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Objectives As heart failure with concomitant sarcopenia has a poor prognosis, simple methods for evaluating the appendicular skeletal muscle mass index (ASMI) are required. Recently, a model incorporating anthropometric data and the sarcopenia index, that is, the ratio of serum creatinine to cystatin C (Cre/CysC), was developed to estimate the appendicular skeletal muscle mass. We hypothesized that this model would be superior to the previous model, which uses only anthropometric data to predict the prognosis. This study aimed to compare the prognostic value of low ASMI as defined by the biomarker and anthropometric models in patients with heart failure. Methods Among 847 patients, we estimated ASMI using an anthropometric model consisting of age, body weight, and height in 791 patients and a biomarker model that incorporates age, body weight, hemoglobin, and Cre/CysC in 562 patients. Patients were divided into low and non-low ASMI groups according to the ASMI estimated by each model, using the cut-off proposed by the Asian Working Group for Sarcopenia. The primary outcome was all-cause mortality. Results Overall, 53.4% and 39.1% of patients were diagnosed with low ASMI by anthropometric and biomarker models, respectively. The agreement of the diagnosis of low ASMI between the two models was poor, with a kappa coefficient of 0.56 (95% confidence interval: 0.49–0.63). Kaplan-Meier curves showed that a low ASMI was significantly associated with all-cause death in both models. However, this association was retained after adjustment for other covariates in the biomarker model (hazard ratio: 2.60, p=0.003), but not in the anthropometric model (hazard ratio: 0.70, p=0.257). Conclusions and implications Among patients hospitalized with heart failure, a low ASMI estimated using the biomarker model, but not the anthropometric model, was significantly associated with all-cause mortality. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development

Aim To clarify the association between changes in the number of foundational medications for heart failure (FMHF) during hospitalization for worsening heart failure and post-discharge prognosis. Methods and results We retrospectively analyzed a combined dataset of three large-scale registries of hospitalized patients with heart failure in Japan (NARA-HF, WET-HF, and REALITY-AHF) and included patients already diagnosed with heart failure with reduced or mildly reduced left ventricular ejection fraction (HFr/mrEF) before admission. Patients were stratified by changes in the number of prescribed FMHF classes, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta blockers, and mineralocorticoid receptor blockers, from admission to discharge. The primary endpoint was defined as the combined endpoint of heart failure rehospitalization and all-cause death within 1-year of discharge. The cohort consisted of 1,113 patients, and 482 combined endpoints were observed. In total, 413 (37.1%) patients were on increased FMHF (increased group), 607 (54.5%) remained unchanged (unchanged group), and 93 (8.4%) had a decreased number of FMHF (decreased group) at discharge compared to the time of admission. In multivariable analysis, the increased group was associated with a significantly lower incidence of the primary endpoint compared with the unchanged group (hazard ratio 0.56, 95% confidence interval 0.45–0.60; P Conclusion Increasing the number of FMHF cases during heart failure hospitalization is associated with a better prognosis in patients with HFr/mrEF. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): REALITY registry was funded by the Cardiovascular Research Fund of Japan.WET-HF registry was supported by a Grant-in-Aid for Young Scientists (Y.S. JSPS KAKENHI, 18K15860).

We report on a new design approach for X-Y symmetric resonator, emphasizing the increase in symmetry by localization of the device anchors. The resonator is mechanized as a z-axis rate gyroscope (RG), and the concept is compatible with the rate-integrating gyroscope mechanization. Our approach is based on strategically placing the critical mechanical elements at the center of the resonator structure, to mitigate the effect of fabrication imperfections across the device. We experimentally demonstrated that the design yields a sub-Hz frequency separation between operational modes, which is attributed to the introduced design approach. The high symmetry of the device led to a temperature stability of 50 mHz over 130 °C temperature range. A ring down test demonstrated the Q -factor greater than 330 K. The thermal stability and preliminary characterization results of the gyro in-run stability are presented. [2017-0177]

We've developed a novel low-noise frontend LSI architecture with chopper stabilization technique combined with noise shaping ADC at chopping frequency for a capacitive MEMS accelerometer. Key features of the architecture are (1) a doubly modulated differential carrier input to MEMS, (2) a 2nd order sigma-delta ADC having a notch in its noise transfer function (NTF) at chopping frequency, and (3) a demodulation after the ADC and a decimation filter. Because the notch frequency of the NTF is precisely adjusted to the second-chopping frequency, an improved signal to noise ratio (SNR) of over 90dB is achieved at the ADC. The notch frequency is adjusted using switched capacitor load in the integrating part of the ADC. By combining the innovations, the frontend provides a 1/10x noise floor reduction and a noise magnitude less than 0.4 mg/VHz with an output signal bandwidth of 60 Hz.

