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Sacubitril/valsartan (sac/val) was launched in China in 2018; however, the adoption of sac/val in real-world clinical practice has yet to be described. This study aimed to analyze real-world treatment patterns of sac/val using data from 3 tertiary hospitals in China. A non-interventional, retrospective cohort study of patients with Heart failure (HF) prescribed sac/val from 3 tertiary hospitals in China between January 1, 2018 and June 30, 2020 was conducted. The analysis included sac/val dose titration patterns and persistence during 6 months post-index. A total of 267 patients were included, with a mean age of 63.9 ± 13.1 years. At index, 27% of patients were prescribed sac/val 12/13 mg b.i.d., 63.7% were prescribed 24/26 mg b.i.d., 4.5% were prescribed the target dose of 49/51 mg b.i.d., and 4.8% were not prescribed according to the recommended dose. During the 6 months post-index, 8.3% of patients had only 1 dose titration record. Good therapeutic persistence was observed across sac/val doses, and only 15.7% of patients discontinued sac/val during the 6 months post-index. In China, the majority of patients prescribed sac/val are not initiated on the recommended dose nor up-titrated according to drug instruction. Notably, good persistence with sac/val is observed in the real-world cohort study.

This paper describes orthogonal experiments to investigat the effects of content of fly ash and slag, sol ratio, modulus of sodium silicate and expander on the compressive strength and shrinkage of alkali activated low-carbon green concrete (AAGC) of different ages. The microstructures and hydration product compositions of AAGC with different proportions were further studied by Scanning Electron Microscopy (SEM), X-ray Diffraction (XRD) and Mercury Intrusion Porosimetry (MIP). The results show that with an increase of fly ash content, the compressive strength of AAGC gradually decreases, the decline of compressive strength at 28 d is smaller than that of 7 d, and the shrinkage strain gradually increases at 28 d. As the sol ratio increases, the compressive strength increases first and then decreases. When the sol ratio is 0.42, the compressive strength is maximal at 28 d; the same is true for compressive strength at 7 d. Additionally, an increase of sol ratio can reduce the shrinkage strain at 28 d. Finally, when the sol ratio was 0.46, the shrinkage decreased by 30.5% compared with 0.40 at 28 d. As the modulus of sodium silicate (Ms) increases, the compressive strength first increases and then decreases. When Ms is 1.4, the compressive strength reaches the maximum. As Ms increases, the shrinkage strain decreases first and then increases at 28 d. When Ms is 1.0, the shrinkage strain is the maximum at 28 d. Finally, with an increase in the content of expander, the compressive strength decreases at 7 d and 28 d, and the shrinkage strain decreases at 28 d. The shrinkage strain at 28 d is the minimum with 9% content. AAGC mixed with a small amount of fly ash and expander has more hydration products and significantly reduced cracks. In addition, the proportion of small hole volume of AAGC increases, while the proportion of large hole volume decreases. AAGC mixed with fly ash and slag without expander has more unhydrated particles and its structure is loose.

Purpose Despite the long-standing demand for research on dynamic lifecycle assessment (LCA) for policymaking, only a few studies have addressed this subject in conjunction with other systems thinking disciplines, such as energy systems models (ESMs) and integrated assessment models (IAMs), which have achieved tremendous success in assessing climate policies in future scenarios. This study explains our methodological advances in the global application of LCA incorporated in IAMs, specifically dose-response functions, models, and future scenarios. Methods We investigate the application of the lifecycle impact assessment method based on endpoint modeling (LIME), developed under the current environmental situation in Japan and globally, to be consistent and compatible with our IAM, which comprises three resource balance models and a simplified climate model. The IAM endogenously generates most inventories consistent with energy scenarios and climate policies linked with the applied LIME. The IAM and LIME are formulated to minimize the discounted sum of supplying the cost of resources over their lifecycles (i.e., from development to end-of-life) to generate time evolutions for the endpoint impacts over this century on a global scale with/without the 2-degree Celsius (2DC) target in a 100% renewable energy scenario. Results and discussion Unlike existing LCA+ESM/IAM studies, which focus on power generation technologies and related (in)direct embedded energy consumption on a lifecycle basis, our model’s expansion to mineral and biomass resources, in addition to energy, has the following novel results: (1) The following inventories in the 2DC target are generally lower than those in business as usual (BAU): temperature and sea level rise, natural resource, and waste discharge; further, SOx emissions are significantly reduced by reducing coal production while increasing forestry. (2) The environmental impacts on the four endpoints of minerals, land use, and land-use change, with the exclusion of energy-related impacts, are significantly larger than those related to energy. (3) Finally, by ensuring inventory reduction, the 2DC target scenario can reduce overall endpoint impacts (by maximum around 20%), except the impacts on biodiversity resulting from forestry expansion to meet predetermined targets. Conclusions Unlike mainstream IAM analyses, we incorporate LIME, instead of energy- and biomass-related resource and climate change impacts alone; our model thus provides a comprehensive perspective on various natural resources and their impacts on a lifecycle basis. The exclusion of the weighting process and retention of the four endpoints enable us to easily interpret the results. Further, this application of LCA to IAM enables us to further understand and assess natural resources and environmental impacts.

