The evolution of red color vision is linked to coordinated rhodopsin tuning in lycaenid butterflies.

Color vision has evolved multiple times in both vertebrates and invertebrates and is largely determined by the number and variation in spectral sensitivities of distinct opsin subclasses. However, because of the difficulty of expressing long-wavelength (LW) invertebrate opsins in vitro, our understanding of the molecular basis of functional shifts in opsin spectral sensitivities has been biased toward research primarily in vertebrates. This has restricted our ability to address whether invertebrate Gq protein-coupled opsins function in a novel or convergent way compared to vertebrate Gt opsins. Here we develop a robust heterologous expression system to purify invertebrate rhodopsins, identify specific amino acid changes responsible for adaptive spectral tuning, and pinpoint how molecular variation in invertebrate opsins underlie wavelength sensitivity shifts that enhance visual perception. By combining functional and optophysiological approaches, we disentangle the relative contributions of lateral filtering pigments from red-shifted LW and blue short-wavelength opsins expressed in distinct photoreceptor cells of individual ommatidia. We use in situ hybridization to visualize six ommatidial classes in the compound eye of a lycaenid butterfly with a four-opsin visual system. We show experimentally that certain key tuning residues underlying green spectral shifts in blue opsin paralogs have evolved repeatedly among short-wavelength opsin lineages. Taken together, our results demonstrate the interplay between regulatory and adaptive evolution at multiple Gq opsin loci, as well as how coordinated spectral shifts in LW and blue opsins can act together to enhance insect spectral sensitivity at blue and red wavelengths for visual performance adaptation.

A hypothesis for robust polarization vision: an example from the Australian imperial blue butterfly, Jalmenus evagoras.

The Australian lycaenid butterfly Jalmenus evagoras has iridescent wings that are sexually dimorphic, spectrally and in their degree of polarization, suggesting that these properties are likely to be important in mate recognition. We first describe the results of a field experiment showing that free-flying individuals of J. evagoras discriminate between visual stimuli that vary in polarization content in blue wavelengths but not in others. We then present detailed reflectance spectrophotometry measurements of the polarization content of male and female wings, showing that female wings exhibit blue-shifted reflectance, with a lower degree of polarization relative to male wings. Finally, we describe a novel method for measuring alignment of ommatidial arrays: by measuring variation of depolarized eyeshine intensity from patches of ommatidia as a function of eye rotation, we show that (a) individual rhabdoms contain mutually perpendicular microvilli; (b) many rhabdoms in the array have their microvilli misaligned with respect to neighboring rhabdoms by as much as 45 deg; and (c) the misaligned ommatidia are useful for robust polarization detection. By mapping the distribution of the ommatidial misalignments in eye patches of J. evagoras, we show that males and females exhibit differences in the extent to which ommatidia are aligned. Both the number of misaligned ommatidia suitable for robust polarization detection and the number of aligned ommatidia suitable for edge detection vary with respect to both sex and eye patch elevation. Thus, J. evagoras exhibits finely tuned ommatidial arrays suitable for perception of polarized signals, likely to match sex-specific life history differences in the utility of polarized signals.

Emergency Department-Initiated Buprenorphine Treatment in a Population with a High Rate of Homelessness: An Observational Study.

BACKGROUND: Buprenorphine is an effective treatment for opioid use disorders. A previous randomized trial comparing emergency department (ED)-initiated buprenorphine to standard care showed dramatic improvement in follow-up. This is encouraging, but must be replicated to understand the generalizability of buprenorphine treatment. OBJECTIVES: Evaluate the efficacy of an ED-initiated buprenorphine protocol similar to a previous randomized trial in a different population. METHODS: This ED-based descriptive study described the results of a project implementing an opioid use disorder treatment protocol that included buprenorphine. Patients with opioid use disorder were offered treatment with buprenorphine, a buprenorphine prescription whenever possible, and a follow-up visit to a clinic providing addiction treatment. The primary outcome was engagement in formal addiction treatment 30 days after the index visit. RESULTS: Of the 210 patients who accepted referral for outpatient medication-assisted treatment, 95 (45.2%) achieved the primary outcome. Two-thirds of these patients received a buprenorphine prescription at discharge; 40% were homeless. A regression analysis revealed one statistically significant predictor of the primary outcome: patients who were housed were 2.49 times more likely to engage in opioid use disorder treatment than patients who were homeless (p = 0.02). CONCLUSIONS: In this descriptive study of an ED-initiated buprenorphine protocol, follow-up was less than that reported in a previous randomized controlled trial. Two important differences between our study and the randomized trial are the high rate of homelessness and the fact that not every patient received a prescription for buprenorphine. The efficacy of ED-initiated treatment may depend on certain population characteristics.

