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Many recently developed Bayesian methods focus on sparse signal detection. However, much less work has been done on the natural follow-up question: how does one make valid inferences for the magnitude of those signals after selection? Ordinary Bayesian credible intervals suffer from selection bias, as do ordinary frequentist confidence intervals. Existing Bayesian methods for correcting this bias produce credible intervals with poor frequentist properties. Further, existing frequentist approaches require sacrificing the benefits of shrinkage typical in Bayesian methods, resulting in confidence intervals that are needlessly wide. We address this gap by proposing a nonparametric empirical Bayes approach to constructing optimal selection-adjusted confidence sets. Our method produces confidence sets that are as short as possible on average, while both adjusting for selection and maintaining exact frequentist coverage uniformly over the parameter space. We demonstrate an important consistency property of our procedure: under mild conditions, it asymptotically converges to the results of an oracle-Bayes analysis in which the prior distribution of signal sizes is known exactly. Across a series of examples, the method is found to outperform existing frequentist techniques for post-selection inference, producing confidence sets that are notably shorter, but with the same coverage guarantee. [ABSTRACT FROM AUTHOR]

The formation of ternary degrader-protein complexes is a key step in the targeted degradation of proteins of interest. Here, the authors explore the structure and dynamics of such complexes applying high-performance computer simulations augmented with experimental data.

Purpose: To compare stiffness, strain, and load to failure of 4- versus 5-strand hamstring anterior cruciate ligament reconstruction human tendon allografts with femoral suspensory and tibial interference screw fixation Methods: Allograft hamstring tendons were used to create 10 four-strand (4S) and 10 five-strand (5S) grafts. Grafts were fixed to a uniaxial electromechanical load system via a femoral cortical suspensory button and a bioabsorbable interference screw in bone analogue. Grafts were cycled from 100 Newtons (N) to 250 N for 1,000 repetitions at 0.5 hertz before load to failure testing. Cyclic displacement was defined as the difference in graft length from the first 20 to 30 cycles compared with the last 10 cycles. Trials were recorded on a high-definition camera to allow for digital image correlation analysis. Results: Cyclic displacement more than 1,000 cycles was significantly lower in the 4S compared with the 5S group (0.87 vs 1.11 mm, P = .037). Digital image correlation analysis confirmed that the fifth strand elongated more than the other 4 strands in the 5S constructs (6.1% vs 3.9%, P = .032). Load to failure was greater in the 4S compared with the 5S group but not statistically significant (762 vs 707 N, P = .35). Stiffness was similar between constructs (138.5 vs 138.3 N/mm, P = .96) Conclusions: Compared with cyclically loaded 4S hamstring grafts, the 5S grafts had significantly increased displacement over time in a model of femoral suspensory and tibial interference screw fixation. Clinical Relevance: Anterior cruciate ligament reconstruction with hamstring tendon autograft is a commonly performed surgery with excellent outcomes. It has been shown that graft diameter influences these outcomes. As surgeons use larger grafts, it is important to investigate how these constructs may affect the outcomes of surgery.

