History and investigation of the chemical odors and explosion in the University Avenue sanitary sewer.

During the summer of 2022, a fire and explosion occurred in a sanitary sewer tunnel adjacent to the University of Minnesota Twin Cities campus, propelling utility maintenance covers several meters into the air and jeopardizing the safety of the public and emergency responders. The investigation into the explosion highlighted the complex variables involved in the response to sanitary sewer events. This case study outlines current approaches and proposes recommendations for agencies to be better prepared to prevent, detect, and respond to sewer-related incidents in the future. Our recommendations include the following: (1) proactive use of remote volatile organic compound (VOC) and lower explosive limit (LEL) monitoring in sanitary sewer tunnels, especially downstream of waste discharge sites; (2) incident responders should have access to instruments that measure oxygen, LEL, VOC concentration, carbon monoxide, and hydrogen sulfide; (3) better characterization of the relationship between sewer pressurization, elevation profiles, and vapor movement; (4) verification processes for oil/water separators used by industrial facilities discharging into the sanitary sewer system; (5) installation of ventilated or anchored pressure relief utility maintenance covers where allowed by code; and (6) building maintenance protocols that include regular drain flushing to keep drain traps filled. These measures are recommended to protect infrastructure and the health and safety of the public and the responders.

Efficacy of the 'Stand and Move at Work' multicomponent workplace intervention to reduce sedentary time and improve cardiometabolic risk: a group randomized clinical trial.

BACKGROUND: Sedentary time is associated with chronic disease and premature mortality. We tested a multilevel workplace intervention with and without sit-stand workstations to reduce sedentary time and lower cardiometabolic risk. METHODS: Stand and Move at Work was a group (cluster) randomized trial conducted between January 2016 and December 2017 among full-time employees; ≥18 years; and in academic, industry/healthcare, and government worksites in Phoenix, Arizona and Minneapolis/St. Paul, Minnesota, USA. Eligible worksites were randomized to (a) MOVE+, a multilevel intervention targeting reduction in sedentary time and increases in light physical activity (LPA); or (b) STAND+, the MOVE+ intervention along with sit-stand workstations to allow employees to sit or stand while working. The primary endpoints were objectively-measured workplace sitting and LPA at 12 months. The secondary endpoint was a clustered cardiometabolic risk score (blood pressure, glucose, insulin, triglycerides, and HDL-cholesterol) at 12 months. RESULTS: Worksites (N = 24; academic [n = 8], industry/healthcare [n = 8], and government [n = 8] sectors) and employees (N = 630; 27 ± 8 per worksite; 45 ± 11 years of age, 74% female) were enrolled. All worksites were retained and 487 participants completed the intervention and provided data for the primary endpoint. The adjusted between arm difference in sitting at 12 months was - 59.2 (CI: - 74.6,-43.8) min per 8 h workday, favoring STAND+, and in LPA at 12 months was + 2.2 (- 0.9,5.4) min per 8 h workday. Change in the clustered metabolic risk score was small and not statistically significant, but favored STAND+. In an exploratory subgroup of 95 participants with prediabetes or diabetes, the effect sizes were larger and clinically meaningful, all favoring STAND+, including blood glucose, triglycerides, systolic blood pressure, glycated hemoglobin, LDL-cholesterol, body weight, and body fat. CONCLUSIONS: Multilevel workplace interventions that include the use of sit-stand workstations are effective for large reductions in sitting time over 12 months. Among those with prediabetes or diabetes, clinical improvements in cardiometabolic risk factors and body weight may be realized. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02566317 . Registered 2 October 2015, first participant enrolled 11 January 2016.

Protective Masks Utilizing Nonendangered Components.

At the beginning of the COVID-19 pandemic when traditional N95 respirators were in short supply in the United States, there was a need for alternative products that did not rely on traditional avenues of sourcing and manufacturing. The purpose of this research was to develop and test alternatives to N95 respirators that could be produced locally without specialized materials and processes. Through an interdisciplinary team of experts, new mask designs that use repurposed filtration media and commercially available components were developed and tested for filtration and fit against current N95 standards. Filtration efficiency test results showed that the filtration media can be used for high-quality facemasks and quantitative fit testing demonstrated that the new mask designs could be viable alternatives to traditional N95 facemasks when those masks are in short supply. Manufacturing viability was tested utilizing a workforce to create 6000 masks over 10 days. The ability to quickly produce masks at scale using a workforce without specialized skills demonstrated the feasibility of the mask designs and manufacturing approach to address shortages of critical healthcare equipment, mitigate risk for healthcare and essential workers, and minimize the transmission and spread of disease.

Design, synthesis and selection of DNA-encoded small-molecule libraries.

Biochemical combinatorial techniques such as phage display, RNA display and oligonucleotide aptamers have proven to be reliable methods for generation of ligands to protein targets. Adapting these techniques to small synthetic molecules has been a long-sought goal. We report the synthesis and interrogation of an 800-million-member DNA-encoded library in which small molecules are covalently attached to an encoding oligonucleotide. The library was assembled by a combination of chemical and enzymatic synthesis, and interrogated by affinity selection. We describe methods for the selection and deconvolution of the chemical display library, and the discovery of inhibitors for two enzymes: Aurora A kinase and p38 MAP kinase.

