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  • Conference paper
    Campos-Pires R, Onggradito H, Ujvari E, Karimi S, Aldhoun J, Edge C, Franks N, Dickinson Ret al., 2021,

    Xenon is neuroprotective and promotes beneficial early neuroinflammation in a rat model of severe traumatic brain injury

    , Society for Neuroscience
  • Conference paper
    Campos-Pires R, Onggradito H, Ujvari E, Karimi S, Valeo F, Edge C, Franks N, Dickinson Ret al., 2021,

    Xenon is neuroprotective and promotes beneficial early neuroinflammation in a rat model of severe traumatic brain injury

    , Society for Neuroscience
  • Journal article
    Edge C, Dickinson R, 2021,

    Argon: a noble, but not inert, treatment for brain trauma?

    , British Jourmal of Anaesthesia, Vol: 126, Pages: 41-43
  • Journal article
    Campos-Pires R, Onggradito H, Ujvari E, Karimi S, Valeo F, Aldhoun J, Edge C, Franks N, Dickinson Ret al., 2020,

    Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

    , Critical Care (UK), Vol: 24, Pages: 1-18, ISSN: 1364-8535

    BackgroundTraumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats.MethodsYoung adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure.ResultsXenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation.ConclusionsOur findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.
  • Journal article
    Turner S, McGregor A, 2020,

    Perceived impact of socket fit on major lower limb prosthetic rehabilitation: a clinician and amputee perspective

    , Archives of Rehabilitation Research and Clinical Translation, Vol: 2, Pages: 1-8, ISSN: 2590-1095

    ObjectiveTo determine amputees’ and rehabilitation clinicians’ perspectives on the impact of socket fit and issues caused by ill-fitting sockets throughout lower limb prosthetic rehabilitation.DesignA survey was developed to identify rehabilitation factors and issues for prosthesis wearers and rehabilitation clinicians. Participants opted to participate in a further telephone interview.SettingOnline and across the United Kingdom.ParticipantsLower limb prosthetic wearers and clinicians that are part of a lower limb prosthetic rehabilitation team.InterventionsNot applicable.Main Outcome Measure(s)A survey and an interview to measure the perceived impact of socket fit on lower limb rehabilitation.Results48.0% of amputees and 65.7% of clinicians identified socket fit related issues as the biggest factor impacting rehabilitation. Amputee interviewees focused on the impact of fit on quality of life and the ability to complete daily tasks, whilst clinicians focused on the lack of widespread ability to adjust the socket and gait re-education.ConclusionsSocket fit has a large impact on and is a large source of frustration to amputees and their clinical teams throughout rehabilitation. From the interviews, it became clear that the interpretation of socket fit is different for each person; thus “socket fit” does not mean the same for all.
  • Journal article
    Nguyen TT, Carpanen D, Rankin I, Ramasamy A, Breeze J, Proud W, Clasper J, Masouros Set al., 2020,

    Mapping the risk of fracture of the tibia from penetrating fragments

    , Frontiers in Bioengineering and Biotechnology, Vol: 8, Pages: 1-11, ISSN: 2296-4185

    Penetrating injuries are commonly inflicted in attacks with explosive devices. The extremities, and especially the leg, are the most commonly affected body areas, presenting high risk of infection, slow recovery, and threat of amputation. The aim of this study was to quantify the risk of fracture to the anteromedial, posterior, and lateral aspects of the tibia from a metal fragment-simulating projectile (FSP). A gas gun system and a 0.78-g cylindrical FSP were employed to perform tests on an ovine tibia model. The results from the animal study were subsequently scaled to obtain fracture-risk curves for the human tibia using the cortical thickness ratio. The thickness of the surrounding soft tissue was also taken into account when assessing fracture risk. The lateral cortex of the tibia was found to be most susceptible tofracture,whose impact velocity at 50% risk of EF1+, EF2+, EF3+, and EF4+ fracture types –according to the modified Winquist-Hansen classification –were 174, 190, 212,and 282 m/s respectively. The findings of this study will be used to increase the fidelity of predictive models of projectile penetration.
  • Journal article
    Rankin I, Nguyen TT, Carpanen D, Clasper J, Masouros Set al., 2020,

    A new understanding of the mechanism of injury to the pelvis and lower limbs in blast

