Tuning the potency and selectivity of ImmTAC molecules by affinity modulation.

T-cell-engaging bispecifics have great clinical potential for the treatment of cancer and infectious diseases. The binding affinity and kinetics of a bispecific molecule for both target and T-cell CD3 have substantial effects on potency and specificity, but the rules governing these relationships are not fully understood. Using immune mobilizing monoclonal TCRs against cancer (ImmTAC) molecules as a model, we explored the impact of altering affinity for target and CD3 on the potency and specificity of the redirected T-cell response. This class of bispecifics binds specific target peptides presented by human leukocyte antigen on the cell surface via an affinity-enhanced T-cell receptor and can redirect T-cell activation with an anti-CD3 effector moiety. The data reveal that combining a strong affinity TCR with an intermediate affinity anti-CD3 results in optimal T-cell activation, while strong affinity of both targeting and effector domains significantly reduces maximum cytokine release. Moreover, by optimizing the affinity of both parts of the molecule, it is possible to improve the selectivity. These results could be effectively modelled based on kinetic proofreading with limited signalling. This model explained the experimental observation that strong binding at both ends of the molecules leads to reduced activity, through very stable target-bispecific-effector complexes leading to CD3 entering a non-signalling dark state. These findings have important implications for the design of anti-CD3-based bispecifics with optimal biophysical parameters for both activity and specificity.

Sulfur Nutrition Affects Garlic Bulb Yield and Allicin Concentration.

Improving bulb yield and allicin content of garlic is important in meeting fresh and pharmaceutical market demands. Garlic plants have a high demand for sulfur (S) since allicin contains S atoms. Two experiments were conducted to identify the effect of S application rate on garlic yield and quality. In a field trial assessing six S application rates (0-150 kg S ha-1), cultivar 'Glenlarge' produced the greatest bulb weight (~90 g) and allicin content (521 mg bulb-1) with the application of 75 kg S ha-1. In contrast, cultivar 'Southern Glen' showed no response in bulb weight or allicin. This was likely due to high soil background S concentrations masking treatment effects. Subsequently, a solution culture experiment with cv. 'Glenlarge' evaluated six S application rates (188 to 1504 mg S plant-1, nominally equivalent to 25-200 kg S ha-1). In solution culture, bulb weight and allicin concentration increased with S rate. Highest bulb weight (~53 g bulb-1) and allicin concentration (~11 mg g-1 DW) were recorded at an S application of 1504 mg S plant-1. This is the first report to conclusively demonstrate the effect of S on yield and allicin in garlic grown in solution culture.

Therapeutic high affinity T cell receptor targeting a KRASG12D cancer neoantigen.

Neoantigens derived from somatic mutations are specific to cancer cells and are ideal targets for cancer immunotherapy. KRAS is the most frequently mutated oncogene and drives the pathogenesis of several cancers. Here we show the identification and development of an affinity-enhanced T cell receptor (TCR) that recognizes a peptide derived from the most common KRAS mutant, KRASG12D, presented in the context of HLA-A*11:01. The affinity of the engineered TCR is increased by over one million-fold yet fully able to distinguish KRASG12D over KRASWT. While crystal structures reveal few discernible differences in TCR interactions with KRASWT versus KRASG12D, thermodynamic analysis and molecular dynamics simulations reveal that TCR specificity is driven by differences in indirect electrostatic interactions. The affinity enhanced TCR, fused to a humanized anti-CD3 scFv, enables selective killing of cancer cells expressing KRASG12D. Our work thus reveals a molecular mechanism that drives TCR selectivity and describes a soluble bispecific molecule with therapeutic potential against cancers harboring a common shared neoantigen.

Unconventional modes of peptide-HLA-I presentation change the rules of TCR engagement.

The intracellular proteome of virtually every nucleated cell in the body is continuously presented at the cell surface via the human leukocyte antigen class I (HLA-I) antigen processing pathway. This pathway classically involves proteasomal degradation of intracellular proteins into short peptides that can be presented by HLA-I molecules for interrogation by T-cell receptors (TCRs) expressed on the surface of CD8+ T cells. During the initiation of a T-cell immune response, the TCR acts as the T cell's primary sensor, using flexible loops to mould around the surface of the pHLA-I molecule to identify foreign or dysregulated antigens. Recent findings demonstrate that pHLA-I molecules can also be highly flexible and dynamic, altering their shape according to minor polymorphisms between different HLA-I alleles, or interactions with different peptides. These flexible presentation modes have important biological consequences that can, for example, explain why some HLA-I alleles offer greater protection against HIV, or why some cancer vaccine approaches have been ineffective. This review explores how these recent findings redefine the rules for peptide presentation by HLA-I molecules and extend our understanding of the molecular mechanisms that govern TCR-mediated antigen discrimination.

