An updated radiocarbon-based ice margin chronology for the last deglaciation of the North American Ice Sheet Complex

The North American Ice Sheet Complex (NAISC; consisting of the Laurentide, Cordilleran and Innuitian ice sheets) was the largest ice mass to repeatedly grow and decay in the Northern Hemisphere during the Quaternary. Understanding its pattern of retreat following the Last Glacial Maximum is critical for studying many facets of the Late Quaternary, including ice sheet behaviour, the evolution of Holocene landscapes, sea level, atmospheric circulation, and the peopling of the Americas. Currently, the most up-to-date and authoritative margin chronology for the entire ice sheet complex is featured in two publications (Geological Survey of Canada Open File 1574 [Dyke et al., 2003]; ‘Quaternary Glaciations – Extent and Chronology, Part II’ [Dyke, 2004]). These often-cited datasets track ice margin recession in 36 time slices spanning 18 ka to 1 ka (all ages in uncalibrated radiocarbon years) using a combination of geomorphology, stratigraphy and radiocarbon dating. However, by virtue of being over 15 years old, the ice margin chronology requires updating to reflect new work and important revisions. This paper updates the aforementioned 36 ice margin maps to reflect new data from regional studies. We also update the original radiocarbon dataset from the 2003/2004 papers with 1541 new ages to reflect work up to and including 2018. A major revision is made to the 18 ka ice margin, where Banks and Eglinton islands (once considered to be glacial refugia) are now shown to be fully glaciated. Our updated 18 ka ice sheet increased in areal extent from 17.81 to 18.37 million km2, which is an increase of 3.1% in spatial coverage of the NAISC at that time. Elsewhere, we also summarize, region-by-region, significant changes to the deglaciation sequence. This paper integrates new information provided by regional experts and radiocarbon data into the deglaciation sequence while maintaining consistency with the original ice margin positions of Dyke et al. (2003) and Dyke (2004) where new information is lacking; this is a pragmatic solution to satisfy the needs of a Quaternary research community that requires up-to-date knowledge of the pattern of ice margin recession of what was once the world’s largest ice mass. The 36 updated isochrones are available in PDF and shapefile format, together with a spreadsheet of the expanded radiocarbon dataset (n = 5195 ages) and estimates of uncertainty for each interval

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Elevated lactate dehydrogenase isoenzyme 1 as a tumour marker in patients with germ cell testicular tumours

In a series of 50 patients with testicular tumours evaluated prior to orchidectomy, 12 out of 19 with pure seminoma and seven out of 31 with non-seminomatous or mixed seminomatous and non-seminomatous germ cell tumours had elevated plasma lactate dehydrogenase isoenzyme 1 concentrations. In contrast, seven of the 19 seminoma patients had elevated serum human chorionic gonadotrophin (hCG) concentrations and 25 of the 31 non-seminomatous and mixed seminomatous and non-seminomatous germ cell tumour patients had elevations of hCG and/or alpha-fetoprotein. Using these three markers, 12 out of 19 seminoma patients and 27 out of 31 non-seminomatous or mixed seminomatous and non-seminomatous tumour patients were positive for one or more of these tumour markers

Neonatal screening and an intensive management programme for galactosaemia: Early evidence of benefits

A prospective study of children with galactosaemia is being undertaken at the Metabolic Clinic, Royal Children's Hospital, Brisbane. The purpose of the study is to collect biochemical, clinical, dietary, developmental and speech and language data. This paper describes the operation of the multiprofessional management programme and reports results for two groups of children: those who were diagnosed before the introduction of neonatal screening in 1982 (the prescreening group) and those who were identified by screening. The eight children in the prescreening group have shown intellectual development in the low-average to moderately-handicapped range. Most of them have speech and language difficulties. The screening group, all of whom are still in infancy or early childhood, appears to be developing normally, with the exception of one child who is showing problems with speech and language. The early results provide a basis for cautious optimism that neonatal screening and careful management will result in improved outcomes for children with galactosaemia