Searching for the Mechanism that Mediates Mefenoxam-Acquired Resistance in Phytophthora infestans and How It Is Regulated.

Phytophthora infestans, the causal agent of late blight disease of potatoes, is mainly controlled by the use of fungicides. Isolates that are resistant to commonly used fungicides have been reported. Also, several studies show that originally mefenoxam-sensitive isolates acquire resistance to this fungicide when exposed to sublethal concentrations. This phenomenon, termed "mefenoxam-acquired resistance," has been observed in different Phytophthora species and seems to be unique to mefenoxam. In this study, we aimed to elucidate the molecular mechanism mediating this type of resistance as well as a possible regulatory process behind it. A combination of computational analyses and experimental approaches was used to identify differentially expressed genes with a potential association to the phenomenon. These genes were classified into seven functional groups. Most of them seem to be associated with a pleiotropic drug resistance (PDR) phenotype, typically involved in the expulsion of diverse metabolites, drugs, or other substances out of the cell. Despite the importance of RNA Polymerase I for the constitutive resistance of P. infestans to mefenoxam, our results indicate no clear interaction between this protein and the acquisition of mefenoxam resistance. Several small non-coding RNAs were found to be differentially expressed and specifically related to genes mediating the PDR phenotype, thus suggesting a possible regulatory process. We propose a model of the molecular mechanisms acting within the cell when P. infestans acquires resistance to mefenoxam after exposed to sublethal concentrations of the fungicide. This study provides important insights into P. infestans' cellular and regulatory functionalities.

Evaluation of the ventilatory effects on human subjects in prolonged hip-flexed/head-down restraint position.

BACKGROUND: The restraint chair is a tool used by law enforcement and correction personnel to control aggressive, agitated individuals. When initiating its use, subjects are often placed in a hip-flexed/head-down (HFHD) position to remove handcuffs. Usually, this period of time is less than two minutes but can become more prolonged in particularly agitated patients. Some have proposed this positioning limits ventilation and can result in asphyxia. The aim of this study is to evaluate if a prolonged HFHD restraint position causes significant ventilatory compromise. METHODS: Subjects exercised on a stationary bicycle until they reached 85% of their predicted maximal heart rate. They were then handcuffed with their hands behind their back and placed into a HFHD seated position for five minutes. The primary outcome measurement was maximal voluntary ventilation (MVV). This was measured at baseline, after initial placement into the HFHD position, and after five minutes of being in the position while still maintaining the HFHD position. Baseline measurements were compared with final measurements for statistically significant differences. RESULTS: We analyzed data for 15 subjects. Subjects had a mean MVV of 165.3 L/min at baseline, 157.8 L/min after initially being placed into the HFHD position, and a mean of 138.7 L/min after 5 min in the position. The mean baseline % predicted MVV was 115%; after 5 min in the HFHD position the mean was 96%. This 19% absolute difference was statistically significant (p = 0.001). CONCLUSIONS: In healthy seated male subjects with recent exertion, up to five minutes in a HFHD position results in a small decrease in MVV compared with baseline MVV levels. Even with this decrease, mean MVV levels were still 96% of predicted after five minutes. Though a measurable decrease was found, there was no clinically significant change that would support that this positioning would lead to asphyxia over a five-minute time period.

An Unusual Case of Neonatal High-Output Heart Failure: Infantile Hepatic Hemangioma.

