The Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT): Study Design and Participants

Background: Lifestyle and life-environment factors have undergone drastic changes in Japan over the last few decades. Further, many molecular epidemiologic studies have reported that genetic, epigenetic, and other biomarker information may be useful in predicting individual disease risk.Methods: The Japan Public Health Center-based Prospective Study for the Next Generation (JPHC-NEXT) was launched in 2011 to identify risk factors for lifestyle-related disease, elucidate factors that extend healthy life expectancy, and contribute toward personalized healthcare based on our more than 20 years’ experience with the JPHC Study. From 2011 through 2016, a baseline survey was conducted at 16 municipalities in seven prefectures across the country. A self-administered questionnaire was distributed to all registered residents aged 40–74, which mainly asked about lifestyle factors, such as socio-demographic situation, personal medical history, smoking, alcohol and dietary habits. We obtained informed consent from each participant to participate in this long follow-up study of at least 20 years, including consent to the potential use of their residence registry, medical records, medical fee receipts, care insurance etc., and to the provision of biospecimens (blood and urine), including genomic analysis.Results: As of December 31, 2016, we have established a population-based cohort of 115,385 persons (Response rate 44.1%), among whom 55,278 (47.9% of participants) have provided blood and urine samples. The participation rate was slightly higher among females and in the older age group.Conclusion: We have established a large-scale population-based cohort for next-generation epidemiological study in Japan

Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires

Background: Although open-ended dietary assessment methods, such as weighed food records (WFRs), are generally considered to be comparable, differences between procedures may influence outcome when WFRs are conducted independently. In this paper, we assess the procedures of WFRs in two studies to describe their dietary assessment procedures and compare the subsequent outcomes. Methods: WFRs of 12 days (3 days for four seasons) were conducted as reference methods for intake data, in accordance with the study protocol, among a subsample of participants of two large cohort studies. We compared the WFR procedures descriptively. We also compared some dietary intake variables, such as the frequency of foods and dishes and contributing foods, to determine whether there were differences in the portion size distribution and intra- and inter-individual variation in nutrient intakes caused by the difference in procedures. Results: General procedures of the dietary records were conducted in accordance with the National Health and Nutrition Survey and were the same for both studies. Differences were seen in 1) selection of multiple days (non-consecutive days versus consecutive days); and 2) survey sheet recording method (individual versus family participation). However, the foods contributing to intake of energy and selected nutrients, the portion size distribution, and intra- and inter-individual variation in nutrient intakes were similar between the two studies. Conclusion: Our comparison of WFR procedures in two independent studies revealed several differences. Notwithstanding these procedural differences, however, the subsequent outcomes were similar

Body mass index and colorectal cancer risk : A Mendelian randomization study

Traditional observational studies have reported a positive association between higher body mass index (BMI) and the risk of colorectal cancer (CRC). However, evidence from other approaches to pursue the causal relationship between BMI and CRC is sparse. A two-sample Mendelian randomization (MR) study was undertaken using 68 single nucleotide polymorphisms (SNPs) from the Japanese genome-wide association study (GWAS) and 654 SNPs from the GWAS catalogue for BMI as sets of instrumental variables. For the analysis of SNP-BMI associations, we undertook a meta-analysis with 36 303 participants in the Japanese Consortium of Genetic Epidemiology studies (J-CGE), comprising normal populations. For the analysis of SNP-CRC associations, we utilized 7636 CRC cases and 37 141 controls from five studies in Japan, and undertook a meta-analysis. Mendelian randomization analysis of inverse-variance weighted method indicated that a one-unit (kg/m2) increase in genetically predicted BMI was associated with an odds ratio of 1.13 (95% confidence interval, 1.06-1.20; P value <.001) for CRC using the set of 68 SNPs, and an odds ratio of 1.07 (1.03-1.11, 0.001) for CRC using the set of 654 SNPs. Sensitivity analyses robustly showed increased odds ratios for CRC for every one-unit increase in genetically predicted BMI. Our MR analyses strongly support the evidence that higher BMI influences the risk of CRC. Although Asians are generally leaner than Europeans and North Americans, avoiding higher BMI seems to be important for the prevention of CRC in Asian populations

Genetic susceptibility to hepatocellular carcinoma in chromosome 22q13.31, findings of a genome-wide association study.

Background and Aim: Chronic hepatitis C virus (HCV) infection, long-term alcohol use, cigarette smoking, and obesity are the major risk factors for hepatocellular carcinoma (HCC) in the United States, but the disease risk varies substantially among individuals with these factors, suggesting host susceptibility to and gene-environment interactions in HCC. To address genetic susceptibility to HCC, we conducted a genome-wide association study (GWAS). Methods: Two case-control studies on HCC were conducted in the United States. DNA samples were genotyped using the Illumian microarray chip with over 710 000 single nucleotide polymorphisms (SNPs). We compared these SNPs between 705 HCC cases and 1455 population controls for their associations with HCC and verified our findings in additional studies. Results: In this GWAS, we found that two SNPs were associated with HCC at Conclusions: SNPs i

Isotope effects on energy, particle transport and turbulence in electron cyclotron resonant heating plasma of the Large Helical Device

Positive isotope effects have been found in electron cyclotron resonant heating plasma of the Large Helical Device (LHD). The global energy confinement time (τE) in deuterium (D) plasma is 16% better than in hydrogen (H) plasma for the same line-averaged density and absorption power. The power balance analyses showed a clear reduction in ion energy transport, while electron energy transport does not change dramatically. The global particle confinement time (τp) is degraded in D plasma; τp in D plasma is 20% worse than in H plasma for the same line-averaged density and absorption power. The difference in the density profile was not due to the neutral or impurity sources, but rather was due to the difference in the transport. Ion scale turbulence levels show isotope effects. The core turbulence (ρ  =  0.5–0.8) level is higher in D plasma than in H plasma in the low collisionality regime and is lower in D plasma than in H plasma. The density gradient and collisionality play a role in the core turbulence level

