K13 gene mutations are a primary marker of artemisinin resistance in Plasmodium falciparum malaria that threatens the long-term clinical utility of artemisinin-based combination therapies, the cornerstone of modern day malaria treatment. Here we describe a multinational drug discovery programme that has delivered a synthetic tetraoxane-based molecule, E209, which meets key requirements of the Medicines for Malaria Venture drug candidate profiles. E209 has potent nanomolar inhibitory activity against multiple strains of P. falciparum and P. vivax in vitro, is efficacious against P. falciparum in in vivo rodent models, produces parasite reduction ratios equivalent to dihydroartemisinin and has pharmacokinetic and pharmacodynamic characteristics compatible with a single-dose cure. In vitro studies with transgenic parasites expressing variant forms of K13 show no cross-resistance with the C580Y mutation, the primary variant observed in Southeast Asia. E209 is a superior next generation endoperoxide with combined pharmacokinetic and pharmacodynamic features that overcome the liabilities of artemisinin derivatives.
human rights are universal, indivisible and interdependent and interrelated. The international community must treat human rights globally in a fair and equal manner, on the same footing, and with the same emphasis. While the significance of national and regional particularities and various historical, cultural and religious backgrounds must be borne in mind, it is the duty of States, regardless of their political, economic and cultural systems, to promote and protect all human rights and fundamental freedoms.' 7 The definition of a child is provided by Article 1: 'for the purposes of the present Convention, a child means every human being below the age of eighteen years unless under the law applicable to the child, majority is attained earlier'. 8 Committee on the Rights of the Child, General Comments N.5 (2003), CRC/GC/2003/5, 4.
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‘Accountability’ is the international legal term du jour. The concept is omnipresent in contemporary discussions about the UN Security Council in particular. From the lack of due process guarantees for individuals implicated in its counter-terrorism sanctions regime, to the (in)compatibility of Council authorized uses of force with international human rights and humanitarian law, no aspect of the Council’s recent practice has been immune from an accountability critique. Driven by the context in which it has emerged, the turn to accountability is seemingly prompted by a felt desire among international lawyers to constrain the arbitrary use of the Council’s considerable powers. However, beyond this felt desire, the concept lacks a robust theoretical foregrounding, both on its own terms and in relation to existential developments in international law. In an attempt to remedy this, this article situates the turn to accountability as a product of the broader turn to ‘constitutionalist’ thinking in international law. Specifically, it suggests that mainstream approaches resonate with a particular ‘liberal-legalist style’ of global constitutionalism. From both an etymological and epistemological perspective, however, I argue that this prevailing style offers an incomplete sense of accountability. The article introduces the dichotomy of ‘liberal-legal’ and more overtly ‘political’ styles of global constitutionalism as a heuristic device in order to offer a broader conception of accountability in the Security Council context. Political constitutionalism, I believe, offers important insights that will allow us to perceive and critique the Security Council in new ways.
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