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Background Hyponatremia and syndrome of inappropriate antidiuretic hormone (SIADH) is a potentially fatal adverse effect of antidepressants (ADs) and antipsychotics (APs), although its frequency and onset time have not been well documented. Objective To analyze the frequency and onset time of AD- or AP-induced hyponatremia/SIADH. Methods We used plural data-mining techniques to search the US Food and Drug Administration Adverse Event Reporting System (FAERS) database for reports on hyponatremia/SIADH induced by psychotropic drugs from January 2004 to June 2020. For each item, we assessed the reporting odds ratio, 95% CI, median onset time, and Weibull distribution parameters. Results We identified 36 422 reports related to hyponatremia/SIADH. Signals were detected for all psychotropic drugs that we analyzed, except for clozapine. The median onset time of total AD-induced hyponatremia/SIADH was shorter than that of AP. For all ADs and APs except clozapine, hazards were considered to be the early failure type. In contrast, the hazard of clozapine was considered to be the random failure type. The limitations of this study included several reporting biases and the presence of confounding variables, particularly age. Conclusion and Relevance Most ADs and APs were found to be associated with a risk for hyponatremia/SIADH. In addition, sufficient attention should be paid to signs of hyponatremia/SIADH in the early phase when most ADs and APs are administered. These data are potentially useful for determining AD- or AP-induced hyponatremia/SIADH in the early stage and for preventing its further aggravation into a serious condition.

An 83-year-old man with stable chronic kidney disease (CKD) exhibited a sudden increase in urinary N-acetyl-β-D-glucosaminidase and protein excretion, suggesting aggravated kidney damage. Simultaneously, he lost diabetic control, requiring up to 54 units of insulin daily. A detailed examination revealed the presence of renal cell carcinoma, which was surgically resected and confirmed to be interleukin-6-positive by immunohistochemistry. Postoperatively, his uni-nephrectomy necessitated hemodialysis, but the patient's insulin resistance was ameliorated; no medication was required to control diabetes, suggesting that the tumor had caused the insulin resistance. This report describes a case of a tumor secreting interleukin-6, which affects both the control of diabetes and CKD progression.

Aim/Introduction Autoantibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) are a valuable diagnostic and predictive marker for type 1 diabetes. Recently, it has been reported that a significant proportion of sera in the commercial RSR radioimmunoassay (RIA) that have tested positive for GADA have then turned negative in RSR enzyme‐linked immunosorbent assay (ELISA) tests in patients with type 1 diabetes. The present study aimed to investigate whether the GADA result discrepancies between RSR‐RIA and RSR‐ELISA are related to autoantibody affinity. Methods GADA affinity was measured by a competitive binding experiment using unlabeled recombinant human GAD65 in 12 discordant samples (5 RIA[+]/ELISA[−] and 7 RIA[−]/ELISA[+] sera). Furthermore, the effect of the initial incubation time on the GADA positivity was also examined using the ELISA test. Results GADA affinities were >1010 L/mol in two of five RIA(+)/ELISA(−) and all of seven RIA(−)/ELISA(+) sera. After an initial incubation time longer than the recommended 1 h, the GADA titer in three of five RIA(+)/ELISA(−) sera and all RIA(−)/ELISA(+) sera increased 1.6‐ to 100‐fold. However, the titer in 12 GADA‐negative sera from healthy controls remained unchanged after the longer incubation. The increment ratio of GADA titer was positively correlated with GADA affinity (r = 0.991, P

In micro machining of monocrystalline diamond by pulsed laser, unique processing characteristics appeared only under a few ten picosecond pulse duration and a certain overlap rate of laser shot. Cracks mostly propagate in parallel direction to top surface of workpiece, although the laser beam axis is perpendicular to the surface. This processed area can keep diamond structure, and its surface roughness is smaller than R-a = 0.2 mu M. New laser micro machining method to keep diamond structure and small surface roughness is proposed. This method can contribute to reduce the polishing process in micro machining of diamond. (C) 2019 Published by Elsevier Ltd on behalf of CIRP.

