The Utility of Non-Specific ECG Findings in the Setting of Low High-Sensitivity Cardiac Troponin Levels

Objective: Our objective was to assess the relationship between non-specific ischemic electrocardiogram (nsi-ECG) findings and the occurrence of major adverse cardiac events (MACE) within a 30-day timeframe among patients in the Emergency Department (ED) with low high-sensitivity cardiac troponin (hs-cTnI) levels. Methods: We conducted a secondary analysis of the RACE-IT trial, a randomized trial performed across 9 EDs from July 2020 through March 2021 that looked at the effectiveness of hs-cTnI in evaluating the risk for acute myocardial infarction (AMI). Our study assessed the association between nsi-ECG findings (left bundle branch block, ST-segment changes, or T-wave inversions) and 30-day MACE (death, AMI, heart failure hospitalization, or coronary revascularization) in patients who had AMI ruled out based on low hs-cTnI levels. Results: 16,606 patients were included in this analysis. Combined, there were 3345 patients with potentially ischemic ECG findings. Thirty-day death or AMI occurred in 66 patients. Death within 30 days occurred in 47 patients, of whom 38 were adjudicated as non-cardiac. There was no difference in MACE events based on potentially ischemic findings (OR 1.38, 95% CI 0.79 - 2.39, p=0.257). The presence of ST-segment changes, however, had a trend towards greater odds of MACE (OR 2.53, 95% CI 0.92 - 6.99). Conclusion: Non-specific ischemic ECG findings in the setting of low hs-cTnI are not associated with greater MACE events within 30 days of discharge for patients with possible AMIs. The use of nsi-ECG findings should be considered in the context of hs-cTnI levels when evaluating risk for coronary disease

Surfactant-enhanced DNA accessibility to nuclease accelerates phenotypic β-lactam antibiotic susceptibility testing of Neisseria gonorrhoeae

Rapid antibiotic susceptibility testing (AST) for Neisseria gonorrhoeae (Ng) is critically needed to counter widespread antibiotic resistance. Detection of nucleic acids in genotypic AST can be rapid, but it has not been successful for β-lactams (the largest antibiotic class used to treat Ng). Rapid phenotypic AST for Ng is challenged by the pathogen’s slow doubling time and the lack of methods to quickly quantify the pathogen’s response to β-lactams. Here, we asked two questions: (1) Is it possible to use nucleic acid quantification to measure the β-lactam susceptibility phenotype of Ng very rapidly, using antibiotic-exposure times much shorter than the 1- to 2-h doubling time of Ng? (2) Would such short-term antibiotic exposures predict the antibiotic resistance profile of Ng measured by plate growth assays over multiple days? To answer these questions, we devised an innovative approach for performing a rapid phenotypic AST that measures DNA accessibility to exogenous nucleases after exposure to β-lactams (termed nuclease-accessibility AST [nuc-aAST]). We showed that DNA in antibiotic-susceptible cells has increased accessibility upon exposure to β-lactams and that a judiciously chosen surfactant permeabilized the outer membrane and enhanced this effect. We tested penicillin, cefixime, and ceftriaxone and found good agreement between the results of the nuc-aAST after 15–30 min of antibiotic exposure and the results of the gold-standard culture-based AST measured over days. These results provide a new pathway toward developing a critically needed phenotypic AST for Ng and additional global-health threats

Solar Thermochemical Energy Storage Through Carbonation Cycles of SrCO₃/SrO Supported on SrZrO₃

Solar thermochemical energy storage has enormous potential for enabling cost-effective concentrated solar power (CSP). A thermochemical storage system based on a SrO/SrCO₃ carbonation cycle offers the ability to store and release high temperature (≈1200 °C) heat. The energy density of SrCO₃/SrO systems supported by zirconia-based sintering inhibitors was investigated for 15 cycles of exothermic carbonation at 1150 °C followed by decomposition at 1235 °C. A sample with 40 wt % of SrO supported by yttria-stabilized zirconia (YSZ) shows good energy storage stability at 1450 MJ m⁻³ over fifteen cycles at the same cycling temperatures. After further testing over 45 cycles, a decrease in energy storage capacity to 1260 MJ m⁻³ is observed during the final cycle. The decrease is due to slowing carbonation kinetics, and the original value of energy density may be obtained by lengthening the carbonation steps.Keywords: energy storage, strontium oxide, concentrated solar power, reactive stabilit

