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  • Journal article
    Grigoriadis G, Carpanen D, Webster CE, Ramasamy A, Newell N, Masouros SDet al., 2019,

    Lower limb posture affects the mechanism of injury in under-body blast

    , Annals of Biomedical Engineering, Vol: 47, Pages: 306-316, ISSN: 0090-6964

    Over 80% of wounded Service Members sustain at least one extremity injury. The 'deck-slap' foot, a product of the vehicle's floor rising rapidly when attacked by a mine to injure the limb, has been a signature injury in recent conflicts. Given the frequency and severity of these combat-related extremity injuries, they require the greatest utilisation of resources for treatment, and have caused the greatest number of disabled soldiers during recent conflicts. Most research efforts focus on occupants seated with both tibia-to-femur and tibia-to-foot angles set at 90°; it is unknown whether results obtained from these tests are applicable when alternative seated postures are adopted. To investigate this, lower limbs from anthropometric testing devices (ATDs) and post mortem human subjects (PMHSs) were loaded in three different seated postures using an under-body blast injury simulator. Using metrics that are commonly used for assessing injury, such as the axial force and the revised tibia index, the lower limb of ATDs were found to be insensitive to posture variations while the injuries sustained by the PMHS lower limbs differed in type and severity between postures. This suggests that the mechanism of injury depends on the posture and that this cannot be captured by the current injury criteria. Therefore, great care should be taken when interpreting and extrapolating results, especially in vehicle qualification tests, when postures other than the 90°-90° are of interest.

  • Journal article
    Campos Pires R, Yonis A, Macdonald W, Harris K, Edge C, Mahoney P, Dickinson Ret al., 2018,

    A novel In vitro model of blast traumatic brain injury

    , Jove-Journal of Visualized Experiments, Vol: 142, ISSN: 1940-087X

    Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

  • Journal article
    Logan N, Camman M, Williams G, Higgins Cet al., 2018,

    Demethylation of ITGAV accelerates osteogenic differentiation in a blast-induced heterotopic ossification in vitro cell culture model

    , BONE, Vol: 117, Pages: 149-160, ISSN: 8756-3282

    Trauma-induced heterotopic ossification is an intriguing phenomenon involving the inappropriate ossification of soft tissues within the body such as the muscle and ligaments. This inappropriate formation of bone is highly prevalent in those affected by blast injuries. Here, we developed a simplified cell culture model to evaluate the molecular events involved in heterotopic ossification onset that arise from the shock wave component of the disease. We exposed three subtypes of human mesenchymal cells in vitro to a single, high-energy shock wave and observed increased transcription in the osteogenic master regulators, Runx2 and Dlx5, and significantly accelerated cell mineralisation. Reduced representation bisulfite sequencing revealed that the shock wave altered methylation of gene promoters, leading to opposing changes in gene expression. Using a drug to target ITGAV, whose expression was perturbed by the shock wave, we found that we could abrogate the deposition of mineral in our model. These findings show how new therapeutics for the treatment of heterotopic ossification can be identified using cell culture models.

  • Journal article
    Rosenberg N, Bull AMJ, 2018,

    Application of a mechanobiological algorithm to investigate mechanical mediation of heterotopic bone in trans-femoral amputees

    , Scientific Reports, Vol: 8, Pages: 1-11, ISSN: 2045-2322

    Heterotopic ossification (HO) is the process of bone formation in tissues that are not usually osseous. It occurs in 60% of those with blast-related amputations. HO can result in reduced range of motion, pain, nerve impingement and can affect prosthesis fitting and is caused by a combination of mechanical, biological, local and systemic factors. As with normal bone formation and remodelling, it is expected that heterotopic bone responds to mechanical stimuli and understanding this relationship can give insight into the pathology. The objective of this research was to investigate whether a physiological 2D computational model that considers both mechanical and biological factors can be used to simulate HO in the residual limb of a trans-femoral amputee. The study found that characteristic morphologies of HO were reproduced by adjusting the loading environment. Significant effects were produced by changing the loading direction on the femur; this is potentially associated with different initial surgical interventions such as muscle myodesis. Also, initial treatment such as negative pressure through a dressing was found to change the shape of heterotopic bone.

