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CT DENSITOMETRY TO PREDICT CONTUSION ENLARGEMENT IN TRAUMATIC BRAIN INJURY (TBI)
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
Interior Weyl-type Solutions of the Einstein-Maxwell Field Equations
Static solutions of the electro-gravitational field equations exhibiting a
functional relationship between the electric and gravitational potentials are
studied. General results for these metrics are presented which extend previous
work of Majumdar. In particular, it is shown that for any solution of the field
equations exhibiting such a Weyl-type relationship, there exists a relationship
between the matter density, the electric field density and the charge density.
It is also found that the Majumdar condition can hold for a bounded perfect
fluid only if the matter pressure vanishes (that is, charged dust). By
restricting to spherically symmetric distributions of charged matter, a number
of exact solutions are presented in closed form which generalise the
Schwarzschild interior solution. Some of these solutions exhibit functional
relations between the electric and gravitational potentials different to the
quadratic one of Weyl. All the non-dust solutions are well-behaved and, by
matching them to the Reissner-Nordstr\"{o}m solution, all of the constants of
integration are identified in terms of the total mass, total charge and radius
of the source. This is done in detail for a number of specific examples. These
are also shown to satisfy the weak and strong energy conditions and many other
regularity and energy conditions that may be required of any physically
reasonable matter distribution.Comment: 21 pages, RevTex, to appear in General Relativity and Gravitatio
Advanced surface treatments for medium-velocity superconducting RF cavities for high accelerating gradient continuous-wave operation
Nitrogen-doping and furnace-baking are advanced high-Q0 recipes developed for
1.3 GHz TESLA-type cavities. These treatments will significantly benefit the
high-Q0 linear accelerator community if they can be successfully adapted to
different cavity styles and frequencies. Strong frequency- and geometry-
dependence of these recipes makes the technology transfer amongst different
cavity styles and frequencies far from straightforward, and requires rigorous
study. Upcoming high-Q0 continuous-wave linear accelerator projects, such as
the proposed Michigan State University Facility for Rare Isotope Beam Energy
Upgrade, and the underway Fermilab's Proton Improvement Plan-II, could benefit
enormously from adapting these techniques to their beta_opt = 0.6 ~650 MHz
5-cell elliptical superconducting rf cavities, operating at an accelerating
gradient of around ~17 MV/m. This is the first investigation of the adaptation
of nitrogen doping and medium temperature furnace baking to prototype 644 MHz
beta_opt = 0.65 cavities, with the aim of demonstrating the high-Q0 potential
of these recipes in these novel cavities for future optimization as part of the
FRIB400 project R&D. We find that nitrogen-doping delivers superior Q0, despite
the sub-GHz operating frequency of these cavities, but is sensitive to the
post-doping electropolishing removal step and experiences elevated residual
resistance. Medium temperature furnace baking delivers reasonable performance
with decreased residual resistance compared to the nitrogen doped cavity, but
may require further recipe refinement. The gradient requirement for the FRIB400
upgrade project is comfortably achieved by both recipes.Comment: 16 pages, 5 figure
Characterising the dynamics of cerebral metabolic dysfunction following traumatic brain injury: A microdialysis study in 619 patients.
Funder: National Institute for Health Research (NIHR)Traumatic brain injury (TBI) is a major cause of death and disability, particularly amongst young people. Current intensive care management of TBI patients is targeted at maintaining normal brain physiology and preventing secondary injury. Microdialysis is an invasive monitor that permits real-time assessment of derangements in cerebral metabolism and responses to treatment. We examined the prognostic value of microdialysis parameters, and the inter-relationships with other neuromonitoring modalities to identify interventions that improve metabolism. This was an analysis of prospective data in 619 adult TBI patients requiring intensive care treatment and invasive neuromonitoring at a tertiary UK neurosciences unit. Patients had continuous measurement of intracranial pressure (ICP), arterial blood pressure (ABP), brain tissue oxygenation (PbtO2), and cerebral metabolism and were managed according to a standardized therapeutic protocol. Microdialysate was assayed hourly for metabolites including glucose, pyruvate, and lactate. Cerebral perfusion pressure (CPP) and cerebral autoregulation (PRx) were derived from the ICP and ABP. Outcome was assessed with the Glasgow Outcome Score (GOS) at 6 months. Relationships between monitoring variables was examined with generalized additive mixed models (GAMM). Lactate/Pyruvate Ratio (LPR) over the first 3 to 7 days following injury was elevated amongst patients with poor outcome and was an independent predictor of ordinal GOS (p70mmHg, PRx 18mmHg, and brain glucose >1mM. Deranged cerebral metabolism is an important determinant of patient outcome following TBI. Variations in cerebral perfusion, oxygenation and glucose supply are associated with changes in cerebral LPR and suggest therapeutic interventions to improve cerebral metabolism. Future prospective studies are required to determine the efficacy of these strategies
Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.
