Recurrent inversion polymorphisms in humans associate with genetic instability and genomic disorders.

Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7 × 10-4 per locus per generation. Recurrent inversions exhibit a sex-chromosomal bias and co-localize with genomic disorder critical regions. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes specific haplotypes to disease-causing CNVs.

The complete sequence and comparative analysis of ape sex chromosomes.

Apes possess two sex chromosomes-the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility1. The X chromosome is vital for reproduction and cognition2. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements-owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.

Assembly of 43 human Y chromosomes reveals extensive complexity and variation.

The prevalence of highly repetitive sequences within the human Y chromosome has prevented its complete assembly to date1 and led to its systematic omission from genomic analyses. Here we present de novo assemblies of 43 Y chromosomes spanning 182,900 years of human evolution and report considerable diversity in size and structure. Half of the male-specific euchromatic region is subject to large inversions with a greater than twofold higher recurrence rate compared with all other chromosomes2. Ampliconic sequences associated with these inversions show differing mutation rates that are sequence context dependent, and some ampliconic genes exhibit evidence for concerted evolution with the acquisition and purging of lineage-specific pseudogenes. The largest heterochromatic region in the human genome, Yq12, is composed of alternating repeat arrays that show extensive variation in the number, size and distribution, but retain a 1:1 copy-number ratio. Finally, our data suggest that the boundary between the recombining pseudoautosomal region 1 and the non-recombining portions of the X and Y chromosomes lies 500 kb away from the currently established1 boundary. The availability of fully sequence-resolved Y chromosomes from multiple individuals provides a unique opportunity for identifying new associations of traits with specific Y-chromosomal variants and garnering insights into the evolution and function of complex regions of the human genome.

Diverse mechanisms of somatic structural variations in human cancer genomes.

Identification of somatic rearrangements in cancer genomes has accelerated through analysis of high-throughput sequencing data. However, characterization of complex structural alterations and their underlying mechanisms remains inadequate. Here, applying an algorithm to predict structural variations from short reads, we report a comprehensive catalog of somatic structural variations and the mechanisms generating them, using high-coverage whole-genome sequencing data from 140 patients across ten tumor types. We characterize the relative contributions of different types of rearrangements and their mutational mechanisms, find that ~20% of the somatic deletions are complex deletions formed by replication errors, and describe the differences between the mutational mechanisms in somatic and germline alterations. Importantly, we provide detailed reconstructions of the events responsible for loss of CDKN2A/B and gain of EGFR in glioblastoma, revealing that these alterations can result from multiple mechanisms even in a single genome and that both DNA double-strand breaks and replication errors drive somatic rearrangements.

Inference of Admixture Origins in Indigenous African Cattle.

Present-day African cattle retain a unique genetic profile composed of a mixture of the Bos taurus and Bos indicus populations introduced into the continent at different time periods. However, details of the admixture history and the exact origins of the source populations remain obscure. Here, we infer the source of admixture in the earliest domestic cattle in Africa, African taurine. We detect a significant contribution (up to ∼20%) from a basal taurine lineage, which might represent the now-extinct African aurochs. In addition, we show that the indicine ancestry of African cattle, although most closely related to so-far sampled North Indian indicine breeds, has a small amount of additional genetic affinity to Southeast Asian indicine breeds. Our findings support the hypothesis of aurochs introgression into African taurine and generate a novel hypothesis that the origin of indicine ancestry in Africa might be different indicine populations than the ones found in North India today.

RNA expression of 6 genes from metastatic mucosal gastric cancer serves as the global prognostic marker for gastric cancer with functional validation.