Detection and Distribution of Viruses Infecting Garlic Crops in Australia.

The distribution of viruses in eastern Australian field garlic was evaluated. Detection assays were developed that involved generic RT-PCR for viruses in the Allexivirus, Carlavirus and Potyvirus genera followed by virus-specific colorimetric dot-blot hybridization. Assays targeted the potyviruses (onion yellow dwarf virus (OYDV), shallot yellow stripe virus (SYSV), and leek yellow stripe virus (LYSV)), the carlaviruses (garlic common latent virus (GCLV) and shallot latent virus (SLV)), and the allexiviruses (garlic viruses A, B, C, X (GarVA, -B, -C, -X) and shallot virus X (ShVX)). Virus incidence in crops was consistently high, with most plants infected with at least one virus from each genus. OYDV, LYSV, SLV, and GCLV were commonly detected. Three of the four allexiviruses were in all districts surveyed but varied in incidence, whereas ShVX and SYSV were not detected. There was no association between virus species complement and bulb size, indicating size is not a good predictor of the virus status of planting material. The variation of virus incidence across different Australian growing districts and in different cultivars implies multiple introductions of viruses rather than spread within the country. The genetic diversity observed within coat protein sequences of some virus species also supports multiple separate introductions.

Comparison of Air Force, Army, and Navy Emergency Medical Technician Candidates' Performance on the National Registry Cognitive Examination.

INTRODUCTION: Military medics function similarly to civilian emergency medical technicians (EMTs); however, they perform their emergency medical care in combat zones and military treatment facilities. Both civilian and military EMTs must take and pass the National Registry of EMT's cognitive examination to be certified as a Nationally Registered EMT; however, there is a discrepancy in requirements for obtaining and maintaining National EMT Certification between the military branches of the DoD. In our study, we aimed to compare the performance of the U.S. Air Force (USAF), U.S. Army (USA), and U.S. Navy (USN) EMT candidates on the National EMT Certification cognitive examination from 2015 to 2017. MATERIALS AND METHODS: We performed a cross-sectional analysis of the National Registry of EMT's database for the examination results of all military EMT candidates who attempted the National EMT Certification cognitive examination between January 1, 2015, and December 31, 2017. First and cumulative third attempt pass rates and cognitive performance from mean ability estimates (MAEs) on the examination were assessed. Descriptive statistics were calculated and comparisons between branches with regard to passing rates and MAEs were made using chi-square tests and ANOVA, respectively, at the alpha level of 0.05. RESULTS: During the 3-year study period, a total of 3,642 USAF, 14,050 USA, and 1,187 USN candidates attempted the cognitive examination one or more times. The USA candidates demonstrated the highest first attempt pass rates (2015: 78%; 2016: 78%; and 2017: 81%) followed by the USAF candidates (2015: 58%; 2016: 62%; and 2017: 64%) and the USN candidates (2015: 41%; 2016: 56%; and 2017: 62%). The cumulative third attempt pass rates followed a similar trend (e.g., USA: 2015: 94%; 2016: 95%; and 2017: 96%). These differences by branch were statistically significant for each year (P < .001). The overall test MAE scores also differed by branch, but only the USN candidates' MAE scores differed by year. The USA candidates demonstrated the highest MAE from 2015 to 2017 (523) followed by the USAF (489) and the USN (464) candidates. The overall test MAE scores for the USN candidates improved over the study period (2015: 449; 2016: 475; and 2017: 479, P < .001). CONCLUSION: Military EMT candidates had different performances on the EMT cognitive examination between branches. The USA candidates demonstrated higher pass rates and cognitive performance on the examination compared to their counterparts from the USAF and USN from 2015 to 2017. Further work should be directed at defining the cause of the differences in military EMT candidate performance and determining the characteristics that impact these differences.

Molecular Rules Underpinning Enhanced Affinity Binding of Human T Cell Receptors Engineered for Immunotherapy.