Background Long-term care (LTC) prevention is a pressing concern in ageing societies. To understand the risk factors of LTC, it is vital to consider psychological and social factors in addition to physical factors. Owing to a lack of relevant data, we aimed to investigate the social, physical and psychological factors associated with LTC using large-scale, nationally representative data to identify a high-risk population for LTC in terms of multidimensional frailty. Methods We performed a cross-sectional study using anonymised data from the 2013 Comprehensive Survey of Living Conditions conducted by the Ministry of Health, Labour and Welfare of Japan. Among the 23,730 eligible people aged 65 years or older and those who were not in hospitals or care facilities during the survey, 1718 stated that they had LTC certification. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with LTC certification. Results Factors positively associated with LTC certification in the multivariate analyses included older age, the interaction term between sex and age group at age 85–89 years, limb movement difficulties, swollen/heavy feet, incontinence, severe psychological distress (indicated by a Kessler Psychological Distress Scale [K6] score ≥ 13), regular hospital visits for dementia, stroke, Parkinson’s disease, chronic obstructive pulmonary disease, fracture, rheumatoid arthritis, kidney disease, diabetes and osteoporosis. Factors negatively associated with LTC certification included the presence of a spouse, regular hospital visits for hypertension and consulting with friends or acquaintances about worries and stress. Conclusions In summary, we identified the physical, psychological and social factors associated with LTC certification using nationally representative data. Our findings highlight the importance of the establishment of multidimensional approaches for LTC prevention in older adults.

Background Heart failure (HF) is increasing in prevalence worldwide. We explored whether adults with trace and positive proteinuria were at a high risk for incident HF compared with those with negative proteinuria using a nationwide epidemiological database. Methods This is an observational cohort study using the JMDC Claims Database collected between 2005 and 2020. This is a population-based sample [n = 1 021 943; median age 44 years (interquartile range 37–52); 54.8% men]. No participants had a known history of cardiovascular disease (CVD). Each participant was categorized into three groups according to the urine dipstick test results: negative proteinuria (n = 902 273), trace proteinuria (n = 89 599) and positive proteinuria (≥1+; n = 30 071). The primary outcome was HF. The secondary outcomes were myocardial infarction (MI), stroke and atrial fibrillation (AF). We performed multivariable Cox regression analyses to identify the association between the proteinuria category and incident HF and other CVD events. Results Over a mean follow-up of 1150 ± 920 days, 17 182 incident HF events occurred. After multivariable adjustment, hazard ratios for HF events were 1.09 [95% confidence interval (CI) 1.03–1.15] and 1.59 (95% CI 1.49–1.70) for trace proteinuria and positive proteinuria versus negative proteinuria, respectively. This association was present irrespective of clinical characteristics. A stepwise increase in the risk of MI, stroke and AF with proteinuria category was also observed. Our primary results were confirmed in participants after multiple imputations for missing values and in those having no medications for hypertension, diabetes mellitus and dyslipidemia. The discriminative predictive value for HF events improved by adding the results of urine dipstick tests to traditional risk factors [net reclassification improvement 0.0497 (95% CI 0.0346–0.0648); P < 0.001]. Conclusions Not only positive proteinuria, but also trace proteinuria was associated with a greater incidence of HF in the general population. Semiquantitative assessment of proteinuria would be informative for the risk stratification of HF.

The decomposition of gaseous toluene as a representative volatile organic compound using 200 kHz ultrasonic waves was investigated as a new air cleaning method that does not require an ultraviolet light source, in accordance with the Minamata Convention on Mercury. Upon applying ultrasonic irradiation to water in a batch reactor, the removal ratio of gaseous toluene above the water reached 91.0% at 10 ppm and 92.7% at 40 ppm. The addition of t-BuOH, a radical scavenger that suppresses ultrasonic decomposition, inhibited the removal of gaseous toluene, indicating that the ultrasonic irradiation not only accelerated the dissolution of toluene into the water but also mediated its decomposition. Further experiments in a flow system revealed that the removal ratio of gaseous toluene decreased with increasing toluene flow rate, whereas the total mass of toluene removed increased, suggesting that sufficient amounts of the active species, such as •OH radicals, required for the initial decomposition of toluene were formed in the liquid phase upon ultrasonic irradiation.

Although diabetes mellitus (DM) was reported to be associated with incident colorectal cancer (CRC), the detailed association between fasting plasma glucose (FPG) and incident CRC has not been fully understood.We assessed whether hyperglycemia is associated with a higher risk for CRC.Analyses were conducted using the JMDC Claims Database (n=1,441,311; median age [IQR], 46 [40-54] years; 56.6% men). None of the participants were taking antidiabetic medication or had a history of CRC, colorectal polyps, or inflammatory bowel disease. Participants were categorized as normal FPG, FPG level100 mg/dL (1,125,647 individuals); normal-high FPG, FPG level=100-109 mg/dL (210,365 individuals); impaired fasting glucose (IFG), FPG level=110-125 mg/dL (74,836 individuals); and DM, FPG level≥126 mg/dL (30,463 individuals).Over a mean follow-up of 1,137±824 days, 5,566 CRC events occurred. After multivariable adjustment, the hazard ratios for CRC events were 1.10 (95% CI,1.03-1.18) for normal-high FPG, 1.24 (95% CI, 1.13-1.37) for IFG, and 1.36 (95% CI, 1.19-1.55) for DM vs. normal FPG. We confirmed this association in sensitivity analyses excluding those with a follow-up of365 days, and or with obese participants.The risk of CRC increased with elevated FPG category. FPG measurements would help identifying people at high-risk for future CRC.

