Three methods to optimise polymyxin B dosing using estimated AUC after first dose: validation with the data generated by Monte Carlo simulation.

To achieve the AUC-guided dosing, we proposed three methods to estimate polymyxin B AUC across 24 h at steady state (AUCSS,24h) using limited concentrations after its first dose.Monte Carlo simulation based on a well-established population PK model was performed to generate the PK profiles of 1000 patients with normal or abnormal renal function. Polymyxin B AUCSS,24h was estimated for each subject using three methods (two-point PK approach, three-point PK approach, and four-point PK approach) based on limited concentration data in its first dose and compared with the actual AUC at steady state calculated using the linear-trapezoidal formula.In patients with normal renal function, the mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -8.73%, 1.37%, and -0.48%, respectively. The corresponding value was -11.15%, 1.99%, and -0.28% in patients with renal impairment, respectively. The largest mean bias of two-point PK approach, three-point PK approach, and four-point PK approach was -12.63%, -6.47%, and -0.54% when the sampling time shifted.The Excel calculators designed based on the three methods can be potentially used to optimise the dosing regimen of polymyxin B in the clinic.

Distribution, mobilization, risk assessment and source identification of heavy metals and nutrients in surface sediments of three urban-rural rivers after long-term water pollution treatment.

Sediments are critical pollution carriers in urban-rural rivers, which can threaten the water quality of the river and downstream lakes for a long time. However, it is still not clear whether conventional water pollution treatments could abate sediment pollution or not. In this study, heavy metals (HMs) and nutrient salts in the surface sediments and overlying water were investigated after decades' water pollution treatment in three urban-rural rivers. HM speciation was determined by the sequential extraction; diffusion fluxes were estimated using Fick's first law; HM ecological risk and nutrient pollution were evaluated; and pollution sources were identified by statistical analysis and GIS. The results showed that the HMs and nutrients were extremely serious in the urban regions. The accumulation level of Pb, Cu and Cd in the sediments of the three rivers were all much higher than the soil background value, and the labile fractions accounted for high proportions (57 % for Pb, 55 % for Cu and 43 % for Cd), which could be easily eluate from the sediments and caused hazards to the aquatic environment. The sediment diffusion fluxes of HMs and ammonia nitrogen were mostly positive, which indicated these sites currently released these pollutants from sediment to overlying water. Cd, Pb, Cu and Cr may mainly originate from industrial discharge and domestic sewage, while Cr was also greatly affected by crustal weathering; nutrient pollution may originate from agricultural activities and domestic sewage. Our study demonstrated that after decades' conventional water treatment in these rivers, the sediment pollution was still in a serious level with high ecological risk, and Cd was the dominant pollutant. At present, the external point source pollution has been effectively controlled, thus, the in-depth understanding of the sediment pollution characteristics after long-term water treatment could provide a scientific basis for the accurate elimination of river pollution.

The clean energy development path and sustainable development of the ecological environment driven by big data for mining projects.

Clean energy is urgently needed to realize mining projects' sustainable development (SD). This study aims to discuss the clean energy development path and the related issues of SD in the ecological environment driven by big data for mining projects. This study adopts a comprehensive research approach, including a literature review, case analysis, and model construction. Firstly, an in-depth literature review of the development status of clean energy is carried out, and the existing research results and technology applications are explored. Secondly, some typical mining projects are selected as cases to discuss the practice and effect of their clean energy application. Finally, the corresponding clean energy development path and the SD analysis model of the ecological environment are constructed based on big data technology to evaluate the feasibility and potential benefits of promoting and applying clean energy in mining projects. (1) It is observed that under different Gross Domestic Product (GDP) growth rates, the new and cumulative installed capacities of wind energy show an increasing trend. In 2022, under the low GDP growth rate, the cumulative installed capacity of global wind energy was 370.60 Gigawatt (GW), and the new installed capacity was 45 GW. With the high GDP growth rate, the cumulative and new installed capacities were 367.83 GW and 46 GW. As the economy grows, new wind energy capacity is expected to increase significantly by 2030. In 2046, 2047, and 2050, carbon dioxide (CO2) emissions reductions are projected to be 8183.35, 8539.22, and 9842.73 Million tons (Mt) (low scenario), 8750.68, 9087.16, and 10,468.75 Mt (medium scenario), and 9083.03, 9458.86, and 10,879.58 Mt (high scenario). By 2060, it is expected that CO2 emissions reduction will continue to increase. (2) The proposed clean energy development path model has achieved a good effect. Through this study, it is hoped to provide empirical support and decision-making reference for the development of mining projects in clean energy, and promote the SD of the mining industry, thus achieving a win-win situation of economic and ecological benefits. This is of great significance for protecting the ecological environment and realizing the sustainable utilization of resources.

