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

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

MAS-MoM Hybrid Method with Wire\u27s Image using in Excitation Problems

An important class of problems is the interaction of an antenna with the cavity of a semi-open metallic structure. In a working environment, an antenna may change its performance due to interactions with its surroundings. This is especially true in automotive applications. Therefore, it is important to consider the interaction of an antenna with possible resonating parts, and to solve these complex electrodynamics problems together. The development of methods for modeling and studying electromagnetic compatibility (EMC) problems has practical value. The method of auxiliary sources (MAS) with the method of moments (MoM) is applied to solve the excitation problem where a wire, with voltage source excitation, is connected to an open metallic surface. For verification of the proposed algorithm, an experimental structure was built and measured. Computer modeling results and the experimental results are in good agreement. Some aspects and principles are described, which provide hybridization of MAS and MoM. Image of objects is effectively applied for the solution of the particular problem

Alcohol and fatal life trajectories in Russia: understanding narrative accounts of premature male death in the family

Background: In the post-Soviet period, Russian working-age men have suffered unusually high mortality rates. Earlier quantitative work found that part of this is attributable to hazardous and harmful patterns of alcohol consumption, which increased in the period of transition at a time of massive social and economic disruption and uncertainty. However, there has been very little work done to document and understand in detail the downward life trajectories of individual men who died prematurely from alcohol-related conditions. Building on an earlier case-control study, this unique qualitative study investigates the perceived interplay between men's drinking careers, their employment and family history, health and eventual death.Methods: In-depth interviews were conducted with close relatives (most often the widow) of 19 men who died between 2003 and 2005 aged 25-54 years whose close relatives reported that alcohol contributed to their death. The study was conducted in a typical medium-sized Russian city. The relative's accounts were analysed using thematic content analysis.Results: The accounts describe how hazardous drinking both contributed to serious employment, family and health problems, and was simultaneously used as a coping mechanism to deal with life crises and a decline in social status. The interviews highlighted the importance of the workplace and employment status for shaping men's drinking patterns. Common themes emerged around a culture of drinking in the workplace, peer pressure from colleagues to drink, use of alcohol as remuneration, consuming non-beverage alcohols,Russian-specific drinking patterns, attitudes to treatment, and passive attitudes towards health and drinking.Conclusions: The study provides a unique insight into the personal decline that lies behind the extremely high working-age mortality due to heavy drinking in Russia, and highlights how health status and hazardous drinking are often closely intertwined with economic and social functioning. Descriptions of the development of drinking careers, hazardous drinking patterns and treatment experiences can be used to plan effective interventions relevant in the Russian context

The Method of Auxiliary Sources as an Efficient Numerical Technique for Large 3D Semi Open Structures

The method of auxiliary sources (MAS) has been demonstrated as suitable for solution of diffraction and inverse problems in complex 2D large objects. Based on MAS numerical study of 3D RCS, EMC/EMI and SAR problems, related to the EM field resonance enhancement inside vehicles and the interaction of the cellular telephone radiation with the user\u27\u27s head are given in other work. The objective of this paper is to present details of MAS application to the wide 3D electrodynamic problems. The area of its efficient application, some features and advantages to achieving efficient solutions, are discussed. The extension of the MAS for semi-open structures with partitions is also presented

Social factors influencing Russian male alcohol use over the life course: a qualitative study investigating age based social norms, masculinity, and workplace context

The massive fluctuations occurring in Russian alcohol-related mortality since the mid-1980s cannot be seen outside of the context of great social and economic change. There is a dearth of qualitative studies about Russian male drinking and especially needed are those that address social processes and individual changes in drinking. Conducted as part of a longitudinal study on men’s alcohol consumption in Izhevsk, this qualitative study uses 25 semi-structured biographical interviews with men aged 33–60 years to explore life course variation in drinking. The dominant pattern was decreasing binge and frequent drinking as men reached middle age which was precipitated by family building, reductions in drinking with work colleagues, and health concerns. A minority of men described chaotic drinking histories with periods of abstinence and heavy drinking. The results highlight the importance of the blue-collar work environment for conditioning male heavy drinking in young adulthood through a variety of social, normative and structural mechanisms. Post-Soviet changes had a structural influence on the propensity for workplace drinking but the important social function of male drinking sessions remained. Bonding with workmates through heavy drinking was seen as an unavoidable and essential part of young men’s social life. With age peer pressure to drink decreased and the need to perform the role of responsible breadwinner put different behavioural demands on men. For some resisting social pressure to drink became an important site of self-determination and a mark of masculine maturity. Over the lifetime the place where masculine identity was asserted shifted from the workplace to the home, which commonly resulted in a reduction in drinking. We contribute to existing theories of Russian male drinking by showing that the performance of age-related social roles influences Russian men’s drinking patterns, drinking contexts and their attitudes. Further research should be conducted investigating drinking trajectories in Russian men

Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls

Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10−16), 6p21 (P = 2.3 × 10−14) and 15q25 (P = 2.2 × 10−63). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16INK4A/p14ARF/CDKN2B/p15INK4B/ANRIL; rs1333040, P = 3.0 × 10−7) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10−8). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cance