Comparison of effectiveness and cost of different HCV testing strategies in high-risk populations in China.

High-risk populations are the predominant populations affected by hepatitis C virus (HCV) infection, and there is an urgent need for efficient and cost-effective HCV testing strategies for high-risk populations to identify potential undiagnosed HCV-infected individuals. This study compared several commonly used testing strategies and conducted effectiveness and cost analysis to select the appropriate testing strategy for diagnosing HCV infection in high-risk populations. Among the 2093 samples from high-risk populations in this study, 1716 were HCV negative, 237 were current HCV infection, 137 were past HCV infection, and three were acute early HCV infection. It was found that out of 237 patients with HCV current infection, Strategy A could detect 225 cases, with a missed detection rate of 5.06%, and the total cost was 33 299 RMB. In addition, Strategy B could detect 237 cases of current HCV infection, and the HCV missed detection rate was 0.00%, and the total cost was 147 221 RMB. While 137 cases of past HCV infection could be distinguished by strategy C, but 14 cases with current HCV infection were missed, with an HCV-positive missed detection rate of 5.91%, and the total cost for Strategy C was 43 059 RMB. In conclusion, in high-risk populations, the HCV positivity rate is typically higher. If feasible, the preferred approach is to directly conduct HCV RNA testing, which effectively minimizes the risk of missing cases. However, in situations with limited resources, it is advisable to initially choose a highly sensitive method for anti-HCV screening, followed by HCV RNA testing on reactive samples.

Assessment of the Enzymatic Dephosphorylation Kinetics in the Assemblies of a Phosphopentapeptide that Forms Intranuclear Nanoribbons.

Although the formation of peptide assemblies catalyzed by alkaline phosphatase (ALP) has received increasing attention in inhibiting cancer cells, the detailed enzyme kinetics of the dephosphorylation of the corresponding phosphopeptide assemblies have yet to be determined. We recently discovered that assemblies from a phosphopentapeptide can form intracellular nanoribbons that kill induced pluripotent stem cells or osteosarcoma cells, but the kinetics of enzymatic dephosphorylation remain unknown. Thus, we chose to examine the enzyme kinetics of the dephosphorylation of the phosphopentapeptide [NBD-LLLLpY (1)] from concentrations below to above its critical micelle concentration (CMC). Our results show that the phosphopeptide exhibits a CMC of 75 µM in phosphate saline buffer, and the apparent Vmax and Km values of alkaline phosphatase catalyzed dephosphorylation are approximately 0.24 µM/s and 5.67 mM, respectively. Despite dephosphorylation remaining incomplete at 60 min in all the concentrations tested, dephosphorylation of the phosphopeptide at concentrations of 200 µM or above mainly results in nanoribbons, dephosphorylation at concentrations of CMC largely produces nanofibers, and dephosphorylation below the CMC largely generates nanoparticles. Moreover, the formation of nanoribbons correlates with the intranuclear accumulation of the pentapeptide. By providing the first examination of the enzymatic kinetics of phosphopeptide assemblies, this work further supports the notion that the assemblies of phosphopentapeptides can act as a new functional entity for controlling cell fates.

Development and validation of a new risk assessment model for immunomodulatory drug-associated venous thrombosis among Chinese patients with multiple myeloma.

BACKGROUND: Individuals with multiple myeloma (MM) receiving immunomodulatory drugs (IMiDs) are at risk of developing venous thromboembolism (VTE), a serious complication. There is no established clinical model for predicting VTE in the Chinese population. We develop a new risk assessment model (RAM) for IMiD-associated VTE in Chinese MM patients. METHODS: We retrospectively selected 1334 consecutive MM patients receiving IMiDs from 16 medical centers in China and classified them randomly into the derivation and validation cohorts. A multivariate Cox regression model was used for analysis. RESULTS: The overall incidence of IMiD-related VTE in Chinese MM patients was 6.1%. Independent predictive factors of VTE (diabetes, ECOG performance status, erythropoietin-stimulating agent use, dexamethasone use, and VTE history or family history of thrombosis) were identified and merged to develop the RAM. The model identified approximately 30% of the patients in each cohort at high risk for VTE. The hazard ratios (HRs) were 6.08 (P < 0.001) and 6.23 (P < 0.001) for the high-risk subcohort and the low-risk subcohort, respectively, within both the derivation and validation cohorts. The RAM achieved satisfactory discrimination with a C statistic of 0.64. The stratification approach of the IMWG guidelines yielded respective HRs of 1.77 (P = 0.053) and 1.81 (P = 0.063). The stratification approach of the SAVED score resulted in HRs of 3.23 (P = 0.248) and 1.65 (P = 0.622), respectively. The IMWG guideline and the SAVED score-based method yielded C statistics of 0.58 and 0.51, respectively. CONCLUSIONS: The new RAM outperformed the IMWG guidelines and the SAVED score and could potentially guide the VTE prophylaxis strategy for Chinese MM patients.

