One of the most important applications of focused ion beam (FIB) systems is sample preparation for transmission electron microscopy (TEM). However, the use of the FIB inherently involves changing and damaging the sample, and thereby degrades the TEM resolution. This paper addresses the beam-induced damage and artifacts, particularly in applications involving silicon semiconductors. The damage appears in the form of amorphization on the surface of the TEM foil. The characteristics of this amorphous damage were studied by making TEM observations of cross sections of the affected foil. The damage is typically 20 to 30 nm thick for a 30 keV FIB, which is generally overly thick for modern silicon devices with feature sizes less than 250 nm. This paper reviews the reported damage depths of FIB-prepared samples, which are determined by experiments and calculations. Several damage reduction techniques, such as the use of gas-assisted etching, low energy FIB, cleaning the FIBfabricated cross section by wet or dry etching and cleaning by broad ion beam (BIB) milling have also been reviewed, with emphasis on applicability to silicon devices. We conclude that the use of low energy FIB and cleaning by argon BIB are particularly efficient techniques.

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Urinary 8-hydroxydeoxyguanosine (8-OH-dG) and 7-methylguanine (m 7 Gua) were measured by a column-switching high performance liquid chromatography method as markers of oxidative and methylating DNA damage, respectively. We investigated the associations between urinary 8-OH-dG or m 7 Gua and various lifestyle and demographic factors, such as age and sex. The urinary 8-OH-dG excretion level was positively correlated with cigarette smoking, but inversely correlated with fruit consumption, physical activity and total energy consumed per day. A multiple regression analysis revealed that daily physical activity and healthy meal combinations decreased the urinary 8-OH-dG level, whereas alcohol consumption increased it. In terms of the urinary m 7 Gua measurement, cigarette smoking, age and consumption of meat, fish, egg, soybean, etc. were positively correlated with the urinary m 7 Gua level, whereas body weight, BMI, physical activity, and dietary index score, which indicates good nutritional balance, were negatively correlated with the amount of m 7 Gua. Based on a multiple regression analysis, cigarette smoking and age correlated with the m 7 Gua level, while high BMI and healthy meal combinations have significant reducing effects on m 7 Gua level. Therefore, the urinary m 7 Gua level is considered to be a useful marker of DNA methylation, not only from smoking, but also from aging and unhealthy dietary habits. (Cancer Sci 2009; 100: 715-721) O xygen radicals are formed in cells by oxygen metabolism and various environmental agents, and they damage DNA, RNA, and proteins.(1) Among the many types of oxidative DNA damage, 8-hydroxydeoxyguanosine (8-OH-dG) is a major product and is frequently analyzed as a marker of cellular oxidative stress related to carcinogenesis, (2,3) because 8-OH-dG induces mutations, (4,5) is excreted in the urine, and it has been analyzed by high performance liquid chromatography-electrochemical detection (HPLC-ECD), (6,7) liquid chromatography-tandem mass spectrometry (LC-MS), (8) gas chromatography-mass spectrometry (GC-MS),and enzyme linked immunosorbent assay (ELISA).(10) However, the reproducibility and accuracy of its measurement are much higher with the HPLC-ECD and LC-MS/MS methods, as compared to the ELISA method. (11,12) We have reported that higher 8-OH-dG levels were observed in the lung DNA of smokers, (13) the liver DNA of chronic hepatitis patients, (14) and in the stomach DNA of patients infected with Helicobacter pylori.(15) It has also been reported that the urinary 8-OH-dG level is higher in cancer patients than in healthy people, (16) higher in smokers than in nonsmokers, (17) and lower in people who exercise moderately. (17) In addition, the urinary 8-OH-dG level was higher in men than in women, (7) and it negatively correlated to body mass index (BMI).(7) As an explanation for the relationship between a lean BMI and high urinary 8-OH-dG excretion, it has been suggested that lean persons have a higher metabolic rate than obese persons, (18) and therefore have higher oxidat...