Management of the negative environmental impact of pesticides used in paddy fields requires the quantification of the emissions reaching relevant environmental compartments and the determination of the factors that influence such emissions. The present study is the first to develop a simulation model for estimating the fractions emitted to the air (fair), surface water (fsw), and the fractions that leach vertically (fvl) of pesticides applied in paddy fields for life cycle assessments (LCA). The emission quantification methods are based on the properties of the active ingredients of the pesticides and management aspects such as formulations (granular or liquid) and the water-holding period following application. The emission fractions of 37 pesticides used commonly in Japan were estimated using the presented model. A sensitivity analysis was conducted by adjusting parameters applied in the model to reveal their influence on the emission fractions. The parameters influencing fair included the formulation applied, while the water-holding period and waterproofing of the levee influenced fsw regardless of the formulation adopted, suggesting that local management could effectively reduce emissions to surface water. In addition, soil organic carbon content influenced fvl greatly, suggesting considerable regional variation in the emission factor. The developed model is expected to greatly improve the realism of impact assessment of pesticide in LCAs for paddy rice cultivation, considering it fills a gap in the fate model used in LCAs to estimate pesticide emissions to air, surface water, and soil in paddy fields.

Bladder cancer is a malignant tumor characterized by high recurrence and persistence due to the limited therapies that are currently available. Hirudin exerts a strong anticancer effect on several tumors. Thus, it is urgent to explore the biological function of hirudin in bladder cancer and the role of bladder cancer-derived exosomes in tumor inhibition.First, a network pharmacology analysis was performed to explore the relationships among hirudin, bladder cancer, and exosomes. Then, the effects of hirudin were examined by CCK-8 assay, flow cytometry, Transwell assay, and tumorigenic ability experiments in vitro. Exosomes derived from cells were identified with transmission electron microscopy, fluorescence labeling, and Western blotting and collected for further microarray analysis. Only CDC6 expression and mRNA abundance in hirudin-treated cells and exosomes was subjected to further validation using quantitative PCR and Western blotting.Through network analysis, we found that hirudin affected bladder cancer, and this effect was related to exosomes. Our studies verified the effects of hirudin by revealing that hirudin inhibits malignant processes of bladder cancer cells in vitro, such as invasion, metastasis, and apoptosis. Similarly, the oncogenic effects of bladder cancer-derived exosomes were successfully isolated and identified. Via microarray assessment of the exosomes, we identified 600 differential mRNAs, of which the expression of the core target CDC6 was found to be significantly different in both The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. We further confirmed that hirudin suppresses CDC6 expression mRNA abundance in both cells and exosomes.Hirudin was able to decrease the expression of CDC6 in bladder cancer cells and exosomes, which effectively repressed the malignant processes of bladder cancer cells.

