Haemostatic resuscitation in practice: a descriptive analysis of blood products administered during Operation HERRICK, Afghanistan.

INTRODUCTION: Life-threatening haemorrhage is the leading cause of potentially survivable injury in battlefield casualties. During Operation HERRICK (Afghanistan), mortality rates improved year on year due to a number of advances in trauma care, including haemostatic resuscitation. Blood transfusion practice has not previously been reported in detail during this period. METHODS: A retrospective analysis of blood transfusion at the UK role 3 medical treatment facility (MTF) at Camp Bastion between March 2006 and September 2014 was performed. Data were extracted from two sources: the UK Joint Theatre Trauma Registry (JTTR) and the newly established Deployed Blood Transfusion Database (DBTD). RESULTS: 3840 casualties were transfused 72 138 units of blood and blood products. 2709 adult casualties (71%) were fully linked with JTTR data and were transfused a total of 59 842 units. Casualties received between 1 unit and 264 units of blood product with a median of 13 units per patient. Casualties wounded by explosion required almost twice the volume of blood product transfusion as those wounded by small arms fire or in a motor vehicle collision (18 units, 9 units, and 10 units, respectively). More than half of blood products were transfused within the first 2 hours following arrival at the MTF. There was a trend towards balanced resuscitation with more equal ratios of blood and blood products being used over time. CONCLUSION: This study has defined the epidemiology of blood transfusion practice during Operation HERRICK. The DBTD is the largest combined trauma database of its kind. It will ensure that lessons learnt during this period are defined and not forgotten; it should also allow further research questions to be answered in this important area of resuscitation practice.

The UK defence anaesthesia experience with the Zambia Anaesthesia Development Programme.

For 18 months UK military anaesthetic trainees have been travelling to Zambia for a 3-month fellowship under the auspices of the Zambia Anaesthesia Development Programme. In this article we will discuss the history, current state and future intent of the fellowship in order to better inform the anaesthetic cadre and wider UK Defence Medical Services.

Dysregulation of the actin scavenging system and inhibition of DNase activity following severe thermal injury.

BACKGROUND: Circulating cell-free DNA (cfDNA) is not found in healthy subjects, but is readily detected after thermal injury and may contribute to the risk of multiple organ failure. The hypothesis was that a postburn reduction in DNase protein/enzyme activity could contribute to the increase in cfDNA following thermal injury. METHODS: Patients with severe burns covering at least 15 per cent of total body surface area were recruited to a prospective cohort study within 24 h of injury. Blood samples were collected from the day of injury for 12 months. RESULTS: Analysis of blood samples from 64 patients revealed a significant reduction in DNase activity on days 1-28 after injury, compared with healthy controls. DNase protein levels were not affected, suggesting the presence of an enzyme inhibitor. Further analysis revealed that actin (an inhibitor of DNase) was present in serum samples from patients but not those from controls, and concentrations of the actin scavenging proteins gelsolin and vitamin D-binding protein were significantly reduced after burn injury. In a pilot study of ten military patients with polytrauma, administration of blood products resulted in an increase in DNase activity and gelsolin levels. CONCLUSION: The results of this study suggest a novel biological mechanism for the accumulation of cfDNA following thermal injury by which high levels of actin released by damaged tissue cause a reduction in DNase activity. Restoration of the actin scavenging system could therefore restore DNase activity, and reduce the risk of cfDNA-induced host tissue damage and thrombosis.

ANTECEDENTES: El ADN libre de las células circulantes (circulating cell-free DNA, cfDNA) no se encuentra en sujetos sanos, pero se detecta fácilmente después de una lesión térmica y puede contribuir al riesgo de fallo multiorgánico. La hipótesis fue que una disminución en la actividad de la proteína/enzima ADNasa tras la lesión térmica podría contribuir a la elevación del cfDNA que ocurre tras la misma. MÉTODOS: Los pacientes con quemaduras graves con una extensión ≥ 15% del área de superficie corporal total (total body surface area, TBSA) se incluyeron en un estudio prospectivo de cohortes durante las primeras 24 horas posteriores a la lesión. Se recogieron muestras de sangre desde el día de la lesión hasta los 12 meses posteriores a la misma. RESULTADOS: El análisis de muestras de sangre de 64 pacientes reveló una reducción significativa de la actividad de la ADNasa en los días 1 a 28 después de la lesión, en comparación con los controles sanos. Los niveles de proteína ADNasa no se vieron afectados, lo que sugiere la presencia de un inhibidor enzimático. Un análisis adicional reveló que la actina (un inhibidor de la ADNasa) estaba presente en las muestras de suero de los pacientes, pero no en los controles, y las concentraciones de la gelsolina, proteína que causa la disociación de la actina, y la proteína de unión a la vitamina D se redujeron significativamente después de la lesión térmica. En un estudio piloto de 10 pacientes con politrauma por lesiones militares, la administración de hemoderivados produjo un aumento en la actividad de la ADNasa y de los niveles de gelsolina. CONCLUSIÓN: Este estudio sugiere un nuevo mecanismo biológico para la acumulación de cfDNA después de una lesión térmica, por el cual los altos niveles de actina liberada por el tejido dañado causarían una reducción en la actividad de la ADNasa. La restauración del sistema eliminador de actina podría, por lo tanto, restaurar la actividad de la ADNasa y reducir el riesgo de daño tisular y trombosis en el huésped inducido por el cfDNA.

