Multivariate analysis of regional-scale geochemical data for environmental monitoring

A compositional multivariate approach is used to analyse regional scale soil geochemical data obtained as part of the Tellus Project generated by the Geological Survey Northern Ireland (GSNI). The multi-element total concentration data presented comprise XRF analyses of 6862 rural soil samples collected at 20cm depths on a non-aligned grid at one site per 2 km2. Censored data were imputed using published detection limits. Using these imputed values for 46 elements (including LOI), each soil sample site was assigned to the regional geology map provided by GSNI initially using the dominant lithology for the map polygon. Northern Ireland includes a diversity of geology representing a stratigraphic record from the Mesoproterozoic, up to and including the Palaeogene. However, the advance of ice sheets and their meltwaters over the last 100,000 years has left at least 80% of the bedrock covered by superficial deposits, including glacial till and post-glacial alluvium and peat. The question is to what extent the soil geochemistry reflects the underlying geology or superficial deposits. To address this, the geochemical data were transformed using centered log ratios (clr) to observe the requirements of compositional data analysis and avoid closure issues. Following this, compositional multivariate techniques including compositional Principal Component Analysis (PCA) and minimum/maximum autocorrelation factor (MAF) analysis method were used to determine the influence of underlying geology on the soil geochemistry signature. PCA showed that 72% of the variation was determined by the first four principal components (PC’s) implying “significant” structure in the data. Analysis of variance showed that only 10 PC’s were necessary to classify the soil geochemical data. To consider an improvement over PCA that uses the spatial relationships of the data, a classification based on MAF analysis was undertaken using the first 6 dominant factors. Understanding the relationship between soil geochemistry and superficial deposits is important for environmental monitoring of fragile ecosystems such as peat. To explore whether peat cover could be predicted from the classification, the lithology designation was adapted to include the presence of peat, based on GSNI superficial deposit polygons and linear discriminant analysis (LDA) undertaken. Prediction accuracy for LDA classification improved from 60.98% based on PCA using 10 principal components to 64.73% using MAF based on the 6 most dominant factors. The misclassification of peat may reflect degradation of peat covered areas since the creation of superficial deposit classification. Further work will examine the influence of underlying lithologies on elemental concentrations in peat composition and the effect of this in classification analysis.

Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis

Background: Esophageal adenocarcinoma (EA) is one of the fastest rising cancers in western countries. Barrett’s Esophagus (BE) is the premalignant precursor of EA. However, only a subset of BE patients develop EA, which complicates the clinical management in the absence of valid predictors. Genetic risk factors for BE and EA are incompletely understood. This study aimed to identify novel genetic risk factors for BE and EA.Methods: Within an international consortium of groups involved in the genetics of BE/EA, we performed the first meta-analysis of all genome-wide association studies (GWAS) available, involving 6,167 BE patients, 4,112 EA patients, and 17,159 representative controls, all of European ancestry, genotyped on Illumina high-density SNP-arrays, collected from four separate studies within North America, Europe, and Australia. Meta-analysis was conducted using the fixed-effects inverse variance-weighting approach. We used the standard genome-wide significant threshold of 5×10-8 for this study. We also conducted an association analysis following reweighting of loci using an approach that investigates annotation enrichment among the genome-wide significant loci. The entire GWAS-data set was also analyzed using bioinformatics approaches including functional annotation databases as well as gene-based and pathway-based methods in order to identify pathophysiologically relevant cellular pathways.Findings: We identified eight new associated risk loci for BE and EA, within or near the CFTR (rs17451754, P=4·8×10-10), MSRA (rs17749155, P=5·2×10-10), BLK (rs10108511, P=2·1×10-9), KHDRBS2 (rs62423175, P=3·0×10-9), TPPP/CEP72 (rs9918259, P=3·2×10-9), TMOD1 (rs7852462, P=1·5×10-8), SATB2 (rs139606545, P=2·0×10-8), and HTR3C/ABCC5 genes (rs9823696, P=1·6×10-8). A further novel risk locus at LPA (rs12207195, posteriori probability=0·925) was identified after re-weighting using significantly enriched annotations. This study thereby doubled the number of known risk loci. The strongest disease pathways identified (P<10-6) belong to muscle cell differentiation and to mesenchyme development/differentiation, which fit with current pathophysiological BE/EA concepts. To our knowledge, this study identified for the first time an EA-specific association (rs9823696, P=1·6×10-8) near HTR3C/ABCC5 which is independent of BE development (P=0·45).Interpretation: The identified disease loci and pathways reveal new insights into the etiology of BE and EA. Furthermore, the EA-specific association at HTR3C/ABCC5 may constitute a novel genetic marker for the prediction of transition from BE to EA. Mutations in CFTR, one of the new risk loci identified in this study, cause cystic fibrosis (CF), the most common recessive disorder in Europeans. Gastroesophageal reflux (GER) belongs to the phenotypic CF-spectrum and represents the main risk factor for BE/EA. Thus, the CFTR locus may trigger a common GER-mediated pathophysiology.

The large- and small-scale Ca IIK structure of the Milky Way from observations of Galactic and Magellanic sightlines

Aims. The large and small-scale (pc) structure of the Galactic interstellar medium can be investigated by utilising spectra of early-type stellar probes of known distances in the same region of the sky. This paper determines the variation in line strength of Ca ii at 3933.661 Å as a function of probe separation for a large sample of stars, including a number of sightlines in the Magellanic Clouds. 

Methods. FLAMES-GIRAFFE data taken with the Very Large Telescope towards early-type stars in 3 Galactic and 4 Magellanic open clusters in Ca ii are used to obtain the velocity, equivalent width, column density, and line width of interstellar Galactic calcium for a total of 657 stars, of which 443 are Magellanic Cloud sightlines. In each cluster there are between 43 and 111 stars observed. Additionally, FEROS and UVES Ca ii K and Na i D spectra of 21 Galactic and 154 Magellanic early-type stars are presented and combined with data from the literature to study the calcium column density - parallax relationship. 

Results. For the four Magellanic clusters studied with FLAMES, the strength of the Galactic interstellar Ca ii K equivalent width on transverse scales from ∼0.05-9 pc is found to vary by factors of ∼1.8-3.0, corresponding to column density variations of ∼0.3-0.5 dex in the optically-thin approximation. Using FLAMES, FEROS, and UVES archive spectra, the minimum and maximum reduced equivalent widths for Milky Way gas are found to lie in the range ∼35-125 mÅ and ∼30-160 mÅ for Ca ii K and Na i D, respectively. The range is consistent with a previously published simple model of the interstellar medium consisting of spherical cloudlets of filling factor ∼0.3, although other geometries are not ruled out. Finally, the derived functional form for parallax (π) and Ca ii column density (N_CaII) is found to be π(mas) = 1 / (2.39 × 10^-13 × N_CaII (cm^-2) + 0.11). Our derived parallax is ∼25 per cent lower than predicted by Megier et al. (2009, A&A, 507, 833) at a distance of ∼100 pc and ∼15 percent lower at a distance of ∼200 pc, reflecting inhomogeneity in the Ca ii distribution in the different sightlines studied.