Chemical tagging can work: Identification of stellar phase-space structures purely by chemical-abundance similarity

Chemical tagging promises to use detailed abundance measurements to identify spatially separated stars that were in fact born together (in the same molecular cloud), long ago. This idea has not yielded much practical success, presumably because of the noise and incompleteness in chemical-abundance measurements. We have succeeded in substantially improving spectroscopic measurements with The Cannon, which has now delivered 15 individual abundances for ~100,000 stars observed as part of the APOGEE spectroscopic survey, with precisions around 0.04 dex. We test the chemical-tagging hypothesis by looking at clusters in abundance space and confirming that they are clustered in phase space. We identify (by the k-means algorithm) overdensities of stars in the 15-dimensional chemical-abundance space delivered by The Cannon, and plot the associated stars in phase space. We use only abundance-space information (no positional information) to identify stellar groups. We find that clusters in abundance space are indeed clusters in phase space. We recover some known phase-space clusters and find other interesting structures. This is the first-ever project to identify phase-space structures at survey-scale by blind search purely in abundance space; it verifies the precision of the abundance measurements delivered by The Cannon; the prospects for future data sets appear very good.Comment: accepted for publication in the Ap

An update on oral cavity cancer:epidemiological trends, prevention strategies and novel approaches in diagnosis and prognosis

In the UK, the incidence of oral cavity cancer continues to rise, with an increase of around 60% over the past 10 years. Many patients still present with advanced disease, often resulting in locoregional recurrence and poor outcomes, which has not changed significantly for over four decades. Changes in aetiology may also be emerging, given the decline of smoking in developed countries. Therefore, new methods to better target prevention, improve screening and detect recurrence are needed. High-throughput ‘omics’ technologies appear promising for future individual-level diagnosis and prognosis. However, given this is a relatively rare cancer with significant intra-tumour heterogeneity and variation in patient response, reliable biomarkers have been difficult to elucidate. From a public health perspective, implementing these novel technologies into current services would require substantial practical, financial and ethical considerations. This may be difficult to justify and implement at present, therefore focus remains on early detection using new patient-led follow-up strategies. This paper reviews the latest evidence on epidemiological trends in oral cavity cancer to help identify at risk groups, population-based approaches for prevention, in addition to potential cutting-edge approaches in the diagnosis and prognosis of this disease. Keywords: Epidemiology, Oral Cancer, Survival, Risk Factors, Squamous Cell Carcinoma, Mouth Neoplasm

Association between general and central adiposity in childhood, and change in these, with cardiovascular risk factors in adolescence: prospective cohort study

Objectives To examine the prospective associations between body mass index (BMI), waist circumference, and fat mass in childhood and cardiovascular risk factors at age 15-16

Dietary Energy Density Affects Fat Mass in Early Adolescence and Is Not Modified by FTO Variants

BACKGROUND: Dietary energy density (DED) does not have a simple linear relationship to fat mass in children, which suggests that some children are more susceptible than others to the effects of DED. Children with the FTO (rs9939609) variant that increases the risk of obesity may have a higher susceptibility to the effects of DED because their internal appetite control system is compromised. We tested the relationship between DED and fat mass in early adolescence and its interaction with FTO variants. METHODS AND FINDINGS: We carried out a prospective analysis on 2,275 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC). Diet was assessed at age 10 y using 3-day diet diaries. DED (kJ/g) was calculated excluding drinks. Children were genotyped for the FTO (rs9939609) variant. Fat mass was estimated at age 13 y using the Lunar Prodigy Dual-energy X-ray Absorptiometry scanner. There was no evidence of interaction between DED at age 10 y and the high risk A allele of the FTO gene in relation to fat mass at age 13 y (beta = 0.005, p = 0.51), suggesting that the FTO gene has no effect on the relation between DED at 10 y and fat mass at 13 y. When DED at 10 y and the A allele of FTO were in the same model they were independently related to fat mass at 13 y. Each A allele of FTO was associated with 0.35+/-0.13 kg more fat mass at 13 y and each 1 kJ/g DED at 10 y was associated with 0.16+/-0.06 kg more fat mass at age 13 y, after controlling for misreporting of energy intake, gender, puberty, overweight status at 10 y, maternal education, TV watching, and physical activity. CONCLUSIONS: This study reveals the multi-factorial origin of obesity and indicates that although FTO may put some children at greater risk of obesity, encouraging a low dietary energy density may be an effective strategy to help all children avoid excessive fat gain

On the discovery of K-enhanced and possibly Mg-depleted stars throughout the Milky Way