Highly structured slow solar wind emerging from an equatorial coronal hole.

During the solar minimum, when the Sun is at its least active, the solar wind1,2 is observed at high latitudes as a predominantly fast (more than 500 kilometres per second), highly Alfvénic rarefied stream of plasma originating from deep within coronal holes. Closer to the ecliptic plane, the solar wind is interspersed with a more variable slow wind3 of less than 500 kilometres per second. The precise origins of the slow wind streams are less certain4; theories and observations suggest that they may originate at the tips of helmet streamers5,6, from interchange reconnection near coronal hole boundaries7,8, or within coronal holes with highly diverging magnetic fields9,10. The heating mechanism required to drive the solar wind is also unresolved, although candidate mechanisms include Alfvén-wave turbulence11,12, heating by reconnection in nanoflares13, ion cyclotron wave heating14 and acceleration by thermal gradients1. At a distance of one astronomical unit, the wind is mixed and evolved, and therefore much of the diagnostic structure of these sources and processes has been lost. Here we present observations from the Parker Solar Probe15 at 36 to 54 solar radii that show evidence of slow Alfvénic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals that are associated with jets of plasma and enhanced Poynting flux and that are interspersed in a smoother and less turbulent flow with a near-radial magnetic field. Furthermore, plasma-wave measurements suggest the existence of electron and ion velocity-space micro-instabilities10,16 that are associated with plasma heating and thermalization processes. Our measurements suggest that there is an impulsive mechanism associated with solar-wind energization and that micro-instabilities play a part in heating, and we provide evidence that low-latitude coronal holes are a key source of the slow solar wind.

Radiation protraction schedules for low-grade gliomas: a comparison between different mathematical models.

We optimize radiotherapy (RT) administration strategies for treating low-grade gliomas. Specifically, we consider different tumour growth laws, both with and without spatial effects. In each scenario, we find the optimal treatment in the sense of maximizing the overall survival time of a virtual low-grade glioma patient, whose tumour progresses according to the examined growth laws. We discover that an extreme protraction therapeutic strategy, which amounts to substantially extending the time interval between RT sessions, may lead to better tumour control. The clinical implications of our results are also presented.

Use of supplemental oxygen in emergency patients: a systematic review and recommendations for military clinical practice.

INTRODUCTION: Supplemental oxygen is a key element of emergency treatment algorithms. However, in the operational environment, oxygen supply poses a challenge. The lack of high-quality evidence alongside emerging technologies provides the opportunity to challenge current guidelines. The aim of this review was to appraise the evidence for the administration of oxygen in emergency patients and give recommendations for its use in clinical practice. METHODS: A critical review of the literature was undertaken to determine the evidence for emergency supplemental oxygen use. RESULTS: Based on interpretation of the limited available evidence, five key recommendations are made: pulse oximetry should be continuous and initiated as early as possible; oxygen should be available to all trauma and medical patients in the forward operating environment; if peripheral oxygen saturations (SpO2) are greater than or equal to 92%, supplemental oxygen is not routinely required; if SpO2 is less than 92%, supplemental oxygen should be titrated to achieve an SpO2 of greater than 92%; and if flow rates of greater than 5 L/min are required, then urgent evacuation and critical care support should be requested. CONCLUSION: Oxygen is not universally required for all patients. Current guidelines aim to prevent hypoxia but with potentially conservative limits. Oxygen should be administered to maintain SpO2 at 92% or above. New areas for research, highlighted in this review, may provide a future approach for oxygen use from point of injury to definitive care.

Global lessons: developing military trauma care and lessons for civilian practice.

