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As shown by COVID-19, infectious diseases with a pandemic potential present a grave threat to health and wellbeing. Although the International Health Regulations provide a framework of binding legal obligations for pandemic prevention, preparedness, and response, many countries do not comply with these regulations. There is a need for a renewed framework for global collective action that ensures conformity with international regulations and promotes effective prevention and response to pandemic infectious diseases. This Health Policy identifies the necessary characteristics for a new global public health security convention designed to optimise prevention, preparedness, and response to pandemic infectious diseases. We propose ten recommendations to strengthen global public health governance and promote compliance with global health security regulations. Recommendations for a new global public health security convention include greater authority for a global governing body, an improved ability to respond to pandemics, an objective evaluation system for national core public health capacities, more effective enforcement mechanisms, independent and sustainable funding, representativeness, and investment from multiple sectors, among others. The next steps to achieve these recommendations include assembling an invested alliance, specifying the operational structures of a global public health security system, and overcoming barriers such as insufficient political will, scarcity of resources, and individual national interests.

Insulin signaling governs many processes including glucose homeostasis and metabolism, and is therapeutically used to treat hyperglycemia in diabetes. We demonstrated that insulin-induced Akt activation enhances the sensitivity to TGF-β by directing an increase in cell surface TGF-β receptors from a pool of intracellular TGF-β receptors. Consequently, increased autocrine TGF-β signaling in response to insulin participates in insulin-induced angiogenic responses of endothelial cells. With TGF-β signaling controlling many cell responses, including differentiation and extracellular matrix deposition, and pathologically promoting fibrosis and cancer cell dissemination, we addressed to which extent autocrine TGF-β signaling participates in insulin-induced gene responses of human endothelial cells. Transcriptome analyses of the insulin response, in the absence or presence of a TGF-β receptor kinase inhibitor, revealed substantial positive and negative contributions of autocrine TGF-β signaling in insulin-responsive gene responses. Furthermore, insulin-induced responses of many genes depended on or resulted from autocrine TGF-β signaling. Our analyses also highlight extensive contributions of autocrine TGF-β signaling to basal gene expression in the absence of insulin, and identified many novel TGF-β-responsive genes. This data resource may aid in the appreciation of the roles of autocrine TGF-β signaling in normal physiological responses to insulin, and implications of therapeutic insulin usage.

Angiogenesis, the development of new blood vessels, is a key process in disease. We reported that insulin promotes translocation of transforming growth factor β (TGF-β) receptors to the plasma membrane of epithelial and fibroblast cells, thus enhancing TGF-β responsiveness. Since insulin promotes angiogenesis, we addressed whether increased autocrine TGF-β signaling participates in endothelial cell responses to insulin. We show that insulin enhances TGF-β responsiveness and autocrine TGF-β signaling in primary human endothelial cells, by inducing a rapid increase in cell surface TGF-β receptor levels. Autocrine TGF-β/Smad signaling contributed substantially to insulin-induced gene expression associated with angiogenesis, including TGF-β target genes encoding angiogenic mediators; was essential for endothelial cell migration; and participated in endothelial cell invasion and network formation. Blocking TGF-β signaling impaired insulin-induced microvessel outgrowth from neonatal aortic rings and modified insulin-stimulated blood vessel formation in zebrafish. We conclude that enhanced autocrine TGF-β signaling is integral to endothelial cell and angiogenic responses to insulin.

There is continuing interest in using the best available research evidence to inform public health policy. However, all too often efforts to do so rely on mechanistic and unrealistic views of the process by which public policy is made. As a result, traditional dyadic knowledge translation (KT) approaches may not be particularly effective when applied to public policy decision making. However, using examples drawn from public health policy, it is clear that work in political science on multiplicity, hierarchy and networks can offer some insight into what effective KT might look like for informing public policy. To be effective, KT approaches must be more appropriately tailored depending on the audience size, audience breadth, the policy context, and the dominant policy instrument.