Immunosuppressive therapy for progressive idiopathic membranous nephropathy: a cost-effectiveness analysis in China.

BACKGROUND: This study aims to evaluate the cost-effectiveness of immunosuppressive therapy for patients with progressive idiopathic membranous nephropathy (IMN) from the Chinese healthcare system perspective. METHODS: To estimate the cost-effectiveness of four regimens namely cyclophosphamide, cyclosporine, rituximab and tacrolimus-rituximab in treatment of IMN recommended by the updated Kidney Disease: Improving Global Outcomes (KDIGO) guideline 2021, a Markov model with five discrete states (active disease, remission, dialysis, kidney transplant and death) based on IMN patients aged 50 or above over a 30-years time horizon was constructed. Total costs were imputed from the Chinese healthcare system perspective, and health outcomes were converted into quality-adjusted life years (QALYs). The incremental cost-effectiveness ratio (ICER) was used to describe the results. The willingness-to-pay (WTP) threshold was set at $12,044 (China's 2021 Gross Domestic Product per capita). Sensitivity analyses were performed to test the uncertainties of the results. RESULT: Compared with cyclophosphamide, both cyclosporine (incremental cost $28,337.09, incremental QALY-1.63) and tacrolimus-rituximab (incremental cost $28,324.13, incremental QALY -0.46) were considered at strictly dominated for their negative values in QALYs, and the ICER value of rituximab was positive (incremental cost $9,162.19, incremental QALY 0.44). Since the ICER of rituximab exceeds the pre-determined threshold, cyclophosphamide was likely to be the best choice for the treatment of IMN within the acceptable threshold range. The results of the sensitivity analysis revealed that the model outcome was mostly affected by the probability of remission in rituximab. In a probabilistic sensitivity analysis, cyclophosphamide had 62.4% probability of being cost-effective compared with other regimens when the WTP was $12,044 per QALY. When WTP exceeded $18,300, rituximab was more cost-effective than cyclophosphamide. CONCLUSION: Compared with cyclosporine, rituximab and tacrolimus-rituximab, our model results indicated that cyclophosphamide represented the most cost-effective regimen for patients with progressive IMN in China.

How to Achieve Carbon Neutrality in Cities? Evidence from China's Low-Carbon Cities Development.

Low-carbon city pilots (LCCP) is a key policy for realizing emission peak and carbon neutrality in China, using China's samples from 280 towns from 2006 to 2016. The article utilizes PSM-DID, mediated effects, and moderating effects approach for validating a CO2 reduction effect, mechanisms, and synergistic elements of LCCP. The regression outcomes suggest that (1) LCCP significantly decreases CO2 emissions levels and average annual carbon emissions in LCCP fall by 2.6 percent. (2) LCCP focus on reducing carbon emissions by increasing R&D investment, the efficiency of energy, and decreasing the high CO2 emissions industry. Among them, the reduction of the high carbon emission industry is mainly FDI, while the reduction of local industry is not obvious. (3) LCCP's carbon reduction effects suggest a reversed U-shape relationship with city size. Digitalization and marketization of LCCP are crucial to the carbon reduction effect. Carbon reduction and pollution reduction have a strong synergistic effect.

Use of artificial sweeteners and caffeine in a population of Hanoi: An assessment by wastewater-based epidemiology.

