An absolute reference frame for clumped isotope thermometry

Analysis of multiply substituted isotopologues of molecules (‘clumped isotope geochemistry’) presents special challenges to both precision and accuracy. Previous discussions have focused on mass spectrometric precision for these rare species and intralaboratory reference frames. This discipline has spread, demanding interlaboratory standardization. We present a four-laboratory study of the calibration of mass-47 anomalies (Δ_(47) values) in CO_2 (especially extracted from carbonate). We consider: instrument linearity, source fragmentation/recombination reactions (which vary between mass spectrometers and with time and instrument settings), and differences in methods, materials and conditions for sample preparation. We address these problems by developing a method for standardizing Δ_(47) measurements to an absolute reference frame based on theoretical predictions of the abundances of multiply-substituted isotopologues of gaseous CO_2 that has reached a thermodynamic equilibrium at a known temperature. By analyzing CO_2 gases that have been subjected to established laboratory procedures known to promote isotopic equilibration (i.e., heated gases and water-equilibrated CO_2), and by reference to the statistical thermodynamic predictions of equilibrium isotopic distributions, it is possible to construct an empirical transfer function that can then be applied to CO_2 samples with unknown Δ_(47) values. This reference frame may be unique in that it is based on thermodynamic equilibrium, rather than the isotopic composition of an arbitrary reference material. We describe the protocol necessary to construct such a reference frame, the method for converting gases with unknown clumped isotope compositions to this frame, and suggest a protocol for ensuring that reported Δ_(47) values can be compared among different laboratories, independent of laboratory-specific analytical or methodological artefacts. Application of this approach to measurements of CO_2 extracted from several carbonate reference materials results in interlaboratory agreement on their Δ_(47) values to within est. ±0.01 ‰, 1σ. Finally, we present a revised paleotemperature scale that applies when using the absolute reference frame described here, as opposed to the previous paleotemperature equation based on data from a single laboratory. More generally, this study presents a model for how interlaboratory standardization might be approached for other ‘clumped isotope’ measurements

Hats off to you, Jim!

Jim’s intellectual curiosity was an inspiration. In addition to those whose comments follow, he clearly touched the careers and lives of many others

Persistence of Resistant Staphylococcus epidermidis after Single Course of Clarithromycin

Short course of antimicrobial therapy can select resistant bacteria that persist for 4 years or longer

Interlaboratory study for coral Sr/Ca and other element/Ca ratio measurements

The Sr/Ca ratio of coral aragonite is used to reconstruct past sea surface temperature (SST). Twentyone laboratories took part in an interlaboratory study of coral Sr/Ca measurements. Results show interlaboratory bias can be significant, and in the extreme case could result in a range in SST estimates of 7°C. However, most of the data fall within a narrower range and the Porites coral reference material JCp- 1 is now characterized well enough to have a certified Sr/Ca value of 8.838 mmol/mol with an expanded uncertainty of 0.089 mmol/mol following International Association of Geoanalysts (IAG) guidelines. This uncertainty, at the 95% confidence level, equates to 1.5°C for SST estimates using Porites, so is approaching fitness for purpose. The comparable median within laboratory error is <0.5°C. This difference in uncertainties illustrates the interlaboratory bias component that should be reduced through the use of reference materials like the JCp-1. There are many potential sources contributing to biases in comparative methods but traces of Sr in Ca standards and uncertainties in reference solution composition can account for half of the combined uncertainty. Consensus values that fulfil the requirements to be certified values were also obtained for Mg/Ca in JCp-1 and for Sr/Ca and Mg/Ca ratios in the JCt-1 giant clam reference material. Reference values with variable fitness for purpose have also been obtained for Li/Ca, B/Ca, Ba/Ca, and U/Ca in both reference materials. In future, studies reporting coral element/Ca data should also report the average value obtained for a reference material such as the JCp-1

Defining the causes of sporadic Parkinson's disease in the global Parkinson's genetics program (GP2)

The Global Parkinson’s Genetics Program (GP2) will genotype over 150,000 participants from around the world, and integrate genetic and clinical data for use in large-scale analyses to dramatically expand our understanding of the genetic architecture of PD. This report details the workflow for cohort integration into the complex arm of GP2, and together with our outline of the monogenic hub in a companion paper, provides a generalizable blueprint for establishing large scale collaborative research consortia

Multi-ancestry genome-wide association meta-analysis of Parkinson?s disease

Although over 90 independent risk variants have been identified for Parkinson’s disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson’s disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations

^(13)C–^(18)O bonds in carbonate minerals: A new kind of paleothermometer

The abundance of the doubly substituted CO_2 isotopologue, ^(13)C^(18)O^(16)O, in CO_2 produced by phosphoric acid digestion of synthetic, inorganic calcite and natural, biogenic aragonite is proportional to the concentration of ^(13)C–^(18)O bonds in reactant carbonate, and the concentration of these bonds is a function of the temperature of carbonate growth. This proportionality can be described between 1 and 50 °C by the function: Δ_(47) = 0.0592 • 10^6 • T^(−2) − 0.02, where Δ_(47) is the enrichment, in per mil, of ^(13)C^(18)O^(16)O in CO_2 relative to the amount expected for a stochastic (random) distribution of isotopes among all CO_2 isotopologues, and T is the temperature in Kelvin. This relationship can be used for a new kind of carbonate paleothermometry, where the temperature-dependent property of interest is the state of ordering of ^(13)C and ^(18)O in the carbonate lattice (i.e., bound together vs. separated into different CO_3^(2−) units), and not the bulk δ^(18)O or δ^(13)C values. Current analytical methods limit precision of this thermometer to ca. ± 2 °C, 1σ. A key feature of this thermometer is that it is thermodynamically based, like the traditional carbonate–water paleothermometer, and so is suitable for interpolation and even modest extrapolation, yet is rigorously independent of the δ^(18)O of water and δ^(13)C of DIC from which carbonate grew. Thus, this technique can be applied to parts of the geological record where the stable isotope compositions of waters are unknown. Moreover, simultaneous determinations of Δ_(47) and δ^(18)O for carbonates will constrain the δ^(18)O of water from which they grew