The forensic educational outreach initiative – Bridging the gap between education and workplace

Skills and knowledge gaps frequently exist between forensic educational programs and practical forensic laboratory needs. An educational outreach project involving three post-secondary academic institutions and a large multidisciplinary forensic laboratory was created to provide lectures to students, enable mentorship with forensic scientists, and provide an interactive experience within the forensic laboratory. Mentorship mixer exercises encouraged meaningful interactions between students and scientists, creating opportunities for practical discussion on employment requirements, optimal class selections based on students’ interests and forensic science requirements, and better understanding of the daily tasks and duties of operational forensic scientists. Feedback from students, professors, and forensic mentors have resulted in program improvements which will inform the educational outreach initiative going forward, including broader community outreach

Computational identification of a systemic antibiotic for gram-negative bacteria

Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the outer membrane, is an attractive target due to its surface location. Darobactins produced by Photorhabdus, a nematode gut microbiome symbiont, target BamA. We reasoned that a computational search for genes only distantly related to the darobactin operon may lead to novel compounds. Following this clue, we identified dynobactin A, a novel peptide antibiotic from Photorhabdus australis containing two unlinked rings. Dynobactin is structurally unrelated to darobactins, but also targets BamA. Based on a BamA-dynobactin co-crystal structure and a BAM-complex-dynobactin cryo-EM structure, we show that dynobactin binds to the BamA lateral gate, uniquely protruding into its β-barrel lumen. Dynobactin showed efficacy in a mouse systemic Escherichia coli infection. This study demonstrates the utility of computational approaches to antibiotic discovery and suggests that dynobactin is a promising lead for drug development

Short Report: Evaluating the Effects of Automated Donor Referral Technology on Deceased Donor Referrals

Background. Automation of deceased donor referrals with standardized clinical triggers allows organ procurement organizations to be rapidly aware of medically eligible potential donors without the need for manual reporting and subjective decision-making of otherwise very busy hospital staff. In October 2018, 3 Texas hospitals (pilot hospitals) began using an automated referral system; our goal was to evaluate the impact of this system on eligible donor referral. Methods. We studied ventilated referrals (n = 28 034) in a single organ procurement organization from January 2015 to March 2021. We estimated the change in referral rate in the 3 pilot hospitals due to the automated referral system using a difference-in-differences analysis with Poisson regression. Results. Ventilated referrals from the pilot hospitals increased from mean 11.7 per month pre-October 2018 to 26.7 per month post-October 2018. The difference-in-differences analysis estimated that automated referral was associated with a 45% increase in referrals (adjusted incidence rate ratio [aIRR] = 1.30 1.45 1.62), an 83% increase in approaches for authorization (aIRR = 1.34 1.83 2.48), a 73% increase in authorizations (aIRR = 1.18 1.73 2.55), and a 92% increase in organ donors (aIRR = 1.13 1.92 3.09). Conclusions. Following deployment of an automated referral system that did not require any actions by the referring hospital, referrals, authorizations, and organ donors increased substantially in the 3 pilot hospitals. Broader deployment of automated referral systems may lead to increases in the deceased donor pool

A new antibiotic selectively kills Gram-negative pathogens

The current need for novel antibiotics is especially acute for drug-resistant Gram-negative pathogens; 1,2; . These microorganisms have a highly restrictive permeability barrier, which limits the penetration of most compounds; 3,4; . As a result, the last class of antibiotics that acted against Gram-negative bacteria was developed in the 1960s; 2; . We reason that useful compounds can be found in bacteria that share similar requirements for antibiotics with humans, and focus on Photorhabdus symbionts of entomopathogenic nematode microbiomes. Here we report a new antibiotic that we name darobactin, which was obtained using a screen of Photorhabdus isolates. Darobactin is coded by a silent operon with little production under laboratory conditions, and is ribosomally synthesized. Darobactin has an unusual structure with two fused rings that form post-translationally. The compound is active against important Gram-negative pathogens both in vitro and in animal models of infection. Mutants that are resistant to darobactin map to BamA, an essential chaperone and translocator that folds outer membrane proteins. Our study suggests that bacterial symbionts of animals contain antibiotics that are particularly suitable for development into therapeutics

Optimizing carbon sequestration in commercial forests by integrating carbon management objectives in wood supply modeling

Carbon sequestration, Forest management planning, Goal programming, Growth and yield, Harvesting, Linear programming, Operational emissions, Optimization, Silviculture, Wood products,

Isotope ratios of H, C, and O in CO2 and H2O of the Martian atmosphere

Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and O-18/O-16 in water and C-13/C-12, O-18/O-16, O-17/O-16, and (CO)-C-13-O-18/(CO)-C-12-O-16 in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established similar to 4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing

Risk of COVID-19 after natural infection or vaccinationResearch in context

Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health

Risk of COVID-19 after natural infection or vaccinationResearch in context

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health