Monitoring the consumption of artificial sweeteners in the population is essential to help public health authorities understand the level of sugar consumption. There is a gap in knowledge of patterns and levels of artificial sweetener consumption in Vietnam. Using wastewater-based epidemiology (WBE), this study aims to evaluate the use of artificial sweeteners in an urban population in Hanoi, Vietnam. A total of 184 wastewater samples were collected at two sampling sites in an urban canal, receiving sewage from over 400,000 people in three different periods between 2018 and 2020. The population normalized per capita consumption of the five detected artificial sweeteners varied from 0.87 mg d-1 p-1 (sucralose) to 5.2 mg d-1 p-1 (aspartame). The daily consumption of artificial sweeteners was found to be stable throughout the week, however the consumption of artificial sweeteners was influenced by season with higher consumption in summer. Significant correlations (p < 0.01) were found among levels of artificial sweeteners and caffeine in urban canal samples, suggesting these chemicals had common sources. Population-weighted consumption load of artificial sweeteners and caffeine was compared in Vietnam, China and Australia, and the per capita consumption load mainly depended on the habitual of tea/coffee drinking in different countries. This was the first study that provided information on the artificial sweetener consumption by wastewater analysis in Vietnam. However, several sources of uncertainty (sample collection, population estimation, other sources of artificial sweeteners in wastewater, etc.) were acknowledged in this study. Further investigations on the spatial-temporal variation of artificial sweetener consumption with more intensive sampling scheme in Vietnam are recommended.

A High-Fidelity Artificial Urological System for the Quantitative Assessment of Endoscopic Skills.

Minimally-invasive surgery is rapidly growing and has become a standard approach for many operations. However, it requires intensive practice to achieve competency. The current training often relies on animal organ models or physical organ phantoms, which do not offer realistic surgical scenes or useful real-time feedback for surgeons to improve their skills. Furthermore, the objective quantitative assessment of endoscopic skills is also lacking. Here, we report a high-fidelity artificial urological system that allows realistic simulation of endourological procedures and offers a quantitative assessment of the surgical performance. The physical organ model was fabricated by 3D printing and two-step polymer molding with the use of human CT data. The system resembles the human upper urinary tract with a high-resolution anatomical shape and vascular patterns. During surgical simulation, endoscopic videos are acquired and analyzed to quantitatively evaluate performance skills by a customized computer algorithm. Experimental results show significant differences in the performance between professional surgeons and trainees. The surgical simulator offers a unique chance to train endourological procedures in a realistic and safe environment, and it may also lead to a quantitative standard to evaluate endoscopic skills.

Suppression of obesity by melatonin through increasing energy expenditure and accelerating lipolysis in mice fed a high-fat diet.

BACKGROUNDS/OBJECTIVES: Melatonin promotes brown adipose tissue (BAT) activity, leading to body mass reduction and energy expenditure. However, the mechanisms governing these beneficial effects are not well-established. This study aimed to assess the effects of (1) melatonin on BAT and energy metabolism, and (2) fibroblast growth factor 21 (FGF21) in BAT-mediated thermogenesis. METHODS: Male C57BL/6 J mice received a high-fat diet (HFD) or normal chow, accompanied by intraperitoneal injection of 20 mg/kg melatonin for 12 weeks. FGF21-/- mice consumed an HFD with or without melatonin for 8 weeks. RESULTS: Melatonin attenuated weight gain, insulin resistance, adipocyte hypertrophy, inflammation, and hepatic steatosis induced by the HFD and increased energy expenditure. Furthermore, melatonin improved cold tolerance by increasing BAT uncoupling protein 1 (UCP1) expression and producing heat. Notably, melatonin resulted in a shift in energy metabolism favouring the utilization of fat, and it increased FGF21 in circulating and metabolic tissues and skeletal muscle phosphorylation of AMP-activated protein kinase. However, melatonin did not protect against obesity, insulin resistance, and energy expenditure in HFD-fed FGF21-/- mice. CONCLUSIONS: Melatonin suppressed obesity and insulin resistance resulting from the HFD by enhancing BAT activity and energy expenditure, and these effects were dependent on FGF21.

Evaluation of Tourism Food Safety and Quality with Neural Networks.

Food safety issues are inextricably linked to people's lives and, in extreme cases, endanger public safety and social stability. People are becoming increasingly concerned about food safety issues in a modern society with high-quality economic development. People's incomes are increasing day by day as the economy continues to grow, and the tourism industry has grown by leaps and bounds. However, many problems arose, such as the issue of food safety in tourism. Tourism food safety issues affect not only the development of the food industry but also the development of tourism. Food safety oversight of tourist attractions has always been a relatively concerning issue in the country, and it is also something that the general public is concerned about. It can be said that food safety supervision of tourist attractions is the most important thing in food safety supervision. In this context, it becomes an important task to evaluate the safety of tourist food. This work proposes a multiscale convolutional neural network (AMCNN) combined with neural networks and attention layers to realize the safety and quality evaluation of tourist food. The algorithm uses the lightweight Xception network as a basic model and utilizes multiscale depth-separable convolution modules of different sizes for feature extraction and fusion to extract richer food safety feature information. Furthermore, the convolutional attention module (CBAM) is embedded on the basis of the multiscale convolutional neural network, which makes the network model focus more on discriminative features.

