Presence of D4 dopamine receptors in human prefrontal cortex: a postmortem study = Presença de receptores dopaminérgicos D4 em córtex cerebral humano: um estudo post-mortem

OBJECTIVE: The aim of our study was to explore the presence and the distribution of D4 dopamine receptors in postmortem human prefrontal cortex, by means of the binding of [³H]YM-09151-2, an antagonist that has equal affinity for D2, D3 and D4 receptors. It was therefore necessary to devise a unique assay method in order to distinguish and detect the D4 component. METHOD: Frontal cortex samples were harvested postmortem, during autopsy sessions, from 5 subjects. In the first assay, tissue homogenates were incubated with increasing concentrations of [³H]YM-09151-2, whereas L-745870, which has a high affinity for D4 and a low affinity for D2/D3 receptors, was used as the displacer. In the second assay, raclopride, which has a high affinity for D2/D3 receptors and a low affinity for D4 receptors, was used to block D2/D3. The L-745870 (500 nM) was added to both assays in order to determine the nonspecific binding. RESULTS: Our experiments revealed the presence of specific and saturable binding of [³H]YM-09151-2. The blockade of D2 and D3 receptors with raclopride ensured that the D4 receptors were labeled. The mean maximum binding capacity was 88 ± 25 fmol/mg protein, and the dissociation constant was 0.8 ± 0.4 nM. DISCUSSION AND CONCLUSIONS: Our findings, although not conclusive, suggest that the density of D4 receptors is low in the human prefrontal cortex

Mandelbrot's stochastic time series models

I survey and illustrate the main time series models that Mandelbrot introduced into time series analysis in the 1960s and 1970s. I focus particularly on the members of the additive fractional stable family including Lévy flights and fractional Brownian motion (fBm), noting some of the less well‐known aspects of this family, such as the cases when the self‐similarity exponent H and the Hurst exponent J differ. I briefly discuss the role of multiplicative models in modeling the physics of cascades. I then recount the still little‐known story of Mandelbrot's work on fractional renewal models in the late 1960s, explaining how these differ from their more familiar fBm counterpart and form a “missing link” between fBm and the problem of random change points. I conclude by highlighting the frontier problem of damped fractional models

Gravitational wave background from sub-luminous GRBs: prospects for second and third generation detectors

We assess the detection prospects of a gravitational wave background associated with sub-luminous gamma-ray bursts (SL-GRBs). We assume that the central engines of a significant proportion of these bursts are provided by newly born magnetars and consider two plausible GW emission mechanisms. Firstly, the deformation-induced triaxial GW emission from a newly born magnetar. Secondly, the onset of a secular bar-mode instability, associated with the long lived plateau observed in the X-ray afterglows of many gamma-ray bursts (Corsi & Meszaros 2009a). With regards to detectability, we find that the onset of a secular instability is the most optimistic scenario: under the hypothesis that SL-GRBs associated with secularly unstable magnetars occur at a rate of (48; 80)Gpc^{-3}yr^{-1} or greater, cross-correlation of data from two Einstein Telescopes (ETs) could detect the GW background associated to this signal with a signal-to-noise ratio of 3 or greater after 1 year of observation. Assuming neutron star spindown results purely from triaxial GW emissions, we find that rates of around (130;350)Gpc^{-3}yr^{-1} will be required by ET to detect the resulting GW background. We show that a background signal from secular instabilities could potentially mask a primordial GW background signal in the frequency range where ET is most sen- sitive. Finally, we show how accounting for cosmic metallicity evolution can increase the predicted signal-to-noise ratio for background signals associated with SL-GRBs.Comment: Accepted by MNRA

Fitoterápicos como coadjuvante no tratamento da síndrome metabólica: uma revisão integrativa

A síndrome metabólica é uma condição complexa caracterizada pela interação de diversos fatores de risco cardiovasculares e metabólicos. O tratamento convencional geralmente envolve modificações no estilo de vida e medicação. No entanto, o interesse crescente em terapias alternativas e complementares tem destacado o potencial dos fitoterápicos. Sumarizar estudos que avaliaram o uso de fitoterápicos como estratégia terapêutica para o tratamento síndrome metabólica. Metodologia: Trata-se de uma revisão integrativa de artigos indexados na base de dados PubMed, Capes Periódicos e Biblioteca Virtual em Saúde e Scielo, publicados entre os anos de 2017 a 2023, a partir da conjugação dos descritores “Fitoterápicos, “Síndrome metabólica”, “Obesidade” e “Fitoterapia”, nos idiomas português e inglês. Foram encontrados um total de 1.832 artigos, destes, 06 foram selecionados para revisão integrativa. O tempo de duração dos estudos, teve variação de 6 semanas até 26 semanas. Quanto aos principais fitoterápicos estudados, verificou-se que 50% (n = 3), utilizaram Camelia sinensis, 33,3% (n= 2) utilizaram Curcuma longa e 16,6% (n = 1) aplicaram em seus estudos o Allium sativum L. Outros fitoterápicos também incluídos foram: Linun usitatissimun L., Zingiber officinale, Capsicum spp, Trigonella foenum graecum e Citrus aurantium. As plantas medicinais demonstraram em estudos, sua capacidade de modular diversos aspectos metabólicos, como controle glicêmico, redução do colesterol e triglicerídeos, e melhoria da sensibilidade à insulina

Efficacy and Safety of High-Dose Rifampin in Pulmonary Tuberculosis. A Randomized Controlled Trial

