Daptomycin Population Pharmacokinetics in Patients Affected by Severe Gram-Positive Infections: An Update

Daptomycin pharmacokinetics may not depend on renal function only and it significantly differs between healthy volunteers and severely ill patients. Herein, we propose a population pharmacokinetics model based on 424 plasma daptomycin concentrations collected from 156 patients affected by severe Gram-positive infections during a routine therapeutic drug monitoring protocol. Model building and validation were performed using NONMEM 7.2 (ICON plc), Xpose4 and Perl-speaks-to-NONMEM. The final pop-PK model was a one-compartment first-order elimination model, with a 2.7% IIV for drug clearance (Cl), influence of creatinine clearance on drug clearance and of sex on distribution volume. After model validation, we simulated 10,000 patients with the Monte-Carlo method to predict the efficacy and tolerability of different daptomycin daily dosages. For the most common 6 mg/kg daily dose, the simulated probability of overcoming the toxic minimum concentration (24.3 mg/L) was 14.8% and the efficacy (expressed as a cumulative fraction of response) against methicillin-resistant S. aureus, S. pneumoniae and E. faecium was 95.77%, 99.99% and 68%, respectively. According to the model-informed precision dosing paradigm, pharmacokinetic models such as ours could help clinicians to perform patient-tailored antimicrobial dosing and maximize the odds of therapy success without neglecting toxicity risk

Desenvolvimento de lesões perirradiculares em ratos normais e diabéticos

Evidence suggests that diabetic patients are more significantly affected by problems of endodontic origin. This study sought to radiographically and histologically examine the development of periradicular inflammation in control and in diabetic rats after induction of pulpal infection. The pulps of the mandibular first molars of normal and streptozotocin-induced diabetic rats were exposed and left in contact with their oral cavities for 21 and 40 days. Afterwards, the animals were sacrificed, the mandibles were surgically removed, fixed in formalin and then radiographed in a standardized position. The radiographic images of the periradicular lesions were scanned and computerized images were evaluated for the total area of the lesions using a specific software. Representative specimens were also prepared for histopathological analysis. Radiographic analysis revealed that diabetic rats presented significantly larger periradicular lesions when compared with control rats, regardless of the experimental period (pEvidências indicam que pacientes diabéticos são mais significativamente afetados por problemas de origem endodôntica. Este estudo avaliou radiográfica e histologicamente o desenvolvimento de inflamação perirradicular em ratos controle e diabéticos depois da indução de infecção pulpar. As polpas dos primeiros molares inferiores de ratos normais ou diabéticos foram expostas e deixadas em contato com a cavidade oral por 21 e 40 dias. Em seguida, os animais foram sacrificados, as mandíbulas removidas cirurgicamente, fixadas em formalina e depois radiografadas em posição padronizada. As imagens radiográficas das lesões perirradiculares foram escaneadas e as imagens computadorizadas avaliadas quanto à área total das lesões usando software específico. Espécimes representativos foram preparados também para análise histológica. A análise radiográfica revelou que os ratos diabéticos apresentaram lesões periradiculares significativamente maiores quando comparados com os ratos normais, independentemente do período experimental (

IBEMCS: IDS baseado em eventos Multi-Contexto para SCADA / IBEMCS: event based IDS Multi-Context for SCADA

Atualmente os mecanismos de segurança utilizados para detecção de intrusão em ambientes de automação industrial utilizam dados exclusivos TIC (Tecnologia da Informação e Comunicação) ou TO (Tecnologia da Operação). Este trabalho propõe um IDS (Intrusion Detection System) que integra informações TIC e TO para identificação das cadeias de eventos TIC e TO que ocasionaram a falha no processo industrial. Medições demonstram que o tempo de resposta e a taxa de acerto são linearmente proporcionais ao volume de dados processados permitindo um planejamento prévio da arquitetura ao ambiente de trabalho

Caminhoneiro de transporte rodoviário de cargas: busca de tratamentos odontológicos

O objetivo desta pesquisa foi explorar hábitos dos caminhoneiros na busca por tratamentos odontológicos. O método da pesquisa utilizado foi quantitativo, exploratório-descritivo e de corte transversal, com 270 sujeitos de pesquisa. O estudo incluiu caminhoneiros com idade de vinte e um a sessenta anos que atuam no ramo de transporte rodoviário de cargas e trafegam na Rodovia Presidente Dutra. Apesar de não estatisticamente diferente, foi detectada tendência de quanto maior o grau de instrução, maior a renda; e quanto maior o grau de instrução, são buscadas melhores formas de tratamentos odontológicos; o fator renda não teve influência forma busca de tratamento odontológico. Como sugestão de futura pesquisa, fazer uma pesquisa mais ampla, de forma a possibilitar melhores análises estatísticas