Two Innovative Approaches to Optimize Vancomycin Dosing Using Estimated AUC after First Dose: Validation Using Data Generated from Population PK Model Coupled with Monte-Carlo Simulation and Comparison with the First-Order PK Equation Approach.

The revised consensus guidelines for optimizing vancomycin doses suggest that maintaining the area under the concentration-time curve to minimal inhibitory concentration ratio (AUC/MIC) of 400-600 mg·h/L is the target pharmacokinetic/pharmacodynamic (PK/PD) index for efficacy. AUC-guided dosing approach uses a first-order pharmacokinetics (PK) equation to estimate AUC using two samples obtained at steady state and one-compartment model, which can cause inaccurate AUC estimation and fail to achieve the effective PK/PD target early in therapy (days 1 and 2). To achieve an efficacy target from the third or fourth dose, two innovative approaches (Method 1 and Method 2) to estimate vancomycin AUC at steady state (AUCSS) using two-compartment model and three or four levels after the first dose are proposed. The feasibility of the proposed methods was evaluated and compared with another published dosing algorithm (Method 3), which uses two samples and a one-compartment approach. Monte Carlo simulation was performed using a well-established population PK model, and concentration-time profiles for virtual patients with various degrees of renal function were generated, with 1000 subjects per group. AUC extrapolated to infinity (AUC0-∞) after the first dose was estimated using the three methods, whereas reference AUC (AUCref) was calculated using the linear-trapezoidal method at steady state after repeated doses. The ratio of AUC0-∞: AUCref and % bias were selected as the indicators to evaluate the accuracy of three methods. Sensitivity analysis was performed to examine the influence of change in each sampling time on the estimated AUC0-∞ using the two proposed approaches. For simulated patients with various creatinine clearance, the mean of AUC0-∞: AUCref obtained from Method 1, Method 2 and Method 3 ranged between 0.98 to 1, 0.96 to 0.99, and 0.44 to 0.69, respectively. The mean bias observed with the three methods was -0.10% to -2.09%, -1.30% to -3.59% and -30.75% to -55.53%, respectively. The largest mean bias observed by changing sampling time while using Method 1 and Method 2 were -4.30% and -10.50%, respectively. Three user-friendly and easy-to-use excel calculators were built based on the two proposed methods. The results showed that our approaches ensured sufficient accuracy and achieved target PK/PD index early and were superior to the published methodologies. Our methodology has the potential to be used for vancomycin dose optimization and can be easily implemented in clinical practice.

Self-Serving Dishonesty Partially Substitutes Fairness in Motivating Cooperation When People Are Treated Fairly.

Fairness is a key expectation in social interactions. Its violation leads to adverse reactions, including non-cooperation and dishonesty. The present study aimed to examine how (1) fair (unfair) treatment may drive cooperation (defection) and honesty (self-serving dishonesty), (2) dishonesty primes further moral disengagement and reduced cooperation, and (3) dishonesty weakens (substitutes) the effect of fairness on cooperation. The prisoner's dilemma (Experiment 1 and 2) and die-rolling task (Experiment 2) were employed for capturing cooperation and dishonest behaviors, respectively. To manipulate perceived unfairness, participants were randomly assigned to play the prisoner's dilemma game, where players either choose more cooperation (fair condition) or defection (unfair condition). Results of Experiment 1 (n = 102) suggested that participants perceive higher unfairness and behave less cooperatively when the other player primarily chooses defection. Results of Exp. 2 (n = 240) (a) confirmed Exp. 1 results, (b) showed that players in the unfair condition also show more self-serving dishonest behavior, and (c) that dishonest behavior weakens the effect of fairness on cooperation. Together, these results extended previous work by highlighting the self-serving lies when the opponent is fair trigger higher cooperation, presumably as a means to alleviate self-reflective moral emotions or restore justice.

Young population consume twice as much artificial sweetener than the general population - A wastewater-based assessment in China.

