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

Aqueous alteration processes in Jezero crater, Mars—implications for organic geochemistry

The Perseverance rover landed in Jezero crater, Mars, in February 2021. We used the Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) instrument to perform deep-ultraviolet Raman and fluorescence spectroscopy of three rocks within the crater. We identify evidence for two distinct ancient aqueous environments at different times. Reactions with liquid water formed carbonates in an olivine-rich igneous rock. A sulfate-perchlorate mixture is present in the rocks, which probably formed by later modifications of the rocks by brine. Fluorescence signatures consistent with aromatic organic compounds occur throughout these rocks and are preserved in minerals related to both aqueous environments

Volatile and Organic Compositions of Sedimentary Rocks in Yellowknife Bay, Gale crater, Mars

H₂O, CO₂, SO₂, O₂, H₂, H₂S, HCl, chlorinated hydrocarbons, NO and other trace gases were evolved during pyrolysis of two mudstone samples acquired by the Curiosity rover at Yellowknife Bay within Gale crater, Mars. H₂O/OH-bearing phases included 2:1 phyllosilicate(s), bassanite, akaganeite, and amorphous materials. Thermal decomposition of carbonates and combustion of organic materials are candidate sources for the CO₂. Concurrent evolution of O₂ and chlorinated hydrocarbons suggest the presence of oxychlorine phase(s). Sulfides are likely sources for S-bearing species. Higher abundances of chlorinated hydrocarbons in the mudstone compared with Rocknest windblown materials previously analyzed by Curiosity suggest that indigenous martian or meteoritic organic C sources may be preserved in the mudstone; however, the C source for the chlorinated hydrocarbons is not definitively of martian origin

A Habitable Fluvio-Lacustrine Environment at Yellowknife Bay, Gale Crater, Mars

The Curiosity rover discovered fine-grained sedimentary rocks, inferred to represent an ancient lake, preserve evidence of an environment that would have been suited to support a Martian biosphere founded on chemolithoautotrophy. This aqueous environment was characterized by neutral pH, low salinity, and variable redox states of both iron and sulfur species. C, H, O, S, N, and P were measured directly as key biogenic elements, and by inference N and P are assumed to have been available. The environment likely had a minimum duration of hundreds to tens of thousands of years. These results highlight the biological viability of fluvial-lacustrine environments in the post-Noachian history of Mars

The Petrochemistry of Jake_M: A Martian Mugearite

“Jake_M,” the first rock analyzed by the Alpha Particle X-ray Spectrometer instrument on the Curiosity rover, differs substantially in chemical composition from other known martian igneous rocks: It is alkaline (>15% normative nepheline) and relatively fractionated. Jake_M is compositionally similar to terrestrial mugearites, a rock type typically found at ocean islands and continental rifts. By analogy with these comparable terrestrial rocks, Jake_M could have been produced by extensive fractional crystallization of a primary alkaline or transitional magma at elevated pressure, with or without elevated water contents. The discovery of Jake_M suggests that alkaline magmas may be more abundant on Mars than on Earth and that Curiosity could encounter even more fractionated alkaline rocks (for example, phonolites and trachytes)

Mineralogy of a Mudstone at Yellowknife Bay, Gale Crater, Mars

Sedimentary rocks at Yellowknife Bay (Gale Crater) on Mars include mudstone sampled by the Curiosity rover. The samples, John Klein and Cumberland, contain detrital basaltic minerals, Ca-sulfates, Fe oxide/hydroxides, Fe-sulfides, amorphous material, and trioctahedral smectites. The John Klein smectite has basal spacing of ~10 Å indicating little interlayer hydration. The Cumberland smectite has basal spacing at ~13.2 Å as well as ~10 Å. The ~13.2 Å spacing suggests a partially chloritized interlayer or interlayer Mg or Ca facilitating H_2O retention. Basaltic minerals in the mudstone are similar to those in nearby eolian deposits. However, the mudstone has far less Fe-forsterite, possibly lost with formation of smectite plus magnetite. Late Noachian/Early Hesperian or younger age indicates that clay mineral formation on Mars extended beyond Noachian time

X-ray Diffraction Results from Mars Science Laboratory: Mineralogy of Rocknest at Gale Crater

