Investigating the regional ecological environment stability and its feedback effect on interference using a novel vegetation resilience assessment model.

Vegetation resilience is critical for understanding the dynamic feedback effect of regional ecological environment stability against interferences. Thus, based on quantify the interferences of climate dryness and vegetation water deficit affecting vegetation growth function, incorporate mechanical Hooke's law to develop a vegetation resilience assessment model by quantitatively expressing vegetation growth function maintenance ability, to reveal the ecological environment stability and its feedback effect on interferences in the study area. The essential discoveries of the study are as follows: (1) with the increase of precipitation and the improvement of afforestation on soil erosion, the interferences intensity of climate dryness and vegetation water deficit in the ecological environment decreased by 5.88 % and 4.92 % respectively, the regional vegetation growth function loss was improved, especially in the southern region; (2) the decrease of vegetation growth function loss promoted the vegetation resilience level fluctuated from class II to class IV, with the average annual vegetation resilience increased by 7.02 %, reflecting that the regional ecological environment stability increased from difficult to rapid recovery after disturbance, and the benefit was especially noticeable in the eastern and southern forested areas; (3) the contribution rates of climate dryness and vegetation water deficit to the variation of vegetation resilience caused by vegetation restoration were -1.38 % and 4.73 %, respectively, and the prominent positive feedback effect of increasing vegetation resilience with decreasing vegetation water deficit degree in forest restoration area, indicating that the vegetation water deficit greatly impacts ecological environment stability in the study area, and forest restoration constantly improves regional ecological environment stability more than grassland restoration. This research has crucial guiding implications for supporting the sustainable development of regional ecological environments.

Spatiotemporal distribution, source apportionment, and ecological risk of bisphenol analogues in a highly urbanized river basin.

Bisphenol analogues (BPs), as one of the endocrine disruptors, have received wide attention due to their adverse impacts on ecosystems. However, the seasonal spatiotemporal distribution, source apportionment, and ecological risk of BPs in natural basins are poorly understood. Especially in highly urbanized river basins with the extensive economic development and anthropogenic activities threaten these critical but ecologically fragile regions. In this study, field investigations of BPs in the waters of the entire Qinhuai River Basin (QRB) were conducted in June (before the annual flood period) and August (after the annual flood period) 2023. The Qinhuai River, an important primary tributary of the lower Yangtze River, is located in eastern China and the QRB is characterized by a high population density and dense urbanization. Thirty-two sites were sampled for six types of BPs known to be ubiquitous in the surface water of the QRB. Significant differences in the concentrations of those BPs were found. Specifically, the concentration of total BPs (ΣBPs) was significantly higher before than after the flood period: 20.3-472 ng/L (mean = 146 ng/L) and 14.1-105 ng/L (mean = 35.9 ng/L), respectively. BPA was the main contributor to ΣBPs before the flood, and BPB followed by BPA after the flood. ΣBP concentrations were 12-241 % higher downstream than upstream of wastewater treatment plants (WWTPs). The results of a principal component analysis followed by multiple linear regression (PCA-MLR) suggested that untreated wastewater discharge from the WWTPs is an important source of BPs in the basin, with urban rainfall runoff as another potential source after the flood period. An assessment of the ecological risk of BPs, based on a calculation of the risk quotient, showed that BPA and BPS should be given due attention, and overall ecological risk of BPs pose a low risk to local algae but high and medium risks to invertebrates and fish, respectively.

Remote sensing traffic scene retrieval based on learning control algorithm for robot multimodal sensing information fusion and human-machine interaction and collaboration.

