595 research outputs found

    Systematic review of prognostic models in traumatic brain injury

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    BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability world-wide. The ability to accurately predict patient outcome after TBI has an important role in clinical practice and research. Prognostic models are statistical models that combine two or more items of patient data to predict clinical outcome. They may improve predictions in TBI patients. Multiple prognostic models for TBI have accumulated for decades but none of them is widely used in clinical practice. The objective of this systematic review is to critically assess existing prognostic models for TBI METHODS: Studies that combine at least two variables to predict any outcome in patients with TBI were searched in PUBMED and EMBASE. Two reviewers independently examined titles, abstracts and assessed whether each met the pre-defined inclusion criteria. RESULTS: A total of 53 reports including 102 models were identified. Almost half (47%) were derived from adult patients. Three quarters of the models included less than 500 patients. Most of the models (93%) were from high income countries populations. Logistic regression was the most common analytical strategy to derived models (47%). In relation to the quality of the derivation models (n:66), only 15% reported less than 10% pf loss to follow-up, 68% did not justify the rationale to include the predictors, 11% conducted an external validation and only 19% of the logistic models presented the results in a clinically user-friendly way CONCLUSION: Prognostic models are frequently published but they are developed from small samples of patients, their methodological quality is poor and they are rarely validated on external populations. Furthermore, they are not clinically practical as they are not presented to physicians in a user-friendly way. Finally because only a few are developed using populations from low and middle income countries, where most of trauma occurs, the generalizability to these setting is limited

    Consumer perceptions of co-branding alliances: Organizational dissimilarity signals and brand fit

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    This study explores how consumers evaluate co-branding alliances between dissimilar partner firms. Customers are well aware that different firms are behind a co-branded product and observe the partner firms’ characteristics. Drawing on signaling theory, we assert that consumers use organizational characteristics as signals in their assessment of brand fit and for their purchasing decisions. Some organizational signals are beyond the control of the co-branding partners or at least they cannot alter them on short notice. We use a quasi-experimental design and test how co-branding partner dissimilarity affects brand fit perception. The results show that co-branding partner dissimilarity in terms of firm size, industry scope, and country-of-origin image negatively affects brand fit perception. Firm age dissimilarity does not exert significant influence. Because brand fit generally fosters a benevolent consumer attitude towards a co-branding alliance, the findings suggest that high partner dissimilarity may reduce overall co-branding alliance performance

    The Proteolipid Protein Promoter Drives Expression outside of the Oligodendrocyte Lineage during Embryonic and Early Postnatal Development

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    The proteolipid protein (Plp) gene promoter is responsible for driving expression of one of the major components of myelin – PLP and its splice variant DM-20. Both products are classically thought to express predominantly in oligodendrocytes. However, accumulating evidence suggests Plp expression is more widespread than previously thought. In an attempt to create a mouse model for inducing oligodendrocyte-specific gene deletions, we have generated transgenic mice expressing a Cre recombinase cDNA under control of the mouse Plp promoter. We demonstrate Plp promoter driven Cre expression is restricted predominantly to mature oligodendrocytes of the central nervous system (CNS) at postnatal day 28. However, crosses into the Rosa26LacZ and mT/mG reporter mouse lines reveal robust and widespread Cre activity in neuronal tissues at E15.5 and E10.5 that is not strictly oligodendrocyte lineage specific. By P28, all CNS tissues examined displayed high levels of reporter gene expression well outside of defined white matter zones. Importantly, our study reinforces the emerging idea that Plp promoter activity is not restricted to the myelinating cell lineage, but rather, has widespread activity both during embryonic and early postnatal development in the CNS. Specificity of the promoter to the oligodendrocyte cell lineage, as shown through the use of a tamoxifen inducible Plp-CreERt line, occurs only at later postnatal stages. Understanding the temporal shift in Plp driven expression is of consequence when designing experimental models to study oligodendrocyte biology

    Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

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    The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

    Hydration level is an internal variable for computing motivation to obtain water rewards in monkeys

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    In the process of motivation to engage in a behavior, valuation of the expected outcome is comprised of not only external variables (i.e., incentives) but also internal variables (i.e., drive). However, the exact neural mechanism that integrates these variables for the computation of motivational value remains unclear. Besides, the signal of physiological needs, which serves as the primary internal variable for this computation, remains to be identified. Concerning fluid rewards, the osmolality level, one of the physiological indices for the level of thirst, may be an internal variable for valuation, since an increase in the osmolality level induces drinking behavior. Here, to examine the relationship between osmolality and the motivational value of a water reward, we repeatedly measured the blood osmolality level, while 2 monkeys continuously performed an instrumental task until they spontaneously stopped. We found that, as the total amount of water earned increased, the osmolality level progressively decreased (i.e., the hydration level increased) in an individual-dependent manner. There was a significant negative correlation between the error rate of the task (the proportion of trials with low motivation) and the osmolality level. We also found that the increase in the error rate with reward accumulation can be well explained by a formula describing the changes in the osmolality level. These results provide a biologically supported computational formula for the motivational value of a water reward that depends on the hydration level, enabling us to identify the neural mechanism that integrates internal and external variables

    Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

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    Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

    Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration.

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    Understanding the molecular mechanisms that promote successful tissue regeneration is critical for continued advancements in regenerative medicine. Vertebrate amphibian tadpoles of the species Xenopus laevis and Xenopus tropicalis have remarkable abilities to regenerate their tails following amputation, through the coordinated activity of numerous growth factor signalling pathways, including the Wnt, Fgf, Bmp, Notch and TGF-β pathways. Little is known, however, about the events that act upstream of these signalling pathways following injury. Here, we show that Xenopus tadpole tail amputation induces a sustained production of reactive oxygen species (ROS) during tail regeneration. Lowering ROS levels, using pharmacological or genetic approaches, reduces the level of cell proliferation and impairs tail regeneration. Genetic rescue experiments restored both ROS production and the initiation of the regenerative response. Sustained increased ROS levels are required for Wnt/β-catenin signalling and the activation of one of its main downstream targets, fgf20 (ref. 7), which, in turn, is essential for proper tail regeneration. These findings demonstrate that injury-induced ROS production is an important regulator of tissue regeneration
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