We report on a new design approach for X-Y symmetric resonator, that can be mechanized as rate (RG) or rate-integrating gyroscope (RIG), with a single digit as-fabricated frequency split between the two mechanical out-of-phase operational modes. We explore concentration of critical mechanical elements (shuttle-spring-anchor modules) close to the center of the die to mitigate the effect of the fabrication tolerances “intra-device”. Characterization results show sub-Hz as-fabricated frequency split of Δf=0.3Hz, the lowest value found in the literature for silicon MEMS gyroscopes. Preliminary ring down test shows Q factor greater than 330K. Both low Δf and high Q factor obtained in this approach makes it a very good candidate for implementation of high performance gyroscope.

Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme for degradation of poly(ADP-ribose) by splitting ribose-ribose bonds. Parg-deficient (Parg(+/-) and Parg(-/-)) mouse ES cell lines have been established by disrupting both alleles of Parg exon 1 through gene-targeting. A transcript encoding a full length isoform of Parg was eliminated and only low amounts of Parg isoforms were detected in Parg(-/-) embryonic stem (ES) cells. Poly(ADP-ribose) degradation activity was decreased to one-tenth of that in Parg(+/+) ES cells. Parg(-/-) ES cells exhibited the same growth rate as Parg(+/+) ES cells in culture. Sensitivity of Parg(-/-) ES cells to various DNA damaging agents, including an alkylating agent dimethyl sulfate, cisplatin, gemcitabine, 5-fluorouracil, camptothecin, and gamma-irradiation was examined by clonogenic survival assay. Parg(-/-) ES cells showed enhanced lethality after treatment with dimethyl sulfate, cisplatin and gamma-irradiation compared with wild-type (Parg(+/+)) ES cells (p0.05, respectively). In contrast, a sensitization effect by Parg-deficiency was not observed with gemcitabine and camptothecin. These results suggest the possibility that functional inhibition of Parg leads to sensitization of tumor cells to some chemo- and radiation therapies.

We developed a gyroscope with less than 1-deg/h bias instability variation in a temperature range from −40 °C to 125 °C while performing around 4-deg/h bias instability. This stability was achieved by using the stable frequency separation between the drive and sense modes of a Coriolis vibratory gyroscope. To achieve this stability, the mechanical part was designed with a one-sided open frame to mitigate the variation of resonant frequencies caused by thermal stress. At the circuit level, we implemented a self-clocking architecture with a bandpass $\Sigma -\Delta $ analog-to-digital converter to maintain low quantization noise level over the operational temperature range. The fabricated gyroscope demonstrated a 2-Hz variation of frequency separation for an operational frequency of 18.5 kHz in the operational temperature range. At a system level, a bias instability variation of 0.9 deg/h in the temperature range while performing bias instability less than 4.21 deg/h was demonstrated. This low-noise variation is potentially beneficial for applications requiring a Kalman filter, such as GPS-denied navigation systems, that demands a precise and predetermined noise property.

This research demonstrates a newly developed anodic bonding-based wafer-level-packaging technique to simultaneously seal an accelerometer in the atmosphere and a gyroscope in a vacuum with a glass cap for micro-electromechanical systems sensors. It is necessary for the accelerometer, with a damping oscillator, to be sealed in the atmosphere to achieve a high-speed response. As the gyroscope can achieve high sensitivity with a large displacement at the resonant frequency without air-damping, the gyroscope must be sealed in a vacuum. The technique consists of three processing steps: the first bonding step in the atmosphere for the accelerometer, the pressure control step and the second bonding step in a vacuum for the gyroscope. The process conditions were experimentally determined to achieve higher shear strength at the interface of the packaging. The packaging performance of the accelerometer and gyroscope after wafer-level packaging was also investigated using a laser Doppler velocimeter at room temperature. The amplitude at the resonant frequency of the accelerometer was reduced by air damping, and the quality factor of the gyroscope showed a value higher than 1000. The reliability of the gyroscope was also confirmed by a thermal cyclic test and an endurance test at high humidity and high temperature.

We developed a capacitive silicon on insulator (SOI) microelectro-mechanical systems (MEMS) tuning-fork gyroscope and describe its structure and performance.

