HIV-1 fitness landscape models for indinavir treatment pressure using observed evolution in longitudinal sequence data are predictive for treatment failure

We previously modeled the in vivo evolution of human immunodeficiency virus-1 (HIV-1) under drug selective pressure from cross-sectional viral sequences. These fitness landscapes (FLs) were made by using first a Bayesian network (BN) to map epistatic substitutions, followed by scaling the fitness landscape based on an HIV evolution simulator trying to evolve the sequences from treatment naïve patients into sequences from patients failing treatment. In this study, we compared four FLs trained with different sequence populations. Epistatic interactions were learned from three different cross-sectional BNs, trained with sequence from patients experienced with indinavir (BNT), all protease inhibitors (PIs) (BNP) or all PI except indinavir (BND). Scaling the fitness landscape was done using cross-sectional data from drug naïve and indinavir experienced patients (Fcross using BNT) and using longitudinal sequences from patients failing indinavir (FlongT using BNT, FlongP using BNP, FlongD using BND). Evaluation to predict the failing sequence and therapy outcome was performed on independent sequences of patients on indinavir. Parameters included estimated fitness (LogF), the number of generations (GF) or mutations (MF) to reach the fitness threshold (average fitness when a major resistance mutation appeared), the number of generations (GR) or mutations (MR) to reach a major resistance mutation and compared to genotypic susceptibility score (GSS) from Rega and HIVdb algorithms. In pairwise FL comparisons we found significant correlation between fitness values for individual sequences, and this correlation improved after correcting for the subtype. Furthermore, FLs could predict the failing sequence under indinavir-containing combinations. At 12 and 48 weeks, all parameters from all FLs and indinavir GSS (both for Rega and HIVdb) were predictive of therapy outcome, except MR for FlongT and FlongP. The fitness landscapes have similar predictive power for treatment response under indinavir-containing regimen as standard rules-based algorithms, and additionally allow predicting genetic evolution under indinavir selective pressure

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO

Measurement of the Radiation Energy in the Radio Signal of Extensive Air Showers as a Universal Estimator of Cosmic-Ray Energy

We measure the energy emitted by extensive air showers in the form of radio emission in the frequency range from 30 to 80 MHz. Exploiting the accurate energy scale of the Pierre Auger Observatory, we obtain a radiation energy of 15.8 \pm 0.7 (stat) \pm 6.7 (sys) MeV for cosmic rays with an energy of 1 EeV arriving perpendicularly to a geomagnetic field of 0.24 G, scaling quadratically with the cosmic-ray energy. A comparison with predictions from state-of-the-art first-principle calculations shows agreement with our measurement. The radiation energy provides direct access to the calorimetric energy in the electromagnetic cascade of extensive air showers. Comparison with our result thus allows the direct calibration of any cosmic-ray radio detector against the well-established energy scale of the Pierre Auger Observatory.Comment: Replaced with published version. Added journal reference and DOI. Supplemental material in the ancillary file

First Look at z > 1 Bars in the Rest-Frame Near-Infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of {\it{JWST}} CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at $z>1$ based on rest-frame NIR F444W images of high resolution (~1.3 kpc at z ~ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at $z>1$ with spectroscopic redshifts, including the two highest redshift bars at ~2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at $z$ ~ 1.1-2.3 presented in our study have projected semi-major axes of ~2.9-4.3 kpc and projected ellipticities of ~0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ~ $1 \times 10^{10}$ to $2 \times 10^{11}$ $M_{\odot}$, star formation rates of ~ 21-295 $M_{\odot}$ yr$^{-1}$, and several have potential nearby companions. Our finding of bars at $z$ ~1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-10 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ~ 0.Comment: 16 pages, 5 figures. Accepted for Publication in Astrophysical Journal Letter

First Look at z > 1 Bars in the Rest-frame Near-infrared with JWST Early CEERS Imaging

Stellar bars are key drivers of secular evolution in galaxies and can be effectively studied using rest-frame near-infrared (NIR) images, which trace the underlying stellar mass and are less impacted by dust and star formation than rest-frame UV or optical images. We leverage the power of JWST CEERS NIRCam images to present the first quantitative identification and characterization of stellar bars at z &gt; 1 based on rest-frame NIR F444W images of high resolution (∼1.3 kpc at z ∼ 1-3). We identify stellar bars in these images using quantitative criteria based on ellipse fits. For this pilot study, we present six examples of robustly identified bars at z &gt; 1 with spectroscopic redshifts, including the two highest-redshift bars at z ∼ 2.136 and 2.312 quantitatively identified and characterized to date. The stellar bars at z ∼ 1.1-2.3 presented in our study have projected semimajor axes of ∼2.9-4.3 kpc and projected ellipticities of ∼0.41-0.53 in the rest-frame NIR. The barred host galaxies have stellar masses ∼1 × 10 10 to 2 × 10 11 M ⊙ and star formation rates of ∼21-295 M ⊙ yr −1, and several have potential nearby companions. Our finding of bars at z ∼ 1.1-2.3 demonstrates the early onset of such instabilities and supports simulations where bars form early in massive dynamically cold disks. It also suggests that if these bars at lookback times of 8-11 Gyr survive out to present epochs, bar-driven secular processes may operate over a long time and have a significant impact on some galaxies by z ∼ 0.</p

