The DmsABC S-oxide reductase is an essential component of a novel, hypochlorite-inducible system of extracellular stress defense in Haemophilus influenzae.

Defenses against oxidative damage to cell components are essential for survival of bacterial pathogens during infection, and here we have uncovered that the DmsABC S-/N-oxide reductase is essential for virulence and in-host survival of the human-adapted pathogen, Haemophilus influenzae. In several different infection models, H. influenzae ΔdmsA strains showed reduced immunogenicity as well as lower levels of survival in contact with host cells. Expression of DmsABC was induced in the presence of hypochlorite and paraquat, closely linking this enzyme to defense against host-produced antimicrobials. In addition to methionine sulfoxide, DmsABC converted nicotinamide- and pyrimidine-N-oxide, precursors of NAD and pyrimidine for which H. influenzae is an auxotroph, at physiologically relevant concentrations, suggesting that these compounds could be natural substrates for DmsABC. Our data show that DmsABC forms part of a novel, periplasmic system for defense against host-induced S- and N-oxide stress that also comprises the functionally related MtsZ S-oxide reductase and the MsrAB peptide methionine sulfoxide reductase. All three enzymes are induced following exposure of the bacteria to hypochlorite. MsrAB is required for physical resistance to HOCl and protein repair. In contrast, DmsABC was required for intracellular colonization of host cells and, together with MtsZ, contributed to resistance to N-Chlorotaurine. Our work expands and redefines the physiological role of DmsABC and highlights the importance of different types of S-oxide reductases for bacterial virulence.

Assessing the prediction of arterial CO2 from end tidal CO2 in adult blunt trauma patients.

BACKGROUND: The control of PaCO2 in ventilated patients is known to be of particular importance in the management and prognosis of trauma patients. Although EtCO2 is often used as a continuous, non-invasive, surrogate marker for PaCO2 in ventilated trauma patients in the emergency department (ED), previous studies suggest a poor correlation in this cohort. However, previous data has predominantly been collected retrospectively, raising the possibility that the elapsed time between PaCO2 sampling and EtCO2 recording may contribute to the poor correlation. As such this study aimed to analyse the correlation of PaCO2 to EtCO2 in the ventilated blunt trauma patient presenting to the ED through contemporaneous sampling. METHODS: This study was conducted as a prospective observational study analysing the near simultaneous recording of EtCO2 and Arterial Blood Gas sampling of ventilated adult trauma patients in the ED of a Level 1 trauma centre over a 12-month period. Data was analysed using linear regression and subgroup analysis by Injury Severity Score (ISS) and Abbreviated Injury Score (AIS) of the Chest. RESULTS: Linear regression of EtCO2 vs PaCO2 demonstrated a moderate correlation with r = 0.54 (p < 0.01, n = 51, 95 % CI 0.31-0.71). Subgroup analysis by ISS, revealed a stronger correlation in those with minor ISS (0-11) (r = 0.76, p < 0.01, n = 13, 95 % CI 0.36-0.92) compared to those more severely injured patients (ISS > 15) (r = 0.44, P < 0.01, n = 38, 95 % CI 0.14-0.67). Analysis by AIS Chest demonstrated similar correlation between patients without chest injuries (AIS 0) (r = 0.55, n = 29, p < 0.01, 95 % CI 0.23-0.76) and those with an AIS >1 (r = 0.51, n = 22, p = 0.02, 95 % CI 0.11-0.77). In patients with traumatic head injuries who had an EtCO2 between 30 and 39 mmHg, only 57 % had a measured PaCO2 within 5 mmHg. CONCLUSIONS: As patients transition from minor to seriously injured, a decreasing strength of PaCO2 to EtCO2 correlation is observed, decreasing the reliability of EtCO2 as a surrogate marker of PaCO2 in this patient group. This inconsistency cannot be accounted for by the presence of chest injuries and worryingly is frequently seen in those with traumatic brain injuries.

Energy Expenditure of Elite Male and Female Professional Tennis Players During Habitual Training.