Improved human greenspace exposure equality during 21st century urbanization.

Greenspace plays a crucial role in urban ecosystems and has been recognized as a key factor in promoting sustainable and healthy city development. Recent studies have revealed a growing concern about urban greenspace exposure inequality; however, the extent to which urbanization affects human exposure to greenspace and associated inequalities over time remains unclear. Here, we incorporate a Landsat-based 30-meter time-series greenspace mapping and a population-weighted exposure framework to quantify the changes in human exposure to greenspace and associated equality (rather than equity) for 1028 global cities from 2000 to 2018. Results show a substantial increase in physical greenspace coverage and an improvement in human exposure to urban greenspace, leading to a reduction in greenspace exposure inequality over the past two decades. Nevertheless, we observe a contrast in the rate of reduction in greenspace exposure inequality between cities in the Global South and North, with a faster rate of reduction in the Global South, nearly four times that of the Global North. These findings provide valuable insights into the impact of urbanization on urban nature and environmental inequality change and can help inform future city greening efforts.

A new interpretable belief rule base model with step-length convergence strategy for aerospace relay health state assessment.

Health state assessment is an important measure to maintain the safety of aerospace relays. Due to the uncertainty within the relay system, the accuracy of the model assessment is challenged. In addition, the opaqueness of the process and incomprehensibility of the results tend to lose trust in the model, especially in high security fields, so it is crucial to maintain the interpretability of the model. Thus, this paper proposes a new interpretable belief rule base model with step-length convergence strategy (IBRB-Sc) for aerospace relay health state assessment. First, general interpretability criteria for BRB are considered, and strategies for maintaining model interpretability are designed. Second, the evidential reasoning (ER) method is used as the inference machine. Then, optimization is performed based on the Interpretable Projection Covariance Matrix Adaptive Evolution Strategy (IP-CMA-ES). Finally, the validity of the model is verified using the JRC-7M aerospace relay as a case study. Comparative experiments show that the proposed model maintains high accuracy and achieves advantages in interpretability.

[Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine].

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Assessment of the Risk and Symptoms of SARS-CoV-2 Infection Among Healthcare Workers During the Omicron Transmission Period: A Multicentric Study from Four Hospitals of Mainland China.

Purpose: The SARS-CoV-2 omicron variant emerged and spread rapidly among the population in the early stage of China's normalized prevention and control in December 2022. Healthcare workers (HCWs) are particularly exposed to SARS-CoV-2, it is important to evaluate the impact of the omicron pandemic on HCWs in China. Methods: A self-administered online survey was conducted on infected HCWs from four hospitals of Taizhou. A total of 748 HCWs received the survey via DingTalk, and 328 responded to the questionnaire. The risk factors were investigated using univariate and multivariate logistic regression analysis. Results: By December 20, 2022, 748 HCWs tested positive by PCR, and the infection rate was 11.4% (748/6581). Among 328 respondents, the most common symptoms were cough (88.4%), fever (83.5%), runny nose (77.1%), sore throat (73.2%), headache (70.1%), muscle aches (67.1%), and fatigue (53.4%). 69.8% (229/328) of the participants had five or more major onset symptoms, while no severe case was observed. The multivariate analysis indicated that the poor sleep quality (OR = 2.29, 95% CI: 1.31-4.02, P = 0.004) was an independent risk factor for more major onset symptoms, while wore gloves ≥95% times in working (OR = 0.49, 95% CI: 0.28-0.85, P = 0.011) was significantly related to fewer symptoms. In addition, 239 (72.9%) recipients reported high fever (temperature ≥38.5°C), less common cold (≤3 vs >3 times/year, OR = 2.20, 95% CI: 1.05-4.65, P = 0.038) was significantly associated with high fever. Conclusion: Our findings imply rapid transmissibility of omicron and multiple-onset symptoms among HCWs. Improved autoimmunity and self-protection measures for HCWs may be helpful in controlling infection and clinical symptoms. Our results provide empirical reference values for improved countermeasures and protective measures for major public health emergencies.