Frequent updates on the evaluation of health risks associated with climate change are made. The existing health damage factors associated with CO2 emission are based on the findings compiled by the 2004 World Health Organization (WHO) report. An updated version of the 2014 WHO report is now available, and based on its contents, this study aimed to estimate relative risk (RR) and calculate health damage factors for each shared socioeconomic pathway (SSP) scenario. Damage factors (DALY/kg-CO2) were calculated as increment of temperature (°C/kg) multiplied by increment of RR per °C, base mortality rate without climate change (−), population, and disability-adjusted life year (DALY) per case of death. RRs and base mortality rates were calculated for each SSP scenario. RRs by SSP scenario were estimated based on the RRs of three economic growth scenarios (high growth, base case, and low growth), which were calculated based on the results of the 2014 WHO report. Base mortality rates for each SSP scenario were calculated based on its relationship with gross domestic product per capita. In relation to undernutrition, diarrhea, malaria, dengue, heat stress, and coastal floods, the health damage factors (DALY/kg) for the SSP1, SSP2, and SSP3 scenarios were 1.3 × 10−6, 1.5 × 10−6, and 2.0 × 10−6, respectively. During a 100-year evaluation period, the damage factors obtained in the current study were 3–5 times higher than those in previous studies mainly because relative risk per degree Celsius (RR/°C) in the 2014 WHO report was larger than that in the 2004 WHO report. When RRs were estimated for each SSP scenario, the RR of SSP3 (with higher base mortality) was relatively low, particularly in case of undernutrition. Therefore, differences in the damage factors between the scenarios were more likely smaller than before when a single RR was used. New health damage factors for the SSP1, SSP2, and SSP3 scenarios were estimated using an updated RR calculated based on the 2014 WHO report. These factors can be further updated in the future using RRs obtained from upcoming researches on climate-related health impact that were based on SSP scenarios.

There has been an increasing number of studies on species extinction because of global warming based on estimations of changes in species distributions. Life cycle impact assessment methods do not have a biodiversity damage factor for global warming that uses the extinction risk index. In this study, a method for determining the extinction risks of individual species per unit CO2 emission was proposed and test calculations of the extinction risks of 216 species of Japanese vascular plants were performed. We also examined the possibility of determining local and global extinction risk factors using this method. This method uses the Expected Increase in the Number of Extinction Species (EINES), which is defined as the inverse of the time to extinction, as the extinction risk index. Procedures for determining the extinction risks of individual species per unit CO2 emission (EINES/species/kg) are as follows. First, based on the base scenario of CO2 emission, a niche-based species distribution model is used to estimate species distribution areas in 2000 and 2100 and calculate the distribution area decrease over 100 years. The number of years before the zero distribution area is then determined by assuming that the decrease is constant. Extinction risk is defined as the inverse of this time. The final step is to determine the extinction risk at specific CO2 emissions in addition to the base emission scenario and divide the difference in the extinction risk by the additional amount of CO2 emissions. The distribution areas of 216 species of Japanese vascular plants having southern distribution limits were estimated to decrease by 40–85% in 100 years. The accuracy of the estimation was sufficient according to the value of area under the curve (AUC). Considering climate models and migration conditions, the extinction risk per unit CO2 emission was estimated between −0.6 × 10−18 and 4.7 × 10−18 (EINES/species/kg). We converted the normalization values of the extinction risk of Japan for the 216 species to compare impact of land use changes and waste processing with that of global warming on the species. We found that global warming has smaller impact compared with land use changes and larger impact compared with waste processing. A method for estimating the extinction risks of species per unit CO2 emission was proposed, and it can be used to determine the local and global extinction risk factors of CO2.

Air pollutants such as tropospheric ozone and PM2.5 travel through large areas. The damage factors (DFs) presented by existing researches in life cycle impact assessment do not take into consideration transboundary movement. A previous study used a global chemistry transport model (CTM), to develop health damage factors for ten different regions around the world by considering the transboundary movement of PM2.5. Under the same assessment procedure, this research is designed to calculate the ozone DFs by region and to find the effects of wide range movement on the DFs. The DFs by regions are defined as changes in disability-adjusted life years (DALYs) derived from changes in tropospheric ozone concentration around the world which is induced by an increase in emissions of the unit amount of nitrogen oxides (NOx) and non-methane volatile organic compounds (NMVOC). DFs for ten regions are calculated as follows. Firstly, the concentration change of worldwide ozone caused by a change in emission of a substance from one region is estimated with a global scale CTM for both NOx and NMVOC. Secondly, DALY changes on the world due to a change in concentration of ozone are estimated by using population data and epidemiological concentration-response functions for mortality and morbidity. Finally, the above calculations are done for all targeted ten regions. DFs of NOx and NMVOC for ten regions were calculated as 0.3–4.2 × 10−5 DALY/kg and 0.2–5.6 × 10−6 DALY/kg, respectively. It was found DFs might be underestimated around 10 to 70 % by region if the transboundary movement is not taken into consideration. In many regions in the northern hemisphere, about 60 % of damage occurs outside the emission area, which is larger than that of southern hemispheric regions due to a larger population exposed to downwind places. In regions of China and India, however, the influence on other regions accounted for only 10 % because these regions involve larger influences in the source region. The impact of NO titration effect can be seen in cold seasons in many regions, but it was found that the effect is remarkable on an annual average only in Europe, a cold region with large emissions. The human health DFs of NOx and NMVOC considering effects of transboundary movement of tropospheric ozone are estimated for ten regions by using a global CTM. As a future work, it is important to show the interannual sensitivity of the DFs through chronological assessments.