We have developed a three-input type single-chip inverter IC for the sine wave drive system in air-conditioner fan motors. The inverter IC integrates a function to generate six signals and dead time. This function generates short dead times, typically 1.5us, to suppress distortion of motor current waveforms. These short dead-times are sufficient to prevent upper and lower arm short-circuits because production variations are reduced by the characteristics of the three-input type single-chip inverter IC. Moreover, the three-input type prevents upper and lower arm short-circuits caused by abnormal input signals, and reduces the number of lines on a circuit board to connect a microcomputer with the inverter IC.

To measure neutron cross-section data of minor actinides, we construct a 4-pi Ge-spectrometer utilizing multiple gamma-ray detection method. This spectrometer consists of 30 Ge crystals (40 detector outputs) and 128 BGO anti-Compton shields. Generally, a data acquisition system for such a big Ge spectrometer consists of many NIM modules; it requires large space and huge cost. To overcome these problems, we developed a new data acquisition system with digital signal processing techniques. This system is mounted in a 19 inches VME sub-rack, and the cost of this system is greatly reduced. Obtained FWHMs (2.5~2.8 keV at 1.33 MeV) show good performances as normal MCA even with short shaping time and much higher channel density. The dead time of this system is only 3.2 micro sec per event. Thus good energy resolution is achieved with short shaping time and short dead time

This study compares the sociodemographic changes and long-term health care needs of the elderly in Japan and South Korea. More specifically, this study deals with demographic transition, urbanization, population aging, changing family structure, and cross-cultural analysis of sociodemographic aspects of the elderly in Japan and South Korea. This study also examines activities of daily living (ADLs), instrumental activities of daily living (IADLs) and conditions of selected items of long-term health care needs of the elderly in Japan and South Korea. This study uses the data from the surveys done in Japan and South Korea, where the same sets of questions were employed at the same time in 1998. The sample size for the Japanese data is 1673 and that of Korean data is 568. A cross-sectional analysis of the Japanese and Korean frail elderly using the 1998 survey data indicates that the proportions of those who are able to do ADLs and IADLs are much greater among the Japanese elderly than the Korean elderly. The analysis also shows that the proportion of the frail elderly who lie down partly or always is much higher among Koreans than Japanese despite the fact that the mean age of Korean respondents is much lower than that of Japanese respondents. Comparing the long-term health care needs of the Japanese and Korean elderly, we may conclude that sociodemographic status of any individual country in conjunction with socioeconomic environment would significantly affect long-term health care needs of the elderly.

The first experiment on Lambda– hypernuclear spectroscopy using high precision CW electron beam was successfully carried out at Jlab. As expected, the experiment E89– 009 (or HNSS) reached sub-MeV resolution (< 800 keV). The HNSS technique and its preliminary results featured by the 12B-Lambda system with proton– hole states were presented. The experiment provided valuable feasibility test of electroproduction and the associated technique. The future extension program is expected to reach much higher yield and even better resolution.

To clarify the occurrence of sarcoid-like reaction in the spleen of the gastric carcinoma patients, 100 consecutive specimens from gastrosplenectomy were examined. Sarcoid-like reaction was observed in the lymph nodes of 13 cases (13%) and the spleen of five cases (5%). All cases of the latter group were included in the former one. None of them showed any symptoms or signs indicative of systemic sarcoidosis. It seems that the cases with sarcoid-like reaction in the spleen ocurred more frequently in an advanced stage of the gastric cancer than those without this phenomenon. Epithelioid cell granulomas (EPGs) appeared to arise in the periarteriolar lymphoid sheaths of the spleen histologically, but were never found in red pulp or germinal centers. They were composed of groups of epithelioid cells and accompanied by the small lymphocytes and plasma cells. In three cases, scattered eosinophils were also observed among the epithelioid cells. Immunohistochemically, the majority of the intragranulomatous small lymphocytes had T-cell phenotype, while B-cells formed only the minor cellular population. None of the 13 cases contained EPGs in the primary tumor. Our study indicates that sarcoid-like reaction in the spleen is possibly not such a rare phenomenon in the gastric cancer as previously considered and more frequently seen in the advanced stage of the gastric cancer. Sarcoid-like reactions of the regional lymph nodes were more frequently seen in the patients with EPGs in the spleen than in those without. We also suggest that the incidence of sarcoid-like reactions in the spleen is closely related to those in pancreaticosplenic nodes and/or nodes of the hilus of the spleen.