Pharmacokinetics of YK-1169 in healthy subjects and pharmacokinetic/pharmacodynamic analysis by Monte Carlo simulation.

OBJECTIVE: This study (NCT05588531) aimed to evaluate the safety and pharmacokinetics of cefepime-avibactam (YK-1169) in healthy Chinese subjects and explore the optimal regimen for treating carbapenem-resistant Klebsiella pneumoniae (CRKP) based on the pharmacokinetic/pharmacodynamic evaluation. METHODS: YK-1169 single-ascending doses (0.5, 1.25, 2.5 or 3.75 g, 2-h infusion) and multiple doses (2.5 or 3.75 g every 8 h [q8h], 2-h infusion) given for 7 days were evaluated in pharmacokinetic studies. Subjects were randomized to receive cefepime (2 g), avibactam (0.5 g) or YK-1169 (2.5 g) to assess drug-drug interactions. The minimum inhibitory concentrations (MICs) of YK-1169 were determined by the broth microdilution method. Monte Carlo simulation was used to evaluate 10 different dose regimens. RESULTS: Cefepime and avibactam both showed a linear pharmacokinetic profile. No accumulation was found after multiple doses. The cefepime Cmax,ss and AUC0-∞,ss were 9.20 and 16.0 µg/mL, 407.2 and 659.45 µg·h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. The avibactam Cmax,ss and AUC0-∞,ss were 0.545 and 0.837 µg/mL, 53.31 and 79.55 µg·h/mL in the 2.5 and 3.75 g multiple-dose groups, respectively. Cefepime and avibactam did not affect each other's pharmacokinetics. No serious adverse events occurred. All regimens achieved 90% probability of target attainment (PTA) goals when the MIC was ≤8 mg/L. The regimens of 2.5 (q8h, 2-h infusion), 3.75 (q8h, 2-, 3- and 4-h infusions) and 7.5 g (24-h continuous infusion) reached a 90% cumulative fraction of response. CONCLUSION: YK-1169 had good antibacterial activity against CRKP and could be an option for CRKP infections. The regimen of 2.5 g q8h intravenously guttae (ivgtt) 2 h should be considered in future clinical trials.

Polar amplification comparison among Earth's three poles under different socioeconomic scenarios from CMIP6 surface air temperature.

The polar amplification (PA) has become the focus of climate change. However, there are seldom comparisons of amplification among Earth's three poles of Arctic (latitude higher than 60 °N), Antarctica (Antarctic Ice Sheet) and the Third Pole (the High Mountain Asia with the elevation higher than 4000 m) under different socioeconomic scenarios. Based on CMIP6 multi-model ensemble, two types of PA index (PAI) have been defined to quantify the PA intensity and variations, and PAI1/PAI2 is defined as the ratio of the absolute value of surface air temperature linear trend over Earth's three poles and that for global mean/over other regions except Earth's three poles. Arctic warms fastest in winter and weakest in summer, followed by the Third Pole, and Antarctica warms least. The similar phenomenon proceeds when global warming of 1.5-2.0 °C, and 2.0-3.0 °C above pre-industrial levels. After removing the Earth's three poles self-influence, all the PAI2s increase much more obviously relative to the PAI1s, especially the Antarctic PAI. Earth's three poles warm faster than the other regions. With the forcing increasing, PA accelerates much more over Antarctica and the Third Pole, but becomes weaker over Arctic. This demonstrates that future warming rate might make a large difference among Earth's three poles under different scenarios.

Contrasting inequality in human exposure to greenspace between cities of Global North and Global South.

The United Nations specified the need for "providing universal access to greenspace for urban residents" in the 11th Sustainable Development Goal. Yet, how far we are from this goal remains unclear. Here, we develop a methodology incorporating fine-resolution population and greenspace mappings and use the results for 2020 to elucidate global differences in human exposure to greenspace. We identify a contrasting difference of greenspace exposure between Global South and North cities. Global South cities experience only one third of the greenspace exposure level of Global North cities. Greenspace exposure inequality (Gini: 0.47) in Global South cities is nearly twice that of Global North cities (Gini: 0.27). We quantify that 22% of the spatial disparity is associated with greenspace provision, and 53% is associated with joint effects of greenspace provision and spatial configuration. These findings highlight the need for prioritizing greening policies to mitigate environmental disparity and achieve sustainable development goals.

Beyond green environments: Multi-scale difference in human exposure to greenspace in China.