The Mars Science Laboratory rover Curiosity scooped samples of soil from the Rocknest aeolian bedform in Gale crater. Analysis of the soil with the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument revealed plagioclase (~An57), forsteritic olivine (~Fo62), augite, and pigeonite, with minor K-feldspar, magnetite, quartz, anhydrite, hematite, and ilmenite. The minor phases are present at, or near, detection limits. The soil also contains 27 ± 14 weight percent x-ray amorphous material, likely containing multiple Fe^(3+)- and volatile-bearing phases, including possibly a substance resembling hisingerite. The crystalline component is similar to the normative mineralogy of certain basaltic rocks from Gusev crater on Mars and of martian basaltic meteorites. The amorphous component is similar to that found on Earth in places such as soils on the Mauna Kea volcano, Hawaii

Elemental Geochemistry of Sedimentary Rocks at Yellowknife Bay, Gale Crater, Mars

Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from approximately average Martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved indicating arid, possibly cold, paleoclimates and rapid erosion/deposition. Absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low temperature, circum-neutral pH, rock-dominated aqueous conditions. High spatial resolution analyses of diagenetic features, including concretions, raised ridges and fractures, indicate they are composed of iron- and halogen-rich components, magnesium-iron-chlorine-rich components and hydrated calcium-sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. Geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early history of Mars

Identification of Climate and Genetic Factors That Control Fat Content and Fatty Acid Composition of \u3ci\u3eTheobroma cacao\u3c/i\u3e L. Beans

The main ingredients of chocolate are usually cocoa powder, cocoa butter, and sugar. Both the powder and the butter are extracted from the beans of the cacao tree (Theobroma cacao L.). The cocoa butter represents the fat in the beans and possesses a unique fatty acid profile that results in chocolate’s characteristic texture and mouthfeel. Here, we used a linkage mapping population and phenotypic data of 3,292 samples from 420 progeny which led to the identification of 27 quantitative trait loci (QTLs) for fatty acid composition and six QTLs for fat content. Progeny showed extensive variation in fat levels and composition, with the level of palmitic acid negatively correlated to the sum of stearic acid, oleic acid, and linoleic acid. A major QTL explaining 24% of the relative level of palmitic acid was mapped to the distal end of chromosome 4, and those higher levels of palmitic acid were associated with the presence of a haplotype from the “TSH 1188” parent in the progeny. Within this region of chromosome 4 is the Thecc1EG017405 gene, an orthologue and isoform of the stearoyl-acyl carrier protein (ACP) desaturase (SAD) gene in plants, which is involved in fatty acid biosynthesis. Besides allelic differences, we also show that climate factors can change the fatty acid composition in the beans, including a significant positive correlation between higher temperatures and the higher level of palmitic acid. Moreover, we found a significant pollen donor effect from the variety “SIAL 70” which was associated with decreased palmitic acid levels

Identification of Climate and Genetic Factors That Control Fat Content and Fatty Acid Composition of Theobroma cacao L. Beans

The main ingredients of chocolate are usually cocoa powder, cocoa butter, and sugar. Both the powder and the butter are extracted from the beans of the cacao tree (Theobroma cacao L.). The cocoa butter represents the fat in the beans and possesses a unique fatty acid profile that results in chocolate’s characteristic texture and mouthfeel. Here, we used a linkage mapping population and phenotypic data of 3,292 samples from 420 progeny which led to the identification of 27 quantitative trait loci (QTLs) for fatty acid composition and six QTLs for fat content. Progeny showed extensive variation in fat levels and composition, with the level of palmitic acid negatively correlated to the sum of stearic acid, oleic acid, and linoleic acid. A major QTL explaining 24% of the relative level of palmitic acid was mapped to the distal end of chromosome 4, and those higher levels of palmitic acid were associated with the presence of a haplotype from the “TSH 1188” parent in the progeny. Within this region of chromosome 4 is the Thecc1EG017405 gene, an orthologue and isoform of the stearoyl-acyl carrier protein (ACP) desaturase (SAD) gene in plants, which is involved in fatty acid biosynthesis. Besides allelic differences, we also show that climate factors can change the fatty acid composition in the beans, including a significant positive correlation between higher temperatures and the higher level of palmitic acid. Moreover, we found a significant pollen donor effect from the variety “SIAL 70” which was associated with decreased palmitic acid levels.</p