IMPORTANCE Hereditary cancer syndromes infer high cancer risks and require intensive cancer surveillance, yet the prevalence and spectrum of these conditions among unselected patients with early-onset colorectal cancer (CRC) is largely undetermined. OBJECTIVE To determine the frequency and spectrum of cancer susceptibility gene mutations among patients with early-onset CRC. DESIGN, SETTING, AND PARTICIPANTS Overall, 450 patients diagnosed with colorectal cancer younger than 50 years were prospectively accrued from 51 hospitals into the Ohio Colorectal Cancer Prevention Initiative from January 1, 2013, to June 20, 2016. Mismatch repair (MMR) deficiency was determined by microsatellite instability and/or immunohistochemistry. Germline DNA was tested for mutations in 25 cancer susceptibility genes using next-generation sequencing. MAIN OUTCOMES AND MEASURES Mutation prevalence and spectrum in patients with early-onset CRC was determined. Clinical characteristics were assessed by mutation status. RESULTS In total 450 patients younger than 50 years were included in the study, and 75 gene mutations were found in 72 patients (16%). Forty-eight patients (10.7%) had MMR-deficient tumors, and 40 patients (83.3%) had at least 1 gene mutation: 37 had Lynch syndrome (13, MLH1 [including one with constitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had the APC c.3920T>A, p.I1307K mutation and a PMS2 variant; 9 patients (18.8%) had double somatic MMR mutations (including 2 with germline biallelic MUTYH mutations); and 1 patient had somatic MLH1 methylation. Four hundred two patients (89.3%) had MMR-proficient tumors, and 32 patients (8%) had at least 1 gene mutation: 9 had mutations in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mutations in high- or moderate-penetrance genes not traditionally associated with CRC (3, ATM; 1, ATM/CHEK2; 2, BRCA1; 4, BRCA2; 1, CDKN2A; 2, PALB2); 10 patients had mutations in low-penetrance CRC genes (3, APC c.3920T>A, p.I1307K; 7, monoallelic MUTYH). Importantly, 24 of 72 patients (33.3%) who were mutation positive did not meet established genetic testing criteria for the gene(s) in which they had a mutation. CONCLUSIONS AND RELEVANCE Of 450 patients with early-onset CRC, 72 (16%) had gene mutations. Given the high frequency and wide spectrum of mutations, genetic counseling and testing with a multigene panel could be considered for all patients with early-onset CRC.

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School climate is a leading factor in explaining student learning and achievement. Less work has explored the impact of both staff and student perceptions of school climate raising interesting questions about whether staff school climate experiences can add “value” to students' achievement. In the current research, multiple sources were integrated into a multilevel model, including staff self-reports, student self-reports, objective school records of academic achievement, and socio-economic demographics. Achievement was assessed using a national literacy and numeracy tests (N = 760 staff and 2,257 students from 17 secondary schools). In addition, guided by the “social identity approach,” school identification is investigated as a possible psychological mechanism to explain the relationship between school climate and achievement. In line with predictions, results show that students' perceptions of school climate significantly explain writing and numeracy achievement and this effect is mediated by students' psychological identification with the school. Furthermore, staff perceptions of school climate explain students' achievement on numeracy, writing and reading tests (while accounting for students' responses). However, staff's school identification did not play a significant role. Implications of these findings for organizational, social, and educational research are discussed.

From 1999-2003, the hygiene of 1061 environmental surfaces from shopping, daycare, and office environments, personal items, and miscellaneous activities (i.e., gymnasiums, airports, movie theaters, restaurants, etc.), in four US cities, was monitored. Samples were analyzed for fecal and total coliform bacteria, protein, and biochemical markers. Biochemical markers, i.e., hemoglobin (blood marker), amylase (mucus, saliva, sweat, and urine marker), and urea (urine and sweat marker) were detected on 3% (26/801); 15% (120/801), and 6% (48/801) of the surfaces, respectively. Protein (general hygiene marker) levels > or = 200 microg/10 cm2 were present on 26% (200/801) of the surfaces tested. Surfaces from children's playground equipment and daycare centers were the most frequently contaminated (biochemical markers on 36%; 15/42 and 46%; 25/54, respectively). Surfaces from the shopping, miscellaneous activities, and office environments were positive for biochemical markers with a frequency of 21% (69/333), 21% (66/308), and 11% (12/105), respectively). Sixty samples were analyzed for biochemical markers and bacteria. Total and fecal coliforms were detected on 20% (12/60) and 7% (4/ 60) of the surfaces, respectively. Half and one-third of the sites positive for biochemical markers were also positive for total and fecal coliforms, respectively. Artificial contamination of public surfaces with an invisible fluorescent tracer showed that contamination from outside surfaces was transferred to 86% (30/ 35) of exposed individual's hands and 82% (29/35) tracked the tracer to their home or personal belongings hours later. Results provide information on the relative hygiene of commonly encountered public surfaces and aid in the identification of priority environments where contaminant occurrence and risk of exposure may be greatest. Children's playground equipment is identified as a priority surface for additional research on the occurrence of and potential exposure to infectious disease causing agents.

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Although the number of illnesses resulting from indirect viral pathogen transmission could be substantial, it is difficult to estimate the relative risks because of the wide variation and uncertainty in human behavior, variable viral concentrations on fomites, and other exposure factors. The purpose of this study was to evaluate the micro-activity approach for assessment of microbial risk by adapting a mathematical model to estimate probability of viral infection from indirect transmission. To evaluate the model, measurements of phage loading on fomites and hands collected before and after implementation of a Healthy Workplace Project™ intervention were used. Parameter distributions were developed from this data, as well as for micro-activity rates, contact surface areas, phage transfer efficiencies, and inactivation rates. Following the Monte Carlo simulations (n=1,000), the estimated phage loading on hands was not significantly different from the loading of phage on hands measured in the experimental trials. The model was then used to demonstrate that the Healthy Workplace Project™ intervention significantly reduced risk of infection by 77% for rotavirus and rhinovirus. This is the first published study to successfully evaluate a model focused on the indirect transmission of viruses via hand contact with measured data and provide an assessment of the micro-activity approach to microbial risk evaluation.

Highlights We used QMRA to relate surface disinfection efficacy to COVID-19 infection risk. Little log 10 reductions may be needed for low viral bioburden conditions. >2 log 10 may be needed to achieve risks <1:1,000,000 for high viral bioburden.