The United States\u27 Engagement in Global Tobacco Control: Proposals for Comprehensive Funding and Strategies

Tobacco use kills more people annually than HIV/AIDS, tuberculosis, and malaria combined. Unless action is taken, tobacco-related diseases will kill hundreds of millions more in coming decades, mostly in low- and middle-income countries. Beyond its effects on morbidity and mortality, tobacco use has dramatic social and economic consequences, consuming healthcare budgets, robbing families of their primary wage earners, and hindering economic development. Tobacco consumption is shifting from industrialized to developing countries, spurred by rising incomes, trade liberalization, and intensive marketing. Although Congress empowered the U.S. Food and Drug Administration to regulate tobacco domestically, the United States has failed to lead globally. The United States is among a small minority of countries that has signed, but not ratified, the World Health Organization (WHO) Framework Convention on Tobacco Control. A tiny percentage of U.S. funding for global health is dedicated to international tobacco control. U.S. trade policy has supported and enabled the industry to expand tobacco use overseas. In this Commentary, we argue for robust U.S. engagement in global tobacco control, first explaining why it is in the national interest of the United States and then suggesting a comprehensive strategy for supporting tobacco control in low- and middle-income countries

Trade, social preferences and regulatory cooperation : the new WTO-think

This paper advocates changes in the corporate governance of the World Trade Organization (WTO) to reflect the decline in tariffs and other border restraints to commerce and the emerging challenges of advancing freer trade and better regulation cooperation in a world economy dominated by global value chains. Together, these changes form an integration strategy that we refer to as the new WTO Think. This strategy remains rooted in the original rationale of the General Agreement on Trade and Tariffs (GATT) of reducing the negative externalities of unilateral action and solving important international coordination challenges, but is more inclusive of regulators and non-state actors and more flexible and positive in its means. In particular, we advocate that the WTO should embrace the confluence of shared social preferences and trade, where it exists, as a motivation for advancing international regulatory cooperation. The WTO should also multilateralize the important regulatory cooperation occurring in smaller clubs of like-minded countries and better facilitate the use of plurilateral agreements where consensus across all WTO members is not yet possible

Trade, Social Preferences, and Regulatory Cooperation: The New WTO-Think

This paper advocates changes in the corporate governance of the World Trade Organization (WTO) to reflect the decline in tariffs and other border restraints to commerce and the emerging challenges of advancing freer trade and better regulation cooperation in a world economy dominated by global value chains. Together, these changes form an integration strategy that we refer to as the new WTO Think. This strategy remains rooted in the original rationale of the General Agreement on Trade and Tariffs (GATT) of reducing the negative externalities of unilateral action and solving important international coordination challenges, but is more inclusive of regulators and non-state actors and more flexible and positive in its means. In particular, we advocate that the WTO should embrace the confluence of shared social preferences and trade, where it exists, as a motivation for advancing international regulatory cooperation. The WTO should also multilateralize the important regulatory cooperation occurring in smaller clubs of like-minded countries and better facilitate the use of plurilateral agreements where consensus across all WTO members is not yet possible

Geographic and species association of hepatitis B virus genotypes in non-human primates

AbstractInfection with hepatitis B virus (HBV) has been detected in human populations thoughout the world, as well as in a number of ape species (Pan troglodytes, Gorilla gorilla, gibbons [Nomascus and Hylobates species] and Pongo pygmaeus). To investigate the distribution of naturally occurring HBV infection in these species and other African Old World monkey species (Cercopithecidae), we screened 137 plasma samples from mainly wild caught animals by polymerase chain reaction (PCR) using several of highly conserved primers from the HB surface (HBs) gene, and for HBs antigen (HBsAg) by ELISA. None of the 93 Cercopithecidae screened (6 species) showed PCR or serology evidence for HBV infection; in contrast 2 from 8 chimpanzees and 5 from 22 gibbons were PCR-positive with each set of primers.Complete genome sequences from each of the positive apes were obtained and compared with all previously published complete and surface gene sequences. This extended phylogenetic analysis indicated that HBV variants from orangutans were interspersed by with HBV variants from southerly distributed gibbon species (H. agilis and H. moloch) occupying overlapping or adjacent habitat ranges with orangutans; in contrast, HBV variants from gibbon species in mainland Asia were phylogenetically distinct. A geographical rather than (sub)species association of HBV would account for the distribution of HBV variants in different subspecies of chimpanzees in Africa, and explain the inlier position of the previously described lowland gorilla sequence in the chimpanzee clade. These new findings have a number of implication for understanding the origins and epidemiology of HBV infection in non-human primates

Perspectives of Phage Therapy in Non-bacterial Infections

While the true value of phage therapy (PT) in human bacterial infections still awaits formal confirmation by clinical trials, new data have been accumulating indicating that in the future PT may be applied in the treatment of non-bacterial infections. Thus, “phage guests” may interact with eukaryotic cells and such interactions with cells of the immune system may protect human health (Guglielmi, 2017) and cause clinically useful immunomodulatory and anti-inflammatory effects when administered for therapeutic purposes (Górski et al., 2017; Van Belleghem et al., 2017). Recently, a vision of how these effects could translate into advances in novel means of therapy in a variety of human pathologies secondary to immune disturbances and allergy was presented (Górski et al., 2018a). In this article we present what is currently known about anti-microbial effects of phage which are not directly related to their antibacterial action and how these findings could be applied in the future in treatment of viral and fungal infections

