Performance of the Mortality in emergency department Sepsis score for predicting hospital mortality among patients with severe sepsis and septic shock

Objective The aim of the study was to test if the Mortality in Emergency Department Sepsis (MEDS) score accurately predicts death among emergency department (ED) patients with severe sepsis and septic shock. Methods This study was a preplanned secondary analysis of a before-and-after interventional study conducted at a large urban ED. Inclusion criteria were suspected infection, 2 or more criteria for systemic inflammation, and either systolic blood pressure of less than 90 mm Hg after a fluid bolus or lactate 4 mmol/L or higher. Exclusion criteria were: age of less than 18 years, no aggressive care desired, or need for immediate surgery. Clinical and outcomes data were prospectively collected on consecutive eligible patients for 1 year before and 1 year after implementing early goal-directed therapy (EGDT). The MEDS scores and probabilities of in-hospital death were calculated. The main outcome was in-hospital mortality. The area under the receiver operating characteristic curve was used to evaluate score performance. Results One hundred forty-three patients, 79 pre-EGDT and 64 post-EGDT, were included. The mean age was 58 ± 17 years, and pneumonia was the source of infection in 37%. The in-hospital mortality rate was 23%. The area under the receiver operating characteristic curve for MEDS to predict mortality was 0.61 (95% confidence interval [CI], 0.50-0.72) overall, 0.69 (95% CI, 0.56-0.82) in pre-EGDT patients, and 0.53 (95% CI, 0.33-0.74) in post-EGDT patients. Conclusions The MEDS score performed with poor accuracy for predicting mortality in ED patients with sepsis. These results suggest the need for further validation of the MEDS score before widespread clinical use

Radio Jet Feedback and Star Formation in Heavily Obscured Quasars at Redshifts ~0.3-3, I: ALMA Observations

We present ALMA 870 micron (345 GHz) data for 49 high redshift (0.47<z<2.85), luminous (11.7 < log L(bol) (Lsun) < 14.2) radio-powerful AGN, obtained to constrain cool dust emission from starbursts concurrent with highly obscured radiative-mode black hole (BH) accretion in massive galaxies which possess a small radio jet. The sample was selected from WISE with extremely steep (red) mid-infrared (MIR) colors and with compact radio emission from NVSS/FIRST. Twenty-six sources are detected at 870 microns, and we find that the sample has large mid- to far-infrared luminosity ratios consistent with a dominant and highly obscured quasar. The rest-frame 3 GHz radio powers are 24.7 < log P3.0 GHz (W/Hz) < 27.3, and all sources are radio-intermediate or radio-loud. BH mass estimates are 7.7 < log M(BH) (Msun) < 10.2. The rest frame 1-5 um SEDs are very similar to the "Hot DOGs" (Hot Dust Obscured Galaxies), and steeper (redder) than almost any other known extragalactic sources. ISM masses estimated for the ALMA detected sources are 9.9 < log M(ISM) (Msun) < 11.75 assuming a dust temperature of 30K. The cool dust emission is consistent with star formation rates (SFRs) reaching several thousand Msun/yr, depending on the assumed dust temperature, however we cannot rule out the alternative that the AGN powers all the emission in some cases. Our best constrained source has radiative transfer solutions with ~ equal contributions from an obscured AGN and a young (10-15 Myr) compact starburst.Comment: 29 pages, 8 figures. To appear in Astrophysical Journal. Update on Sept 14 to correct the ALMA proposal id. to ADS/JAO.ALMA#2011.0.00397.S and to add a missing acknowledgemen

Randomized Trial of Tenecteplase or Placebo with Low Molecular Weight Heparin for Acute Submassive Pulmonary Embolism: Assessment of Patient-Oriented Cardiopulmonary Outcomes at Three Months