To help cells cope with protein misfolding and aggregation, Hsp70 molecular chaperones selectively bind a variety of sequences (“selective promiscuity”). Statistical analyses from substrate-derived peptide arrays reveal that DnaK, the E. coli Hsp70, binds to sequences containing three to five branched hydrophobic residues, although otherwise the specific amino acids can vary considerably. Several high-resolution structures of the substrate -binding domain (SBD) of DnaK bound to peptides reveal a highly conserved configuration of the bound substrate and further suggest that the substrate-binding cleft consists of five largely independent sites for interaction with five consecutive substrate residues. Importantly, both substrate backbone orientations (N- to C- and C- to N-) allow essentially the same backbone hydrogen-bonding and side-chain interactions with the chaperone. In order to rationalize these observations, we performed atomistic molecular dynamics simulations to sample the interactions of all 20 amino acid side chains in each of the five sites of the chaperone in the context of the conserved substrate backbone configurations. The resulting interaction energetics provide the basis set for deriving a predictive model that we call Paladin (Physics-based model of DnaK-Substrate Binding). Trained using available peptide array data, Paladin can distinguish binders and nonbinders of DnaK with accuracy comparable to existing predictors and further predicts the detailed configuration of the bound sequence. Tested using existing DnaK-peptide structures, Paladin correctly predicted the binding register in 10 out of 13 substrate sequences that bind in the N- to C- orientation, and the binding orientation in 16 out of 22 sequences. The physical basis of the Paladin model provides insight into the origins of how Hsp70s bind substrates with a balance of selectivity and promiscuity. The approach described here can be extended to other Hsp70s where extensive peptide array data is not available. Author summary Molecular chaperones are proteins that help prevent misfolding and aggregation of their substrates. This is a complex task, as the cell is very crowded, and the chaperone must efficiently bind to misfolded regions of the client protein while avoiding well-folded proteins. An additional confounding detail is that proteins can enter the binding cleft of some Hsp70s in two orientations, a fact often unaccounted for by existing sequence-based models. Here, we developed a model to describe how client proteins bind to DnaK, the E. coli Hsp70, using physics-based molecular dynamics simulations to quantify the interactions between a variety of peptide substrates and key sites on DnaK. The resulting model, which we call Paladin, provides a physical basis to understand how DnaK binds to specific peptides. Given a sequence, Paladin can predict the precise residues that bind at a specific site on DnaK and can further explain challenging features like the binding orientation, which are typically not predicted by sequence-only models. The Paladin model could be used to design ‘super-binder’ therapeutic peptides to inhibit chaperones like DnaK in E. coli.

Recent findings have suggested some potential psychological vulnerability factors for development of obsessive-compulsive (OC) symptoms, including cognitive factors of appraisal and thought control, religiosity, self-esteem and personality characteristics such as neuroticism. Studies demonstrating these associations usually come from Western cultures, but there may be cultural differences relevant to these vulnerability factors and OC symptoms. The present study examined the relationship between putative vulnerability factors and OC symptoms by comparing non-clinical samples from Turkey and Canada, two countries with quite different cultural characteristics. The findings revealed some common correlates such as neuroticism and certain types of metacognition, including appraisals of responsibility/threat estimation and perfectionism/need for certainty, as well as thought-action fusion. However, culture-specific factors were also indicated in the type of thought control participants used. For OC disorder symptoms, Turkish participants were more likely to utilize worry and thought suppression, while Canadian participants tended to use self-punishment more frequently. The association with common factors supports the cross-cultural validity of some factors, whereas unique factors suggest cultural features that may be operative in cognitive processes relevant to OC symptoms. Copyright © 2009 John Wiley & Sons, Ltd. Key Practitioner Message: · Despite cross-cultural validity in the cognitive accounts for OCD, there are some evidences implying the impact of cultural characteristics on some cognitive factors across different cultures. Thus, it is important for clinicians who work with people from different cultural backgrounds to be vigilant for possible variations in the cognitive processes during psychotherapy and psychological assessment. [ABSTRACT FROM AUTHOR]

Summary Reasons for performing study: Colic is a serious disease syndrome in horses. Much of the mortality is associated with ischaemic-injured intestine during strangulating obstruction, yet there is limited understanding of the associated molecular events. Identification of differentially expressed genes during ischaemic injury should expand our understanding of colic and may lead to novel targeted therapeutic approaches in the future. Objective: To isolate and identify differentially expressed genes in equine jejunum following a 2 h ischaemic event compared to normally perfused jejunum. Methods: Suppressive subtractive hybridisation was used to clone genes that are differentially expressed in equine jejunum injured by 2 h of complete ischaemia as compared to time-matched control jejunal tissues. Expression of selected clones was further evaluated by northern blot analysis. Results: Of the 384 clones selected, 157 were confirmed to possess cDNAs corresponding differentially expressed genes by dot blot analysis. Two genes, fatty acid binding protein 2 and calcium-activated chloride channel 4 were further confirmed to be differentially expressed by northern blot analysis. Conclusions: Suppressive subtractive hybridisation can be used to detect changes in expression of a broad array of genes, as confirmed by northern blot analysis of selected genes. Potential relevance: These initial results have identified a pool of equine intestinal epithelial genes that are differentially expressed following a 2 h ischaemic event. In particular, genes indicative of deranged metabolic activity and those potentially involved in early repair events were identified and may ultimately provide clues as to the nature of epithelial ischaemic injury in horses. [ABSTRACT FROM AUTHOR]

Provides information on a study which targeted habitat patches in England's Chiltern Hills Area for conservation using a Geographical Information System. Habitat evaluation schemes; Landscape criteria; Method of the study; Results and discussion.