Understanding the daily energy expenditure of athletes during training is important to support recovery, adaptation, and the maintenance of performance. The aim of the current research was to assess the total daily energy expenditure (TDEE) and the acute energy expenditure (EE) of tennis training sessions during habitual training of elite tennis players. Using a cohort study design, 27 (n = 10, male; age; 22.3 ± 3.2 years and n = 17, female; age: 23.8 ± 3.5 years) elite singles tennis players were assessed for TDEE and tennis training EE. Using Actiheart activity monitors during a 2- to 5-day training period, male players were analyzed for 26 days and 33 (1.3 ± 0.5 sessions/day) tennis training sessions, and female players for 43 days and 58 (1.2 ± 0.4 sessions/day) tennis training sessions. Male TDEE (4,708 ± 583 kcal/day) was significantly higher than female (3,639 ± 305 kcal/day). Male absolute and relative tennis training EEs (10.2 ± 2.3 kcal/min and 7.9 ± 1.4 kcal·hr-1·kg-1) were significantly higher than those of females (7.6 ± 1.0 kcal/min and 6.8 ± 0.9 kcal·hr-1·kg-1). The resting metabolic rate was assessed via indirect calorimetry. The physical activity level for both groups was 2.3 AU. The TDEE of male and female players during habitual training now highlights the continual cycle of high energy demands experienced by the elite tennis player. The broad ranges of TDEE and EE reported here suggest individual assessment and nutritional planning be prioritized, with a particular focus on carbohydrate requirements.

Macromolecular Cargo Encapsulation via In Vitro Assembly of Two-Component Protein Nanoparticles.

Self-assembling protein nanoparticles are a promising class of materials for targeted drug delivery. Here, the use of a computationally designed, two-component, icosahedral protein nanoparticle is reported to encapsulate multiple macromolecular cargoes via simple and controlled self-assembly in vitro. Single-stranded RNA molecules between 200 and 2500 nucleotides in length are encapsulated and protected from enzymatic degradation for up to a month with length-dependent decay rates. Immunogenicity studies of nanoparticles packaging synthetic polymers carrying a small-molecule TLR7/8 agonist show that co-delivery of antigen and adjuvant results in a more than 20-fold increase in humoral immune responses while minimizing systemic cytokine secretion associated with free adjuvant. Coupled with the precise control over nanoparticle structure offered by computational design, robust and versatile encapsulation via in vitro assembly opens the door to a new generation of cargo-loaded protein nanoparticles that can combine the therapeutic effects of multiple drug classes.

Hfe Permease and Haemophilus influenzae Manganese Homeostasis.

Haemophilus influenzae is a commensal of the human upper respiratory tract that can infect diverse host niches due, at least in part, to its ability to withstand both endogenous and host-mediated oxidative stresses. Here, we show that hfeA, a gene previously linked to iron import, is essential for H. influenzae manganese recruitment via the HfeBCD transporter. Structural analyses show that metal binding in HfeA uses a unique mechanism that involves substantial rotation of the C-terminal lobe of the protein. Disruption of hfeA reduced H. influenzae manganese acquisition and was associated with decreased growth under aerobic conditions, impaired manganese-superoxide dismutase activity, reduced survival in macrophages, and changes in biofilm production in the presence of superoxide. Collectively, this work shows that HfeA contributes to H. influenzae manganese acquisition and virulence attributes. High conservation of the hfeABCD permease in Haemophilus species suggests that it may serve similar roles in other pathogenic Pasteurellaceae.

Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses.

The receptor-binding domain (RBD) of influenza virus hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies. Here, we evaluate the ability of several immunofocusing techniques to enhance the functional breadth of vaccine-elicited immune responses against the HA RBD. We present a series of "trihead" nanoparticle immunogens that display native-like closed trimeric RBDs from the HAs of several H1N1 influenza viruses. The series includes hyperglycosylated and hypervariable variants that incorporate natural and designed sequence diversity at key positions in the receptor-binding site periphery. Nanoparticle immunogens displaying triheads or hyperglycosylated triheads elicit higher hemagglutination inhibition (HAI) and neutralizing activity than the corresponding immunogens lacking either trimer-stabilizing mutations or hyperglycosylation. By contrast, mosaic nanoparticle display and antigen hypervariation do not significantly alter the magnitude or breadth of vaccine-elicited antibodies. Our results yield important insights into antibody responses against the RBD and the ability of several structure-based immunofocusing techniques to influence vaccine-elicited antibody responses.

Antigen spacing on protein nanoparticles influences antibody responses to vaccination.

