The ‘Unwilling or Unable’ Test and the Law of Self-defence

Recent events related to the rise of ISIS have catapulted the ‘unwilling or unable’ test to the forefront of the legal debate concerning the fight against terrorism. The still controversial test offers a justification for unilateral use of force in self-defence on behalf of a victim state on the territory of a host state that is unwilling or unable to prevent a non-state actor located on its soil from carrying out attacks against the victim state. The aim of this chapter is to analyse the history, current status and content of the ‘unwilling or unable’ test with a view to highlighting the main concerns that come with it. This chapter argues that if the ‘unwilling or unable’ test is here to stay, governments and authors alike must make considerable effort to clarify its content, delineate its limits and set out its requirements in the context of the law of self-defence. Subject to evolving state practice, the ‘unwilling or unable’ test may fit into the necessity requirement of the law of self-defence. If so, emphasis should be put on the victim state’s duty to show, by way of a thorough assessment, the host state’s continuous and evident unwillingness or inability to prevent terrorist organizations from using its territory. This requirement should only come after the victim state has shown that the occurred or imminent armed attack creates an immediate need for action. In any case, measures based on consent, which would circumvent the need to apply the test, should always be prioritized. To present its argument, Sect. 4.2 will embark on a brief review of relevant (state) practice. Next, it will assess the current status of the test on the basis of the conducted review. Section 4.4 will look into the anatomy of the ‘unwilling or unable’ test and Sect. 4.5 will analyse the use of the test in relation to the US-led intervention in Syria to neutralize ISIS targets

The Protection of Nationals Abroad: A Return to Old Practice?

The use of armed force by the Russian Federation in actions claimed as protection of Russian nationals outside Russian Federation territory, most recently in 2014 in the Crimea and Eastern Ukraine, and earlier in 2008 in South Ossetia and Abkhazia, once again brought the discussion around the doctrine of the protection of nationals abroad (PNA) to the foreground. This chapter will start with examining the early theories of PNA, in particular its legality and legitimacy, followed by the current discussion of the different elements that play an important role in the debate, such as the relation of PNA with diplomatic protection, whether the right to exercise diplomatic protection includes the right to use force, and whether the protection of nationals in danger can be justified as self-defence. The chapter will also briefly discuss the impact of consent and UN Security Council mandates, and what the different grounds for, and the forms PNA can take, could mean in terms of state responsibility, both for the state taking action as well as for the states on whose territory the action is executed. The chapter concludes with the observation that the recent RF actions in the Crimea (and South Ossetia and Abkhazia) have not contributed to the clarification of the disputed issues surrounding the protection of nationals abroad

Analysis of 108 patients with endometrial carcinoma using the PROMISE classification and additional genetic analyses for MMR-D

OBJECTIVES: To apply the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) to a consecutive series of endometrial cancer (EC) patients diagnosed at a tertiary referral center and assign EC specimens to one of four molecular subgroups using immunohistochemistry (IHC) for p53/mismatch repair protein expression and sequencing for Polymerase Epsilon Exonuclease Domain Mutations (POLE-EDM). Mismatch Repair Deficient (MMR-D) cases were more thoroughly investigated to identify underlying somatic or germline genetic defects. METHODS: Hundred-and eight consecutive endometrial cancer patients, diagnosed between March 2017 and April 2019, were subjected to immunohistochemical and molecular analysis, according to ProMisE. IHC for p53 and the mismatch repair proteins (MLH1, PMS2, MSH6 and PMS2) was performed. All patients were also tested for POLE-EDM by Sanger sequencing. In addition, tumor and corresponding normal tissue of cases with abnormal MMR IHC were tested by PCR for microsatellite instability (MSI) (MSI analysis system, Promega). Hypermethylation of MLH1 promotor was tested with (methylation specific) multiplex ligation dependent probe amplification. MMR-D cases were subjected to germline mutation analysis of the mismatch repair genes, using next generation sequencing on MiSeq (Illumina) with the BRCA Hereditary Cancer MASTR Plus, (Multiplicom/Agilent), RNA mutation analysis and MLPA. RESULTS: FIGO classification was stage IA (n = 54), IB (n = 22) II(n = 8), III(n = 18) and IV(n = 6). Of the 33 patients with MMR-D on IHC (31%), 26 showed MLH1 promotor hypermethylation as the probable cause of MMR-D. The remaining 7 patients without MLH1 promotor hypermethylation were referred for germline analysis of Lynch syndrome. Six patients carried a pathogenic germline mutation in one of the mismatch repair genes: MSH6(n = 3), PMS2(n = 1), MLH1(n = 1) and MSH2 (n = 1). Pathogenic POLE-EDM were identified in 7 (6%) patients. Multiple molecular features (POLE-EDM + MMR-D or POLE-EDM + p53 abnormal) were observed in 4 patients (4%). A high concordance between MMR-D and microsatellite instability was observed in our cohort. In cases of a genetic defect in the MMR genes, we do note a large proportion of cases exhibiting microsatellite instability. On the contrary a hypermutation state, as seen in POLE EDM, does not result in accompanied phenotypic changes in MSI status. CONCLUSION: The ProMisE classification proved to be an efficient and easily implementable system. Future research should elucidate the precise biological and prognostic meaning of the cases with multiple molecular markers.status: publishe