Context Insulinoma is the most common pancreatic functional neuroendocrine neoplasm, yet little information on recent clinical practice in patients with insulinoma, especially malignant insulinoma, is available. Objective This work aims to clarify the characteristics and practice patterns in patients with insulinoma using a national inpatient database. Methods Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified patients with insulinoma admitted between 2010 and 2018. We compared background characteristics and therapeutic interventions between patients with benign and malignant insulinoma. We also estimated the incidence of insulinoma using the number of patients with newly diagnosed insulinoma in 2012. Results We identified 844 patients with benign insulinoma and 102 patients with malignant insulinoma. Patients with malignant insulinoma were younger (median, 55.5 vs 66.0 years, P Conclusion The present study using a nationwide database had a larger sample size than previous studies and revealed definitive differences in patient characteristics and therapeutic patterns between benign and malignant insulinoma.

Ultrashort pulsed laser has been expected to be a powerful and reliable tool for micro-welding of glass. Picosecond pulsed laser with high pulse repetition rate leads to melting of glass at the vicinity of focal region by the heat accumulation, in which the absorption point of laser energy moves periodically in beam axis. Thus, the control of focusing situation in beam axis is very important to investigate the mechanical strength of weld part. In the microwelding of borosilicate glass by picosecond pulsed laser of 1064 nm, characteristics of molten area creation and weld joint were discussed. Numerical aperture (N.A.) greatly affects characteristics of molten area formation, and superior focusing characteristics, such as N.A. 0.65 enable a long region of high power density in beam axis, which can create a large molten area without cracks even under high energy condition. An appropriately large molten area inside glass has high mechanical strength, when continuous and large molten areas were formed. In addition, high density and large size of molten area without crack led to increasing Young’s modulus, and uniform and high Young’s modulus of molten area results in higher breaking stress.

Background A rapid infusion rate for intravenous lipid emulsion (ILE) can cause adverse effects; therefore, safe and efficient infusion rates are desired. This study aimed to develop a triglyceride (TG) kinetic model after soybean oil-based ILE (SO-ILE) administration and individualize the infusion rate via a population pharmacokinetic approach. Methods Eighty-three inpatients were enrolled in this prospective observational study. A TG kinetic model was applied to the observations based on population pharmacokinetics using a non-linear mixed-effect model. The patients' characteristics and laboratory parameters were evaluated to identify predictors of TG kinetics, and the maximum acceptable infusion rate was defined as that for which the maximum TG concentration did not exceed 400 mg/dL in 90% of patients. Results No adverse events associated with SO-ILE administration were observed. The developed TG kinetic model explained the observed TG concentrations and identified the baseline TG concentration and body weight as predictors of TG kinetics. The estimated maximum acceptable infusion rates greatly varied among individuals, ranging from 0.025 to 0.3 g/kg/h. Conclusion The present study suggested the necessity and demonstrated the feasibility of individualizing the infusion rates of SO-ILE using a population pharmacokinetic approach. This article is protected by copyright. All rights reserved.

DNA methylation alteration is tissue-specific and play a pivotal role in regulating gene transcription during cell proliferation and survival. We aimed to detect genes regulated by DNA methylation, and then investigated whether the gene influenced cell proliferation or survival in adrenal cells. DNA methylation and qPCR analyses were performed in nonfunctioning adrenocortical adenoma (NFA, n = 12) and aldosterone-producing adenoma (APA, n = 35) samples. The VDR gene promoter was markedly hypomethylated in APA with ATP1A1 mutation, and the promoter methylation levels showed a significant inverse association with the transcripts in APA. ATP1A1 mutation led to VDR transcription in HAC15 cells, and VDR suppression abrogated ATP1A1 mutation-mediated cell proliferation in HAC15 cells. We demonstrated that APA with ATP1A1 mutation showed entire hypomethylation in the VDR promoter and abundant VDR mRNA and protein expression. VDR suppression abrogated ATP1A1 mutation-mediated cell proliferation in HAC15 cells. Abundant VDR expression would be essential for ATP1A1 mutation-mediated cell proliferation.