Greenspace exposure metrics can allow for comparisons of green space supply across time, space, and population groups, and for inferring patterns of variation in opportunities for people to enjoy the health and recreational benefits of nearby green environments. A better understanding of greenspace exposure differences across various spatial scales is a critical requirement for lessening environmental health disparities. However, existing studies are typically limited to a single city or across selected cities, which severely limits the use of results in measuring systemic national and regional scale differences that might need policy at above individual city planning level. To close this knowledge gap, our study aims to provide a holistic assessment of multi-scale greenspace exposure across provinces, cities, counties, towns, and land parcels for the whole of China. We mapped the nationwide fractional greenspace coverage at 10 m with Sentinel-2 satellite imagery, and then modeled population-weighted greenspace exposure to examine variation of greenspace exposure across scales. Our results show a prominent scaling effect of greenspace exposure across multi-scale administrative divisions in China, suggesting, as expected, an increase in heterogeneity with finer spatial scales. We also identify an asymmetric pattern of the difference between greenspace exposure and greenspace coverage, across a geo-demographic demarcation boundary (i.e., along the Heihe-Tengchong Line). In general, the greenspace coverage rate will overestimate more realistic human exposure to greenspace in East China while underestimating in West China. We further found that, in China, more recently urbanized areas have much better greenspace exposure than older urban areas. Our study provides a spatially explicit greenspace exposure metric for discovering multi-scale greenspace exposure difference, which will enhance governments' capacity to quantify environmental justice, detect vulnerable greenspace exposure risk hotspots, prioritize greenspace management at the supra-city scale, and monitor the balance between greenspace supply and demand.

Supply-demand matching of medical services at a city level under the background of hierarchical diagnosis and treatment - based on Didi Chuxing Data in Haikou, China.

BACKGROUND: Implementation of the Healthy China Strategy and the hierarchical diagnosis and treatment system has injected new vitality into medical services. Given the insufficient supply of medical services and increasing demand for medical treatment, exploring the supply-demand pattern of medical services has become an urgent theoretical and practical problem to be solved. The equity of healthcare facilities has received widespread attention, but due to limited data, there is little research on the supply-demand pattern of medical services. This study focuses on evaluating the supply-demand matching pattern of medical services at different levels in Haikou City with big geographic data and promoting the realization of a balance between medical supply and demand. METHODS: This study utilizes spatial data of medical institutions, Didi Chuxing Data, and population density data. Firstly, use the two-step floating catchment area method and GIS spatial analysis to explore characteristics of the supply-demand patterns of medical services at different levels in Haikou. Secondly, we mine residents' demand for medical treatment based on Didi Chuxing Data. Then combined with population density data, divide supply-demand matching of medical institutions into four types. Finally, propose optimization strategies for the problems. RESULTS: The accessibility pattern of high-level medical institutions in Haikou presents high in the north and low in the south. The accessibility pattern of low-level medical institutions is the opposite. High-level medical institutions have a strong demand for medical treatment, which is less hampered by distance. The healthcare demand of low-level medical institutions is small, and they mainly are medium- and short-distance medical travel. The types of medical services at different levels are mainly "low supply - low demand" and "high supply - low demand" types. CONCLUSIONS: Medical services at different levels in Haikou are mainly in supply-demand imbalance. Therefore, we put forward optimization strategies to promote the equity of primary medical services, such as propelling the establishment and improvement of the hierarchical diagnosis and treatment system, building a new model of medical and health service supply, and strengthening balanced coverage of primary medical institutions. The mining of big geographic data is beneficial to alleviate the mismatch between medical supply and demand, although the data and methods need to be improved.

Energy market uncertainty and the impact on the crude oil prices.

Our paper proposes a novel measure of global energy market uncertainty and studies its impact on oil prices. The current literature primarily relies on a single or small number of observable variables, or general macroeconomic uncertainty (JLN) and economic policy uncertainty (EPU) indices to reflect energy market uncertainty. Using a Factor Augmented Vector Autoregression model (FAVAR), we construct time-varying global energy market uncertainty in a data-rich environment. Our estimates show variations from JLN and EPU proxies. The results reveal that real oil prices respond strongly to our proposed aggregate energy market uncertainty shocks. We also find heterogeneous responses to different types and magnitudes of uncertainty shocks. The real price of oil is affected the most under unexpected strong demand for alternative energy sources scenario.

Population pharmacokinetics of the anti-PD-1 antibody camrelizumab in patients with multiple tumor types and model-informed dosing strategy.