The wars in Iraq and Afghanistan have helped to shape the modern Defence Medical Services. Many lessons were learnt including the need for rapid haemorrhage control, senior decision-making and the evolution of deployed transfusion support. These changes were implemented simultaneously with a coherent, end-to-end medical plan from point of wounding through to rehabilitation. Implementation of the medical plan is harmonious with the NHS trauma pathway, and is key to ensuring effective delivery. Military anaesthetists have a long pre-deployment training pathway starting with a Certificate of Completion of Training (CCT) in anaesthesia and/or critical care, and with an emphasis on military skills related to their specific role. Pre-deployment training includes additional skill training, team training and finally whole hospital collective training. This pathway ensures ongoing and continuing competence on an individual basis, and assurance that hospital management systems and clinical staff can function effectively as a deploying unit.

The impact of socially-accountable, community-engaged medical education on graduates in the Central Philippines: Implications for the global rural medical workforce.

INTRODUCTION: Developing and retaining a high quality medical workforce, especially within low-resource countries has been a world-wide challenge exacerbated by a lack of medical schools, the maldistribution of doctors towards urban practice, health system inequities, and training doctors in tertiary centers rather than in rural communities. AIM: To describe the impact of socially-accountable health professional education on graduates; specifically: their motivation towards community-based service, preparation for addressing local priority health issues, career choices, and practice location. METHODS: Cross-sectional survey of graduates from two medical schools in the Philippines: the University of Manila-School of Health Sciences (SHS-Palo) and a medical school with a more conventional curriculum. RESULTS: SHS-Palo graduates had significantly (p < 0.05) more positive attitudes to community service. SHS-Palo graduates were also more likely to work in rural and remote areas (p < 0.001) either at district or provincial hospitals (p = 0.032) or in rural government health services (p < 0.001) as Municipal or Public Health Officers (p < 0.001). Graduates also stayed longer in both their first medical position (p = 0.028) and their current position (p < 0.001). CONCLUSIONS: SHS-Palo medical graduates fulfilled a key aim of their socially-accountable institution to develop a health professional workforce willing and able, and have a commitment to work in underserved rural communties.

Dissecting the self-assembly kinetics of multimeric pore-forming toxins.

Pore-forming toxins are ubiquitous cytotoxins that are exploited by both bacteria and the immune response of eukaryotes. These toxins kill cells by assembling large multimeric pores on the cell membrane. However, a quantitative understanding of the mechanism and kinetics of this self-assembly process is lacking. We propose an analytically solvable kinetic model for stepwise, reversible oligomerization. In biologically relevant limits, we obtain simple algebraic expressions for the rate of pore formation, as well as for the concentration of pores as a function of time. Quantitative agreement is obtained between our model and time-resolved kinetic experiments of Bacillus thuringiensis Cry1Ac (tetrameric pore), aerolysin, Staphylococcus aureus α-haemolysin (heptameric pores) and Escherichia coli cytolysin A (dodecameric pore). Furthermore, our model explains how rapid self-assembly can take place with low concentrations of oligomeric intermediates, as observed in recent single-molecule fluorescence experiments of α-haemolysin self-assembly. We propose that suppressing the concentration of oligomeric intermediates may be the key to reliable, error-free, self-assembly of pores.

Predictive utility of cardiac ultrasound in traumatic cardiac arrest in a combat casualty.

We report a case of traumatic cardiac arrest in a combat casualty who was resuscitated to return of spontaneous circulation despite asystole and no visible cardiac activity on initial ultrasound examination. This return of spontaneous circulation suggests that survival may be possible in traumatic cardiac arrest due to exsanguination, even when there is no demonstrable cardiac activity on ultrasound. Cardiac ultrasonography was performed for 10 s only. We suggest that cardiac ultrasonography should be performed for a minimum of 1 min during volume resuscitation. If absence of cardiac activity is confirmed once the heart is full, and there are no other signs of life (including pupillary reaction), then termination of resuscitation should be considered.

Sebia Capillarys 2 versus the Helena Biosciences V8 capillary electrophoresis analyser for carbohydrate-deficient transferrin measurement: comparison and analytical evaluation.