ObjectivesThis study aimed to assess whether adults with proteinuria were at a higher risk of incident colorectal cancer (CRC) than those without proteinuria using a large-scale population-based database.DesignA retrospective observational study.SettingThe JMDC Claims Database, an administrative health claims database, was used. Data were collected between 2005 and 2020.ParticipantsWe selected records of participants (n=3 543 705) who underwent health check-ups, including physical examinations, blood tests and urine dipstick tests. We excluded participants who were aged Main outcome measuresThe primary outcome was CRC at any stage.ResultsParticipants were categorised as having no proteinuria (n=2 435 872), trace proteinuria (n=231 153) or positive proteinuria (n=78 271). Over a mean follow-up period of 1189±914 days, 10 615 CRC diagnoses were recorded. The incidence of CRC (95% CI) was lowest in participants without proteinuria (11.7; 95% CI, 11.5 to 11.9 per 10 000 person-years), followed by trace proteinuria (12.5; 95% CI, 11.7 to 13.3 per 10 000 person-years) and positive proteinuria (16.1; 95% CI, 14.6 to 17.7 per 10 000 person-years). After multivariable adjustment, compared with no proteinuria, HRs for incident CRC were 1.20 (95% CI, 1.12 to 1.29) and 1.23 (95% CI, 1.11 to 1.36) for trace and positive proteinuria, respectively. The association between proteinuria and incident CRC existed in participants after multiple imputations for missing data, with a follow-up period of ≥365 days, regardless of age, sex, obesity, hypertension, diabetes mellitus and estimated glomerular filtration rate.ConclusionsTrace and positive proteinuria were associated with a greater risk of incident CRC. Assessment of proteinuria could help identify individuals at an increased risk of CRC.

Context Guidelines worldwide recommend potassium replacement of 10 to 40 mmol/L in the initial fluid therapy for patients with diabetic ketoacidosis. However, evidence is lacking as to the association between infused potassium concentration and mortality. Objective We aimed to determine the association between infused potassium concentration and in-hospital mortality. Methods Using the Japanese Diagnosis Procedure Combination database, we retrospectively identified inpatients admitted for treatment of diabetic ketoacidosis from July 2010 to March 2018. Patients with kidney dysfunction or serum potassium abnormalities were excluded. We evaluated the association of the potassium concentration in the total infused solutions in the first 2 days of hospitalization with 28-day in-hospital mortality using multivariable regression analysis with a cubic spline model. We also assessed the association between potassium concentration and occurrence of hyperkalemia. Results We identified 14 216 patients with diabetic ketoacidosis and observed 261 deaths. The quartile cut-points for potassium concentration were 7.7, 11.4, and 16.1 mmol/L. Within the range of approximately 10 to 40 mmol/L, potassium concentration was not associated with occurrence of hyperkalemia or death. Lower potassium concentrations were associated with higher 28-day in-hospital mortality; the odds ratio for patients receiving 8 mmol/L was 1.69 (95% CI, 1.03 to 2.78; reference: 20 mmol/L), and the odds ratio increased monotonically as potassium concentration decreased further. Conclusion Patients receiving potassium replacement at concentrations of 10 to 40 mmol/L had similar in-hospital mortality rates, whereas lower concentrations were associated with higher mortality.

Background: Intraductal papillary mucinous neoplasm (IPMN) is a well-established premalignant pancreatic lesion. It is known that mild hyperlipasemia, elevated serum lipase levels, is the risk of malignancy and poor prognosis in patients with IPMN. The purpose of this study is to reveal whether hyperlipasemia is useful in identifying patients with IPMN. Methods: The consecutive 91 patients aged 40-89 years who underwent magnetic resonance cholangio-pancreatography (MRCP) from 2016 to 2019 and who showed elevated serum lipase values above the reference range (>51 U/L) in one year were enrolled. Patients were categorized into three as having IPMN, other pancreatic cystic lesion, and non-cysts groups by MRCP. Results: IPMN was found in 22% and other pancreatic cystic lesion was found in 17% of patients. The prevalence of IPMN was higher in patients with mild hyperlipasemia (60-79 U/L) compared to those with borderline hyperlipasemia (1kg/year also showed higher risk of IPMN (39% vs. 15% and 32% vs. 19%, respectively), and patients with both mild hyperlipasemia and taking H2-blockers showed the highest risk of IPMN compared to those with neither of them (75% vs. 13%). Conclusions: Patients with mild hyperlipasemia showed five times higher risk of having IPMN compared to those with borderline hyperlipasemia. Further investigation with MRCP should be considered for patients with mild hyperlipasemia, especially when they had episodes of epigastric discomfort or weight loss, to find high risk patients for future pancreatic carcinoma.