Immunogen design approaches aim to control the specificity and quality of antibody responses elicited by next-generation vaccines. Here, we use computational protein design to generate a nanoparticle vaccine platform based on the receptor-binding domain (RBD) of influenza hemagglutinin (HA) that enables precise control of antigen conformation and spacing. HA RBDs are presented as either monomers or native-like closed trimers that are connected to the underlying nanoparticle by a rigid linker that is modularly extended to precisely control antigen spacing. Nanoparticle immunogens with decreased spacing between trimeric RBDs elicit antibodies with improved hemagglutination inhibition and neutralization potency as well as binding breadth across diverse H1 HAs. Our "trihead" nanoparticle immunogen platform provides insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used in next-generation vaccines against influenza and other viruses.

Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive antibody response against diverse coronavirus subgenera.

Multivalent antigen display is a fast-growing area of interest toward broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable viruses. In coronaviruses, this work is predominantly aimed at targeting conserved epitopes of the receptor binding domain. However, targeting conserved non-RBD epitopes could limit the potential for antigenic escape. To explore new potential targets, we engineered protein nanoparticles displaying coronavirus prefusion-stabilized spike (CoV_S-2P) trimers derived from MERS-CoV, SARS-CoV-1, SARS-CoV-2, hCoV-HKU1, and hCoV-OC43 and assessed their immunogenicity in female mice. Monotypic SARS-1 nanoparticles elicit cross-neutralizing antibodies against MERS-CoV and protect against MERS-CoV challenge. MERS and SARS nanoparticles elicit S1-focused antibodies, revealing a conserved site on the S N-terminal domain. Moreover, mosaic nanoparticles co-displaying distinct CoV_S-2P trimers elicit antibody responses to distant cross-group antigens and protect male and female mice against MERS-CoV challenge. Our findings will inform further efforts toward the development of pan-coronavirus vaccines.

Increased distance or time from a major trauma centre in South Australia is not associated with worse outcomes after moderate to severe traumatic brain injury.

OBJECTIVE: Considerations in traumatic brain injury (TBI) management include time to critical interventions and neurosurgical care, which can be influenced by the geographical location of injury. In Australia, these distances can be vast with varying degrees of first-responder experience. The present study aimed to evaluate the association that distance and/or time to a major trauma centre (MTC) had on patient outcomes with moderate to severe TBI. METHODS: A retrospective cohort study was conducted using data from the Royal Adelaide Hospital's (RAH) Trauma Registry over a 3-year period (1 January 2018 to 31 December 2020). All patients with a moderate to severe TBI (Glasgow Coma Scale [GCS] ≤13 and abbreviated injury score head of ≥2) were included. The association of distance and time to the RAH and patient outcomes were compared by calculating the odds ratio utilising a logistic regression model. RESULTS: A total of 378 patients were identified; of these, 226 met inclusion criteria and comprised our study cohort. Most patients were male (79%), injured in a major city (55%), with median age of 38 years old and median injury severity score (ISS) of 25. After controlling for age, ISS, ED GCS on arrival and pre-MTC intubation, increasing distance or time from injury site to the RAH was not shown to be associated with mortality or discharge destination in any of the models investigated. CONCLUSION: Our analysis revealed that increasing distance or time from injury site to a MTC for patients with moderate to severe TBI was not significantly associated with adverse patient outcomes.

Combinatorial immune refocusing within the influenza hemagglutinin head elicits cross-neutralizing antibody responses.

The head domain of influenza hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies during infection and vaccination. Here we evaluated a series of immunogens that combined several immunofocusing techniques for their ability to enhance the functional breadth of vaccine-elicited immune responses. We designed a series of "trihead" nanoparticle immunogens that display native-like closed trimeric heads from the HAs of several H1N1 influenza viruses, including hyperglycosylated variants and hypervariable variants that incorporate natural and designed sequence diversity at key positions in the periphery of the receptor binding site (RBS). Nanoparticle immunogens displaying triheads or hyperglycosylated triheads elicited higher HAI and neutralizing activity against vaccine-matched and -mismatched H1 viruses than corresponding immunogens lacking either trimer-stabilizing mutations or hyperglycosylation, indicating that both of these engineering strategies contributed to improved immunogenicity. By contrast, mosaic nanoparticle display and antigen hypervariation did not significantly alter the magnitude or breadth of vaccine-elicited antibodies. Serum competition assays and electron microscopy polyclonal epitope mapping revealed that the trihead immunogens, especially when hyperglycosylated, elicited a high proportion of antibodies targeting the RBS, as well as cross-reactive antibodies targeting a conserved epitope on the side of the head. Our results yield important insights into antibody responses against the HA head and the ability of several structure-based immunofocusing techniques to influence vaccine-elicited antibody responses.