Poly(ADP-ribose) glycohydrolase (PARG) is the primary enzyme responsible for the degradation of poly(ADP-ribose). PARG dysfunction sensitizes cells to alkylating agents and induces cell death; however, the details of this effect have not been fully elucidated. Here, we investigated the mechanism by which PARG deficiency leads to cell death in different cell types using methylmethanesulfonate (MMS), an alkylating agent, and Parg(-/-) mouse ES cells and human cancer cell lines. Parg(-/-) mouse ES cells showed increased levels of γ-H2AX, a marker of DNA double strand breaks (DSBs), accumulation of poly(ADP-ribose), p53 network activation, and S-phase arrest. Early apoptosis was enhanced in Parg(-/-) mouse ES cells. Parg(-/-) ES cells predominantly underwent caspase-dependent apoptosis. PARG was then knocked down in a p53-defective cell line, MIAPaCa2 cells, a human pancreatic cancer cell line. MIAPaCa2 cells were sensitized to MMS by PARG knockdown. Enhanced necrotic cell death was induced in MIAPaCa2 cells after augmenting γ-H2AX levels and S-phase arrest. Taken together, these data suggest that DSB repair defect causing S-phase arrest, but p53 status was not important for sensitization to alkylation DNA damage by PARG dysfunction, whereas the cell death pathway is dependent on the cell type. This study demonstrates that functional inhibition of PARG may be useful for sensitizing at least particular cancer cells to alkylating agents.

The prospective association of social integration reported in 1987 with change in activities of daily living (ADL) over three years was examined in a cohort of 2200 Japanese elderly, aged 60 years and over. Social integration data was obtained from a national survey which measured both the quantity and frequency of attachment. Social ties were classified into five types: spouse, child(ren) living together, child(ren) living separately, friend, neighbor, and community group. Eight potential confounding variables--age, educational attainment, existence of chronic diseases, subjective well-being, drinking, sleeping hours, cigarette smoking, and exercise--were controlled using logistic regression analysis for each sex. Men who attended community group meetings more frequently had significantly less decline in ADL during the follow-up period for those who were ADL unimpaired at the baseline survey, and were also significantly more improved for those who were ADL impaired people at the baseline survey. Trends for women were not significant.

5105 Background: Synchronous cancers involving ovaries as well as uterine corpus are well-known events in gynecologic malignancies. These tumors may be independently derived, non-metastatic tumors ...

Random samples of middle-aged (35-64) male residents of two different areas in Tokyo, Bunkyo-ku, a low-mortality area (n = 767) and Koto-ku a high mortality area (n = 790) were interviewed between March and April in 1988, concerning health and life style. The two populations were compared regarding, 1) health status which was examined from the view point of fatigue, symptoms and self-rated health, 2) factors related to the three health indices. The main results were as follows: 1. No significant differences were seen between the two populations in the gross means for health indices. However when the health indices were stratified by age group, mental fatigue and minor symptoms were more prevalent in Bunkyo-ku than Koto-ku among young people, while prevalence of physical fatigue and major symptoms was higher in Koto-ku among old people. 2. The relationship between the health indices and job type, income, education and marital status was examined. In Bunkyo-ku, no relationship was seen after controlling for age, working conditions and life style. On the other hand, in Koto-ku, significant relationships were seen with age, job type and marital status, and health problems were prevalent not only among those with low socioeconomic status but also in other socioeconomic groups. These results were maintained even after controlling for age, working conditions and life style, similar to the analysis for Bunkyo-ku, indicating that health problems in this population do not appear to be solely the result of working conditions or life style.

Factors related to health behavior of older adults in Japan and the United States were compared. A total of 900 persons from three age groups (45 to 59, 60 to 74 and 75 and over) were interviewed in three communities (major metropolitan, midsized city, and small town), in both Kanagawa Prefecture and Ohio State. To determine the reliability of the results, in addition to analysis for all subjects, each of communities were analyzed separately. Health behaviors were divided into 2 separate levels: 1) preventive health behaviors and 2) coping behaviors for symptoms which may be signs of a serious illness. The latter behaviors were classified into three types: 1) seeing a physician, 2) changing lifestyle and 3) taking OTC drugs. The following results were obtained: 1) In both Kanagawa Prefecture and Ohio State, good preventive health behaviors were unrelated to coping behaviors associated with potentially serious illness. Interviewees who used OTC drugs when experiencing a potentially serious illness had a low tendency toward seeing a physician. In Kanagawa Prefecture, individuals who saw a physician showed a strong tendency toward changing their lifestyle, for symptoms which were potential signs of a serious illness. 2) There were some differences in factors related to preventive health behaviors between Kanagawa Prefecture and Ohio State. In Kanagawa Prefecture, there were sex differences, with males exhibiting preventive health behaviors. In Ohio State, good preventive health behaviors were few among interviewees who were black. 3) There was little difference between Kanagawa and Ohio State as far as the tendency toward seeing a physician when experiencing potentially serious illness. In both places, interviewees with good self-rated health status and having strong self-treatment attitudes showed a lower tendency to see a physician when experiencing symptoms which were potential signs of a serious illness.