The area of land transformed by the mining of mineral resources greatly varies depending on the type of mineral deposit and mining methods used. Existing factors for the land area transformed per unit of ore mined (land transformation factor) only consider differences in mining methods. In this study, key parameters impacting the area of land transformed were determined and taken into account for nickel with the objective of developing a method for efficiently estimating land transformation factors for mines. The land transformation factor (m2/t) was defined as the land area transformed to produce 1 t of crude nickel ore, nickel metal (grade >99 %), or ferronickel (grade 20 %). Formulae for calculating the land transformation factor that considered parameters, such as the specific gravity of ores and depth of mining, were built by first classifying mines into three types: laterite ore surface mines, sulfide ore surface mines, and sulfide ore underground mines. Uncertainty analysis for the land transformation factor for each type of mine was conducted, and the key parameters affecting results were identified. Finally, the land transformation factors for 38 mines were calculated using the proposed method. Land transformation factors for the three types of mines showed that for both surface and underground mines, the values were smaller than the values reported in previous research that were calculated using mining area and production data for a single year. This difference was due to our use of a method assuming the area at the point of maximum extraction depth and maximum overburden dump height. For surface mining, the stripping ratio and ore grade were determined to be key parameters that combined to contribute approximately 80 % of the uncertainty for the land transformation factors of nickel metal. For underground mining, the ore grade and backfilling ratio were determined as the key parameters. The assessment results for mines showed that for surface mining methods, differences in the ore grade and stripping ratio could result in the land transformation factor differing by a maximum of a factor of 10 between mines. These results suggested that the proposed method could efficiently determine the difference between mines. The proposed method, taking into account key parameters for each mine type, provided a good base for estimating land transformation factors for nickel mining for countries or regions.

Global warming is exerting a damaging effect on human health. This damage is not only influenced by future climate conditions but also projected economic development and population growth. That being said, there are no health damage factors related to CO2 emissions which take into account future socioeconomic scenarios in life cycle impact assessment (LCIA). Thus, the purpose of the current research is to calculate human health damage factors based on the Special Report on Emission Scenarios (SRESs) developed by the Intergovernmental Panel on Climate Change (IPCC). The procedure used to calculate the SRES-based damage factors is as follows. First, a framework was developed to calculate damage factors based on multiple parameters: rise in temperature, relative risk increase, mortality rate increase, rise in number of deaths, and disability-adjusted life year (DALY) increase. Secondly, these parameters were calculated for each individual SRES based on the relationship among the parameters and CO2 emissions, GDP, and population values of each scenario. Finally, the damage factor for each SRES was calculated by multiplying all the parameters that had been calculated based on the CO2 emission, GDP, and population data in the corresponding scenarios. Using this method, the human health damage factors for four SRESs (A1B, A2, B1, and B2) were calculated. The damage factors consisted of six different items: malaria, diarrhea, cardiovascular disease, malnutrition, coastal flooding, and inland flooding. The calculated results by scenario were 2.0 × 10−7, 6.2 × 10−7, 2.1 × 10−7, and 4.2 × 10−7 DALY/kg CO2, respectively. The damage caused by malnutrition is the greatest, followed by diarrhea. Regions of Southeast Asia, Africa, and the Middle East showed the highest damages due to their high damage from malnutrition and diarrhea. With regard to the differences among the four damage factors, the difference between the projected future mortality rate and DALY per death based on the future GDP per capita is greater than the difference between the increases in temperature among scenarios dependent on future CO2 emission. The human health damage factors related to CO2 emissions for four SRESs were estimated. As a result of differences between future socioeconomic scenarios, the largest amount of damage per CO2 emission unit was three times greater than the smallest amount. Therefore, sensitive analysis is highly recommended when seeking to compare damage caused by global warming and other impact categories.

