Enantiomers of nifurtimox do not exhibit stereoselective anti-Trypanosoma cruzi activity, toxicity, or pharmacokinetic properties

With the aim of improving the available drugs for the treatment of Chagas disease, individual enantiomers of nifurtimox were characterized. The results indicate that the enantiomers are equivalent in their in vitro activity against a panel of Trypanosoma cruzi strains; in vivo efficacy in a murine model of Chagas disease; in vitro toxicity and absorption, distribution, metabolism, and excretion characteristics; and in vivo pharmacokinetic properties. There is unlikely to be any therapeutic benefit of an individual nifurtimox enantiomer over the racemic mixture

Developing a predictive modelling capacity for a climate change-vulnerable blanket bog habitat: Assessing 1961-1990 baseline relationships

Aim: Understanding the spatial distribution of high priority habitats and developing predictive models using climate and environmental variables to replicate these distributions are desirable conservation goals. The aim of this study was to model and elucidate the contributions of climate and topography to the distribution of a priority blanket bog habitat in Ireland, and to examine how this might inform the development of a climate change predictive capacity for peat-lands in Ireland. Methods: Ten climatic and two topographic variables were recorded for grid cells with a spatial resolution of 1010 km, covering 87% of the mainland land surface of Ireland. Presence-absence data were matched to these variables and generalised linear models (GLMs) fitted to identify the main climatic and terrain predictor variables for occurrence of the habitat. Candidate predictor variables were screened for collinearity, and the accuracy of the final fitted GLM was evaluated using fourfold cross-validation based on the area under the curve (AUC) derived from a receiver operating characteristic (ROC) plot. The GLM predicted habitat occurrence probability maps were mapped against the actual distributions using GIS techniques. Results: Despite the apparent parsimony of the initial GLM using only climatic variables, further testing indicated collinearity among temperature and precipitation variables for example. Subsequent elimination of the collinear variables and inclusion of elevation data produced an excellent performance based on the AUC scores of the final GLM. Mean annual temperature and total mean annual precipitation in combination with elevation range were the most powerful explanatory variable group among those explored for the presence of blanket bog habitat. Main conclusions: The results confirm that this habitat distribution in general can be modelled well using the non-collinear climatic and terrain variables tested at the grid resolution used. Mapping the GLM-predicted distribution to the observed distribution produced useful results in replicating the projected occurrence of the habitat distribution over an extensive area. The methods developed will usefully inform future climate change predictive modelling for Irelan

In vitro evaluation of sustained released matrix tablets containing ibuprofen: a model poorly water-soluble drug

ABSTRACT A matrix system was developed that releases ibuprofen (IB) over a 12-hour period and the influence of the polymer type and concentration on the release rate of the drug was evaluated. Tablets containing different concentrations of Carbopol (CP), hydroxypropyl methylcellulose (HPMC), or ethyl cellulose (EC) were prepared using direct compression and the drug content, content uniformity, hardness, friability, dissolution performance, and in vitro release kinetics were examined. Formulated tablets were found to be within acceptable limits for physical and chemical parameters. The release kinetics of the Carbopol(r)971P 8% formulation showed the best linearity (r 2 =0.977) in fitting zero-order kinetics, suggesting the release rate was time independent. The drug release from tablets containing 8% CP was extended over approximately 18 hours and the release kinetics were nearly linear, suggesting that this system has the potential to maintain constant plasma drug concentrations over 12 hours, which could reduce the frequency of administration and the occurrence of adverse effects associated with repeated administration of conventional IB tablets

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio

Search for flavour-changing neutral currents in processes with one top quark and a photon using 81 fb⁻¹ of pp collisions at \sqrts = 13 TeV with the ATLAS experiment

A search for flavour-changing neutral current (FCNC) events via the coupling of a top quark, a photon, and an up or charm quark is presented using 81 fb−1 of proton–proton collision data taken at a centre-of-mass energy of 13 TeV with the ATLAS detector at the LHC. Events with a photon, an electron or muon, a b-tagged jet, and missing transverse momentum are selected. A neural network based on kinematic variables differentiates between events from signal and background processes. The data are consistent with the background-only hypothesis, and limits are set on the strength of the tqγ coupling in an effective field theory. These are also interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tuγ coupling of 36 fb (78 fb) and on the branching ratio for t→γu of 2.8×10−5 (6.1×10−5). In addition, they are interpreted as 95% CL upper limits on the cross section for FCNC tγ production via a left-handed (right-handed) tcγ coupling of 40 fb (33 fb) and on the branching ratio for t→γc of 22×10−5 (18×10−5). © 2019 The Author(s

