Geochemical and isotopic insights into the assembly, evolution and disruption of a magmatic plumbing system before and after a cataclysmic caldera-collapse eruption at Ischia volcano (Italy)

New geochemical and isotopic data on volcanic rocks spanning the period ~75–50 ka BP on Ischia volcano, Italy, shed light on the evolution of the magmatic system before and after the catastrophic, caldera-forming Monte Epomeo Green Tuff (MEGT) eruption. Volcanic activity during this period was influenced by a large, composite and differentiating magmatic system, replenished several times with isotopically distinct magmas of deep provenance. Chemical and isotopic variations highlight that the pre-MEGT eruptions were fed by trachytic/phonolitic magmas from an isotopically zoned reservoir that were poorly enriched in radiogenic Sr and became progressively less radiogenic with time. Just prior to the MEGT eruption, the magmatic system was recharged by an isotopically distinct magma, relatively more enriched in radiogenic Sr with respect to the previously erupted magmas. This second magma initially fed several SubPlinian explosive eruptions and later supplied the climactic, phonolitic-to-trachytic MEGT eruption(s). Isotopic data, together with erupted volume estimations obtained for MEGT eruption(s), indicate that >5–10 km3 of this relatively enriched magma had accumulated in the Ischia plumbing system. Geochemical modelling indicates that it accumulated at shallow depths (4–6 km), over a period of ca. 20 ka. After the MEGT eruption, volcanic activity was fed by a new batch of less differentiated (trachyte-latite) magma that was slightly less enriched in radiogenic Sr. The geochemical and Sr–Nd-isotopic variations through time reflect the upward flux of isotopically distinct magma batches, variably contaminated by Hercynian crust at 8–12 km depth. The deep-sourced latitic to trachytic magmas stalled at shallow depths (4–6 km depth), differentiated to phonolite through crystal fractionation and assimilation of a feldspar-rich mush, or ascended directly to the surface and erupted

Stopping renin-angiotensin system inhibitors in patients with advanced CKD and risk of adverse outcomes: a nationwide study

Background It is unknown whether stopping renin-angiotensin system (RAS) inhibitor therapy in patients with advanced CKD affects outcomes.Methods We studied patients referred to nephrologist care, listed on the Swedish Renal Registry during 2007-2017, who developed advanced CKD (eGFR 30 ml/min per 1.73 m(2), 1553 (15%) stopped RAS inhibitor therapy within 6 months. Median eGFR was 23 ml/min per 1.73 m(2). Compared with continuing RAS inhibition, stopping this therapy was associated with a higher absolute 5-year risk of death (40.9% versus 54.5%) and major adverse cardiovascular events (47.6% versus 59.5%), but with a lower risk of KRT (36.1% versus 27.9%); these corresponded to absolute risk differences of 13.6 events per 100 patients, 11.9 events per 100 patients, and -8.3 events per 100 patients, respectively. Results were consistent whether patients stopped RAS inhibition at higher or lower eGFR, across prespecified subgroups, after adjustment and stratification for albuminuria and potassium, and when modeling RAS inhibition as a time-dependent exposure using a marginal structural model.Conclusions In this nationwide observational study of people with advanced CKD, stopping RAS inhibition was associated with higher absolute risks of mortality and major adverse cardiovascular events, but also with a lower absolute risk of initiating KRT.Clinical epidemiolog

Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation

Background:Some individuals living with obesity may be relatively metabolically healthy, whilst others suffer from multiple conditions that may be linked to adverse metabolic effects or other factors. The extent to which the adverse metabolic component of obesity contributes to disease compared to the non-metabolic components is often uncertain. We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases.Methods:We selected 37 chronic diseases associated with obesity and genetic variants associated with different aspects of excess weight. These genetic variants included those associated with metabolically ‘favourable adiposity’ (FA) and ‘unfavourable adiposity’ (UFA) that are both associated with higher adiposity but with opposite effects on metabolic risk. We used these variants and two sample MR to test the effects on the chronic diseases.Results:MR identified two sets of diseases. First, 11 conditions where the metabolic effect of higher adiposity is the likely primary cause of the disease. Here, MR with the FA and UFA genetics showed opposing effects on risk of disease: coronary artery disease, peripheral artery disease, hypertension, stroke, type 2 diabetes, polycystic ovary syndrome, heart failure, atrial fibrillation, chronic kidney disease, renal cancer, and gout. Second, 9 conditions where the non-metabolic effects of excess weight (e.g. mechanical effect) are likely a cause. Here, MR with the FA genetics, despite leading to lower metabolic risk, and MR with the UFA genetics, both indicated higher disease risk: osteoarthritis, rheumatoid arthritis, osteoporosis, gastro-oesophageal reflux disease, gallstones, adult-onset asthma, psoriasis, deep vein thrombosis, and venous thromboembolism.Conclusions:Our results assist in understanding the consequences of higher adiposity uncoupled from its adverse metabolic effects, including the risks to individuals with high body mass index who may be relatively metabolically healthy.Funding:Diabetes UK, UK Medical Research Council, World Cancer Research Fund, National Cancer Institute

Disease consequences of higher adiposity uncoupled from its adverse metabolic effects using Mendelian randomisation

Background:Some individuals living with obesity may be relatively metabolically healthy, whilst others suffer from multiple conditions that may be linked to adverse metabolic effects or other factors. The extent to which the adverse metabolic component of obesity contributes to disease compared to the non-metabolic components is often uncertain. We aimed to use Mendelian randomisation (MR) and specific genetic variants to separately test the causal roles of higher adiposity with and without its adverse metabolic effects on diseases.Methods:We selected 37 chronic diseases associated with obesity and genetic variants associated with different aspects of excess weight. These genetic variants included those associated with metabolically ‘favourable adiposity’ (FA) and ‘unfavourable adiposity’ (UFA) that are both associated with higher adiposity but with opposite effects on metabolic risk. We used these variants and two sample MR to test the effects on the chronic diseases.Results:MR identified two sets of diseases. First, 11 conditions where the metabolic effect of higher adiposity is the likely primary cause of the disease. Here, MR with the FA and UFA genetics showed opposing effects on risk of disease: coronary artery disease, peripheral artery disease, hypertension, stroke, type 2 diabetes, polycystic ovary syndrome, heart failure, atrial fibrillation, chronic kidney disease, renal cancer, and gout. Second, 9 conditions where the non-metabolic effects of excess weight (e.g. mechanical effect) are likely a cause. Here, MR with the FA genetics, despite leading to lower metabolic risk, and MR with the UFA genetics, both indicated higher disease risk: osteoarthritis, rheumatoid arthritis, osteoporosis, gastro-oesophageal reflux disease, gallstones, adult-onset asthma, psoriasis, deep vein thrombosis, and venous thromboembolism.Conclusions:Our results assist in understanding the consequences of higher adiposity uncoupled from its adverse metabolic effects, including the risks to individuals with high body mass index who may be relatively metabolically healthy.Funding:Diabetes UK, UK Medical Research Council, World Cancer Research Fund, National Cancer Institute

A research agenda for seed-trait functional ecology

Trait-based approaches have improved our understanding of plant evolution, community assembly and ecosystem functioning. A major challenge for the upcoming decades is to understand the functions and evolution of early life-history traits, across levels of organization and ecological strategies. Although a variety of seed traits are critical for dispersal, persistence, germination timing and seedling establishment, only seed mass has been considered systematically. Here we suggest broadening the range of morphological, physiological and biochemical seed traits to add new understanding on plant niches, population dynamics and community assembly. The diversity of seed traits and functions provides an important challenge that will require international collaboration in three areas of research. First, we present a conceptual framework for a seed ecological spectrum that builds upon current understanding of plant niches. We then lay the foundation for a seed-trait functional network, the establishment of which will underpin and facilitate trait-based inferences. Finally, we anticipate novel insights and challenges associated with incorporating diverse seed traits into predictive evolutionary ecology, community ecology and applied ecology. If the community invests in standardized seed-trait collection and the implementation of rigorous databases, major strides can be made at this exciting frontier of functional ecology.Commonwealth Scientific and Industrial Research Organisation. Grant Number: R‐90470‐0

Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1

High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk, and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites