Research Evaluating Sports ConcUssion Events-Rapid Assessment of Concussion and Evidence for Return (RESCUE-RACER): a two-year longitudinal observational study of concussion in motorsport.

INTRODUCTION: Concussion is a clinical diagnosis, based on self-reported patient symptoms supported by clinical assessments across many domains including postural control, ocular/vestibular dysfunction, and neurocognition. Concussion incidence may be rising in motorsport which, combined with unresolved challenges to accurate diagnosis and lack of guidance on the optimal return-to-race timeframe, creates a difficult environment for healthcare practitioners. METHODS AND ANALYSIS: Research Evaluating Sports ConcUssion Events-Rapid Assessment of Concussion and Evidence for Return (RESCUE-RACER) evaluates motorsports competitors at baseline (Competitor Assessment at Baseline; Ocular, Neuroscientific (CArBON) study) and post-injury (Concussion Assessment and Return to motorSport (CARS) study), including longitudinal data. CArBON collects pre-injury neuroscientific data; CARS repeats the CArBON battery sequentially during recovery for competitors involved in a potentially concussive event. As its primary outcome, RESCUE-RACER will develop the evidence base for an accurate trackside diagnostic tool. Baseline objective clinical scoring (Sport Concussion Assessment Tool-5th edition (SCAT5)) and neurocognitive data (Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT)) will be assessed for specificity to motorsport and relationship to existing examinations. Changes to SCAT5 and ocular, vestibular, and reaction time function (Dx 100) will be estimated by the reliability change index as a practical tool for trackside diagnosis. Neuropsychological (Cambridge Neuropsychological Test Automated Battery (CANTAB)) assessments, brain MRI (7 Tesla) and salivary biomarkers will be compared with the new tool to establish utility in diagnosing and monitoring concussive injuries. ETHICS AND DISSEMINATION: Ethical approval was received from East of England-Cambridge Central Research Ethics Committee (18/EE/0141). Participants will be notified of study outcomes via publications (to administrators) and summary reports (funder communications). Ideally, all publications will be open access. TRIAL REGISTRATION NUMBER: February 2019 nationally (Central Portfolio Management System 38259) and internationally (ClinicalTrials.gov NCT03844282)

The extinct, giant giraffid Sivatherium giganteum: skeletal reconstruction and body mass estimation

Sivatherium giganteum is an extinct giraffid from the Plio–Pleistocene boundary of the Himalayan foothills. To date, there has been no rigorous skeletal reconstruction of this unusual mammal. Historical and contemporary accounts anecdotally state that Sivatherium rivalled the African elephant in terms of its body mass, but this statement has never been tested. Here, we present a three-dimensional composite skeletal reconstruction and calculate a representative body mass estimate for this species using a volumetric method. We find that the estimated adult body mass of 1246 kg (857—1812 kg range) does not approach that of an African elephant, but confirms that Sivatherium was certainly a large giraffid, and may have been the largest ruminant mammal that has ever existed. We contrast this volumetric estimate with a bivariate scaling estimate derived from Sivatherium's humeral circumference and find that there is a discrepancy between the two. The difference implies that the humeral circumference of Sivatherium is greater than expected for an animal of this size, and we speculate this may be linked to a cranial shift in centre of mass

Unpicking the Gordian knot: a systems approach to traumatic brain injury care in low-income and middle-income countries.

The Global Burden of Diseases, Injuries, and Risk Factors Study showed that in 2010 trauma accounted for 9% of the world's deaths - around 5 million people - while also resulting in millions of non-fatal injuries with resultant disability. Around 90% of injury-related deaths occurred in low and middle income countries (LMICs) which also saw the greatest rise in these injuries due to road traffic collisions.1 More recent Global Health Estimates from the World Health Organisation for 2015 show a similar picture.2 As a disease subtype, Traumatic Brain Injury (TBI) is one of the most devastating, with clinical, societal, and economic sequelae.3 It is also startlingly common with an estimated 50 million or more cases per year; enough for half of the world's population to suffer a TBI in their lifetime and again disproportionately affecting lower-income regions.

Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

Background: Dried blood spot (DBS) testing for hepatitis C (HCV) was introduced to Scotland in 2009. This minimally invasive specimen provides an alternative to venipuncture and can overcome barriers to testing in people who inject drugs (PWID). Objectives: The objective of this study was to determine rates and predictors of: exposure to HCV, attendance at specialist clinics and anti-viral treatment initiation among the DBS tested population in Scotland. Study design: DBS testing records were deterministically linked to the Scottish HCV Clinical database prior to logistic regression analysis. Results: In the first two years of usage in Scotland, 1322 individuals were tested by DBS of which 476 were found to have an active HCV infection. Linkage analysis showed that 32% had attended a specialist clinic within 12 months of their specimen collection date and 18% had begun anti-viral therapy within 18 months of their specimen collection date. A significantly reduced likelihood of attendance at a specialist clinic was evident amongst younger individuals (<35 years), those of unknown ethnic origin and those not reporting injecting drug use as a risk factor. Conclusion: We conclude that DBS testing in non-clinical settings has the potential to increase diagnosis and, with sufficient support, treatment of HCV infection among PWID

Vitamin D Receptor Variants and Uncontrolled Asthma

BACKGROUND: Asthma is a common childhood respiratory disease, affecting around 20% of Irish children. In other populations, vitamin D receptor (VDR) polymorphisms have been associated with asthma risk. We aimed to investigate the association between 2 VDR polymorphisms and uncontrolled paediatric asthma. METHODS: 44 asthmatic children and 57 healthy volunteers were studied. The VDR TaqI gene variant in exon 9 (T/C) (rs731236) and ApaI (rs7975232) in intron 8 (C/T) were determined, using TaqMan®Assays. The lung function, serum 25-hydroxyvitamin D (25OHD) levels and other biomarkers of allergy, immunity, airway and systemic inflammation were assessed. RESULTS: The distribution of T and C alleles and genotype frequencies differed significantly between asthmatics and controls for both polymorphisms (

Matrix Metalloproteinase Expression in Contusional Traumatic Brain Injury: A Paired Microdialysis Study.

