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Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. S. has received research funding from Abbott, Edwards Lifesciences, Vifor, Pfizer, Bayer, General Prognostics, Story Health, Acorai, Boston Scientific, and Impulse Dynamics; is on the steering committees of Abbott, Boston Scientific, Biotronik, Story Health, RIVUS, Bayer, and General Prognostics; and is a consultant for Abbott, Boston Scientific, Edwards Lifesciences, Impulse Dynamics, Acorai, Story Health, General Prognostics, and Bayer. None declared (M. G., K. M., H. S., E. V., M. B., T. A. B., K. B., A. B., A. G., T. F., M. F., J. T. H., E. M., O. J., L. K., P. M., M. R.).

Mutations causing depigmentation are relatively common in Equus caballus (horse). Over 40 alleles in multiple genes are associated with increased white spotting (as of February 2023). The splashed white phenotype, a coat spotting pattern described as appearing like the horse has been splashed with white paint, was previously associated with variants in the PAX3 and MITF genes. Both genes encode transcription factors known to control melanocyte migration and pigmentation. We report two novel mutations, a stop-gain mutation in PAX3 (XM_005610643.3:c.927C>T, ECA6:11,196,181, EquCab3.0) and a missense mutation in a binding domain of MITF (NM_001163874.1:c.993A>T, ECA16:21,559,940, EquCab3.0), each with a strong association with increased depigmentation in Pura Raza Española horses (P = 1.144E-11, N = 30, P = 4.441E-16, N = 39 respectively). Using a quantitative method to score depigmentation, the PAX3 and MITF mutations were found to have average white scores of 25.50 and 24.45, respectively, compared to the average white coat spotting score of 1.89 in the control set. The functional impact for each mutation was predicted to be moderate to extreme (I-TASSER, SMART, Variant Effect Predictor, SIFT). We propose to designate the MITF mutant allele as Splashed White 9 and the PAX3 mutant allele as Splashed White 10 per convention., Competing Interests: Declaration of Competing Interest AM, K.Martin, K.McLoone, MV, GF, EL, EV, RE, EM, and CL are affiliated with Etalon Diagnostics which offers diagnostic testing for white-spotting mutations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mutations in KIT, a gene that influences melanoblast migration and pigmentation, often result in mammalian white spotting. As of February 2023, over 30 KIT variants associated with white spotting were documented in Equus caballus (horse). Here we report an association of increased white spotting on the skin and coat with a variant in the 5'UTR of KIT (rs1149701677: g.79,618,649A>C). Horses possessing at least one alternate allele demonstrate phenotypic characteristics similar to other KIT mutations: clear borders around unpigmented regions on the body, face, and limbs. Using a quantitative measure of depigmentation, we observed an average white score of 10.70 among individuals with rs1149701677, while the average score of the control, homozygous reference sample was 2.23 (P = 1.892e-11, n = 109, t-test). The rs1149701677 site has a cross-species conservation score of 3.4, one of the highest scores across the KIT 5'UTR, implying regulatory importance for this site. Ensembl also predicted a "moderately impactful" functional effect for the rs1149701677 variant. We propose that this single nucleotide variant likely alters the regulation of KIT, which in turn may disrupt melanoblast migration causing an increase in white spotting on the coat. Alternatively, the rs1149701677 variant may be in linkage with another nearby variant with an as-yet-undiscovered functional impact. We propose to term this new allele "Holiday White" or W35 based on conventional nomenclature., Competing Interests: Declaration of Competing Interest AM, K.Martin, K.McLoone, MV, GF, EL, EV, RE, EM, and CL are affiliated with Etalon Diagnostics which offers diagnostic testing for white-spotting mutations., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The omicron variant (B.1.1.529) of SARS-CoV-2 has demonstrated partial vaccine escape and high transmissibility, with early studies indicating lower severity of infection than that of the delta variant (B.1.617.2). We aimed to better characterise omicron severity relative to delta by assessing the relative risk of hospital attendance, hospital admission, or death in a large national cohort., Methods: Individual-level data on laboratory-confirmed COVID-19 cases resident in England between Nov 29, 2021, and Jan 9, 2022, were linked to routine datasets on vaccination status, hospital attendance and admission, and mortality. The relative risk of hospital attendance or admission within 14 days, or death within 28 days after confirmed infection, was estimated using proportional hazards regression. Analyses were stratified by test date, 10-year age band, ethnicity, residential region, and vaccination status, and were further adjusted for sex, index of multiple deprivation decile, evidence of a previous infection, and year of age within each age band. A secondary analysis estimated variant-specific and vaccine-specific vaccine effectiveness and the intrinsic relative severity of omicron infection compared