Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age 65 36 weeks and a birth weight 65 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017

Measurement of forward charged hadron flow harmonics in peripheral PbPb collisions at √sNN = 5.02 TeV with the LHCb detector

Flow harmonic coefficients, v n , which are the key to studying the hydrodynamics of the quark-gluon plasma (QGP) created in heavy-ion collisions, have been measured in various collision systems and kinematic regions and using various particle species. The study of flow harmonics in a wide pseudorapidity range is particularly valuable to understand the temperature dependence of the shear viscosity to entropy density ratio of the QGP. This paper presents the first LHCb results of the second- and the third-order flow harmonic coefficients of charged hadrons as a function of transverse momentum in the forward region, corresponding to pseudorapidities between 2.0 and 4.9, using the data collected from PbPb collisions in 2018 at a center-of-mass energy of 5.02 TeV . The coefficients measured using the two-particle angular correlation analysis method are smaller than the central-pseudorapidity measurements at ALICE and ATLAS from the same collision system but share similar features

Helium identification with LHCb

The identification of helium nuclei at LHCb is achieved using a method based on measurements of ionisation losses in the silicon sensors and timing measurements in the Outer Tracker drift tubes. The background from photon conversions is reduced using the RICH detectors and an isolation requirement. The method is developed using pp collision data at √(s) = 13 TeV recorded by the LHCb experiment in the years 2016 to 2018, corresponding to an integrated luminosity of 5.5 fb-1. A total of around 105 helium and antihelium candidates are identified with negligible background contamination. The helium identification efficiency is estimated to be approximately 50% with a corresponding background rejection rate of up to O(10^12). These results demonstrate the feasibility of a rich programme of measurements of QCD and astrophysics interest involving light nuclei

Curvature-bias corrections using a pseudomass method

Momentum measurements for very high momentum charged particles, such as muons from electroweak vector boson decays, are particularly susceptible to charge-dependent curvature biases that arise from misalignments of tracking detectors. Low momentum charged particles used in alignment procedures have limited sensitivity to coherent displacements of such detectors, and therefore are unable to fully constrain these misalignments to the precision necessary for studies of electroweak physics. Additional approaches are therefore required to understand and correct for these effects. In this paper the curvature biases present at the LHCb detector are studied using the pseudomass method in proton-proton collision data recorded at centre of mass energy √(s)=13 TeV during 2016, 2017 and 2018. The biases are determined using Z→μ + μ - decays in intervals defined by the data-taking period, magnet polarity and muon direction. Correcting for these biases, which are typically at the 10-4 GeV-1 level, improves the Z→μ + μ - mass resolution by roughly 18% and eliminates several pathological trends in the kinematic-dependence of the mean dimuon invariant mass

Study of CP violation in B0 → DK⋆(892)0 decays with D → Kπ(ππ), ππ(ππ), and KK final states

A measurement of CP-violating observables associated with the interference of B0 → D0K⋆ (892)0 and B0 → D¯ 0K⋆ (892)0 decay amplitudes is performed in the D0 → K∓π ±(π +π −), D0 → π +π −(π +π −), and D0 → K+K− fnal states using data collected by the LHCb experiment corresponding to an integrated luminosity of 9 fb−1 . CP-violating observables related to the interference of B0 s → D0K¯ ⋆ (892)0 and B0 s → D¯ 0K¯ ⋆ (892)0 are also measured, but no evidence for interference is found. The B0 observables are used to constrain the parameter space of the CKM angle γ and the hadronic parameters r DK⋆ B0 and δ DK⋆ B0 with inputs from other measurements. In a combined analysis, these measurements allow for four solutions in the parameter space, only one of which is consistent with the world average

Blood-brain Barrier Breakdown Following Gliotoxic Drug Injection In The Brainstem Of Wistar Rats [ruptura Da Barreira Hematoencefàlica Após Injeção De Droga Gliotóxica No Tronco Encefálico De Ratos Wistar]