Immuno-oncology approaches that utilize T cell receptors (TCRs) are becoming highly attractive because of their potential to target virtually all cellular proteins, including cancer-specific epitopes, via the recognition of peptide-human leukocyte antigen (pHLA) complexes presented at the cell surface. However, because natural TCRs generally recognize cancer-derived pHLAs with very weak affinities, efforts have been made to enhance their binding strength, in some cases by several million-fold. In this study, we investigated the mechanisms underpinning human TCR affinity enhancement by comparing the crystal structures of engineered enhanced affinity TCRs with those of their wild-type progenitors. Additionally, we performed molecular dynamics simulations to better understand the energetic mechanisms driving the affinity enhancements. These data demonstrate that supra-physiological binding affinities can be achieved without altering native TCR-pHLA binding modes via relatively subtle modifications to the interface contacts, often driven through the addition of buried hydrophobic residues. Individual energetic components of the TCR-pHLA interaction governing affinity enhancements were distinct and highly variable for each TCR, often resulting from additive, or knock-on, effects beyond the mutated residues. This comprehensive analysis of affinity-enhanced TCRs has important implications for the future rational design of engineered TCRs as efficacious and safe drugs for cancer treatment.

T cell receptor interactions with human leukocyte antigen govern indirect peptide selectivity for the cancer testis antigen MAGE-A4.

T cell-mediated immunity is governed primarily by T cell receptor (TCR) recognition of peptide-human leukocyte antigen (pHLA) complexes and is essential for immunosurveillance and disease control. This interaction is generally stabilized by interactions between the HLA surface and TCR germline-encoded complementarity-determining region (CDR) loops 1 and 2, whereas peptide selectivity is guided by direct interactions with the TCR CDR3 loops. Here, we solved the structure of a newly identified TCR in complex with a clinically relevant peptide derived from the cancer testis antigen melanoma antigen-A4 (MAGE-A4). The TCR bound pHLA in a position shifted toward the peptide's N terminus. This enabled the TCR to achieve peptide selectivity via an indirect mechanism, whereby the TCR sensed the first residue of the peptide through HLA residue Trp-167, which acted as a tunable gateway. Amino acid substitutions at peptide position 1 predicted to alter the HLA Trp-167 side-chain conformation abrogated TCR binding, indicating that this indirect binding mechanism is essential for peptide recognition. These findings extend our understanding of the molecular rules that underpin antigen recognition by TCRs and have important implications for the development of TCR-based therapies.

Variation in zinc concentration of sweetcorn kernels reflects source-sink dynamics influenced by kernel number.

Grain yield and mineral nutrient concentration in cereal crops are usually inversely correlated, undermining biofortification efforts. Here, sink size, expressed as kernel number per cob, was manipulated by controlling the time when the silks of sweetcorn (Zea mays) cv. Hybrix 5 and var. HiZeax 103146 were exposed to pollen. Twelve other varieties were manually pollinated to achieve the maximum potential kernel number per cob, and kernel Zn concentration was correlated with kernel number and kernel mass. As kernel number increased, kernel Zn concentration decreased, with the decrease occurring to similar extents in the embryo tissue and the rest of the kernel. However, total kernel Zn accumulated per cob increased with increasing kernel number, as the small decreases in individual kernel Zn concentration were more than offset by increases in kernel number. When both kernel number and mass were considered, 90% of the variation in kernel Zn concentration was accounted for. Differential distribution of assimilates and Zn to sweetcorn cobs led to significant decreases in kernel Zn concentration with increasing kernel number. This suggests there will be challenges to achieving high kernel Zn concentrations in modern high-yielding sweetcorn varieties unless genotypes with higher Zn translocation rates into kernels can be identified.

Specificity of bispecific T cell receptors and antibodies targeting peptide-HLA.

Tumor-associated peptide-human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface-expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.

TCRs with Distinct Specificity Profiles Use Different Binding Modes to Engage an Identical Peptide-HLA Complex.

The molecular rules driving TCR cross-reactivity are poorly understood and, consequently, it is unclear the extent to which TCRs targeting the same Ag recognize the same off-target peptides. We determined TCR-peptide-HLA crystal structures and, using a single-chain peptide-HLA phage library, we generated peptide specificity profiles for three newly identified human TCRs specific for the cancer testis Ag NY-ESO-1157-165-HLA-A2. Two TCRs engaged the same central peptide feature, although were more permissive at peripheral peptide positions and, accordingly, possessed partially overlapping peptide specificity profiles. The third TCR engaged a flipped peptide conformation, leading to the recognition of off-target peptides sharing little similarity with the cognate peptide. These data show that TCRs specific for a cognate peptide recognize discrete peptide repertoires and reconciles how an individual's limited TCR repertoire following negative selection in the thymus is able to recognize a vastly larger antigenic pool.