  • Conference paper
    Nguyen TT, Carpanen D, Tear G, Stinner D, Clasper J, Proud W, Masouros Set al., 2018,

    Fragment Penetrating Injury to the tibia

    , Personal Armour Systems Symposia 2018
  • Journal article
    Zaharie DZ, Phillips ATM, 2018,

    Pelvic construct prediction of trabecular and cortical bone structural architecture

    , Journal of Biomechanical Engineering, Vol: 140, Pages: 1-11, ISSN: 0148-0731

    The pelvic construct is an important part of the body as it facilitates the transfer of upper body weight to the lower limbs and protects a number of organs and vessels in the lower abdomen. In addition, the importance of the pelvis is highlighted by the high mortality rates associated with pelvic trauma. This study presents a mesoscale structural model of the pelvic construct and the joints and ligaments associated with it. Shell elements were used to model cortical bone, while truss elements were used to model trabecular bone and the ligaments and joints. The finite element (FE) model was subjected to an iterative optimization process based on a strain-driven bone adaptation algorithm. The bone model was adapted to a number of common daily living activities (walking, stair ascent, stair descent, sit-to-stand, and stand-to-sit) by applying onto it joint and muscle loads derived using a musculoskeletal modeling framework. The cortical thickness distribution and the trabecular architecture of the adapted model were compared qualitatively with computed tomography (CT) scans and models developed in previous studies, showing good agreement. The sensitivity of the model to changes in material properties of the ligaments and joint cartilage and changes in parameters related to the adaptation algorithm was assessed. Changes to the target strain had the largest effect on predicted total bone volumes. The model showed low sensitivity to changes in all other parameters. The minimum and maximum principal strains predicted by the structural model compared to a continuum CT-derived model in response to a common test loading scenario showed good agreement with correlation coefficients of 0.813 and 0.809, respectively. The developed structural model enables a number of applications such as fracture modeling, design, and additive manufacturing of frangible surrogates.

  • Journal article
    Webster CE, Clasper J, Stinner DJ, Eliahoo J, Masouros SDet al., 2018,

    Characterization of Lower Extremity Blast Injury

    , MILITARY MEDICINE, Vol: 183, Pages: E448-E453, ISSN: 0026-4075
  • Conference paper
    Campos-Pires R, Armstrong S, Sebastiani A, Luh C, Gruss M, Radyushkin K, Hirnet T, Werner C, Engelhard K, Franks NP, Thal SC, Dickinson Ret al., 2018,

    Xenon treatment improves short-term and long-term outcomes in a rodent model of traumatic brain injury

    , British Journal of Anaesthesia Research Forum, Publisher: Elsevier, Pages: e21-e21, ISSN: 0007-0912
  • Conference paper
    Campos-Pires R, Yonis A, Pau A, Macdonald W, Harris K, Edge CJ, Franks NP, Mahoney PF, Dickinson Ret al., 2018,

    Xenon is neuroprotective against blast traumatic brain injury in vitro

    , British Journal of Anaesthesia Research Forum, Publisher: Elsevier, Pages: e23-e23, ISSN: 0007-0912
  • Conference paper
    Nguyen T-TN, Tear GR, Masouros SD, Proud WGet al., 2018,

    Fragment Penetrating Injury to Long Bones

    , 20th Biennial Conference of the Topical-Group of the American-Physical-Society (APS) on Shock Compression of Condensed Matter (SCCM), Publisher: AMER INST PHYSICS, ISSN: 0094-243X
  • Conference paper
    Brown KA, Butler BJ, Sory D, Nguyen T-TN, Williams A, Proud WGet al., 2018,

    Challenges in the Characterization of Failure and Resilience of Biological Materials