In light of advancing socio-economic development and urban infrastructure, urban traffic congestion and accidents have become pressing issues. High-resolution remote sensing images are crucial for supporting urban geographic information systems (GIS), road planning, and vehicle navigation. Additionally, the emergence of robotics presents new possibilities for traffic management and road safety. This study introduces an innovative approach that combines attention mechanisms and robotic multimodal information fusion for retrieving traffic scenes from remote sensing images. Attention mechanisms focus on specific road and traffic features, reducing computation and enhancing detail capture. Graph neural algorithms improve scene retrieval accuracy. To achieve efficient traffic scene retrieval, a robot equipped with advanced sensing technology autonomously navigates urban environments, capturing high-accuracy, wide-coverage images. This facilitates comprehensive traffic databases and real-time traffic information retrieval for precise traffic management. Extensive experiments on large-scale remote sensing datasets demonstrate the feasibility and effectiveness of this approach. The integration of attention mechanisms, graph neural algorithms, and robotic multimodal information fusion enhances traffic scene retrieval, promising improved information extraction accuracy for more effective traffic management, road safety, and intelligent transportation systems. In conclusion, this interdisciplinary approach, combining attention mechanisms, graph neural algorithms, and robotic technology, represents significant progress in traffic scene retrieval from remote sensing images, with potential applications in traffic management, road safety, and urban planning.

Combining the Real-Time Vial Sharing Strategy with Daily-Rate Charge Mode for Antimicrobial Drugs of Inpatients: An Economical and Practical Method for Patients and Hospitals.

Background: Antimicrobial agents' wastage is a huge problem, especially for pediatric patients, resulting in excessive drug expenditure and increasing the economic burden on patients' families. Moreover, the cost of disposing of antimicrobial agents' waste and the risk of environmental and occupational exposure also increased. This study aimed to explore the cost-effectiveness of the vial-sharing strategy combined with the daily-rate charge mode for pediatric inpatients to provide a strategy for reducing patients' expenditures, saving medical costs, and reducing drug proportion. Methods: This retrospective study was conducted at Pharmacy Intravenous Admixture Service (PIVAS), Shenzhen Children's Hospital, Guangdong Province, China, in 2022. Data on prescription drugs were collected from the PIVAS system. Ten antimicrobial drugs with a frequency of prescriptions no less than twice once daily were selected, and the drug costs, drug weight, and drug saved were further analyzed according to the combination of real-time vial sharing strategy and daily-rate charge mode. Traditional single vial charge mode without vial sharing was set as a control strategy. The actual expenditure of the hospital was also calculated and analyzed. Results: During 2022, ¥ 4,122,099 (34.4%) was saved for inpatients by applying a vial-sharing strategy on ten antibacterial agents, and more than 46,343,750 mg (24.6%) of drugs were totally saved. The top 5 drugs saved by the real-time vial-sharing strategy were cefoperazone-sulbactam, vancomycin, amoxicillin-sulbactam, ceftazidime, and meropenem. Taken the price into consideration, the top five payment-saved drugs were vancomycin (¥ 1,522,385), meropenem (¥ 1,311,475), cefoperazone-sulbactam (¥ 736,697), imipenem-cilastatin (¥ 406,092), and amoxicillin-sulbactam (¥ 51,394). Moreover, the account balance of the hospital was up to ¥ 426,499. Conclusion: The real-time vial sharing strategy combined with the daily-rate charge mode greatly reduces drug wastage and patients' payments. It may be useful for hospitals with PIVAS to achieve vial-sharing while protecting the best interest of inpatients.

Atom-economic and stereoselective catalytic synthesis of fully substituted enol esters/carbonates of amides in acyclic systems enabled by boron Lewis acid catalysis.

Carboacyloxylation of internal alkynes is emerging as a powerful and straightforward strategy for enol ester synthesis. However, the reported examples come with limitations, including the utilization of noble metal catalysts, the control of regio- and Z/E selectivity, and an application in the synthesis of enol carbonates. Herein, a boron Lewis acid-catalyzed intermolecular carboacyloxylation of ynamides with esters to access fully substituted acyclic enol esters in high yield with generally high Z/E selectivity (up to >96 : 4) is reported. Most importantly, readily available allylic carbonates are also compatible with this difunctionalization reaction, representing an atom-economic, catalytic and stereoselective protocol for the construction of acyclic ß,ß-disubstituted enol carbonates of amides for the first time. The application of the carboacyloxylation products to decarboxylative allylations provided a ready access to enantioenriched α-quaternary amides. Moreover, experimental studies and theoretical calculations were performed to illustrate the reaction mechanism and rationalize the stereochemistry.