    , Frontiers in Bioengineering and Biotechnology, Vol: 8, ISSN: 2296-4185

    Dismounted complex blast injury (DCBI) has been one of the most severe forms of trauma sustained in recent conflicts. This injury has been partially attributed to limb flail; however, the full causative mechanism has not yet been fully determined. Soil ejecta has been hypothesized as a significant contributor to the injury but remains untested. In this study, a small-animal model of gas-gun mediated high velocity sand blast was used to investigate this mechanism. The results demonstrated a correlation between increasing sand blast velocity and injury patterns of worsening severity across the trauma range. This study is the first to replicate high velocity sand blast and the first model to reproduce the pattern of injury seen in DCBI. These findings are consistent with clinical and battlefield data. They represent a significant change in the understanding of blast injury, producing a new mechanistic theory of traumatic amputation. This mechanism of traumatic amputation is shown to be high velocity sand blast causing the initial tissue disruption, with the following blast wind and resultant limb flail completing the amputation. These findings implicate high velocity sand blast, in addition to limb flail, as a critical mechanism of injury in the dismounted blast casualty.
  • Report
    Foss L, Belli A, Brody D, Brookes M, Bull A, Craner M, Dunkley B, Evangelou N, Furlong P, Gibb I, Goldstone A, Green G, Hettiaratchy S, Hodgetts T, Lee R, Mistlin A, Nader K, Perl D, Reid A, Scadding J, Seri S, Sharp D, Sherwood D, Simms A, Sinclair A, Wessely S, Wilde E, Woods Det al., 2020,

    Setting a national consensus for managing mild and blast traumatic brain injury: post-meeting consensus report

    A meeting was held on Wednesday 15 January 2020 to examine the current evidence for non-routine imaging and for neuroendocrine screening in the management of military personnel with brain injury and overlapping symptom domains. The Summit aimed to specifically address the relative utility of magnetoencephalography (MEG), diffusion tensor imaging (DTI) and susceptibility weighted imaging (SWI) in the UK context. This Consensus Report discusses points of consensus, points for further discussion/points of equipoise and recommendations that arose during, and following, the meeting.
  • Journal article
    Stewart S, Tenenbaum O, Masouros S, Ramasamy Aet al., 2020,

    Fracture non-union rates across a century of war: a systematic review of the literature

    , BMJ Military Health, Vol: 166, Pages: 271-276, ISSN: 2633-3767

    IntroductionFractures have been a common denominator of the injury patterns observed over the past century of warfare. The fractures typified by the blast and ballistic injuries of war lead to high rates of bone loss, soft tissue injury and infection, greatly increasing the likelihood of non-union. Despite this, no reliable treatment strategy for non-union exists. This literature review aims to explore the rates of non-union across a century of conflict and war, in order to determine whether our ability to heal the fractures of war has improved.MethodsA systematic review of the literature was conducted, evaluating the rates of union in fractures sustained in a combat environment over a one hundred year period. Only those fractures sustained through a ballistic or blast mechanism were included. The review was in accordance with the Preferred Items for Systematic Reviews and Meta-Analyses (PRISMA). Quality and bias assessment was also undertaken. ResultsThirty studies met the inclusion criteria, with a total of 3232 fractures described across fifteen different conflicts from the period 1919-2019. Male subjects made up 96% of cases, and tibial fractures predominated (39%). The lowest fracture union rate observed in a series was 50%. Linear regression analysis demonstrated that increasing years had no statistically significant impact on union rate.ConclusionFailure to improve fracture union rates is likely a result of numerous factors, including greater use of blast weaponry and better survivability of casualties. Finding novel strategies to promote fracture healing is a key defence research priority, in order to improve the rates of fractures sustained in a combat environment.
  • Conference paper
    Valeo F, Campos-Pires R, Soumalias P, Martinez-Gili L, Chilloux J, Dickinson R, Dumas Met al., 2020,

    Serum metabolic profiling following traumatic brain injury in rats using ¹H nuclear magnetic resonance spectroscopy

    , Federation of European Neuroscience Societies
  • Journal article
    Saiz-Alia M, Reichenbach T, 2020,

    Computational modeling of the auditory brainstem response to continuous speech.

