Circulating Concentrations of Vitamin B6 and Kidney Cancer Prognosis: A Prospective Case-Cohort Study

Prospective cohort studies have found that prediagnostic circulating vitamin B6 is inversely associated with both risk of kidney cancer and kidney cancer prognosis. We investigated whether circulating concentrations of vitamin B6 at kidney cancer diagnosis are associated with risk of death using a case-cohort study of 630 renal cell carcinoma (RCC) patients. Blood was collected at the time of diagnosis, and vitamin B6 concentrations were quantified using LC-MS/MS. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. After adjusting for stage, age, and sex, the hazard was 3 times lower among those in the highest compared to the lowest fourth of B6 concentration (HR4vs1 0.33, 95% CI [0.18, 0.60]). This inverse association was solely driven by death from RCC (HR4vs1 0.22, 95% CI [0.11, 0.46]), and not death from other causes (HR4vs1 0.89, 95% CI [0.35, 2.28], p-interaction = 0.008). These results suggest that circulating vitamin B6 could provide additional prognostic information for kidney cancer patients beyond that afforded by tumour stage

Variability and redistribution of heat in the Atlantic Water boundary current north of Svalbard

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Geophysical Research: Oceans 123 (2018): 6373-6391, doi:10.1029/2018JC013814.We quantify Atlantic Water heat loss north of Svalbard using year‐long hydrographic and current records from three moorings deployed across the Svalbard Branch of the Atlantic Water boundary current in 2012–2013. The boundary current loses annually on average 16 W m−2 during the eastward propagation along the upper continental slope. The largest vertical fluxes of >100 W m−2 occur episodically in autumn and early winter. Episodes of sea ice imported from the north in November 2012 and February 2013 coincided with large ocean‐to‐ice heat fluxes, which effectively melted the ice and sustained open water conditions in the middle of the Arctic winter. Between March and early July 2013, a persistent ice cover‐modulated air‐sea fluxes. Melting sea ice at the start of the winter initiates a cold, up to 100‐m‐deep halocline separating the ice cover from the warm Atlantic Water. Semidiurnal tides dominate the energy over the upper part of the slope. The vertical tidal structure depends on stratification and varies seasonally, with the potential to contribute to vertical fluxes with shear‐driven mixing. Further processes impacting the heat budget include lateral heat loss due to mesoscale eddies, and modest and negligible contributions of Ekman pumping and shelf break upwelling, respectively. The continental slope north of Svalbard is a key example regarding the role of ocean heat for the sea ice cover. Our study underlines the complexity of the ocean's heat budget that is sensitive to the balance between oceanic heat advection, vertical fluxes, air‐sea interaction, and the sea ice cover.Arctic Ocean program at the FRAM-High North Research Centre for Climate and the environment; National Science Foundation (NSF) Grant Number: ARC-1264098; Polish-Norwegian Research Programme Grant Number: POL-NOR/202006/10/2013; Research Council of Norway Grant Number: 276730; Steven Grossman Family Foundatio

Loss of chromosome Y leads to down regulation of KDM5D and KDM6C epigenetic modifiers in clear cell renal cell carcinoma

Recent genomic studies of sporadic clear cell renal cell carcinoma (ccRCC) have uncovered novel driver genes and pathways. Given the unequal incidence rates among men and women (male:female incidence ratio approaches 2:1), we compared the genome-wide distribution of the chromosomal abnormalities in both sexes. We observed a higher frequency for the somatic recurrent chromosomal copy number variations (CNVs) of autosomes in male subjects, whereas somatic loss of chromosome X was detected exclusively in female patients (17.1%). Furthermore, somatic loss of chromosome Y (LOY) was detected in about 40% of male subjects, while mosaic LOY was detected in DNA isolated from peripheral blood in 9.6% of them, and was the only recurrent CNV in constitutional DNA samples. LOY in constitutional DNA, but not in tumor DNA was associated with older age. Amongst Y-linked genes that were downregulated due to LOY, KDM5D and KDM6C epigenetic modifiers have functionally-similar X-linked homologs whose deficiency is involved in ccRCC progression. Our findings establish somatic LOY as a highly recurrent genetic defect in ccRCC that leads to downregulation of hitherto unsuspected epigenetic factors, and suggest that different mechanisms may underlie the somatic and mosaic LOY observed in tumors and peripheral blood, respectively

A rare truncating BRCA2 variant and genetic susceptibility to upper aerodigestive tract cancer

© The Author 2015. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact [email protected] Funding This work was supported the National Institutes of Health (R01CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116). Notes The authors thank all of the participants who took part in this research and the funders and technical staff who made this study possible. We acknowledge and thank Simone Benhamou (INSERM, France) for sample contributions. We also acknowledge and thank The Cancer Genome Atlas initiative, whose data contributed heavily to this study.Peer reviewedPublisher PD

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field

The 12p13.33/RAD52 locus and genetic susceptibility to squamous cell cancers of upper aerodigestive tract

Acknowledgments: The authors thank all of the participants who took part in this research and the funders and support and technical staff who made this study possible. We also acknowledge and thank The Cancer Genome Atlas initiative whose data contributed heavily to this study. Funding: Funding for study coordination, genotyping of replication studies and statistical analysis was provided by the US National Institutes of Health (R01 CA092039 05/05S1) and the National Institute of Dental and Craniofacial Research (1R03DE020116). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Eddies and the distribution of Eddy Kinetic Energy in the Arctic Ocean

© The Author(s), 2022. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in von Appen, W.-J., Baumann, T. M., Janout, M., Koldunov, N., Lenn, Y.-D., Pickart, R. S., Scott, R. B., & Wang, Q. Eddies and the distribution of eddy kinetic energy in the Arctic Ocean. Oceanography, 35(2), (2022), https://doi.org/10.5670/oceanog.2022.122.Mesoscale eddies are important to many aspects of the dynamics of the Arctic Ocean. Among others, they maintain the halocline and interact with the Atlantic Water circumpolar boundary current through lateral eddy fluxes and shelf-basin exchanges. Mesoscale eddies are also important for transporting biological material and for modifying sea ice distribution. Here, we review what is known about eddies and their impacts in the Arctic Ocean in the context of rapid climate change. Eddy kinetic energy (EKE) is a proxy for mesoscale variability in the ocean due to eddies. We present the first quantification of EKE from moored observations across the entire Arctic Ocean and compare those results to output from an eddy resolving numerical model. We show that EKE is largest in the northern Nordic Seas/Fram Strait and it is also elevated along the shelf break of the Arctic Circumpolar Boundary Current, especially in the Beaufort Sea. In the central basins, EKE is 100–1,000 times lower. Generally, EKE is stronger when sea ice concentration is low versus times of dense ice cover. As sea ice declines, we anticipate that areas in the Arctic Ocean where conditions typical of the North Atlantic and North Pacific prevail will increase. We conclude that the future Arctic Ocean will feature more energetic mesoscale variability