SPECTRE: a Suite of PhylogEnetiC Tools for Reticulate Evolution

Split-networks are a generalization of phylogenetic trees that have proven to be a powerful tool in phylogenetics. Various ways have been developed for computing such networks, including split-decomposition, NeighborNet, QNet and FlatNJ. Some of these approaches are implemented in the user-friendly SplitsTree software package. However, to give the user the option to adjust and extend these approaches and to facilitate their integration into analysis pipelines, there is a need for robust, open-source implementations of associated data structures and algorithms. Here we present SPECTRE, a readily available, open-source library of data structures written in Java, that comes complete with new implementations of several pre-published algorithms and a basic interactive graphical interface for visualizing planar split networks. SPECTRE also supports the use of longer running algorithms by providing command line interfaces, which can be executed on servers or in High Performance Computing (HPC) environments

Defects in IL-2R Signaling Contribute to Diminished Maintenance of FOXP3 Expression in CD4+CD25+ Regulatory T-Cells of Type 1 Diabetic Subjects

OBJECTIVE In humans, multiple genes in the interleukin (IL)-2/IL-2 receptor (IL-2R) pathway are associated with type 1 diabetes. However, no link between IL-2 responsiveness and CD4+CD25+FOXP3+ regulatory T-cells (Tregs) has been demonstrated in type 1 diabetic subjects despite the role of these IL-2–dependent cells in controlling autoimmunity. Here, we address whether altered IL-2 responsiveness impacts persistence of FOXP3 expression in Tregs of type 1 diabetic subjects. RESEARCH DESIGN AND METHODS Persistence of Tregs was assessed by culturing sorted CD4+CD25hi natural Tregs with IL-2 and measuring FOXP3 expression over time by flow cytometry for control and type 1 diabetic populations. The effects of IL-2 on FOXP3 induction were assessed 48 h after activation of CD4+CD25− T-cells with anti-CD3 antibody. Cytokine receptor expression and signaling upon exposure to IL-2, IL-7, and IL-15 were determined by flow cytometry and Western blot analysis. RESULTS Maintenance of FOXP3 expression in CD4+CD25+ Tregs of type 1 diabetic subjects was diminished in the presence of IL-2, but not IL-7. Impaired responsiveness was not linked to altered expression of the IL-2R complex. Instead, IL-2R signaling was reduced in Tregs and total CD4+ T-cells of type 1 diabetic subjects. In some individuals, decreased signal transducer and activator of transcription 5 phosphorylation correlated with significantly higher expression of protein tyrosine phosphatase N2, a negative regulator of IL-2R signaling. CONCLUSIONS Aberrant IL-2R signaling in CD4+ T-cells of type 1 diabetic subjects contributes to decreased persistence of FOXP3 expression that may impact establishment of tolerance. These findings suggest novel targets for treatment of type 1 diabetes within the IL-2R pathway and suggest that an altered IL-2R signaling signature may be a biomarker for type 1 diabetes

Regulatory T Cells Resist Cyclosporine-Induced Cell Death via CD44-Mediated Signaling Pathways

Cyclosporine A (CSA) is an immunosuppressive agent that specifically targets T cells and also increases the percentage of pro-tolerogenic CD4+Foxp3+ regulatory T cells (Treg) through unknown mechanisms. We previously reported that CD44, a receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA), promotes Treg stability in IL-2-low environments. Here, we asked whether CD44 signaling also promotes Treg resistance to CSA. We found that CD44 cross-linking promoted Foxp3 expression and Treg viability in the setting of CSA treatment. This effect was IL-2 independent but could be suppressed using sc-355979, an inhibitor of Stat5-phosphorylation. Moreover, we found that inhibition of HA synthesis impairs Treg homeostasis but that this effect could be overcome with exogenous IL-2 or CD44-cross-linking. Together, these data support a model whereby CD44 cross-linking by HA promotes IL-2-independent Foxp3 expression and Treg survival in the face of CSA

Global susceptibility and response to noncommunicable diseases.

Globalization and human interdependence have created immeasurable value for humanity. These forces, however, also provide channels for health risks to spread throughout the world. Global functions for health, such as international partnerships or research and development, are a rational response to global health risks like pandemics or globalized supply chains. Self-interest compels governments – or donors – to provide global functions even though their benefits are widely shared the world over

Regulatory bindings, policy uncertainty, and market access in services

Unlike trade in goods, market access commitments for services usually comprise regulatory measures as opposed to trade taxes. In other words, they are generally about non-tariff measures (NTMs). In some sectors foreign access may be limited or completely prohibited through quantitative restrictions, e.g. bans on foreign provision of broadcasting or transport services, or requirements that government officials fly on the national airline. More generally, services activities are often regulated. Differences in regulation may then result in additional costs for foreign providers when they contest a market. Because they involve sale of intangibles in the form of service flows rather than physical goods, there is usually some form of direct interaction between service producers and customers. This means that establishment is more likely to be important for service exports than goods exports, resulting in an effective mix of cross-border and FDI related regulatory measures when we discuss market access in services