In order to understand the attitudes of older adults toward medical care, we interviewed 480 persons living in Yokohama, and 180 persons living in Aikawa, Kanagawa, aged 45 to 84 years old. The following results were obtained; 1) Attitudes toward medical care can be classified into four types; self-determined medical care, self treatment attitudes, high dependence on the medical care system, and distrust of medical care. Those interviewees who had high self-determination in medical care and self treatment attitudes showed strong distrust of medical care. 2) There were two groups with trend toward low compliance to the advice of a physician for a physician diagnosed illness: the group that had strong self-determination in medical care, and the group that had high distrust of medical care. The interviewees who had a strong tendency to see a physician for potentially serious illness had high self treatment attitudes, but disease prevention behaviors was not associated with all of four types. 3) In both communities, those interviewees who were younger and with higher educational levels showed strong distrust of medical care and had more self-determination attitudes. Those interviewees who had actually experienced problems in medical treatment showed less dependence on medical care and more distrust of medical care compared to those who had not. In Yokohama, distrust of medical care appeared to be higher among those interviewees who did not have a family doctor than those who had. 4) Distrust of medical care and self-determination in medical care was significantly higher in Yokohama than in Aikawa. The differences in the distribution of educational level and family doctors were a part of the reason for area differences in attitudes of distrust of medical care.

Coping behaviors of middle-aged men living in areas of Tokyo with differing mortality rates were analyzed to determine if regional differences exist and if so why. Coping behaviors were divided into 3 separate levels: 1) coping behavior for slight symptoms, where a small change in lifestyle would seem to be a countermeasure, 2) coping behavior for symptoms which may be signs of a serious illness, and 3) coping behaviors for illness which have been identified and diagnosed by a physician. The sample was randomly selected from men 35 to 64 years of age living in two separate communities, Koto-Ward with a high middle-aged male mortality rate and Bunkyo-Ward where it is low. The following results were obtained. 1) In both communities, the proportion of interviewees who modified their lifestyle when slight symptoms occurred was associated with educational level and occupational status. The individuals who were junior high school graduates, and blue-collar workers in small enterprises, showed a low tendency toward changing their lifestyle when confronted with slight symptoms. College graduates, and white-collar workers who were members of large or medium sized enterprises, showed a strong tendency toward changing their lifestyle when confronted with slight symptoms. 2) In both communities, there were differences in coping behaviors when confronted with potentially serious illness dependent upon self-rated health and working hours per day. Interviewees with good self-rated health status and working more than ten hours a day showed a lower tendency to see a physician. 3) Compliance with the advice of a physician was lower among those interviewees who were younger and among those who did not have a family physician. In Koto-Ward, a correlation was seen between a low rate of compliance to physician advice and the non-availability of adequate medical facilities nearby. 4) In Koto-Ward where middle-aged male mortality is high, the proportion of interviewees who changed lifestyle in response to slight symptoms was significantly lower than in Bunkyo-Ward. The proportion of those who complied with the advice of a physician was also lower. 5) Regional differences in coping behaviors associated with slight symptoms appears to be due to differences in educational level and occupational status. Differences in availability of family physicians and nearby clinics could account for regional differences in the coping behavior of individuals with diagnosed illnesses.

The important factors affecting general job satisfaction of caregivers in nursing homes in Tokyo were analyzed. The general job satisfaction of caregivers proved to be strongly correlated with such factors as frequency of night shifts, relationship with supervisors and length of employment, feeling of self-esteem and motive for taking the present job, satisfaction with work itself and tension and/or frustration experienced in working with the aged, and education. Such factors as cognition of the necessity of the aged services and knowledge of ageing and old people did not have any great impact on general job satisfaction of caregivers. These findings suggest the necessity of improving work conditions and human relations in workplace, the importance of attitudes and feelings of caregivers when hiring them, and the necessity of the adequate cognition and knowledge in working with the aged in nursing homes.