Is comparability of C-14 dates an issue?: A status report on the fourth international radiocarbon intercomparison

For more than 15 years, the radiocarbon community has participated in a series of laboratory intercomparisons in response to the issue of comparability of measurements as perceived within the wider user communities (Scott et al. 1990; Rozanski et al. 1992; Guiliksen and Scott 1995; Scott et al. 1997).<br/> In this report, we provide an update on the current C-14 laboratory intercomparison and reflect on future issues linked to the laboratory intercomparison program, not least those resulting from a significant growth in the number of accelerator mass spectrometry (AMS) facilities providing routine dating of small samples (milligram size)

Classification of Supernovae

The current classification scheme for supernovae is presented. The main observational features of the supernova types are described and the physical implications briefly addressed. Differences between the homogeneous thermonuclear type Ia and similarities among the heterogeneous core collapse type Ib, Ic and II are highlighted. Transforming type IIb, narrow line type IIn, supernovae associated with GRBs and few peculiar objects are also discussed.Comment: 16 Pages, 4 figures, to be published in "Supernovae and Gamma-Ray Bursters," ed. Kurt W. Weile

Best practice methodology for 14C calibration of marine and mixed terrestrial/marine samples

There is a lack of detailed guidance in the published literature on how to calibrate 14C measurements made on marine or mixed marine/terrestrial (primarily human remains) samples. We describe what we consider to be the best approach towards achieving the most accurate calibrated age ranges, using the most appropriate ΔR and percentage marine diet estimates, and associated, realistic error terms on these values. However, this approach will increase the calibrated age range(s) by fully accounting for the variability in both the model and the material. While the discussion is based on examples from the UK and Iceland, the same fundamental arguments can be applied in any geographic location largely devoid of C4 plants as the high δ13C values from such plants can make identification of marine intake difficult to determine

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92–0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88–0.94). Conclusions Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer

Prognostic indicators and outcomes of hospitalised COVID-19 patients with neurological disease: An individual patient data meta-analysis

Background Neurological COVID-19 disease has been reported widely, but published studies often lack information on neurological outcomes and prognostic risk factors. We aimed to describe the spectrum of neurological disease in hospitalised COVID-19 patients; characterise clinical outcomes; and investigate factors associated with a poor outcome. Methods We conducted an individual patient data (IPD) meta-analysis of hospitalised patients with neurological COVID-19 disease, using standard case definitions. We invited authors of studies from the first pandemic wave, plus clinicians in the Global COVID-Neuro Network with unpublished data, to contribute. We analysed features associated with poor outcome (moderate to severe disability or death, 3 to 6 on the modified Rankin Scale) using multivariable models. Results We included 83 studies (31 unpublished) providing IPD for 1979 patients with COVID-19 and acute new-onset neurological disease. Encephalopathy (978 [49%] patients) and cerebrovascular events (506 [26%]) were the most common diagnoses. Respiratory and systemic symptoms preceded neurological features in 93% of patients; one third developed neurological disease after hospital admission. A poor outcome was more common in patients with cerebrovascular events (76% [95% CI 67–82]), than encephalopathy (54% [42–65]). Intensive care use was high (38% [35–41]) overall, and also greater in the cerebrovascular patients. In the cerebrovascular, but not encephalopathic patients, risk factors for poor outcome included breathlessness on admission and elevated D-dimer. Overall, 30-day mortality was 30% [27–32]. The hazard of death was comparatively lower for patients in the WHO European region. Interpretation Neurological COVID-19 disease poses a considerable burden in terms of disease outcomes and use of hospital resources from prolonged intensive care and inpatient admission; preliminary data suggest these may differ according to WHO regions and country income levels. The different risk factors for encephalopathy and stroke suggest different disease mechanisms which may be amenable to intervention, especially in those who develop neurological symptoms after hospital admission

