Targeted Quantification of Glutathione/Arginine Redox Metabolism Based on a Novel Paired Mass Spectrometry Probe Approach for the Functional Assessment of Redox Status.

Glutathione (GSH) redox control and arginine metabolism are critical in regulating the physiological response to injury and oxidative stress. Quantification assessment of the GSH/arginine redox metabolism supports monitoring metabolic pathway shifts during pathological processes and their linkages to redox regulation. However, assessing the redox status of organisms with complex matrices is challenging, and single redox molecule analysis may not be accurate for interrogating the redox status in cells and in vivo. Herein, guided by a paired derivatization strategy, we present a new ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)-based approach for the functional assessment of biological redox status. Two structurally analogous probes, 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) and newly synthesized 2-methyl-6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (MeAQC), were set for paired derivatization. The developed approach was successfully applied to LPS-stimulated RAW 264.7 cells and HDM-induced asthma mice to obtain quantitative information on GSH/arginine redox metabolism. The results suggest that the redox status was remarkably altered upon LPS and HDM stimulation. We expect that this approach will be of good use in a clinical biomarker assay and potential drug screening associated with redox metabolism, oxidative damage, and redox signaling.

Disparities of Heatwave-Related Preterm Birth in Climate Types - China, 2012-2019.

What is already known about this topic?: An association between prenatal heatwave exposure and the risk of preterm birth was found. However, the disparities in heatwave-related preterm birth across different climate types have not been examined. What is added by this report?: This nationwide case-crossover study investigated the association between heatwave exposure and preterm birth across different Köppen-Geiger climate types. Among pregnant women residing in the arid-desert-cold climate type, exposure to compound heatwaves was found to be associated with a significantly higher risk of preterm birth {adjusted odds ratios (AORs) ranged from 1.55 [95% confidence interval ( CI): 1.21-1.97] to 2.11 (95% CI: 1.35-3.31)}. In contrast, among pregnant women residing in the tropical monsoonal climate type, exposure to daytime-only heatwaves was associated with an increased risk of preterm birth [AORs ranged from 1.25 (95% CI: 1.03-1.51) to 1.37 (95% CI: 1.05-1.77)]. What are the implications for public health practice?: Specific interventions should be implemented in China to mitigate the risk of preterm birth related to heatwaves, particularly for pregnant women residing in arid-desert-cold and tropical monsoonal climates.

Global Variations in Heart Failure Etiology, Management, and Outcomes.

Importance: Most epidemiological studies of heart failure (HF) have been conducted in high-income countries with limited comparable data from middle- or low-income countries. Objective: To examine differences in HF etiology, treatment, and outcomes between groups of countries at different levels of economic development. Design, Setting, and Participants: Multinational HF registry of 23 341 participants in 40 high-income, upper-middle-income, lower-middle-income, and low-income countries, followed up for a median period of 2.0 years. Main Outcomes and Measures: HF cause, HF medication use, hospitalization, and death. Results: Mean (SD) age of participants was 63.1 (14.9) years, and 9119 (39.1%) were female. The most common cause of HF was ischemic heart disease (38.1%) followed by hypertension (20.2%). The proportion of participants with HF with reduced ejection fraction taking the combination of a ß-blocker, renin-angiotensin system inhibitor, and mineralocorticoid receptor antagonist was highest in upper-middle-income (61.9%) and high-income countries (51.1%), and it was lowest in low-income (45.7%) and lower-middle-income countries (39.5%) (P < .001). The age- and sex- standardized mortality rate per 100 person-years was lowest in high-income countries (7.8 [95% CI, 7.5-8.2]), 9.3 (95% CI, 8.8-9.9) in upper-middle-income countries, 15.7 (95% CI, 15.0-16.4) in lower-middle-income countries, and it was highest in low-income countries (19.1 [95% CI, 17.6-20.7]). Hospitalization rates were more frequent than death rates in high-income countries (ratio = 3.8) and in upper-middle-income countries (ratio = 2.4), similar in lower-middle-income countries (ratio = 1.1), and less frequent in low-income countries (ratio = 0.6). The 30-day case-fatality rate after first hospital admission was lowest in high-income countries (6.7%), followed by upper-middle-income countries (9.7%), then lower-middle-income countries (21.1%), and highest in low-income countries (31.6%). The proportional risk of death within 30 days of a first hospital admission was 3- to 5-fold higher in lower-middle-income countries and low-income countries compared with high-income countries after adjusting for patient characteristics and use of long-term HF therapies. Conclusions and Relevance: This study of HF patients from 40 different countries and derived from 4 different economic levels demonstrated differences in HF etiologies, management, and outcomes. These data may be useful in planning approaches to improve HF prevention and treatment globally.