CEERS Key Paper V: A triality on the nature of HST-dark galaxies

The new capabilities that JWST offers in the near- and mid-infrared (IR) are used to investigate in unprecedented detail the nature of optical/near-IR faint, mid-IR bright sources, HST-dark galaxies among them. We gather JWST data from the CEERS survey in the EGS, jointly with HST data, and analyze spatially resolved optical-to-mid-IR spectral energy distributions (SEDs) to estimate both photometric redshifts in 2 dimensions and stellar populations properties in a pixel-by-pixel basis. We select 138 galaxies with F150W-F356W>1.5 mag, F356W<27.5 mag. The nature of these sources is threefold: (1) 71% are dusty star-forming galaxies at 2<z<6 with masses 9<log M/M_sun<11 and a variety of specific SFRs (100 Gyr^-1); (2) 18% are quiescent/dormant (i.e., subject to reignition and rejuvenation) galaxies at 3<z<5, masses log M/M_sun~10 and post-starburst stellar mass-weighted ages (0.5-1 Gyr); and (3) 11% are strong young starbursts with indications of high-EW emission lines (typically, [OIII]+Hbeta) at 6<z<7 and log M/M_sun~9.5. The sample is dominated by disk-like galaxies with a remarkable compactness for XELG-z6 (effective radii smaller than 0.4 kpc). Large attenuations in SFGs, 2<A(V)<5 mag, are found within 1.5 times the effective radius, approximately 2 kpc, while QGs present A(V)~0.2 mag. Our SED-fitting technique reproduces the expected dust emission luminosities of IR-bright and sub-millimeter galaxies. This study implies high levels of star formation activity between z~20 and z~10, where virtually 100% of our galaxies had already formed 10^8 M_sun of their stellar content, 60% of them had assembled 10^9 M_sun, and 10% up to 10^10 M_sun (in situ or ex situ). (abridged)Comment: Published in CEERS ApJL Focus Issue, ApJL 946, L1

WSES/GAIS/WSIS/SIS-E/AAST global clinical pathways for patients with skin and soft tissue infections

Skin and soft-tissue infections (SSTIs) encompass a variety of pathological conditions that involve the skin and underlying subcutaneous tissue, fascia, or muscle, ranging from simple superficial infections to severe necrotizing infections. Together, the World Society of Emergency Surgery, the Global Alliance for Infections in Surgery, the Surgical Infection Society-Europe, The World Surgical Infection Society, and the American Association for the Surgery of Trauma have jointly completed an international multi-society document to promote global standards of care in SSTIs guiding clinicians by describing reasonable approaches to the management of SSTIs. An extensive non-systematic review was conducted using the PubMed and MEDLINE databases, limited to the English language. The resulting evidence was shared by an international task force with different clinical backgrounds.Peer reviewe

The Physical Conditions of Emission-Line Galaxies at Cosmic Dawn from JWST/NIRSpec Spectroscopy in the SMACS 0723 Early Release Observations

We present rest-frame optical emission-line flux ratio measurements for five $z>5$ galaxies observed by the JWST Near-Infared Spectrograph (NIRSpec) in the SMACS 0723 Early Release Observations. We add several quality-control and post-processing steps to the NIRSpec pipeline reduction products in order to ensure reliable relative flux calibration of emission lines that are closely separated in wavelength, despite the uncertain \textit{absolute} spectrophotometry of the current version of the reductions. Compared to $z\sim3$ galaxies in the literature, the $z>5$ galaxies have similar [OIII]$\lambda$5008/H$\beta$ ratios, similar [OIII]$\lambda$4364/H$\gamma$ ratios, and higher ($\sim$0.5 dex) [NeIII]$\lambda$3870/[OII]$\lambda$3728 ratios. We compare the observations to MAPPINGS V photoionization models and find that the measured [NeIII]$\lambda$3870/[OII]$\lambda$3728, [OIII]$\lambda$4364/H$\gamma$, and [OIII]$\lambda$5008/H$\beta$ emission-line ratios are consistent with an interstellar medium that has very high ionization ($\log(Q) \simeq 8-9$, units of cm~s$^{-1}$), low metallicity ($Z/Z_\odot \lesssim 0.2$), and very high pressure ($\log(P/k) \simeq 8-9$, units of cm$^{-3}$). The combination of [OIII]$\lambda$4364/H$\gamma$ and [OIII]$\lambda$(4960+5008)/H$\beta$ line ratios indicate very high electron temperatures of $4.1<\log(T_e/{\rm K})<4.4$, further implying metallicities of $Z/Z_\odot \lesssim 0.2$ with the application of low-redshift calibrations for ``$T_e$-based'' metallicities. These observations represent a tantalizing new view of the physical conditions of the interstellar medium in galaxies at cosmic dawn.Comment: Accepted for publication in AAS Journals. 14 pages, 6 figures, 3 table