Ethidium bromide (EB) causes local astrocytic disappearance, with glia limitans disruption and supposed blood-brain barrier (BBB) breakdown The aim of this study was to investigate the BBB integrity after the injection of 0.1% EB (group E) or 0.9% saline solution (group C) into cisterna pontis of Wistar rats. Brainstem fragments were collected from 24 hours to 31 days post-injection for ultrastructural study and GFAP immuno-histochemical staining. Some animals received colloidal carbon ink by intravenous route at the same periods. In rats from group C, there was no sign of astrocyte loss and no leakage of ink from blood vessels in the injection site. In group E, astrocyte disappearance began at 48 hours and some areas were still devoid of astrocytic processes 31 days after. Leakage of carbon particles was seen from 48 hours to 7 days in the EB-induced lesions. Tight junctions did not show any detectable ultrastructural change due to the lack of perivascular astrocytes.603 A582589Bondan, E.F., Lallo, M.A., Graça, D.L., Desmielinizaçao experimental por brometo de etídio no sistema nervoso central (1998) Rev Univ Guarulhos -Ciênc Biol Saúde, 5, pp. 19-32Bondan, E.F., Lallo, M.A., Graça, D.L., (1998) Efeitos do brometo de etídio no tronco encefálico de ratos Wistar imunossuprimidos com ciclosporina, pp. 1-46. , São Paulo: Coleção Cadernos de Estudos e Pesquisas UNIPBondan, E.F., Graça, D.L., Sinhorini, I.L., Lallo, M.A., Silva, I.M., Pharmacological interference on remyelination in rats submitted to the ethidium bromide model (1998) Arch Anat Cytol Path/Clin Exp Path, 46, p. 536Bondan, E.F., Lallo, M.A., Sinhorini, I.L., Graça, D.L., Schwann cells may express an oligodendrocyte-like remyelinating pattern following ethidium bromide injection in the rat brainstem (1999) Acta Microscopica, 8, pp. 707-708Bondan, E.F., Lallo, M.A., Sinhorini, I.L., Baz, E.I., Paulino, C.A., Graça, D.L., Ultrastructural investigation on the brainstem remyelination after local ethidium bromide injection in rats immunosuppressed with dexamethasone (1999) Acta Microscopica, 8, pp. 709-710Bondan, E.F., Lallo, M.A., Sinhorini, I.L., Pereira, L.A.V., Graça, D.L., The effect of cyclophosphamide on brainstem remyelination following ethidium bromide injection in Wistar rats (2000) J Submicrosc Cytol Pathol, 32, pp. 603-612Graça, D.L., (1986) Investigation into ethidium bromide induced-demyelination in the central nervous system, , Thesis (PhD), University of Cambridge, CambridgeGraça, D.L., Blakemore, W.F., Delayed remyelination in rat spinal cord following ethidium bromide injection (1986) Neuropathol Appl Neurobiol, 12, pp. 593-605Graça, D.L., Pereira, L.A.V., (1990) Dinâmica da impregnaça̧o celular pelo brometo de etídio "in vitro" e "in vivo" (Abstr), pp. 430-431. , Porto Alegre: Anais