Antigen spacing on protein nanoparticles influences antibody responses to vaccination.

Immunogen design approaches aim to control the specificity and quality of antibody responses to enable the creation of next-generation vaccines with improved potency and breadth. However, our understanding of the relationship between immunogen structure and immunogenicity is limited. Here we use computational protein design to generate a self-assembling nanoparticle vaccine platform based on the head domain of influenza hemagglutinin (HA) that enables precise control of antigen conformation, flexibility, and spacing on the nanoparticle exterior. Domain-based HA head antigens were presented either as monomers or in a native-like closed trimeric conformation that prevents exposure of trimer interface epitopes. These antigens were connected to the underlying nanoparticle by a rigid linker that was modularly extended to precisely control antigen spacing. We found that nanoparticle immunogens with decreased spacing between closed trimeric head antigens elicited antibodies with improved hemagglutination inhibition (HAI) and neutralization potency as well as binding breadth across diverse HAs within a subtype. Our "trihead" nanoparticle immunogen platform thus enables new insights into anti-HA immunity, establishes antigen spacing as an important parameter in structure-based vaccine design, and embodies several design features that could be used to generate next-generation vaccines against influenza and other viruses.

An Observational Case Series Measuring the Energy Expenditure of Elite Tennis Players During Competition and Training by Using Doubly Labeled Water.

PURPOSE: An understanding of an athlete's total daily energy expenditure (TEE) is necessary to inform nutritional strategies, particularly where daily training and competitive demands are highly variable. This observational case series assessed the TEE of elite tennis players during high-level competition. METHODS: Senior female singles participants (FS: n = 3; 21 [1] y; ranked  Women's Tennis Association [WTA] top 125-375), an FS junior (n = 1; 16 y; ranked WTA top 350), and a men's doubles player (n = 1; 26 y; ranked Association of Tennis Professionals [ATP] top 5) were assessed for TEE (using the doubly labeled water method) during a 9- to 14-day period, which included training, Wimbledon Championships, WTA/ATP International Tournaments, Junior/Senior International Tennis Federation, and Wimbledon Junior Championships. One female (FS3) did not exercise from day 4 following injury. RESULTS: TEE for men's doubles was 4586 kcal·d-1 (67 kcal·kg-1 fat-free mass [FFM]; daily activity 98 [74] min). Noninjured adult female participants' TEEs were 3396 and 3948 kcal·d-1 (66 and 81 kcal·kg-1 FFM; daily activity durations were 139 [84] min and 150 [66] min, respectively), while TEE for the injured athlete was 2583 kcal·d-1 (45.7 kcal·kg-1; daily nonexercise activity duration was <45 min). The junior player TEE was 3988 kcal·d-1 (78.2 kcal·kg-1 FFM; daily activity of 131 [66] min). CONCLUSION: This observational case series positions tennis as a highly energetically demanding sport with variability evident between individuals (ie, TEE between 60 and 90 kcal·kg-1 FFM). Accordingly, nutritional strategies that promote sufficient energy availability should be emphasized with individual variability suitably assessed prior to prescription.

Improving the secretion of designed protein assemblies through negative design of cryptic transmembrane domains.

Computationally designed protein nanoparticles have recently emerged as a promising platform for the development of new vaccines and biologics. For many applications, secretion of designed nanoparticles from eukaryotic cells would be advantageous, but in practice, they often secrete poorly. Here we show that designed hydrophobic interfaces that drive nanoparticle assembly are often predicted to form cryptic transmembrane domains, suggesting that interaction with the membrane insertion machinery could limit efficient secretion. We develop a general computational protocol, the Degreaser, to design away cryptic transmembrane domains without sacrificing protein stability. The retroactive application of the Degreaser to previously designed nanoparticle components and nanoparticles considerably improves secretion, and modular integration of the Degreaser into design pipelines results in new nanoparticles that secrete as robustly as naturally occurring protein assemblies. Both the Degreaser protocol and the nanoparticles we describe may be broadly useful in biotechnological applications.

