The first two months of the third Advanced LIGO and Virgo observing run (2019 April-May) showed that distant gravitational-wave (GW) events can now be readily detected. Three candidate mergers ...containing neutron stars (NS) were reported in a span of 15 days, all likely located more than 100 Mpc away. However, distant events such as the three new NS mergers are likely to be coarsely localized, which highlights the importance of facilities and scheduling systems that enable deep observations over hundreds to thousands of square degrees to detect the electromagnetic counterparts. On 2019 May 10 02:59:39.292 UT the GW candidate S190510g was discovered and initially classified as a binary neutron star (BNS) merger with 98% probability. The GW event was localized within an area of 3462 deg2, later refined to 1166 deg2 (90%) at a distance of 227 92 Mpc. We triggered Target-of-Opportunity observations with the Dark Energy Camera (DECam), a wide-field optical imager mounted at the prime focus of the 4 m Blanco Telescope at Cerro Tololo Inter-American Observatory in Chile. This Letter describes our DECam observations and our real-time analysis results, focusing in particular on the design and implementation of the observing strategy. Within 24 hr of the merger time, we observed 65% of the total enclosed probability of the final skymap with an observing efficiency of 94%. We identified and publicly announced 13 candidate counterparts. S190510g was reclassified 1.7 days after the merger, after our observations were completed, with a "BNS merger" probability reduced from 98% to 42% in favor of a "terrestrial classification.
Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis ...have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.
Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated “hot” tumors demonstrate higher treatment response ...rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts “cold” tumors to hot, generates systemic CD8⁺ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.
The American Thoracic Society (ATS) published guidelines based on expert opinion and published data--but not clinically derived or validated--for treating adult outpatients with community-acquired ...pneumonia.
To compare medical outcomes and antimicrobial costs for patients whose antimicrobial therapy was consistent or inconsistent with ATS guidelines.
Multicenter, prospective cohort study.
Emergency departments, medical clinics, and practitioner offices affiliated with 3 university hospitals, 1 community teaching hospital, and 1 health maintenance organization.
A total of 864 immunocompetent, adult outpatients with community-acquired pneumonia: 546 aged 60 years or younger with no comorbidity and 318 older than 60 years or with 1 comorbidity or more.
Patients' antimicrobial therapy was classified as being consistent or inconsistent with the ATS guidelines. Mortality, subsequent hospitalization, medical complications, symptom resolution, return to work and usual activities, health-related quality of life, and antimicrobial costs were compared among those treated consistently or inconsistently with the guidelines.
Outpatients aged 60 years or younger with no comorbidity who were prescribed therapy consistent with ATS guidelines (ie, erythromycin with some exceptions) had 3-fold lower antimicrobial costs ($5.43 vs $18.51; P<.001) and no significant differences in medical outcomes. Outpatients older than 60 years or with 1 comorbidity or more who were prescribed therapy consistent with ATS guidelines (ie, second-generation cephalosporin, sulfamethoxazole-trimethoprim, or beta-lactam and beta-lactamase inhibitor with or without a macrolide) had 10-fold higher antimicrobial costs ($73.50 vs $7.50; P<.001); despite trends toward higher mortality and subsequent hospitalization, no significant differences in medical outcomes were observed.
Our findings support the use of erythromycin as recommended by the ATS guidelines for outpatients aged 60 years or younger with no comorbidity. Although the antimicrobial therapy recommended in outpatients older than 60 years or with 1 comorbidity or more is more costly, this observational study provides no evidence of improved medical outcomes in the small subgroup who received ATS guideline-recommended therapy.
Porphyra umbilicalis (laver) belongs to an ancient group of red algae (Bangiophyceae), is harvested for human food, and thrives in the harsh conditions of the upper intertidal zone. Here we present ...the 87.7-Mbp haploid Porphyra genome (65.8% G + C content, 13,125 gene loci) and elucidate traits that inform our understanding of the biology of red algae as one of the few multicellular eukaryotic lineages. Novel features of the Porphyra genome shared by other red algae relate to the cytoskeleton, calcium signaling, the cell cycle, and stress-tolerance mechanisms including photoprotection. Cytoskeletal motor proteins in Porphyra are restricted to a small set of kinesins that appear to be the only universal cytoskeletal motors within the red algae. Dynein motors are absent, and most red algae, including Porphyra, lack myosin. This surprisingly minimal cytoskeleton offers a potential explanation for why red algal cells and multicellular structures are more limited in size than in most multicellular lineages. Additional discoveries further relating to the stress tolerance of bangiophytes include ancestral enzymes for sulfation of the hydrophilic galactan-rich cell wall, evidence for mannan synthesis that originated before the divergence of green and red algae, and a high capacity for nutrient uptake. Our analyses provide a comprehensive understanding of the red algae, which are both commercially important and have played a major role in the evolution of other algal groups through secondary endosymbioses.
We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of ...natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly summarized, and key knowledge gaps are highlighted. A lack of quantitative estimates of human exposure to environmental bacteria, in general, and antibiotic‐resistant bacteria, specifically, is a significant data gap hindering the assessment of effects on human health. The contribution of horizontal gene transfer to resistance in the environment and conditions that might foster the horizontal transfer of antibiotic resistance genes into human pathogens also need further research. Existing research has focused heavily on human health effects, with relatively little known about the effects of antibiotics and antibiotic resistance on natural and agricultural ecosystems. The proposed causal model is used to elucidate gaps in knowledge that must be addressed by the research community and may provide a useful starting point for the design and analysis of future research efforts.
Core Ideas
We propose a simple causal model of antibiotics and antibiotic resistance in agroecosystems.
Lack of data on human exposure to resistance in the environment hinders risk assessment.
The contribution of horizontal gene transfer to resistance in the environment requires research.
Antibiotics in environment may mediate effect of antibiotic use on resistance in the environment.
Effects of antibiotics and antibiotic resistance on natural and agricultural ecosystems are largely unknown.
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