This study compares two automated capillary electrophoresis (CE) systems, the Capillarys 2 (Sebia, Surrey, UK) and V8 (Helena Biosciences, Tyne and Wear, UK) for the measurement of carbohydrate-deficient transferrin (CDT). Analytical imprecision was calculated for both platforms using internal quality control material from Sebia and Helena Biosciences, while a patient comparison was performed on 150 patient samples with CDT% levels ranging from 0.3% to 23.7%. Inter- and intra-assay imprecision between the two platforms were comparable. The correlation between platforms using patient samples was r2 = 0.985. However, there was a significant proportional bias at higher CDT concentration ranges, with the Helena system showing negative bias but good correlation over the clinically significant range. Analytical performances from both CE systems have been proven as suitable for routine laboratory use. The V8 CDT results were comparable to the Capillarys 2 in human sera over the clinical range of interest.

The use of spatial manipulation to examine goalkeepers' anticipation.

This study investigated whether anticipation and search strategies of goalkeepers are influenced by temporally and spatially manipulated video of a penalty. Participants were clustered into three groups depending on skill: goalkeepers (n = 17), field players (n = 20) and control group (n = 20). An eye tracker was worn whilst watching 40 videos of a striker kicking to four corners of a goal in random order. All 40 videos were temporally occluded at foot-to-ball contact, and the non-kicking leg of 20 videos was spatially manipulated. Results showed that goalkeepers had significantly better predictions than the two groups with no differences between the two testing conditions. According to effect size, the percentage of fixation location and viewing time of the kicking leg and ball were greater for the goalkeepers and field players group than the control group irrespective of testing conditions. The fixations on the kicking leg and ball in conjunction with comparable predictions between spatially manipulated and control conditions suggest that goalkeepers may not rely on the non-kicking leg. Furthermore, goalkeepers appear to use a global perceptual approach by anchoring on a distal fixation point/s of the penalty taker whilst using peripheral vision to obtain additional information.

Deployed research.

The Role 3 Medical Treatment Facility (Field Hospital) in Camp Bastion (R3 Bastion) is acknowledged to be one of the busiest dedicated trauma facilities in the world. Casualties typically present with severe injuries and in physiological extremis. These casualties form a unique cohort representing the most relevant population to evaluate the effectiveness of treating battlefield injuries as academic clinicians and scientists interested in trauma seek to improve outcomes for such patients in the future. This article describes four separate but related research projects that have been undertaken in Camp Bastion, Afghanistan, over the last year. They traverse the spectrum of clinical research, ranging from data collection to a randomised control trial. The aim is to discuss some of the problems encountered and the solutions that made it possible to undertake research in a theatre of operations, thereby providing a starting point for others who may wish to initiate research in a similar environment.

Positive impacts on rural and regional workforce from the first seven cohorts of James Cook University medical graduates.

INTRODUCTION: The regionally-based James Cook University (JCU) School of Medicine aims to meet its mission to address the health needs of the region by combining selection and curriculum strategies shown to increase rural career recruitment outcomes. The School has graduated 536 students in its first seven cohorts from 2005 to 2011. This paper presents the early career practice locations and the specialty training undertaken by these cohorts, and describes the association between later practice location with both hometown at application and internship location. METHODS: Hometown at application' data for JCU Bachelor of Medicine, Bachelor of Surgery (MBBS) graduates was retrieved from administrative databases held by the university, while postgraduate location and career data were obtained either from personal contact via email, telephone, Facebook or electronically from the Australian Health Practitioner Regulation Authority website. Practice location was described across Australian Standard Geographical Classification Remoteness Area (RA) categories. RESULTS: Data for the primary practice location of 536 JCU MBBS graduates across postgraduate years (PGY) 1 to 7 is 99% complete. A total of 65% of JCU graduates undertook their internship in non-metropolitan locations including 20% in RA 2 and 44% in RA 3-5, a pattern of practice different to that of other Australian clinicians. For the internship year, 'non-metropolitan-origin' JCU MBBS graduates predominantly worked in RA 2-5 locations, while 'metropolitan origin' graduates were more likely to work in major cities. However, by PGY 7, the distribution of 'rural' and 'metropolitan' origin JCU graduates across RA categories was similar. The RA category of internship location - either 'metropolitan (RA 1) or 'non-metropolitan' (RA 2-5) - was associated with the location of subsequent practice across PGY 2-7. CONCLUSION: This comprehensive data set provides the first real evidence from one of Australia's new medical schools on actual postgraduate practice location, as compared to 'intent to practice'. The geographic profile by RA of JCU graduates' hometown and patterns of postgraduate practice is different to that of other Australian medical students and doctors. This early evidence supports the JCU model of distributed non-metropolitan medical education, and suggests more regionally-located internship and specialty training places would further increase the medical workforce in northern and/or rural Australia. The workforce impact of the seven cohorts of graduates in this study is starting to be felt in rural and regional Australia, and, if these trends continue, will result in significant workforce improvements over the next decade. These results support further investment in regional and rural medical education.