with delta (ie, the relative risk in unvaccinated cases)., Findings: The adjusted hazard ratio (HR) of hospital attendance (not necessarily resulting in admission) with omicron compared with delta was 0·56 (95% CI 0·54-0·58); for hospital admission and death, HR estimates were 0·41 (0·39-0·43) and 0·31 (0·26-0·37), respectively. Omicron versus delta HR estimates varied with age for all endpoints examined. The adjusted HR for hospital admission was 1·10 (0·85-1·42) in those younger than 10 years, decreasing to 0·25 (0·21-0·30) in 60-69-year-olds, and then increasing to 0·47 (0·40-0·56) in those aged at least 80 years. For both variants, past infection gave some protection against death both in vaccinated (HR 0·47 [0·32-0·68]) and unvaccinated (0·18 [0·06-0·57]) cases. In vaccinated cases, past infection offered no additional protection against hospital admission beyond that provided by vaccination (HR 0·96 [0·88-1·04]); however, for unvaccinated cases, past infection gave moderate protection (HR 0·55 [0·48-0·63]). Omicron versus delta HR estimates were lower for hospital admission (0·30 [0·28-0·32]) in unvaccinated cases than the corresponding HR estimated for all cases in the primary analysis. Booster vaccination with an mRNA vaccine was highly protective against hospitalisation and death in omicron cases (HR for hospital admission 8-11 weeks post-booster vs unvaccinated: 0·22 [0·20-0·24]), with the protection afforded after a booster not being affected by the vaccine used for doses 1 and 2., Interpretation: The risk of severe outcomes following SARS-CoV-2 infection is substantially lower for omicron than for delta, with higher reductions for more severe endpoints and significant variation with age. Underlying the observed risks is a larger reduction in intrinsic severity (in unvaccinated individuals) counterbalanced by a reduction in vaccine effectiveness. Documented previous SARS-CoV-2 infection offered some protection against hospitalisation and high protection against death in unvaccinated individuals, but only offered additional protection in vaccinated individuals for the death endpoint. Booster vaccination with mRNA vaccines maintains over 70% protection against hospitalisation and death in breakthrough confirmed omicron infections., Funding: Medical Research Council, UK Research and Innovation, Department of Health and Social Care, National Institute for Health Research, Community Jameel, and Engineering and Physical Sciences Research Council., Competing Interests: Declaration of interests GD declares that his employer UK Health Security Agency (previously operating as Public Health England) received funding from GlaxoSmithKline for a research project related to influenza antiviral treatment. This preceded and had no relation to COVID-19, and GD had no role in and received no funding from the project. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: In this data collation study, we aimed to provide a comprehensive database describing the epidemic trends and responses during the first wave of coronavirus disease 2019 (COVID-19) throughout the main provinces in China., Methods: From mid-January to March 2020, we extracted publicly available data regarding the spread and control of COVID-19 from 31 provincial health authorities and major media outlets in mainland China. Based on these data, we conducted descriptive analyses of the epidemic in the six most-affected provinces., Results: School closures, travel restrictions, community-level lockdown, and contact tracing were introduced concurrently around late January but subsequent epidemic trends differed among provinces. Compared with Hubei, the other five most-affected provinces reported a lower crude case fatality ratio and proportion of critical and severe hospitalised cases. From March 2020, as the local transmission of COVID-19 declined, switching the focus of measures to the testing and quarantine of inbound travellers may have helped to sustain the control of the epidemic., Conclusions: Aggregated indicators of case notifications and severity distributions are essential for monitoring an epidemic. A publicly available database containing these indicators and information regarding control measures is a useful resource for further research and policy planning in response to the COVID-19 epidemic., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Assuring quality in cancer care through peer review has become increasingly important in radiation oncology. In 2012, our department implemented an automated electronic system for managing radiation treatment plan peer review. The purpose of this study was to compare the overall impact of this electronic system to our previous manual, paper-based system., Methods and Materials: In an effort to improve management, an automated electronic system for case finding and documentation of review was developed and implemented. The rates of missed initial reviews, late reviews, and missed re-reviews were compared for the pre- versus postelectronic system cohorts using Pearson χ 2 test and relative risk. Major and minor changes or recommendations were documented and shared with the assigned clinical provider., Results: The overall rate of missed reviews was 