Camrelizumab, a programmed cell death 1 (PD-1) inhibitor, has been approved for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma, nasopharyngeal cancer and non-small cell lung cancer. The aim of this study was to perform a population pharmacokinetic (PK) analysis of camrelizumab to quantify the impact of patient characteristics and to investigate the appropriateness of a flat dose in the dosing regimen. A total of 3092 camrelizumab concentrations from 133 patients in four clinical trials with advanced melanoma, relapsed or refractory classical Hodgkin lymphoma and other solid tumor types were analyzed using nonlinear mixed effects modeling. The PKs of camrelizumab were properly described using a two-compartment model with parallel linear and nonlinear clearance. Then, covariate model building was conducted using stepwise forward addition and backward elimination. The results showed that baseline albumin had significant effects on linear clearance, while actual body weight affected intercompartmental clearance. However, their impacts were limited, and no dose adjustments were required. The final model was further evaluated by goodness-of-fit plots, bootstrap procedures, and visual predictive checks and showed satisfactory model performance. Moreover, dosing regimens of 200 mg every 2 weeks and 3 mg/kg every 2 weeks provided similar exposure distributions by model-based Monte Carlo simulation. The population analyses demonstrated that patient characteristics have no clinically meaningful impact on the PKs of camrelizumab and present evidence for no advantage of either the flat dose or weight-based dose regimen for most patients with advanced solid tumors.

Fresh Agricultural Products Supply Chain Coordination and Volume Loss Reduction Based on Strategic Consumer.

The reduction of fresh agricultural product volume loss throughout the supply chain system is of high importance due to their perishable nature and impact on society, the economy, and environment. In this paper, three models for two-stage pricing, coordination, and volume loss reduction of the supply chain where third-party logistics service providers and retailers act as a Stackelberg leader and a follower for fresh agricultural products are developed, taking into account both volume loss during transport and quality loss in retail in the presence of strategic consumers. The following results are drawn from the contract for sharing revenues and service costs: (1) The supply chain achieve coordination and the products are healthier for consumers; (2) the coordination leads to a reduction in the three types of volume losses simultaneously only if the lowest marginal costs of the supply chain occur under certain conditions; and (3) the increase in the service sensitivity coefficient, the increase in the freshness discount coefficient under certain conditions, the decrease in the consumer benefit discount coefficient under certain conditions, and the decrease in the price sensitivity coefficient lead to an increase in the profit of the supply chain and a reduction in the three types of volume losses.

Global supply-chain effects of COVID-19 control measures.

Countries have sought to stop the spread of coronavirus disease 2019 (COVID-19) by severely restricting travel and in-person commercial activities. Here, we analyse the supply-chain effects of a set of idealized lockdown scenarios, using the latest global trade modelling framework. We find that supply-chain losses that are related to initial COVID-19 lockdowns are largely dependent on the number of countries imposing restrictions and that losses are more sensitive to the duration of a lockdown than its strictness. However, a longer containment that can eradicate the disease imposes a smaller loss than shorter ones. Earlier, stricter and shorter lockdowns can minimize overall losses. A 'go-slow' approach to lifting restrictions may reduce overall damages if it avoids the need for further lockdowns. Regardless of the strategy, the complexity of global supply chains will magnify losses beyond the direct effects of COVID-19. Thus, pandemic control is a public good that requires collective efforts and support to lower-capacity countries.

Evaluation of the pharmacokinetics and food intake effect of generic sofosbuvir in healthy Chinese subjects
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OBJECTIVE: Sofosbuvir is an NS5B nucleotide inhibitor that was approved for hepatitis C treatment. Generic sofosbuvir has been produced to improve the affordability. The present study investigated the pharmacokinetics (PK) and safety of generic sofosbuvir as well as the effect of food intake on its PK parameters in healthy Chinese subjects. MATERIALS AND METHODS: This open-label, randomized, multiple-dose, dose-escalating, and food effect trial enrolled 12 healthy Chinese subjects. The subjects received a single oral dose of 400 mg of generic sofosbuvir in fasted state or after a high-fat meal, or 800 mg in fasted state, in a three-way crossover design, and then all subjects were administered with 400 mg daily for 8 days. The PK parameters for sofosbuvir and its metabolites were determined, and the safety was monitored. RESULTS: Sofosbuvir was absorbed rapidly into plasma, with a half-life of 0.46 - 0.48 hours. Plasma exposure to sofosbuvir and its metabolite GS-566500 was increased in an approximately proportional manner to the increased dose. Repeated dosing did not result in drug accumulation in the blood. Sofosbuvir was mainly excreted as the metabolite GS-331007 in the urine. Drug administration after a high-fat meal increased the plasma sofosbuvir exposure by 1.29-fold, without substantially altering the absorption rate. No serious adverse events were observed, and all subjects tolerated the doses well. CONCLUSION: This generic sofosbuvir was well absorbed, the plasma concentration was increased with an increased dose, and it was safe in healthy subjects. A high-fat meal appeared to promote the bioavailability of sofosbuvir and the metabolite GS-566500.

