Thalidomide is Associated With Increased T Cell Activation and Inflammation in Antiretroviral-naive HIV-infected Individuals in a Randomised Clinical Trial of Efficacy and Safety

Trial Design: Open-label, randomised, controlled, pilot proof-of-concept clinical trial. Methods: Participants: Antiretroviral naive adult males with CD4 count >= 350 cells/mm(3). Interventions: Patients were randomised to receive thalidomide 200 mg QD for 3 weeks (Thalidomide group) or not (Control group) and followed for 48 weeks. Objective: We hypothesized that short-term Thalidomide use would reduce HIV related inflammation and HIV replication among antiretroviral naive HIV infected individuals. Outcome: Viral loads, CD4/CD8 counts, ultra-sensitive C-reactive protein (US-CRP), cell activation markers, and plasma lipopolysaccharide (LPS) were analyzed. Randomisation: Unrestricted randomisation. Blinding: No blinding was used. Results: Numbers randomised: Thirty recruited individuals were randomised to Thalidomide (16 patients) or Control (14 patients) groups. Recruitment: Patients were recruited from April 2011 to January 2013. Outcome: Viral loads remained stable in both groups. During thalidomide treatment, a decrease in CD4/CD8 ratio (p = 0.04), a decrease in CD4 count (p = 0.04), an increase in cell activation calculated by the percentage of CD38 (+)/HLA-DR+ CD8 cells (p < 0.05) and an increase in US-CRP (p < 0.01) were observed in the Thalidomide group, with all parameters returning to baseline levels after thalidomide interruption. We confirmed that thalidomide increased HIV replication in vitro of 6 of 7 samples from long-term antiretroviral suppressed individuals. Harms: No class 3/4 adverse events occurred. Conclusions: Short-termuse of thalidomide led to an intense transient increase in T cell activation and inflammation, with a decrease in the CD4(+) cell count without changes to the CD8(+) cell count. We confirmed that thalidomide acts in vitro as a latency reversal agent and speculate that the in vivo results obtained were due to an increase in HIV replication. (C) 2017 The Authors. Published by Elsevier B.V.Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP)Univ Fed São Paulo, Lab Retrovirol, São Paulo, BrazilFiocruz MS, Inst Oswaldo Cruz, Lab Interdisciplinar Pesquisas Med, Rio De Janeiro, BrazilSecretaria Municipal Saude Antonio Ribeiro Neto, Rio De Janeiro, BrazilOncohiv, Rio De Janeiro, BrazilUniv Fed Rio de Janeiro, Rio De Janeiro, BrazilInst Fed Educ Ciencia & Tecnol Rio de Janeiro IF, Rio De Janeiro, BrazilUniv Fed São Paulo, Lab Retrovirol, São Paulo, BrazilFAPESP: 04/15856-9Web of Scienc

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at sNN\sqrt{s_{NN}} = 5.02 TeV

Two-particle angular correlations between unidentified charged trigger and associated particles are measured by the ALICE detector in p-Pb collisions at a nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum range 0.7 $< p_{\rm{T}, assoc} < p_{\rm{T}, trig} <$ 5.0 GeV/$c$ is examined, to include correlations induced by jets originating from low momen\-tum-transfer scatterings (minijets). The correlations expressed as associated yield per trigger particle are obtained in the pseudorapidity range $|\eta|<0.9$. The near-side long-range pseudorapidity correlations observed in high-multiplicity p-Pb collisions are subtracted from both near-side short-range and away-side correlations in order to remove the non-jet-like components. The yields in the jet-like peaks are found to be invariant with event multiplicity with the exception of events with low multiplicity. This invariance is consistent with the particles being produced via the incoherent fragmentation of multiple parton--parton scatterings, while the yield related to the previously observed ridge structures is not jet-related. The number of uncorrelated sources of particle production is found to increase linearly with multiplicity, suggesting no saturation of the number of multi-parton interactions even in the highest multiplicity p-Pb collisions. Further, the number scales in the intermediate multiplicity region with the number of binary nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/161

Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider

Measurements of multi-particle azimuthal correlations (cumulants) for charged particles in p-Pb and Pb-Pb collisions are presented. They help address the question of whether there is evidence for global, flow-like, azimuthal correlations in the p-Pb system. Comparisons are made to measurements from the larger Pb-Pb system, where such evidence is established. In particular, the second harmonic two-particle cumulants are found to decrease with multiplicity, characteristic of a dominance of few-particle correlations in p-Pb collisions. However, when a $|\Delta \eta|$ gap is placed to suppress such correlations, the two-particle cumulants begin to rise at high-multiplicity, indicating the presence of global azimuthal correlations. The Pb-Pb values are higher than the p-Pb values at similar multiplicities. In both systems, the second harmonic four-particle cumulants exhibit a transition from positive to negative values when the multiplicity increases. The negative values allow for a measurement of $v_{2}\{4\}$ to be made, which is found to be higher in Pb-Pb collisions at similar multiplicities. The second harmonic six-particle cumulants are also found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find $v_{2}\{4\} \simeq v_{2}\{6\}\neq 0$ which is indicative of a Bessel-Gaussian function for the $v_{2}$ distribution. For very high-multiplicity Pb-Pb collisions, we observe that the four- and six-particle cumulants become consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and Pb-Pb are measured. These are found to be similar for overlapping multiplicities, when a $|\Delta\eta| > 1.4$ gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20, published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87