ObjectiveRisk models and scores have been developed to predict incidence of type 2 diabetes in Western populations, but their performance may differ when applied to non-Western populations. We developed and validated a risk score for predicting 3-year incidence of type 2 diabetes in a Japanese population.MethodsParticipants were 37,416 men and women, aged 30 or older, who received periodic health checkup in 2008–2009 in eight companies. Diabetes was defined as fasting plasma glucose (FPG) ≥126 mg/dl, random plasma glucose ≥200 mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or receiving medical treatment for diabetes. Risk scores on non-invasive and invasive models including FPG and HbA1c were developed using logistic regression in a derivation cohort and validated in the remaining cohort.ResultsThe area under the curve (AUC) for the non-invasive model including age, sex, body mass index, waist circumference, hypertension, and smoking status was 0.717 (95% CI, 0.703–0.731). In the invasive model in which both FPG and HbA1c were added to the non-invasive model, AUC was increased to 0.893 (95% CI, 0.883–0.902). When the risk scores were applied to the validation cohort, AUCs (95% CI) for the non-invasive and invasive model were 0.734 (0.715–0.753) and 0.882 (0.868–0.895), respectively. Participants with a non-invasive score of ≥15 and invasive score of ≥19 were projected to have >20% and >50% risk, respectively, of developing type 2 diabetes within 3 years.ConclusionsThe simple risk score of the non-invasive model might be useful for predicting incident type 2 diabetes, and its predictive performance may be markedly improved by incorporating FPG and HbA1c.

Because poor sleep quality can reduce quality of life and increase prevalence of illness in workers, interventions are becoming increasingly important for businesses. To evaluate how sleep quality is affected by one-on-one behavioral modification when combined with group education, we conducted a randomized, controlled trial among day-shift white-collar employees working for an information-technology service company in Japan. Participants were randomly allocated to groups receiving either sleep hygiene group education (control group), or education combined with individual sleep modification training (one-on-one group). Occupational health professionals carried out both procedures, and sleep quality was assessed using the Pittsburgh Sleep Quality index (PSQi). PSQi scores were obtained before and after the intervention period, and changes in scores were compared across groups after adjustments for age, gender, job title, smoking and drinking habits, body-mass index, and mental health as assessed using k6 scores. The average PSQi score for the control group decreased by 0.8, whereas that of the one-on-one group decreased by 1.8 (difference of 1), resulting in a significantly greater decrease in score for the one-on-one group (95% confidence interval: 0.02 to 2.0). These results show that, compared to sleep hygiene group education alone, the addition of individual behavioral training significantly improved the sleep quality of workers after only three months.

In focused ion beam (FIB) fabrication of cross-sectional transmission electron microscopy (X-TEM) specimens, highly accelerated ion beams sometimes cause serious damage. The damage can be induced in both the specimen surface and the side walls. We used the X-TEM technique to investigate the sidewall damage in crystalline Si. The damaged layer was found to be about 20 nm thick in the case of 30-keV-FIB etching. We evaluated several techniques for reducing the damage, such as gas-assisted etching (GAE) with iodine, low-energy FIB etching, and cleaning by broad argon ion milling or by wet etching. The damage depth was 19 nm for GAE and 10 nm for 10 keV FIB etching, and was reduced to 7 nm by 3 keV argon ion milling with a beam current of 20 μA and a tilt angle between the beam and the specimen of 4°. Wet etching using a mixture of nitric and hydrofluoric acid removed most of the damaged layer. The effect of the damaged layer on TEM observation was also investigated, and it was shown that removal of the damaged layer results in a high-resolution TEM image.

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AimsTo examine the association of smoking status, smoking intensity, and smoking cessation with the risk of type 2 diabetes (T2D) using a large database.MethodsThe present study included 53,930 Japanese employees, aged 15 to 83 years, who received health check-up and did not have diabetes at baseline. Diabetes was defined as fasting plasma glucose ≥126 mg/dl, random plasma glucose ≥200 mg/dl, HbA1c ≥6.5% (≥48 mmol/mol), or receiving medication for diabetes. Cox proportional-hazards regression models were used to investigate the association between smoking and the risk of diabetes.ResultsDuring 3.9 years of median follow-up, 2,441 (4.5%) individuals developed T2D. The multivariable-adjusted hazard ratios (95% CI) for diabetes were 1 (reference), 1.16 (1.04 to 1.30) and 1.34 (1.22 to 1.48) for never smokers, former smokers, and current smokers, respectively. Diabetes risk increased with increasing numbers of cigarette consumption among current smokers (P for trend <0.001). Although the relative risk of diabetes was greater among subjects with lower BMIs (< 23 kg/m2), attributable risk was greater in subjects with higher BMIs (≥ 23 kg/m2). Compared with individuals who had never smoked, former smokers who quit less than 5 years, 5 to 9 years, and 10 years or more exhibited hazards ratios for diabetes of 1.36 (1.14 to 1.62), 1.23 (1.01 to 1.51), and 1.02 (0.85 to 1.23), respectively.ConclusionsResults suggest that cigarette smoking is associated with an increased risk of T2D, which may decrease to the level of a never smoker after 10 years of smoking cessation.