Implications of the VHE Gamma-Ray Detection of the Quasar 3C279

The MAGIC collaboration recently reported the detection of the quasar 3C279 at > 100 GeV gamma-ray energies. Here we present simultaneous optical (BVRI) and X-ray (RXTE PCA) data from the day of the VHE detection and discuss the implications of the snap-shot spectral energy distribution for jet models of blazars. A one-zone synchrotron-self-Compton origin of the entire SED, including the VHE gamma-ray emission can be ruled out. The VHE emission could, in principle, be interpreted as Compton upscattering of external radiation (e.g., from the broad-line regions). However, such an interpretation would require either an unusually low magnetic field of B ~ 0.03 G or an unrealistically high Doppler factor of Gamma ~ 140. In addition, such a model fails to reproduce the observed X-ray flux. This as well as the lack of correlated variability in the optical with the VHE gamma-ray emission and the substantial gamma-gamma opacity of the BLR radiation field to VHE gamma-rays suggests a multi-zone model. In particular, an SSC model with an emission region far outside the BLR reproduces the simultaneous X-ray -- VHE gamma-ray spectrum of 3C279. Alternatively, a hadronic model is capable of reproducing the observed SED of 3C279 reasonably well. However, the hadronic model requires a rather extreme jet power of L_j ~ 10^{49} erg s^{-1}, compared to a requirement of L_j ~ 2 X 10^{47} erg s^{-1} for a multi-zone leptonic model.Comment: Accepted for pulication. Several clarifications and additions to the manuscript to match the accepted versio

Broadband multi-wavelength properties of M87 during the 2018 EHT campaign including a very high energy flaring episode

Context. The nearby elliptical galaxy M87 contains one of only two supermassive black holes whose emission surrounding the event horizon has been imaged by the Event Horizon Telescope (EHT). In 2018, more than two dozen multi-wavelength (MWL) facilities (from radio to γ-ray energies) took part in the second M87 EHT campaign. Aims. The goal of this extensive MWL campaign was to better understand the physics of the accreting black hole M87*, the relationship between the inflow and inner jets, and the high-energy particle acceleration. Understanding the complex astrophysics is also a necessary first step towards performing further tests of general relativity. Methods. The MWL campaign took place in April 2018, overlapping with the EHT M87* observations. We present a new, contemporaneous spectral energy distribution (SED) ranging from radio to very high-energy (VHE) γ-rays as well as details of the individual observations and light curves. We also conducted phenomenological modelling to investigate the basic source properties. Results. We present the first VHE γ-ray flare from M87 detected since 2010. The flux above 350 GeV more than doubled within a period of ≈36 hours. We find that the X-ray flux is enhanced by about a factor of two compared to 2017, while the radio and millimetre core fluxes are consistent between 2017 and 2018. We detect evidence for a monotonically increasing jet position angle that corresponds to variations in the bright spot of the EHT image. Conclusions. Our results show the value of continued MWL monitoring together with precision imaging for addressing the origins of high-energy particle acceleration. While we cannot currently pinpoint the precise location where such acceleration takes place, the new VHE γ-ray flare already presents a challenge to simple one-zone leptonic emission model approaches, and it emphasises the need for combined image and spectral modelling

Head and neck cancer surgery during the COVID-19 pandemic: An international, multicenter, observational cohort study