With recent improvement in adhesive performance, adhesive joints are used more in various industrial fields. Despite their advantage in connecting dissimilar adherends, adhesive joints are considered not suitable for key components of mechanical structures due to their large scatter in joint strengths. There are many factors that affect the strength of adhesive joint. However, the general bonding factors are (1) mechanical bond, (2) physical bonding, (3) chemical bonding. The adhesion mechanism is complex because these theories occur at same time. Thus, it is necessary to consider the factors separately. And it is important to understand the bonding mechanism on interfaces in adhesive joint and to improve the reliability of the joint strength more. In this study, the tensile strength of single lap joint was measured in order to investigate the influence of various surface treatments and strength characterization of adhesive. Specimens consist of aluminum alloy plates (A6061). Large-area electron beam (EB) and plasma were used for surface treatment. Each one of specimens were examined from the view of wettability, roughness parameter. Compared with unirradiated specimens, other joints improved the wettability and tensile strength. The inference of large-area EB irradiation on adhesive mechanism was discussed.

BACKGROUND Postoperative complications after flap-coverage in sarcoma treatment can postpone postoperative adjunct treatments. Here, we present our experience with the use of the superficial circumflex iliac artery perforator (SCIP) flap after sarcoma resection. PATIENTS AND METHODS Patients undergoing immediate reconstruction surgery with a flap after sarcoma resection at a single institution from February 2017 to April 2020 were identified. Patient demographics, tumor characteristics, surgical characteristics, and complications were examined. RESULTS Thirty-five consecutive patients underwent reconstructions using a SCIP flap (34 free and one pedicled SCIP flaps). We also identified 47 consecutive patients who underwent reconstruction with other pedicled or free flaps over the same time period. No significant differences were found in patient age, gender, defect size, or operative time between these two groups. The incidences of overall complications (20/47 [42.6%] vs. 3/35 [8.5%], p

Background: Information about factors related to better adherence to continuous glucose monitoring (CGM) sensor adherence is quite limited. Materials and Methods: Forty-six participants with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) without CGM were recruited. The participants’ characteristics and diabetes-related quality of life (QOL) were evaluated at baseline and one year after starting to use CGM. Participants wearing the sensor for ≥60% of the time were considered as adherent. Results: The mean age of the 46 participants was 44.1 ± 15.0 years old and the mean glycohemoglobin (HbA1c) was 7.7 ± 1.0%; 60.9% of the participants were classified as adherent. The duration of using CSII was longer in the adherent group, and the degree of diabetic retinopathy was significantly different. There were no significant differences in age, frequency of self-monitoring of blood glucose, or Hypoglycemia Fear Survey (HFS-B for behavior, HFS-W for worry) score at baseline between the adherent and nonadherent groups. The Problem Areas in Diabetes (PAID) score at baseline was significantly higher and the total CSII-QOL score at baseline was significantly lower in the adherent group. The usage of dual-wave bolus was significantly increased in the adherent group (34.6%-61.5%, P = .016), but not in the nonadherent group (33.3%-33.3%, P > .999). The HbA1c level showed a significant improvement in the adherent group (7.8%-7.3%, P Conclusions: Higher adherence to CGM sensors may be associated with a heavier emotional burden of diabetes and a worse QOL in relation to CSII at baseline.

Aims/Introduction This study aimed to investigate the dynamics associated with autoantibodies to insulinoma‐associated antigen‐2 (IA‐2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes. Methods Using bridging‐type enzyme‐linked immunosorbent assay, IA‐2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.8–86 years; median diabetes duration 7 years, range 0–58 years). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using the Cochran–Armitage trend test and multivariate logistic regression analysis. Results The prevalence of IA‐2A, ZnT8A and glutamic acid decarboxylase autoantibodies in patients with duration of ≤3 years was 41.1, 36.7 and 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration (P, In the present study, we showed that there was a significant interaction between the onset age and duration of diabetes in patients diagnosed when aged ≤10 years regarding all of the autoantibodies to insulinoma‐associated antigen‐2, zinc transporter 8 and glutamic acid decarboxylase (P

This prospective observational study analyzed the pharmacokinetics of busulfan in Japanese children and evaluated the predicting accuracy of previous pediatric PPK models of busulfan. This study enrolled five patients (aged 2-12 years, BW 14-48 kg) receiving a busulfan-based conditioning regimen for hematopoietic stem cell transplantation at our hospital between January 2017 and December 2018. All patients received a 2-hour intravenous busulfan infusion four times daily for a total of 16 doses. After the infusions, 51 plasma samples were collected with the plasma busulfan concentration measured by liquid chromatography-tandem mass spectrometry. PPK model fitting was analyzed using the (%MPE) and the (%MAPE). Limited sampling strategies for estimating busulfan AUC were also evaluated. High interpatient variability was observed in the PK parameters. The most suitable PPK model that reflected our data was McCune's two-compartment model (%MPE -8.7, %MAPE 19.3). A combination sampling method using the busulfan concentration at 2 and 6 hours after the start of the first busulfan dose was found to be able to estimate AUC4 day . These results provide useful information on busulfan therapeutic drug monitoring in the Japanese pediatric population.