Understanding artificial sweetener consumption patterns and levels in different demographics is important for formulating public health policies on controlling sugar consumption. There is a considerable knowledge gap with respect to the pattern of artificial sweetener consumption in China. To narrow this gap, wastewater analysis was used to assess the temporal patterns of consumption of seven artificial sweeteners in an urban population and a university town in a megacity in South China over a one-year period. Daily influent wastewater samples were collected from an urban catchment and weekly samples collected from a university sub-catchment. Population normalized per capita consumption of the four detected artificial sweeteners (cyclamate, acesulfame, sucralose and saccharin) in the university catchment (1.0-5.9 mg d-1 p-1) was much higher than those in urban catchment (0.5-1.3 mg d-1 p-1), indicating younger population consume more artificial sweeteners than the general population. The daily consumption of artificial sweeteners was found to be stable throughout the week in the urban catchment. Time-series analysis showed that an average increase in temperature of 1 °C was associated with an increase consumption of 33 µg d-1 p-1 for acesulfame, 15 µg d-1 p-1 for sucralose and 14 µg d-1 p-1 for saccharin. This was the first study that objectively quantified the greater consumption of artificial sweeteners (proxy for consumption of artificially sweetened food and beverages) in a younger age group when compared to the general population, which could potentially pose a risk of health related diseases.

Transformation performance and subsystem coupling of resource-based cities in China: An analysis based on the support-pressure framework.

The sustainable development of resource-based cities is vital to China's high-quality development. Based on the support-pressure framework, this study simplifies the city system into an economy-society subsystem (ESS) and a resource-environment subsystem (RES), and measures the economy social developmental level (ESDL) and resource environmental carrying capacity (RECC) of China's 116 resource-based cities using the improved entropy-TOPSIS model. Then, it applies the coupling coordination degree (CCD) and relative development models to explore their coupling coordination relationships and relative developmental types. The results are as follows. (1) The ESDL and RECC of China's resource-based cities have improved significantly, and there is a large divergence between cities in different regions, development stages, and dominant resource types. (2) The CCD between the ESDL and RECC of China's resource-based cities is still not ideal, and no city qualifies for the high coordination category. (3) Overall, the RECC lags behind the ESDL, and the cities with a lagging ESDL are concentrated in the western and northeastern regions. Based on these conclusions, three specific suggestions are put forth. This study may provide a scientific reference for the Chinese government to formulate a sustainable development plan for resource-based cities. Integr Environ Assess Manag 2022;18:770-783. © 2021 SETAC.

Model-informed assessment of ethnic sensitivity and dosage justification for Asian populations in the global clinical development and use of cladribine tablets.

Cladribine tablets have been approved in many countries for the treatment of patients with various forms of relapsing multiple sclerosis (MS). Cladribine has a unique pharmacokinetic/pharmacodynamic (PK/PD) profile with a short elimination half-life (~ 1 day) relative to a prolonged PD effect on specific immune cells (most notably a reversible reduction in B and T lymphocyte counts). This results in a short dosing schedule (up to 20 days over 2 years of treatment) to sustain efficacy for at least another 2 years. Global clinical studies were conducted primarily in White patients, in part due to the distinctly higher prevalence of MS in White patients. Given the very low prevalence in Asian countries, MS is considered as a rare disease there. In spite of the limited participation of Asian patients, to demonstrate favorable benefit/risk profile in the treatment of MS demanded application of a Totality of Evidence approach to assess ethnic sensitivity for informing regulatory filings in Asian countries and supporting clinical use of cladribine in Asian patients. Population PD modeling and simulation of treatment-related reduction in absolute lymphocyte count, as a mechanism-related biomarker of drug effect, confirmed consistent PDs in Asian and non-Asian patients with MS, supporting absence of ethnic sensitivity and a common dosage across populations. Through this example, we demonstrate the value of holistic integration of all available data using a model-informed drug development (MIDD) framework and a Totality of Evidence mindset to evaluate ethnic sensitivity in support of Asia-inclusive development and use of the drug across populations.

Association between dietary patterns and cognitive ability in Chinese children aged 10-15 years: evidence from the 2010 China Family Panel Studies.