[Reflections on supervision strategies of new Tibetan drug registration].

Tibetan medicine is an essential part of Chinese medicine and has unique theoretical experience and therapeutic advantages. According to the development principle of inheriting the essence, sticking to the truth, and keeping innovative, the supervision department should give clear and reasonable guidance considering the characteristics of Tibetan medicine, establish a standard system for quality control, clinical verification and evaluation, and accelerate the research and commercialization of new drugs. In view of the needs of drug supply-side reform and the current situation of Tibetan medicine and new pharmaceutical research, we ponder and provide suggestions on the confusion faced by the current supervision of Tibetan drug registration, hoping to contribute to the supervision strategy of Tibetan drug registration and the high-quality development of Tibetan medicine industry.

Phytoplankton community variation and ecological health assessment for impounded lakes along the eastern route of China's South-to-North Water Diversion Project.

Interbasin water diversion projects have been proven to effectively alleviate water resource shortages in areas along water diversion lines, but few studies have focused on ecological health in impounded lakes compared with research on water quality and pollutants. Herein, monitoring data were collected during the nonwater diversion period (NWDP) and the water diversion period (WDP) from 2018 to 2019, and the index of biological integrity (IBI) method based on phytoplankton communities was used to evaluate the ecological health of the impounded lakes (Nansi Lake and Dongping Lake) along the eastern route of the South-to-North Water Diversion Project. The results demonstrated that water diversion improved the water quality of the impounded lakes during the WDP, especially total nitrogen and ammonia nitrogen. Meanwhile, the water diversion affected the phytoplankton community structure and diversity, and network analysis further revealed water diversion could be beneficial to the ecological health of impounded lakes. Furthermore, the P-IBI showed that the overall ecological health assessment was "good" during the WDP. Water diversion substantially improved the ecological health status and stability of the impounded lakes during the dry season. Finally, the direct correlations between the water quality parameters and the P-IBI were weak, and water quality parameters could indirectly affect the P-IBI by changing the phytoplankton community structure. These findings will enhance our understanding of the ecological health of the impounded lakes of the South-to-North Water Diversion Project. Furthermore, this study will provide a reference to support the ecosystem security of impounded lakes in other large water diversion projects.

Multi-scale assessment of water security under climate change in North China in the past two decades.

Climate change is projected to affect the hydrological cycles in China, while the effects are expected to vary spatiotemporally. Understanding the variations in water security conditions and their sensitivity to climatic variables is crucial for assessing regional ecosystem responses to climate change. In the present study, we estimated the water yield capacity, an important indicator of water security in North China (NC), at a spatial resolution of 1 km during the last two decades based on the Budyko framework and quantified the sensitivity of water yield change to climate change among different vegetation types. The results showed that the performances of the Budyko framework were reliable both at the pixel scale and across large watersheds. The annual water yield in North China was estimated to be 7.61 ± 2.67 ∗ 1010 m3/yr, with an average mean water yield (MWY) of 49.51 ± 17.49 mm/yr. The spatial pattern of mean water yield change (MWYC) exhibited high heterogeneity; 46% of the study region was dominated by an increasing trend, while 9.84% was statistically significant (P < 0.05). Compared with temperature, the water yield capacity was more sensitive to precipitation variation. A consistent trend of variation was found in cropland between water yield and precipitation, while negative sensitivity coefficients were found in natural vegetation types. The variation in sensitivity coefficients (Swyp) in natural vegetation showed that in regions with a decrease in precipitation, the variation in water yield capacity also decreased, while in regions with an increase in precipitation from 0 to 8 mm/yr, the water yield capacity first decreased and then increased with precipitation. Our findings suggest that grass and shrubs would be more beneficial to regional water security in North China's revegetation, while afforestation would provide protection for the regional environment from extreme rainfall events.

Spatiotemporal dynamics and influencing factors of the global material footprint.