Background: Acute submassive pulmonary embolism (PE) with right ventricular (RV) injury and/or concomitant deep venous thrombosis can cause persistent symptoms that degrade quality of life. We tested the hypothesis that intravenous tenecteplase would improve the probability of a favorable outcome at three months after submassive PE. Methods: Multicenter randomized double-blind, placebo controlled trial. Eligible patients were ambulatory at baseline, had image-proven acute PE, a systolic blood pressure > 90 mm Hg and RV dysfunction (abnormal echocardiography, troponin or brain natriuretic peptide). Patients received anticoagulation with low molecular weight heparin (LMWH) and either tiered-dose tenecteplase or saline in an opaque syringe. Composite favorable outcome: 5 day survival to hospital discharge without shock, intubation, or major hemorrhage (any intracranial bleed or need for surgical or medical intervention for acute anemia), and at 90 days, normal RV on resting echocardiography, 6 minute walk distance>330 m, no dyspnea at rest, and no recurrent PE or DVT. Self-perception of wellness was assessed by the SF-16, VEINES-QOL and rank on 1-10 ordinal scale. Results: 83 patients were enrolled, including 33 women, 52 Caucasians, mean age 55+/-14 years, 43 received placebo, 40 received tenecteplase, and 38 had concomittant DVT. A favorable composite outcome occurred in 17/43(40%, 95% CI: 25-56%) treated with placebo, versus 26/40 (65%, 95% CI: 48-79%) treated with tenecteplase, p=0.02 Fisher’s exact. Acute deterioration occurred in 3 patients treated with placebo: fatal PE (1), intubation (1), thrombectomy (1) and in one patient treated with tenecteplase who had a fatal intracranial hemorrhage. At three months, a nonfavorable outcome was found in 23 additional patients treated with placebo, versus 13 patients treated with tenecteplase. Assessments of wellness were consistently higher in the tenecteplase group (e.g., p=0.03 for ordinal scale rank). Conclusions: In this randomized trial, patients with submassive PE treated with LMWH and tenecteplase were more likely to have a favorable patient-oriented outcome at three months than patients treated with LMWH and saline placebo

Maternal Restricted- and Over-Feeding During Gestation Result in Distinct Lipid and Amino Acid Metabolite Profiles in the Longissimus Muscle of the Offspring

Maternal over- and restricted-feeding during gestation have similar negative consequences for the offspring, including decreased muscularity, increased adiposity, and altered metabolism. Our objective was to determine the effects of poor maternal nutrition during gestation (over- and restricted-feeding) on the offspring muscle metabolite profile. Pregnant ewes (n = 47) were fed 60% (RES), 100% (CON), or 140% (OVER) of NRC requirements starting at day 30.2 ± 0.2 of gestation. Offspring sample collection occurred at days 90 and 135 of gestation, and within 24 h of birth. C2C12 myoblasts were cultured in serum collected from offspring at birth (n = 18; 6 offspring per treatment) for analysis of oxidative and glycolytic capacity. Unbiased metabolite analysis of longissimus muscle samples (n = 72; 8 fetuses per treatment per time point) was performed using mass spectrometry. Data were analyzed by ANOVA for main effects of treatment, time point, and their interaction. Cells cultured in serum from RES offspring exhibited increased proton leak 49% (p = 0.01) compared with CON, but no other variables of mitochondrial respiration or glycolytic function were altered. Mass spectrometry identified 612 metabolites. Principle component analysis identified day of gestation as the primary driver of metabolic change; however, maternal diet also altered the lipid and amino acid profiles in offspring. The abundance of 53 amino acid metabolites and 89 lipid metabolites was altered in RES compared with CON (p ≤ 0.05), including phospholipids, sphingolipids, and ceramides within the lipid metabolism pathway and metabolites involved in glutamate, histidine, and glutathione metabolism. Similarly, abundance of 63 amino acid metabolites and 70 lipid metabolites was altered in OVER compared with CON (p ≤ 0.05). These include metabolites involved in glutamate, histidine, lysine, and tryptophan metabolism and phosphatidylethanolamine, lysophospholipids, and fatty acids involved in lipid metabolism. Further, the amino acid and lipid profiles diverged between RES and OVER, with 69 amino acid and 118 lipid metabolites differing (p ≤ 0.05) between groups. Therefore, maternal diet affects metabolite abundance in offspring longissimus muscle, specifically metabolites involved in lipid and amino metabolism. These changes may impact post-natal skeletal muscle metabolism, possibly altering energy efficiency and long-term health

Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism

Acute pulmonary embolism (PE) can diminish patient quality of life (QoL). The objective was to test whether treatment with tenecteplase has an independent effect on a measurement that reflects QoL in patients with submassive PE. This was a secondary analysis of an 8-center, prospective randomized controlled trial, utilizing multivariate regression to control for predefined predictors of worsened QoL including: age, active malignancy, history of PE or deep venous thrombosis (DVT), recurrent PE or DVT, chronic obstructive pulmonary disease and heart failure. QoL was measured with the physical component summary (PCS) of the SF-36. Analysis included 76 patients (37 randomized to tenecteplase, 39 to placebo). Multivariate regression yielded an equation f(8, 67), P<0.001, with R2 = 0.303. Obesity had the largest effect on PCS (β = −8.6, P<0.001), with tenecteplase second (β = 4.73, P = 0.056). After controlling for all interactions, tenecteplase increased the PCS by +5.37 points (P = 0.027). In patients without any of the defined comorbidities, the coefficient on the tenecteplase variable was not significant (−0.835, P = 0.777). In patients with submassive PE, obesity had the greatest influence on QoL, followed by use of fibrinolysis. Fibrinolysis had a marginal independent effect on patient QoL after controlling for comorbidities, but was not significant in patients without comorbid conditions