Modelling biological invasions: Individual to population scales at interfaces.

Extracting the population level behaviour of biological systems from that of the individual is critical in understanding dynamics across multiple scales and thus has been the subject of numerous investigations. Here, the influence of spatial heterogeneity in such contexts is explored for interfaces with a separation of the length scales characterising the individual and the interface, a situation that can arise in applications involving cellular modelling. As an illustrative example, we consider cell movement between white and grey matter in the brain which may be relevant in considering the invasive dynamics of glioma. We show that while one can safely neglect intrinsic noise, at least when considering glioma cell invasion, profound differences in population behaviours emerge in the presence of interfaces with only subtle alterations in the dynamics at the individual level. Transport driven by local cell sensing generates predictions of cell accumulations along interfaces where cell motility changes. This behaviour is not predicted with the commonly used Fickian diffusion transport model, but can be extracted from preliminary observations of specific cell lines in recent, novel, cryo-imaging. Consequently, these findings suggest a need to consider the impact of individual behaviour, spatial heterogeneity and especially interfaces in experimental and modelling frameworks of cellular dynamics, for instance in the characterisation of glioma cell motility.

Utility of interim ROTEM(®) values of clot strength, A5 and A10, in predicting final assessment of coagulation status in severely injured battle patients.

BACKGROUND: Proactive management of trauma-related coagulopathy requires early identification and rapid assessment in order to allow targeted resuscitation. This study determined whether early (interim) ROTEM(®) (TEM International GmbH, Munich, Germany) values could predict hypocoagulopathy in seriously injured military patients. METHODS: Normal ranges for ROTEM(®) values were obtained from 50 volunteers. 108 samples were collected during the early phase of clinical management from 48 severe trauma patients. The blood was subject to EXTEM analysis and compared to the 95% tolerance limits from the volunteers. Coagulopathy (was deemed to be present if EXTEM MCF was below 40 mm, which is in the range indicating clinical concern defined by the ROTEM(®) Expert Working Group. RESULTS: The normal range data was broadly similar to ROTEM(®) published data. Admission samples were available from 31 battlefield casualties, and 39% of these were coagulopathic 51% of the samples from all 48 patients were coagulopathic (EXTEM MCF<40 mm) and interim EXTEM values of these at 5 and 10 min (A5 and A10) predicted coagulopathy with sensitivities/specificities of 0.96/0.58 (A5) and 1.00/0.70 (A10). In addition, statistical comparison of clotting domains between normal volunteers and trauma patients suggests a difference in clot strengths due to a difference in platelet function rather than platelet number (mean 142 × 10(9)l(-1)). CONCLUSIONS: The A10 value of ROTEM(®) provides an early sensitive and specific assessment of coagulopathy after military trauma and may be of utility in guiding bespoke resuscitation. We found some speculative evidence that in major trauma platelet function is particularly affected.

Haemorrhage and coagulopathy in the Defence Medical Services.

Over the past 12 years, the United Kingdom Defence Medical Services have evolved an integrated 'damage control resuscitation - damage control surgery' sequence for the management of patients sustaining complex injuries. During 2009, over 3200 units of blood products were administered as massive transfusions to severely injured UK personnel. An important part of the approach to traumatic bleeding is the early, empirical use of predefined ratios of blood and clotting products. As soon as control of bleeding is achieved, current practice is to switch towards a tailored transfusion, based on clinical and laboratory assessments, including point-of-care coagulation testing. A key goal is to provide resuscitation seamlessly throughout surgery, so that patients leave the operating room with their normal physiology restored. This article outlines the current management of haemorrhage and coagulation employed in Afghanistan from the point of wounding to transfer back to the National Health Service.

Nonlinear effects on Turing patterns: time oscillations and chaos.

We show that a model reaction-diffusion system with two species in a monostable regime and over a large region of parameter space produces Turing patterns coexisting with a limit cycle which cannot be discerned from the linear analysis. As a consequence, the patterns oscillate in time. When varying a single parameter, a series of bifurcations leads to period doubling, quasiperiodic, and chaotic oscillations without modifying the underlying Turing pattern. A Ruelle-Takens-Newhouse route to chaos is identified. We also examine the Turing conditions for obtaining a diffusion-driven instability and show that the patterns obtained are not necessarily stationary for certain values of the diffusion coefficients. These results demonstrate the limitations of the linear analysis for reaction-diffusion systems.