Environmental pressures have rapidly increased in various regions worldwide due to globalization. Thus, sustainable consumption and production are crucial for sustainable resource development. The material footprint (MF) of 180 countries was calculated from 1995 to 2015, and spatial autocorrelation analysis was conducted to investigate the spatiotemporal trend of the global MF. The results show that the global MF presented an upward trend from 1995 to 2015, increasing by 83%, and we find that the global per capita MF exhibits clustering, with an increasing trend during the study period. The findings indicate that resource consumption is similar in neighboring areas, especially in countries with a high MF surrounded by countries with a high MF (high-high clustering) and countries with low-low clustering. In addition, the number of countries with high clustering increased during the study period. We should take advantage of clustering, improve resource utilization, increase the technical carrying capacity, and develop energy-saving technologies. In African regions with low-low clustering, the economy of the surrounding areas should be stimulated to strengthen economic and technological clustering. In addition, advanced technology should be incorporated to improve the efficiency of using natural resources. This study can provide a reference for the spatial distribution of sustainable resource development.

Cellular automata based framework for evaluating mitigation strategies of sponge city.

Urban surface water flooding is increasing because of climate change and urbanization, and brings great challenges to urban sustainable development. It is, therefore, most important to develop urban flood management approaches to alleviate the consequences of floods. China is implementing a "sponge city" initiative to tackle urban surface water flooding and improve urban water management. There is, however, limited cost-effectiveness evaluation to support the choice of economically efficient mitigation strategies. To address this gap, this study developed an evaluation framework based on cellular automata and cost-benefit analysis to assess the performance of mitigation strategies in sponge city construction. This approach is demonstrated with a case study of Siergou (Dalian, China), which has a total area of 10.1 km2. The mitigation measures of green roofs, permeable pavements and bio-retention were used to generate mitigation scenarios. A two-dimensional cellular automata-based model was used to simulate urban surface water flooding. The results obtained from the case study indicate that the framework can achieve cost-effective mitigation strategies for sponge city construction, which can support robust decision making. The distribution of mitigation strategies has great impacts on the effectiveness of alleviating urban flood risk. This study provides new insight into the development of cost-effective mitigation strategies for sponge city construction.

Effects of ecological protection and restoration on phytoplankton diversity in impounded lakes along the eastern route of China's South-to-North Water Diversion Project.

Traditional lake phytoplankton diversity studies do not take into account the impact of ecological protection and restoration project policies. Here, a difference-in-differences (DID) model, which is commonly used to analyze the relative importance of economic factors, was used to evaluate the impact of such policies on phytoplankton diversity in lakes. Dongping Lake was used as the experimental group, and the upstream Nansi Lake was used as the control group. The phytoplankton diversity index of the experimental group and the control group was used as the explanatory variable of the DID model. Six environmental and socioeconomic factors, temperature and precipitation, were used as control variables in the DID model. The effects of ecological protection and restoration project policy on phytoplankton diversity in lakes were analyzed. Under the influence of policy implementation, the phytoplankton diversity in the experimental lake was improved by 2.79% compared with that in the control lake. Temperature and precipitation were the main factors affecting phytoplankton diversity in the two connected shallow lakes in the Shandong Peninsula. This study verified that DID models can be used to quantitatively analyze the impact of ecological protection and restoration project policies on phytoplankton diversity in lakes.

Current practice and barriers to ICU-acquired weakness assessment: a cross-sectional survey.