Breast cancer risk genes: association analysis in more than 113,000 women

BACKGROUNDGenetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.METHODSWe used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.RESULTSProtein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.CONCLUSIONSThe results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.)Molecular tumour pathology - and tumour geneticsMTG1 - Moleculaire genetica en pathologie van borstkanke

A coherent high-precision radiocarbon chronology for the Late- glacial sequence at Sluggan Bog, Co. Antrim, Northern Ireland

Seventy-five radiocarbon dates are presented from Sluggan Bog in Co. Antrim, Northern Ireland. The Holocene peats are underlain by Late-glacial sediments, which also appear to have accumulated largely in a mire environment. The radiocarbon dates, from the Late-glacial and early Holocene part of the profile, were obtained from the humic and humin fractions of the sedimentary matrix, and from plant macrofossils. The last- named were dated by AMS and the sediment samples by radiometric (beta counting) methods. Age-depth models for the three dating series show a very high level of agreement between the two fractions and the macrofossils. No statistically significant difference is found between the beta counting and AMS results. Three tephras were located in the profile, the uppermost of which is in a stratigraphical position Suggestive of the Vedde Ash, but the geochemical and radiocarbon evidence do not support this interpretation. The lower ashes are in the correct stratigraphical position for the Laacher See and Borrobol tephras, attributions substantiated by the radiocarbon evidence, but not by the geochemical data. The Sluggan sequence has generated one of the most internally consistent radiocarbon chronologies for any Late-glacial site in the British Isles, and it is suggested that in future more effort should be devoted to the search for, and analysis of, Late-glacial mire sequences, rather than the limnic records that have formed the principal focus of Late-glacial investigations hitherto

Stable isotopes, radiocarbon and the Mesolithic-Neolithic transition in the Iron Gates

The results of stable carbon and nitrogen-isotope analyses of human bone collagen from the Iron Gates sites of Lepenski Vir, Vlasac and Schela Cladovei are reconsidered in the light of recent developments in stable isotope palaeodietary research and new information on chronology. The revised data have implications for the interpretation of Lepenski Vir and Vlasac, and the timing of the Mesolithic-Neolithic transition in the Iron Gates

Consensus dating of mammoth remains from Wrangel Island

Previous results from remains of tusks, teeth and bones collected from Wrangel Island (Vartanyan et al. 1995) had given results in the range 3730 BP to 20,000 BP and the authors had concluded that mammoths inhabited Wrangel Island for as long as 6000 yr after the estimated extinction on the Siberian continent. There still remained the question of the earliest date for such remains. Further, the authors had noted such samples may present some difficulty in dating and therefore duplicate samples had been measured in a second laboratory with satisfactory results. The replicate dating of important or controversial samples in more than one laboratory is well-established (e.g., Turin Shroud) and in this paper, we present results for 5 mammoth samples dated by 6 laboratories. Such interlaboratory comparisons provide an independent means of verification of laboratory comparability, and give added confidence in the results, particularly when applied to more controversial samples. A further objective of the work has been to evaluate the material for inclusion in any large-scale interlaboratory comparison, such comparisons having in the past formed part of laboratory quality assurance protocols. The design and organization of a laboratory intercomparison requires homogeneous samples in sufficient quantity to satisfy participants, and so in principle, a single mammoth tusk would meet these criteria. Samples such as the mammoth tusk have been used in previous intercomparisons: e.g., in the last large-scale international intercomparison (Gulliksen and Scott 1995), whalebone was one of the materials distributed. One of the key advantages of such material is that a single sample (a mammoth tusk) can be resampled for analysis by multiple labs and thus does not require bulk homogenization. Therefore, as part of a preselection process for a future intercomparison, five samples from separate mammoth tusks were collected from Wrangel Island in 1995 in sufficient quantity to allow multiple dating. The aim was to identify five separate samples of young age, sample up to 1 kg from each tusk and mark the location so that after preliminary dating, samples could be retrieved as required in the future. Six laboratories received samples for dating. The paper will discuss the results from the laboratories, present consensus values, and make recommendations concerning use of these samples in a future laboratory intercomparison