The isotope effect on impurities and bulk ion particle transport in the Large Helical Device

The isotope effect on impurities and bulk ion particle transport is investigated by using the deuterium, hydrogen, and isotope mixture plasma in the Large Helical Device (LHD). A clear isotope effect is observed in the impurity transport but not the bulk ion transport. The isotope effects on impurity transport and ion heat transport are observed as a primary and a secondary effect, respectively, in the plasma with an internal transport barrier (ITB). In the LHD, an ion ITB is always transient because the impurity hole triggered by the increase of ion temperature gradient causes the enhancement of ion heat transport and gradually terminates the ion ITB. The formation of an impurity hole becomes slower in the deuterium (D) plasma than the hydrogen (H) plasma. This primary isotope effect on impurity transport contributes the longer sustainment of the ion ITB state because the low ion thermal diffusivity can be sustained as long as the normalized carbon impurity gradient R/Ln,c, where , is above the critical value (~−5). Therefore, the longer sustainment of the ITB state in the deuterium plasma is considered to be a secondary isotope effect due to the mitigation of the impurity hole. The radial profile of H and D ion density is measured using bulk charge exchange spectroscopy inside the isotope mixture plasma. The decay time of H ion density after the H-pellet injection and the decay time of D ion density after D-pellet injection are almost identical, which demonstrates that there is no significant isotope effect on ion particle transport

Extended investigations of isotope effects on ECRH plasma in LHD

Isotope effects of ECRH plasma in LHD were investigated in detail. A clear difference of transport and turbulence characteristics in H and D plasmas was found in the core region, with normalized radius ρ < 0.8 in high collisionality regime. On the other hand, differences of transport and turbulence were relatively small in low collisionality regime. Power balance analysis and neoclassical calculation showed a reduction of the anomalous contribution to electron and ion transport in D plasma compared with H plasma in the high collisionality regime. In core region, density modulation experiments also showed more reduced particle diffusion in D plasma than in H plasma, in the high collisionality regime. Ion scale turbulence was clearly reduced at ρ < 0.8 in high collisionality regime in D plasma compared with H plasma. The gyrokinetic linear analyses showed that the dominant instability ρ = 0.5 and 0.8 were ion temperature gradient mode (ITG). The linear growth rate of ITG was reduced in D plasma than in H plasma in high collisionality regime. This is due to the lower normalized ITG and density gradient. More hollowed density profile in D plasma is likely to be the key control parameter. Present analyses suggest that anomalous process play a role to make hollower density profiles in D plasma rather than neoclassical process. Electron scale turbulence were also investigated from the measurements and linear gyrokinetic simulations

Realization of high Ti plasmas and confinement characteristics of ITB plasmas in the LHD deuterium experiments

The deuterium (D) operation was initiated in the LHD in 2017. In the first campaign of the D experiments, we successfully extended the high temperature regime in the LHD. The new record of the ion temperature (Ti) of 10 keV associated with the ion internal transport barrier (ITB) was achieved due to several operational optimization. The thermal confinement characteristics of ITB plasmas were compared between hydrogen and D discharges. The effective ion thermal diffusivity of the ion-ITB plasmas was found to be smaller in the D discharges than that in the H discharges. The profiles of the Ti, the electron density, and the impurity of the high Ti plasmas strongly depended on the magnetic configuration and these profiles tended to peaked in the inward-shifted configuration. It was also found that the electron thermal confinement of the electron-ITB plasmas was clearly improved in the deuterium case. The GKV simulation showed the linear growth rate of TEM/ITG reduced in the plasmas with D both for the ion ITB and the electron ITB plasmas and qualitatively agreed with the tendency of the change in the thermal diffusivity obtained from the power balance analysis

Isotope effects on transport in LHD

Isotope effects are one of the most important issues for predicting future reactor operations. Large helical device (LHD) is the presently working largest stellarator/helical device using super conducting helical coils. In LHD, deuterium experiments started in 2017. Extensive studies regarding isotope effects on transport have been carried out. In this paper, the results of isotope effect studies in LHD are reported. The systematic studies were performed adjusting operational parameters and nondimensional parameters. In L mode like normal confinement plasma, where internal and edge transport barriers are not formed, the scaling of global energy confinement time (τE) with operational parameters shows positive mass dependence (M0.27; where M is effective ion mass) in electron cyclotron heating plasma and no mass dependence (M0.0) in neutral beam injection heating plasma. The non-negative ion mass dependence is anti-gyro-Bohm scaling. The role of the turbulence in isotope effects was also found by turbulence measurements and gyrokinetic simulation. Better accessibility to electron and ion internal transport barrier (ITB) plasma is found in deuterium (D) plasma than in hydrogen (H). Gyro kinetic non-linear simulation shows reduced ion heat flux due to the larger generation of zonal flow in deuterium plasma. Peaked carbon density profile plays a prominent role in reducing ion energy transport in ITB plasma. This is evident only in plasma with deuterium ions. New findings on the mixing and non-mixing states of D and H particle transports are reported. In the mixing state, ion particle diffusivities are higher than electron particle diffusivities and D and H ion density profiles are almost identical. In the non-mixing state, ion particle diffusivity is much lower than electron diffusivity. Deuterium and hydrogen ion profiles are clearly different. Different turbulence structures were found in the mixing and non-mixing states suggesting different turbulence modes play a role