Comparative study of 4D CTA and DSA for vascular assessment in moyamoya disease.

PURPOSE: To evaluate the vascular stenosis and collateral circulation in moyamoya disease using 4D CTA. METHODS: Two neuroradiologists evaluated 4D CTA and DSA for 101 moyamoya patients. The performance of 4D CTA relative to DSA was determined using consistency checks (kappa values, 95% CI) and correlation analysis. RESULTS: The kappa values were 0.714 (modified Suzuki score), 0.846 (Houkin score), 0.594 (basicranial moyamoya vessels), 0.435 (posterior circulation collaterals) and 0.591 (ECA collaterals). The correlation coefficients were 0.843, 0.872, 0.792, 0.635 and 0.797. CONCLUSIONS: 4D CTA showed strong consistency and correlation with DSA in the vascular stenosis score, but was insufficient in collateral circulation evaluation.

Predictive assessment in pharmacogenetics of Glutathione S-transferases genes on efficacy of platinum-based chemotherapy in non-small cell lung cancer patients.

The influences of glutathione s-transferase P1, M1, and T1 variants on the efficacy of platinum-based chemotherapy in non-small cell lung cancer (NSCLC) patients were inconsistent in previous studies. Our meta-analysis enrolled 31 publications including 5712 patients and provided more convincing and reliable conclusions. Results showed that GSTP1 IIe105Val IIe/Val and Val/Val Asian patients were more likely to have better response rates compared to IIe/IIe patients (odds ratio (OR) = 1.592, 95% confidence intervals (CIs), 1.087-2.332, P = 0.017). The Asian patients bearing the favorable GSTM1 null genotype were more likely to have better response rates to platinum-based chemotherapy compared to those patients with the unfavorable GSTM1 present genotype (OR = 1.493 (1.192-1.870), P < 0.001). Caucasian lung cancer patients bearing GSTT1 null genotype might be more closely associated with shorter survival time and higher risks of death than the GSTT1 present patients (hazard ratio (HR) = 1.423, CI = 1.084-1.869, P = 0.011). Our meta-analysis suggested that the GSTP1 IIe105Val, GSTM1 and GSTT1 null variants might be predictive factors for the efficacy of platinum-based chemotherapy to NSCLC patients. The use of GSTP1 IIe105Val, GSTM1 and GSTT1 null polymorphisms as predictive factors of efficacy of personalized platinum-based chemotherapy to NSCLC patients requires further verification with multi-center, multi-ethnic and large-sample-size pharmacogenetic studies.

The Lancet Countdown: tracking progress on health and climate change.

The Lancet Countdown: tracking progress on health and climate change is an international, multidisciplinary research collaboration between academic institutions and practitioners across the world. It follows on from the work of the 2015 Lancet Commission, which concluded that the response to climate change could be "the greatest global health opportunity of the 21st century". The Lancet Countdown aims to track the health impacts of climate hazards; health resilience and adaptation; health co-benefits of climate change mitigation; economics and finance; and political and broader engagement. These focus areas form the five thematic working groups of the Lancet Countdown and represent different aspects of the complex association between health and climate change. These thematic groups will provide indicators for a global overview of health and climate change; national case studies highlighting countries leading the way or going against the trend; and engagement with a range of stakeholders. The Lancet Countdown ultimately aims to report annually on a series of indicators across these five working groups. This paper outlines the potential indicators and indicator domains to be tracked by the collaboration, with suggestions on the methodologies and datasets available to achieve this end. The proposed indicator domains require further refinement, and mark the beginning of an ongoing consultation process-from November, 2016 to early 2017-to develop these domains, identify key areas not currently covered, and change indicators where necessary. This collaboration will actively seek to engage with existing monitoring processes, such as the UN Sustainable Development Goals and WHO's climate and health country profiles. The indicators will also evolve over time through ongoing collaboration with experts and a range of stakeholders, and be dependent on the emergence of new evidence and knowledge. During the course of its work, the Lancet Countdown will adopt a collaborative and iterative process, which aims to complement existing initiatives, welcome engagement with new partners, and be open to developing new research projects on health and climate change.