    , Journal of Neural Engineering, Vol: 17, Pages: 1-12, ISSN: 1741-2552

    OBJECTIVE: The auditory brainstem response can be recorded non-invasively from scalp electrodes and serves as an important clinical measure of hearing function. We have recently shown how the brainstem response at the fundamental frequency of continuous, non-repetitive speech can be measured, and have used this measure to demonstrate that the response is modulated by selective attention. However, different parts of the speech signal as well as several parts of the brainstem contribute to this response. Here we employ a computational model of the brainstem to elucidate the influence of these different factors. APPROACH: We developed a computational model of the auditory brainstem by combining a model of the middle and inner ear with a model of globular bushy cells in the cochlear nuclei and with a phenomenological model of the inferior colliculus. We then employed the model to investigate the neural response to continuous speech at different stages in the brainstem, following the methodology developed recently by ourselves for detecting the brainstem response to running speech from scalp recordings. We compared the simulations with recordings from healthy volunteers. MAIN RESULTS: We found that the auditory-nerve fibers, the cochlear nuclei and the inferior colliculus all contributed to the speech-evoked brainstem response, although the dominant contribution came from the inferior colliculus. The delay of the response corresponded to that observed in experiments. We further found that a broad range of harmonics of the fundamental frequency, up to about 8 kHz, contributed to the brainstem response. The response declined with increasing fundamental frequency, although the signal-to-noise ratio was largely unaffected. SIGNIFICANCE: Our results suggest that the scalp-recorded brainstem response at the fundamental frequency of speech originates predominantly in the inferior colliculus. They further show that the response is shaped by a large number of higher harmonics of
  • Journal article
    Yu X, Azor A, Sharp DJ, Mazdak Get al., 2020,

    Mechanisms of tensile failure of cerebrospinal fluid in blast traumatic brain injury

    , Extreme Mechanics Letters, Vol: 38, Pages: 1-9, ISSN: 2352-4316

    Mechanisms of blast-induced Traumatic Brain Injury (BTBI), particularly those linked to the primary pressure wave, are still not fully understood. One possible BTBI mechanism is cavitation in the cerebrospinal fluid (CSF) caused by CSF tensile failure, which is likely to increase strain and strain rate in the brain tissue near the CSF. Blast loading of the head can generate rarefaction (expansion) waves and rapid head motion, which both can produce tensile forces in the CSF. However, it is not clear which of these mechanisms is more likely to cause CSF tensile failure. In this study, we used a high-fidelity 3-dimensional computational model of the human head to test whether the CSF tensile failure increases brain deformation near the brain/CSF boundary and to determine the key failure mechanisms. We exposed the head model to a frontal blast wave and predicted strain and strain rate distribution in the cortex. We found that CSF tensile failure significantly increased strain and strain rate in the cortex. We then studied whether the rapid head motion or the rarefaction wave causes strain and strain rate concentration in cortex. We isolated these two effects by conducting simulations with pure head motion loading (i.e. prescribing the skull velocity but eliminating the pressure wave) and pure blast wave loading (i.e. eliminating head motion by fixing the skull base). Our results showed that the strain increase in the cortex was mainly caused by head motion. In contrast, strain rate increase was caused by both rapid head motion and rarefaction waves, but head motion had a stronger effect on elevating strain rate. Our results show that rapid motion of the head produced by blast wave is the key mechanism for CSF tensile failure and subsequent concentration of strain and strain rate in cortex. This finding suggests that mitigation of rapid head motion caused by blast loading needs to be addressed in the design of protective equipment in order to prevent the tensile failure
  • Journal article
    Nguyen TT, Meek G, Breeze J, Masouros Set al., 2020,

    Gelatine backing affects the performance of single-layer ballistic-resistant materials against blast fragments

    , Frontiers in Bioengineering and Biotechnology, Vol: 8, Pages: 1-10, ISSN: 2296-4185

