Conformational analysis of 2,5-diaryl-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones: Multinuclear NMR and DFT calculations

Conformational exploration of five 2,5-diaryl-4-methyl-2,4-dihydro-3H-1,2,4-triazol-3-ones has been carried out based on a combination of their NMR chemical shifts determined in CDCl and the scrutiny of their computed relative energies and absolute shieldings calculated at the DFT/GIAO/B3LYP/6–311++G(d,p) level. The very flat potential energy curves corresponding to the three relevant single bond rotations were explored by calculating the energy of the rotational barriers and comparing the experimental chemical shifts with those theoretically calculated in each rotamer by statistical analysis.Comunidad de Madrid, Grant/Award Number: P2018/EMT-4329 AIRTEC-CM; Fundación Seneca-CARM, Grant/Award Number: Project 20811/PI/18; Spanish MICINN, Grant/Award Number: PGC2018-094644-B-C22 and CTQ2017-87231-

A structural analysis of 2,5-diaryl-4H-2,4-dihydro-3H-1,2,4-triazol-3-ones: NMR in the solid-state, X-ray crystallography and GIPAW calculations

The 1H, 13C, 15N, and 19F nuclear magnetic resonance (NMR) spectra of 11 2,5-diaryl-2,4-dihydro-3H-1,2,4-triazol-3-ones have been acquired in DMSO-d6 solution and the 13C, 15N, and 19F NMR spectra have also been acquired in the solid state (solid-state nuclear magnetic resonance [SSNMR] and magic angle spinning [MAS]). The X-ray structures of Compounds 3, 5, and 6 have been determined by X-ray diffraction. Theoretical calculations at the gauge-independent atomic orbital (GIAO)/B3LYP/6-311++G(d,p) level have provided a set of 321 chemical shifts that were compared with 310 experimental values in DMSO-d6. To obtain good agreements, some effects need to be included. The SSNMR chemical shifts have been compared with gauge-including projector-augmented wave (GIPAW) calculations and with the heavy atom–light atom (HALA) effects

Impact of Pneumococcal Vaccination in the Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy Children of the Murcia Region in Spain.

An epidemiological study of Streptococcus pneumoniae nasopharyngeal carriage in healthy children was carried out five years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Study the impact of pediatric vaccination with PCV13, and other associated epidemiological factors on the status of nasopharyngeal carriage, the circulating pneumococcal serotypes, and the antibiotic susceptibility to more frequently used antibiotics. A multi-center study was carried out in Primary Health Care, which included 1821 healthy children aged 1 to 4 years old. All isolates were sent to the Spanish Pneumococcal Reference Laboratory for serotyping and antimicrobial susceptibility testing. At least one dose of PCV13 had been received by 71.9% of children and carriage pneumococcal prevalence was 19.7%. The proportion of PCV13 serotypes was low (14.4%), with an observed predominance of non-vaccine serotypes, 23B, 11A, 10A, 35B/F, and 23A were the five most frequent. A high rate of resistance to penicillin, erythromycin, and trimethoprim sulfamethoxazole was found. A low proportion of PCV13 serotypes were detected, confirming the impact of pediatric vaccination for reducing the serotypes vaccine carriage. High resistance rates to clinically important antibiotics were observed.This work was supported by Ministerio de Economía, Industria y Competitividad (MINECO)[grant SAF2017-83388].S

Search for High-energy Neutrinos from Binary Neutron Star Merger GW170817 with ANTARES, IceCube, and the Pierre Auger Observatory

The Advanced LIGO and Advanced Virgo observatories recently discovered gravitational waves from a binary neutron star inspiral. A short gamma-ray burst (GRB) that followed the merger of this binary was also recorded by the Fermi Gamma-ray Burst Monitor (Fermi-GBM), and the Anti-Coincidence Shield for the Spectrometer for the International Gamma-Ray Astrophysics Laboratory (INTEGRAL), indicating particle acceleration by the source. The precise location of the event was determined by optical detections of emission following the merger. We searched for high-energy neutrinos from the merger in the GeV–EeV energy range using the Antares, IceCube, and Pierre Auger Observatories. No neutrinos directionally coincident with the source were detected within ±500 s around the merger time. Additionally, no MeV neutrino burst signal was detected coincident with the merger. We further carried out an extended search in the direction of the source for high-energy neutrinos within the 14 day period following the merger, but found no evidence of emission. We used these results to probe dissipation mechanisms in relativistic outflows driven by the binary neutron star merger. The non-detection is consistent with model predictions of short GRBs observed at a large off-axis angle

Multi-messenger Observations of a Binary Neutron Star Merger

International audienceOn 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of $\sim 1.7\,{\rm{s}}$ with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg(2) at a luminosity distance of ${40}_{-8}^{+8}$ Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 $\,{M}_{\odot }$. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at $\sim 40\,{\rm{Mpc}}$) less than 11 hours after the merger by the One-Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ∼10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position $\sim 9$ and $\sim 16$ days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC 4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Switching TNF antagonists in patients with chronic arthritis: An observational study of 488 patients over a four-year period

The objective of this work is to analyze the survival of infliximab, etanercept and adalimumab in patients who have switched among tumor necrosis factor (TNF) antagonists for the treatment of chronic arthritis. BIOBADASER is a national registry of patients with different forms of chronic arthritis who are treated with biologics. Using this registry, we have analyzed patient switching of TNF antagonists. The cumulative discontinuation rate was calculated using the actuarial method. The log-rank test was used to compare survival curves, and Cox regression models were used to assess independent factors associated with discontinuing medication. Between February 2000 and September 2004, 4,706 patients were registered in BIOBADASER, of whom 68% had rheumatoid arthritis, 11% ankylosing spondylitis, 10% psoriatic arthritis, and 11% other forms of chronic arthritis. One- and two-year drug survival rates of the TNF antagonist were 0.83 and 0.75, respectively. There were 488 patients treated with more than one TNF antagonist. In this situation, survival of the second TNF antagonist decreased to 0.68 and 0.60 at 1 and 2 years, respectively. Survival was better in patients replacing the first TNF antagonist because of adverse events (hazard ratio (HR) for discontinuation 0.55 (95% confidence interval (CI), 0.34-0.84)), and worse in patients older than 60 years (HR 1.10 (95% CI 0.97-2.49)) or who were treated with infliximab (HR 3.22 (95% CI 2.13-4.87)). In summary, in patients who require continuous therapy and have failed to respond to a TNF antagonist, replacement with a different TNF antagonist may be of use under certain situations. This issue will deserve continuous reassessment with the arrival of new medications. © 2006 Gomez-Reino and Loreto Carmona; licensee BioMed Central Ltd