BACKGROUND: Limited information is available concerning the association between dietary patterns and cognitive ability during adolescence, especially in regards to the epidemiological studies in China. Therefore, this study aimed to analyze the association between dietary patterns and cognitive ability in Chinese children aged 10-15 years. METHODS: The dietary information, cognitive ability and sociodemographic data of 2029 children were retrieved from the 2010 China Family Panel Studies. Dietary patterns were assessed by principal component analysis. Ordinal logistic regression models were used to determine the association between dietary patterns and cognitive ability in these children. RESULTS: Three dietary patterns were identified, namely, 'High protein', 'High fat' and 'High salt-oil'. Following adjustment for gender, age, nationality, household registration, school type, parental education level, family learning environment, annual household income and family size, we found that an increase in 'High protein' pattern score was significantly associated with higher mathematics test scores (OR = 1.62, CI: 1.23 ~ 2.15; P = 0.001), but not with vocabulary test scores (OR = 1.21, CI: 0.93 ~ 1.58; P = 0.149). On the contrary, an increase in 'High fat' pattern score was significantly associated with lower scores of mathematics (OR = 0.76, CI: 0.59 ~ 0.98; P = 0.031) and vocabulary (OR = 0.77, CI: 0.61 ~ 0.97; P = 0.029) tests. However, there was no significant association between 'High salt-oil' pattern and the scores of mathematics (OR = 0.99, CI: 0.77 ~ 1.27; P = 0.915) and vocabulary (OR = 0.93, CI: 0.73 ~ 1.18; P = 0.544) tests. CONCLUSION: The findings of this study demonstrated that 'High protein' pattern was positively associated with cognitive ability in Chinese children, while 'High fat' pattern exhibited a negative association.

PAAR Proteins Are Versatile Clips That Enrich the Antimicrobial Weapon Arsenals of Prokaryotes.

Protein toxins secreted by prokaryotes have been found to affect the pathogenicity of pathogens or directly mediate antagonistic interactions between prokaryotes. PAAR proteins are important carriers of toxic effectors and are located at the forefront of either the type VI secretion system (T6SS) or the extracellular contractile injection system (eCIS). This study systematically investigated PAAR homologues and related toxic effectors. We found that PAAR homologues were divided into 8 types and 16 subtypes and distributed in 23.1% of bacterial genomes and 7.8% of archaeal genomes. PAAR proteins of all types fold into a highly similar conical structure, even from relatively diverse underlying sequences. PAAR homologues associated with different secretion systems display a mixed phylogenetic relationship, indicating that PAAR proteins from such a subtype can be assembled on either a T6SS or an eCIS. More than 1,300 PAAR-related toxic effector genes were identified; one PAAR subtype can be associated with toxins of over 40 families, and toxins from one family can be associated with more than 10 PAAR subtypes. A large-scale comparison of Earth Microbiome Project data and prokaryotic genomes revealed that prokaryotes encoding PAAR genes are widely present in diverse environments worldwide, and taxa encoding multiple PAAR gene copies exhibit a wider distribution in environments than other taxa. Overall, our studies highlighted that PAAR proteins are versatile clips loaded with antimicrobial toxin bullets for secretion weapons (T6SS and eCIS), greatly enriching the weapon arsenal of prokaryotes, which, often together with VgrG, help prokaryotes fight for survival advantages in crowded environments. IMPORTANCE Infectious diseases caused by microbial pathogens are severe threats to human health and economic development. To respond to these threats, it is necessary to understand how microorganisms survive in and adapt to complex environments. Microorganic toxins, which are widely distributed in nature, are the key weapons in life domain interactions. PAAR proteins are important carriers of prokaryotic toxic effectors. We reveal the versatility of PAAR proteins between secretory systems and the massive diversity of toxic effectors carried by PAAR proteins, which helps prokaryotes enrich their arsenal and expand their ability to attack their neighbors. A large number of PAAR homologues and related toxic effectors enhance the survival competitiveness of prokaryotic populations. In conclusion, our work provides an example for large-scale analysis of the global distribution and ecological functions of prokaryotic functional genes.

Perfluorooctanoic Acid (PFOA) and Perfluorooctanesulfonic Acid (PFOS) in Surface Water of China: National Exposure Distributions and Probabilistic Risk Assessment.