BACKGROUND: Infantile hepatic hemangioma (IHH) is a rare but life-threatening disorder that must be considered in the newborn presenting with high-output heart failure (HF). IHH is a tumor comprised of large vascular beds, which require a significant increase in blood flow as the lesion grows. This, in turn, creates an undue burden on the cardiovascular system, leading to high-output HF and potentially, respiratory distress. Recent changes have been made in the classification of certain hepatic hemangiomas and their treatments. CASE REPORT: A 10-day-old girl presented to the Emergency Department with increased respiratory effort and an episode of apnea and cyanosis. A chest x-ray study was obtained and showed cardiomegaly and pulmonary edema concerning for HF. The patient was promptly admitted to the pediatric intensive care unit, where advanced imaging was obtained revealing findings consistent with IHH. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: HF in an infant is a critical condition often requiring prompt intervention and rapid diagnosis of the correct etiology to save a life. IHH is an example of an extrathoracic etiology of pediatric HF that has undergone recent changes in terminology and diagnosis. Increased awareness among emergency physicians of this disease process and its treatments can lead to expeditious diagnosis and treatment of this potentially life-threatening illness.

Is the Phenomenon of Mefenoxam-Acquired Resistance in Phytophthora infestans Universal?

Phytophthora infestans is the causal agent of late blight disease of potatoes and tomatoes. This disease causes devastating economic losses each year, and control is mainly achieved by the use of fungicides. Unfortunately, populations of P. infestans resistant to fungicides have been documented. Furthermore, studies have reported that sensitive isolates to the phenylamide fungicide, mefenoxam, become less sensitive in vitro after a single passage through sublethal concentrations of fungicide-amended medium. The first objective of this study was to investigate if isolates of P. infestans are capable of acquiring resistance to two additional systemic fungicides, fluopicolide (benzamide) and cymoxanil (cyanoacetamide-oxime). In contrast to the situation with mefenoxam, exposure of isolates to sublethal concentrations of fluopicolide and cymoxanil did not induce reduced sensitivity to these two fungicides. The second objective was to assess if reduced sensitivity to mefenoxam could occur in naturally sensitive isolates of other Phytophthora species and of Phytopythium sp., another oomycete plant pathogen. All Phytophthora spp. assessed (P. infestans, P. betacei, and P. pseudocryptogea) as well as Phytopythium sp. acquired resistance to mefenoxam after previous exposure through medium containing 1 µg ml-1 of mefenoxam. Interestingly, isolate 66 of Phytopythium sp. and the isolate of P. pseudocryptogea tested do not seem to be acquiring resistance to mefenoxam after exposure to medium containing 5 µg ml-1 of this fungicide. The tested isolates of P. palmivora and P. cinnamomi were extremely sensitive to mefenoxam, and thus it was not possible to perform a second transfer to access acquisition of resistance to this fungicide.

Systematic Review: The Role of Intravenous and Oral Contrast in the Computed Tomography Evaluation of Acute Appendicitis.

BACKGROUND: This systematic review provides practicing emergency physicians updated information regarding the role of oral and intravenous contrast in the computed tomography (CT) evaluation of acute appendicitis. METHODS: A PubMed literature search was conducted from January 1, 1996 to December 31, 2018 and limited to human clinical trials written in English with relevant keywords. High-quality studies were identified and then underwent a structured review. Recommendations are made based on the literature review. RESULTS: Fifty-seven articles met criteria for rigorous review, of which 14 were appropriate for citation in this review. Excellent evidence shows that oral contrast does not improve the test characteristics of CT with intravenous contrast (IVCT) in the evaluation of adults suspected of having acute appendicitis. Good evidence shows that noncontrast abdominal CTs have excellent test characteristics for this same group of patients. CONCLUSIONS: Considering its downsides and lack of utility, the medical literature does not support using oral contrast in the evaluation of acute appendicitis. There is no direct evidence showing that IVCT is better than a noncontrast CT in the evaluation of acute appendicitis; however, the available literature is consistent with slightly better test characteristics for IVCTs. Still, if IVCT cannot be obtained in a timely manner, noncontrast CTs are extremely accurate in detecting this disease.

Systematic Review: The Role of Thrombolysis in Intermediate-Risk Pulmonary Embolism.