Comprehensive evaluation of water ecological environment in watersheds: a case study of the Yangtze River Economic Belt, China.

The Yangtze River Economic Belt, an inland economic zone with global influence, has shown a trend of prosperous economic development in recent years. Economic development, water pollution, resource depletion, and other environmental problems continue to emerge. The steady state of the water ecological environment is an important aspect of ecological security. To investigate the regional water ecological security state, this study constructs a comprehensive evaluation indicator system within the framework of "driving force-carrying source-state-management" (DCSM). The entropy weight method was used to determine the weight of each indicator, and the weighted rank sum ratio model was introduced to classify the water ecological environment of the Yangtze River Economic Belt from 2010 to 2019. Finally, an adversarial interpretative structure model is used to refine the ranking of each region. The results show that the bearing state and driving force subsystems are closely related to the water ecological environment. The top three indicators are wastewater discharge of industrial added value of 10,000 yuan, water consumption per 10,000 yuan of industrial gross product, and water consumption per 10,000 yuan of tertiary gross domestic product. In addition, there are clear differences in the water ecological environment of the Yangtze River Economic Belt. The classification results show that Zhejiang and Jiangsu are rated as "excellent''; Yunnan, Guizhou, Anhui, and Jiangxi are in the "good" level; and Sichuan, Hunan, Chongqing, and Hubei are in the "medium" level. Shanghai is "poor." As a whole, the downstream is superior, the upstream is second, and the midstream is poor in an asymmetric "U"-shaped distribution. During the study period, the overall state of water ecology in the Yangtze River Economic Belt was at a medium level and has not yet reached a safe and steady state. The performance of areas with traditional industrialization as the main development path was poor. Therefore, it is necessary to pay attention to the overall water ecological security in the basin in the future, strengthen the regulatory role of the government's water ecological management, promote reform of traditional industries and resource-based regions, and achieve the sustainable development of the water ecological environment.

Role of Up-Regulated Transmembrane Channel-Like Protein 5 in Pancreatic Adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a malignant tumor responsible for a heavy disease burden. Previously, only one pan-cancer study of Transmembrane channel-like protein 5 (TMC5) showed that TMC5 was highly expressed in PAAD, but the results lacked comprehensive verification, and the mechanism of TMC5 in PAAD was still unclear. METHODS: For exploring the expression and clinical value of TMC5 in PAAD better, we adopted a comprehensive evaluation method, using internal immunohistochemistry (IHC) data combined with microarray and RNA-sequencing data collected from public databases. The single cell RNA-sequencing (scRNA-seq) data were exploited to explore the TMC5 expression in cell populations and intercellular communication. The potential mechanism of TMC5 in PAAD was analyzed from the aspects of immune infiltration, transcriptional regulation, function and pathway enrichment. RESULTS: Our IHC data includes 148 PAAD samples and 19 non-PAAD samples, along with the available microarray and RNA-sequencing data (1166 PAAD samples, 704 non-PAAD samples). The comprehensive evaluation results showed that TMC5 was evidently up-regulated in PAAD (SMD = 1.17). Further analysis showed that TMC5 was over-expressed in cancerous epithelial cells. Furthermore, TMC5 was up-regulated in more advanced tumor T and N stages. Interestingly, we found that STAT3 as an immune marker of Th17 cells was not only positively correlated with TMC5 and up-regulated in PAAD tissues, but also the major predicted TMC5 transcription regulator. Moreover, STAT3 was involved in cancer pathway of PAAD. CONCLUSION: Up-regulated TMC5 indicates advanced tumor stage in PAAD patients, and its role in promoting PAAD development may be regulated by STAT3.

Aberrant gray matter volume and functional connectivity in Parkinson's disease with minor hallucination.

