International treaties have mostly failed to produce their intended effects.

There are over 250,000 international treaties that aim to foster global cooperation. But are treaties actually helpful for addressing global challenges? This systematic field-wide evidence synthesis of 224 primary studies and meta-analysis of the higher-quality 82 studies finds treaties have mostly failed to produce their intended effects. The only exceptions are treaties governing international trade and finance, which consistently produced intended effects. We also found evidence that impactful treaties achieve their effects through socialization and normative processes rather than longer-term legal processes and that enforcement mechanisms are the only modifiable treaty design choice with the potential to improve the effectiveness of treaties governing environmental, human rights, humanitarian, maritime, and security policy domains. This evidence synthesis raises doubts about the value of international treaties that neither regulate trade or finance nor contain enforcement mechanisms.

A Typology of Scientific Advisory Committees.

The era of evidence-informed decision-making has seen increased use of the scientific advisory committee (SAC) to provide decision-makers with scientific advice, despite limited evidence of the effectiveness or best strategies for designing these committees. In this study, an in-depth review of academic and gray literature is undertaken to outline the global landscape of SACs. The development of a typology is also undertaken that categorizes SACs along six dimensions: 1) sector, 2) level of operation, 3) permanence, 4) target audience, 5) autonomy, and 6) nature of advice. It is found that SACs differ profoundly in each of these dimensions and provide examples demonstrating this variation. The landscape and typology can help decision-makers understand the key elements of SAC design and reform, and the results will also inform future research on the design and effectiveness of SACs. With SACs expected to promote evidence-informed decision-making, it is imperative that the design of these committees themselves is guided by evidence.

Ebola Again Shows the International Health Regulations Are Broken: What Can Be Done Differently to Prepare for the Next Epidemic?

Epidemics are among the greatest threats to humanity, and the International Health Regulations are the world's key legal instrument for addressing this threat. Since their revision in 2005, the IHR have faced two big tests: the 2009 H1N1 influenza pandemic and the 2014 Ebola epidemic in West Africa. Both exposed major shortcomings of the IHR, and both offered profound lessons for the future. The objective of this Article is twofold. First, we seek to compare the lessons learned from H1N1 and Ebola for reforming the IHR in order to test the hypothesis that they are similar. Second, we seek to examine the barriers to implementing these lessons and to identify strategies for overcoming those barriers. We find that the lessons from H1N1 and Ebola are indeed similar, and that opportunities to act on lessons from H1N1 were woefully missed. We identify many political barriers to global collective action and implementation of lessons for the IHR. On that basis, we describe strategies to overcome these barriers, which will hopefully be deployed now to reform the IHR before the policy window following Ebola closes, and before the inevitable next epidemic comes. The emerging threat of the Zika virus underscores that we have no time to waste.

Nfkb1 activation by the E26 transformation-specific transcription factors PU.1 and Spi-B promotes Toll-like receptor-mediated splenic B cell proliferation.

Generation of antibodies against T-independent and T-dependent antigens requires Toll-like receptor (TLR) engagement on B cells for efficient responses. However, the regulation of TLR expression and responses in B cells is not well understood. PU.1 and Spi-B (encoded by Sfpi1 and Spib, respectively) are transcription factors of the E26 transformation-specific (ETS) family and are important for B cell development and function. It was found that B cells from mice knocked out for Spi-B and heterozygous for PU.1 (Sfpi1(+/-) Spib(-/-) [PUB] mice) proliferated poorly in response to TLR ligands compared to wild-type (WT) B cells. The NF-κB family member p50 (encoded by Nfkb1) is required for lipopolysaccharide (LPS) responsiveness in mice. PUB B cells expressed reduced Nfkb1 mRNA transcripts and p50 protein. The Nfkb1 promoter was regulated directly by PU.1 and Spi-B, as shown by reporter assays and chromatin immunoprecipitation analysis. Occupancy of the Nfkb1 promoter by PU.1 was reduced in PUB B cells compared to that in WT B cells. Finally, infection of PUB B cells with a retroviral vector encoding p50 substantially restored proliferation in response to LPS. We conclude that Nfkb1 transcriptional activation by PU.1 and Spi-B promotes TLR-mediated B cell proliferation.