Navigating Social and Emotional Learning from the Inside Out: ?????????????????????Looking Inside and Across 33 leading SEL Programs: A Practical Resource for Schools and OST Providers

The field of social and emotional learning (SEL) is rapidly expanding, as educators bring a sharper focus to helping children build skills beyond academic knowledge. School climate initiatives, anti-bullying work, positive behavior supports and other SEL efforts are now steering programs in schools and out-of-school-time (OST) settings across the country. Building children's SEL skills has taken on even more urgency in the wake of the COVID-19 pandemic.This updated and expanded guide to evidence-based SEL programs offers detailed information on 33 pre-K through elementary school programs, encompassing curricular content and program highlights. Practitioners from schools, early childhood education (ECE) providers and out-of-school time (OST) can use this resource to look "inside and across" programs to better understand program content and assess program fit with their district or community needs.New chapters in the 2021 edition include recommendations for achieving equitable SEL (including common barriers and best practices) and guidance on trauma-informed or trauma-sensitive approaches to SEL, which includes principles, practices and recommendations for integrating SEL into regular practice

Impact of antiretroviral therapy in primary HIV infection on natural killer cell function and the association with viral rebound and HIV DNA following treatment interruption

Natural Killer (NK) cells play a key role in controlling HIV replication, with potential downstream impact on the size of the HIV reservoir and likelihood of viral rebound after antiretroviral therapy (ART) cessation. It is therefore important to understand how primary HIV infection (PHI) disrupts NK cell function, and how these functions are restored by early ART. We examined the impact of commencing ART during PHI on phenotypic and functional NK cell markers at treatment initiation (baseline), 3 months, 1 year, and 2 years in seven well-characterised participants in comparison to HIV seronegative volunteers. We then examined how those NK cell properties differentially impacted by ART related to time to viral rebound and HIV DNA levels in 44 individuals from the SPARTAC trial who stopped ART after 48 weeks treatment, started during PHI. NK cell markers that were significantly different between the seven people with HIV (PWH) treated for 2 years and HIV uninfected individuals included NKG2C levels in CD56dim NK cells, Tim-3 expression in CD56bright NK cells, IFN-γ expressed by CD56dim NK cells after IL-12/IL-18 stimulation and the fraction of Eomes-/T-bet+ in CD56dim and CD56bright NK cells. When exploring time to viral rebound after stopping ART among the 44 SPARTAC participants, no single NK phenotypic marker correlated with control. Higher levels of IL-12/IL-18 mediated NK cell degranulation at baseline were associated with longer times to viral rebound after treatment interruption (P=0.028). Additionally, we found higher fractions of CD56dim NK cells in individuals with lower levels of HIV DNA (P=0.048). NKG2A and NKp30 levels in CD56neg NK cells were higher in patients with lower HIV DNA levels (p=0.00174, r=-0.49 and p=0.03, r= -0.327, respectively) while CD27 levels were higher in those with higher levels of HIV DNA (p=0.026). These data show NK cell functions are heterogeneously impacted by HIV infection with a mixed picture of resolution on ART, and that while NK cells may affect HIV DNA levels and time to viral rebound, no single NK cell marker defined delayed viral rebound

Watson Brake, A Middle Archaic Mound Complex in Northeast Louisiana

Middle Archaic earthen mound complexes in the lower Mississippi valley are remote antecedents of the famous but much younger Poverty Point earthworks. Watson Brake is the largest and most complex of these early mound sites. Wry extensive coring and stratigraphic studies, aided by 25 radiocarbon dates and six huninescence dates, show that minor earthworks were begun here at ca. 3500 B.C. in association with an oval arrangement of burned rock middens at the edge of a stream terrace. The full extent of the first earthworks is not yet known. Substantial moundraising began ca. 3350 B.C. and continued in stages until some time after 3000 B.C. when the site was abandoned. All 11 mounds and their connecting ridges were occupied between building bursts. Soils,formed on some of these temporary surfaces, while lithics. fire-cracked rock. and,fired clay/loam objects became scattered throughout the mound fills. Faunal and floral remains from a basal midden indicate all-season occupation, supported by broad-spectrum foraging centered on nuts, fish, and deer All the overlying fills are so acidic that organics have not survived. The area enclosed by the mounds was kept clean of debris, suggesting its use as ritual space. The reasons why such elaborate activities first occurred here remain elusive. However some building bursts covary with very well-documented increases in El Nino/Southern Oscillation events. During such rapid increases in ENSO frequencies, rainfall becomes extremely erratic and unpredictable. It may be that early moundraising was a communal response to new stresses of droughts and flooding that created a suddenly more unpredictable food base