    Penetrating trauma by energized fragments is the most common injury from explosive devices, the main threat in the contemporary battlefield. Such devices produce projectiles dependent upon their design, including preformed fragments, casings, glass, or stones; these are subsequently energized to high velocities and cause serious injuries to the body. Current body armor focuses on the essential coverage, which is mainly the thoracic and abdominal area, and can be heavy and cumbersome. In addition, there may be coverage gaps that can benefit from the additional protection provided by one or more layers of lightweight ballistic fabrics. This study assessed the performance of single layers of commercially available ballistic protective fabrics such as Kevlar®, Twaron®, and Dyneema®, in both woven and knitted configurations. Experiments were carried out using a custom-built gas-gun system, with a 0.78-g cylindrical steel fragment simulating projectile (FSP) as the impactor, and ballistic gelatine as the backing material. FSP velocity at 50% risk of material perforation, gelatine penetration, and high-risk wounding to soft tissue, as well as the depth of penetration (DoP) against impact velocity and the normalized energy absorption were used as metrics to rank the performance of the materials tested. Additional tests were performed to investigate the effect of not including a soft-tissue simulant backing material on the performance of the fabrics. The results show that a thin layer of ballistic material may offer meaningful protection against the penetration of this FSP. Additionally, it is essential to ensure a biofidelic boundary condition as the protective efficacy of fabrics was markedly altered by a gelatine backing.
  • Journal article
    Rankin IA, Webster CE, Gibb I, Clasper JC, Masouros SDet al., 2020,

    Pelvic injury patterns in blast: Morbidity and mortality

    , JOURNAL OF TRAUMA AND ACUTE CARE SURGERY, Vol: 88, Pages: 832-838, ISSN: 2163-0755
  • Conference paper
    Campos-Pires R, Mohamed-Ali N, Franks N, Aldhoun J, Dickinson Ret al., 2020,

    Hypothermia combined with xenon reduces secondary injury development and enhances neuroprotection by preventing neuronal cell loss in a rat model of traumatic brain injury

    , European Journal of Anaesthesia vol e37, Pages: 300-300
  • Journal article
    Reichenbach J, Keshavarzi M, 2020,

    Transcranial alternating current stimulation with the theta-band portion of the temporally-aligned speech envelope improves speech-in-noise comprehension

    , Frontiers in Human Neuroscience, Vol: 14, Pages: 1-8, ISSN: 1662-5161

    Transcranial alternating current stimulation with the speech envelope can modulate the comprehension of speech in noise. The modulation stems from the theta- but not the delta-band portion of the speech envelope, and likely reflects the entrainment of neural activity in the theta frequency band, which may aid the parsing of the speech stream. The influence of the current stimulation on speech comprehension can vary with the time delay between the current waveform and the audio signal. While this effect has been investigated for current stimulation based on the entire speech envelope, it has not yet been measured when the current waveform follows the theta-band portion of the speech envelope. Here, we show that transcranial current stimulation with the speech envelope filtered in the theta frequency band improves speech comprehension as compared to a sham stimulus. The improvement occurs when there is no time delay between the current and the speech stimulus, as well as when the temporal delay is comparatively short, 90 ms. In contrast, longer delays, as well as negative delays, do not impact speech-in-noise comprehension. Moreover, we find that the improvement of speech comprehension at no or small delays of the current stimulation is consistent across participants. Our findings suggest that cortical entrainment to speech is most influenced through current stimulation that follows the speech envelope with at most a small delay. They also open a path to enhancing the perception of speech in noise, an issue that is particularly important for people with hearing impairment.
  • Journal article
    Keshavarzi M, Kegler M, Kadir S, Reichenbach Jet al., 2020,

    Transcranial alternating current stimulation in the theta band but not in the delta band modulates the comprehension of naturalistic speech in noise

    , NeuroImage, Vol: 210, ISSN: 1053-8119

    Auditory cortical activity entrains to speech rhythms and has been proposed as a mechanism for online speech processing. In particular, neural activity in the theta frequency band (4–8 ​Hz) tracks the onset of syllables which may aid the parsing of a speech stream. Similarly, cortical activity in the delta band (1–4 ​Hz) entrains to the onset of words in natural speech and has been found to encode both syntactic as well as semantic information. Such neural entrainment to speech rhythms is not merely an epiphenomenon of other neural processes, but plays a functional role in speech processing: modulating the neural entrainment through transcranial alternating current stimulation influences the speech-related neural activity and modulates the comprehension of degraded speech. However, the distinct functional contributions of the delta- and of the theta-band entrainment to the modulation of speech comprehension have not yet been investigated. Here we use transcranial alternating current stimulation with waveforms derived from the speech envelope and filtered in the delta and theta frequency bands to alter cortical entrainment in both bands separately. We find that transcranial alternating current stimulation in the theta band but not in the delta band impacts speech comprehension. Moreover, we find that transcranial alternating current stimulation with the theta-band portion of the speech envelope can improve speech-in-noise comprehension beyond sham stimulation. Our results show a distinct contribution of the theta- but not of the delta-band stimulation to the modulation of speech comprehension. In addition, our findings open up a potential avenue of enhancing the comprehension of speech in noise.
  • Journal article
    Hopkins M, Vaidyanathan R, McGregor AH, 2020,