Dispatcher Identification of Out-of-Hospital Cardiac Arrest and Neurologically Intact Survival: A Retrospective Cohort Study.

INTRODUCTION: To date, there are no published data on the association of patient-centered outcomes and accurate public-safety answering point (PSAP) dispatch in an American population. The goal of this study is to determine if PSAP dispatcher recognition of out-of-hospital cardiac arrest (OHCA) is associated with neurologically intact survival to hospital discharge. METHODS: This retrospective cohort study is an analysis of prospectively collected Quality Assurance/Quality Improvement (QA/QI) data from the San Antonio Fire Department (SAFD; San Antonio, Texas USA) OHCA registry from January 2013 through December 2015. Exclusion criteria were: Emergency Medical Services (EMS)-witnessed arrest, traumatic arrest, age <18 years old, no dispatch type recorded, and missing outcome data. The primary exposure was dispatcher recognition of cardiac arrest. The primary outcome was neurologically intact survival (defined as Cerebral Performance Category [CPC] 1 or 2) to hospital discharge. The secondary outcomes were: bystander cardiopulmonary resuscitation (CPR), automated external defibrillator (AED) use, and prehospital return of spontaneous return of circulation (ROSC). RESULTS: Of 3,469 consecutive OHCA cases, 2,569 cases were included in this analysis. The PSAP dispatched 1,964/2,569 (76.4%) of confirmed OHCA cases correctly. The PSAP dispatched 605/2,569 (23.6%) of confirmed OHCA cases as another chief complaint. Neurologically intact survival to hospital discharge occurred in 99/1,964 (5.0%) of the recognized cardiac arrest group and 28/605 (4.6%) of the unrecognized cardiac arrest group (OR = 1.09; 95% CI, 0.71-1.70). Bystander CPR occurred in 975/1,964 (49.6%) of the recognized cardiac arrest group versus 138/605 (22.8%) of the unrecognized cardiac arrest group (OR = 3.34; 95% CI, 2.70-4.11). CONCLUSION: This study found no association between PSAP dispatcher identification of OHCA and neurologically intact survival to hospital discharge. Dispatcher identification of OHCA remains an important, but not singularly decisive link in the OHCA chain of survival.

Acute Flares of Knee Osteoarthritis (the ACT-FLARE Study): Protocol for a Web-Based Case-Crossover Study in Community-Dwelling Adults.

BACKGROUND: The cardinal feature of osteoarthritis (OA) is pain. Although heterogeneity in pain and function have been demonstrated in the long-term course of OA, the more proximate determinants of acute flare-ups remain less clear. How short-term intermittent or transient exposures trigger acute flare-ups has important implications for effective and sustainable self-management strategies. OBJECTIVE: The primary objective of this study is to identify potential triggers of acute flares in knee OA. Secondary objectives are to determine their course and consequences and describe high-risk participant profiles. METHODS: We carried out a Web-based case-crossover study. This study aims to recruit 620 community-dwelling adults aged ≥40 years, resident in England, and who have knee pain, with or without a recorded diagnosis of knee OA, and no preexisting diagnosis of inflammatory arthropathy. Participants will be recruited via 3 routes: (1) general practice registers, (2) offline community advertisement, and (3) online social media advertisement. By using questionnaires comparing periods before participants' self-reported flare-up episodes (hazard periods) with periods during the study when their knee OA symptoms are stable (control periods), triggers preceding flare-ups will be identified and examined using conditional logistic regression. Time-to-resolution of flare-up will be examined by monitoring people's daily pain, bothersomeness, and medication usage until the participant reports when their flare-up episode ends. Rates of flare-ups will be examined across different participant and flare characteristics using regression models to identify high-risk participant profiles. A study-specific Patient Advisory Group (PAG) is providing suggestion, input, and ongoing support for all stages of the research process. RESULTS: Participant recruitment opened in July 2018 and is anticipated to continue for 6 months. The study results will be disseminated through a number of channels, including relevant national or international conferences and peer-reviewed publication in a medical journal, via advocacy or charity organizations, such as Versus Arthritis and across social media. Findings will be fed back to members of our PAG, study participants, and clinicians from participating primary care general practices. The PAG will also take an active role in the overall dissemination strategy. CONCLUSIONS: This study will provide empirical evidence to help patients identify common knee OA flare triggers and provide health care professionals with questions to identify patients at most risk of frequent flare-ups. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13428.