BACKGROUND: Molecular analysis of advanced tumors can increase tumor heterogeneity and selection bias. We developed a robust prognostic signature for gastric cancer by comparing RNA expression between very rare early gastric cancers invading only mucosal layer (mEGCs) with lymph node metastasis (Npos) and those without metastasis (Nneg). METHODS: Out of 1003 mEGCs, all Npos were matched to Nneg using propensity scores. Machine learning approach comparing Npos and Nneg was used to develop prognostic signature. The function and robustness of prognostic signature was validated using cell lines and external datasets. RESULTS: Extensive machine learning with cross-validation identified the prognostic classifier consisting of four overexpressed genes (HDAC5, NPM1, DTX3, and PPP3R1) and two downregulated genes (MED12 and TP53), and enabled us to develop the risk score predicting poor prognosis. Cell lines engineered to high-risk score showed increased invasion, migration, and resistance to 5-FU and Oxaliplatin but maintained sensitivity to an HDAC inhibitor. Mouse models after tail vein injection of cell lines with high-risk score revealed increased metastasis. In three external cohorts, our risk score was identified as the independent prognostic factor for overall and recurrence-free survival. CONCLUSION: The risk score from the 6-gene classifier can successfully predict the prognosis of gastric cancer.

Expectations and blind spots for structural variation detection from long-read assemblies and short-read genome sequencing technologies.

Virtually all genome sequencing efforts in national biobanks, complex and Mendelian disease programs, and medical genetic initiatives are reliant upon short-read whole-genome sequencing (srWGS), which presents challenges for the detection of structural variants (SVs) relative to emerging long-read WGS (lrWGS) technologies. Given this ubiquity of srWGS in large-scale genomics initiatives, we sought to establish expectations for routine SV detection from this data type by comparison with lrWGS assembly, as well as to quantify the genomic properties and added value of SVs uniquely accessible to each technology. Analyses from the Human Genome Structural Variation Consortium (HGSVC) of three families captured ~11,000 SVs per genome from srWGS and ~25,000 SVs per genome from lrWGS assembly. Detection power and precision for SV discovery varied dramatically by genomic context and variant class: 9.7% of the current GRCh38 reference is defined by segmental duplication (SD) and simple repeat (SR), yet 91.4% of deletions that were specifically discovered by lrWGS localized to these regions. Across the remaining 90.3% of reference sequence, we observed extremely high (93.8%) concordance between technologies for deletions in these datasets. In contrast, lrWGS was superior for detection of insertions across all genomic contexts. Given that non-SD/SR sequences encompass 95.9% of currently annotated disease-associated exons, improved sensitivity from lrWGS to discover novel pathogenic deletions in these currently interpretable genomic regions is likely to be incremental. However, these analyses highlight the considerable added value of assembly-based lrWGS to create new catalogs of insertions and transposable elements, as well as disease-associated repeat expansions in genomic sequences that were previously recalcitrant to routine assessment.

Characterization of a thermostable protease from Bacillus subtilis BSP strain.

This study used conservative one variable-at-a-time study and statistical surface response methods to increase the yields of an extracellular thermostable protease secreted by a newly identified thermophilic Bacillus subtilis BSP strain. Using conventional optimization techniques, physical parameters in submerged fermentation were adjusted at the shake flask level to reach 184 U/mL. These physicochemical parameters were further optimized by statistical surface response methodology using Box Behnken design, and the protease yield increased to 295 U/mL. The protease was purified and characterized biochemically. Both Ca2+ and Fe2+ increased the activity of the 36 kDa protease enzyme. Based on its strong inhibition by ethylenediaminetetracetate (EDTA), the enzyme was confirmed to be a metalloprotease. The protease was also resistant to various organic solvents (benzene, ethanol, methanol), surfactants (Triton X-100), sodium dodecyl sulfate (SDS), Tween 20, Tween-80 and oxidants hydrogen per oxide (H2O2). Characteristics, such as tolerance to high SDS and H2O2 concentrations, indicate that this protease has potential applications in the pharmaceutical and detergent industries.

Health care utilization and behavior changes after workplace genetic testing at a large US health care system.

