Publications

PURPOSE

To understand transnational tobacco companies' (TTCs) practices in low and middle-income countries which serve to block tobacco-control policies and promote tobacco use.

METHODS

Systematic review of published research on tobacco industry activities to promote tobacco use and oppose tobacco-control policies in low and middle-income countries.

RESULTS

TTCs' strategies used in low and middle-income countries followed four main themes-economic activity; marketing/promotion; political activity; and deceptive/manipulative activity. Economic activity, including foreign investment and smuggling, was used to enter new markets. Political activities included lobbying, offering voluntary self-regulatory codes, and mounting corporate social responsibility campaigns. Deceptive activities included manipulation of science and use of third-party allies to oppose smoke-free policies, delay other tobacco-control policies, and maintain support of policymakers and the public for a pro-tobacco industry policy environment. TTCs used tactics for marketing, advertising, and promoting their brands that were tailored to specific market environments. These activities included direct and indirect tactis, targeting particular populations, and introducing new tobacco products designed to limit marketing restrictions and taxes, maintain the social acceptability of tobacco use, and counter tobacco-control efforts.

CONCLUSIONS

TTCs have used similar strategies in high-income countries as these being described in low and middle-income countries. As required by FCTC Article 5.3, to counter tobacco industry pressures and to implement effective tobacco-control policies, governments and health professionals in low and middle-income countries should fully understand TTCs practices and counter them.

The functional consequences of genetic variation in mammalian regulatory elements are poorly understood. We report the in vivo dissection of three mammalian enhancers at single-nucleotide resolution through a massively parallel reporter assay. For each enhancer, we synthesized a library of >100,000 mutant haplotypes with 2-3% divergence from the wild-type sequence. Each haplotype was linked to a unique sequence tag embedded within a transcriptional cassette. We introduced each enhancer library into mouse liver and measured the relative activities of individual haplotypes en masse by sequencing the transcribed tags. Linear regression analysis yielded highly reproducible estimates of the effect of every possible single-nucleotide change on enhancer activity. The functional consequence of most mutations was modest, with ∼22% affecting activity by >1.2-fold and ∼3% by >2-fold. Several, but not all, positions with higher effects showed evidence for purifying selection, or co-localized with known liver-associated transcription factor binding sites, demonstrating the value of empirical high-resolution functional analysis.

Cell adhesion molecules govern leukocyte-endothelial cell (EC) interactions that are essential in regulating leukocyte recruitment, adhesion, and transmigration in areas of inflammation. In this paper, we synthesized hydrogel matrices modified with antibodies against vascular cell adhesion molecule-1 (VCAM1) and endothelial leukocyte adhesion molecule-1 (E-Selectin) to mimic leukocyte-EC interactions. Adhesion of human umbilical vein ECs to polyvinyl alcohol (PVA) hydrogels was examined as a function of the relative antibody ratio (anti-VCAM1:anti-E-Selectin) and substrate elasticity. Variation of PVA backbone methacrylation was used to affect hydrogel matrix stiffness, ranging from 130 to 720 kPa. Greater EC adhesion was observed on hydrogels presenting 1:1 anti-VCAM1:anti-E-Selectin than on gels presenting either arginine-glycine-asparagine (RGD) peptide, anti-VCAM1, or anti-E-Selectin alone. Engineered cell adhesion - based on complementing the EC surface presentation - may be used to increase the strength of EC-matrix interactions. Hydrogels with tunable and synergistic adhesion may be useful in vascular remodeling.