Speciation and accumulation of Zn in sweetcorn kernels for genetic and agronomic biofortification programs.

MAIN CONCLUSION: In sweetcorn (Zea mays L.), embryo Zn is accumulated mainly as Zn-phytate, whereas endosperm Zn is complexed with a N- or S-containing ligand. Understanding the speciation of Zn in crop plants helps improve the effectiveness of biofortification efforts. Kernels of four sweetcorn (Zea mays L.) varieties were analysed for Zn concentration and content. We also assessed the speciation of the Zn in the embryo, endosperm, and pericarp in situ using synchrotron-based X-ray absorption spectroscopy. The majority of the Zn was in the endosperm and pericarp (72%), with the embryo contributing 28%. Approximately 79% of the Zn in the embryo accumulated as Zn-phytate, whereas in the endosperm most of the Zn was complexed with a N- or S-containing ligand, possibly as Zn-histidine and Zn-cysteine. This suggests that whilst the Zn in the endosperm and pericarp is likely to be bioavailable for humans, the Zn in the embryo is of low bioavailability. This study highlights the importance of targeting the endosperm of sweetcorn kernels as the tissue for increasing bioavailable Zn concentration.

Prehospital Double Sequential Defibrillation: A Matched Case-Control Study.

OBJECTIVES: The goal of our study was to determine whether prehospital double sequential defibrillation (DSD) is associated with improved survival to hospital admission in the setting of refractory ventricular fibrillation/pulseless ventricular tachycardia (VF/pVT). METHODS: This project is a matched case-control study derived from prospectively collected quality assurance/quality improvement data obtained from the San Antonio Fire Department out-of-hospital cardiac arrest (OHCA) database between January 2013 and December 2015. The cases were defined as OHCA patients with refractory VF/pVT who survived to hospital admission. The control group was defined as OHCA patients with refractory VF/pVT who did not survive to hospital admission. The primary variable in our study was prehospital DSD. The primary outcome of our study was survival to hospital admission. RESULTS: Of 3,469 consecutive OHCA patients during the study period, 205 OHCA patients met the inclusion criterion of refractory VF/pVT. Using a predefined algorithm, two blinded researchers identified 64 unique cases and matched them with 64 unique controls. Survival to hospital admission occurred in 48.0% of DSD patients and 50.5% of the conventional therapy patients (p > 0.99; odds ratio = 0.91, 95% confidence interval = 0.40-2.1). CONCLUSION: Our matched case-control study on the prehospital use of DSD for refractory VF/pVT found no evidence of associated improvement in survival to hospital admission. Our current protocol of considering prehospital DSD after the third conventional defibrillation in OHCA is ineffective.

In situ analyses of inorganic nutrient distribution in sweetcorn and maize kernels using synchrotron-based X-ray fluorescence microscopy.

BACKGROUND AND AIMS: Understanding the spatial distribution of inorganic nutrients within edible parts of plant products helps biofortification efforts to identify and focus on specific uptake pathways and storage mechanisms. METHODS: Kernels of sweetcorn (Zea mays) variety 'High zeaxanthin 103146' and maize inbred line 'Thai Floury 2' were harvested at two different maturity stages, and the distributions of K, P, S, Ca, Zn, Fe and Mn were examined in situ using synchrotron-based X-ray fluorescence microscopy. KEY RESULTS: The distribution of inorganic nutrients was largely similar between maize and sweetcorn, but differed markedly depending upon the maturity stage after further embryonic development. The micronutrients Zn, Fe and Mn accumulated primarily in the scutellum of the embryo during early kernel development, while trace amounts of these were found in the aleurone layer at the mature stage. Although P accumulated in the scutellum, there was no direct relationship between the concentrations of P and those of the micronutrients, compared with the linear trend between Zn and Fe concentrations. CONCLUSIONS: This study highlights the important role of the embryo as a micronutrient reserve for sweetcorn and maize kernels, and the need to understand how biofortification efforts can further increase the inorganic nutrient concentration of the embryo for human consumption.

Airway Management for Trauma Patients.

Trauma airway management is a critical skill for medical providers supporting combat casualties since it is an integral component of damage control resuscitation and surgery. This clinical practice guideline presents methods for optimizing the airway management of patients with traumatic injury in the operational medical treatment facility environment. The guidelines represent the knowledge and experience of 10 co-authors from 3 allied countries representing Emergency Medicine, Surgery and Anesthesia.