To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome
Jasmonate promotes auxin-induced adventitious rooting in dark-grown Arabidopsis thaliana seedlings and stem thin cell layers by a cross-talk with ethylene signalling and a modulation of xylogenesis
Background: Adventitious roots (ARs) are often necessary for plant survival, and essential for successful micropropagation. In Arabidopsis thaliana dark-grown seedlings AR-formation occurs from the hypocotyl and is enhanced by application of indole-3-butyric acid (IBA) combined with kinetin (Kin). The same IBA + Kin-treatment induces AR-formation in thin cell layers (TCLs). Auxin is the main inducer of AR-formation and xylogenesis in numerous species and experimental systems. Xylogenesis is competitive to AR-formation in Arabidopsis hypocotyls and TCLs. Jasmonates (JAs) negatively affect AR-formation in de-etiolated Arabidopsis seedlings, but positively affect both AR-formation and xylogenesis in tobacco dark-grown IBA + Kin TCLs. In Arabidopsis the interplay between JAs and auxin in AR-formation vs xylogenesis needs investigation. In de-etiolated Arabidopsis seedlings, the Auxin Response Factors ARF6 and ARF8 positively regulate AR-formation and ARF17 negatively affects the process, but their role in xylogenesis is unknown. The cross-talk between auxin and ethylene (ET) is also important for AR-formation and xylogenesis, occurring through EIN3/EIL1 signalling pathway. EIN3/EIL1 is the direct link for JA and ET-signalling. The research investigated JA role on AR-formation and xylogenesis in Arabidopsis dark-grown seedlings and TCLs, and the relationship with ET and auxin. The JA-donor methyl-jasmonate (MeJA), and/or the ET precursor 1-aminocyclopropane-1-carboxylic acid were applied, and the response of mutants in JA-synthesis and -signalling, and ET-signalling investigated. Endogenous levels of auxin, JA and JA-related compounds, and ARF6, ARF8 and ARF17 expression were monitored. Results: MeJA, at 0.01 μM, enhances AR-formation, when combined with IBA + Kin, and the response of the early-JA-biosynthesis mutant dde2–2 and the JA-signalling mutant coi1–16 confirmed this result. JA levels early change during TCL-culture, and JA/JA-Ile is immunolocalized in AR-tips and xylogenic cells. The high AR-response of the late JA-biosynthesis mutant opr3 suggests a positive action also of 12-oxophytodienoic acid on AR-formation. The crosstalk between JA and ET-signalling by EIN3/EIL1 is critical for AR-formation, and involves a competitive modulation of xylogenesis. Xylogenesis is enhanced by a MeJA concentration repressing AR-formation, and is positively related to ARF17 expression. Conclusions: The JA concentration-dependent role on AR-formation and xylogenesis, and the interaction with ET opens the way to applications in the micropropagation of recalcitrant species
Root apoplastic barriers block Na+ transport to shoots in rice (Oryza sativa L.)
Rice is an important crop that is very sensitive to salinity. However, some varieties differ greatly in this feature, making investigations of salinity tolerance mechanisms possible. The cultivar Pokkali is salinity tolerant and is known to have more extensive hydrophobic barriers in its roots than does IR20, a more sensitive cultivar. These barriers located in the root endodermis and exodermis prevent the direct entry of external fluid into the stele. However, it is known that in the case of rice, these barriers are bypassed by most of the Na+ that enters the shoot. Exposing plants to a moderate stress of 100 mM NaCl resulted in deposition of additional hydrophobic aliphatic suberin in both cultivars. The present study demonstrated that Pokkali roots have a lower permeability to water (measured using a pressure chamber) than those of IR20. Conditioning plants with 100 mM NaCl effectively reduced Na+ accumulation in the shoot and improved survival of the plants when they were subsequently subjected to a lethal stress of 200 mM NaCl. The Na+ accumulated during the conditioning period was rapidly released when the plants were returned to the control medium. It has been suggested that the location of the bypass flow is around young lateral roots, the early development of which disrupts the continuity of the endodermal and exodermal Casparian bands. However, in the present study, the observed increase in lateral root densities during stress in both cultivars did not correlate with bypass flow. Overall the data suggest that in rice roots Na+ bypass flow is reduced by the deposition of apoplastic barriers, leading to improved plant survival under salt stress
Static charged perfect fluid spheres in general relativity
Interior perfect fluid solutions for the Reissner-Nordstrom metric are
studied on the basis of a new classification scheme. General formulas are found
in many cases. Explicit new global solutions are given as illustrations. Known
solutions are briefly reviewed.Comment: 23 pages, Revtex (galley), journal version, to appear in Phys.Rev.
Latest Development of Electropolishing Optimization for 650 MHz Niobium Cavity
Electropolishing (EP) of 1.3 GHz niobium superconducting RF cavities is
conducted to achieve a desired smooth and contaminant-free surface that yields
good RF performance. Achieving a smooth surface of a large-sized elliptical
cavity with the standard EP conditions was found to be challenging. This work
aimed to conduct a systematic parametric EP study to understand the effects of
various EP parameters on the surface of 650 MHz niobium cavities used in the
Proton Improvement Plan-II (PIP-II) linear accelerator. Parameters optimized in
this study provided a smooth surface of the cavities. The electropolished
cavity showed significantly a higher accelerating gradient meeting baseline
requirement and qualified for further surface treatment to improve the cavity
quality factor.Comment: SRF202
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