Electronic Cigarettes Regulation in the UK: A Case Study in Evidence Informed Policy Making

This chapter argues that policy debates on electronic cigarettes (e-cigarettes) are structured around competing evidence claims between proponents and sceptics, who remain bitterly divided on the issue. The confusion and intransigence which has emerged between these camps is, in part, the result of an insufficiently nuanced understanding of the value-centred and highly political nature of the policy process, and the highly circumscribed (yet nonetheless important) role which evidence can play within this. Key policy actors, often from biomedical backgrounds, or trained in the natural sciences, have been unable to recognise the limits of evidence to resolve protracted policy controversies such as that surrounding e-cigarettes. The chapter highlights the value of insights, derived from interpretative social science, about the multiple potential framings of an issue and the need for reflexivity on the part of policy actors to move beyond the current impasse

Dynamic and diverse changes in the functional properties of vascular smooth muscle cells in pulmonary hypertension

Pulmonary hypertension (PH) is the end result of interaction between pulmonary vascular tone and a complex series of cellular and molecular events termed 'vascular remodelling'. The remodelling process, which can involve the entirety of pulmonary arterial vasculature, almost universally involves medial thickening, driven by increased numbers and hypertrophy of its principal cellular constituent, smooth muscle cells (SMCs). It is noted, however that SMCs comprise heterogeneous populations of cells, which can exhibit markedly different proliferative, inflammatory, and extracellular matrix production changes during remodelling. We further consider that these functional changes in SMCs of different phenotype and their role in PH are dynamic and may undergo significant changes over time (which we will refer to as cellular plasticity); no single property can account for the complexity of the contribution of SMC to pulmonary vascular remodelling. Thus, the approaches used to pharmacologically manipulate PH by targeting the SMC phenotype(s) must take into account processes that underlie dominant phenotypes that drive the disease. We present evidence for time- and location-specific changes in SMC proliferation in various animal models of PH; we highlight the transient nature (rather than continuous) of SMC proliferation, emphasizing that the heterogenic SMC populations that reside in different locations along the pulmonary vascular tree exhibit distinct responses to the stresses associated with the development of PH. We also consider that cells that have often been termed 'SMCs' may arise from many origins, including endothelial cells, fibroblasts and resident or circulating progenitors, and thus may contribute via distinct signalling pathways to the remodelling process. Ultimately, PH is characterized by long-lived, apoptosis-resistant SMC. In line with this key pathogenic characteristic, we address the acquisition of a pro-inflammatory phenotype by SMC that is essential to the development of PH. We present evidence that metabolic alterations akin to those observed in cancer cells (cytoplasmic and mitochondrial) directly contribute to the phenotype of the SM and SM-like cells involved in PH. Finally, we raise the possibility that SMCs transition from a proliferative to a senescent, pro-inflammatory and metabolically active phenotype over time