Dietary antioxidant and mineral intake in humans is associated with reduced risk of esophageal adenocarcinoma but not reflux esophagitis or Barrett's esophagus

The role of antioxidants in the pathogenesis of reflux esophagitis (RE), Barrett's esophagus (BE), and esophageal adenocarcinoma (EAC) remains unknown. We evaluated the associations among dietary antioxidant intake and these diseases. We performed an assessment of dietary antioxidant intake in a case control study of RE (n = 219), BE (n = 220), EAC (n = 224), and matched population controls (n = 256) (the Factors Influencing the Barrett's Adenocarcinoma Relationship study) using a modification of a validated FFQ. We found that overall antioxidant index, a measure of the combined intake of vitamin C, vitamin E, total carotenoids, and selenium, was associated with a reduced risk of EAC [odds ratio (OR) = 0.57; 95% CI = 0.33-0.98], but not BE (OR = 0.95; 95% CI = 0.53-1.71) or RE (OR = 1.60; 95% CI = 0.86-2.98), for those in the highest compared with lowest category of intake. Those in the highest category of vitamin C intake had a lower risk of EAC (OR = 0.37; 95% CI = 0.21-0.66; P-trend = 0.001) and RE (OR = 0.46; 95% CI = 0.24-0.90; P-trend = 0.03) compared with those in the lowest category. Vitamin C intake was not associated with BE, and intake of vitamin E, total carotenoids, zinc, copper, or selenium was not associated with EAC, BE, or RE. In conclusion, the overall antioxidant index was associated with a reduced risk of EAC. Higher dietary intake of vitamin C was associated with a reduced risk of EAC and RE. These results suggest that antioxidants may play a role in the pathogenesis of RE and EAC and may be more important in terms of progression rather than initiation of the disease process.

Mushroom: An Oracular Sound Processor

Composers of digital music today have a bewildering variety of sound-processing tools and techniques at their disposal. At their best, these tools allow composers to hone a sound to perfection. However, they can also lead us into a routine which bypasses avenues of experimentation, simply because the known tools work so well and their sonic output is so attractive. An alternative strategy is oracular sound processing. An oracular sound processor creates a derived version of its input whose characteristics could not have been fully predicted, while affording the user little or no parametric control over the process.

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10 -5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10 -5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10 -10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Late Pleistocene history of turbidite sedimentation in a submarine canyon off the northern Great Barrier Reef, Australia

Cores from slopes east of the Great Barrier Reef (GBR) challenge traditional models for sedimentation on tropical mixed siliciclastic-carbonate margins. However, satisfactory explanations of sediment accumulation on this archetypal margin that include both hemipelagic and turbidite sedimentation remain elusive, as submarine canyons and their role in delivering coarse-grained turbidite deposits, are poorly understood. Towards addressing this problem we investigated the shelf and canyon system bordering the northern Ribbon Reefs and reconstructed the history of turbidite deposition since the Late Pleistocene. High-resolution bathymetric and seismic data show a large paleo-channel system that crosses the shelf before connecting with the canyons via the inter-reef passages between the Ribbon Reefs. High-resolution bathymetry of the canyon axis reveals a complex and active system of channels, sand waves, and local submarine landslides. Multi-proxy examination of three cores from down the axis of the canyon system reveals 18 turbidites and debrites, interlayered with hemipelagic muds, that are derived from a mix of shallow and deep sources. Twenty radiocarbon ages indicate that siliciclastic-dominated and mixed turbidites only occur prior to 31 ka during Marine Isotope Stage (MIS) 3, while carbonate-dominated turbidites are well established by 11 ka in MIS1 until as recently as 1.2 ka. The apparent lack of siliciclastic-dominated turbidites and presence of only a few carbonate-dominated turbidites during the MIS2 lowstand are not consistent with generic models of margin sedimentation but might also reflect a gap in the turbidite record. These data suggest that turbidite sedimentation in the Ribbon Reef canyons, probably reflects the complex relationship between the prolonged period (> 25 ka) of MIS3 millennial sea level changes and local factors such as the shelf, inter-reef passage depth, canyon morphology and different sediment sources. On this basis we predict that the spatial and temporal patterns of turbidite sedimentation could vary considerably along the length of the GBR margin.

Association of MYH9/APOL1 with chronic kidney disease in a UK population

Following the first report on the association between MYH9 gene variants and glomerular disorders [1], many studies have evaluated MYH9 loci for association with a range of kidney diseases [2]. In 2010, functional mutations in the adjacent APOL1 gene were identified as the primary variants responsible for associations with kidney disease that had previously been attributed to the MHY9 gene [3]. Nevertheless, several loci within MHY9 continue to be independently reported as risk factors for chronic kidney disease (CKD) [2, 4].