Stars with unusual elemental abundances offer clues about rare astrophysical events or nucleosynthetic pathways. Stars with significantly depleted magnesium and enhanced potassium ([Mg/Fe] 1) have to date only been found in the massive globular cluster NGC 2419 and, to a lesser extent, NGC 2808. The origin of this abundance signature remains unknown, as does the reason for its apparent exclusivity to these two globular clusters. Here we present 112 field stars, identified from 454 180 LAMOST giants, that show significantly enhanced [K/Fe] and possibly depleted [Mg/Fe] abundance ratios. Our sample spans a wide range of metallicities (−1.5 < [Fe/H] < 0.3), yet none show abundance ratios of [K/Fe] or [Mg/Fe] that are as extreme as those observed in NGC 2419. If confirmed, the identified sample of stars represents evidence that the nucleosynthetic process producing the anomalous abundances ratios of [K/Fe] and [Mg/Fe] probably occurs at a wide range of metallicities. This would suggest that pollution scenarios that are limited to early epochs (such as Population III supernovae) are an unlikely explanation, although they cannot be ruled out entirely. This sample is expected to help guide modelling attempts to explain the origin of the Mg–K abundance signature

Genetic Markers of Obesity Risk: Stronger Associations with Body Composition in Overweight Compared to Normal-Weight Children

Genetic factors are important determinants of overweight. We examined whether there are differential effect sizes depending on children's body composition. We analysed data of n = 4,837 children recorded in the Avon Longitudinal Study of Parents and Children (ALSPAC), applying quantile regression with sex- and age-specific standard deviation scores (SDS) of body mass index (BMI) or with body fat mass index and fat-free mass index at 9 years as outcome variables and an "obesity-risk-allele score" based on eight genetic variants known to be associated with childhood BMI as the explanatory variable. The quantile regression coefficients increased with increasing child's BMI-SDS and fat mass index percentiles, indicating larger effects of the genetic factors at higher percentiles. While the associations with BMI-SDS were of similar size in medium and high BMI quantiles (40th percentile and above), effect sizes with fat mass index increased over the whole fat mass index distribution. For example, the fat mass index of a normal-weight (50th percentile) child was increased by 0.13 kg/m(2) (95% confidence interval (CI): 0.09, 0.16) per additional allele, compared to 0.24 kg/m(2) per allele (95% CI: 0.15, 0.32) in children at the 90th percentile. The genetic associations with fat-free mass index were weaker and the quantile regression effects less pronounced than those on fat mass index. Genetic risk factors for childhood overweight appear to have greater effects on fatter children. Interaction of known genetic factors with environmental or unknown genetic factors might provide a potential explanation of these findings

Epigenetic biomarkers of ageing are predictive of mortality risk in a longitudinal clinical cohort of individuals diagnosed with oropharyngeal cancer

Background: Epigenetic clocks are biomarkers of ageing derived from DNA methylation levels at a subset of CpG sites. The difference between age predicted by these clocks and chronological age, termed “epigenetic age acceleration”, has been shown to predict age-related disease and mortality. We aimed to assess the prognostic value of epigenetic age acceleration and a DNA methylation-based mortality risk score with all-cause mortality in a prospective clinical cohort of individuals with head and neck cancer: Head and Neck 5000. We investigated two markers of intrinsic epigenetic age acceleration (IEAAHorvath and IEAAHannum), one marker of extrinsic epigenetic age acceleration (EEAA), one optimised to predict physiological dysregulation (AgeAccelPheno), one optimised to predict lifespan (AgeAccelGrim) and a DNA methylation-based predictor of mortality (ZhangScore). Cox regression models were first used to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for associations of epigenetic age acceleration with all-cause mortality in people with oropharyngeal cancer (n = 408; 105 deaths). The added prognostic value of epigenetic markers compared to a clinical model including age, sex, TNM stage and HPV status was then evaluated. Results: IEAAHannum and AgeAccelGrim were associated with mortality risk after adjustment for clinical and lifestyle factors (HRs per standard deviation [SD] increase in age acceleration = 1.30 [95% CI 1.07, 1.57; p = 0.007] and 1.40 [95% CI 1.06, 1.83; p = 0.016], respectively). There was weak evidence that the addition of AgeAccelGrim to the clinical model improved 3-year mortality prediction (area under the receiver operating characteristic curve: 0.80 vs. 0.77; p value for difference = 0.069). Conclusion: In the setting of a large, clinical cohort of individuals with head and neck cancer, our study demonstrates the potential of epigenetic markers of ageing to enhance survival prediction in people with oropharyngeal cancer, beyond established prognostic factors. Our findings have potential uses in both clinical and non-clinical contexts: to aid treatment planning and improve patient stratification