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Background Intravenous fluids, an essential component of sepsis resuscitation, may paradoxically worsen outcomes by exacerbating endothelial injury. Preclinical models suggest that fluid resuscitation degrades the endothelial glycocalyx, a heparan sulfate-enriched structure necessary for vascular homeostasis. We hypothesized that endothelial glycocalyx degradation is associated with the volume of intravenous fluids administered during early sepsis resuscitation. Methods We used mass spectrometry to measure plasma heparan sulfate (a highly sensitive and specific index of systemic endothelial glycocalyx degradation) after 6 h of intravenous fluids in 56 septic shock patients, at presentation and after 24 h of intravenous fluids in 100 sepsis patients, and in two groups of non-infected patients. We compared plasma heparan sulfate concentrations between sepsis and non-sepsis patients, as well as between sepsis survivors and sepsis non-survivors. We used multivariable linear regression to model the association between volume of intravenous fluids and changes in plasma heparan sulfate. Results Consistent with previous studies, median plasma heparan sulfate was elevated in septic shock patients (118 [IQR, 113–341] ng/ml 6 h after presentation) compared to non-infected controls (61 [45–79] ng/ml), as well as in a second cohort of sepsis patients (283 [155–584] ng/ml) at emergency department presentation) compared to controls (177 [144–262] ng/ml). In the larger sepsis cohort, heparan sulfate predicted in-hospital mortality. In both cohorts, multivariable linear regression adjusting for age and severity of illness demonstrated a significant association between volume of intravenous fluids administered during resuscitation and plasma heparan sulfate. In the second cohort, independent of disease severity and age, each 1 l of intravenous fluids administered was associated with a 200 ng/ml increase in circulating heparan sulfate ( p  = 0.006) at 24 h after enrollment. Conclusions Glycocalyx degradation occurs in sepsis and septic shock and is associated with in-hospital mortality. The volume of intravenous fluids administered during sepsis resuscitation is independently associated with the degree of glycocalyx degradation. These findings suggest a potential mechanism by which intravenous fluid resuscitation strategies may induce iatrogenic endothelial injury.

The Nancy Grace Roman Space Telescope will conduct a High Latitude Spectroscopic Survey (HLSS) over a large volume at high redshift, using the near-IR grism (1.0–1.93 μm, R = 435–865) and the 0.28 deg2 wide-field camera. We present a reference HLSS that maps 2000 deg2 and achieves an emission-line flux limit of 10−16 erg s−1 cm−2 at 6.5σ, requiring ∼0.6 yr of observing time. We summarize the flowdown of the Roman science objectives to the science and technical requirements of the HLSS. We construct a mock redshift survey over the full HLSS volume by applying a semianalytic galaxy formation model to a cosmological N-body simulation and use this mock survey to create pixel-level simulations of 4 deg2 of HLSS grism spectroscopy. We find that the reference HLSS would measure ∼10 million Hα galaxy redshifts that densely map large-scale structure at z = 1–2 and 2 million [O iii] galaxy redshifts that sparsely map structures at z = 2–3. We forecast the performance of this survey for measurements of the cosmic expansion history with baryon acoustic oscillations and the growth of large-scale structure with redshift-space distortions. We also study possible deviations from the reference design and find that a deep HLSS at f line > 7 × 10−17 erg s−1 cm−2 over 4000 deg2 (requiring ∼1.5 yr of observing time) provides the most compelling stand-alone constraints on dark energy from Roman alone. This provides a useful reference for future optimizations. The reference survey, simulated data sets, and forecasts presented here will inform community decisions on the final scope and design of the Roman HLSS.

Severe acute kidney injury (AKI) is associated with subsequent infection. Whether AKI followed by a return to baseline creatinine is associated with incident infection is unknown. We hypothesized that risk of both short and long term infection would be higher among patients with AKI and return to baseline creatinine than in propensity score matched peers without AKI in the year following a non-infectious hospital admission. Retrospective, propensity score matched cohort study. We identified 494 patients who were hospitalized between January 1, 1999 and December 31, 2009 and had AKI followed by return to baseline creatinine. These were propensity score matched to controls without AKI. The predictor variable was AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and by the Kidney Disease Improving Global Outcomes definition, with return to baseline creatinine defined as a decrease in serum creatinine level to within 10% of the baseline value within 7 days of hospital discharge. The outcome variable was incident infection defined by ICD-9 code within 1 year of hospital discharge. AKI followed by return to baseline creatinine was associated with a 4.5-fold increased odds ratio for infection (odds ratio 4.53 [95% CI, 2.43-8.45]; p<0.0001) within 30 days following discharge. The association between AKI and subsequent infection remained significant at 31-60 days and 91 to 365 days but not during 61-90 days following discharge. Among patients from an integrated health care delivery system, non-infectious AKI followed by return to baseline creatinine was associated with an increased odds ratio for infection in the year following discharge.