This study presents a comprehensive application of the probabilistic risk assessment methodology for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), which are two types of perfluoroalkyl acids frequently studied in recent years. The exposure characteristics of PFOA and PFOS in Chinese surface water on a nationwide scale were summarized. Individual predicted no-effect concentration (PNEC) and the sensitivities for taxonomic groups of primary producers, invertebrates, and vertebrates were derived by the species sensitivity distributions method. Both hazard quotients (HQs) and joint probability curves were calculated to assess the risks to aquatic organisms. Among seven Chinese river basins, the mean concentrations of PFOA and PFOS in the Yangtze River Basin were the highest (58 ng/L and 22 ng/L, respectively), while the lowest concentrations (< 1 ng/L) were in the Songhua River Basin. The acute PNEC value was 2.43 mg/L for PFOA and 0.96 mg/L for PFOS, and the chronic PNEC value was 0.0067 mg/L for PFOA and 0.0012 mg/L for PFOS, respectively. The sensitivities of different taxonomic groups revealed higher sensitivity of primary producers for PFOA and higher sensitivity of invertebrates for PFOS. The acute HQs of PFOA and PFOS were less than 1. The probabilities of exposure concentrations exceeding 5th percentile toxicity value of the chronic data for all aquatic organisms were 1.65% for PFOA and 1.23% for PFOS, respectively, suggesting a low probability of effects to aquatic organisms. Compared with the risk scenarios worldwide, the ecological risks for chronic effects decreased in the order of PFOS (worldwide) > PFOA (China) > PFOS (China) > PFOA (worldwide).

Decision analysis of the optimal freight structure at provincial level in China.

In recent years, considering the railway and waterway are cleaner ways of freight transportation, the Chinese government has vigorously promoted the adjustment of the transportation structure of the freight industry to reduce carbon emissions. However, with such a macroscopic objective, it remains a crucial problem for the policy-maker to further determine: how to estimate the optimal value of the share of freight volume among roadway, railway, and waterway regionally? To this end, this paper first quantified and analyzed the economic benefits, carbon emission intensity, and input-output efficiency of different transportation modes in each province. Then, with the goal of maximizing the efficiency of the freight transportation system, considering the carbon emission intensity reduction constraint and the economic output non-reduction constraint, an optimization model is constructed to obtain the freight structure adjustment plan in each province. Finally, taking the constraint of the carbon emission reduction targets by the 13th Five-Year Plan period as a case, the specific volume of roadway turnover transferred to waterway and railway in each province is given; the results show that Anhui, Beijing, Jiangxi, Tibet Autonomous Region, and Heilongjiang should focus on transferring the freight share of roadway to the railway, and the transferred shares are 15.36%, 14.12%, 10.21%, 8.22%, and 7.36% of road freight turnover. Tianjin, Hebei, and Shandong should focus on transferring the freight share of the roadway to the waterway, and the transferred shares are 18.44%, 7.90%, and 6.45% of road freight turnover, providing a reference for relevant government departments to formulate measures.

Cost-effectiveness analysis of dabigatran, rivaroxaban and warfarin in the prevention of stroke in patients with atrial fibrillation in China.

BACKGROUND AND OBJECTIVE: To evaluate the cost-effectiveness of new anticoagulants and warfarin in the prevention of stroke in Chinese patients with atrial fibrillation (AF). METHODS: The Markov model was constructed to compare patients' quality-adjusted life-years (QALYs) using drug cost, the cost of the examination after taking a drug, and the incremental cost of other treatments. Both dabigatran (110 and 150 mg, twice a day) and rivaroxaban (20 mg, once a day) were compared with warfarin (3-6 mg, once a day). Willingness to pay, three times the 2018 China GDP per capita (9481.88 $), was the cost-effect threshold in our study. RESULTS: The total cost were was 5317.31$, 29673.33$, 23615.49$, and 34324.91$ for warfarin, rivaroxaban, dabigatran 110 mg bid, and dabigatran 150 mg bid, respectively. The QALYs for each of the four interventions were 11.07 years, 15.46 years, 12.4 years, and 15 years, respectively. The cost-effectiveness analysis of the three new oral anticoagulants and warfarin showed that the incremental cost-effectiveness ratio (ICER) was 5548.07$/QALY when rivaroxaban was compared with warfarin. Rivaroxaban was the most cost-effective choice and warfarin was the least. CONCLUSIONS: In Chinese patients with AF, although warfarin is cheaper, rivaroxaban has a better cost-effectiveness advantage from an economic point of view.