PURPOSE: This study explored employee health behavior changes and health care utilization after workplace genetic testing (wGT). Wellness-program-associated wGT seeks to improve employee health, but the related health implications are unknown. METHODS: Employees of a large US health care system offering wGT (cancer, heart disease, and pharmacogenomics [PGx]) were sent electronic surveys. Self-reported data from those who received test results were analyzed. Descriptive statistics characterized responses, whereas logistic regression analyses explored correlates of responses to wGT. RESULTS: 53.9% (n = 418/776) of respondents (88.3% female, mean age = 44 years) reported receiving wGT results. 12.0% (n = 48/399) received results indicating increased risk (IR) of cancer, 9.5% (n = 38/398) had IR of heart disease, and 31.4% (n = 125/398) received informative PGx results. IR results for cancer and/or heart disease (n = 67) were associated with health behavior changes (adjusted odds ratio: 3.23; 95% CI 1.75, 6.13; P < .001) and health care utilization (adjusted odds ratio: 8.60; 95% CI 4.43, 17.5; P < .001). Informative PGx results (n = 125) were associated with medication changes (PGx-informative: 15.2%; PGx-uninformative: 4.8%; P = .002). CONCLUSION: This study explored employee responses to wGT, contributing to the understanding of the ethical and social implications of wGT. Receiving IR results from wGT may promote health behavior changes and health care utilization in employees.

An integrative approach for exploring the nature of fibroepithelial neoplasms.

BACKGROUND: Malignant phyllodes tumour (MPT) is a rare breast malignancy with epithelial and mesenchymal features. Currently, there are no appropriate research models or effective targeted therapeutic approaches for MPT. METHODS: We collected fresh frozen tissues from nine patients with MPT and performed whole-exome and RNA sequencing. Additionally, we established patient-derived xenograft (PDX) models from patients with MPT and tested the efficacy of targeting dysregulated pathways in MPT using the PDX model from one MPT. RESULTS: MPT has unique molecular characteristics when compared to breast cancers of epithelial origin and can be classified into two groups. The PDX model derived from one patient with MPT showed that the mouse epithelial component increased during tumour growth. Moreover, targeted inhibition of platelet-derived growth factor receptor (PDGFR) and phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) by imatinib mesylate and PKI-587 showed in vivo tumour suppression effects. CONCLUSIONS: This study revealed the molecular profiles of MPT that can lead to molecular classification and potential targeted therapy, and suggested that the MPT PDX model can be a useful tool for studying the pathogenesis of fibroepithelial neoplasms and for preclinical drug screening to find new therapeutic strategies for MPT.

iCSDB: an integrated database of CRISPR screens.

High-throughput screening based on CRISPR-Cas9 libraries has become an attractive and powerful technique to identify target genes for functional studies. However, accessibility of public data is limited due to the lack of user-friendly utilities and up-to-date resources covering experiments from third parties. Here, we describe iCSDB, an integrated database of CRISPR screening experiments using human cell lines. We compiled two major sources of CRISPR-Cas9 screening: the DepMap portal and BioGRID ORCS. DepMap portal itself is an integrated database that includes three large-scale projects of CRISPR screening. We additionally aggregated CRISPR screens from BioGRID ORCS that is a collection of screening results from PubMed articles. Currently, iCSDB contains 1375 genome-wide screens across 976 human cell lines, covering 28 tissues and 70 cancer types. Importantly, the batch effects from different CRISPR libraries were removed and the screening scores were converted into a single metric to estimate the knockout efficiency. Clinical and molecular information were also integrated to help users to select cell lines of interest readily. Furthermore, we have implemented various interactive tools and viewers to facilitate users to choose, examine and compare the screen results both at the gene and guide RNA levels. iCSDB is available at https://www.kobic.re.kr/icsdb/.

Comparison of Tumescent Anesthesia Versus Pectoral Nerve Block in Bilateral Reduction Mammaplasty.