Self-emulsifying therapeutic system: a potential approach for delivery of lipophilic drugs

Self-emulsifying therapeutic system (SETs) provide an effective and intelligent solution to the various issues related to the formulation of hydrophobic drugs with limited solubility in gastrointestinal fluid. Although the potential utility of SETs is well known, only in recent years has a mechanistic understanding of the impact of these systems on drug disposition emerged. These in situ emulsion-forming systems have a high stability when incorporated in various dosage forms. SETs are being looked upon as systems which can overcome the problems associated with delivery of poorly water soluble drugs. An in-depth knowledge about lipids and surfactants that can contribute to these systems, criterion for their selection and the proportion in which they can be used, represent some crucial factors determining the in vivo performance of these systems. This article presents a comprehensive account of various types of self-emulsifying formulations with emphasis on their composition and examples of currently marketed preparations.O sistema terapêutico auto-emulsionante (SETs) fornece solução eficaz e inteligente para os vários problemas relativos à formulação de fármacos hidrofóbicos com solubilidade limitada no fluido gastrintestinal. Embora a utilidade potencial dos SETs seja bem conhecida, só recentemente se compreendeu, mecanisticamente,o impacto desses sistemas na disposição de fármacos. Estes sistemas de formação de emulsão in situ têm alta estabilidade, quando incorporados em várias formas de dosagem. Os SETs têm sido considerados como sistemas que podem resolver problemas associados à liberação de fármacos pouco solúveis em água. O conhecimento profundo dos lipídios e tensoativos que podem ser utilizados para estes sistemas e o critério para a sua seleção e proporção na qual eles são utilizados são alguns dos fatores cruciais que determinam o desempenho do sistema in vivo. Este artigo apresenta o relato abrangente de vários tipos de formulações auto-emulsificantes, com ênfase em sua composição e exemplos das preparações que são correntemente comercializadas

Search for heavy resonances decaying into a Z or W boson and a Higgs boson in final states with leptons and b-jets in 139 fb−1 of pp collisions at s√ = 13 TeV with the ATLAS detector

This article presents a search for new resonances decaying into a Z or W boson and a 125 GeV Higgs boson h, and it targets the νν¯¯¯bb¯¯, ℓ+ℓ−bb¯¯, or ℓ±νbb¯¯ final states, where ℓ = e or μ, in proton-proton collisions at s√ = 13 TeV. The data used correspond to a total integrated luminosity of 139 fb−1 collected by the ATLAS detector during Run 2 of the LHC at CERN. The search is conducted by examining the reconstructed invariant or transverse mass distributions of Zh or Wh candidates for evidence of a localised excess in the mass range from 220 GeV to 5 TeV. No significant excess is observed and 95% confidence-level upper limits between 1.3 pb and 0.3 fb are placed on the production cross section times branching fraction of neutral and charged spin-1 resonances and CP-odd scalar bosons. These limits are converted into constraints on the parameter space of the Heavy Vector Triplet model and the two-Higgs-doublet model

Search for boosted diphoton resonances in the 10 to 70 GeV mass range using 138 fb−1 of 13 TeV pp collisions with the ATLAS detector

A search for diphoton resonances in the mass range between 10 and 70 GeV with the ATLAS experiment at the Large Hadron Collider (LHC) is presented. The analysis is based on pp collision data corresponding to an integrated luminosity of 138 fb−1 at a centre-of-mass energy of 13 TeV recorded from 2015 to 2018. Previous searches for diphoton resonances at the LHC have explored masses down to 65 GeV, finding no evidence of new particles. This search exploits the particular kinematics of events with pairs of closely spaced photons reconstructed in the detector, allowing examination of invariant masses down to 10 GeV. The presented strategy covers a region previously unexplored at hadron colliders because of the experimental challenges of recording low-energy photons and estimating the backgrounds. No significant excess is observed and the reported limits provide the strongest bound on promptly decaying axion-like particles coupling to gluons and photons for masses between 10 and 70 GeV