BACKGROUND: This systemic review provides practicing emergency physicians updated information about the role of thrombolysis in the treatment of intermediate-risk pulmonary embolism. METHODS: A PubMed literature search from January 1, 2005 to December 31, 2018 was conducted and limited to human clinical trials written in English with relevant keywords. High-quality studies were identified and then underwent a structured review. Recommendations are made based on the literature review. RESULTS: Sixty-three articles met criteria for rigorous review, of which 13 were appropriate for citation in this review. Of these 13, there were 6 prospective studies and 7 retrospective studies. CONCLUSIONS: Thrombolysis, either catheter-directed or systemic, is a treatment option in the management of patients with intermediate-risk pulmonary embolism and a high likelihood of clinical deterioration. Each method of thrombolysis carries risks and benefits. Based on the available evidence, transfer to a facility for the purpose of catheter-directed thrombolysis is not recommended.

Emergency Department Evaluation After Conducted Energy Weapon Use: Review of the Literature for the Clinician.

BACKGROUND: Conductive energy weapons (CEWs) are used daily by law enforcement, and patients are often brought to emergency departments (EDs) for medical clearance. OBJECTIVE: Our aim was to review the medical literature on the topic of CEWs and to offer evidence-based recommendations to emergency physicians for evaluation and treatment of patients who have received a CEW exposure. METHODS: A MEDLINE literature search from 1988 to 2018 was performed and limited to human studies published from January 1, 1988 to November 1, 2018 written in English with the following keywords: TASER, conductive energy device(s), electronic weapon(s), conductive energy weapon(s), non-lethal weapon(s), conducted energy device(s), conducted energy weapon(s), conductive electronic device(s), and electronic control device(s). Studies identified then underwent a structured review from which results could be evaluated. RESULTS: Two hundred and sixty-three articles on CEWs were screened and 37 appropriate articles were rigorously reviewed. Evaluation and treatment recommendations are presented. These studies did not report any evidence of dangerous laboratory abnormalities, physiologic changes, or immediate or delayed cardiac ischemia or dysrhythmias after exposure to CEW electrical discharges of up to 15 s. CONCLUSIONS: The current medical literature does not support routine performance of laboratory studies, electrocardiography, or prolonged ED observation or hospitalization for ongoing cardiac monitoring after CEW exposure in an otherwise asymptomatic awake and alert patient.

Acquired Resistance to Mefenoxam in Sensitive Isolates of Phytophthora infestans.

The systemic fungicide mefenoxam has been important in the control of late blight disease caused by Phytophthora infestans. This phenylamide fungicide has a negative effect on the synthesis of ribosomal RNA; however, the genetic basis for inherited field resistance is still not completely clear. We recently observed that a sensitive isolate became tolerant after a single passage on mefenoxam-containing medium. Further analyses revealed that all sensitive isolates tested (in three diverse genotypes) acquired this resistance equally quickly. In contrast, isolates that were "resistant" to mefenoxam in the initial assessment (stably resistant) did not increase in resistance upon further exposure. However, there appeared to be a cost associated with acquired resistance in the initially sensitive isolates, in that isolates with acquired resistance grew more slowly on mefenoxam-free medium than did the same isolates that had never been exposed to mefenoxam. The acquired resistance of the sensitive isolates declined slightly with subsequent culturing on medium free of mefenoxam. To investigate the mechanism of acquired resistance, we employed strand-specific RNA sequencing. Many differentially expressed genes were genotype specific, but one set of genes was differentially expressed in all genotypes. Among these were several genes (a phospholipase "Pi-PLD-like-3," two ATP-binding cassette superfamily [ABC] transporters, and a mannitol dehydrogenase) that were up-regulated and whose function might contribute to a resistance phenotype.

A global phylogeny of butterflies reveals their evolutionary history, ancestral hosts and biogeographic origins.

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin ~100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants.

Urine testing is associated with inappropriate antibiotic use and increased length of stay in emergency department patients.