With advances in the diagnosis and treatment of diabetic ketoacidosis (DKA), its rate of in-hospital mortality has declined. However, the risk factors for in-hospital mortality in patients with DKA remain to be elucidated.Using a Japanese national inpatient database from 01 July 2010 to 31 March 2018, we performed multivariable logistic regression analyses to identify factors associated with in-hospital mortality of DKA patients.We identified 25,627 DKA patients and 839 (3.3%) in-hospital deaths. Factors associated with increased in-hospital mortality included higher Charlson comorbidity index (≥4) (odds ratio, 3.38; 95% confidence interval, 2.30-4.96; p 0.001), sepsis (odds ratio, 3.09; 95% confidence interval, 2.38-4.00; p 0.001), type 2 diabetes mellitus (odds ratio, 2.67; 95% confidence interval, 2.09-3.41; p 0.001), and obesity (odds ratio, 2.51; 95% confidence interval, 2.05-3.07; p 0.001). Other factors positively associated with in-hospital mortality included male sex, age ≥ 60 years, consciousness disturbance, lower activities of daily living score at admission, admission requiring ambulance, and admission at non-academic hospital.The present findings may help clinicians to identify DKA patients at higher risk of in-hospital mortality.

We consider a dynamic process of collective choice under majority rule in which a status quo policy evolves. The analysis is based on stochastic evolutionary game theory. The Condorcet winner is uniquely a long-run equilibrium for all (super-)majority rules. When the Condorcet winner does not exist, the long-run equilibria under all majority voting rules belong to the top cycle of policies under a simple majority. When the policy space is multidimensional and the voting quota is larger than the min-max quota, the long-run equilibrium belongs to the min-max set. Finally, the Borda winner appears as a long-run equilibrium under unanimity if voters' behavior is governed by a logit choice rule.

Objectives It is unclear whether mandatory health examination is effective for employees who are already being treated for chronic diseases. We focused on patients being treated for hypertension and evaluated the association between employer‐based health examination attendance and diabetes treatment initiation. Methods Using a database that stores health insurance claims and health examination results of subscribers enrolled in society‐managed health insurance plans in Japan, we identified employees aged 40‐59 years who were being treated for hypertension when starting diabetes treatment from April 2012 to December 2016. A case‐crossover analysis was conducted using 90, 180, and 270 days prior to diabetes treatment initiation as reference points and 90 days after the mandatory health examination as the exposure period. We conducted a subgroup analysis by hemoglobin A1c (HbA1c) level and frequency of outpatient blood glucose testing before the mandatory health examination. Results We identified 1464 individuals starting treatment for diabetes while on antihypertensive drugs. The overall odds ratio for starting diabetes treatment within 90 days of the health examination was 1.89 (95% confidence interval: 1.70‐2.10). The subgroup analysis showed that this odds ratio increased as HbA1c level increased and as blood glucose testing frequency decreased. Conclusions Among employees starting treatment for diabetes while being treated for hypertension, employer‐based mandatory health examination attendance was associated with initiation of diabetes treatment. The health examinations may be functioning as a complement to screening in outpatient settings.

The flat plane of small surface roughness below 0.1 µm average roughness was obtained for monocrystalline diamond by nanosecond pulsed laser irradiation of 1060 nm and post-process acid cleaning, at a laser fluence around the material removal threshold value. The glossy and flat plane at the bottom of the micro-groove was parallel to the top surface of the specimen, although the round beam of Gaussian mode was irradiated in the direction perpendicular to the top surface of specimen. The square beam of top-hat mode produced a shallower micro-groove with a wider, flatter bottom compared with the round beam in Gaussian mode. The creation method of the flat plane with small surface roughness was discussed in the arrangement strategy of linear micro-grooving by the square beam of top-hat mode. Normal side-by-side repetition of linear micro-grooving did not create a flat plane with constant depth. Therefore, a two-step scanning method was proposed in order to overcome the problem in the normal side-by-side repetition of liner micro-grooving. Non-removal areas were partly retained between the processing lines in the first step, and the laser scanning was conducted on the retained area in the second step. The newly proposed two-step scanning method was practical and useful to create a widely flat plane with small surface roughness, and the two-step scanning method provided superior control over the micro-groove depth. This proposed method can reduce the surface roughness in addition to the shape creation of monocrystalline diamond, and it can be used as a high-quality micro-shape fabrication method of monocrystalline diamond.

