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40Ar/39Ar in situ UV laser ablation of white mica, Rb–Sr mineral isochrons and zircon fission track dating were applied to determine ages of very low- to low-grade metamorphic processes at 3.5±0.4 kbar, 280±30°C in the Avalonian Mira terrane of SE Cape Breton Island (Nova Scotia). The Mira terrane comprises Neoproterozoic volcanic-arc rocks overlain by Cambrian sedimentary rocks. Crystallization of metamorphic white mica was dated in six metavolcanic samples by 40Ar/39Ar spot age peaks between 396±3 and 363±14 Ma. Rb–Sr systematics of minerals and mineral aggregates yielded two isochrons at 389±7 Ma and 365±8 Ma, corroborating equilibrium conditions during very low- to low-grade metamorphism. The dated white mica is oriented parallel to foliations produced by sinistral strike-slip faulting and/or folding related to the Middle–Late Devonian transpressive assembly of Avalonian terranes during convergence and emplacement of the neighbouring Meguma terrane. Exhumation occurred earlier in the NW Mira terrane than in the SE. Transpression was related to the closure of the Rheic Ocean between Gondwana and Laurussia by NW-directed convergence. The 40Ar/39Ar spot age spectra also display relict age peaks at 477–465 Ma, 439 Ma and 420–428 Ma attributed to deformation and fluid access, possibly related to the collision of Avalonia with composite Laurentia or to earlier Ordovician–Silurian rifting. Fission track ages of zircon from Mira terrane samples range between 242±18 and 225±21 Ma and reflect late Palaeozoic reburial and reheating close to previous peak metamorphic temperatures under fluid-absent conditions during rifting prior to opening of the Central Atlantic Ocean.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
This study pushes our understanding of research reliability by reproducing and replicating claims from 110 papers in leading economic and political science journals. The analysis involves computational reproducibility checks and robustness assessments. It reveals several patterns. First, we uncover a high rate of fully computationally reproducible results (over 85%). Second, excluding minor issues like missing packages or broken pathways, we uncover coding errors for about 25% of studies, with some studies containing multiple errors. Third, we test the robustness of the results to 5,511 re-analyses. We find a robustness reproducibility of about 70%. Robustness reproducibility rates are relatively higher for re-analyses that introduce new data and lower for re-analyses that change the sample or the definition of the dependent variable. Fourth, 52% of re-analysis effect size estimates are smaller than the original published estimates and the average statistical significance of a re-analysis is 77% of the original. Lastly, we rely on six teams of researchers working independently to answer eight additional research questions on the determinants of robustness reproducibility. Most teams find a negative relationship between replicators' experience and reproducibility, while finding no relationship between reproducibility and the provision of intermediate or even raw data combined with the necessary cleaning codes.