Rationale: We examined whether increased rifampin doses could shorten standard therapy for tuberculosis without increased toxicity. Objectives: To assess the differences across three daily oral doses of rifampin in change in elimination rate of Mycobacterium tuberculosis in sputum and frequency of rifampin-related adverse events. Methods: We conducted a blinded, randomized, controlled phase 2 clinical trial of 180 adults with new smear-positive pulmonary tuberculosis, susceptible to isoniazid and rifampin. We randomized 1:1:1 to rifampin at 10, 15, and 20 mg/kg/d during the intensive phase. We report the primary efficacy and safety endpoints: change in elimination rate of M. tuberculosis log10 colony-forming units and frequency of grade 2 or higher rifampin-related adverse events. We report efficacy by treatment arm and by primary (area under the plasma concentration–time curve [AUC]/minimum inhibitory concentration [MIC]) and secondary (AUC) pharmacokinetic exposure. Measurements and Main Results: Each 5-mg/kg/d increase in rifampin dose resulted in differences of −0.011 (95% confidence interval, −0.025 to +0.002; P = 0.230) and −0.022 (95% confidence interval, −0.046 to −0.002; P = 0.022) log10 cfu/ml/d in the modified intention-to-treat and per-protocol analyses, respectively. The elimination rate in the per-protocol population increased significantly with rifampin AUC0–6 (P = 0.011) but not with AUC0–6/MIC99.9 (P = 0.053). Grade 2 or higher rifampin-related adverse events occurred with similar frequency across the three treatment arms: 26, 31, and 23 participants (43.3%, 51.7%, and 38.3%, respectively) had at least one event (P = 0.7092) up to 4 weeks after the intensive phase. Treatment failed or disease recurred in 11 participants (6.1%). Conclusions: Our findings of more rapid sputum sterilization and similar toxicity with higher rifampin doses support investigation of increased rifampin doses to shorten tuberculosis treatment

Evaluation of high-dose rifampin in patients with new, smear-positive tuberculosis (HIRIF): study protocol for a randomized controlled trial.

BACKGROUND: Evidence has existed for decades that higher doses of rifampin may be more effective, but potentially more toxic, than standard doses used in tuberculosis treatment. Whether increased doses of rifampin could safely shorten treatment remains an open question. METHODS/DESIGN: The HIRIF study is a phase II randomized trial comparing rifampin doses of 20 and 15 mg/kg/day to the standard 10 mg/kg/day for the first 2 months of tuberculosis treatment. All participants receive standard doses of companion drugs and a standard continuation-phase treatment (4 months, 2 drugs). They are followed for 6 months post treatment. Study participants are adults with newly diagnosed, previously untreated, smear positive (≥2+) pulmonary tuberculosis. The primary outcome is rifampin area under the plasma concentration-time curve (AUC0-24) after at least 14 days of study treatment/minimum inhibitory concentration. 180 randomized participants affords 90 % statistical power to detect a difference of at least 14 mcg/mL*hr between the 20 mg/kg group and the 10 mg/kg group, assuming a loss to follow-up of up to 17 %. DISCUSSION: Extant evidence suggests the potential for increased doses of rifampin to shorten tuberculosis treatment duration. Early studies that explored this potential using intermittent, higher dosing were derailed by toxicity. Given the continued large, global burden of tuberculosis with nearly 10 million new cases annually, shortened regimens with existing drugs would offer an important advantage to patients and health systems. TRIAL REGISTRATION: This trial was registered with clinicaltrials.gov (registration number: NCT01408914 ) on 2 August 2011

Observation of the diphoton decay of the Higgs boson and measurement of its properties

Peer reviewe

Measurement of the Zγ production cross section in pp collisions at 8 TeV and search for anomalous triple gauge boson couplings

Open Access, Copyright CERN, for the benefit of the CMS Collaboration. Article funded by SCOAP3.Abstract: The cross section for the production of Zγ in proton-proton collisions at 8 TeV is measured based on data collected by the CMS experiment at the LHC corresponding to an integrated luminosity of 19.5 fb−1. Events with an oppositely-charged pair of muons or electrons together with an isolated photon are selected. The differential cross section as a function of the photon transverse momentum is measured inclusively and exclusively, where the exclusive selection applies a veto on central jets. The observed cross sections are compatible with the expectations of next-to-next-to-leading-order quantum chromodynamics. Limits on anomalous triple gauge couplings of ZZγ and Zγγ are set that improve on previous experimental results obtained with the charged lepton decay modes of the Z boson

Reconstruction and identification of τ lepton decays to hadrons and ντ at CMS

This paper describes the algorithms used by the CMS experiment to reconstruct and identify tau -> hadrons + nu(tau) decays during Run 1 of the LHC. The performance of the algorithms is studied in proton-proton collisions recorded at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 fb(-1). The algorithms achieve an identification efficiency of 50-60%, with misidentification rates for quark and gluon jets, electrons, and muons between per mille and per cent levels

Reconstruction and identification of tau lepton decays to hadrons and tau neutrino at CMS

This paper describes the algorithms used by the CMS experiment to reconstruct and identify tau to hadrons + tau neutrino decays during Run 1 of the LHC. The performance of the algorithms is studied in proton-proton collisions recorded at a centre-of-mass energy of 8 TeV, corresponding to an integrated luminosity of 19.7 inverse femtobarns. The algorithms achieve an identification efficiency of 50-60%, with misidentification rates for quark and gluon jets, electrons, and muons between per mille and per cent levels.Comment: Replaced with published version. Added journal referenc