Genetic analyses reveal a role for vitamin D insufficiency in HCV-associated hepatocellular carcinoma development

BACKGROUND: Vitamin D insufficiency has been associated with the occurrence of various types of cancer, but causal relationships remain elusive. We therefore aimed to determine the relationship between genetic determinants of vitamin D serum levels and the risk of developing hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). METHODOLOGY/PRINCIPAL FINDINGS: Associations between CYP2R1, GC, and DHCR7 genotypes that are determinants of reduced 25-hydroxyvitamin D (25[OH]D3) serum levels and the risk of HCV-related HCC development were investigated for 1279 chronic hepatitis C patients with HCC and 4325 without HCC, respectively. The well-known associations between CYP2R1 (rs1993116, rs10741657), GC (rs2282679), and DHCR7 (rs7944926, rs12785878) genotypes and 25(OH)D3 serum levels were also apparent in patients with chronic hepatitis C. The same genotypes of these single nucleotide polymorphisms (SNPs) that are associated with reduced 25(OH)D3 serum levels were found to be associated with HCV-related HCC (P = 0.07 [OR = 1.13, 95% CI = 0.99-1.28] for CYP2R1, P = 0.007 [OR = 1.56, 95% CI = 1.12-2.15] for GC, P = 0.003 [OR = 1.42, 95% CI = 1.13-1.78] for DHCR7; ORs for risk genotypes). In contrast, no association between these genetic variations and liver fibrosis progression rate (P>0.2 for each SNP) or outcome of standard therapy with pegylated interferon-α and ribavirin (P>0.2 for each SNP) was observed, suggesting a specific influence of the genetic determinants of 25(OH)D3 serum levels on hepatocarcinogenesis. CONCLUSIONS/SIGNIFICANCE: Our data suggest a relatively weak but functionally relevant role for vitamin D in the prevention of HCV-related hepatocarcinogenesis.

Variability of apparently homogeneous soilscapes in São Paulo state, Brazil: I. spatial analysis

The spatial variability of strongly weathered soils under sugarcane and soybean/wheat rotation was quantitatively assessed on 33 fields in two regions in São Paulo State, Brazil: Araras (15 fields with sugarcane) and Assis (11 fields with sugarcane and seven fields with soybean/wheat rotation). Statistical methods used were: nested analysis of variance (for 11 fields), semivariance analysis and analysis of variance within and between fields. Spatial levels from 50 m to several km were analyzed. Results are discussed with reference to a previously published study carried out in the surroundings of Passo Fundo (RS). Similar variability patterns were found for clay content, organic C content and cation exchange capacity. The fields studied are quite homogeneous with respect to these relatively stable soil characteristics. Spatial variability of other characteristics (resin extractable P, pH, base- and Al-saturation and also soil colour), varies with region and, or land use management. Soil management for sugarcane seems to have induced modifications to greater depths than for soybean/wheat rotation. Surface layers of soils under soybean/wheat present relatively little variation, apparently as a result of very intensive soil management. The major part of within-field variation occurs at short distances (< 50 m) in all study areas. Hence, little extra information would be gained by increasing sampling density from, say, 1/km² to 1/50 m². For many purposes, the soils in the study regions can be mapped with the same observation density, but residual variance will not be the same in all areas. Bulk sampling may help to reveal spatial patterns between 50 and 1.000 m.

Variability of apparently homogeneous soilscapes in São Paulo state, Brazil: II. quality of soil maps

The quality of semi-detailed (scale 1:100.000) soil maps and the utility of a taxonomically based legend were assessed by studying 33 apparently homogeneous fields with strongly weathered soils in two regions in São Paulo State: Araras and Assis. An independent data set of 395 auger sites was used to determine purity of soil mapping units and analysis of variance within and between mapping units and soil classification units. Twenty three soil profiles were studied in detail. The studied soil maps have a high purity for some legend criteria, such as B horizon type (> 90%) and soil texture class (> 80%). The purity for the "trophic character" (eutrophic, dystrophic, allic) was only 55% in Assis. It was 88% in Araras, where many soil units had been mapped as associations. In both regions, the base status of clay-textured soils was generally better than suggested by the maps. Analysis of variance showed that mapping was successful for "durable" soil characteristics such as clay content (> 80% of variance explained) and cation exchange capacity (≥ 50% of variance explained) of 0-20 and 60-80 cm layers. For soil characteristics that are easily modified by management, such as base saturation of the 0-20 cm layer, the maps had explained very little (< 15%) of the total variance in the study areas. Intermediate results were obtained for base saturation of the 60-80 cm layer (56% in Assis; 42% in Araras). Variance explained by taxonomic groupings that formed the basis for the legend of the soil maps was similar to, often even smaller than, variance explained by mapping units. The conclusion is that map boundaries have been very carefully located, but descriptions of mapping units could be improved. In future mappings, this could possibly be done at low cost by (a) bulk sampling to remove short range variation and enhance visualization of spatial patterns at distances > 100 m; (b) taking advantage of correlations between easily measured soil characteristics and chemical soil properties and, (c) unbending the link between legend criteria and a taxonomic system. The maps are well suited to obtain an impression of land suitability for high-input farming. Additional field work and data on former land use/management are necessary for the evaluation of chemical properties of surface horizons.

Documents et pièces diverses, en majeure partie originaux, conservés jadis dans le TRESOR DES CHARTES DE LORRAINE. — Nombreux sceaux. — Voy. l'analyse détaillée de la plupart de ces pièces dans l'Inventaire de Dufourny (Bibl. nat., ms. fr. 4880-4886 ; Bibl. de Nancy, mss. 754-765). On ne relève ici que les pièces qui n'y figurent pas. VII — Portefeuille-layette 5 (1400-1422)

Duc des Monts, n os 1-12. — Voy. Bibl. nat., ms. fr. 4882, pp. 3593-3598 ; Bibl. de Nancy, ms. 758, pp. 295-301. — Pièces concernant les prétentions d'Adolphe, duc de Berg, sur le duché de Bar, à cause de son mariage avec Yolande, fille de Robert, duc de Bar.

Feministinen pedagogiikka

Summary: Feminist pedagogy