Predicting changes in protein binding affinity due to single amino acid mutations helps us better understand the driving forces underlying protein-protein interactions and design improved biotherapeutics. Here, we use the MM-GBSA approach with the OPLS2005 force field and the VSGB2.0 solvent model to calculate differences in binding free energy between wild type and mutant proteins. Crucially, we made no changes to the scoring model as part of this work on protein-protein binding affinity--the energy model has been developed for structure prediction and has previously been validated only for calculating the energetics of small molecule binding. Here, we compare predictions to experimental data for a set of 418 single residue mutations in 21 targets and find that the MM-GBSA model, on average, performs well at scoring these single protein residue mutations. Correlation between the predicted and experimental change in binding affinity is statistically significant and the model performs well at picking "hotspots," or mutations that change binding affinity by more than 1 kcal/mol. The promising performance of this physics-based method with no tuned parameters for predicting binding energies suggests that it can be transferred to other protein engineering problems.

This study investigated an implicit measure of cognitive processing, the Implicit Association Test (IAT; A. G. Greenwald, D. E. McGhee, & J. L. K. Schwartz, 1998), as a measure of fear-related automatic associations. Sixty-seven students with snake or spider fears completed 4 IAT tasks in which they classified pictures of snakes and spiders along with descriptive words indicating valence, fear, danger, or disgust. Results indicated that all 4 tasks discriminated between fear groups in terms of their implicit associations, and fear-specific effects were significant even after controlling for the impact of valence evaluation. Findings are discussed in terms of applications of the IAT methodology to examine cognitive processing and schemata in anxiety and potential uses for assessing anxiety disorders. [ABSTRACT FROM AUTHOR]

Colleges and universities in the US struggled to provide safe in-person education throughout the COVID-19 pandemic. Testing coupled with isolation is a nimble intervention strategy that can be tailored to mitigate the changing health and economic risks associated with SARS-CoV-2. We developed a decision-support tool to aid in the design of university-based screening strategies using a mathematical model of SARS-CoV-2 transmission. Applying this framework to a large public university reopening in the fall of 2021 with a 60% student vaccination rate, we find that the optimal strategy, in terms of health and economic costs, is twice weekly antigen testing of all students. This strategy provides a 95% guarantee that, throughout the fall semester, case counts would not exceed twice the CDC's original high transmission threshold of 100 cases per 100k persons over 7 days. As the virus and our medical armament continue to evolve, testing will remain a flexible tool for managing risks and keeping campuses open. We have implemented this model as an online tool to facilitate the design of testing strategies that adjust for COVID-19 conditions as well as campus-specific populations, resources, and priorities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Communities worldwide have used vaccines and facemasks to mitigate the COVID-19 pandemic. When an individual opts to vaccinate or wear a mask, they may lower their own risk of becoming infected as well as the risk that they pose to others while infected. The first benefit-reducing susceptibility-has been established across multiple studies, while the second-reducing infectivity-is less well understood. Using a new statistical method, we estimate the efficacy of vaccines and facemasks at reducing both types of risks from contact tracing data collected in an urban setting. We find that vaccination reduced the risk of onward transmission by 40.7% [95% CI 25.8-53.2%] during the Delta wave and 31.0% [95% CI 19.4-40.9%] during the Omicron wave and that mask wearing reduced the risk of infection by 64.2% [95% CI 5.8-77.3%] during the Omicron wave. By harnessing commonly-collected contact tracing data, the approach can broadly provide timely and actionable estimates of intervention efficacy against a rapidly evolving pathogen., (© 2023. The Author(s).)