7.6% (38/500) before system implementation versus 0.4% (28/6985) under the electronic system (P < .001). In terms of relative risk, courses were 19.0 times (95% confidence interval, 11.8-30.7) more likely to be missed for initial review before the automated system. Missed re-reviews occurred in 23.1% (3/13) of courses in the preelectronic system cohort and 6.6% (10/152) of courses in the postelectronic system cohort (P = .034). Late reviews were more frequent during high travel or major holiday periods. Major changes were recommended in 2.2% and 2.8% in the pre- versus postelectronic systems, respectively. Minor changes were recommended in 5.3% of all postelectronic cases., Conclusions: The implementation of an automated electronic system for managing peer review in a large, complex department was effective in significantly reducing the number of missed reviews and missed re-reviews when compared to our previous manual system., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Unlabelled: In 2010, the American Society for Radiation Oncology launched a national campaign to improve patient safety in radiation therapy. One recommendation included the expansion of educational programs dedicated to quality and safety. We subsequently implemented a quality and safety culture education program (Q-SCEP) in our large radiation oncology department. The purpose of this study is to describe the design, implementation, and impact of this Q-SCEP., Methods and Materials: In 2010, we instituted a comprehensive Q-SCEP, consisting of a longitudinal series of lectures, meetings, and interactive workshops. Participation was mandatory for all department members across all network locations. Electronic surveys were administered to assess employee engagement, knowledge retention, preferred learning styles, and the program's overall impact. The Agency for Healthcare Research and Quality (AHRQ) Survey on Patient Safety Culture was administered. Analysis of variance was used for statistical analysis., Results: Between 2010 and 2015, 100% of targeted staff participated in Q-SCEP. Thirty-three percent (132 of 400) and 30% (136 of 450) responded to surveys in 2012 and 2014, respectively. Mean scores improved from 73% to 89% (P < .001), with the largest improvement seen among therapists (+21.7%). The majority strongly agreed that safety culture education was critical to performing their jobs well., Conclusions: Full course compliance was achieved despite the sizable number of personnel and treatment centers. Periodic assessments demonstrated high knowledge retention, which significantly improved over time in nearly all department divisions. Additionally, our AHRQ patient safety grade remains high and continues to improve. These results will be used to further enhance ongoing internal safety initiatives and to inform future innovative efforts., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Social networks are increasingly recognized as important points of intervention, yet relatively few intervention studies of respiratory infection transmission have utilized a network design. Here we describe the design, methods, and social network structure of a randomized intervention for isolating respiratory infection cases in a university setting over a 10-week period., Methodology/principal Findings: 590 students in six residence halls enrolled in the eX-FLU study during a chain-referral recruitment process from September 2012-January 2013. Of these, 262 joined as "seed" participants, who nominated their social contacts to join the study, of which 328 "nominees" enrolled. Participants were cluster-randomized by 117 residence halls. Participants were asked to respond to weekly surveys on health behaviors, social interactions, and influenza-like illness (ILI) symptoms. Participants were randomized to either a 3-Day dorm room isolation intervention or a control group (no isolation) upon illness onset. ILI cases reported on their isolation behavior during illness and provided throat and nasal swab specimens at onset, day-three, and day-six of illness. A subsample of individuals (N=103) participated in a sub-study using a novel smartphone application, iEpi, which collected sensor and contextually-dependent survey data on social interactions. Within the social network, participants were significantly positively assortative by intervention group, enrollment type, residence hall, iEpi participation, age, gender, race, and alcohol use (all P<0.002)., Conclusions/significance: We identified a feasible study design for testing the impact of isolation from social networks in a university setting. These data provide an unparalleled opportunity to address questions about isolation and infection transmission, as well as insights into social networks and behaviors among college-aged students. Several important lessons were learned over the course of this project, including feasible isolation durations, the need for extensive organizational efforts, as well as the need for specialized programmers and server space for managing survey and smartphone data., (Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Pediatric patients may receive complex treatment. In our department, an electronic incident reporting system (condition