ethic and ability to assume responsibility," "Ability to work in a team, and "Ability to communicate a caring nature," were associated with their SLOE. "Commitment to EM" correlated more with GA for UIM than for non-UIM applicants., Conclusions: This study shows a difference in SLOE rating, with UIM applicants receiving lower ratings than non-UIM applicants., Competing Interests: Conflict of interest: The authors declare they have no competing interests.

Purpose: Neurodevelopmental disorders (NDDs), such as intellectual disability (ID) and autism spectrum disorder (ASD), exhibit genetic and phenotypic heterogeneity, making them difficult to differentiate without a molecular diagnosis. The Clinical Genome Resource Intellectual Disability/Autism Gene Curation Expert Panel (GCEP) uses systematic curation to distinguish ID/ASD genes that are appropriate for clinical testing (ie, with substantial evidence supporting their relationship to disease) from those that are not., Methods: Using the Clinical Genome Resource gene-disease validity curation framework, the ID/Autism GCEP classified genes frequently included on clinical ID/ASD testing panels as Definitive, Strong, Moderate, Limited, Disputed, Refuted, or No Known Disease Relationship., Results: As of September 2021, 156 gene-disease pairs have been evaluated. Although most (75%) were determined to have definitive roles in NDDs, 22 (14%) genes evaluated had either Limited or Disputed evidence. Such genes are currently not recommended for use in clinical testing owing to the limited ability to assess the effect of identified variants., Conclusion: Our understanding of gene-disease relationships evolves over time; new relationships are discovered and previously-held conclusions may be questioned. Without periodic re-examination, inaccurate gene-disease claims may be perpetuated. The ID/Autism GCEP will continue to evaluate these claims to improve diagnosis and clinical care for NDDs., Competing Interests: Conflict of Interest A.Br. is a shareholder of and employed by Natera. A.Br. has also been an employee of Invitae and Quest Diagnostics commercial laboratories. A.R.C. and K.B. are shareholders of and employed by Illumina, Inc. A.Be. is a shareholder of and is employed by Invitae. B.B. has received research support from Biomarin Pharmaceuticals Inc. He is currently employed by and is a shareholder of Alnylam Pharmaceuticals, Inc. All other authors declare no conflicts of interest., (Copyright © 2022 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.)

A mosaic state arises when pathogenic variants are acquired in certain cell lineages during postzygotic development, and mosaic individuals may present with a generalized or localized phenotype. Here, we review the current state of knowledge regarding mosaicism for eight common tumor suppressor genes- NF1 , NF2 , TSC1 , TSC2 , PTEN , VHL , RB1 , and TP53 -and their related genetic syndromes/entities. We compare and discuss approaches for comprehensive diagnostic genetic testing, the spectrum of variant allele frequency, and disease severity. We also review affected individuals who have no mutation identified after conventional genetic analysis, as well as genotype-phenotype correlations and transmission risk for each tumor suppressor gene in full heterozygous and mosaic patients. This review provides new insight into similarities as well as marked differences regarding the appreciation of mosaicism in these tumor suppressor syndromes.

Introduction: Medical students lack adequate training on how to correctly don and doff personal protective equipment (PPE). Simulation-based mastery learning (SBML) is an effective technique for procedural education. The aim of this study was to determine whether SBML improves proper PPE donning and doffing by medical students., Methods: This was a prospective, pre-test/post-test study of 155 medical students on demonstration of correct PPE use before and after a SBML intervention. Subjects completed standard hospital training by viewing a US Centers for Disease Control and Prevention training video on proper PPE use prior to the intervention. They then participated in a SBML training session that included baseline testing, deliberate practice with expert feedback, and post-testing until mastery was achieved. Students were assessed using a previously developed 21-item checklist on donning and doffing PPE with a minimum passing standard (MPS) of 21/21 items. We analyzed differences between pre-test and post-test scores using paired t-tests. Students at preclinical and clinical levels of training were compared with an independent t-test., Results: Two participants (1.3%) met the MPS on pre-test. Of the remaining 153 subjects who participated in the intervention, 151 (98.7%) reached mastery. Comparison of mean scores from pre-test to final post-test significantly improved from an average raw score of 12.55/21 (standard deviation [SD] = 2.86), to 21/21(SD = 0), t(150) = 36.3, P <0.001. There was no difference between pre-test scores of pre-clinical and clinical students., Conclusion: Simulation-based mastery learning improves medical student performance in PPE donning and doffing in a simulated environment. This approach standardizes PPE training for students in advance of clinical experiences.

