Silver Lining Study: Missileer Fatigue Mitigation During 2020 Coronavirus Pandemic.

INTRODUCTION: The U.S. Air Force's Intercontinental Ballistic Missile (ICBM) force stands ready to launch weapons 365 days per year. Since its inception, missileers vigilantly operate launch consoles on a 3-day cycle: minimum 24-hour alert-shift/24-hour travel-admin/24-hour off, leading to concerns that health, morale, and alertness are chronically impacted. In 2020, a Missileer Occupational Health Assessment (OHA) revealed 76% of respondents struggle with being rested for duty and 29% of respondents never feel adequately rested for duty. Later that year, 20th Air Force initiated long-duration operations to safeguard from the SARS CoV-2 (COVID-19) Pandemic, resulting in increased operations tempo, and exacerbating crew fatigue.341st Operations Group and 341st Medical Group at Malmstrom Air Force Base enacted interventions to mitigate crew fatigue and support continued readiness during pandemic operations. They recorded, analyzed, and compiled findings in this report, including recommendations for long-term ICBM operations at Missile Wings. MATERIALS AND METHODS: All participants were Nuclear and Missile Operations Officers, or missileers, were continuously evaluated with qualitative and quantitative measures to ensure safety of the force during a period of unprecedented change. Interventions implemented and evaluated during the 9-month period included: environmental modifications, scheduling changes, and crew education on fatigue management, nutrition, anticipatory sleep preparation, and fitness. Most notably, the 341st Operations Group examined various 3-person and 4-person shift-length and alert duration schedules. Psychomotor vigilance testing results validated safety of operators and delta between pre- and post-shift measurements. Crew force readiness trends were analyzed for force-health awareness. Pre- and post-OHA results were compared for subjective changes. Fatigue and health-related outcomes were collected from a safety monitoring effort during standard and COVID-19 operations at 341st Missile Wing. RESULTS: Findings from qualitative and quantitative data indicate the optimal schedule is a 3-week cycle:7-day alert/7-day recovery/7-day training-administrative utilizing 4-member or 3-member crews for low tempo operations. Crews experimented with shift-lengths of 24hrs-on/24hrs-off, 16hrs-on/8hrs-off, and 12hrs-on/12hrs-off. Maximum safe alert duration is 7 days due to task fatigue onset between 8 and 10 days. Short and long duration Duties Not to Include Flight (DNIF) (also known as Duties Not to Include Alert (DNIA) among missileers) rates decreased from the first to last month of the period by 74.6% and 79.2%, respectively. The number of alerts missed per month decreased 86% from baseline. The 2021 OHA found a 7% decline in members seeking separation, and absence of sleep, fatigue, and physical or mental health as missileer concerns. CONCLUSIONS: This analysis has identified a sustainable alert rotation of 7/7/7 with emphasis on protected recovery and training time and has been continued after concluding pandemic operations, creating consistent schedule stability where there once was none. If executed properly, this alert rotation, regardless of shift-length selected, has potential to improve trust between crews and leadership, provides adequate recovery time between alerts to maintain health, and improves wellness, family stability, morale, unit cohesion, and crew force retention. Notably, all Air Force Global Strike Missile Operations Groups adjusted scheduling practices to align with these findings.

Successful Use of Colistin Monotherapy as Outpatient Parenteral Antibiotic Therapy for XDR Acinetobacter Hepatic Abscesses.

Acinetobacter baumannii is naturally resistant to several classes of antibiotics and readily develops further resistance mechanisms under antibiotic pressure. For patients infected with extremely drug-resistant organisms, effective antibiotic treatments are intravenous and often require inpatient hospitalization for monitoring and dose adjustment. A 31-year-old active duty service member, stationed in Southeast Asia, sustained thermal burns from an electrical arc injury to over 40% of his total body surface area. His hospital course was complicated by multiple extensively drug resistant (XDR) A. baumanii infections including bacteremia and hepatic abscesses. To facilitate discharge to his family, his hepatic abscesses were treated successfully as an outpatient with several weeks of parenteral colistin monotherapy. With regular renal function testing, his dosages were held and/or adjusted to compensate for acute kidney injuries, and he was successfully cleared of his infection. Up to 50% of A. baumannii isolates in American hospitals, including major DOD facilities, are carbapenem resistant. As a result, historically last-line therapies, such as polymyxins, are increasingly used as treatment. New dosing guidance is emphasized to minimize renal toxicities. This case demonstrates the ability to administer parenteral colistin as an outpatient under close supervision.

Quaternized starch-based carrier for siRNA delivery: from cellular uptake to gene silencing.

RNAi therapeutics is a powerful tool for treating diseases by sequence-specific targeting of genes using siRNA. Since its discovery, the need for a safe and efficient delivery system for siRNA has increased. Here, we have developed and characterized a delivery platform for siRNA based on the natural polysaccharide starch in an attempt to address unresolved delivery challenges of RNAi. Modified potato starch (Q-starch) was successfully obtained by substitution with quaternary reagent, providing Q-starch with cationic properties. The results indicate that Q-starch was able to bind siRNA by self-assembly formation of complexes. For efficient and potent gene silencing we monitored the physical characteristics of the formed nanoparticles at increasing N/P molar ratios. The minimum ratio for complete entrapment of siRNA was 2. The resulting complexes, which were characterized by a small diameter (~30 nm) and positive surface charge, were able to protect siRNA from enzymatic degradation. Q-starch/siRNA complexes efficiently induced P-glycoprotein (P-gp) gene silencing in the human ovarian adenocarcinoma cell line, NCI-ADR/Res (NAR), over expressing the targeted gene and presenting low toxicity. Additionally, Q-starch-based complexes showed high cellular uptake during a 24-hour study, which also suggested that intracellular siRNA delivery barriers governed the kinetics of siRNA transfection. In this study, we have devised a promising siRNA delivery vector based on a starch derivative for efficient and safe RNAi application.

Detection of bacterial 16S rRNA and identification of four clinically important bacteria by real-time PCR.

Within the paradigm of clinical infectious disease research, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa represent the four most clinically relevant, and hence most extensively studied bacteria. Current culture-based methods for identifying these organisms are slow and cumbersome, and there is increasing need for more rapid and accurate molecular detection methods. Using bioinformatic tools, 962,279 bacterial 16S rRNA gene sequences were aligned, and regions of homology were selected to generate a set of real-time PCR primers that target 93.6% of all bacterial 16S rRNA sequences published to date. A set of four species-specific real-time PCR primer pairs were also designed, capable of detecting less than 100 genome copies of A. baumannii, E. coli, K. pneumoniae, and P. aeruginosa. All primers were tested for specificity in vitro against 50 species of Gram-positive and -negative bacteria. Additionally, the species-specific primers were tested against a panel of 200 clinical isolates of each species, randomly selected from a large repository of clinical isolates from diverse areas and sources. A comparison of culture and real-time PCR demonstrated 100% concordance. The primers were incorporated into a rapid assay capable of positive identification from plate or broth cultures in less than 90 minutes. Furthermore, our data demonstrate that current targets, such as the uidA gene in E.coli, are not suitable as species-specific genes due to sequence variation. The assay described herein is rapid, cost-effective and accurate, and can be easily incorporated into any research laboratory capable of real-time PCR.