Longer times in computed tomography for trauma patients result in a decrease in body temperature.

OBJECTIVE: To determine if lower ambient temperatures in computed tomography (CT) rooms contribute to accidental hypothermia (≤35°C) in trauma patients. METHODS: Prospective, observational study of trauma patients undergoing a CT scan at the Royal Adelaide Hospital. RESULTS: Among a cohort of 81 trauma patients, 54 met level 1 call-out criteria. Mean time in CT was 11 min. Longer time spent in CT contributes to greater decrease in body temperature (∆T/t = -0.1483°C/min, P = 0.0026). CONCLUSION: Increasing time spent in CT leads to a decrease in body temperature in trauma patients. Clinicians should actively reduce time spent in the CT room and take active warming measures.

Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive protection across divergent subgroups.

Multivalent antigen display is a fast-growing area of interest towards broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable viruses. In coronaviruses, this work is predominantly aimed at targeting conserved epitopes of the receptor-binding domain. However, targeting other conserved non-RBD epitopes could further limit the potential for antigenic escape. To further explore new potential targets, we engineered protein nanoparticles displaying CoV_S-2P trimers derived from MERS-CoV, SARS-CoV-1, SARS-CoV-2, hCoV-HKU1, and hCoV-OC43 and assessed their immunogenicity in mice. Monotypic SARS-1_S-2P nanoparticles elicited cross-neutralizing antibodies against MERS_S and protected against MERS-CoV challenge. MERS and SARS-I53_dn5 nanoparticles elicited S1-focused antibodies, revealing a conserved site on the NTD. Moreover, mosaic nanoparticles co-displaying distinct CoV_S-2P trimers elicited antibody responses to distant cross-group antigens while protecting against MERS challenge despite diminished valency of MERS_S-2P. Our findings will inform further efforts towards the development of pan-coronavirus vaccines.

Antigen- and scaffold-specific antibody responses to protein nanoparticle immunogens.

Protein nanoparticle scaffolds are increasingly used in next-generation vaccine designs, and several have established records of clinical safety and efficacy. Yet the rules for how immune responses specific to nanoparticle scaffolds affect the immunogenicity of displayed antigens have not been established. Here we define relationships between anti-scaffold and antigen-specific antibody responses elicited by protein nanoparticle immunogens. We report that dampening anti-scaffold responses by physical masking does not enhance antigen-specific antibody responses. In a series of immunogens that all use the same nanoparticle scaffold but display four different antigens, only HIV-1 envelope glycoprotein (Env) is subdominant to the scaffold. However, we also demonstrate that scaffold-specific antibody responses can competitively inhibit antigen-specific responses when the scaffold is provided in excess. Overall, our results suggest that anti-scaffold antibody responses are unlikely to suppress antigen-specific antibody responses for protein nanoparticle immunogens in which the antigen is immunodominant over the scaffold.

Durable protection against the SARS-CoV-2 Omicron variant is induced by an adjuvanted subunit vaccine.

Despite the remarkable efficacy of COVID-19 vaccines, waning immunity and the emergence of SARS-CoV-2 variants such as Omicron represents a global health challenge. Here, we present data from a study in nonhuman primates demonstrating durable protection against the Omicron BA.1 variant induced by a subunit SARS-CoV-2 vaccine comprising the receptor binding domain of the ancestral strain (RBD-Wu) on the I53-50 nanoparticle adjuvanted with AS03, which was recently authorized for use in individuals 18 years or older. Vaccination induced neutralizing antibody (nAb) titers that were maintained at high concentrations for at least 1 year after two doses, with a pseudovirus nAb geometric mean titer (GMT) of 1978 and a live virus nAb GMT of 1331 against the ancestral strain but not against the Omicron BA.1 variant. However, a booster dose at 6 to 12 months with RBD-Wu or RBD-ß (RBD from the Beta variant) displayed on I53-50 elicited high neutralizing titers against the ancestral and Omicron variants. In addition, we observed persistent neutralization titers against a panel of sarbecoviruses, including SARS-CoV. Furthermore, there were substantial and persistent memory T and B cell responses reactive to Beta and Omicron variants. Vaccination resulted in protection against Omicron infection in the lung and suppression of viral burden in the nares at 6 weeks after the final booster immunization. Even at 6 months after vaccination, we observed protection in the lung and rapid control of virus in the nares. These results highlight the durable and cross-protective immunity elicited by the AS03-adjuvanted RBD-I53-50 nanoparticle vaccine.

