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Short-term associations between air pollution and mortality have been well reported in Japan, but the historical changes in mortality risk remain unknown. We examined temporal changes in the mortality risks associated with short-term exposure to four criteria air pollutants in selected Japanese cities., This work was supported by JSPS KAKENHI [grant numbers JP20H03942, JP19K10644] and the Nagasaki University WISE Program.

Expanding the use of a recently introduced low-cost particle monitor (DC1700 Dylos Air Quality Monitor) for sensing atmospheric PM2.5 requires comparison with data obtained using a certified method for PM2.5 based on appropriate atmospheric observations. Full-year measurements of atmospheric aerosols were taken in Nagoya, Japan during March 2017-March 2018 using the DC1700 to measure the particle number concentrations of >0.5 and >2.5 μm diameter particles and to measure the PM2.5 mass concentration (Mdry, PM2.5) using an automated β attenuation mass monitor (PM712). The number-size distribution was measured using an optical particle counter (KC01D). The dried mass concentration of 0.5-2.5 μm particles (Mdry, 0.5-2.5) was estimated from the ambient relative humidity and the DC1700 number concentration. The values of Mdry, 0.5-2.5 were invariably less than those of Mdry, PM2.5. The coefficient of determination and slope of Mdry, 0.5-2.5 to Mdry, PM2.5 for the year were, respectively, 0.68 and 0.40. Slope values changed seasonally from 0.24 in July and August 2017 to 0.55 in May and April 2017. Light absorbing particles, smaller-fine particles, and the estimation method of Mdry, 0.5-2.5 were inferred as causes of the difference between Mdry, 0.5-2.5 and Mdry, PM2.5. Especially, we estimated a large contribution (ca. 54% underestimation of Mdry, 0.5-2.5 into Mdry, PM2.5) of particles smaller than the minimum detection diameter of DC1700. The seasonal variation of Mdry, 0.5-2.5/Mdry, PM2.5 was related to the volume fraction of particles smaller than 0.5 μm. Good correlation of Mdry, 0.5-2.5 to Mdry, PM2.5 suggests that data obtained using DC1700 with a correction factor are useful as a rough proxy of atmospheric PM2.5 within a season. However, precise estimation of PM2.5 from the DC1700 number concentrations should include appropriate corrections of the size distribution, not only hygroscopicity.

Background Seasonal variation and regional heterogeneity have been observed in the estimated effect of fine particulate matter (PM2.5) mass on mortality. Differences in the chemical compositions of PM2.5 may cause this variation. We investigated the association of the daily concentration of PM2.5 components with mortality in Nagoya, Japan. Methods We combined daily mortality counts for all residents aged 65 years and older with concentration data for PM2.5 mass and components in Nagoya from April 2003 to December 2007. A time-stratified case-crossover design was used to examine the association of daily mortality with PM2.5 mass and each component (chloride, nitrate, sulfate, sodium, potassium, calcium, magnesium, ammonium, elemental carbon [EC], and organic carbon [OC]). Results We found a stronger association between mortality and PM2.5 mass in transitional seasons. In analysis for each PM2.5 component, sulfate, nitrate, chloride, ammonium, potassium, EC, and OC were significantly associated with mortality in a single-pollutant model. In a multi-pollutant model, an interquartile range increase in the concentration of sulfate was marginally associated with an increase in all-cause mortality of 2.1% (95% confidence interval, -0.1 to 4.4). Conclusions These findings suggest that some specific PM components have a more hazardous effect than others and contribute to seasonal variation in the health effects of PM2.5.

In May 2003, high concentrations of organic carbon (OC) in PM2.5 were measured in Nagoya, a representative metropolitan area in Japan. To investigate the influence of possible forest fires on PM2.5 in Japan via long-range aerosol transport, the radiocarbon (14C) concentrations of PM2.5 samples from April 2003 to March 2004 were measured. 14C concentrations in total carbon (TC) from May to early June showed higher values than those in other periods. The OC/elemental carbon (EC) ratios from May to early June were also significantly higher than the ones in other periods. In addition, OC concentrations from May to early June were typically high. These results indicate that the abundant OC fraction from May to early June in Nagoya consisted predominantly of contemporary carbon. Furthermore, simulations of diffusion and transport of organic matter (OM) in East Asia showed that abundant OM originating from East Siberia spread over East Asia and Japan in May and early June. Backward air mass trajectories from this time frame indicate that the air mass in Nagoya likely first passed through East Siberia where fire events were prevalent. However, the backward trajectories showed that the air mass after early June did not originate mainly from Siberia, and correspondingly, the 14C and OC concentrations showed lower values than those from May to early June. Therefore, the authors conclude that contemporary carbon originating from the forest fire in East Siberia was transported to Nagoya, where it significantly contributed to the high observed concentrations of both OC and 14C.

