Unbiased Tail Estimation by an Extension of the Generalized Pareto Distribution

AMS classifications: 62G20; 62G32;bias;exchange rate;heavy tails;peaks-over-threshold;regular variation;tail index

The “Ultimate Prize” for Big Tobacco: Opening the Chinese Cigarette Market by Cigarette Smuggling

Novotny discusses a new study in PLoS Medicine that documents how British American Tobacco has exploited China's large cigarette smuggling problem

Unbiased Tail Estimation by an Extension of the Generalized Pareto Distribution

AMS classifications: 62G20; 62G32;

“Key to the Future”: British American Tobacco and Cigarette Smuggling in China

BACKGROUND: Cigarette smuggling is a major public health issue, stimulating increased tobacco consumption and undermining tobacco control measures. China is the ultimate prize among tobacco's emerging markets, and is also believed to have the world's largest cigarette smuggling problem. Previous work has demonstrated the complicity of British American Tobacco (BAT) in this illicit trade within Asia and the former Soviet Union. METHODS AND FINDINGS: This paper analyses internal documents of BAT available on site from the Guildford Depository and online from the BAT Document Archive. Documents dating from the early 1900s to 2003 were searched and indexed on a specially designed project database to enable the construction of an historical narrative. Document analysis incorporated several validation techniques within a hermeneutic process. This paper describes the huge scale of this illicit trade in China, amounting to billions of (United States) dollars in sales, and the key supply routes by which it has been conducted. It examines BAT's efforts to optimise earnings by restructuring operations, and controlling the supply chain and pricing of smuggled cigarettes. CONCLUSIONS: Our research shows that smuggling has been strategically critical to BAT's ongoing efforts to penetrate the Chinese market, and to its overall goal to become the leading company within an increasingly global industry. These findings support the need for concerted efforts to strengthen global collaboration to combat cigarette smuggling

Serological markers for prediction of response to anti-tumor necrosis factor treatment in Crohn's disease

peer reviewedOBJECTIVES: The use of monoclonal anti-tumor necrosis factor (TNF) antibodies (infliximab, Remicade) is a new therapeutic approach for severe refractory luminal or fistulizing, Crohn's disease (CD). However, up to 30% of patients do not respond to this treatment. So far, no parameters predictive of response to anti-TNT have been identified. Our aim was to determine whether serological markers ASCA (anti-Saccharomyces cerevisiae antibodies) or pANCA (perinuclear antineutrophil cytoplasmic antibodies) could identify Crohn's patients likely to benefit from anti-TNF therapy. METHODS: Serum samples of 279 CID patients were analyzed for ASCA and pANCA before anti-TNF therapy. A blinded physician determined clinical response at week 4 (refractory luminal CD) or week 10 (fistulizing CD) after the first infusion of infliximab (5 mg/kg). RESULTS: Overall, there was no relationship between ASCA or pANCA and response to therapy. However, lower response rates were observed for patients with refractory intestinal disease carrying the pANCA+/ASCA- combination, although this lacked significance (p = 0.067). CONCLUSIONS: In this cohort of infliximab-treated patients, neither ASCA nor pANCA could predict response to treatment. However, the combination pANCA+/ASCA- might warrant further investigation for its value in predicting nonresponse in patients with refractory luminal disease

EURL ECVAM Workshop on New Generation of Physiologically-Based Kinetic Models in Risk Assessment

The European Union Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) Strategy Document on Toxicokinetics (TK) outlines strategies to enable prediction of systemic toxicity by applying new approach methodologies (NAM). The central feature of the strategy focuses on using physiologically-based kinetic (PBK) modelling to integrate data generated by in vitro and in silico methods for absorption, distribution, metabolism, and excretion (ADME) in humans for predicting whole-body TK behaviour, for environmental chemicals, drugs, nano-materials, and mixtures. In order to facilitate acceptance and use of this new generation of PBK models, which do not rely on animal/human in vivo data in the regulatory domain, experts were invited by EURL ECVAM to (i) identify current challenges in the application of PBK modelling to support regulatory decision making; (ii) discuss challenges in constructing models with no in vivo kinetic data and opportunities for estimating parameter values using in vitro and in silico methods; (iii) present the challenges in assessing model credibility relying on non-animal data and address strengths, uncertainties and limitations in such an approach; (iv) establish a good kinetic modelling practice workflow to serve as the foundation for guidance on the generation and use of in vitro and in silico data to construct PBK models designed to support regulatory decision making. To gauge the current state of PBK applications, experts were asked upfront of the workshop to fill a short survey. In the workshop, using presentations and discussions, the experts elaborated on the importance of being transparent about the model construct, assumptions, and applications to support assessment of model credibility. The experts offered several recommendations to address commonly perceived limitations of parameterization and evaluation of PBK models developed using non-animal data and its use in risk assessment, these include: (i) develop a decision tree for model construction; (ii) set up a task force for independent model peer review; (iii) establish a scoring system for model evaluation; (iv) attract additional funding to develop accessible modelling software.; (v) improve and facilitate communication between scientists (model developers, data provider) and risk assessors/regulators; and (vi) organise specific training for end users. The experts also acknowledged the critical need for developing a guidance document on building, characterising, reporting and documenting PBK models using non-animal data. This document would also need to include guidance on interpreting the model analysis for various risk assessment purposes, such as incorporating PBK models in integrated strategy approaches and integrating them with in vitro toxicity testing and adverse outcome pathways. This proposed guidance document will promote the development of PBK models using in vitro and silico data and facilitate the regulatory acceptance of PBK models for assessing safety of chemicals