INTRODUCTION: With an increasing focus on multimodal pain control to reduce opioid requirements, regional and local anesthesia techniques have been investigated in bilateral reduction mammaplasty with variable results. The purpose of this study is to compare tumescent anesthesia with pectoral nerve block II (PECS II) in patients undergoing bilateral reduction mammaplasty with respect to postoperative pain and nausea, opioid consumption, length of stay, and cost. METHODS: A retrospective review of patients undergoing bilateral reduction mammaplasty for macromastia between November 2020 and December 2021 was performed. Demographic information, operative and anesthesia times, antiemetic and morphine equivalent requirements, postoperative numeric pain rating scales, and time until hospital discharge were compared between groups. χ2 and Fisher exact tests examined subgroup differences in categorical variables. Two-sample t test and Wilcoxon rank-sum test evaluated differences in continuous parametric and nonparametric variables, respectively. RESULTS: Fifty-three patients underwent bilateral reduction mammaplasty by 3 surgeons, 71.7% (n = 38) with tumescent anesthesia infiltrated by the operating surgeon before the start of the procedure and 28.3% (n = 15) with bilateral PECS II blocks performed by anesthesia before the start of the procedure. There was no difference in age, body mass index, weight resected, intraoperative medication, or immediate postoperative complications. Postoperative pain scores and opioid requirements were similar between the 2 groups. Twenty-one percent (n = 8) of tumescent patients compared with 66.7% (n = 10) of block patients required 1 or more doses of postoperative antiemetics ( P = 0.002). Patients who received blocks spent longer in the postoperative recovery area (5.3 vs 7.1 hours, P < 0.01). However, this did not translate to a significant increase in overnight stays. The block group had significantly higher hospitalization cost by an average of $4000, driven by pharmacy and procedural cost ( P < 0.01). CONCLUSION: In this cohort of multimodal perioperative pain-controlled reduction mammaplasty patients, tumescent anesthesia was associated with decreased antiemetic requirements, less time in recovery before discharge, and lower cost compared with PECS II blocks. Therefore, tumescent anesthesia may be favored over PECS II blocks when considering multimodal pain control strategies in reduction mammaplasty patients.

Comprehensive Molecular Characterization of Adenocarcinoma of the Gastroesophageal Junction Between Esophageal and Gastric Adenocarcinomas.

OBJECTIVE: To investigate the molecular characteristics of AGEJ compared with EAC and gastric adenocarcinoma. SUMMARY OF BACKGROUND DATA: Classification of AGEJ based on differential molecular characteristics between EAC and gastric adenocarcinoma has been long-standing controversy but rarely conducted due to anatomical ambiguity and epidemiologic difference. METHODS: The molecular classification model with Bayesian compound covariate predictor was developed based on differential mRNA expression of EAC (N = 78) and GCFB (N = 102) from the Cancer Genome Atlas (TCGA) cohort. AGEJ/cardia (N = 48) in TCGA cohort and AGEJ/upper third GC (N = 46 pairs) in Seoul National University cohort were classified into the EAC-like or GCFB-like groups whose genomic, transcriptomic, and proteomic characteristics were compared. RESULTS: AGEJ in both cohorts was similarly classified as EAC-like (31.2%) or GCFB-like (68.8%) based on the 400-gene classifier. The GCFB-like group showed significantly activated phosphoinositide 3-kinase-AKT signaling with decreased expression of ERBB2. The EAC-like group presented significantly different alternative splicing including the skipped exon of RPS24, a significantly higher copy number amplification including ERBB2 amplification, and increased protein expression of ERBB2 and EGFR compared with GCFB-like group. High-throughput 3D drug test using independent cell lines revealed that the EAC-like group showed a significantly better response to lapatinib than the GCFB-like group (P = 0.015). CONCLUSIONS: AGEJ was the combined entity of the EAC-like and GCFB-like groups with consistently different molecular characteristics in both Seoul National University and TCGA cohorts. The EAC-like group with a high Bayesian compound covariate predictor score could be effectively targeted by dual inhibition of ERBB2 and EGFR.

muCNV: Genotyping Structural Variants for Population-level Sequencing.

MOTIVATION: There are high demands for joint genotyping of structural variations with short-read sequencing, but efficient and accurate genotyping in population scale is a challenging task. RESULTS: We developed muCNV that aggregates per-sample summary pileups for joint genotyping of > 100,000 samples. Pilot results show very low Mendelian inconsistencies. Applications to large-scale projects in cloud show the computational efficiencies of muCNV genotyping pipeline. AVAILABILITY: muCNV is publicly available for download at: https://github.com/gjun/muCNV. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Adverse Events Reported by Patients With Cancer After Administration of a 2-Dose mRNA COVID-19 Vaccine.