We developed a new method for removing gaseous substances by using high frequency (200 kHz) ultrasonic irradiation of water, and the effects of ultrasonic irradiation on gas-phase toluene were evaluated quantitatively for the first time. The removal ratio of gaseous toluene increased with increasing ultrasonic power, but the reaction was inhibited by the addition of radical scavengers, indicating that ultrasonic irradiation not only accelerated the dissolution of gaseous toluene but also induced toluene decomposition. The contribution made by OH radicals to the decomposition of gaseous toluene at the gas–liquid interface was confirmed by the difference in removal ratios between addition of KI and addition of tert-butyl alcohol. The toluene removal mechanism was investigated by studying the logarithmic plots for toluene concentration at specified times. The results of this study clearly showed the promotion of gaseous toluene dissolution and the reaction via OH radicals at the gas–liquid interface by sonophysical and sonochemical effects with both effects contributing to the removal of gaseous toluene. Furthermore, the total organic carbon concentration in the aqueous phase increased with increasing reaction time, indicating that the toluene degradation products were trapped and decomposed into low-molecular-weight organic compounds in the aqueous phase.

Unstable and low absorption of laser energy is experienced in copper welding at around 1000 nm wavelength. At 532 nm wavelength, there is stable and high laser absorption by copper. Past researches have shown that transitional processing condition between keyhole and heat conduction welding results in a stable micro-welding process characterized by good surface quality and deep penetration. In order to adapt laser welding to copper using pulsed Nd:YAG lasers, investigations of welding quality and efficiency were addressed. Processing was done under transitional processing condition between heat conduction and keyhole welding. Copper C1020 specimens were processed using superposed laser wavelengths of 1064 nm and 532 nm. Effects of irradiation delay and power density on the process were clarified by taking measurements of absorption rates and molten volumes, and by analyzing the weld beads. In addition, the dynamics of molten area and keyhole formation were investigated through three-dimensional FEM analysis. A stabilized laser absorption and increased molten volume was achieved by superposition using 532 nm laser of an appropriate high power density coupled with a short irradiation delay for the 1064 nm laser, which resulted in high-efficiency welding of copper.

Background Nivolumab is a fully humanized IgG4 monoclonal antibody that targets the programmed death-1 (PD-1) receptor, disrupting PD-1-mediated signaling and restoring antitumor immunity. The objective of this study was to develop a nivolumab quantification method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to evaluate its application in clinical therapeutic drug monitoring. Methods Nivolumab was purified from human plasma using rProtein A resin and then digested with trypsin. The ASGITFSNSGMHWVR peptide (multiple reaction monitoring transition: m/z 550.6→661.4) was detected as a surrogate peptide of nivolumab by triple quadrupole mass spectrometry. Plasma samples (126) were collected from 14 patients with non-small cell lung cancer who were undergoing clinical dosing regimen with nivolumab. The pharmacokinetic data were analyzed using Phoenix NLME software (Version 7.0, Certara, St. Louis, MO) based on a previously reported population pharmacokinetics (PPK) model of nivolumab. Results Nivolumab was selectively detected in human plasma and the linear range was 5-200 mcg/mL (R = 0.99). The accuracy and intraday and interday imprecision were within ±15% of the quality control values of 5 (lower limit of quantification), 10 (low), 80 (medium), and 160 (high) mcg/mL. The nivolumab concentrations measured using LC-MS/MS were consistent with those of previously reported PPK models, and the pharmacokinetic parameters could be adequately predicted from a single trough concentration using a Bayesian approach. Conclusions An absolute quantification method for nivolumab using LC-MS/MS was successfully developed and validated. Combined with PPK analysis, this method should be useful for the therapeutic drug monitoring of nivolumab in clinical practice.

A method to improve penetration and stabilize the welding phenomenon at a high welding speed has been described through experimental and numerical investigations. Using a high power laser beam consisting of a center and a ring part, influences of shielding gas direction and flow rate, laser power density, and welding mode defined by variable intensity distribution have been clarified. The weld bead was evaluated in terms of width, height, shape and roughness. Dual-mode laser irradiation of center and ring power made it possible to stabilize the welding process. The center power helps to achieve sufficient deep penetration, while ring power ensures good temperature distribution. Good surface quality and deep penetration welding could be achieved with dual-mode welding, using low flow rate of shielding gas supplied from the backside direction.