We found a significant geographic gradient (longitudinal and latitudinal) in the sulfate (SO42−) concentrations measured at multiple sites over the East Asian Pacific Rim region. Furthermore, the observed gradient was well reproduced by a regional chemical transport model. The observed and modeled SO42− concentrations were higher at the sites closer to the Asian continent. The concentrations of SO42− from China as calculated by the model also showed the fundamental features of the longitudinal/latitudinal gradient. The proportional contribution of Chinese SO42− to the total in Japan throughout the year was above 50–70% in the control case, using data for Chinese sulfur dioxide (SO2) emission from the Regional Emission Inventory in Asia (40–60% in the low Chinese emissions case, using Chinese SO2 emissions data from the State Environmental Protection Administration of China), with a winter maximum of approximately 65–80%, although the actual concentrations of SO42− from China were highest in summer. The multiple-site measurements and the model analysis strongly suggest that the SO42− concentrations in Japan were influenced by the outflow from the Asian continent, and this influence was greatest in the areas closer to the Asian continent. In contrast, we found no longitudinal/latitudinal gradient in SO2 concentrations; instead SO2 concentrations were significantly correlated with local SO2 emissions. Our results show that large amounts of particulate sulfate are transported over long distances from the East Asian Pacific Rim region, and consequently the SO42− concentrations in Japan are controlled by the transboundary outflow from the Asian continent.

We evaluated the applicability of a simple passive sampling method to quantify HNO3(g) in ambient air. The method has the advantages of not only ease of operation but also low cost. A sampling velocity of 214 m day−1 was determined based on the concentration of HNO3(g) measured by the four-stage filter-pack method at nine sites located within a 250 × 250-km area in Japan. This sampling velocity was applied at sites located outside of area to verify the applicability and accuracy of the simple passive sampling method. The variation in the results for the application of the sampling velocity ranged from 0.39 to 0.95. The simple passive sampling method should be applied to sites with different meteorological conditions, and the obtained data should be used to obtain more significant information and/or to indicate the need for further developments in the methodology.

We reviewed the data on the atmospheric SO2 and SO42− concentrations measured in a survey conducted by the Japan Environmental Laboratories Association (JELA). The data collected in the Tokai–Kinki–Hokuriku branch, which covers a 250-km×250-km region, were reviewed as one of the activities of the Tokai–Kinki–Hokuriku branch. The atmospheric SO2 and SO42− concentrations were measured using the four-stage filter-pack method. The data collected for 3 years (Campaign III by JELA) were reviewed. The SO2 concentration was affected by the eruption episode of the Miyakejima Volcano. In contrast, the SO42− concentration (annual mean in 1999: 35.0 nmol m−3) was scarcely affected by the eruption episode. The SO42− concentration level was within or slightly higher than the level of the European Monitoring Evaluation Program (EMEP) (lower than 30 nmol m−3) and that of mid-latitude North America. The particularity of the site would be potentially clarified by the relationship of the SO42−/(SO2+SO42−) ratio with the SO2 concentration and the correlation with the results of the Community Multi-scale Air Quality (CMAQ). The peculiar pattern of the monthly variation of the SO2 concentration clarified the particularity of the site, which was deeply associated to the spatial relationship with an express highway with heavy traffic and the wind rose.