BACKGROUND: Intensive-care-unit-acquired weakness (ICU-AW) not only leads to difficulty weaning off mechanical ventilation, prolonged hospital stay and increased medical costs, but also reduces the patient's quality of life after discharge and increases the 1-year mortality rate. Early identification and intervention can improve the prognosis of critically ill patients. However, much remains unknown about current clinical practice for ICU-AW assessment by ICU staff in China. OBJECTIVES: To investigate current practices and barriers to ICU-AW assessment among ICU staff, and provide insights to improve ICU-AW assessment in ICUs in China. METHODS: Qualitative interviews were used to construct a survey questionnaire (test-retest reliability 0.92, validity 0.96). This survey was subsequently completed by 3206 ICU staff from 31 provinces, municipalities and autonomous regions in China. RESULTS: In total, 3206 ICU staff responded to the survey (response rate 90%): 616 doctors (19%), 2371 nurses (74%), 129 respiratory therapists (4%), 51 physiotherapists (2%) and 39 dieticians (1%). Only 27% of the respondents had treated/cared for patients with ICU-AW. Reported methods for ICU-AW assessment were clinical experience (53%), ICU-AW assessment tools (12%), and physiotherapy consultation (35%). Forty-three percent of respondents felt that their ICU-AW-related knowledge did not meet clinical needs, only 10% had received ICU-AW-related training, and 19% proactively assessed whether their patients had ICU-AW. In terms of frequency of assessment, 42%, 16% and 11% of respondents considered that ICU-AW should be assessed daily, every 3 days, and on ICU admission and discharge, respectively. The Medical Research Council scale, electrophysiological assessment and the Manual Muscle Testing scale were considered to be optimal tools for ICU-AW diagnosis by 79%, 70%, and 73% of respondents, respectively. The main reported barriers to ICU-AW assessment were lack of knowledge, cognitive impairment among patients, and lack of ICU-AW assessment guidelines and procedures. CONCLUSION: Current practices for ICU-AW assessment are non-specific, and the main barriers include lack of skills and knowledge.

Chinesisation, adaptation and validation of the Chelsea Critical Care Physical Assessment Tool in critically ill patients: a cross-sectional observational study.

PURPOSE: To translate and adapt the Chelsea Critical Care Physical Assessment Tool (CPAx) into Chinese version ('CPAx-Chi'), test the reliability and validity of CPAx-Chi, and verify the cut-off point for the diagnosis of intensive care unit-acquired weakness (ICU-AW). STUDY DESIGN: Cross-sectional observational study. METHODS: Forward and back translation, cross-cultural adaptation and pretesting of CPAx into CPAx-Chi were based on the Brislin model. Participants were recruited from the general ICU of five third-grade class-A hospitals in western China. Two hundred critically ill adult patients (median age: 53 years; 64% men) with duration of ICU stay ≥48 hours and Glasgow Coma Scale ≥11 were included in this study. Two researchers simultaneously and independently assessed eligible patients using the Medical Research Council Muscle Score (MRC-Score) and CPAx-Chi. RESULTS: The content validity index of items was 0.889. The content validity index of scale was 0.955. Taking the MRC-Score scale as standard, the criterion validity of CPAx-Chi was r=0.758 (p<0.001) for researcher A, and r=0.65 (p<0.001) for researcher B. Cronbach's α was 0.939. The inter-rater reliability was 0.902 (p<0.001). The area under the receiver operating characteristic curves of CPAx-Chi for diagnosing ICU-AW based on MRC-Score ≤48 were 0.899 (95% CI 0.862 to 1.025) and 0.874 (95% CI 0.824 to 0.925) for researcher B. The best cut-off point for CPAx-Chi for the diagnosis of ICU-AW was 31.5. The sensitivity was 87% and specificity was 77% for researcher A, whereas it was 0.621, 31.5, 75% and 87% for researcher B, respectively. The consistency was high when taking CPAx-Chi ≤31 and MRC-Score ≤48 as the cut-off points for the diagnosis of ICU-AW. Cohen's kappa=0.845 (p=0.02) in researcher A and 0.839 (p=0.04) for researcher B. CONCLUSIONS: CPAx-Chi demonstrated content validity, criterion-related validity and reliability. CPAx-Chi showed the best accuracy in assessment of patients at risk of ICU-AW with good sensitivity and specificity at a recommended cut-off of 31.

[Current practice and obstacle factors of intensive care unit-acquired weakness assessment].