BACKGROUND: Most safety and efficacy trials of the SARS-CoV-2 vaccines excluded patients with cancer, yet these patients are more likely than healthy individuals to contract SARS-CoV-2 and more likely to become seriously ill after infection. Our objective was to record short-term adverse reactions to the COVID-19 vaccine in patients with cancer, to compare the magnitude and duration of these reactions with those of patients without cancer, and to determine whether adverse reactions are related to active cancer therapy. PATIENTS AND METHODS: A prospective, single-institution observational study was performed at an NCI-designated Comprehensive Cancer Center. All study participants received 2 doses of the Pfizer BNT162b2 vaccine separated by approximately 3 weeks. A report of adverse reactions to dose 1 of the vaccine was completed upon return to the clinic for dose 2. Participants completed an identical survey either online or by telephone 2 weeks after the second vaccine dose. RESULTS: The cohort of 1,753 patients included 67.5% who had a history of cancer and 12.0% who were receiving active cancer treatment. Local pain at the injection site was the most frequently reported symptom for all respondents and did not distinguish patients with cancer from those without cancer after either dose 1 (39.3% vs 43.9%; P=.07) or dose 2 (42.5% vs 40.3%; P=.45). Among patients with cancer, those receiving active treatment were less likely to report pain at the injection site after dose 1 compared with those not receiving active treatment (30.0% vs 41.4%; P=.002). The onset and duration of adverse events was otherwise unrelated to active cancer treatment. CONCLUSIONS: When patients with cancer were compared with those without cancer, few differences in reported adverse events were noted. Active cancer treatment had little impact on adverse event profiles.

Glucose metabolic profiles evaluated by PET associated with molecular characteristic landscape of gastric cancer.

BACKGROUND: Although FDG-PET is widely used in cancer, its role in gastric cancer (GC) is still controversial due to variable [18F]fluorodeoxyglucose ([18F]FDG) uptake. Here, we sought to develop a genetic signature to predict high FDG-avid GC to plan individualized PET and investigate the molecular landscape of GC and its association with glucose metabolic profiles noninvasively evaluated by [18F]FDG-PET. METHODS: Based on a genetic signature, PETscore, representing [18F]FDG avidity, was developed by imaging data acquired from thirty patient-derived xenografts (PDX). The PETscore was validated by [18F]FDG-PET data and gene expression data of human GC. The PETscore was associated with genomic and transcriptomic profiles of GC using The Cancer Genome Atlas. RESULTS: Five genes, PLS1, PYY, HBQ1, SLC6A5, and NAT16, were identified for the predictive model for [18F]FDG uptake of GC. The PETscore was validated in independent PET data of human GC with qRT-PCR and RNA-sequencing. By applying PETscore on TCGA, a significant association between glucose uptake and tumor mutational burden as well as genomic alterations were identified. CONCLUSION: Our findings suggest that molecular characteristics are underlying the diverse metabolic profiles of GC. Diverse glucose metabolic profiles may apply to precise diagnostic and therapeutic approaches for GC.

Pathogenesis and Amelioration of Radiation-Induced Oral Mucositis.

OPINION STATEMENT: Oral mucositis (OM) causes significant detriment to patient quality of life. Despite advances in RT, chemotherapy, and surgery for HNC which have led to improved local control and survival, management of certain toxicities such as OM have not kept pace. Numerous strategies have emerged with demonstrable benefit in preventing severe OM. However, ones which are not only effective, but practical and affordable to implement are rare. For example, infusion of growth factors or free radical scavengers, and daily treatment of intra-oral sites with lasers are supported by high-quality evidence but have not become widely adopted. It falls to familiarity of the physician with the available preventative measures and ultimately, patient preference in accepting which strategies for OM amelioration are used. In this review, we present a pathophysiological-based review of prevention techniques available for reducing the incidence and duration of severe OM.

Vitamin D attenuated 6-OHDA-induced behavioural deficits, dopamine dysmetabolism, oxidative stress, and neuro-inflammation in mice.