reporting system [CRS]) was developed and made available to all members., Methods and Materials: The CRS system is available on all departmental computers. Entered events are evaluated and graded by a supervisor as follows: "A"(dose deviation or patient harm), "B" (near miss), "C" (interruption in care process), or "D" (inconvenience). Data for pediatric patients for whom events were entered were reviewed retrospectively and compared to the entire treated pediatric population., Results: Over 2 years, 503 pediatric patients received radiation therapy (median age 10.1 years; range, 0.5-18.8 years), and 592 pediatric CRS events were entered (9.8% of 6020 total institutional CRS entries). These concerned 275 patients with an average of 2.1 entries each; 59% (348) were graded as severity D, 39% (230) as C, 2% (14) as B, and none as A. Events were most commonly related to treatment process (32%, n = 188), followed by planning/dosimetry (19%, n = 109), anesthesia (15%, n = 86), scheduling/transport (13%, n = 73), and physics (10%, n = 62). Delays associated with events were ≤1 hour for most cases (83%, n = 474). Patient and treatment factors associated with CRS entry included total duration of radiation therapy, primary brain tumor, receipt of proton therapy, and receipt of double-scattered proton therapy. No significant differences were found based on age, sex, race, treatment intent (curative vs palliative), type of photon treatment (conformal vs intensity modulated radiation therapy vs arc), use of total body irradiation, or use of pencil beam scanning proton therapy., Conclusions: An incident reporting system is a widely used part of the safety culture at our institution, which treats one of the largest pediatric patient volumes in North America. Most pediatric CRS-reported events are of minor severity. Longer treatment course and use of new and complex technologies appear to increase the likelihood of a CRS event within the pediatric population, which supports the need for increased safety processes when new techniques are initiated., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Incident learning programs have been recognized as cornerstones of safety and quality assurance in so-called high reliability organizations in industries such as aviation and nuclear power. High reliability organizations are distinguished by their drive to continuously identify and proactively address a broad spectrum of latent safety issues. Many radiation oncology institutions have reported on their experience in tracking and analyzing adverse events and near misses but few have incorporated the principles of high reliability into their programs. Most programs have focused on the reporting and retrospective analysis of a relatively small number of significant adverse events and near misses. To advance a large, multisite radiation oncology department toward high reliability, a comprehensive, cost-effective, electronic condition reporting program was launched to enable the identification of a broad spectrum of latent system failures, which would then be addressed through a continuous quality improvement process., Methods: A comprehensive program, including policies, work flows, and information system, was designed and implemented, with use of a low reporting threshold to focus on precursors to adverse events., Results: In a 46-month period from March 2011 through December 2014, a total of 8,504 conditions (average, 185 per month, 1 per patient treated, 3.9 per 100 fractions [individual treatments]) were reported. Some 77.9% of clinical staff members reported at least 1 condition. Ninety-eight percent of conditions were classified in the lowest two of four severity levels, providing the opportunity to address conditions before they contribute to adverse events., Conclusions: Results after approximately four years show excellent employee engagement, a sustained rate of reporting, and a focus on low-level issues leading to proactive quality improvement interventions.

The risk of acquiring sexually transmitted infections (STIs) depends on individual behavior and the network of risky partnerships in which an individual participates. STI epidemics often spread rapidly and primarily among individuals central to transmission networks; and thus they often defy the mass-action principle since incidence is not proportional to the infectious fraction of the population. Here, we estimate the contact network structure for an Atlanta, Georgia community with heterogeneous sexual and drug-related risk behaviors and build a detailed transmission model for HIV through this population. We show that accurate estimation of epidemic incidence requires careful measurement and inclusion of diverse factors including concurrency (having multiple partners), the duration of partnerships, serosorting (preference for partners with matching disease state), and heterogeneity in the number and kinds of partners. In the focal population, we find that injection drug users (IDUs) do not directly cause many secondary infections; yet they bridge the heterosexual and men-who-have-sex-with-men (MSM) populations and are thereby indirectly responsible for extensive transmission., (Copyright © 2010 Elsevier B.V. All rights reserved.)