Leave no one behind: response to new evidence and guidelines for the management of cryptococcal meningitis in low-income and middle-income countries

In 2018, WHO issued guidelines for the diagnosis, prevention, and management of HIV-related cryptococcal disease. Two strategies are recommended to reduce the high mortality associated with HIV-related cryptococcal meningitis in low-income and middle-income countries (LMICs): optimised combination therapies for confirmed meningitis cases and cryptococcal antigen screening programmes for ambulatory people living with HIV who access care. WHO's preferred therapy for the treatment of HIV-related cryptococcal meningitis in LMICs is 1 week of amphotericin B plus flucytosine, and the alternative therapy is 2 weeks of fluconazole plus flucytosine. In the ACTA trial, 1-week (short course) amphotericin B plus flucytosine resulted in a 10-week mortality of 24% (95% CI −16 to 32) and 2 weeks of fluconazole and flucytosine resulted in a 10-week mortality of 35% (95% CI −29 to 41). However, with widely used fluconazole monotherapy, mortality because of HIV-related cryptococcal meningitis is approximately 70% in many African LMIC settings. Therefore, the potential to transform the management of HIV-related cryptococcal meningitis in resource-limited settings is substantial. Sustainable access to essential medicines, including flucytosine and amphotericin B, in LMICs is paramount and the focus of this Personal View

Surfactant-enhanced DNA accessibility to nuclease accelerates phenotypic β-lactam antibiotic susceptibility testing of Neisseria gonorrhoeae.

Rapid antibiotic susceptibility testing (AST) for Neisseria gonorrhoeae (Ng) is critically needed to counter widespread antibiotic resistance. Detection of nucleic acids in genotypic AST can be rapid, but it has not been successful for β-lactams (the largest antibiotic class used to treat Ng). Rapid phenotypic AST for Ng is challenged by the pathogen's slow doubling time and the lack of methods to quickly quantify the pathogen's response to β-lactams. Here, we asked two questions: (1) Is it possible to use nucleic acid quantification to measure the β-lactam susceptibility phenotype of Ng very rapidly, using antibiotic-exposure times much shorter than the 1- to 2-h doubling time of Ng? (2) Would such short-term antibiotic exposures predict the antibiotic resistance profile of Ng measured by plate growth assays over multiple days? To answer these questions, we devised an innovative approach for performing a rapid phenotypic AST that measures DNA accessibility to exogenous nucleases after exposure to β-lactams (termed nuclease-accessibility AST [nuc-aAST]). We showed that DNA in antibiotic-susceptible cells has increased accessibility upon exposure to β-lactams and that a judiciously chosen surfactant permeabilized the outer membrane and enhanced this effect. We tested penicillin, cefixime, and ceftriaxone and found good agreement between the results of the nuc-aAST after 15-30 min of antibiotic exposure and the results of the gold-standard culture-based AST measured over days. These results provide a new pathway toward developing a critically needed phenotypic AST for Ng and additional global-health threats

Effects of Dopant Metal Variation and Material Synthesis Method on the Material Properties of Mixed Metal Ferrites in Yttria Stabilized Zirconia for Solar Thermochemical Fuel Production

Mixed metal ferrites have shown much promise in two-step solar-thermochemical fuel production. Previous work has typically focused on evaluating a particular metal ferrite produced by a particular synthesis process, which makes comparisons between studies performed by independent researchers difficult. A comparative study was undertaken to explore the effects different synthesis methods have on the performance of a particular material during redox cycling using thermogravimetry. This study revealed that materials made via wet chemistry methods and extended periods of high temperature calcination yield better redox performance. Differences in redox performance between materials made via wet chemistry methods were minimal and these demonstrated much better performance than those synthesized via the solid state method. Subsequently, various metal ferrite samples (NiFe2O4, MgFe2O4, CoFe2O4, and MnFe2O4) in yttria stabilized zirconia (8YSZ) were synthesized via coprecipitation and tested to determine the most promising metal ferrite combination. It was determined that 10 wt.% CoFe2O4 in 8YSZ produced the highest and most consistent yields of O2 and CO. By testing the effects of synthesis methods and dopants in a consistent fashion, those aspects of ferrite preparation which are most significant can be revealed. More importantly, these insights can guide future efforts in developing the next generation of thermochemical fuel production materials