Background: Minor hallucination (MH) is the most common psychotic symptom in Parkinson's disease (PD); it can develop into well-structured visual hallucination (VH), suggesting that MH may be a staccato form of well-structured VH. However, it remains unclear whether the pathogenesis is the same. Therefore, the aim of this study was to investigate the altered gray matter volume (GMV) and functional connectivity (FC) of MH in PD to further understand the complex mechanisms. Materials and methods: We included 67 PD patients who attended the outpatient clinic of Nanjing Medical University Affiliated Brain Hospital and recruited 31 healthy controls (HC). Demographic data and clinical characteristics of all subjects were recorded, and cranial structural magnetic resonance imaging (MRI) and resting-state functional MRI data were acquired. Patients were classified into the PD with MH (PD-MH) group and PD without hallucinations or delusions (PD-NH) group. Voxel-based morphometry was used to analyze the differences in GMV in the structural pattern. Seed-based FC was used to analyze the functional pattern. Gaussian random field correction was used, with voxel level P < 0.001 and cluster level P < 0.05 representing statistically significant differences. Finally, the correlation between FC values and scores on the clinical characteristics assessment scale was analyzed. Results: In the GMV analysis, compared to the PD-NH group, the PD-MH group had reduced GMV in the medial superior frontal gyrus (SFGmed). In the FC analysis, the FC between the SFGmed and the left middle occipital gyrus and right calcarine sulcus decreased in the PD-MH group compared with the PD-NH group, while the FC between SFGmed and the left middle temporal gyrus increased. Correlation analysis revealed that the FC values of the SFGmed and right calcarine sulcus were correlated with the assessment scores for anxiety and sleep symptoms. The FC values of the SFGmed and left middle occipital gyrus were correlated with assessment scores for rapid eye movement disorder. Conclusion: The aberrant structure and function of the default mode network and visual processing areas seems to facilitate the generation of MH in PD, as the alteration was previously found in well-structured VH, suggesting that the two hallucinations have similar pathophysiological mechanisms.

Analysis of the Application Value of Echocardiography Combined with CK-MB, Alb, and CysC in the Prognosis Assessment of Patients with Chronic HF.

In order to evaluate the diagnostic and prognostic value of echocardiography combined with serum creatine kinase-MB (CK-MB), albumin (Alb), and cystatin C (CysC) in patients with chronic heart failure (HF), 93 patients diagnosed with chronic HF in our hospital from March 2019 to January 2020 are retrospectively analyzed and included in the HF group. Another 100 healthy subjects who come to our hospital for general physical examination are selected as the control group. Echocardiography is used to detect the cardiac parameters of each group. The experimental results show that echocardiography parameters combined with CK-MB, Alb, and CysC have high application value in diagnosis and evaluation of patients with chronic HF, which can provide theoretical basis for improving the prognosis of patients with chronic HF through real-time monitoring of the above indicators.

Adaptive soft sensing of river flow prediction for wastewater treatment operation and risk management.

Many wastewater utilities have discharge permits directly tied with the receiving river flow, so it is critical to have accurate prediction of the hydraulic throughput to ensure safe operation and environment protection. Current empirical knowledge-based operation faces many challenges, so in this study we developed and assessed daily-adaptive, probabilistic soft sensor prediction models to forecast the next month's average receiving river flowrate and guide the utility operations. By comparing 11 machine-learning methods, extra trees regression exhibits desired deterministic prediction accuracy at day 0 (overall accuracy index: 3.9 × 10-3 1/cms2) (cms: cubic meter per second), which also increases steadily over the course of the month (e.g., MAPE and RMSE decrease from 41.46% and 23.31 cms to 3.31% and 2.81 cms, respectively). The overall classification accuracy of three river flow classes reaches 0.79 at the beginning and increases to about 0.97 over the course of the predicted month. To manage the uncertainty caused by potential false negative classification as overestimations, a probabilistic assessment on the predictions based on 95% lower PI is developed and successfully reduces the false negative classification from 17% to nearly zero with a slight sacrifice of overall classification accuracy.

Assessment of the Characteristics of Waxy Rice Mutants Generated by CRISPR/Cas9.