Discovery of a Bromodomain and Extraterminal Inhibitor with a Low Predicted Human Dose through Synergistic Use of Encoded Library Technology and Fragment Screening.

The bromodomain and extraterminal (BET) family of bromodomain-containing proteins are important regulators of the epigenome through their ability to recognize N-acetyl lysine (KAc) post-translational modifications on histone tails. These interactions have been implicated in various disease states and, consequently, disruption of BET-KAc binding has emerged as an attractive therapeutic strategy with a number of small molecule inhibitors now under investigation in the clinic. However, until the utility of these advanced candidates is fully assessed by these trials, there remains scope for the discovery of inhibitors from new chemotypes with alternative physicochemical, pharmacokinetic, and pharmacodynamic profiles. Herein, we describe the discovery of a candidate-quality dimethylpyridone benzimidazole compound which originated from the hybridization of a dimethylphenol benzimidazole series, identified using encoded library technology, with an N-methyl pyridone series identified through fragment screening. Optimization via structure- and property-based design led to I-BET469, which possesses favorable oral pharmacokinetic properties, displays activity in vivo, and is projected to have a low human efficacious dose.

The office changes leading to sit-to-stand ergonomics.

The office ergonomic design from the late 1980s to the present has undergone significant changes during the transition from typewriters to the various human computer interfaces that evolved to the present day. Designs to accommodate various sized monitors and pointing devices have posed a challenge for ergonomist and designers of office workstations. Recent research suggesting adverse health effects associated with sedentary work environments have put additional pressure to incorporate the option to stand while working. This article reviews the current available options and suggests approaches to workplace design to meet the desire for employees to vary their work environment and the concern by management for worker health.

Efficacy and perioperative timing of bromfenac in the management of ocular discomfort after femtosecond laser-assisted laser in situ keratomileusis.

PURPOSE: To evaluate the safety, efficacy, and appropriate perioperative timing of the use of topical bromfenac ophthalmic solution 0.07% after femtosecond laser-assisted laser in situ keratomileusis (LASIK). SETTING: Keil LASIK Vision Center, Grand Rapids, Michigan, USA. DESIGN: Prospective case series. METHODS: Ocular discomfort was assessed 1, 2, and 5 hours postoperatively and the following morning using the Ocular Comfort Grading Assessment in patients treated with topical bromfenac 0.07% or artificial tears just before, just after, or before and after femtosecond laser-assisted LASIK. Visual outcomes and complications were noted up to 24 hours. RESULTS: The study enrolled 64 patients (120 eyes). Patients who were treated with bromfenac 0.07% just before or before and after femtosecond laser-assisted LASIK showed the greatest statistically significant decrease in several discomfort scores within the first few hours in comparison with the control group. Two hours after surgery, the majority of patients who were treated before and after LASIK were sleeping comfortably. There were no significant differences in visual acuity; 1 day postoperatively, the uncorrected distance visual acuity was 20/20 in 106 eyes (89%) and 20/25 or better in 116 eyes (97%). At 3 months, all patients had binocular distance visual acuity of 20/20 or better and 86% of patients had 20/15 or better. CONCLUSION: Ocular discomfort after femtosecond laser-assisted LASIK was reduced with a single dose of topical bromfenac 0.07% given immediately before surgery or given just before and after surgery and was typically minimal in all groups the morning after surgery.

Effect of computerized prescriber order entry on pharmacy: experience of one health system.

PURPOSE: Pharmacists' satisfaction with a computerized prescriber order-entry (CPOE) system and the impact of CPOE on pharmacy workflows and order verification were investigated. SUMMARY: A mixed-method study was conducted to evaluate the implementation of a CPOE system in three hospitals of a large Michigan-based health system and early user experience with the system. Surveys of pharmacists before (n = 54) and after (n = 42) CPOE implementation indicated that they held generally positive expectations about CPOE prior to and during system implementation and continued to hold positive views about CPOE after several months of system use. In interviews and focus group discussions, pharmacists reported a number of important CPOE benefits, but they also cited challenges related to CPOE provider alerts, uncertainty about medication timing, and the need to support providers by serving as informal CPOE system trainers. Direct observation of pharmacists before and after CPOE implementation indicated decreases in both the rate of order clarification events (from 0.89 to 0.35 per hour, p < 0.001) and the average time spent per hour clarifying orders (from 4.75 to 2.11 minutes, p = 0.008). CONCLUSION: Several months after CPOE implementation, pharmacists indicated that several aspects of their workload had improved, including the process of medication order clarification, their ability to prioritize work, and their ability to move around within the hospital to respond to demand. However, pharmacists also noted that order ambiguity still existed and that the system needed to be optimized to gain efficiencies and increase clarity.