    , 20th Biennial Conference of the Topical-Group of the American-Physical-Society (APS) on Shock Compression of Condensed Matter (SCCM), Publisher: AMER INST PHYSICS, ISSN: 0094-243X
  • Journal article
    Newell N, Pearce AP, Spurrier E, Gibb I, Webster CE, Masouros SD, Clasper JCet al., 2018,

    Analysis of isolated transverse process fractures sustained during blast related events

    , Journal of Trauma and Acute Care Surgery, Vol: 85, Pages: S129-S133, ISSN: 2163-0763

    BACKGROUND: A range of devastating blast injuries have been sustained by personnel during recent conflicts. Previous studies have focused on severe injuries, including to the spine, however, no study has specifically focused on the most common spinal injury; transverse process (TP) fractures. Although their treatment usually requires limited intervention, analysis of TP fractures may help determine injury mechanisms. METHODS: Data was collected from victims with spinal fractures injured in Improvised Explosive Device (IED) attacks, from the UK's Joint Theatre Trauma Registry. The level and side of each TP fracture was recorded, as well as associated injuries, whether they were mounted or dismounted, and outcome (survivor or fatality). RESULTS: The majority of TP fractures were lumbar (80%). More bilateral (both left and right fractures at the same level), and L5 TP fractures, were seen in fatalities than survivors. In the mounted group, lumbar TP fractures were statistically significantly associated with fatality, head injury, non-compressible torso haemorrhage, pelvic injury, and other spinal injuries. In the dismounted group, thoracic TP fractures were associated with head, chest wall, and other spinal injuries, and lumbar TP fractures were associated with pelvic, and other spinal injuries. CONCLUSIONS: Different injury mechanisms of the TP in the mounted and dismounted groups are likely. Inertial forces acting within the torso due to rapid loading being transferred through the seat, or high intra-abdominal pressures causing the tensile forces acting through the lumbar fascia to avulse the TPs are likely mechanisms in the mounted group. Blunt trauma, violent lateral flexion-extension forces, or rapid flail of the lower extremities causing tension of the psoas muscle, avulsing the TP are likely causes in the dismounted group. Isolated lumbar TP fractures can be used as markers for more severe injuries, and fatality, in mounted blast casualties. LEVEL OF EVIDENCE: P

  • Journal article
    Nguyen TN, Sory DR, Rankin SM, Proud WG, Amin HDet al., 2018,

    Platform development for primary blast injury studies

    , Trauma (United Kingdom), ISSN: 1460-4086

    © 2018, The Author(s) 2018. Explosion-related injuries are currently the most commonly occurring wounds in modern conflicts. They are observed in both military and civilian theatres, with complex injury pathophysiologies. Primary blast injuries are the most frequently encountered critical injuries experienced by victims close to the explosion. They are caused by large and rapid pressure changes of the blast waves which produce a wide range of loading patterns resulting in varied injuries. Well-characterised experimental loading devices which can reproduce the real mechanical characteristics of blast loadings on biological specimens in in vivo, ex vivo, and in vitro models are essential in determining the injury mechanisms. This paper discusses the performance and application of platforms, including shock tubes, mechanical testing machines, drop-weight rigs, and split-Hopkinson pressure bar, with regards to the replication of primary blast.

  • Journal article
    Campos Pires R, Koziakova M, Yonis A, Pau A, Macdonald W, Harris K, Edge C, Franks N, Mahoney P, Dickinson Ret al., 2018,

