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Modeling the relationship between multiple financial markets has had a great deal of attention in both literature and real-life applications. One state-of-the-art technique is that the individual financial market is modeled by generalized autoregressive conditional heteroskedasticity (GARCH) process, while market dependence is modeled by copula, e.g. dynamic asymmetric copula-GARCH. As an extension, we propose a dynamic double asymmetric copula (DDAC)-GARCH model to allow for the joint asymmetry caused by the negative shocks as well as by the copula model. Furthermore, our model adopts a more intuitive way of constructing the sample correlation matrix. Our new model yet satisfies the positive-definite condition as found in dynamic conditional correlation-GARCH and constant conditional correlation-GARCH models. The simulation study shows the performance of the maximum likelihood estimate for DDAC-GARCH model. As a case study, we apply this model to examine the dependence between China and US stock markets since 1990s. We conduct a series of likelihood ratio test tests that demonstrate our extension (dynamic double joint asymmetry) is adequate in dynamic dependence modeling. Also, we propose a simulation method involving the DDAC-GARCH model to estimate value at risk (VaR) of a portfolio. Our study shows that the proposed method depicts VaR much better than well-established variance–covariance method. [ABSTRACT FROM AUTHOR]

Inorganic arsenic is an environmental carcinogen that poses a major global public health risk. A high percentage of drinking water from wells in the U.S. contains higher-than-normal levels of arsenic, suggesting an increased risk of arsenic-induced deleterious effects. In addition to primary preventive measures, therapeutic strategies need to effectively address and integrate multiple molecular mechanisms underlying arsenic-induced carcinogenesis. We previously showed that the loss of miR-199a-5p in arsenic-transformed cells is pivotal to promote arsenic-induced angiogenesis and tumor growth in lung epithelial cells. In this study, we further showed that subacute or chronic exposure to arsenic diminished miR-199a-5p levels largely due to DNA methylation, which was achieved by increased DNA methyltransferase-1 (DNMT1) activity, mediated by the formation of specific protein 1 (Sp1)/DNMT1 complex. In addition to the DNA hypermethylation, arsenic exposure also repressed miR-199a transcription through a transcriptional repressor Sp1. We further identified an association between miR-199a-5p repression and the arsenic-mediated energy metabolic shift, as reflected by mitochondria defects and a switch to glycolysis, in which a glycolytic enzyme pyruvate kinase 2 (PKM2) was a functional target of miR-199a-5p. Taken together, the repression of miR-199a-5p through both Sp1-dependent DNA methylation and Sp1 transcriptional repression promotes an arsenic-mediated metabolic shift from mitochondria respiration to aerobic glycolysis via PKM2. Unlabelled Image • Sp-1-dependent DNA methylation contributes to arsenic-induced miR-199a-5p repression. • Loss of miR-199a-5p associates with an arsenic-mediated energy metabolic shift. • PKM2 is the key effector of miR-199a-5p to promote arsenic-induced glycolysis. • The study links the aberrant epigenetic changes to metabolic dysfunction in arsenic-mediated malignant transformation. [ABSTRACT FROM AUTHOR]

Background: Docosahexaenoic acid (DHA) has been reported to be associated with the children's neurodevelopment, who may be exposed to tobacco smoke simultaneously. The evidence about joint effect of DHA intake and tobacco smoke exposure on children and adolescents' learning disabilities (LD) was limited. The objective of this study was to assess the joint effect of DHA intake and tobacco smoke exposure on children and adolescents' LD., Methods: A cross-sectional analysis of the NHANES 1999-2004 was performed. Children and adolescents aged 6-15 years old were included. The outcome was diagnosed by parental report of ever health professionals or school representative-identified LD. Dietary DHA intake data were obtained by food frequency questionnaire and tobacco smoke exposure levels were evaluated by serum cotinine levels. Weighted univariable and multivariate logistic regression analyses were conducted to determine the joint effect of DHA intake and tobacco smoke exposure on LD in children and adolescents, with odds ratios (ORs) and 95% confidence intervals (CIs). This joint association was further assessed after stratification by age, gender, body mass index, the history of attention deficit disorder and seen mental health professional., Results: We identified 5,247 children and adolescents in present study, of whom 593 (11.30%) had LD. After adjusting covariates, we observed children and adolescents with DHA intake (OR = 0.76, 95%CI: 0.61-0.96) was related to lower incidence of LD; children who exposure to tobacco smoke was related to higher incidence of LD (OR = 1.54, 95%CI: 1.07-2.23); children and adolescents who exposure to tobacco smoke and without DHA intake were related to highest odds of LD (OR = 2.08, 95%CI: 1.37-3.17, P for trend = 0.042), that was, DHA and tobacco smoke exposure may have a joint effect on the odds of LD in children and adolescents. Subgroup analyses suggested this joint effect was robust especially among children and adolescents with normal & underweight BMI and without the history of attention deficit disorder and seen mental health professional., Conclusion: Increasing the DHA intake and reducing tobacco smoke exposure may have a potential role in the prevention of LD in children and adolescents. This joint effect warrants further investigation by large-scale prospective study., (© 2024. The Author(s).)