Does Experience Matter? Paramedic Cardiac Resuscitation Experience Effect on Out-of-Hospital Cardiac Arrest Outcomes.

OBJECTIVE: Outcomes of Out-of-Hospital Cardiac Arrest (OHCA) are influenced by many factors. We postulate that paramedics who have participated in a greater number of OHCA resuscitations will have improved patient outcomes when compared to paramedics who participated in fewer resuscitations. METHODS: We conducted a retrospective analysis of prospectively collected data abstracted from the cardiac arrest database of a large urban EMS system. All OHCA cases where resuscitation was attempted during the year 2014 were reviewed. Our outcome of interest was the rate of sustained Return of Spontaneous Circulation (ROSC), which is defined as ROSC for five continuous minutes or greater. The rate of sustained ROSC was calculated from cases when paramedics served in the role of the lead medic. These rates were then analyzed using the Chi-Square test. RESULTS: A total of 1,145 cases of OHCA met criteria for inclusion in this study, of which 343 paramedics participated in at least one cardiac arrest in 2014. The median number of resuscitations was 10 with a range from 1 to 26 resuscitations. The paramedics were dichotomized into two groups; those who participated in <10 OHCAs (120/343), labeled "less experienced," and those who participated in ≥10 OHCAs (223/343), labeled "more experienced." Paramedics in the less experienced group had a sustained ROSC rate of 22.2% for resuscitations in which they were the lead medic, while those in the more experienced group had a rate of 28.9% (p-value = 0.047), RR 1.30 (95% CI 1.001, 1.692). CONCLUSIONS: This study demonstrated that more experienced paramedics had a statistically significant increase in achieving sustained ROSC when they were functioning in a lead role compared to less experienced paramedics. We found no other clinically significant patient outcomes related to the provider's experience.

Navy En Route Care: A 3-Year Review of 428 Navy Air Evacuations.

BACKGROUND: Navy medical personnel have been recording en route care (ERC) missions through Search and Rescue (SAR) reports since the 1970's. Our objective was to report clinical ERC cases treated by Navy operational assets from January 2012 to January 2015. METHODS: The Search and Rescue Model Manager office collects SAR reports for all patient transports involving Navy personnel and equipment. From these reports, descriptive statistics to include total number of patients transported, percentages of Advanced Life Support versus Basic Life Support transports, time of transport, and type of ERC provider for the transport were collected. Data reported as median (interquartile range) or percentages. RESULTS: During a 3-year period, 428 patients were transported. Transport time was 54 (30-78) minutes. Missions were staffed by more than one provider 22% of the time. Individual providers included 76% Search and Rescue Medical Technicians, 25% Flight Surgeons, and 21% Other. Patients required ALS transport 54% of the time. Less than half (48%) of the patients were trauma related. CONCLUSION: In our review of 428 SAR reports from Navy ERC (2012-2015), we found that 76% of the missions were performed by Search and Rescue Medical Technicians and 54% met Advanced Life Support transport criteria.

Military Emergency Medical Service System Assessment: Application of the National Park Service Needs Assessment and Program Audit to Objectively Evaluate the Military EMS System of Okinawa, Japan.

INTRODUCTION: As part of a Military Emergency Medical Services (EMS) system process improvement initiative, the authors sought to objectively evaluate the U.S. military EMS system for the island of Okinawa. They applied a program evaluation tool currently utilized by the U.S. National Park Service (NPS). METHODS: A comprehensive needs assessment was conducted to evaluate the current Military EMS system in Okinawa, Japan. The NPS EMS Program Audit Worksheet was used to get an overall "score" of our assessment. After all the data had been collected, a joint committee of Military EMS physicians reviewed the findings and made formal recommendations. RESULTS: From 2011 to 2014, U.S. military EMS on Okinawa averaged 1,345 ± 137 patient transports annually. An advanced life support (ALS) provider would have been dispatched on 558 EMS runs (38%) based on chief complaint in 2014 had they been available. Over 36,000 man-hours were expended during this period to provide National Registry Emergency Medical Technician (EMT)-accredited instruction to certify 141 Navy Corpsman as EMT Basics. The NPS EMS Program Audit Worksheet was used and the program scored a total of 31, suggesting the program is well planned and operating within standards. CONCLUSION: This evaluation of the Military EMS system on Okinawa using the NPS program assessment and audit worksheet demonstrates the NPS evaluation instruments may offer a useful assessment tool for the evaluation of Military EMS systems.