The cooking and eating quality of rice grains is a major focus from a consumer's perspective and is mainly determined by the apparent amylose content (AAC) of the starch. Waxy rice, a type of rice with an AAC of less than 2%, is an important goal for the breeding of high-quality rice. In recent years, the cloning of the Waxy (Wx) gene has revealed the molecular mechanism of the formation of waxy traits in rice. However, there have been limited studies on the physicochemical properties, such as gelatinization temperature, rapid viscosity analyzer profile, and amylopectin fine structure of wx mutants. In the current study, a rapid and highly efficient strategy was developed through the CRISPR/Cas9 gene-editing system for generating wx mutants in the background of five different rice varieties. The wx mutation significantly reduced the AAC and starch viscosity but did not affect the major agronomic traits (such as plant height, panicle number per plant, grain number per panicle, and seed-setting frequency). Incorporation of the wx mutation into varieties with low initial AAC levels resulted in further reduction in AAC, but without significantly affecting the original, desirable gelatinization traits and amylopectin structure types, suggesting that parents with low initial AAC should be preferred in breeding programs.

Risk Assessment in Diffuse Large B-Cell Lymphoma by Combining Baseline Metabolic Tumor Volume and Peking Criteria When Evaluating Series 18F-Fluorodeoxyglucose Positron Emission Tomography Scans.

This study aimed to determine the predictive and prognostic value of baseline metabolic tumor volume (MTV) and the Peking criteria from serial positron emission tomography (PET) scans in diffuse large B-cell lymphoma, including 300 newly diagnosed patients who were prospectively treated with 2-4 cycles of standard first-line treatment (clinicaltrials.gov identifier: NCT02928861). PET/computed tomography (CT) examinations were performed at baseline, after two (PET-2) or four cycles (PET-4). PET during the interim was evaluated using Deauville 5-point scales (5-PS), ΔSUVmax criteria, and the Peking criteria which interpreted based on the maximum standard uptake of the liver (SUVmax-liver). Peking criteria had better accuracy, positive predictive value (PPV), and specificity than other two methods. The MTV and Peking criteria both significantly predicted progression-free survival (PFS) and overall survival (OS). An MTV > 191 cm2 and Peking criteria of PET-2 and PET-4 > 1.6-fold SUVmax-liver was used as the cutoff for a positive result. PET-4 achieved higher accuracy, PPV, and specificity for 2-year PFS (83.3%, 86.7%, and 98.4%, respectively) and OS (92.6%, 73.3%, and 97.2%, respectively) than PET-2. Various prognostic models containing different risk factors were established via Cox regression analysis. The MTV and PET-2/PET-4 results were used to categorized patients into low-risk, intermediate-risk, and high-risk prognostic groups (with 0, 1, and 2 risk factors, respectively) (P < 0.0001). High burden MTV and positive PET-2 and PET-4 (>1.6-fold SUVmax-liver) could identify high-risk patients with 2-year PFS and OS of 0.0% and 26.3% (95% confidence interval [CI]: N/A to 54.3%). When PET-2 and PET-4 were evaluated by 5-PS, the 2-year PFS and OS from high risk patients of three-parameters model achieved 31.4% (95%CI: 6.9%-55.9%) and 42.7% (95%CI: 14.6%-70.7%). In conclusion, combining baseline MTV and any regular response on PET/CT evaluated using the Peking criteria can improve prognostic value. Serial PET/CT from baseline MTV to PET-4 may have relatively greater predictive power for poor prognosis in diffuse large B-cell lymphoma. Clinical Trial Registration: ClinicalTrials.gov, identifier (NCT02928861).

Hybrid modelling of water resource recovery facilities: status and opportunities.

Mathematical modelling is an indispensable tool to support water resource recovery facility (WRRF) operators and engineers with the ambition of creating a truly circular economy and assuring a sustainable future. Despite the successful application of mechanistic models in the water sector, they show some important limitations and do not fully profit from the increasing digitalisation of systems and processes. Recent advances in data-driven methods have provided options for harnessing the power of Industry 4.0, but they are often limited by the lack of interpretability and extrapolation capabilities. Hybrid modelling (HM) combines these two modelling paradigms and aims to leverage both the rapidly increasing volumes of data collected, as well as the continued pursuit of greater process understanding. Despite the potential of HM in a sector that is undergoing a significant digital and cultural transformation, the application of hybrid models remains vague. This article presents an overview of HM methodologies applied to WRRFs and aims to stimulate the wider adoption and development of HM. We also highlight challenges and research needs for HM design and architecture, good modelling practice, data assurance, and software compatibility. HM is a paradigm for WRRF modelling to transition towards a more resource-efficient, resilient, and sustainable future.