OBJECTIVE: To investigate the current status of intensive care unit-acquired weakness (ICU-AW) assessment, analyze the assessment barriers, and to provide reference to improve ICU-AW assessment. METHODS: A convenient sampling cross-sectional survey was conducted. First, an interview outline which based on related domestic and international literatures and combining with the research purpose of this study were designed. Thirteen medical personnel (8 ICU nurses, 3 ICU doctors, 1 respiratory therapist and 1 physiotherapist) who worked in the intensive care unit (ICU) of the First Hospital of Lanzhou University were enrolled with convenience sampling method to interview. Second, the topics were comprehensively analyzed and extracted, and then a questionnaire was constructed, and the reliability and validity was assessed. Finally, the questionnaire survey including the general situation of ICU medical staffs, the current practices of ICU-AW and influencing factors was implemented in China. RESULTS: The retest reliability was 0.92 and expert validity was 0.96 of the questionnaire. There were 3 563 respondents in 31 provinces, municipalities and autonomous regions which eliminated 357 unqualified questionnaires, including 173 respondents from neonatal or pediatric ICU, 89 respondents whose working time was less than 6 months, and 95 invalid respondents, and then there were finally 3 206 valid questionnaires and the response rate were 90.0%. Those 3 206 respondents included 616 doctors (19.2%), 2 371 nurses (74.0%), 129 respiratory therapists (4.0%), 51 physiotherapist (1.6%) and 39 dietitians (1.2%). The mean age was (30.7±6.3) years old. Most of them had bachelor's degree (65.9%), master and above was 14.1%. Associate senior physician and above was 8.0%; ICU working time was (5.94±4.50) years. In clinical practice, only 26.5% of the ICU medical staffs confirmed that they had treated or taken care for ICU-AW patients; 52.9% of medical staffs evaluated ICU-AW only based on clinical experience, and only 12.3% used ICU-AW assessment tools. The majority of respondents believed that ICU-AW knowledge training should be performed (81.8%), ICU-AW assessment should be as important as other complications (pressure sore, infected ventilator associated pneumonia, etc., 75.1%), and ICU-AW assessment should be part of daily treatment and care activities (61.2%). However, only 10.2% of respondents had received ICU-AW related knowledge training, and 42.7% respondents believed that their ICU-AW related knowledge could not meet clinical needs. Only 18.7% respondents would actively assess whether patients suffered from ICU-AW or not, and 42.3% respondents thought that ICU-AW should be assessed every day, and the assessment tools were also inconsistent. There were 44.0% respondents considered the Medical Research Council Muscle score (MRC-score) scale was the optimal tool for diagnosing ICU-AW, the following were neuro-electrophysiological examination (17.2%) and manual muscle strength (MMT, 11.1%). The main cause of the ICU-AW assessment barriers was the lack of ICU-AW related knowledge (88.1%), and the following were lack of ICU-AW assessment guidelines (76.5%), patients' cognitive impairment or limited understanding ability (84.6%), unable to cooperate with the assessment due to critical illness (83.0%), and inadequate attention to ICU-AW assessment by the department (77.5%). CONCLUSIONS: The current status of ICU-AW assessment were unsatisfying in China, and the main barriers were lack of skills and knowledge.

Assessment of lake eutrophication using a novel multidimensional similarity cloud model.

Lake eutrophication is characterized by a variety of indicators, including nitrogen and phosphorus concentrations, chemical oxygen demand, chlorophyll levels, and water transparency. In this study, a multidimensional similarity cloud model (MSCM) is combined with a random weighting method to reduce the impacts of random errors in eutrophication monitoring data and the fuzziness of lake eutrophication definitions on the consistency and reliability of lake eutrophication evaluations. Measured samples are assigned to lake eutrophication levels based on the cosine of the angle between the cloud digital characteristics vectors of each sample and those of each eutrophication grade. To field test this method, the eutrophication level of Nansi Lake in Shandong Province was evaluated based on monitoring data collected in 2009-2016. Results demonstrate that, in 2009 and in 2011-2015, the upper lake of Nansi Lake exhibited moderate eutrophication while the lower lake exhibited mild eutrophication. In 2010, 2016, elevated concentrations of total nitrogen and total phosphorus led to an increase in the eutrophication level of the lower lake, matching that of the upper lake. Based on the results of these field tests, we conclude that the MSCM presented in this study provides a more flexible and effective method for evaluating lake eutrophication data than the existing multidimensional normal cloud model.