The largest deep-ocean silicic volcanic eruption of the past century

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Science Advances 4 (2018): e1701121, doi:10.1126/sciadv.1701121.The 2012 submarine eruption of Havre volcano in the Kermadec arc, New Zealand, is the largest deep-ocean eruption in history and one of very few recorded submarine eruptions involving rhyolite magma. It was recognized from a gigantic 400-km2 pumice raft seen in satellite imagery, but the complexity of this event was concealed beneath the sea surface. Mapping, observations, and sampling by submersibles have provided an exceptionally high fidelity record of the seafloor products, which included lava sourced from 14 vents at water depths of 900 to 1220 m, and fragmental deposits including giant pumice clasts up to 9 m in diameter. Most (>75%) of the total erupted volume was partitioned into the pumice raft and transported far from the volcano. The geological record on submarine volcanic edifices in volcanic arcs does not faithfully archive eruption size or magma production.This research was funded by Australian Research Council Postdoctoral fellowships (DP110102196 and DE150101190 to R. Carey), a short-term postdoctoral fellowship grant from the Japan Society for the Promotion of Science (to R. Carey), National Science Foundation grants (OCE1357443 to B.H., OCE1357216 to S.A.S., and EAR1447559 to J.D.L.W.), and a New Zealand Marsden grant (U001616 to J.D.L.W.). J.D.L.W. and A.M. were supported by a research grant and PhD scholarship from the University of Otago. R.W. was supported by NIWA grant COPR1802. J.D.L.W. and F.C.-T. were supported by GNS Science grants CSA-GHZ and CSA-EEZ. M.J. was supported by the U.S. Department of Defense (DoD) through the National Defense Science and Engineering Graduate Fellowship (NDSEG) Program

Maternal Restricted- and Over-Feeding During Gestation Result in Distinct Lipid and Amino Acid Metabolite Profiles in the Longissimus Muscle of the Offspring

Maternal over- and restricted-feeding during gestation have similar negative consequences for the offspring, including decreased muscularity, increased adiposity, and altered metabolism. Our objective was to determine the effects of poor maternal nutrition during gestation (over- and restricted-feeding) on the offspring muscle metabolite profile. Pregnant ewes (n = 47) were fed 60% (RES), 100% (CON), or 140% (OVER) of NRC requirements starting at day 30.2 ± 0.2 of gestation. Offspring sample collection occurred at days 90 and 135 of gestation, and within 24 h of birth. C2C12 myoblasts were cultured in serum collected from offspring at birth (n = 18; 6 offspring per treatment) for analysis of oxidative and glycolytic capacity. Unbiased metabolite analysis of longissimus muscle samples (n = 72; 8 fetuses per treatment per time point) was performed using mass spectrometry. Data were analyzed by ANOVA for main effects of treatment, time point, and their interaction. Cells cultured in serum from RES offspring exhibited increased proton leak 49% (p = 0.01) compared with CON, but no other variables of mitochondrial respiration or glycolytic function were altered. Mass spectrometry identified 612 metabolites. Principle component analysis identified day of gestation as the primary driver of metabolic change; however, maternal diet also altered the lipid and amino acid profiles in offspring. The abundance of 53 amino acid metabolites and 89 lipid metabolites was altered in RES compared with CON (p ≤ 0.05), including phospholipids, sphingolipids, and ceramides within the lipid metabolism pathway and metabolites involved in glutamate, histidine, and glutathione metabolism. Similarly, abundance of 63 amino acid metabolites and 70 lipid metabolites was altered in OVER compared with CON (p ≤ 0.05). These include metabolites involved in glutamate, histidine, lysine, and tryptophan metabolism and phosphatidylethanolamine, lysophospholipids, and fatty acids involved in lipid metabolism. Further, the amino acid and lipid profiles diverged between RES and OVER, with 69 amino acid and 118 lipid metabolites differing (p ≤ 0.05) between groups. Therefore, maternal diet affects metabolite abundance in offspring longissimus muscle, specifically metabolites involved in lipid and amino metabolism. These changes may impact post-natal skeletal muscle metabolism, possibly altering energy efficiency and long-term health