Burden of lymphoma in China, 1990-2019: an analysis of the global burden of diseases, injuries, and risk factors study 2019.

BACKGROUND: China is facing an aggravating disease burden of lymphoma. However, accurate information about lymphoma burden at the national and provincial levels is limited. RESULTS: The estimated number of disability-adjusted life years were 86,171.85 for Hodgkin lymphoma and 1,306,247.77 for non-Hodgkin lymphoma with the age-standardized rates of 4.95 and 71.00, respectively, per 100,000 population. There were estimated 9,468 new cases and 2,709 Hodgkin lymphoma-related deaths, and 91,954 new cases and 44,310 non-Hodgkin lymphoma-related deaths. Older individuals had a higher lymphoma burden. The age-standardized disability-adjusted life year rate in men was approximately two-folds higher than that in women. Moreover, disparities in lymphoma burden were observed across the provinces. Between 1990 and 2019, the disability-adjusted life year number decreased by 57.8% for Hodgkin lymphoma, and increased by 100.9% for non-Hodgkin lymphoma. CONCLUSION: Burden of lymphoma showed heterogeneous change patterns varied according to sex, age, and provinces, with a steady decrease in Hodgkin lymphoma and a significant increase in non-Hodgkin lymphoma during the past three decades. METHODS: Following the analytical strategy used in the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, age-, sex-, and province-specific incidence, mortality, and prevalence of Hodgkin lymphoma and non-Hodgkin lymphoma were analyzed. Lymphoma burden was assessed by incidence, mortality, prevalence, and disability-adjusted life year.

Produce individual medium chain carboxylic acids (MCCA) from swine manure: Performance evaluation and economic analysis.

Environmental issues caused by untreated animal manure require the development of resource recovery from waste through a circular economy approach. Producing medium chain carboxylic acids (MCCA) with higher value than biogas from manure has become promising. The objective of this study was to develop an effective individual MCCA produce process utilizing manure. In this study, animal manure was firstly anaerobic fermentation into short chain fatty acids (SCFA), then acidified manure and ethanol were fed into the chain elongation reactor with gradually increasing the organic loading rate (OLR) from 7.0 to 18.5 gCOD/L/d, and the mixed MCCA was separated individually via a fractional distillation process. The SCFA fermentation occurred mainly at the first 10 days, and the optimum concentrations of SCFA for treatments at 2 %VS, 4 %VS and 6 %VS were 6.58, 10.40 and 14.10 g/L, respectively. For the chain elongation reactor, the maximum concentrations of n-caproate and n-caprylate were 10.25 and 0.63 g/L, respectively, which were comparable with that obtained from other complex wastes. Over 90% MCCA can be recovered from the fermentation broth via the optimized extractant of methyl tert-butyl ether (MTBE) and the fractional distillation system. Preliminary economic analysis shows that this MCCA production process presented a higher economic benefit (9.25 $/m3 manure) than traditional biogas production (2.65 $/m3 manure), making MCCA production from swine manure economically competitive. This work provides a new route for manure resource recovery besides the biogas process.

Low cost, robust, environmentally friendly, wood supported 3D-hierarchical Cu3SnS4 for efficient solar powered steam generation.

Solar steam generation has great potential in alleviating freshwater crises, particularly in regions with accessible seawater and abundant insolation. Inexpensive, efficient, and eco-friendly photothermal materials are desired to fabricate sunlight-driven evaporation devices. Here, we have designed an economical strategy to fabricate a high-performance wood-based solar steam generation device. In current study, 3D-hierarchical Cu3SnS4 has been loaded on wood substrates of variable sizes via an in-situ solvothermal method. Considering the water transportation capacity and thermal insulation property of wood, an enhanced light absorption was achieved by a uniform coating of Cu3SnS4 on the inside and outside of the 3D porous structure of the wood. Thanks for the synergistic effect of Cu3SnS4 and wood substrate, the obtained composite endorsed high-performance solar steam generation with a steam generation efficiency of 90% and an evaporation rate as high as 1.35 kg m-2h-1 under one sun.