COVID-19 has disproportionately impacted individuals depending on where they live and work, and based on their race, ethnicity, and socioeconomic status. Studies have documented catastrophic disparities at critical points throughout the pandemic, but have not yet systematically tracked their severity through time. Using anonymized hospitalization data from March 11, 2020 to June 1, 2021 and fine-grain infection hospitalization rates, we estimate the time-varying burden of COVID-19 by age group and ZIP code in Austin, Texas. During this 15-month period, we estimate an overall 23.7% (95% CrI: 22.5-24.8%) infection rate and 29.4% (95% CrI: 28.0-31.0%) case reporting rate. Individuals over 65 were less likely to be infected than younger age groups (11.2% [95% CrI: 10.3-12.0%] vs 25.1% [95% CrI: 23.7-26.4%]), but more likely to be hospitalized (1,965 per 100,000 vs 376 per 100,000) and have their infections reported (53% [95% CrI: 49-57%] vs 28% [95% CrI: 27-30%]). We used a mixed effect poisson regression model to estimate disparities in infection and reporting rates as a function of social vulnerability. We compared ZIP codes ranking in the 75th percentile of vulnerability to those in the 25th percentile, and found that the more vulnerable communities had 2.5 (95% CrI: 2.0-3.0) times the infection rate and only 70% (95% CrI: 60%-82%) the reporting rate compared to the less vulnerable communities. Inequality persisted but declined significantly over the 15-month study period. Our results suggest that further public health efforts are needed to mitigate local COVID-19 disparities and that the CDC's social vulnerability index may serve as a reliable predictor of risk on a local scale when surveillance data are limited., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objective: To design and establish a prospective biospecimen repository that integrates multi-omics assays with clinical data to study mechanisms of controlled injury and healing., Background: Elective surgery is an opportunity to understand both the systemic and focal responses accompanying controlled and well-characterized injury to the human body. The overarching goal of this ongoing project is to define stereotypical responses to surgical injury, with the translational purpose of identifying targetable pathways involved in healing and resilience, and variations indicative of aberrant peri-operative outcomes., Methods: Clinical data from the electronic medical record combined with large-scale biological data sets derived from blood, urine, fecal matter, and tissue samples are collected prospectively through the peri-operative period on patients undergoing 14 surgeries chosen to represent a range of injury locations and intensities. Specimens are subjected to genomic, transcriptomic, proteomic, and metabolomic assays to describe their genetic, metabolic, immunologic, and microbiome profiles, providing a multidimensional landscape of the human response to injury., Results: The highly multiplexed data generated includes changes in over 28,000 mRNA transcripts, 100 plasma metabolites, 200 urine metabolites, and 400 proteins over the longitudinal course of surgery and recovery. In our initial pilot dataset, we demonstrate the feasibility of collecting high quality multi-omic data at pre- and postoperative time points and are already seeing evidence of physiologic perturbation between timepoints., Conclusions: This repository allows for longitudinal, state-of-the-art geno-mic, transcriptomic, proteomic, metabolomic, immunologic, and clinical data collection and provides a rich and stable infrastructure on which to fuel further biomedical discovery., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose/objectives: The abscopal effect could theoretically be potentiated when combined with immunomodulating drugs through increased antigen production. The optimal dosing and schedule of radiotherapy with immunotherapy are unknown, although they are actively investigated in laboratory and clinical models. Clinical data in patients treated for metastatic disease with both modalities may guide future studies., Materials and Methods: This is a single-institution retrospective review of all patients treated with stereotactic body radiotherapy (SBRT)/stereotactic radiosurgery (SRS) and immunomodulating therapy within 6 months before or after SBRT/SRS for metastatic cancer. Clinical and tumor characteristics were recorded, as well as SBRT/SRS details, immunotherapy details, and survival. Log-rank tests on Kaplan-Meier curves for overall survival (OS) that were calculated from the end of SBRT/SRS were used in univariate analysis and Cox proportional hazards regression for multivariate analysis., Results: A total of 125 patients were identified who met the inclusion criteria; 70 received SBRT, and 57 received SRS. Eighty-three patients were treated for non-small cell lung cancer, 7 patients for small cell lung cancer, and 35 patients for other cancers, with the most common one being melanoma. Fifty-three percent of patients received nivolumab, 29% pembrolizumab, 13% atezolizumab, 5% other. Twenty percent received immunotherapy before SBRT/SRS, 39% during SBRT/SRS, 41% after. Eighty-six patients had died by the time of the analysis; the median OS for the whole cohort was 9.7 months. Patients who had completed immunotherapy prior to SBRT/SRS had worse OS than those who received concurrent therapy or immunotherapy after SBRT/SRS, with a difference in median OS of 3.6 months vs. 13.0 months (p = 0.010) that was retained on multivariate analysis (p = 0.011). There was no significant difference in OS between patients receiving SRS vs. SBRT (p = 0.20), sex (p = 0.53), age >62 years (p = 0.76), or lung primary vs. others (p = 0.73) on univariate or multivariate analysis. When comparing before/concurrent to after/concurrent administration, there is a difference in survival with after/concurrent survival of 8.181 months and before survival of 13.010 months, but this was not significant (p = 0.25)., Conclusions: OS appears to be worse in patients who complete immunotherapy prior to SBRT/SRS compared to those receiving it concurrently or after. The design of this retrospective review may be prone to lead time bias, although the difference in median survival is longer than the 6-month window before SBRT/SRS and could only account for part of this difference. Further analysis into causes of death and toxicity and prospective studies are needed to confirm the results of this analysis., Competing Interests: Author PW was employed by Circulogene, Birmingham, AL, United States. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Woody, Hegde, Arastu, Peach, Sharma, Walker and Ju.)