da 42a Reunia̧o da Sociedade Brasileira para o Progresso da Ciência (SBPC)Pereira, L.A.V., Dertkigill, M.S.J., Graça, D.L., Cruz-Höfling, M.A., Dynamics of remyelination in the brain of adult rats after exposure to ethidium bromide (1998) J Submicrosc Cytol Pathol, 30, pp. 341-348Yajima, K., Suzuki, K., Ultrastructural changes of oligodendroglia and myelin sheats induced by ethidium bromide (1979) Neuropathol Appl Neurobiol, 5, pp. 49-62Yajima, K., Suzuki, K., Demyelination and remyelination in the rat central nervous system following ethidium bromide injection (1979) Lab Invest, 41, pp. 385-392Bondan, E.F., Lallo, M.A., Mielinizaça̧o, desmielinizaça̧o e remielinizaça̧o no SNC: Aspectos histofisiológicos relevantes à formaça̧o e integridade da mielina central (1998) Rev Inst Ciênc Saúde, 16, pp. 103-111Leibowitz, S., Hughes, R.A.C., (1983) Immunology of the nervous system, pp. 2-16. , London: Edward ArnoldSternberger, N.H., Multiple sclerosis as a autoimunne disease: Vascular antigens (1989) Res Immunol, 140, pp. 181-187Janzer, R.C., Raff, M.C., Astrocytes induce blood-brain barrier properties in endothelial cells (1987) Nature, 325, pp. 253-257Risau, W., Induction of blood-brain barrier endothelial cell differentiation (1991) Ann NY Acad Sci, 405, pp. 405-419Peters, A., Palay, S.L., Webster HdeF, (1991) The fine structure of the nervous system. 3. Ed., pp. 290-295. , New York: Oxford Univ PressStewart, P.A., Coomber, B.L., Astrocytes and the blood-brain barrier (1986) Astrocytes: development, morphology and regional specializations of astrocytes, pp. 311-323. , Fedoroff S, Verdanakis A (eds.). London: Academic PressBundgaard, M., Pathways across the vertebrate blood-brain barrier: Morphological viewpoints (1986) Ann NY Acad Sci, 481, pp. 7-18Reese, T.S., Karnovsky, M.J., Fine structural localization of a blood-brain barrier to exogenous peroxidase (1967) J Cell Biol, 34, pp. 207-217Felts, P.A., Smith, K.J., Tilt, E., Blood-brain barrier function in central demyelinating lesions repaired by Schwann cell remyelination (1991) Ann NY Acad Sci, 633, pp. 615-616Weller, R.O., Pathology of multiple sclerosis (1985) Mc Alpine's multiple sclerosis, pp. 301-343. , Matthews WB, Acheson ED, Batchelor Jr (eds.). Edinburgh: Churchill LivingstoneHsu, S.-M., Raine, L., Fanger, H., A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies (1981) Am J Clin Pathol, 75, pp. 734-738Majno, G., Palade, G.E., Studies on inflammation: I. The effect of histamine and serotonin on vascular permeability. An electron microscope study (1961) J Biophys Biochem Cytol, 11, pp. 571-605Reynolds, R., Wilkin, G.P., Cellular reaction to an acute demyelinating/ remyelinating lesion of the rat brainstem: Localization of GD3 ganglioside immunoreactivity (1993) J Neurosc Res, 36, pp. 405-42