    Xenon protects against blast-induced traumatic brain injury in an in vitro model

    , Journal of Neurotrauma, Vol: 35, Pages: 1037-1044, ISSN: 0897-7151

    The aim of this study was to evaluate the neuroprotective efficacy of the inert gas xenon as a treatment for patients with blast-induced traumatic brain injury in an in vitro laboratory model. We developed a novel blast traumatic brain injury model using C57BL/6N mouse organotypic hippocampal brain-slice cultures exposed to a single shockwave, with the resulting injury quantified using propidium iodide fluorescence. A shock tube blast generator was used to simulate open field explosive blast shockwaves, modeled by the Friedlander waveform. Exposure to blast shockwave resulted in significant (p < 0.01) injury that increased with peak-overpressure and impulse of the shockwave, and which exhibited a secondary injury development up to 72 h after trauma. Blast-induced propidium iodide fluorescence overlapped with cleaved caspase-3 immunofluorescence, indicating that shock-wave–induced cell death involves apoptosis. Xenon (50% atm) applied 1 h after blast exposure reduced injury 24 h (p < 0.01), 48 h (p < 0.05), and 72 h (p < 0.001) later, compared with untreated control injury. Xenon-treated injured slices were not significantly different from uninjured sham slices at 24 h and 72 h. We demonstrate for the first time that xenon treatment after blast traumatic brain injury reduces initial injury and prevents subsequent injury development in vitro. Our findings support the idea that xenon may be a potential first-line treatment for those with blast-induced traumatic brain injury.

  • Conference paper
    Forte AE, Etard OE, Reichenbach JDT, 2018,

    Selective Auditory Attention At The Brainstem Level

    , ARO 2018
  • Conference paper
    Saiz Alia M, Askari A, Forte AE, Reichenbach JDTet al., 2018,

    A model of the human auditory brainstem response to running speech

    , ARO 2018
  • Conference paper
    Kegler M, Etard OE, Forte AE, Reichenbach JDTet al., 2018,

    Complex Statistical Model for Detecting the Auditory Brainstem Response to Natural Speech and for Decoding Attention from High-Density EEG Recordings

    , ARO 2018
  • Journal article
    Karunaratne A, Li S, Bull A, 2018,

    Nano-scale mechanisms explain the stiffening and strengthening of ligament tissue with increasing strain rate

    , Scientific Reports, Vol: 8, ISSN: 2045-2322

    Ligament failure is a major societal burden causing disability and pain. Failure is caused by trauma at high loading rates. At the macroscopic level increasing strain rates cause an increase in failure stress and modulus, but the mechanism for this strain rate dependency is not known. Here we investigate the nano scale mechanical property changes of human ligament using mechanical testing combined with synchrotron X-ray diffraction. With increasing strain rate, we observe a significant increase in fibril modulus and a reduction of fibril to tissue strain ratio, revealing that tissue-level stiffening is mainly due to the stiffening of collagen fibrils. Further, we show that the reduction in fibril deformation at higher strain rates is due to reduced molecular strain and fibrillar gaps, and is associated with rapid disruption of matrix-fibril bonding. This reduction in number of interfibrillar cross-links explains the changes in fibril strain; this is verified through computational modelling.

  • Journal article
    Rosenberg N, Bull AMJ, 2018,

    Simulating localised cellular inflammation and substrate properties in a strain energy density based bone remodelling algorithm for use in modelling trauma

    , Computer Methods in Biomechanics and Biomedical Engineering, Vol: 21, Pages: 208-218, ISSN: 1025-5842

    Bone responds to mechanical stimulus and a range of pre-existing finite element models have been suggested to reproduce the internal physiological structure of bone. Inflammation effects are not included in these models, yet inflammation is a key component of bone repair in trauma. Therefore, a model is proposed and tested here that extends these methods to include parameters that could be considered to represent the behaviour of bone remodelling when influenced by inflammation. The proposed model regulates remodelling based on findings from recent studies into the nature of heterotopic ossification, the formation of heterotopic bone, which have revealed information about the nature of bone after high levels of trauma. These parameters include consideration of the distance from the zone of trauma, the density of mesenchymal stem cells, and substrate stiffness as a trigger for cells becoming osteogenic. The method is tested on a two-dimensional plate model and shows that the new extended algorithm can produce a range of structures depending on inputs that could be used in the future to replicate physiological scenarios.

  • Journal article
    Etard OE, Kegler M, Braiman C, Forte AE, Reichenbach JDTet al., 2018,

    Real-time decoding of selective attention from the human auditory brainstem response to continuous speech

    , BioRxiv

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