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. Starting in April 2020, the US COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized tens of millions of specific predictions from more than 90 different academic, industry, and independent research groups. A multimodel ensemble forecast that combined predictions from dozens of groups every week provided the most consistently accurate probabilistic forecasts of incident deaths due to COVID-19 at the state and national level from April 2020 through October 2021. The performance of 27 individual models that submitted complete forecasts of COVID-19 deaths consistently throughout this year showed high variability in forecast skill across time, geospatial units, and forecast horizons. Two-thirds of the models evaluated showed better accuracy than a naïve baseline model. Forecast accuracy degraded as models made predictions further into the future, with probabilistic error at a 20-wk horizon three to five times larger than when predicting at a 1-wk horizon. This project underscores the role that collaboration and active coordination between governmental public-health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.

Forecasting the burden of COVID-19 has been impeded by limitations in data, with case reporting biased by testing practices, death counts lagging far behind infections, and hospital census reflecting time-varying patient access, admission criteria, and demographics. Here, we show that hospital admissions coupled with mobility data can reliably predict severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission rates and healthcare demand. Using a forecasting model that has guided mitigation policies in Austin, TX, we estimate that the local reproduction number had an initial 7-d average of 5.8 (95% credible interval [CrI]: 3.6 to 7.9) and reached a low of 0.65 (95% CrI: 0.52 to 0.77) after the summer 2020 surge. Estimated case detection rates ranged from 17.2% (95% CrI: 11.8 to 22.1%) at the outset to a high of 70% (95% CrI: 64 to 80%) in January 2021, and infection prevalence remained above 0.1% between April 2020 and March 1, 2021, peaking at 0.8% (0.7-0.9%) in early January 2021. As precautionary behaviors increased safety in public spaces, the relationship between mobility and transmission weakened. We estimate that mobility-associated transmission was 62% (95% CrI: 52 to 68%) lower in February 2021 compared to March 2020. In a retrospective comparison, the 95% CrIs of our 1, 2, and 3 wk ahead forecasts contained 93.6%, 89.9%, and 87.7% of reported data, respectively. Developed by a task force including scientists, public health officials, policy makers, and hospital executives, this model can reliably project COVID-19 healthcare needs in US cities., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)

A growth-mindset intervention teaches the belief that intellectual abilities can be developed. Where does the intervention work best? Prior research examined school-level moderators using data from the National Study of Learning Mindsets (NSLM), which delivered a short growth-mindset intervention during the first year of high school. In the present research, we used data from the NSLM to examine moderation by teachers' mindsets and answer a new question: Can students independently implement their growth mindsets in virtually any classroom culture, or must students' growth mindsets be supported by their teacher's own growth mindsets (i.e., the mindset-plus-supportive-context hypothesis)? The present analysis (9,167 student records matched with 223 math teachers) supported the latter hypothesis. This result stood up to potentially confounding teacher factors and to a conservative Bayesian analysis. Thus, sustaining growth-mindset effects may require contextual supports that allow the proffered beliefs to take root and flourish.

