Reforming the investment treaty regime: A ‘backward-looking’ approach

- Investor-state dispute settlement (ISDS) — which allows foreign investors to sue governments through international arbitration — has become increasingly controversial. Reasonable observers disagree about the value and fairness of the mechanism, but ISDS has become politically toxic even in capital-exporting states. - The most important reform effort lies not with future treaties but with those already in place. Even if all newly negotiated investment treaties were improved, or governments stopped negotiating agreements with ISDS provisions altogether, the existing stock of 3,000 investment treaties continues to provide access to ISDS on the same terms as before. - This briefing paper outlines a practical, flexible and low-cost option for catalysing reform of ISDS: plurilateral “interpretative statements,” whereby governments endorse joint statements clarifying and defining their positions on contentious clauses in their existing investment treaties. - The mechanism provides a viable alternative, or complement, to renegotiations and terminations. It should be prioritized within the broader reform discussions in the United Nations Commission on International Trade Law (UNCITRAL). Alternatively, the new U.S. administration could fast-track the initiative by taking the lead through the OECD, possibly together with the U.K

Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin

The interplay between BDNF signaling and the serotonergic system remains incompletely understood. Using a highly sensitive enzyme-linked immunosorbent assay, we studied BDNF concentrations in hippocampus and cortex of two mouse models of altered serotonin signaling: tryptophan hydroxylase (Tph)2-deficient (Tph2 (-/-)) mice lacking brain serotonin and serotonin transporter (SERT)-deficient (SERT(-/-)) mice lacking serotonin re-uptake. Surprisingly, hippocampal BDNF was significantly elevated in Tph2 (-/-) mice, whereas no significant changes were observed in SERT(-/-) mice. Furthermore, BDNF levels were increased in the prefrontal cortex of Tph2 (-/-) but not of SERT(-/-) mice. Our results emphasize the interaction between serotonin signaling and BDNF. Complete lack of brain serotonin induces BDNF expression

Why growth equals power - and why it shouldn't : constructing visions of China

When discussing the success of China's transition from socialism, there is a tendency to focus on growth figures as an indication of performance. Whilst these figures are indeed impressive, we should not confuse growth with development and assume that the former necessarily automatically generates the latter. Much has been done to reduce poverty in China, but the task is not as complete as some observers would suggest; particularly in terms of access to health, education and welfare, and also in dealing with relative (rather than absolute) depravation and poverty. Visions of China have been constructed that exaggerate Chinese development and power in the global system partly to serve political interests, but partly due to the failure to consider the relationship between growth and development, partly due to the failure to disaggregate who gets what in China, and partly due to the persistence of inter-national conceptions of globalised production, trade, and financial flows

Variables influencing sentencing severity: Intercourt differences in Connecticut

Studies of criminal-court dispositions have traditionally aggregated courts along political and geographic boundaries. This article suggests that courts should be analyzed individually, even within the same jurisdiction, as a means of increasing the explanatory capacity of the variables involved. Further, it is contended that intercourt differences are a result of organizational influences operating within each court.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25848/1/0000411.pd

Rationale, application and clinical qualification for NT-proBNP as a surrogate end point in pivotal clinical trials in patients with AL amyloidosis

Amyloid light-chain (LC) amyloidosis (AL amyloidosis) is a rare and fatal disease for which there are no approved therapies. In patients with AL amyloidosis, LC aggregates progressively accumulate in organs, resulting in organ failure that is particularly lethal when the heart is involved. A significant obstacle in the development of treatments for patients with AL amyloidosis, as well as for those with any disease that is rare, severe and heterogeneous, has been satisfying traditional clinical trial end points (for example, overall survival or progression-free survival). It is for this reason that many organizations, including the United States Food and Drug Administration through its Safety and Innovation Act Accelerated Approval pathway, have recognized the need for biomarkers as surrogate end points. The international AL amyloidosis expert community is in agreement that the N-terminal fragment of the pro-brain natriuretic peptide (NT-proBNP) is analytically validated and clinically qualified as a biomarker for use as a surrogate end point for survival in patients with AL amyloidosis. Underlying this consensus is the demonstration that NT-proBNP is an indicator of cardiac response in all interventional studies in which it has been assessed, despite differences in patient population, treatment type and treatment schedule. Furthermore, NT-proBNP expression is directly modulated by amyloidogenic LC-elicited signal transduction pathways in cardiomyocytes. The use of NT-proBNP will greatly facilitate the development of targeted therapies for AL amyloidosis. Here, we review the data supporting the use of NT-proBNP, a biomarker that is analytically validated, clinically qualified, directly modulated by LC and universally accepted by AL amyloidosis specialists, as a surrogate end point for survival.Leukemia advance online publication, 2 August 2016; doi:10.1038/leu.2016.191