Background: L-DOPA, the predominant therapy for Parkinson's disease (PD) is associated with motor deficits after prolonged use. The nigrostriatal tract, a primary target of neurodegeneration in PD, contains abundant Vitamin-D receptors, suggesting a potential role for VD in the disease. Therefore, we tested the impact of Vitamin D3 (VD3) in a mouse model of PD.Methods: PD was induced in adult male C57BL6 mice by a single intrastriatal injection of 6-hydroxydopamine. Two weeks post lesion, these mice received injections of a vehicle, VD3, L-DOPA, or a combination of VD3/L-DOPA and compared with sham controls. Treatment lasted three weeks, during which motor-cognitive neurobehaviour was assessed. Five weeks post lesion, brains were collected and striatal levels of the following proteins assessed: tyrosine hydroxylase (TH), dopamine decarboxylase (DDC), monoamine oxidase (MAO-B), Catechol-O-methyl transferase (COMT), dopamine transporter (DAT), brain-derived neurotrophic factor (BDNF), microglia marker (CD11b), inflammation (IL-1ß), apoptotic signaling (BAX) and oxidative stress (p47phox).Results: Treatment with VD3 attenuated behavioural deficits induced by 6-OHDA, protein associated with dopamine metabolism and biomarkers of oxidative stress. VD3 significantly increased contralateral wall touches, exploratory motor and cognitive activities. VD3 significantly enhanced the expression of TH, DAT, BDNF, while significantly reducing expression of MAO-B, CD11b, IL-I ß and p47phox.Conclusion: VD3 reversed some of the 6-OHDA induced changes in proteins involved in modulating the dopamine system, behavioural deficits and oxidative stress biomarkers. The data suggests that VD3 might be beneficial in reducing L-DOPA dosage, thereby reducing problems associated with dosage and prolonged use of L-DOPA in PD management.

Association of staffing with Incidence of delayed retinal break or detachment after posterior vitreous detachment in a resident urgent care clinic.

PURPOSE: To compare the incidence rate of delayed retinal break or detachment after diagnosis of acute, symptomatic posterior vitreous detachment (PVD) in a resident-run urgent care clinic (UCC) when staffed by a retina attending, non-retina ophthalmology attending, optometrist, or ophthalmology resident only. METHODS: Retrospective consecutive case series. Of the 594 patients with acute, symptomatic PVD evaluated in the UCC at Penn State Eye Center between 1/1/2016 and 10/10/2019, 454 were included in the study; 140 were excluded because they were diagnosed with a retinal break or detachment on presentation to the UCC, had media opacity precluding examination, or had no follow-up within one year. Demographics, presenting examination findings, and type of staffing were recorded; subsequent visits up to 1 year were analyzed for presence of delayed retinal break or detachment. RESULTS: Among 491 eyes of 454 patients with a mean follow-up of 147 days, ten delayed breaks (10/491, 2.0%) and three delayed detachments (3/491, 0.6%) were discovered. Incidence rates of delayed breaks and detachments were 1.8% (5/282) and 0.7% (2/282), respectively, in the retina attending group, 1.0% (1/105) and 1.0% (1/105) in the non-retina ophthalmology attending group, 4.7% (3/64) and 0% (0/64) in the optometrist group, and 2.5% (1/40) and 0% (0/40) in the ophthalmology resident only group. There was no statistically significant difference in the incidence of delayed break or detachment among the staffing groups (P = 0.7312), but this study was underpowered to detect a statistically significant difference among staffing groups. Patients with a delayed break or detachment were more likely to have lattice degeneration (P = 0.0265) or a history of retinal break in the contralateral eye (P = 0.0014), and most eyes (10 [76.9%]) with a delayed break or detachment were left eyes (P = 0.0466). CONCLUSIONS: The overall rate of delayed retinal break or detachment in the current study is similar to previously published rates among retinal physician and retinal fellow examiners. Although no statistically significant difference among staffing groups in the incidence rates of delayed retinal tears or detachments was identified in the study, it is important to note that the optometry and ophthalmology resident only groups had higher incidence rates of delayed retinal breaks than did the retina and non-retina ophthalmology attending groups, and this may be clinically important. Larger cohort studies would be needed in order to have the power to detect statistically significant differences among staffing groups. Varied staffing for acute, symptomatic PVD may assist with resource allocation in similar settings.