A new scoring system for predicting short-term outcomes in Chinese patients with critically-ill acute decompensated heart failure.

BACKGROUND: Acute decompensated heart failure (ADHF) contributes millions of emergency department (ED) visits and it is associated with high in-hospital mortality. The aim of this study was to develop and validate a multiparametric score for critically-ill ADHF patients. METHODS: In this single-center, retrospective study, a total of 1268 ADHF patients in China were enrolled and divided into derivation (n = 1014) and validation (n = 254) cohorts. The primary endpoint was any in-hospital death, cardiac arrest or utilization of mechanical support devices. Logistic regression model was preformed to identify risk factors and build the new scoring system. The assigning point of each parameter was determined according to its ß coefficient. The discrimination was validated internally using C statistic and calibration was evaluated by the Hosmer-Lemeshow goodness-of-fit test. RESULTS: We constructed a predictive score based on six significant risk factors [systolic blood pressure (SBP), white blood cell (WBC) count, hematocrit (HCT), total bilirubin (TBIL), estimated glomerular filtration rate (eGFR) and NT-proBNP]. This new model was computed as (1 × SBP < 90 mmHg) + (2 × WBC > 9.2 × 109/L) + (1 × HCT ≤ 0.407) + (2 × TBIL > 34.2 µmol/L) + (2 × eGFR < 15 ml/min/1.73 m2) + (1 × NTproBNP ≥ 10728.9 ng/ml). The C statistic for the new score was 0.758 (95% CI 0.667-0.838) higher than APACHE II, AHEAD and ADHERE score. It also demonstrated good calibration for detecting high-risk patients in the validation cohort (χ2 = 6.681, p = 0.463). CONCLUSIONS: The new score including SBP, WBC, HCT, TBIL, eGFR and NT-proBNP might be used to predict short-term prognosis of Chinese critically-ill ADHF patients.

Neonatal mortality and leading causes of deaths: a descriptive study in China, 2014-2018.

OBJECTIVE: The present study estimated the national and urban-rural levels and causes of neonatal deaths in China annually between 2014 and 2018 to provide data support for the further end of preventable neonatal deaths for China and other low-income and middle-income countries. METHODS: The study was based on data from the National Maternal and Child Health Surveillance System. All neonates of surveillance districts (gestational week: ≥28 weeks) who died after delivery have been involved in the study. The mortality rate and the leading causes of death for neonates were analysed. RESULTS: The neonatal mortality rate (NMR) of China has steadily decreased from 5.9 deaths per 1000 live births in 2014 to 3.9 deaths per 1000 live births in 2018. The NMR in 2018 of urban and rural areas was 2.2 deaths per 1000 live births and 4.7 deaths per 1000 live births, respectively. The leading preventable causes of neonatal deaths are the same in the urban and rural areas were same, which were preterm birth, intrapartum complications and pneumonia. Mortality rates of these three causes fell significantly between 2014 and 2018 but contributed to a higher proportion of deaths in rural areas than urban areas. The proportion of preventable deaths accounted for 74.6% in 2018. CONCLUSIONS: The NMR of China has decreased steadily from 2014 to 2018. However, the inequality between urban and rural areas still exists. The goal of government interventions should be to reduce the health inequality of neonates and further take targeted measures to eliminate preventable neonatal death.

Efficacy and safety of rivaroxaban plus aspirin in women and men with chronic coronary or peripheral artery disease.

