Strategic satisficing : civil-military relations and French intervention in Africa

Few issues are more important yet less understood than outside interventions in intra-state conflicts. Under what circumstances do intervening states further their interests and when, contrarily, do they plunge into quagmires? France is a critical case. It is, statistically, the world’s second intervenor and earned the sobriquet of Africa’s gendarme through frequent interventions in African wars. The ability of such a medium-sized state to intervene with greater regularity and ostensible success than larger powers raises questions about how France manages its interventions. Do French interventions draw on the French Army’s distinctive “school” of population-centric counterinsurgency, which emphasizes the need to militarize governance in pursuit of comprehensive victories? Or do the French Fifth Republic’s civil-military institutions encourage policymakers to carefully regulate force’s employment in pursuit of limited ends? This study draws on declassified archives to test which approach most characterizes French interventions. To preview my conclusions, strategic satisficing—the use of minimal force for short durations to produce satisfactory outcomes—distinguishes the Fifth Republic’s interventions from other powers’ practices and prior French counterinsurgencies. This particular form of interventionism enables France to influence a disproportionately large number of intra-state conflicts and maintain a network of security agreements with African states.PostprintPeer reviewe

Quantifying circulating cell-free DNA in humans

Abstract To our knowledge, this is the first comprehensive study on the influence of several pre-analytical and demographic parameters that could be a source of variability in the quantification of nuclear and mitochondrial circulating DNA (NcirDNA and McirDNA). We report data from a total of 222 subjects, 104 healthy individuals and 118 metastatic colorectal cancer (mCRC) patients. Approximately 50,000 and 3,000-fold more mitochondrial than nuclear genome copies were found in the plasma of healthy individuals and mCRC patients, respectively. In healthy individuals, NcirDNA concentration was statistically influenced by age (p = 0.009) and gender (p = 0.048). Multivariate analysis with logistic regression specified that age over 47 years-old was predictive to have higher NcirDNA concentration (OR = 2.41; p = 0.033). McirDNA concentration was independent of age and gender in healthy individuals. In mCRC patients, NcirDNA and McirDNA levels were independent of age, gender, delay between food intake and blood collection, and plasma aspect, either with univariate or multivariate analysis. Nonetheless, ad hoc study suggested that menopause and blood collection time might have tendency to influence cirDNA quantification. In addition, high significant statistical differences were found between mCRC patients and healthy individuals for NcirDNA (p < 0.0001), McirDNA (p < 0.0001) and McirDNA/NcirDNA ratio (p < 0.0001). NcirDNA and McirDNA levels do not vary in the same way with regards to cancer vs healthy status, pre-analytical and demographic factors

Monitoring levels of circulating cell‐free DNA in patients with metastatic colorectal cancer as a potential biomarker of responses to regorafenib treatment

International audienceCirculating cell-free DNA (cfDNA) contains circulating tumor DNA (ctDNA), which can be obtained from serial liquid biopsies to enable tumor genome analysis throughout the course of treatment. We investigated cfDNA and mutant ctDNA as potential biomarkers to predict the best outcomes of regorafenib-treated metastatic colorectal cancer (mCRC) patients. We analyzed longitudinally collected plasma cfDNA of 43 mCRC patients prospectively enrolled in the phase II TEXCAN trial by IntPlex qPCR. Qualitative (KRAS, NRAS, BRAFV600E mutations) and quantitative (total cfDNA concentration, mutant ctDNA concentration, mutant ctDNA fraction) parameters were correlated with overall survival (OS) and progression-free survival (PFS). When examined as classes or continuous variables, the concentrations of total cfDNA, mutant ctDNA, and partly, mutant ctDNA fraction prior to regorafenib treatment correlated with OS. Patients with baseline-cfDNA >26 ng/mL had shorter OS than those with cfDNA value below this threshold (4.0 vs 6.9 months; logrank P=0.0366). Patients with baseline mutant ctDNA >2 ng/mL had shorter OS than those with mutant ctDNA below this threshold (logrank P=0.0154). We show that pre-treatment cfDNA and mutant ctDNA levels may identify mCRC patients that may benefit from regorafenib treatment

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old