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      Responding to chemical weapons violations in Syria: legal, health, and humanitarian recommendations

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          Abstract

          Background

          The repeated use of prohibited chemical weapons in the Syrian conflict poses serious health, humanitarian, and security threats to civilians, healthcare personnel, and first responders. Moreover, the use of chemical weapons constitutes a clear and egregious violation of international law—likely amounting to a war crime—for which continued impunity is setting a dangerous precedent in relation to current and future conflicts. This debate article calls upon concerned states, organizations, and individuals to respond urgently and unequivocally to this serious breach of international legal and humanitarian norms.

          Main Body

          Based on health, humanitarian, and legal findings, this article calls for concrete action to: 1) reduce the risk of chemical weapons being used in current and future conflicts; 2) review and support the preparedness equipment and antidote supplies of first responders, humanitarian organizations, and military forces operating in Syria; 3) support international mechanisms for monitoring and enforcing the prohibition on chemical weapons, including through criminal accountability; 4) support civilian victims of chemical weapons attacks, including refugees; and 5) re-commit to the complete elimination of chemical weapons in compliance with the Chemical Weapons Convention (1993), a comprehensive treaty that bans chemical weapons and requires their complete destruction.

          Conclusion

          All involved states and organizations should take urgent steps to ensure the protection of the most vulnerable victims of conflict, including victims of chemical weapons attacks in Syria, and to reinforce international law in the face of such serious violations.

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          Most cited references4

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          Recurrent failings of medical humanitarianism: intractable, ignored, or just exaggerated?

          Humanitarian health workers operate in dangerous and uncertain contexts, in which mistakes and failures are common, often have severe consequences, and are regularly repeated, despite being documented by many reviews. This Series paper aims to discuss the failures of medical humanitarianism. We describe why some of these recurrent failings, which are often not identified until much later, seem intractable: they are so entrenched in humanitarian action that they cannot be addressed by simple technical fixes. We argue that relief health-care interventions should be contextualised. Perhaps medical humanitarianism deserves a better reputation than the one at times tarnished by unfair criticism, resulting from inapplicable guiding principles and unrealistic expectations. The present situation is not conducive to radical reforms of humanitarian medicine; complex crises multiply and no political, diplomatic, or military solutions are in sight. Relief agencies have to compete for financial resources that do not increase at the same pace as health needs. Avoiding the repetition of failures requires recognising previous mistakes and addressing them through different policies by donors, stronger documentation and analysis of humanitarian programmes and interventions, increased professionalisation, improved, opportunistic relationships with the media, and better ways of working together with local health stakeholders and through indigenous institutions.
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            Novel brain-penetrating oximes for reactivation of cholinesterase inhibited by sarin and VX surrogates.

            Current oxime reactivators for organophosphate-inhibited cholinesterase (ChE) do not effectively cross the blood-brain barrier and therefore cannot restore brain ChE activity in vivo. Our laboratories have studied highly relevant sarin and VX surrogates, which differ from their respective nerve agents only in the leaving group and thereby leave ChE phosphylated with the same chemical moiety as sarin and VX. Our laboratories have developed novel substituted phenoxyalkyl pyridinium oximes that lead to reduced ChE inhibition in the brains of rats challenged with a high sublethal dosage of the sarin surrogate, whereas 2-PAM did not, using a paradigm designed to demonstrate brain penetration. In addition, treatment of rats with these novel oximes is associated with attenuation of seizure-like behavior compared to rats treated with 2-PAM, providing additional evidence that the oximes penetrate the blood-brain barrier. Further, some of the oximes provided 24-h survival superior to 2-PAM, and shortened the duration of seizure-like behavior when rats were challenged with lethal dosages of the sarin and VX surrogates, providing additional support for the conclusion that these oximes penetrate the brain.
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              Preparing for chemical terrorism: a study of the stability of expired pralidoxime (2-PAM).

              Oximes such as pralidoxime (2-PAM) are essential antidotes for life-threatening organophosphate poisoning. Unfortunately, oximes are expensive, have limited use, and have short shelf lives. As such, maintaining large stockpiles in preparation for terrorist activity is not always possible. We have demonstrated that atropine is stable well beyond its labeled shelf life and that recently expired 2-PAM was clinically efficacious in a series of poisoned patients. Because 2-PAM is often dosed empirically, clinical improvement does not guarantee pharmacological stability. We therefore chose to analyze the chemical stability of expired 2-PAM. Samples of lyophylized 2-PAM were maintained according to the manufacturer's recommendations for 20 years beyond the published shelf life. We studied 2-PAM contained in a MARK I autoinjector that was stored properly for 3 years beyond its expiration date. An Agilent LC/MSD 1100 with diode-array detector and an Agilent Sorbax SB-C-18, 4.6 × 150-mm, 5-μm column were used with the following solvent systems: water with 0.01% trifluoroacetic acid and methanol with 0.01% trifluoroacetic acid. Fresh reagent grade 2-PAM was used as a standard. Results were repeated for consistency. Lyophylized 2-PAM was a white powder that was clear and colorless in solution. Liquid chromatography was identical to the standard and resulted in 2 isolated peaks with identical mass spectra, suggesting that they are stereoisomers. The autoinjector discharged a clear, yellowish solution. In addition to the 2 peaks identified for lyophylized 2-PAM, a small third peak was identified with a mass spectra corresponding to the reported N -methyl pyridinium carboxaldehyde degradation product. When properly stored, lyophylized 2-PAM appears to be chemically stable well beyond its expiration date. Although the relative amount of degradation product found in solubilized (autoinjector) 2-PAM was small, it is unclear whether this may be toxic and therefore is of concern. Further studies performed with lots of drug stored under varied conditions would be required to fully determine the stability of expired 2-PAM.
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                Author and article information

                Contributors
                jbrooks@hsph.harvard.edu
                terickson@bwh.harvard.edu
                skayden@hsph.harvard.edu
                CARuizRaul@mail.house.gov
                swilkinson@hsph.harvard.edu
                skipmd77@aol.com
                Journal
                Confl Health
                Confl Health
                Conflict and Health
                BioMed Central (London )
                1752-1505
                19 February 2018
                19 February 2018
                2018
                : 12
                : 12
                Affiliations
                [1 ]Harvard Humanitarian Initiative, Cambridge, MA USA
                [2 ]Department of Emergency Medicine, Brigham and Women’s Hospital; Harvard Medical School, Harvard Humanitarian Initiative, Cambridge, MA USA
                [3 ]Department of Emergency Medicine, Brigham and Women’s Hospital, Harvard Medical School; and Core Faculty, Harvard Humanitarian Initiative, Cambridge, MA USA
                [4 ]GRID grid.431407.5, U.S. House of Representatives for California’s 36th congressional district, ; Washington, D.C. USA
                Author information
                http://orcid.org/0000-0002-9003-4057
                Article
                143
                10.1186/s13031-018-0143-3
                5817898
                29479374
                e0a8d16a-48a9-4041-9f4f-7f0cea59ca15
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 10 August 2017
                : 12 January 2018
                Categories
                Debate
                Custom metadata
                © The Author(s) 2018

                Health & Social care
                syria,chemical weapons,nerve agents,disaster preparedness,conflict zones,humanitarian response,protection of civilians,international law,international treaties,united nations

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