Observation of the γγ→ττ process in Pb+Pb collisions and constraints on the τ-lepton anomalous magnetic moment with the ATLAS detector

This Letter reports the observation of τ-lepton-pair production in ultraperipheral lead-lead collisions Pb+Pb→Pb(γγ→ττ)Pb and constraints on the τ-lepton anomalous magnetic moment a_{τ}. The dataset corresponds to an integrated luminosity of 1.44 nb^{-1} of LHC Pb+Pb collisions at sqrt[s_{NN}]=5.02 TeV recorded by the ATLAS experiment in 2018. Selected events contain one muon from a τ-lepton decay, an electron or charged-particle track(s) from the other τ-lepton decay, little additional central-detector activity, and no forward neutrons. The γγ→ττ process is observed in Pb+Pb collisions with a significance exceeding 5 standard deviations and a signal strength of μ_{ττ}=1.03_{-0.05}^{+0.06} assuming the standard model value for a_{τ}. To measure a_{τ}, a template fit to the muon transverse-momentum distribution from τ-lepton candidates is performed, using a dimuon (γγ→μμ) control sample to constrain systematic uncertainties. The observed 95% confidence-level interval for a_{τ} is -0.057<0.024

Search for resonant WZ production in the fully leptonic final state in proton–proton collisions at √s=13 TeV with the ATLAS detector

A search for a WZ resonance, in the fully leptonic final state (electrons or muons), is performed using 139 fb - 1 of data collected at a centre-of-mass energy of 13 TeV by the ATLAS detector at the Large Hadron Collider. The results are interpreted in terms of a singly charged Higgs boson of the Georgi–Machacek model, produced by WZ fusion, and of a Heavy Vector Triplet, with the resonance produced by WZ fusion or the Drell–Yan process. No significant excess over the Standard Model prediction is observed and limits are set on the production cross-section times branching ratio as a function of the resonance mass for these processes

Measurements of W+W- production in decay topologies inspired by searches for electroweak supersymmetry

This paper presents a measurement of fiducial and differential cross-sections for W+W- production in proton–proton collisions at s=13 TeV with the ATLAS experiment at the Large Hadron Collider using a dataset corresponding to an integrated luminosity of 139 fb - 1 . Events with exactly one electron, one muon and no hadronic jets are studied. The fiducial region in which the measurements are performed is inspired by searches for the electroweak production of supersymmetric charginos decaying to two-lepton final states. The selected events have moderate values of missing transverse momentum and the ‘stransverse mass’ variable mT2 , which is widely used in searches for supersymmetry at the LHC. The ranges of these variables are chosen so that the acceptance is enhanced for direct W+W- production and suppressed for production via top quarks, which is treated as a background. The fiducial cross-section and particle-level differential cross-sections for six variables are measured and compared with two theoretical SM predictions from perturbative QCD calculations

Measurements of the suppression and correlations of dijets in Xe+Xe collisions at √ sNN = 5.44 TeV

Measurements of the suppression and correlations of dijets is performed using 3 μ b − 1 of Xe+Xe data at s N N = 5.44 TeV collected with the ATLAS detector at the CERN Large Hadron Collider. Dijets with jets reconstructed using the R = 0.4 anti- k t algorithm are measured differentially in jet p T over the range of 32 to 398 GeV and the centrality of the collisions. Significant dijet momentum imbalance is found in the most central Xe+Xe collisions, which decreases in more peripheral collisions. Results from the measurement of per-pair normalized and absolutely normalized dijet p T balance are compared with previous Pb + Pb measurements at s N N = 5.02 TeV. The differences between the dijet suppression in Xe+Xe and Pb + Pb are further quantified by the ratio of pair nuclear-modification factors. The results are found to be consistent with those measured in Pb + Pb data when compared in classes of the same event activity and when taking into account the difference between the center-of-mass energies of the initial parton scattering process in Xe+Xe and Pb + Pb collisions. These results should provide input for a better understanding of the role of energy density, system size, path length, and fluctuations in the parton energy loss