Assessment of the critical behavior in the multiferroic Bi0.8Ba0.1Er0.1Fe0.96Cr0.02Co0.02O3 material, Multi-substitution effect on magnetic and Mössbauer properties

International audienc

Immunohistochemical Staining Of The Macrophagic And Astrocytic Response In The Brainstem Of Wistar Rats Submitted To The Ethidium Bromide Gliotoxic Model And Treated With Cyclophosphamide [marcação Imuno-histoquímica Da Resposta Macrofágica E Astrocitária No Tronco Encefálico De Ratos Wistar Submetidos Ao Modelo Gliotóxico Do Brometo De Etídio E Tratados Com Ciclofosfamida]

The gliotoxic ethidium bromide (EB) was used to study morphologically the macrophagic and astrocytic response under immunosuppression by cyclophosphamide (CY). Astrocyte immunoreactivity to glial fibrillary acidic protein (GFAP) and vimentin (VIM) and macrophagic immunoreactivity to ED1 were investigated after EB injection. Male Wistar rats were injected with 0.9% saline solution (group I), 0.1% BE (group II) and 0.1% EB associated with CY treatment (group III). Brainstem samples were collected from the 1st to the 21st day post-injection for GFAP, VIM and ED1 immunostaining. In groups II and III, it was observed increased immunoreactivity to GFAP and reexpression of VIM. In group II, ED1-positive cells were noted after the 2nd day and in group III, after the 3rd day. On the 14th day post-injection, it was observed a greater quantity of ED1- positive cells in group III than in group II. Apparently, CY did not change the astrocytic response pattern.643 B787793Graça, D.L., Mielinização, desmielinização e remielinização no sistema nervoso central (1998) Arq Neuro-psiquiatr, 46, pp. 292-297Raine, C.S., Morphology of myelin and myelination (1984) Myelin. 2.Ed., pp. 1-50. , Morell P (ed). New York: Plenum PressRaine, C.S., The neuropathology of myelin diseases (1984) Myelin. 2. Ed., pp. 259-310. , Morell P (ed). New York: Plenum PressGraça, D.L., Blakemore, W.F., Delayed remyelination in rat spinal cord following ethidium bromide injection (1986) Neuropathol Appl Neurobiol, 12, pp. 593-605Riet-Correa, G., Fernandes, C.G., Pereira, L.A., Graca, D.L., Ethidium bromide-induced demyelination of the sciatic nerve of adult Wistar rats (2002) Braz J Med Biol Res, 35, pp. 99-104Benveniste, E.N., Cytokines: Influence on glial cell gene expression and function (1992) Neuroimmunoendocrinology. 2.Ed., pp. 106-153. , Blalack JE (ed). 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New York: Raven PressVan't Wout, J.W., Linde, I., Leijh, P.C.J., Van Furth, R., Effect of irradiation, cyclophosphamide, and etoposide (VP-16) on number of peripheral blood and peritonial leukocytes in mice under normal conditions and during acute inflammatory reaction (1989) Inflammation, 3, pp. 1-14Bach, J.F., Immunosuppressive therapy of autoimmune diseases (1993) Trends Pharmacol Sci, 14, pp. 213-216Counihan, T.J., Feighery, C., Immunosuppressive therapy in autoimmune disease: A review (1991) Irish J Med Sci, 160, pp. 199-205Hoffman, G.S., Immunosuppressive therapy for autoimmune diseases (1993) Ann Allergy, 70, pp. 263-270Bondan, E.F., Lallo, M.A., Sinhorini, I.L., Pereira, L.A.V.D., Graça, D.L., The effect of cyclophosphamide on brainstem remyelination following local ethidium bromide injection in Wistar rats (2000) J Submicroscopic Cytol Pathol, 32, pp. 603-612Hsu, S.M., Raine, L., Fanger, H., A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies (1981) Am J Clin Pathol, 75, pp. 734-738Fernaud-Espinosa, I., Nietro-Sampedro, M., Bovolenta, P., Diffferential activation of microglia and astrocytes in aniso- and isomorphic gliotic tissue (1993) Glia, 8, pp. 277-291Bondan, E.F., Lallo, M.A., Sinhorini, I.L., Baz, E.I., Paulino, C.A., Graça, D.L., Ultrastructural investigation on the brainstem remyelination after local ethidium bromide injection in rats immunosuppressed with dexamethasone (1999) Acta Microscopica, 8, pp. 709-710Schiffer, D., Giordana, M.T., Migheli, A., Giaccone, G., Pezzotta, S., Mauro, A., Glial fibrillary acidic protein and vimentin in experimental glial reaction of the rat brain (1986) Brain Res, 374, pp. 110-118Petito, C.K., Morgello, S., Felix, J.C., Lesse, M.L., The two patterns of reactive astrocytosis in postischemic rat brain (1990) J Cer Blood Flow Metab, 10, pp. 850-859Fujita, T., Yoshimine, T., Maruno, M., Hayakawa, T., Cellular dynamics of macrophages and microglial cells in reaction to stab wounds in rat cerebral cortex (1998) Acta Neurochir, 140, pp. 275-27