The MAMMOTH–Grism slitless spectroscopic survey is a Hubble Space Telescope (HST) cycle 28 medium program, which is obtaining 45 orbits of WFC3/IR grism spectroscopy in the density peak regions of three massive galaxy protoclusters at z = 2–3 discovered using the MAMMOTH technique. We introduce this survey by presenting the first measurement of the mass–metallicity relation (MZR) at high redshift in overdense environments via grism spectroscopy. From the completed MAMMOTH–Grism observations in the field of the BOSS1244 protocluster at z = 2.24 ± 0.02, we secure a sample of 36 protocluster member galaxies at z ≈ 2.24, showing strong nebular emission lines ([O III], Hβ, and [O II]) in their G141 spectra. Using the multi-wavelength broadband deep imaging from HST and ground-based telescopes, we measure their stellar masses in the range of [109, 1010.4] M ⊙, instantaneous star formation rates (SFR) from 10 to 240 M ⊙ yr−1, and global gas-phase metallicities [13,1] of solar. Compared with similarly selected field-galaxy samples at the same redshift, our galaxies show, on average, increased SFRs by ∼0.06 dex and ∼0.18 dex at ∼1010.1 M ⊙ and ∼109.8 M ⊙, respectively. Using the stacked spectra of our sample galaxies, we derive the MZR in the BOSS1244 protocluster core as 12+log(O/H)=0.136±0.018 × log(M*/M⊙)+7.082±0.175 , showing a significantly shallower slope than that in the field. This shallow MZR slope is likely caused by the combined effects of efficient recycling of feedback-driven winds and cold-mode gas accretion in protocluster environments. The former effect helps low-mass galaxies residing in overdensities retain their metal production, whereas the latter effect dilutes the metal content of high-mass galaxies, making them more metal-poor than their coeval field counterparts.

In February, we invited you to share your opinion about the medicinal use of marijuana. We now present the polling results. Readers recently joined in a lively debate about the use of medicinal marijuana. In Clinical Decisions, 1 an interactive feature in which experts discuss a controversial topic and readers vote and post comments, we presented the case of Marilyn, a 68-year-old woman with metastatic breast cancer. We asked whether she should be prescribed marijuana to help alleviate her symptoms. To frame this issue, we invited experts to present opposing viewpoints about the medicinal use of marijuana. J. Michael Bostwick, M.D., a professor of psychiatry at Mayo Clinic, proposed the use of marijuana “only when conservative options have failed for fully informed . . .

We introduce the Bias-free Extragalactic Analysis for Cosmic Origins with NIRCam (BEACON) survey, a JWST Cycle 2 program allocated up to 600 pure-parallel hours of observations. BEACON explores high-latitude areas of the sky with JWST/NIRCam over ∼100 independent sight lines, totaling ∼0.3 deg2, reaching a median F444W depth of ≈28.2 AB mag (5σ). Based on existing JWST observations in legacy fields, we estimate that BEACON will photometrically identify 25–150 galaxies at z > 10 and 500–1000 at z ∼ 7–10 uniquely enabled by an efficient multiple filter configuration spanning 0.9–5.0 μm. The expected sample size of z > 10 galaxies will allow us to obtain robust number density estimates and to discriminate between different models of early star formation. In this paper, we present an overview of the survey design and initial results using the first 19 fields. We present 129 galaxy candidates at z ≳7 identified in those fields, including 11 galaxies at z ≳10 and several UV-luminous (MUV < −21 mag) galaxies at z ∼ 8. The number densities of z < 13 galaxies inferred from the initial fields are overall consistent with those in the literature. Despite reaching a considerably large volume (∼105 Mpc3), however, we find no galaxy candidates at z > 13, providing us with a complimentary insight into early galaxy evolution with minimal cosmic variance. We publish imaging and catalog data products for these initial fields. Upon survey completion, all BEACON data will be coherently processed and distributed to the community along with catalogs for redshift and other physical quantities.

