Palaeoproterozoic reworking of early Archaean lithospheric blocks: Rocks and zircon records from charnockitoids in Volgo-Uralia

The Volgo-Uralia segment, which constitutes one fourth of the East European Craton, is covered by sedimentary deposits. From geophysical studies and examination of thousands of drillcores, Volgo-Uralia has been recognised as a vast high-grade terrain with a complex crustal history extending from the Palaeoarchaean to the Palaeoproterozoic. Our recent studies are focused on the search for the oldest crust formation event by extracting whole rock Sm-Nd and zircon U-Th-Pb and Lu-Hf isotope information from samples recovered by drilling in southern Volgo-Uralia. Particular attention is devoted to the Kolyvan charnockitoid rock suite, which makes up several large areas of gneisses and granitoids of enderbite, charnockite and tonalite composition. The zircon from the granitoids show complex internal structures and consists of large magmatic cores with oscillatory zoning, surrounded by CL black-and-bright bands of metamorphic rims. The crystallisation age of the cores is defined as 3140 ± 7 Ma (SHRIMP) and 3127 ± 46 Ma (LA-ICPMS), while the CL-bright rims are dated at 1950 ± 25 Ma (LA-ICPMS). The ingressive recrystallisation of primary magmatic zircon correlates with depletion in REE, which is observed in each studied core-rim pair. No differences in O-isotopic compositions have been detected between the cores and the rims. δO18 values with an average of 5.8 ± 0.3‰ (1SD) implying that no supracrustal rocks were involved in the source of the Kolyvan melts. The Hf-isotope compositions of magmatic cores (−3 to −9 εHfT) and metamorphic rims (−14 to −28 εHfT), and their similar crustal model ages from 3.42 to 3.86 Ga indicate Eo- to Palaeoarchaean crustal sources for the charnockitic magmas. Sm-Nd model ages of ca 3.46 Ga for the Kolyvan rocks are consistent with the zircon Hf-isotope data and indicate a long crustal prehistory of a source of the Mesoarchaean magmas. We conclude that the Mesoarchaean Kolyvan suite rocks was formed by reworking of Eo- to Palaeoarchaean lithosphere, which probably had been widespread throughout Volgo-Uralia. The obtained geochemical and isotope data can be reconciled in a model of deep mantle-plume activity at 3.1 Ga causing mantle underplating, extension of the Palaeoarchaean crust and high-T magmatism

Impact of uncertainties in exposure assessment on estimates of thyroid cancer risk among Ukrainian children and adolescents exposed from the chernobyl accident

The 1986 accident at the Chernobyl nuclear power plant remains the most serious nuclear accident in history, and excess thyroid cancers, particularly among those exposed to releases of iodine-131 remain the best-documented sequelae. Failure to take dose-measurement error into account can lead to bias in assessments of dose-response slope. Although risks in the Ukrainian-US thyroid screening study have been previously evaluated, errors in dose assessments have not been addressed hitherto. Dose-response patterns were examined in a thyroid screening prevalence cohort of 13,127 persons aged <18 at the time of the accident who were resident in the most radioactively contaminated regions of Ukraine. We extended earlier analyses in this cohort by adjusting for dose error in the recently developed TD-10 dosimetry. Three methods of statistical correction, via two types of regression calibration, and Monte Carlo maximum-likelihood, were applied to the doses that can be derived from the ratio of thyroid activity to thyroid mass. The two components that make up this ratio have different types of error, Berkson error for thyroid mass and classical error for thyroid activity. The first regression-calibration method yielded estimates of excess odds ratio of 5.78 Gy-1 (95% CI 1.92, 27.04), about 7% higher than estimates unadjusted for dose error. The second regression-calibration method gave an excess odds ratio of 4.78 Gy-1 (95% CI 1.64, 19.69), about 11% lower than unadjusted analysis. The Monte Carlo maximum-likelihood method produced an excess odds ratio of 4.93 Gy-1 (95% CI 1.67, 19.90), about 8% lower than unadjusted analysis. There are borderline-significant (p= 0.101-0.112) indications of downward curvature in the dose response, allowing for which nearly doubled the low-dose linear coefficient. In conclusion, dose-error adjustment has comparatively modest effects on regression parameters, a consequence of the relatively small errors, of a mixture of Berkson and classical form, associated with thyroid dose assessment

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry.

BACKGROUND: Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. METHODS: We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes' coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. RESULTS: In European ancestry samples, 14 genes were significantly associated (q < 0.05) with BC. Of those, two genes, FMNL3 (P = 6.11 × 10-6) and AC058822.1 (P = 1.47 × 10-4), represent new associations. High FMNL3 expression has previously been linked to poor prognosis in several other cancers. Meta-analysis of samples with diverse ancestry discovered further associations including established candidate genes ESR1 and CBLB. Furthermore, literature review and database query found further support for a biologically plausible link with cancer for genes CBLB, FMNL3, FGFR2, LSP1, MAP3K1, and SRGAP2C. CONCLUSIONS: Using extended gene-based aggregation tests including coding and regulatory variation, we report identification of plausible target genes for previously identified single-marker associations with BC as well as the discovery of novel genes implicated in BC development. Including multi ancestral cohorts in this study enabled the identification of otherwise missed disease associations as ESR1 (P = 1.31 × 10-5), demonstrating the importance of diversifying study cohorts

Measurement of inclusive very forward jet cross sections in proton-lead collisions at \sqrt{sNN} = 5:02 TeV

Measurements of differential cross sections for inclusive very forward jet production in proton-lead collisions as a function of jet energy are presented. The data were collected with the CMS experiment at the LHC in the laboratory pseudorapidity range −6.6 < η < −5.2. Asymmetric beam energies of 4 TeV for protons and 1.58 TeV per nucleon for Pb nuclei were used, corresponding to a center-of-mass energy per nucleon pair of \sqrt{sNN} = 5:02 TeV. Collisions with either the proton (p+Pb) or the ion (Pb+p) traveling towards the negative η hemisphere are studied. The jet cross sections are unfolded to stable-particle level cross sections with p_{T} ≳ 3 GeV, and compared to predictions from various Monte Carlo event generators. In addition, the cross section ratio of p+Pb and Pb+p data is presented. The results are discussed in terms of the saturation of gluon densities at low fractional parton momenta. None of the models under consideration describes all the data over the full jet-energy range and for all beam configurations. Discrepancies between the differential cross sections in data and model predictions of more than two orders of magnitude are observed