53 research outputs found

    Two-pronged kill mechanism at the end-Triassic mass extinction

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    High-resolution biomarker and compound-specific isotope distributions coupled with the degradation of calcareous fossil remnants reveal that intensive euxinia and decalcification (acidification) driven by Central Atlantic magmatic province (CAMP) activity formed a twopronged kill mechanism at the end-Triassic mass extinction. In a newly proposed extinction interval for the basal Blue Lias Formation (Bristol Channel Basin, UK), biomarker distributions reveal an episode of persistent photic zone euxinia (PZE) that extended further upward into the surface waters. In the same interval, shelly taxa almost completely disappear. Beginning in the basal paper shales of the Blue Lias Formation, a Lilliput assemblage is preserved consisting of only rare calcitic oysters (Liostrea) and ghost fossils of decalcified aragonitic bivalves. The stressors of PZE and decalcification parsimoniously explain the extinction event and inform possible combined causes of other biotic crises linked to emplacement of large igneous provinces, notably the end-Permian mass extinction, when PZE occurred on a broad and perhaps global scal

    The paleolimnologist's guide to compound-specific stable isotope analysis - An introduction to principles and applications of CSIA for quaternary lake sediments

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    The stable isotope composition of key chemical elements for life on Earth (e.g., carbon, hydrogen, nitrogen, oxygen, sulfur) tracks changes in fluxes and turnover of these elements in the biogeosphere. Over the past 15-20 years, the potential to measure these isotopic compositions for individual, source-specific organic molecules (biomarkers) and to link them to a range of environmental conditions and processes has been unlocked and amplified by increasingly sensitive, affordable and wide-spread analytical technology. Paleoenvironmental research has seen enormous step-changes in our understanding of past ecosystem dynamics. Vital to these paradigm shifts is the need for well-constrained modern and recent analogues. Through increased understanding of these environments and their biological pathways we can successfully unravel past climatic changes and associated ecosystem adaption. With this review, we aim to introduce scientists working in the field of Quaternary paleolimnology to the tools that compound-specific isotope analysis (CSIA) provides for the gain of information on biogeochemical conditions in ancient environments. We provide information on fundamental principles and applications of novel and established CSIA applications based on the carbon, hydrogen, nitrogen, oxygen and sulfur isotopic composition of biomarkers. While biosynthesis, sources and associated isotope fractionation patterns of compounds such as n-alkanes are relatively well-constrained, new applications emerge from the increasing use of functionalized alkyl lipids, steroids, hopanoids, isoprenoids, GDGTs, pigments or cellulose. Biosynthesis and fractionation are not always fully understood

    Global surveillance of cancer survival 1995-2009: analysis of individual data for 25,676,887 patients from 279 population-based registries in 67 countries (CONCORD-2)

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    BACKGROUND: Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. METHODS: Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15-99 years) and 75,000 children (age 0-14 years) diagnosed with cancer during 1995-2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. FINDINGS: 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005-09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15-19% in North America, and as low as 7-9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10-20% between 1995-99 and 2005-09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer, national estimates of 5-year survival range from less than 50% to more than 70%; regional variations are much wider, and improvements between 1995-99 and 2005-09 have generally been slight. For women diagnosed with ovarian cancer in 2005-09, 5-year survival was 40% or higher only in Ecuador, the USA, and 17 countries in Asia and Europe. 5-year survival for stomach cancer in 2005-09 was high (54-58%) in Japan and South Korea, compared with less than 40% in other countries. By contrast, 5-year survival from adult leukaemia in Japan and South Korea (18-23%) is lower than in most other countries. 5-year survival from childhood acute lymphoblastic leukaemia is less than 60% in several countries, but as high as 90% in Canada and four European countries, which suggests major deficiencies in the management of a largely curable disease. INTERPRETATION: International comparison of survival trends reveals very wide differences that are likely to be attributable to differences in access to early diagnosis and optimum treatment. Continuous worldwide surveillance of cancer survival should become an indispensable source of information for cancer patients and researchers and a stimulus for politicians to improve health policy and health-care systems

    Whole-genome sequencing reveals host factors underlying critical COVID-19

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    Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

    Medical symbiotics

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    Arboreal stromatolites: a 210-million year record

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    Design explained: The Goldilocks paradox

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