Introduction: Resident achievement data is a powerful but underutilized means of program evaluation, allowing programs to empirically measure whether they are meeting their program aims, facilitate refinement of curricula and improve resident recruitment efforts. The goal was to provide an overview of available metrics of resident achievement and how these metrics can be used to inform program aims., Methods: A literature search was performed using PubMed and Google Scholar between May and November of 2020. Publications were eligible for inclusion if they discussed or assessed "excellence" or "success" during residency training. A narrative review structure was chosen due to the intention to provide an examination of the literature on available resident achievement metrics., Results: 57 publications met inclusion criteria and were included in the review. Metrics of excellence were grouped into larger categories, including success defined by program factors, academics, national competencies, employer factors, and possible new metrics., Conclusions: Programs can best evaluate whether they are meeting their program aims by creating a list of important resident-level metrics based on their stated goals and values using one or more of the published definitions as a foundation. Each program must define which metrics align best with their individual program aims and mission.

Retinitis pigmentosa (RP) is the most common group of inherited retinal degenerative diseases, whose most debilitating phase is cone photoreceptor death. Perimetric and electroretinographic methods are the gold standards for diagnosing and monitoring RP and assessing cone function. However, these methods lack the spatial resolution and sensitivity to assess disease progression at the level of individual photoreceptor cells, where the disease originates and whose degradation causes vision loss. High-resolution retinal imaging methods permit visualization of human cone cells in vivo but have only recently achieved sufficient sensitivity to observe their function as manifested in the cone optoretinogram. By imaging with phase-sensitive adaptive optics optical coherence tomography, we identify a biomarker in the cone optoretinogram that characterizes individual cone dysfunction by stimulating cone cells with flashes of light and measuring nanometer-scale changes in their outer segments. We find that cone optoretinographic responses decrease with increasing RP severity and that even in areas where cone density appears normal, cones can respond differently than those in controls. Unexpectedly, in the most severely diseased patches examined, we find isolated cones that respond normally. Short-wavelength-sensitive cones are found to be more vulnerable to RP than medium- and long-wavelength-sensitive cones. We find that decreases in cone response and cone outer-segment length arise earlier in RP than changes in cone density but that decreases in response and length are not necessarily correlated within single cones., Competing Interests: Competing interest statement: D.T.M., K.K., and F.Z. have a patent on adaptive optics optical coherence tomography technology and stand to benefit financially from any commercialization of the technology., (Copyright © 2021 the Author(s). Published by PNAS.)

It is known that urologic surgeons are at risk of work-place injury due to the physical requirements of operating and exposure to hazards. These hazards include radiation, exposure to body fluids, use of laser energy, and orthopedic injury due to the physical nature of operating. The risks that these hazards present can be mitigated by implementing several evidence-based safety measures. The methods to protect against radiation exposure include keeping radiation usage in the operating room as low as reasonably achievable, donning lead aprons, and wearing protective glasses. Additionally, protective glasses decrease the risk of eye injury from laser injury and exposure to body fluids. Finally, practicing sound surgical ergonomics is essential to minimize the risk of orthopedic injury and promote career longevity. The interventions discussed herein are simple and easy to implement in one's daily practice of urology., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Miller and Semins.)

Chromosomal microarray technologies, including array comparative genomic hybridization and single-nucleotide polymorphism array, are widely applied in the diagnostic evaluation for both constitutional and neoplastic disorders. In a constitutional setting, this technology is accepted as the first-tier test for the evaluation of chromosomal imbalances associated with intellectual disability, autism, and/or multiple congenital anomalies. Furthermore, chromosomal microarray analysis is recommended for patients undergoing invasive prenatal diagnosis with one or more major fetal structural abnormalities identified by ultrasonographic examination, and in the evaluation of intrauterine fetal demise or stillbirth when further cytogenetic analysis is desired. This technology also provides important genomic data in the diagnosis, prognosis, and therapy of neoplastic disorders, including both hematologic malignancies and solid tumors. To assist clinical laboratories in the validation of chromosomal microarray methodologies for constitutional and neoplastic applications, the American College of Medical Genetics and Genomics (ACMG) Laboratory Quality Assurance Committee has developed these updated technical laboratory standards, which replace the ACMG technical standards and guidelines for microarray analysis in constitutional and neoplastic disorders previously published in 2013., (© 2021. The Author(s), under exclusive licence to the American College of Medical Genetics and Genomics.)

Microaggressions are frequently experienced by learners in the workplace and can create a hostile learning environment. Many faculty educators lack formal training in supporting their learners after incidents of microaggressions. Supervising faculty should be able to recognize and respond to microaggressions against trainees in the clinical environment. In this commentary, we will briefly review the definition of microaggressions, summarize the impact of microaggressions on trainees, provide a framework for managing microaggressions on an individual level when the patient offends the learner, and highlight strategies to mitigate microaggressions on a programmatic and institutional level., Competing Interests: The authors have no potential conflicts to disclose., (© 2021 by the Society for Academic Emergency Medicine.)

Objectives: The standardized letter of evaluation (SLOE) in emergency medicine (EM) is a widely used metric for determining interview invitations and ranking of candidates. Previous research has questioned the validity of certain sections of the SLOE. However, there remains a paucity of literature on the qualifications for EM section, which evaluates seven attributes of applicants. The aim of this study was to determine the correlation between the qualifications questions and grades, global assessment, and anticipated rank list position for EM applicants., Methods: A multi-institutional cross-sectional study was performed using SLOEs from applicants to three geographically distinct U.S. EM residency programs during the 2019-2020 application cycle. We abstracted EM rotation grade, qualifications scores, global assessment, and anticipated rank list position from the SLOEs. A Spearman correlation was calculated between each of the qualifications scores and the applicant's grades, global assessment, and anticipated rank list position in a pairwise fashion., Results: In total, 2,106 unique applicants (4,939 SLOEs) were included. Of the seven qualifications for EM questions, three were moderately to strongly correlated with global assessment and anticipated rank list position: "ability to develop and justify an appropriate differential and a cohesive treatment plan" (ρ = 0.65 and ρ = 0.63, respectively; p < 0.001), "how much guidance do you predict this applicant will need during residency?" (ρ = 0.68 and ρ = 0.68, respectively; p < 0.001), and "what is your prediction of success for the applicant?" (ρ = 0.69 and ρ = 0.69, respectively; p < 0.001). There was no strong correlation between the seven qualifications and grades., Conclusions: There was a moderate to strong correlation between three of seven qualifications for EM questions (ability to develop and justify a differential and develop a cohesive plan, anticipated need for the amount of guidance, and prediction of success) with both global assessment and anticipated rank list position, suggesting that these qualifications may provide the most useful data to residency selection while some of the other factors may not be needed., Competing Interests: The authors have no potential conflicts to disclose., (© 2021 by the Society for Academic Emergency Medicine.)

Background: We aimed to define the clinical and variant spectrum and to provide novel molecular insights into the DHX30-associated neurodevelopmental disorder., Methods: Clinical and genetic data from affected individuals were collected through Facebook-based family support group, GeneMatcher, and our network of collaborators. We investigated the impact of novel missense variants with respect to ATPase and helicase activity, stress granule (SG) formation, global translation, and their effect on embryonic development in zebrafish. SG formation was additionally analyzed in CRISPR/Cas9-mediated DHX30-deficient HEK293T and zebrafish models, along with in vivo behavioral assays., Results: We identified 25 previously unreported individuals, ten of whom carry novel variants, two of which are recurrent, and provide evidence of gonadal mosaicism in one family. All 19 individuals harboring heterozygous missense variants within helicase core motifs (HCMs) have global developmental delay, intellectual disability, severe speech impairment, and gait abnormalities. These variants impair the ATPase and helicase activity of DHX30, trigger SG formation, interfere with global translation, and cause developmental defects in a zebrafish model. Notably, 4 individuals harboring heterozygous variants resulting either in haploinsufficiency or truncated proteins presented with a milder clinical course, similar to an individual harboring a de novo mosaic HCM missense variant. Functionally, we established DHX30 as an ATP-dependent RNA helicase and as an evolutionary conserved factor in SG assembly. Based on the clinical course, the variant location, and type we establish two distinct clinical subtypes. DHX30 loss-of-function variants cause a milder phenotype whereas a severe phenotype is caused by HCM missense variants that, in addition to the loss of ATPase and helicase activity, lead to a detrimental gain-of-function with respect to SG formation. Behavioral characterization of dhx30-deficient zebrafish revealed altered sleep-wake activity and social interaction, partially resembling the human phenotype., Conclusions: Our study highlights the usefulness of social media to define novel Mendelian disorders and exemplifies how functional analyses accompanied by clinical and genetic findings can define clinically distinct subtypes for ultra-rare disorders. Such approaches require close interdisciplinary collaboration between families/legal representatives of the affected individuals, clinicians, molecular genetics diagnostic laboratories, and research laboratories.

Cell-level quantitative features of retinal ganglion cells (GCs) are potentially important biomarkers for improved diagnosis and treatment monitoring of neurodegenerative diseases such as glaucoma, Parkinson's disease, and Alzheimer's disease. Yet, due to limited resolution, individual GCs cannot be visualized by commonly used ophthalmic imaging systems, including optical coherence tomography (OCT), and assessment is limited to gross layer thickness analysis. Adaptive optics OCT (AO-OCT) enables in vivo imaging of individual retinal GCs. We present an automated segmentation of GC layer (GCL) somas from AO-OCT volumes based on weakly supervised deep learning (named WeakGCSeg), which effectively utilizes weak annotations in the training process. Experimental results show that WeakGCSeg is on par with or superior to human experts and is superior to other state-of-the-art networks. The automated quantitative features of individual GCLs show an increase in structure-function correlation in glaucoma subjects compared to using thickness measures from OCT images. Our results suggest that by automatic quantification of GC morphology, WeakGCSeg can potentially alleviate a major bottleneck in using AO-OCT for vision research.