The status of cryptococcosis in Latin America

Cryptococcosis is a life-threatening fungal infection caused by the encapsulated yeasts Cryptococcus neoformans and C. gattii, acquired from the environment. In Latin America, as occurring worldwide, C. neoformans causes more than 90% of the cases of cryptococcosis, affecting predominantly patients with HIV, while C. gattii generally affects otherwise healthy individuals. In this region, cryptococcal meningitis is the most common presentation, with amphotericin B and fluconazole being the antifungal drugs of choice. Avian droppings are the predominant environmental reservoir of C. neoformans, while C. gattii is associated with several arboreal species. Importantly, C. gattii has a high prevalence in Latin America and has been proposed to be the likely origin of some C. gattii populations in North America. Thus, in the recent years, significant progress has been made with the study of the basic biology and laboratory identification of cryptococcal strains, in understanding their ecology, population genetics, host-pathogen interactions, and the clinical epidemiology of this important mycosis in Latin America.Fil: Firacative, Carolina. University of Sydney; AustraliaFil: Lizarazo, Jairo. Universidad de Pamplona; EspañaFil: Illnait Zaragozí, María Teresa. Tropical Medicine Institute Pedro Kourí; CubaFil: Castañeda, Maria Elizabeth. Instituto Nacional de Salud; Colombia. Latin American Cryptococcal Study Group; BrasilFil: Arechavala, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Latin American Cryptococcal Study Group; BrasilFil: Córdoba, Susana Beatríz. Latin American Cryptococcal Study Group; Brasil. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Mazza, Mariana. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina. Latin American Cryptococcal Study Group; BrasilFil: Taverna, Constanza Giselle. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; Argentina. Latin American Cryptococcal Study Group; BrasilFil: Isla, Guillermina. Latin American Cryptococcal Study Group; Brasil. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”; ArgentinaFil: Chiapello, Laura Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Latin American Cryptococcal Study Group; BrasilFil: Vergara, Mario León Silva. Universidade Federal do Triangulo Mineiro; Brasil. Latin American Cryptococcal Study Group; BrasilFil: Melhem, Marcia S. C.. Governo do Estado de São Paulo. Secretaria da Saúde. Instituto Adolfo Lutz; Brasil. Latin American Cryptococcal Study Group; BrasilFil: Szeszs, Maria Walderez. Governo do Estado de São Paulo. Secretaria da Saúde. Instituto Adolfo Lutz; Brasil. Latin American Cryptococcal Study Group; BrasilFil: Martins, Marilena dos Anjos. Latin American Cryptococcal Study Group; Brasil. Governo do Estado de São Paulo. Secretaria da Saúde. Instituto Adolfo Lutz; BrasilFil: Bonfietti, Lucas Xavier. Latin American Cryptococcal Study Group; Brasil. Governo do Estado de São Paulo. Secretaria da Saúde. Instituto Adolfo Lutz; BrasilFil: Oliveira, Rogério Antonio de. Governo do Estado de São Paulo. Secretaria da Saúde. Instituto Adolfo Lutz; Brasil. Latin American Cryptococcal Study Group; BrasilFil: Oliveira, Lidiane de. Governo do Estado de São Paulo. Secretaria da Saúde. Instituto Adolfo Lutz; Brasil. Latin American Cryptococcal Study Group; BrasilFil: Santos, Dayane Christine Silva. Latin American Cryptococcal Study Group; Brasil. Governo do Estado de São Paulo. Secretaria da Saúde. Instituto Adolfo Lutz; BrasilFil: Lazera, Marcia S.. Latin American Cryptococcal Study Group; Brasil. Fundación Oswaldo Cruz; BrasilFil: Wanke, Bodo. Fundación Oswaldo Cruz; Brasil. Latin American Cryptococcal Study Group; BrasilFil: Díaz, María Cristina. Latin American Cryptococcal Study Group; Brasil. Universidad de Chile; ChileFil: Escandón, Patricia. Instituto Nacional de Salud; Colombia. Latin American Cryptococcal Study Group; BrasilFil: Noguera, María Clara. Latin American Cryptococcal Study Group; Brasil. Universidad Metropolitana; ColombiaFil: Andreu, Carlos Manuel Fernández. Latin American Cryptococcal Study Group; BrasilFil: Castril­Lón, Laura. Universidad Nacional Autónoma de México; México. Latin American Cryptococcal Study Group; BrasilFil: Bustamante, Beatriz. Hospital Cayetano Heredia. Instituto de Medicina Tropical Alexander von Humboldt; Perú. Hospital Cayetano Heredia; Perú. Latin American Cryptococcal Study Group; BrasilFil: Dolande, Maribel. Universidad Central de Venezuela; Venezuela. Latin American Cryptococcal Study Group; BrasilFil: Ferrara, Giussepe. Universidad Central de Venezuela; Venezuela. Latin American Cryptococcal Study Group; Brasi