Non-point source pollution risks in a drinking water protection zone based on remote sensing data embedded within a nutrient budget model.

A simple, transparent and reliable method for evaluating non-point source pollution (NPSP) risks to drinking water source areas lacking observational data is proposed herein. The NPSP risks are assessed by using nutrient budget models for total nitrogen and total phosphorus, making the best use of remote sensing and field survey data. We demonstrate its potential using a case study of the Chaihe Reservoir in northeastern China. Fertilizer inputs and crop-uptake outputs were estimated based on normalized difference vegetation index, which is derived from remote sensing as indicators of crop growth and production. The nutrient balances for this area showed surpluses of both N and P within the soil system. Estimated imbalances per unit area were consistent with statistical relationships derived from all Chinese counties, demonstrating that the proposed method is reliable. The surplus P amounts were higher than the standard threshold for NPSP risks, indicating the existence of a potential contamination risk of P to this drinking water source.

Assessment of Blood Tumor Mutational Burden as a Potential Biomarker for Immunotherapy in Patients With Non-Small Cell Lung Cancer With Use of a Next-Generation Sequencing Cancer Gene Panel.

IMPORTANCE: Tumor mutational burden (TMB), as measured by whole-exome sequencing (WES) or a cancer gene panel (CGP), is associated with immunotherapy responses. However, whether TMB estimated by circulating tumor DNA in blood (bTMB) is associated with clinical outcomes of immunotherapy remains to be explored. OBJECTIVES: To explore the optimal gene panel size and algorithm to design a CGP for TMB estimation, evaluate the panel reliability, and further validate the feasibility of bTMB as a clinical actionable biomarker for immunotherapy. DESIGN, SETTING, AND PARTICIPANTS: In this cohort study, a CGP named NCC-GP150 was designed and virtually validated using The Cancer Genome Atlas database. The correlation between bTMB estimated by NCC-GP150 and tissue TMB (tTMB) measured by WES was evaluated in matched blood and tissue samples from 48 patients with advanced NSCLC. An independent cohort of 50 patients with advanced NSCLC was used to identify the utility of bTMB estimated by NCC-GP150 in distinguishing patients who would benefit from anti-programmed cell death 1 (anti-PD-1) and anti-programmed cell death ligand 1 (anti-PD-L1) therapy. The study was performed from July 19, 2016, to April 20, 2018. MAIN OUTCOMES AND MEASURES: Assessment of the Spearman correlation coefficient between bTMB estimated by NCC-GP150 and tTMB calculated by WES. Evaluation of the association of bTMB level with progression-free survival and response to anti-PD-1 and anti-PD-L1 therapy. RESULTS: This study used 2 independent cohorts of patients with NSCLC (cohort 1: 48 patients; mean [SD] age, 60 [13] years; 15 [31.2%] female; cohort 2: 50 patients; mean [SD] age, 58 [8] years; 15 [30.0%] female). A CGP, including 150 genes, demonstrated stable correlations with WES for TMB estimation (median r2 = 0.91; interquartile range, 0.89-0.92), especially when synonymous mutations were included (median r2 = 0.92; interquartile range, 0.91-0.93), whereas TMB estimated by the NCC-GP150 panel found higher correlations with TMB estimated by WES than most of the randomly sampled 150-gene panels. Blood TMB estimated by NCC-GP150 correlated well with the matched tTMB calculated by WES (Spearman correlation = 0.62). In the anti-PD-1 and anti-PD-L1 treatment cohort, a bTMB of 6 or higher was associated with superior progression-free survival (hazard ratio, 0.39; 95% CI, 0.18-0.84; log-rank P = .01) and objective response rates (bTMB ≥6: 39.3%; 95% CI, 23.9%-56.5%; bTMB <6: 9.1%; 95% CI, 1.6%-25.9%; P = .02). CONCLUSIONS AND RELEVANCE: The findings suggest that established NCC-GP150 with an optimized gene panel size and algorithm is feasible for bTMB estimation, which may serve as a potential biomarker of clinical benefit in patients with NSCLC treated with anti-PD-1 and anti-PD-L1 agents.