The development of new and useful pharmaceutical drugs is essential in order to improve the quality of drug therapeutics. Clinical trials play a central role in drug development. Over time, the clinical trial infrastructure has improved and is now integrating the contribution of clinical research coordinators (CRC). Nevertheless, the attitude of doctors towards clinical trials still favors conventional/historical methodologies. In the present study, we explored the view of doctors towards clinical trials for drug development, in order to improve communication among participants, sponsors, and investigators. A questionnaire was designed for this pilot study. The questionnaire included general attitudes, difficult points, the benefit of doctors in participating as investigators, special attention requirements, and the expected role of CRC in clinical trials for drug approval. In addition, the appropriate use of the outpatient clinic was examined. The questionnaire was provided to doctors in each department of Tokushima University Hospital in 2000 and 2004. Because of the small number of subjects included in this pilot study, no statistical analysis is presented. A total of 89 (81%) and62 (56%) doctors among 110 responded to the survey in 2000 and 2004, respectively. Inquiries about the familiarity of the physicians with clinical trials for drug approval revealed that 84% in 2000 and 66% in 2004 were aware of such trials. The attitude towards participating as investigators in the clinical trials was favorable, with a response of 66% in 2000 and 58% in 2004. Patients’ refusal and the informed consent process were considered difficult areas by many doctors. Expected roles of CRC included activities based on the nurse’s specialty. Although many doctors agreed to take care of the study participants separately from the clinical practice, they lacked the time to do so. In spite of the doctors’ workload reduction by introduction of the CRC concept, their views regarding clinical trials for drug approval remain conventional. Further refinement in the support process by CRC should be considered in our hospital, and the views of the doctors should be investigated in a larger study, in order to promote clinical trials for drug approval in Japan.

Background: Clinical trials leading to regulatory approval, or registration trials, play a central role in the development of drugs and medical devices. The contribution of support staff, such as the clinical research coordinator (CRC) and administrative officers, in registration trials is now widely recognized. Attending to serious adverse events is an important duty of the CRC and investigators alike, and managing these complications and compensation constitutes a key responsibility. We retrospectively examined the frequency of serious adverse events and compensation events reported from 2007 through 2011 at Tokushima University Hospital, an academic hospital in rural Japan. We present herein the results of our analysis. Results: Over the five-year period, 284 subjects participating in 106 registration trials experienced a total of 43 serious adverse events, and eight compensation events were documented. Among the serious adverse events, 35 (81.4%) were considered not related to the investigational drug, and 17 (39.5%) resulted in withdrawal of the study drug. Patients with malignant diseases experienced serious adverse events significantly more frequently compared to those with non-malignant diseases (28.3% versus 8.2%, respectively; P < 0.01). Conclusions: The CRC should be vigilant for serious adverse events in oncology clinical trials due to the generally higher frequency of these complications in subjects with malignancy. However, on an individual basis, the CRC may be seldom involved in the process for compensating serious adverse events. Therefore, the CRC’s ability to share such experiences may serve as an opportunity for educating clinical trial support staff at the study site as well as those at other sites. However, further study is warranted to determine the role of the clinical trial support staff in optimizing methods for managing adverse events requiring compensation in registration trials.

application/pdf, text/plain, 学術雑誌論文, A proteoglycan (PG) monomer is a macromolecule consisting of one or more glycosaminoglycan (GAG) chains attached to a core protein. PGs have signaling roles and modulatory functions in the extracellular matrix and at the cell surface. To elucidate the functions of higher-order PG structures, pseudoPGs that imitate the PG structure were prepared to develop probes and affinity adsorbents. Poly-L-lysine (PLL) or polyacrylamide (PAA) was coupled with various GAGs, then biotinylated, and the remaining amino groups were blocked to obtain the pseudoPG probes, biotinyl PLL (BPL)- or PAA (BPA)-GAGs. Lactoferrin exhibited 30-times higher affinity toward BPL-heparin than the conventional single-strand probe, biotin-hydrazide-heparin.Heparin-PLL was immobilized on a formyl-Sepharose and compared with the Hep-Sepharose in which heparin was directly immobilized to amino-Sepharose. Screening for ligands in normal rat brain revealed several proteins that specifically bound to either of the two adsorbents, indicating that the heparin-binding proteins exhibit specific recognition depending on the higher-order structure of the PG., online first / Received: 28 July 2008 / Revised: 30 September 2008 / Accepted: 8 December 2008 / Published online: 21 February 2009, The original publication is available at www.springerlink.com