Background: Hepatic cancer is a common cancer in clinical practice. Current drug therapies for this condition include targeted therapy, chemotherapy, and immunotherapy. Tumor lysis syndrome (TLS) is the most serious complication of oncology treatment. According to the literature, several cases reported TLS occurred with targeted therapies for hepatic cancer., Methods: Reporting odds ratio and information component were used to measure the disproportionate signals for TLS associated with targeted therapies, using data from the FDA's Adverse Event Reporting System (FAERS). A stepwise sensitivity analysis was conducted to test the robustness of signals. Time-to-onset analysis was used to describe the latency of TLS events associated with targeted therapies. The Bradford Hill criteria were used to perform a global assessment of the evidence., Results: Sorafenib, lenvatinib, cabozantinib, and bevacizumab showed higher disproportionate signals for TLS than chemotherapy. The median number of days to TLS occurrence after drug therapy was 5.5, 6.5, and 6.5 days for sorafenib, lenvatinib, and bevacizumab, respectively., Conclusions: There is a significant association between tumor lysis syndrome and targeted therapies for hepatic carcinoma, with particularly strong signals for sorafenib and lenvatinib. Clinicians should be aware of the potential for tumor lysis syndrome in targeted therapies for hepatic carcinoma.

Objective: Globally, developed countries such as the United States, Canada, Germany, Korea, have carried out long-term and systematic biomonitoring programs for environmental chemicals in their populations. The China National Human Biomonitoring (CNHBM) was to document the extent of human exposure to a wide array of environmental chemicals, to understand exposure profiles, magnitude and ongoing trends in exposure in the general Chinese population, and to establish a national biorepository., Methods: CNHBM adopted three-stage sampling method to obtain a nationally representative sample of the population. A total of 21,888 participants who were permanent residents in 31 provinces were designed to interviewed in this national biomonitoring (152 monitoring sites × 3 survey units × 2 sexes × 6 age groups × 4 persons = 21,888 persons) in 2017-2018. Unlike the US National Health and Nutrition Examination Survey, the CNHBM will follow the same participants in subsequent cycles allowing for dynamic, longitudinal data sets for epidemiologic follow-up. Each survey cycle of CNHBM will last 2 years and each subsequent cycle will occur 3 years after the prior cycle's completion., Results: In 2017-2018, the CNHBM created a large cohort of Chinese citizens that included districts/counties questionnaire, community questionnaire collecting information on villages/communities, individual questionnaire, household questionnaire, comprehensive medical examination, and collection of blood and urine samples for measurement of clinical and exposure biomarkers. A total of 21,746 participants were finally included in CNHBM, accounting for 99.4% of the designed sample size; and 152 PSUs questionnaires, 454 community questionnaires, 21,619 family questionnaires, 21,712 cases of medical examinations, 21,700 individual questionnaires, 21,701 blood samples and 21,704 urine samples were collected, respectively. Planned analyses of blood and urine samples were to measure both inorganic and organic chemicals, including 13 heavy metals and metalloids, 18 poly- and per-fluorinated alkyl substances, 12 phthalate metabolites, 9 polycyclic aromatic hydrocarbons metabolites, 4 environmental alkylated phenols, and 2 benzene metabolites., Conclusions: CNHBM established the first nationally representative, prospective cohort in the Chinese population to understand the baseline and trend of internal exposure of environmental chemicals in general population, and to understand environmental toxicity., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyse the spatial-temporal clustering of the HIV/AIDS epidemic in Chongqing and to explore its association with the economic indices of AIDS prevention and treatment., Methods: Data on the HIV/AIDS epidemic and economic indices of AIDS prevention and treatment were obtained from the annual reports of the Chongqing Municipal Center for Disease Control for 2006-2012. Spatial clustering analysis, temporal-spatial clustering analysis, and spatial regression were used to conduct statistical analysis., Results: The annual average new HIV infection rate, incidence rate for new AIDS cases, and rate of people living with HIV in Chongqing were 5.97, 2.42 and 28.12 per 100,000, respectively, for 2006-2012. The HIV/AIDS epidemic showed a non-random spatial distribution (Moran's I≥0.310; p<0.05). The epidemic hotspots were distributed in the 15 mid-western counties. The most likely clusters were primarily located in the central region and southwest of Chongqing and occurred in 2010-2012. The regression coefficients of the total amount of special funds allocated to AIDS and to the public awareness unit for the numbers of new HIV cases, new AIDS cases, and people living with HIV were 0.775, 0.976 and 0.816, and -0.188, -0.259 and -0.215 (p<0.002), respectively., Conclusions: The Chongqing HIV/AIDS epidemic showed temporal-spatial clustering and was mainly clustered in the mid-western and south-western counties, showing an upward trend over time. The amount of special funds dedicated to AIDS and to the public awareness unit showed positive and negative relationships with HIV/AIDS spatial clustering, respectively., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The effectiveness of safety belt usage in reducing mortality and morbidity among traffic crash victims has been well established. Population safety belt usage rates have been increasing from 11% in 1980 to 68% in 1995, as measured by observational surveys sponsored by the National Highway Traffic Safety Administration (NHTSA). Safety incentive grants from NHTSA to the States with higher than average usage rates are expected to total $500 million during 1999-2003. In this paper, longitudinal annual motor vehicle-related fatality levels are analyzed by state to estimate the effect of the population safety belt usage rate on traffic fatality rates in the presence of known confounders such as alcohol use and youthful drivers. Consideration of alternative models applied to 14 years of data shows that the population safety belt usage rate (at least, at the current rates) is associated with little or no effect on reducing fatality rates. On the other hand, higher safety belt usage rates arising from states with primary enforcement laws tend to suggest reductions in fatality rates. Such results call into question the NHTSA policy of basing incentive programs on overall safety belt usage rates.