Purpose Health damage from ambient fine particulate matter (PM2.5) shows large regional variations and can have an impact on a global scale due to its transboundary movement. However, existing damage factors (DFs) for human health in life cycle assessments (LCA) are calculated only for a few limited regions based on various regional chemical transport models (CTMs). The aim of this research is to estimate the human health DFs of PM2.5 originating from ten different regions of the world by using one global CTM.

Soil quality varies greatly with the management of agricultural land such as the application of fertilizer. Quantifying the impact on soil quality at a management level has been recognized as an urgent issue in life cycle assessment (LCA). This study is the first to estimate characterization factors for land occupation under different soil type, fertilizer type, and application period, which is defined as 1 (the optimum quality of a soil) minus the soil quality index (SQI). The SQI for paddy field of Japan are estimated as follows. First, SQI at each site per year was calculated by considering five soil functions and 17 soil properties collected from a long-term soil monitoring database. Then, time-dependent SQIs over 20 years were then estimated using a statistical model for different combinations of three soil types and five fertilizer types (chemical fertilizers, chemical fertilizers with rice straw, chemical fertilizers with rice straw compost, rice straw, and rice straw compost). The results showed that the SQI is influenced by both soil type and fertilizer type. For fertilizer type, continuous use of chemical fertilizers lowered the SQI. The addition of rice straw to chemical fertilizers mitigated the decrease of the SQI, but the addition of more compost increased the SQI. Longer application periods led to larger differences between the SQI of each fertilizer type, which suggests that it is important to calculate time-dependent characterization factors. The introduction of soil quality impact assessment based on the new characterization factors into an LCA of agricultural system is expected to improve to capture the difference among managements of agricultural land.

This study evaluates the potential environmental impacts of deployment of carbon capture and storage (CCS) for pulverized coal power plants in Japan by using LCA, focusing on selected environmental impact categories including global warming. The LIME (Life-cycle impact assessment method based on endpoint modeling) method is used to assess and compare the environmental impacts between three cases, a typical ultra-supercritical pulverized coal-fired power generation system (case 1) and two CCS systems, one comprised of CO2 capture with monoethanolamine (MEA) solvent, compression, seafloor pipeline transportation and below seafloor storage (case 2) and the other case was the same as case 2 except that CO2 transportation by ship was used (case 3). The life cycle GHG emissions for case 1 were 0.89 kg-CO2 (eq.)/kWh. GHG emissions for case 2 and case 3 were 20% and 29%, respectively, of emissions for case 1. However non-GHG emissions increased for case 2 and case 3, especially emissions of NH3 from the CO2 capture process and ethylene oxide from the MEA production process. The results for the 3 cases at the endpoint level, which estimated the damage on four safeguard subjects (human health, social asset, biodiversity and primary production), showed that for case 2 and 3, damage to biodiversity and primary productivity increase by 40% respectively caused by increased feed coal to meet energy consumption on CO2 capture process while the damage to human health decreased by approximately 60% due to the large reduction in CO2 emissions. The increased damage to social assets caused by NH3 emission and increased energy consumption due to CCS is similar with the reduction in damage due to reduction of CO2 emissions.

Impacts on ecosystem services that are related to agricultural land use greatly differ depending on management practices employed. This study aimed to reveal issues associated with evaluating ecosystem services related to land use at the management level during life cycle assessment (LCA) and to consider future challenges. Firstly, a relationship between agricultural ecosystem services and management practices was outlined. Then, a survey was performed to disclose the current status of assessment of impact of land use in agricultural LCA case studies that compared between different management practices. In addition, this study also investigated how management practices have been differently considered by factors that characterize ecosystem services that are related to land use. The results show that the number of agricultural LCA cases where land use impacts instead of land areas were assessed was still small. The results of limited LCA case studies, which using factors could differentiate between various management practices, suggest that although organic farming methods have been employed over large land areas, lower impact may be caused by agricultural land use. For factors developed in existing research, services related to soil quality, and some of the regulatory services were considered, those unique to agriculture were missing. Although most of factors were calculated at levels of intensity or land use type, some of them were based on a process-based model that could consider management practices. In the future, factors that characterize the impacts of land use on ecosystem services, such as carbon storage and erosion prevention, will need to be calculated at the management level. For ecosystem services, such as habitat conservation and pollination, further efforts in accumulating evaluation case studies that collect and accumulate foreground data are important.