Utilisation of Mucin Glycans by the Human Gut Symbiont Ruminococcus gnavus Is Strain-Dependent

Commensal bacteria often have an especially rich source of glycan-degrading enzymes which allow them to utilize undigested carbohydrates from the food or the host. The species Ruminococcus gnavus is present in the digestive tract of ≥90% of humans and has been implicated in gut-related diseases such as inflammatory bowel diseases (IBD). Here we analysed the ability of two R. gnavus human strains, E1 and ATCC 29149, to utilize host glycans. We showed that although both strains could assimilate mucin monosaccharides, only R. gnavus ATCC 29149 was able to grow on mucin as a sole carbon source. Comparative genomic analysis of the two R. gnavus strains highlighted potential clusters and glycoside hydrolases (GHs) responsible for the breakdown and utilization of mucin-derived glycans. Transcriptomic and functional activity assays confirmed the importance of specific GH33 sialidase, and GH29 and GH95 fucosidases in the mucin utilisation pathway. Notably, we uncovered a novel pathway by which R. gnavus ATCC 29149 utilises sialic acid from sialylated substrates. Our results also demonstrated the ability of R. gnavus ATCC 29149 to produce propanol and propionate as the end products of metabolism when grown on mucin and fucosylated glycans. These new findings provide molecular insights into the strain-specificity of R. gnavus adaptation to the gut environment advancing our understanding of the role of gut commensals in health and disease

Impact of tobacco control policies on smoking prevalence and quit ratios in 27 European Union countries from 2006 to 2014

BACKGROUND: Tobacco use is still highly prevalent in Europe, despite the tobacco control efforts made by the governments. The development of tobacco control policies varies substantially across countries. The Tobacco Control Scale (TCS) was introduced to quantify the implementation of tobacco control policies across European countries OBJECTIVE: To assess the midterm association of tobacco control policies on smoking prevalence and quit ratios among 27 European Union (EU) Member States (EU27). METHODS: Ecological study. We used the TCS in EU27 in 2007 and the prevalence of tobacco and quit ratios data from the Eurobarometer survey (2006 (n=27 585) and 2014 (n=26 793)). We analysed the relationship between the TCS scores and smoking prevalence and quit ratios and their relative changes (between 2006 and 2014) by means of scatter plots and multiple linear regression models. RESULTS: In EU27, countries with higher scores in the TCS, which indicates higher tobacco control efforts, have lower prevalence of smokers, higher quit ratios and higher relative decreases in their prevalence rates of smokers over the last decade. The correlation between TCS scores and smoking prevalence (rsp=-0.444; P=0.02) and between the relative changes in smoking prevalence (rsp=-0.415; P=0.03) was negative. A positive correlation was observed between TCS scores and quit ratios (rsp=0.373; P=0.06). The percentage of smoking prevalence explained by all TCS components was 28.9%. CONCLUSION: EU27 should continue implementing comprehensive tobacco control policies as they are key for reducing the prevalence of smoking and an increase tobacco cessation rates in their population

Impact of tobacco control policies on smoking prevalence and quit ratios in 27 European Union countries from 2006-2014

Background: Smoking is still highly prevalent in Europe. According to the WHO, tobacco control policies vary substantially across countries. The Tobacco Control Scale (TCS) was developed to quantify the implementation of tobacco control policies at country level in Europe. The objective was to assess the impact of tobacco control policies (quantified by TCS scores) on smoking prevalence and quit ratios and their relative changes from 2006-2014 in 27 European Union (EU27) countries. Methods: We conducted an ecological study at the country level. We used TCS scores in EU27 in 2007, and the prevalence of tobacco and quit ratios (No. ex-smokers/ No. ever smokers) data from the Eurobarometer surveys (2006 and 2014 waves). We analysed the relationship between the TCS scores and smoking prevalence and quit ratios and their relative changes by means of scatter plots, Spearman rank-correlation coefficients (rsp), and a multiple linear regression model adjusted for all TCS components. Results: In EU27, the smoking prevalence decreased by 14% (95%CI:7.3%-20.6%) (2006-2014) and varied from a relative decrease of 48.9% in Sweden to 0.4% in Bulgaria. The increase in the quit ratio in EU27 was 19.2% (95%CI:5.4%-33.1%) (2006-2014) and ranged from 125.8% in Sweden to 4.3% in Bulgaria. The correlation between TCS scores and smoking prevalence was negative (rsp=-0.444;p=0.02). A positive correlation was observed between TCS scores and quit ratios in 2014 (rsp=0.373;p=0.06) and in the relative changes in smoking prevalence (rsp=0.415;p=0.03). The percentage of smoking prevalence in 2014 explained by all TCS components in the regression model was 28.9% Conclusions: European countries with higher TCS scores, which indicates higher tobacco control efforts, have lower prevalence of smokers, higher quit ratios, and higher relative decreases in their smoking prevalence over the last decade. Funding: EC Horizon2020 HCO-6-2015 (EUREST-PLUS No. 681109); Government of Spain & European Regional Development Fund (RTICC RD12/0036/0053); Government of Catalonia (2014SGR999)