Certified reference materials (CRMs) of the fish meat powder and the fish bone ash for validation of measurement of anthropogenic nuclides (134Cs, 137Cs and 90Sr) related the Fukushima Daiichi nuclear power plant accident were developed using an inter-laboratory comparison. This paper discusses the strategy of development including selection of raw material, the preparation and certification procedures applied for CRM production. In particular, some detailed data are presented for the homogeneity study and inter-laboratory experiment for the certification. The results of inter-laboratory comparison not only to certify CRMs but also showed analytical performance of the anthropogenic nuclides in Japanese laboratories.

Background Irinotecan (CPT-11) is the key drug used in chemotherapy for many malignant tumors. CPT-11 has cholinergic activity and induces perspiration during intravenous administration. In this study, concentrations of CPT-11 and its active metabolite, SN-38, released during perspiration were measured and risk of exposure of these drugs was assessed. Method Beads of sweat were collected using a dropper from four patients undergoing a chemotherapy regimen involving intravenous administration of CPT-11. The concentrations of CPT-11 and SN-38 in sweat were measured using liquid chromatography tandem mass spectrometry. Result Chemotherapy regimens were capecitabine and irinotecan plus bevacizumab (n = 1), CPT-11 monotherapy (n = 1), and oxaliplatin–irinotecan–leucovorin–5-fluorouracil (n = 2). Uridine diphosphate-glucuronosyltransferase 1A1 phenotypes were *6 homo-type (n = 1), *6 hetero-type (n = 1), and wild type (n = 2). CPT-11 dose was 292.3 ± 75.5 mg/body weight (mean ± standard deviation). CPT-11 was detected in sweat secreted by all the four patients, and its mean (±standard deviation) concentration was 252.6 (±111.9) ng/ml. SN-38 was detected in only one of the patients who received oxaliplatin–irinotecan–leucovorin–5-fluorouracil treatment and who had the wild-type uridine diphosphate-glucuronosyltransferase 1A1 phenotype at a concentration of 74.37 ng/ml. Conclusion CPT-11 and SN-38 are detected in sweat released during intravenous CPT-11 administration. Beads of sweat or linen clothes that absorb the sweat might be the source of CPT-11 and SN-38 exposure.

In large-area electron beam (EB) irradiation method developed recently, high energy density EB can be obtained without focusing the beam. Therefore, large-area EB of 60 mm in diameter can be used for instant melting and evaporation of the wide area material surface, and high efficient surface finishing is possible. However, if the workpiece has a hole shape, the EB concentrates in the entrance edge or inside wall of the hole. Thus, it is difficult to smooth the hole bottom surface. Previous study showed that the surface smoothing and micro-deburring effects for non-magnetic workpiece could be improved by setting a magnetic block under the workpiece, since the electrons tend to concentrate the magnetic block along magnetic lines. In this study, smoothing of hole bottom surface was experimentally investigated by setting a magnetic block under a workpiece in large-area EB irradiation. Expansion of smoothing area of the bottom surface was also tried by setting a through hole at the center of the magnetic block. It was clarified that wide area of hole bottom surface could be smoothed by large- area EB irradiation by setting the magnetic block under workpiece. The surface roughness decreased to less than 3.0 μmRz at the area of hole bottom surface. When the hole diameter was 20 mm and hole depth was less than 40 mm, smoothing area of 10 mm in diameter was obtained by using the magnetic block. Moreover, the smoothing area was sufficiently expanded by setting a through hole with an appropriate diameter in magnetic block.

In large-area electron beam (EB) irradiation method developed recently, high energy density of EB can be obtained without focusing the beam. Therefore, the wide area of material surface can be melted instantly, and high efficient surface finishing is possible. Moreover, surface functions such as corrosion resistance and water repellency of the metal molds were improved by the large-area EB irradiation, since thin resolidified layer was formed on the metal surface. It is expected that thick modified layer is effective to maintain their surface functions for long-term. Therefore, control and prediction of the modified layer thickness are important in order to obtain appropriate modified layer thickness on metals with different material properties. In this study, variations of modified layer thickness on metals with different material property are experimentally investigated. Furthermore, electron behavior during large-area EB irradiation is simulated by using an electron track analysis, and prediction of the modified layer thickness is tried with temperature distributions by using an unsteady heat conduction analysis. Experimental results show that the modified layer thickness increases with increasing energy density. The thickness with high relative permeability is larger than that with low one. Analytical results of the modified layer thickness in unsteady heat conduction analysis show quantitative agreement with experimental ones. Furthermore, the modified layer thickness on the metals with different thermal property and density is also discussed. Then, the modified layer thickness of metals with different material property can be predicted by using our unsteady heat conduction analysis model.