We used the incidence of spike gene target failures identified during PCR testing to provide an early projection of the prevalence of severe acute respiratory syndrome coronavirus 2 variant B.1.1.7 in a university setting in Texas, USA, before sequencing results were available. Findings from a more recent evaluation validated those early projections.

Intraoperative delineation of tumor margins is critical for effective pancreatic cancer surgery. Yet, intraoperative frozen section analysis of tumor margins is a time-consuming and often challenging procedure that can yield confounding results due to histologic heterogeneity and tissue-processing artifacts. We have previously described the development of the MasSpec Pen technology as a handheld mass spectrometry-based device for nondestructive tissue analysis. Here, we evaluated the usefulness of the MasSpec Pen for intraoperative diagnosis of pancreatic ductal adenocarcinoma based on alterations in the metabolite and lipid profiles in in vivo and ex vivo tissues. We used the MasSpec Pen to analyze 157 banked human tissues, including pancreatic ductal adenocarcinoma, pancreatic, and bile duct tissues. Classification models generated from the molecular data yielded an overall agreement with pathology of 91.5%, sensitivity of 95.5%, and specificity of 89.7% for discriminating normal pancreas from cancer. We built a second classifier to distinguish bile duct from pancreatic cancer, achieving an overall accuracy of 95%, sensitivity of 92%, and specificity of 100%. We then translated the MasSpec Pen to the operative room and predicted on in vivo and ex vivo data acquired during 18 pancreatic surgeries, achieving 93.8% overall agreement with final postoperative pathology reports. Notably, when integrating banked tissue data with intraoperative data, an improved agreement of 100% was achieved. The result obtained demonstrate that the MasSpec Pen provides high predictive performance for tissue diagnosis and compatibility for intraoperative use, suggesting that the technology may be useful to guide surgical decision-making during pancreatic cancer surgeries., Competing Interests: Competing interest statement: M.E.K., J.Z., R.J.D., J.Q.L., C.L.F., J.S., and L.S.E. are inventors in US Patent 10,643,832 and/or in other patent applications related to the MasSpec Pen technology licensed by the University of Texas to MS Pen Technologies, Inc. J.Z., J.S., and L.S.E. are shareholders in MS Pen Technologies, Inc. J.S., L.S.E., and C.L.F. serve as chief medical officer, chief scientific officer, and a consultant, respectively, for MS Pen Technologies, Inc.

Introduction: Early and adequate administration of enteral nutrition (EN) improves outcomes in critical care patients. However, the environment where Critical Care Air Transport teams provide patient care poses particular challenges to achieving the same standard of nutritional support readily administered in civilian intensive care units. Providing the highest standard of nutritional care in austere military environments remains the goal for all patients despite inherent challenges. Enteral nutrition, specifically, is not currently a standard of practice in-flight because of concerns for microaspiration and the associated risk of developing ventilator-associated pneumonia. Clinical concern for aspiration combines with the lack of an EN pump approved for use through Safe-to-Fly testing to further decrease the likelihood of initiating EN in trauma patients. Early EN significantly reduces morbidity and mortality risks; therefore, the lack of nutritional support is contrary to established standards of care in civilian intensive care units. Hence, this literature review proposes to provide a clearer understanding of current EN practices as well as any associated risks within the En Route Care system., Method: A narrative review of literature related to EN in military and civilian flight settings using the PRISMA methodology., Results: A search using the key terms of critical care, air ambulance, EN, nutritional status, and aspiration returned a total of 51,990 articles. A title review followed by a more targeted abstract analysis by the research team generated 39 articles for full-text review. The full-text review then yielded a total of 10 relevant articles for inclusion in the final synthesis table., Conclusions: Overall, the consensus of the literature supports that early evaluation and initiation of standard EN feeding protocols on the ground and during transport improves patient outcomes and enhances injury recovery. However, additional research will determine the current number of patients fed in-flight along with the actual risks and benefits of EN in this population., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)