Building the health-economic case for scaling up the WHO-HEARTS hypertension control package in low- and middle-income countries

Generally, hypertension control programs are cost-effective, including in low- and middle-income countries, but country governments and civil society are not likely to support hypertension control programs unless value is demonstrated in terms of public health benefits, budget impact, and value-for-investment for the individual country context. The World Health Organization (WHO) and the Pan American Health Organization (PAHO) established a standard, simplified Global HEARTS approach to hypertension control, including preferred antihypertensive medicines and blood pressure measurement devices. The objective of this study is to report on health economic studies of HEARTS hypertension control package cost (especially medication costs), cost-effectiveness, and budget impact and describe mathematical models designed to translate hypertension control program data into the optimal approach to hypertension care service delivery and financing, especially in lowand middle-income countries. Early results suggest that HEARTS hypertension control interventions are either cost-saving or cost-effective, that the HEARTS package is affordable at between US$18-44 per person treated per year, and that antihypertensive medicines could be priced low enough to reach a global standard of an average <US$ 5 per patient per year in the public sector. This health economic evidence will make a compelling case for government ownership and financial support for national scale hypertension control programs

Impact Earth: A review of the terrestrial impact record

Over the past few decades, it has become increasingly clear that the impact of interplanetary bodies on other planetary bodies is one of the most ubiquitous and important geological processes in the Solar System. This impact process has played a fundamental role throughout the history of the Earth and other planetary bodies, resulting in both destructive and beneficial effects. The impact cratering record of Earth is critical to our understanding of the processes, products, and effects of impact events. In this contribution, we provide an up-to-date review and synthesis of the impact cratering record on Earth. Following a brief history of the Impact Earth Database (available online at http://www.impactearth.com), the definition of the main categories of impact features listed in the database, and an overview of the impact cratering process, we review and summarize the required evidence to confirm impact events. Based on these definitions and criteria, we list 188 hypervelocity impact craters and 13 impact craters (i.e., impact sites lacking evidence for shock metamorphism). For each crater, we provide details on key attributes, such as location, date confirmed, erosional level, age, target properties, diameter, and an overview of the shock metamorphic effects and impactites that have been described in the literature. We also list a large number of impact deposits, which we have classified into four main categories: tektites, spherule layers, occurrences of other types of glass, and breccias. We discuss the challenges of recognizing and confirming impact events and highlight weaknesses, contradictions, and inconsistencies in the literature. We then address the morphology and morphometry of hypervelocity impact craters. Based on the Impact Earth Database, it is apparent that the transition diameter from simple to complex craters for craters developed in sedimentary versus crystalline target rocks is less pronounced than previously reported, at approximately 3 km for both. Our analysis also yields an estimate for stratigraphic uplift of 0.0945D0.6862, which is lower than previous estimates. We ascribe this to more accurate diameter estimates plus the variable effects of erosion. It is also clear that central topographic peaks in terrestrial complex impact craters are, in general, more subdued than their lunar counterparts. Furthermore, a number of relatively well-preserved terrestrial complex impact structures lack central peaks entirely. The final section of this review provides an overview of impactites preserved in terrestrial hypervelocity impact craters. While approximately three quarters of hypervelocity impact craters on Earth preserve some portion of their crater-fill impactites, ejecta deposits are known from less than 10%. In summary, the Impact Earth Database provides an important new resource for researchers interested in impact craters and the impact cratering process and we welcome input from the community to ensure that the Impact Earth website (http://www.impactearth.com) is a living resource that is as accurate and as up-to-date, as possible

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Probing the hydrothermal system of the Chicxulub impact crater

The ~180-km-diameter Chicxulub peak-ring crater and ~240-km multiring basin, produced by the impact that terminated the Cretaceous, is the largest remaining intact impact basin on Earth. International Ocean Discovery Program (IODP) and International Continental Scientific Drilling Program (ICDP) Expedition 364 drilled to a depth of 1335 m below the sea floor into the peak ring, providing a unique opportunity to study the thermal and chemical modification of Earth’s crust caused by the impact. The recovered core shows the crater hosted a spatially extensive hydrothermal system that chemically and mineralogically modified ~1.4 × 105 km3 of Earth’s crust, a volume more than nine times that of the Yellowstone Caldera system. Initially, high temperatures of 300° to 400°C and an independent geomagnetic polarity clock indicate the hydrothermal system was long lived, in excess of 106 years

Enzyme-cargo encapsulation peptides bind between tessellating tiles of the bacterial microcompartment shell.

Bacterial microcompartments are prokaryotic organelles comprising encapsulated enzymes within a thin protein shell. They facilitate metabolic processing including propanediol, choline, glycerol, and ethanolamine utilization, and they accelerate carbon fixation in cyanobacteria. Enzymes targeted to the inside of the microcompartment frequently possess a cargo-encapsulation peptide, but the site to which the peptide binds is unclear. We provide evidence that the encapsulation peptides bind to the hydrophobic groove formed between tessellating subunits of the shell proteins. In silico docking studies provide a compelling model of peptide binding to this prominent hydrophobic groove. This result is consistent with the now widely accepted view that the convex side of the shell oligomers faces the lumen of the microcompartment. Binding of the encapsulation peptide to the groove between tessellating shell protein tiles explains why it has been difficult to define the peptide binding site using other methods, provides a mechanism by which encapsulation-peptide bearing enzymes can promote shell assembly, and explains how the presence of cargo affects the size and shape of the bacterial microcompartment. This knowledge may be exploited in engineering microcompartments or in disease prevention by hampering cargo-encapsulation

The Winchcombe meteorite, a unique and pristine witness from the outer solar system

Direct links between carbonaceous chondrites and their parent bodies in the solar system are rare. The Winchcombe meteorite is the most accurately recorded carbonaceous chondrite fall. Its pre-atmospheric orbit and cosmic-ray exposure age confirm that it arrived on Earth shortly after ejection from a primitive asteroid. Recovered only hours after falling, the composition of the Winchcombe meteorite is largely unmodified by the terrestrial environment. It contains abundant hydrated silicates formed during fluid-rock reactions, and carbon- and nitrogen-bearing organic matter including soluble protein amino acids. The near-pristine hydrogen isotopic composition of the Winchcombe meteorite is comparable to the terrestrial hydrosphere, providing further evidence that volatile-rich carbonaceous asteroids played an important role in the origin of Earth’s water.Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). The linked file is the published version of the article.NHM Repositor

The Winchcombe meteorite, a unique and pristine witness from the outer solar system.

Direct links between carbonaceous chondrites and their parent bodies in the solar system are rare. The Winchcombe meteorite is the most accurately recorded carbonaceous chondrite fall. Its pre-atmospheric orbit and cosmic-ray exposure age confirm that it arrived on Earth shortly after ejection from a primitive asteroid. Recovered only hours after falling, the composition of the Winchcombe meteorite is largely unmodified by the terrestrial environment. It contains abundant hydrated silicates formed during fluid-rock reactions, and carbon- and nitrogen-bearing organic matter including soluble protein amino acids. The near-pristine hydrogen isotopic composition of the Winchcombe meteorite is comparable to the terrestrial hydrosphere, providing further evidence that volatile-rich carbonaceous asteroids played an important role in the origin of Earth's water