    Examination of the performance characteristics of velostat as an in-socket pressure sensor

    , IEEE Sensors Journal, Vol: 20, Pages: 6992-7000, ISSN: 1530-437X

    Velostat is a low-cost, low-profile electrical bagging material with piezoresistive properties, making it an attractive option for in-socket pressure sensing. The focus of this research was to explore the suitability of a Velostat-based system for providing real-time socket pressure profiles. The prototype system performance was explored through a series of bench tests to determine properties including accuracy, repeatability and hysteresis responses, and through participant testing with a single subject. The fabricated sensors demonstrated mean accuracy errors of 110 kPa and significant cyclical and thermal drift effects of up to 0.00715 V/cycle and leading to up to a 67% difference in voltage range respectively. Despite these errors the system was able to capture data within a prosthetic socket, aligning to expected contact and loading patterns for the socket and amputation type. Distinct pressure maps were obtained for standing and walking tasks displaying loading patterns indicative of posture and gait phase. The system demonstrated utility for assessing contact and movement patterns within a prosthetic socket, potentially useful for improvement of socket fit, in a low cost, low profile and adaptable format. However, Velostat requires significant improvement in its electrical properties before proving suitable for accurate pressure measurement tools in lower limb prosthetics.
  • Journal article
    Nguyen TT, Carpanen D, Stinner D, Rankin I, Ramasamy A, Breeze J, Proud W, Clasper J, Masouros Set al., 2020,

    The risk of fracture to the tibia from a fragment simulating projectile

    , Journal of The Mechanical Behavior of Biomedical Materials, Vol: 102, ISSN: 1751-6161

    Penetrating injuries due to fragments energised by an explosive event are life threatening and are associated with poor clinical and functional outcomes. The tibia is the long bone most affected in survivors of explosive events, yet the risk of penetrating injury to it has not been quantified. In this study, an injury-risk assessment of penetrating injury to the tibia was conducted using a gas-gun system with a 0.78-g cylindrical fragment simulating projectile. An ovine tibia model was used to generate the injury-risk curves and human cadaveric tests were conducted to validate and scale the results of the ovine model. The impact velocity at 50% risk (±95% confidence intervals) for EF1+, EF2+, EF3+, and EF4+ fractures to the human tibia – using the modified Winquist-Hansen classification – was 271 ± 30, 363 ± 46, 459 ± 102, and 936 ± 182 m/s, respectively. The scaling factor for the impact velocity from cadaveric ovine to human was 2.5. These findings define the protection thresholds to improve the injury outcomes for fragment penetrating injury to the tibia.
  • Journal article
    Stewart S, Darwood A, Masouros S, Higgins C, Ramasamy Aet al., 2020,

    Mechanotransduction in osteogenesis

    , Bone and Joint Research, Vol: 9, Pages: 1-14, ISSN: 2046-3758

    Bone is one of the most highly adaptive tissues in the body, possessing the capability to alter its morphology and function in response to stimuli in its surrounding environment. The ability of bone to sense and convert external mechanical stimuli into a biochemical response, which ultimately alters the phenotype and function of the cell, is described as mechanotransduction. This review aims to describe the fundamental physiology and biomechanisms that occur to induce osteogenic adaptation of a cell following application of a physical stimulus. Considerable developments have been made in recent years in our understanding of how cells orchestrate this complex interplay of processes, and have become the focus of research in osteogenesis. We will discuss current areas of preclinical and clinical research exploring the harnessing of mechanotransductive properties of cells and applying them therapeutically, both in the context of fracture healing and de novo bone formation in situations such as nonunion.

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