Comprehensive assessment of groundwater pollution risk based on HVF model: A case study in Jilin City of northeast China.

A comprehensive model for groundwater risk assessment was proposed by combining the hazard of contaminated sources (H), groundwater intrinsic vulnerability (V) and groundwater function value (F), and verified in Jilin City of northeast China. This model is characterized by integrating groundwater resource, ecology, and geological environment under the impact of climate change and human activities. The hazard of potential polluted sources was assessed by quantifying the properties and the potential infiltrating load of contaminants. The groundwater intrinsic vulnerability was evaluated by the DRASTIC model. The groundwater function value was assessed by multiplying seventeen indexes with their corresponding weightings. The groundwater pollution risk mapping of Jilin City was generated based on ArcGIS and validated by the level difference method between the risk classification and the pollution classification. The results showed that groundwater has a relatively low possibility of pollution because the area with less than, or equal to, the medium classification of risk accounted for 67.61% of the study area. The hazard harmfulness from the different contaminant sources played the most important role in determining the high groundwater pollution risk areas. Different influencing factors lead to relatively high pollution risk in specific areas. According to the validation of the level difference method, areas correctly identified by groundwater pollution risk mapping accounted for 95.81% of the study area, which is nearly twice as high as that of specific vulnerability mapping. The HVF model proved to be suitable for assessing groundwater pollution risk in Jilin City of northeast China. The groundwater pollution risk mapping can be applied for the effective protection and sustainable supply of groundwater.

Historical accumulation and ecological risk assessment of heavy metals in sediments of a drinking water lake.

Heavy metal contamination in sediments is progressively being recognized as a challenging problem in large parts of the developing world, particularly in Asian countries. A drinking water lake in Yunnan-Guizhou plateau, China named Hongfeng Lake was selected as the research target. Forty surface sediment samples and 4 sediment cores were collected to reveal the accumulation of heavy metals in the sediments of the lake. The mean concentrations of Cr, Cu, Pb, Cd, As, and Hg in surface sediments were 81.67, 45.61, 29.78, 0.53, 22.71, and 0.25 mg/kg, respectively, which exceeded the background levels of sediment 1.1~3.3 times. The calculation of geoaccumulation (Igeo) and potential ecological risk (PER) index analysis were preformed, and the results showed a considerable risk for Cd and Hg on the whole. Spatially, the northern part showed a higher risk than the southern part and tributaries of the lake, and a moderate risk in the overall sediment of the lake. The historical level of heavy metals in Hongfeng Lake was traced by vertical sediments study and it was dated back approximately 35 years. The EF trends of a feature sampling site HF8 showed strong temporal variations, and peaked in the year 1995. After that, the EFs exhibited a declining trend, which reflects productive environmental protection and management by the local government. For the Hongfeng Lake, a typical lake with heavy metal-contaminated sediments, the in-situ remediation technique could be a suitable method for its remediation.

Assessment of the impacts of land use changes on nonpoint source pollution inputs upstream of the Three Gorges Reservoir.

In recent years, land use upstream of the Three Gorges Reservoir (TGR) has changed significantly because of the TGR project. In this study, the Soil and Water Assessment Tool (SWAT) model was examined for its ability to assess relationships between land use changes and nonpoint pollutant indexes upstream of the TGR. Results indicated that the SWAT model, calibrated with the adjusted parameters, could successfully reproduce the nonpoint indexes at the water quality monitoring sites in the two rivers. The different land use change types were shown to be sensitive to nonpoint pollutants in the study area. The land use change type from upland to water was the strongest influence on changes in total nitrogen and total phosphorus. An empirical regression equation between nonpoint indexes and different land use change types was developed for the study area by partial least squares regression (PLSR) as follows: Y = b 0 + ∑ i=1 (m) b i X i. This regression equation was useful for evaluating the influence of land use change types on changes in nonpoint pollutants over a long time period. The results from this study may be useful for the TGR management and may help to reduce nonpoint pollutant loads into downstream water bodies.