The endothelial glycocalyx is a heparan sulfate (HS)–rich endovascular structure critical to endothelial function. Accordingly, endothelial glycocalyx degradation during sepsis contributes to tissue edema and organ injury. We determined the endogenous mechanisms governing pulmonary endothelial glycocalyx reconstitution, and if these reparative mechanisms are impaired during sepsis. We performed intravital microscopy of wild-type and transgenic mice to determine the rapidity of pulmonary endothelial glycocalyx reconstitution after nonseptic (heparinase-III mediated) or septic (cecal ligation and puncture mediated) endothelial glycocalyx degradation. We used mass spectrometry, surface plasmon resonance, and in vitro studies of human and mouse samples to determine the structure of HS fragments released during glycocalyx degradation and their impact on fibroblast growth factor receptor (FGFR) 1 signaling, a mediator of endothelial repair. Homeostatic pulmonary endothelial glycocalyx reconstitution occurred rapidly after nonseptic degradation and was associated with induction of the HS biosynthetic enzyme, exostosin (EXT)-1. In contrast, sepsis was characterized by loss of pulmonary EXT1 expression and delayed glycocalyx reconstitution. Rapid glycocalyx recovery after nonseptic degradation was dependent upon induction of FGFR1 expression and was augmented by FGF-promoting effects of circulating HS fragments released during glycocalyx degradation. Although sepsis-released HS fragments maintained this ability to activate FGFR1, sepsis was associated with the downstream absence of reparative pulmonary endothelial FGFR1 induction. Sepsis may cause vascular injury not only via glycocalyx degradation, but also by impairing FGFR1/EXT1–mediated glycocalyx reconstitution.

We report the first spatially resolved measurements of gas-phase metallicity radial gradients in star-forming galaxies in overdense environments at z ≳ 2. The spectroscopic data are acquired by the MAMMOTH-Grism survey, a Hubble Space Telescope (HST) cycle 28 medium program. This program is obtaining 45 orbits of WFC3/IR grism spectroscopy in the density peak regions of three massive galaxy protoclusters (BOSS 1244, BOSS 1542, and BOSS 1441) at z = 2–3. Our sample in the BOSS 1244 field consists of 20 galaxies with stellar mass ranging from 109.0 to 1010.3 M ⊙, star formation rate (SFR) from 10 to 240 M ⊙ yr−1, and global gas-phase metallicity ( 12+log(O/H) ) from 8.2 to 8.6. At 1σ confidence level, 2/20 galaxies in our sample show positive (inverted) gradients—the relative abundance of oxygen increasing with galactocentric radius, opposite the usual trend. Furthermore, 1/20 shows negative gradients, and 17/20 are consistent with flat gradients. This high fraction of flat/inverted gradients is uncommon in simulations and previous observations conducted in blank fields at similar redshifts. To understand this, we investigate the correlations among various observed properties of our sample galaxies. We find an anticorrelation between metallicity gradient and global metallicity of our galaxies residing in extreme overdensities, and a marked deficiency of metallicity in our massive galaxies as compared to their coeval field counterparts. We conclude that the cold-mode gas accretion plays an active role in shaping the chemical evolution of galaxies in the protocluster environments, diluting their central chemical abundance, and flattening/inverting their metallicity gradients.

The UltraViolet Imaging of the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey Fields (UVCANDELS) survey is a Hubble Space Telescope (HST) Cycle-26 Treasury Program, allocated in total 164 orbits of primary Wide-Field Camera 3 Ultraviolet and VISible light F275W imaging with coordinated parallel Advanced Camera for Surveys F435W imaging, on four of the five premier extragalactic survey fields: GOODS-N, GOODS-S, EGS, and COSMOS. We introduce this survey by presenting a comprehensive analysis of the absolute escape fraction ( fescabs ) of Lyman continuum radiation through stacking the UV images of a population of star-forming galaxies with secure redshifts at 2.4 ≤ z ≤ 3.0. Our stacking benefits from the catalogs of high-quality spectroscopic redshifts compiled from archival ground-based data and HST slitless spectroscopy, carefully vetted by dedicated visual inspection efforts. We develop a robust stacking method to apply to 10 samples of in total 56 galaxies, and perform detailed Monte Carlo simulations of the intergalactic medium (IGM) attenuation, to take into account the sample variance of the mean IGM transmission when measuring fescabs . The full stack at z ≈ 2.44 from 28 galaxies places a stringent 1σ upper limit of fescabs≲5% , whereas the full stack at z ≈ 2.72 of an equal number of galaxies gives an upper limit of fescabs≲26% at 1σ confidence level. These new F275W and F435W imaging mosaics from UVCANDELS have been made publicly available on the Barbara A. Mikulski Archive for Space Telescopes.