Matrix metalloproteinases (MMPs) are extracellular enzymes that have been implicated in the pathophysiology of blood-brain barrier (BBB) breakdown, contusion expansion, and vasogenic edema after traumatic brain injury (TBI). Specifically, in focal injury models, increased MMP-9 expression has been observed in pericontusional brain, and MMP-9 inhibitors reduce brain swelling and final lesion volume. The aim of this study was to examine whether there is a similarly localized increase of MMP concentrations in patients with contusional TBI. Paired microdialysis catheters were inserted into 12 patients with contusional TBI (with or without associated mass lesion) targeting pericontusional and radiologically normal brain defined on admission computed tomography scan. Microdialysate was pooled every 8 h and analyzed for MMP-1, -2, -7, -9, and -10 using a multiplex immunoassay. Concentrations of MMP-1, -2, and -10 were similar at both monitoring sites and did not show discernible temporal trends. Overall, there was a gradual increase in MMP-7 concentrations in both normal and injured brain over the monitoring period, although this was not consistent in every patient. MMP-9 concentrations were elevated in pericontusional, compared to normal, brain, with the maximal difference at the earliest monitoring times (i.e., <24 h postinjury). Repeated-measures analysis of variance showed that MMP-9 concentrations were significantly higher in pericontusional brain (p=0.03) and within the first 72 h of injury, compared with later in the monitoring period (p=0.04). No significant differences were found for the other MMPs assayed. MMP-9 concentrations are increased in pericontusional brain early post-TBI and may represent a potential therapeutic target to reduce hemorrhagic progression and vasogenic edema.M.R.G. was supported by a National Institute for Health Research (NIHR) Academic Clinical Fellowship, a Royal College of Surgeons/Philip King Research Fellowship, and a Beverley and Raymond Sackler Fellowship. A.H. was supported by a joint Medical Research Council/ Royal College of Surgeons of England Clinical Research Training Fellowship. K.L.H.C. is supported by the NIHR Biomedical Research Center, Cambridge (Neuroscience Theme; Brain Injury and Repair Theme). J.D.P. is supported by the Traumatic Brain Injury NIHR Health Technology Cooperative. D.K.M. is supported by an NIHR Senior Investigator Award. P.J.A.H. is supported by the Cambridge NIHR BRC and an NIHR Research Professorship.This is the final published version. It was first made available by Mary Ann Liebert at http://dx.doi.org/10.1089/neu.2014.376

A noninvasive estimation of cerebral perfusion pressure using critical closing pressure.

OBJECT: Cerebral blood flow is associated with cerebral perfusion pressure (CPP), which is clinically monitored through arterial blood pressure (ABP) and invasive measurements of intracranial pressure (ICP). Based on critical closing pressure (CrCP), the authors introduce a novel method for a noninvasive estimator of CPP (eCPP). METHODS: Data from 280 head-injured patients with ABP, ICP, and transcranial Doppler ultrasonography measurements were retrospectively examined. CrCP was calculated with a noninvasive version of the cerebrovascular impedance method. The eCPP was refined with a predictive regression model of CrCP-based estimation of ICP from known ICP using data from 232 patients, and validated with data from the remaining 48 patients. RESULTS: Cohort analysis showed eCPP to be correlated with measured CPP (R = 0.851, p < 0.001), with a mean ± SD difference of 4.02 ± 6.01 mm Hg, and 83.3% of the cases with an estimation error below 10 mm Hg. eCPP accurately predicted low CPP (< 70 mm Hg) with an area under the curve of 0.913 (95% CI 0.883-0.944). When each recording session of a patient was assessed individually, eCPP could predict CPP with a 95% CI of the SD for estimating CPP between multiple recording sessions of 1.89-5.01 mm Hg. CONCLUSIONS: Overall, CrCP-based eCPP was strongly correlated with invasive CPP, with sensitivity and specificity for detection of low CPP that show promise for clinical use.G. Varsos is supported by an A. G. Leventis Foundation Scholarship and a Charter Studentship from St. Edmund’s College, Cambridge. Dr. Kolias is supported by a Royal College of Surgeons of England Research Fellowship, a National Institute for Health Research (NIHR) Academic Clinical Fellowship, and a Raymond and Beverly Sackler Studentship. He also chairs the British Neurosurgical Trainee Research Collaborative, which has been supported with an educational grant from Codman. Dr. Hutchinson is supported by an NIHR Research Professorship, the NIHR Cambridge Biomedical Research Centre, and has been appointed as the Surgical Specialty Lead for Neurosurgery, Royal College of Surgeons of England Clinical Research Initiative. He is a director of Technicam, a manufacturer of cranial access devices for neuromonitoring. He has also received honoraria from Codman. J. Pickard’s research (excluding salary) is supported by the NIHR Cambridge Biomedical Research Centre and an NIHR Senior Investigator Award. ICM+ Software is licensed by Cambridge Enterprise, Cambridge, UK, and Dr. Czosnyka and Dr. Smielewski have a financial interest in a fraction of the licensing fee. Dr. Czosnyka has also served as a consultant to Codman.This is the author accepted manuscript. The final version is available from American Association of Neurological Surgeons via http://dx.doi.org/10.3171/2014.10.JNS14613