Management of traumatic brain injury (TBI): a clinical neuroscience-led pathway for the NHS.

Following hyperacute management after traumatic brain injury (TBI), most patients receive treatment which is inadequate or inappropriate, and delayed. This results in suboptimal rehabilitation outcome and avoidable detrimental chronic effects on patients' recovery. This worsens long-term disability, and magnifies costs to the individual and society. We believe that accurate diagnosis (at the level of pathology, impairment and function) of the causes of disability is a prerequisite for appropriate care and for accessing effective rehabilitation. An expert-led, integrated care pathway is needed to deliver accurate and timely diagnosis and optimal treatment at all stages during a TBI patient's care.We propose the introduction of a specialist interdisciplinary traumatic brain injury team, led by a neurosciences-trained brain injury consultant. This team would engage acutely and for a longer term after TBI to provide accurate diagnoses, which guides subsequent management and rehabilitation. This approach would also encourage more efficient collaboration between research and the clinic. We propose that the current major trauma network is leveraged to introduce and evaluate this proposal. Improvements to patient outcomes through this approach would lead to reduced personal, societal and economic impact of TBI

Sprint interval and sprint continuous training increases circulating CD34+ cells and cardio-respiratory fitness in young healthy women

The improvement of vascular health in the exercising limb can be attained by sprint interval training (SIT). However, the effects on systemic vascular function and on circulating angiogenic cells (CACs) which may contribute to endothelial repair have not been investigated. Additionally, a comparison between SIT and sprint continuous training (SCT) which is less time committing has not been made

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

Carbon stable isotope analysis of cereal remains as a way to reconstruct water availability: preliminary results

Reconstructing past water availability, both as rainfall and irrigation, is important to answer questions about the way society reacts to climate and its changes and the role of irrigation in the development of social complexity. Carbon stable isotope analysis of archaeobotanical remains is a potentially valuable method for reconstructing water availability. To further define the relationship between water availability and plant carbon isotope composition and to set up baseline values for the Southern Levant, grains of experimentally grown barley and sorghum were studied. The cereal crops were grown at three stations under five different irrigation regimes in Jordan. Results indicate that a positive but weak relationship exists between irrigation regime and total water input of barley grains, but no relationship was found for sorghum. The relationship for barley is site-specific and inter-annual variation was present at Deir ‘Alla, but not at Ramtha and Khirbet as-Samra

Imaging in population science: cardiovascular magnetic resonance in 100,000 participants of UK Biobank - rationale, challenges and approaches

PMCID: PMC3668194SEP was directly funded by the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. SN acknowledges support from the Oxford NIHR Biomedical Research Centre and from the Oxford British Heart Foundation Centre of Research Excellence. SP and PL are funded by a BHF Senior Clinical Research fellowship. RC is supported by a BHF Research Chair and acknowledges the support of the Oxford BHF Centre for Research Excellence and the MRC and Wellcome Trust. PMM gratefully acknowledges training fellowships supporting his laboratory from the Wellcome Trust, GlaxoSmithKline and the Medical Research Council

Phylogeography of Japanese encephalitis virus:genotype is associated with climate

The circulation of vector-borne zoonotic viruses is largely determined by the overlap in the geographical distributions of virus-competent vectors and reservoir hosts. What is less clear are the factors influencing the distribution of virus-specific lineages. Japanese encephalitis virus (JEV) is the most important etiologic agent of epidemic encephalitis worldwide, and is primarily maintained between vertebrate reservoir hosts (avian and swine) and culicine mosquitoes. There are five genotypes of JEV: GI-V. In recent years, GI has displaced GIII as the dominant JEV genotype and GV has re-emerged after almost 60 years of undetected virus circulation. JEV is found throughout most of Asia, extending from maritime Siberia in the north to Australia in the south, and as far as Pakistan to the west and Saipan to the east. Transmission of JEV in temperate zones is epidemic with the majority of cases occurring in summer months, while transmission in tropical zones is endemic and occurs year-round at lower rates. To test the hypothesis that viruses circulating in these two geographical zones are genetically distinct, we applied Bayesian phylogeographic, categorical data analysis and phylogeny-trait association test techniques to the largest JEV dataset compiled to date, representing the envelope (E) gene of 487 isolates collected from 12 countries over 75 years. We demonstrated that GIII and the recently emerged GI-b are temperate genotypes likely maintained year-round in northern latitudes, while GI-a and GII are tropical genotypes likely maintained primarily through mosquito-avian and mosquito-swine transmission cycles. This study represents a new paradigm directly linking viral molecular evolution and climate

Natural Infection of the Ground Squirrel (Spermophilus spp.) with Echinococcus granulosus in China

Echinococcus granulosus and E. multilocularis are important zoonotic pathogens that cause serious disease in humans. E. granulosus can be transmitted through sylvatic cycles, involving wild carnivores and ungulates; or via domestic cycles, usually involving dogs and farm livestock. E. multilocularis is primarily maintained in a sylvatic life-cycle between foxes and rodents. As part of extensive investigations that we undertook to update available epidemiological data and to monitor the transmission patterns of both E. granulosus and E. mulilocularis in Ningxia Hui Autonomous Region (NHAR) in northwest China, we captured small mammals on the southern slopes of Yueliang Mountain, Xiji, an area co-endemic for human alveolar echinococcosis and cystic echinococcosis. Of 500 trapped small mammals (mainly ground squirrels; Spermophilus dauricus/alashanicus), macroscopic cyst-like lesions (size range 1–10 mm) were found on the liver surface of approximately 10% animals. One of the lesions was shown by DNA analysis to be caused by E. granulosus and by histology to contain viable protoscoleces. This is the first report of a natural infection of the ground squirrel with E. granulosus. We have no definitive proof of a cycle involving ground squirrels and dogs/foxes but it is evident that there is active E. granulosus transmission occurring in this area