Background: Exposing patients with a low probability of disease to diagnostic testing with poor test characteristics leads to false positive results. Providers often act on these false results, which can cause unnecessary evaluation and treatment. The treatment of asymptomatic bacteriuria is discouraged, but it still frequently occurs in the inpatient setting; it is less studied in the Emergency Department (ED). In this study, we examine associations between urine testing, inappropriate antibiotic use, and length of stay in discharged ED patients at risk of urinary tract infection (UTI) misdiagnosis. Methods: A cohort of discharged ED patients at risk of UTI misdiagnosis was created by pulling visit information for patients presenting with abdominal pain, chest pain, headache, vaginal bleeding in pregnancy, and elderly females with weakness or confusion. Predictors of urine testing, and urinary tract infection treatment were determined with logistic regression analysis. A chart review of a representative sample of this cohort was then completed screening for the presence of urinary tract symptoms and urine culture results. Linear regression analysis was then used to generate an adjusted mean difference in length of stay between patients who had urine testing compared to those who did not. Results: About a quarter of chest pain and headache patients had urine testing, while approximately 75% of abdominal pain patients, vaginal bleeding in pregnancy, and elderly females with weakness or confusion did. Except for chest pain patients, the UTI treatment rate was more than double the positive culture rate, indicating overtreatment. A diagnosis of UTI is based on a combination of UTI symptoms and positive urine cultures, yet only about 15% of patients treated for UTI met these criteria. Lastly, in all chief complaint groups, the length of stay was significantly longer-30 min or more-for those who had urine testing compared to matched controls. Conclusions: In this observational study of patients at risk of UTI misdiagnosis, urine testing was associated with inappropriate antibiotic use and delayed discharge. There is pressure on providers to perform diagnostic testing, but in patients without specific UTI symptoms, urine testing might cause more harm than benefit.

A retrospective review of antibiotic use for acute respiratory infections in urgent-care patients.

Objective: We examined the use of antibiotics for acute respiratory infections in an urgent-care setting. Design: Retrospective database review. Setting: The study was conducted in 2 urgent-care clinics staffed by academic emergency physicians in San Diego, California. Patients: Visits for acute respiratory infections were identified based on presenting complaints. Methods: The primary outcome was a discharge prescription for an antibiotic. The patient and provider characteristics that predicted this outcome were analyzed using logistic regression. The variation in antibiotic prescriptions between providers was also analyzed. Results: In total, 15,160 visits were analyzed. The patient characteristics were not predictive of antibiotic treatment. Physicians were more likely than advanced practice practitioners to prescribe antibiotics (1.31; 95% confidence interval [CI], 1.21-1.42). For every year of seniority, a provider was 1.03 (95% CI, 1.02-1.03) more likely to prescribe an antibiotic. Although the providers saw similar patients, we detected significant variation in the antibiotic prescription rate between providers: the mean antibiotic prescription rate within the top quartile was 54.3% and the mean rate in the bottom quartile was 21.7%. Conclusions: The patient and provider characteristics we examined were either not predictive or were only weakly predictive of receiving an antibiotic prescription for acute respiratory infection. However, we detected a marked variation between providers in the rate of antibiotic prescription. Provider differences, not patient differences, drive variations in antibiotic prescriptions. Stewardship efforts may be more effective if directed at providers rather than patients.

A high-throughput multispectral imaging system for museum specimens.

We present an economical imaging system with integrated hardware and software to capture multispectral images of Lepidoptera with high efficiency. This method facilitates the comparison of colors and shapes among species at fine and broad taxonomic scales and may be adapted for other insect orders with greater three-dimensionality. Our system can image both the dorsal and ventral sides of pinned specimens. Together with our processing pipeline, the descriptive data can be used to systematically investigate multispectral colors and shapes based on full-wing reconstruction and a universally applicable ground plan that objectively quantifies wing patterns for species with different wing shapes (including tails) and venation systems. Basic morphological measurements, such as body length, thorax width, and antenna size are automatically generated. This system can increase exponentially the amount and quality of trait data extracted from museum specimens.

Evidence of nutrient translocation in response to smoke exposure by the East African ant acacia, Vachellia drepanolobium.