Structure-based design of stabilized recombinant influenza neuraminidase tetramers.

Influenza virus neuraminidase (NA) is a major antiviral drug target and has recently reemerged as a key target of antibody-mediated protective immunity. Here we show that recombinant NAs across non-bat subtypes adopt various tetrameric conformations, including an "open" state that may help explain poorly understood variations in NA stability across viral strains and subtypes. We use homology-directed protein design to uncover the structural principles underlying these distinct tetrameric conformations and stabilize multiple recombinant NAs in the "closed" state, yielding two near-atomic resolution structures of NA by cryo-EM. In addition to enhancing thermal stability, conformational stabilization improves affinity to protective antibodies elicited by viral infection, including antibodies targeting a quaternary epitope and the broadly conserved catalytic site. Stabilized NAs can also be integrated into viruses without affecting fitness. Our findings provide a deeper understanding of NA structure, stability, and antigenicity, and establish design strategies for reinforcing the conformational integrity of recombinant NA proteins.

Combining physics-based and Kriging models to improve the estimation of noise exposure.

Worker exposure to occupational hazards is traditionally measured by equipping workers with wearable exposure monitors. An emerging alternative measurement first generates time-varying hazard maps from permanent monitors within the facility, then estimating worker exposure by integrating hazard levels traversed in map, following the tracked movement of workers. Complex environments may require many monitors to produce a hazard map with the necessary accuracy, but effective interpolation functions can reduce the required number of monitors needed. This work assesses the effectiveness of three models for accurately interpolating hazard levels among monitors: a traditional Kriging model, a physics-based model, and a hybrid model that combines the Kriging and physics-based models. The effectiveness of each interpolation function was tested with sound levels collected in four environmental settings. These detailed experimental data were used to generate over 10,000 simulation trials, where each trial configured the experimental data into a unique arrangement of simulated monitoring and sampling positions. For each simulation trial, the effectiveness of the three models was assessed with the root mean square error of the sound levels at the simulated sampling positions, using the simulated monitoring positions as input. The interpolated values between the monitored positions were analyzed separately from the extrapolated values beyond the monitored positions. The hybrid model consistently reported among the lowest errors in each trial. The Kriging model performed best for the densest networks (those with the most monitors). Even in these cases, the hybrid model performed within 10% of the Kriging model with less than a third of the monitors. The experiment demonstrates that the hybrid model is highly effective at estimating hazardous sound levels; future work may demonstrate similar advantages for gas and aerosol hazards.

Pre-hospital emergency anaesthesia in trauma patients: An observational study from a state-wide Australian pre-hospital and retrieval service.

OBJECTIVE: To assess the performance of an Australian pre-hospital and retrieval medicine (PHRM) service against the National Institute for Health and Care Excellence (NICE) standard which recommends that pre-hospital emergency anaesthesia (PHEA) in trauma patients should be conducted within 45-min of first contact with emergency services. METHODS: Retrospective observational study of all adult trauma patients in which PHEA was conducted by the PHRM service covering a 5-year period from January 2015 to December 2019. RESULTS: Over the 5-year study period, 1509 (22%) of the PHRM service workload comprised primary retrievals from scene. Most 1346 (89%) of these cases had a primary diagnosis of trauma. Of these we have complete data for 328 of the 337 cases requiring a PHEA and 121 (37%) patients received this within the recommended 45-min time frame. The service attended in rapid response vehicles (n = 160, 49%), rotary wing (n = 151, 46%) and fixed wing (n = 17, 5%) transport modalities. For a service covering 983 482 km2 , the median distance travelled to patients was 35 (16-71) km and the median time to PHEA was 54 (38-80) min. CONCLUSIONS: In a cohort of 337 patients treated by a dedicated PHRM service in South Australia, the median time to PHEA was 54 (38-80) min with only 37% of patients receiving PHEA within 45 min from the activation of the team. Despite differing patient demographics, the percentage of patients receiving PHEA within the recommended time frame was greater than a similar cohort from the UK. However, both data sets still fall short of recommended targets.