AIMS: The COMPASS trial demonstrated that the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily compared with aspirin 100 mg once daily reduced major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease or peripheral artery disease by 24% during a mean follow-up of 23 months. We explored whether this effect varies by sex. METHODS AND RESULTS: The effects were examined in women and men using log-rank tests and Kaplan-Meier curve. Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were obtained from stratified Cox proportional hazards models to explore subgroup effects including subgroup of women and men according to baseline modified REACH risk score. Of 27 395 patients randomized, 18 278 were allocated to receive rivaroxaban plus aspirin (n = 9152) or aspirin alone (n = 9126), and of these, 22.1% were women. Women compared with men had similar incidence rates for MACE and major bleeding but borderline lower rates for myocardial infarction (1.7% vs. 2.2%, P = 0.05). The effect of combination therapy compared with aspirin in women and men was consistent for MACE (women: 3.8% vs. 5.2%, HR 0.72, 95% CI 0.54-0.97; men: 4.2% vs. 5.5%, HR 0.76, 95% CI 0.66-0.89; P interaction 0.75) and major bleeding (women: 3.1% vs. 1.4%, HR 2.22, 95% CI 1.42-3.46; men: 3.2% vs. 2.0%, HR 1.60, 95% CI 1.29-1.97; P interaction 0.19). There was no significant interaction between randomized treatment and baseline modified REACH score above or below the median for MACE or major bleeding. CONCLUSION: In patients with stable coronary artery disease or peripheral artery disease, the combination of rivaroxaban (2.5 mg twice daily) and aspirin compared with aspirin alone appears to produce consistent benefits in women and men, independent of baseline cardiovascular risk.

Variations in incidence of venous thromboembolism in low-, middle-, and high-income countries.

AIMS: To examine the rates of venous thromboembolism (VTE) in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification). METHODS AND RESULTS: We examined the rates of VTE in high-income, upper middle-income, and lower middle/low-income countries (World Bank Classification) in a cohort derived from four prospective international studies (PURE, HOPE-3, ORIGIN, and COMPASS). The primary outcome was a composite of pulmonary embolism, deep vein thrombosis, and thrombophlebitis. We calculated age- and sex-standardized incidence rates (per 1000 person-years) and used a Cox frailty model adjusted for covariates to examine associations between the incidence of VTE and country income level. A total of 215 307 individuals (1.5 million person-years of follow-up) from high-income (n = 60 403), upper middle-income (n = 42 066), and lower middle/low-income (n = 112 838) countries were included. The age- and sex-standardized incidence rates of VTE per 1000 person-years in high-, upper middle-, and lower middle/low-income countries were 0.87, 0.25, and 0.06, respectively. After adjusting for age, body mass index (BMI), smoking, antiplatelet therapy, anticoagulant therapy, education level, ethnicity, and incident cancer diagnosis or hospitalization, individuals from high-income and upper middle-income countries had a significantly higher risk of VTE than those from lower middle/low-income countries [hazard ratio (HR) 3.57, 95% confidence interval (CI) 2.40-5.30 and HR 2.27, 95% CI 1.59-3.23, respectively]. The effect of country income level on VTE risk was markedly stronger in people with a lower BMI, hypertension, diabetes, non-White ethnicity, and higher education. CONCLUSION: The rates of VTE are substantially higher in high-income than in low-income countries. The factors underlying the increased VTE risk in higher-income countries remain unknown.

Unsupervised aided investigation on the associations between municipal solid waste characteristics and socio-economic conditions.

Better municipal solid waste (MSW) management can help to address environmental concerns and supports economic and social development. Because MSW characteristics can change over time, management strategies should also evolve and be applied correspondingly. However, many previous studies have focused on MSW characterization or investigated specific management strategies for a target MSW. Few studies have assessed the spatial variations of MSW characteristics and socio-economic (SE) conditions as well as their associations. This study evaluated the feasibility of using an integrated unsupervised method (cluster analysis and cross-tabulation analysis) to explore these topics for MSW management. Results suggest that the integrated method can successfully help to reveal key information. Seven jointed MSW-SE scenarios were investigated based on 259 individual observations of Taiwan. Associations between MSW compositions and SE conditions were identified statistically significant for four MSW-SE scenarios. In general, the general SE type (SE1) is very likely to generate high food wastes and other combustible, low paper, wood, and rubber wastes (MSW1). The small island SE type (SE3) is more likely to produce high paper and low wood, rubber, textile, and other noncombustible wastes (MSW2). Overall, the method applied in this study could help to reveal statistical associations between MSW and SE, which can help decision-makers comprehend underlying facts and develop effective management strategies.

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.