Fire is a major selective force on arid grassland communities, favoring traits such as the smoke-induced seed germination response seen in a wide variety of plant species. However, little is known about the relevance of smoke as a cue for plants beyond the seedling stage.We exposed a fire-adapted savanna tree, Vachellia (=Acacia) drepanolobium, to smoke and compared nutrient concentrations in leaf and root tissues to unexposed controls. Experiments were performed on three age cohorts: 2-year-old, 9-month-old, and 3-month-old plants.For the 2-year-old plants exposed to smoke, carbon and nitrogen concentrations were lower in the leaves and higher in the roots than controls. Less pronounced trends were found for boron and magnesium.In contrast, smoke-exposed 3-month-old plants had lower root nitrogen concentrations than controls. No significant differences were found in the 9-month-old plants, and no significant shifts in other nutrient concentrations were observed between plant tissues for any of the three age cohorts. Synthesis: Our findings are consistent with smoke-induced translocation of nutrients from leaves to roots in 2-year-old V. drepanolobium. This could represent a novel form of fire adaptation, with variation over the course of plant development. The translocation differences between age cohorts highlight the need to investigate smoke response in older plants of other species. Accounting for this adaptation could better inform our understanding of savanna community structure and nutrient flows under fire regimes altered by anthropogenic land use and climate change.

Tourniquets exposed to the Afghanistan combat environment have decreased efficacy and increased breakage compared to unexposed tourniquets.

We hypothesize that an anecdotally observed increase in tourniquet breakage and decrease in efficacy may be secondary to environmental exposure during military deployment. This was a study comparing efficacy and breakage of 166 Afghanistan-exposed tourniquets to 166 unexposed tourniquets. Afghanistan exposure was defined as tourniquet carriage by field staff in the operational environment for approximately 6 months. In a controlled environment in the United States, a previously exposed tourniquet was tested on one thigh of each subject, while an unexposed tourniquet was tested on the opposite thigh. We recorded tourniquet efficacy (absence of distal pedal pulse for at least 30 seconds), breakage, and the number of turns required to stop the distal pedal pulse. A Wilcoxon sign-rank test was used to test differences between exposed and unexposed tourniquets. Tourniquets exposed to the environment broke more often (14/166 versus 0/166) and had decreased efficacy (63% versus 91%; p < 0.001). Three turns were required for most tourniquets to be efficacious. Environmental exposure of military tourniquets is associated with decreased efficacy and increased breakage. In most cases, tourniquets require three turns to stop the distal lower extremity pulse.

Physical and behavioral adaptations to prevent overheating of the living wings of butterflies.

The wings of Lepidoptera contain a matrix of living cells whose function requires appropriate temperatures. However, given their small thermal capacity, wings can overheat rapidly in the sun. Here we analyze butterfly wings across a wide range of simulated environmental conditions, and find that regions containing living cells are maintained at cooler temperatures. Diverse scale nanostructures and non-uniform cuticle thicknesses create a heterogeneous distribution of radiative cooling that selectively reduces the temperature of structures such as wing veins and androconial organs. These tissues are supplied by circulatory, neural and tracheal systems throughout the adult lifetime, indicating that the insect wing is a dynamic, living structure. Behavioral assays show that butterflies use wings to sense visible and infrared radiation, responding with specialized behaviors to prevent overheating of their wings. Our work highlights the physiological importance of wing temperature and how it is exquisitely regulated by structural and behavioral adaptations.

The Cost of Deploying a Role 2 Medical Asset to Afghanistan.

OBJECTIVES: The costs of military assets, including medical resources, are necessary for military planners when determining their force make up. The monetary cost of operating a Role 3 unit, the most comprehensive medical asset in the combat theater, has been determined. The cost of operating a Role 2 (R2) facility-the less comprehensive but more common asset-has not been assessed. Here we estimate the cost of operating an R2 medical asset in Afghanistan. METHODS: Personnel costs were assessed by combining the U.S. Department of Defense estimate for personnel cost with the replacement costs for deployed staff. Manning was for a U.S. Marine Corps Shock Trauma Platoon and Forward Resuscitative Surgical System. RESULTS: It costs $2,956,873 a month to operate an R2 medical facility in Afghanistan. It also takes the place of a rifle platoon and disrupts the domestic military health care mission. CONCLUSION: The costs of operating an R2 medical facility are significant and should be considered when the medical benefits of an R2 are unclear.