Background: The aims of this study were to provide data on the safety of head and neck cancer surgery currently being undertaken during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This international, observational cohort study comprised 1137 consecutive patients with head and neck cancer undergoing primary surgery with curative intent in 26 countries. Factors associated with severe pulmonary complications in COVID-19–positive patients and infections in the surgical team were determined by univariate analysis. Results: Among the 1137 patients, the commonest sites were the oral cavity (38%) and the thyroid (21%). For oropharynx and larynx tumors, nonsurgical therapy was favored in most cases. There was evidence of surgical de-escalation of neck management and reconstruction. Overall 30-day mortality was 1.2%. Twenty-nine patients (3%) tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within 30 days of surgery; 13 of these patients (44.8%) developed severe respiratory complications, and 3.51 (10.3%) died. There were significant correlations with an advanced tumor stage and admission to critical care. Members of the surgical team tested positive within 30 days of surgery in 40 cases (3%). There were significant associations with operations in which the patients also tested positive for SARS-CoV-2 within 30 days, with a high community incidence of SARS-CoV-2, with screened patients, with oral tumor sites, and with tracheostomy. Conclusions: Head and neck cancer surgery in the COVID-19 era appears safe even when surgery is prolonged and complex. The overlap in COVID-19 between patients and members of the surgical team raises the suspicion of failures in cross-infection measures or the use of personal protective equipment. Lay Summary: Head and neck surgery is safe for patients during the coronavirus disease 2019 pandemic even when it is lengthy and complex. This is significant because concerns over patient safety raised in many guidelines appear not to be reflected by outcomes, even for those who have other serious illnesses or require complex reconstructions. Patients subjected to suboptimal or nonstandard treatments should be carefully followed up to optimize their cancer outcomes. The overlap between patients and surgeons testing positive for severe acute respiratory syndrome coronavirus 2 is notable and emphasizes the need for fastidious cross-infection controls and effective personal protective equipment

Sustained circulation of enterovirus D68 in Europe in 2023 and the continued evolution of enterovirus D68 B3-lineages associated with distinct amino acid substitutions in VP1 protein

Background: Enterovirus D68 (EV-D68) causes respiratory disease ranging from mild to severe and in rare cases a paralytic syndrome, called acute flaccid myelitis (AFM). Since the global EV-D68 outbreak in 2014, the virus has mainly circulated in biennial epidemic cycles with peaks detected during even years. However, following the COVID-19 pandemic, the seasonal pattern of EV-D68 has been characterized by large yearly upsurges. Here, we describe the circulation of EV-D68 in Europe in 2023 and track its genetic evolution. Study design: Data was compiled from members of the European Non-Polio Network (ENPEN). This included monthly data on the total number of EV samples tested, EV positive samples, EV-D68 positive samples and cases, and other EV positive samples detected in 2023. Information on sample types and surveillance system was recorded. Sequence data from the VP1 gene was used for phylogenetic and amino acid sequence analysis. Results: EV was detected in 13,585 out of 203,622 diagnostic samples tested (6.7 %), of which 402 (3.0 %) were determined as EV-D68, representing 386 cases. EV-D68 infections peaked in October 2023 (136/386; 35.2 %). 267/386 (69.2 %) of EV-D68 cases were captured through clinical EV surveillance, almost all of which (202/204 of positive samples with sample type information) were detected in respiratory specimens. Phylogenetic analysis performed on 99 VP1 sequences revealed a distinct B3-derived lineage with a previously undescribed residue change, D554E, in Europe. Conclusions: The study documents sustained circulation of EV-D68 in Europe in 2023, the evolution of B3-derived lineages, and appearance of previously undescribed amino acid substitutions in Europe. This stresses the need for continuous EV-D68 surveillance and harmonization of EV-D68 detection practices towards better data comparability across countries

Showdomycin as a Versatile Chemical Tool for the Detection of Pathogenesis-Associated Enzymes in Bacteria

Showdomycin is a potent nucleoside antibiotic that displays a high structural similarity to uridine and pseudouridine. No detailed target analysis of this very unusual electrophilic natural product has been carried out so far. To unravel its biological function, we synthesized a showdomycin probe that can be appended with a fluorophor or a biotin marker via click chemistry and identified diverse enzymes which were important for either the viability or virulence of pathogenic bacteria. Our results indicate that the antibiotic effect of showdomycin against Staphylococcus aureus may be due to the inhibition of various essential enzymes, especially MurA1 and MurA2, which are required for cell wall biosynthesis. Although real-time polymerase chain reaction revealed that the MurA2 gene was expressed equally in four S. aureus strains, our probe studies showed that MurA2 was activated in only one multiresistant S. aureus strain, and only this strain was resistant to elevated concentrations of the MurA inhibitor fosfomycin, suggesting its potential role as an antibiotic bypass mechanism in the case of MurA1 inhibition. Moreover, we utilized this tool to compare enzyme profiles of different pathogenic strains, which provided unique insights in regulatory differences as well as strain-specific signatures