Virus-like particle secretion and genotype-dependent immunogenicity of dengue virus serotype 2 DNA vaccine

Dengue virus (DENV), composed of four distinct serotypes, is the most important and rapidly emerging arthropod-borne pathogen and imposes substantial economic and public health burdens. We constructed candidate vaccines containing the DNA of five of the genotypes of dengue virus serotype 2 (DENV-2) and evaluated the immunogenicity, the neutralizing (Nt) activity of the elicited antibodies, and the protective efficacy elicited in mice immunized with the vaccine candidates. We observed a significant correlation between the level of in vitro virus-like particle secretion, the elicited antibody response, and the protective efficacy of the vaccines containing the DNA of the different DENV genotypes in immunized mice. However, higher total IgG antibody levels did not always translate into higher Nt antibodies against homologous and heterologous viruses. We also found that, in contrast to previous reports, more than 50% of total IgG targeted ectodomain III (EDIII) of the E protein, and a substantial fraction of this population was interdomain highly neutralizing flavivirus subgroup-cross-reactive antibodies, such as monoclonal antibody 1B7-5. In addition, the lack of a critical epitope(s) in the Sylvatic genotype virus recognized by interdomain antibodies could be the major cause of the poor protection of mice vaccinated with the Asian 1 genotype vaccine (pVD2-Asian 1) from lethal challenge with virus of the Sylvatic genotype. In conclusion, although the pVD2-Asian 1 vaccine was immunogenic, elicited sufficient titers of Nt antibodies against all DENV-2 genotypes, and provided 100% protection against challenge with virus of the homologous Asian 1 genotype and virus of the heterologous Cosmopolitan genotype, it is critical to monitor the potential emergence of Sylvatic genotype viruses, since vaccine candidates under development may not protect vaccinated humans from these viruses

Gendered Practices of Counterinsurgency

Current US counterinsurgency doctrine is gendered diversely in the different geographic locations where it is formulated, put in practice, and experienced. Where Iraqi and Afghan populations are subjected to counterinsurgency and its attendant development policy, spaces are made legible in gendered ways, and people are targeted – for violence or ‘nation-building’ – on the basis of gender-categorisation. Second, this gendering takes its most incendiary form in the seam of encounter between counterinsurgent foot-soldiers and the locals, where sexuality is weaponised and gender is most starkly cross-hatched with class and race. Finally, in the Metropole, new masculinities and femininities are forged in the domain of counterinsurgency policymaking: While new soldier-scholars represent a softened masculinity, counterinsurgent women increasingly become visible in policy circles, with both using ostensibly feminist justifications for their involvement

The prevalence and pattern of antibiotic prescription among insured patients in Dar es Salaam Tanzania

Introduction: high prevalence of antibiotic prescriptions may contribute to the problem of antibiotic resistance. Understanding the pattern of antibiotic prescriptions in a country may inform monitoring and stewardship activities, which are crucial in the fight against antibiotic resistance. We aimed to determine the prevalence and describe the pattern of antibiotic prescriptions among National Health Insurance Fund (NHIF) insured patients receiving treatment at health facilities in Ilala Municipality, Dar es Salaam, Tanzania. Methods: a cross-sectional analysis of claim forms of NHIF insured patients. A data extraction form was used to capture data for September, 2019 submitted to the Ilala NHIF offices. Results: among 993 insured patients (mean [±SD] age 36.3 [±23.2] years; 581 [58.5%] females; 535 [53.9%] adults) a total of 357 (46.4%, 95% CI, 42.8-50.0) received an antibiotic prescription. Of the 357 patients who received an antibiotic prescription, 71(19.9%) received more than one antibiotic prescription. The most common antibiotic prescribed was amoxicillin/clavulanate (17.1%) followed by amoxicillin (16.5%) whereas the most commonly prescribed antibiotic class was the penicillins (51.3%) followed by the nitroimidazoles (14.0%). Among patients who received more than one antibiotic, the most commonly co-prescribed antibiotics were Ampicillin/Cloxacillin plus Metronidazole (11.4%) followed by Amoxicillin plus Metronidazole (7.1%). According to 2019 WHO Access, Watch, Reserve (AWaRe) Classification of antibiotics, 60.8% of patients received the access antibiotics, 33.3% received the watch antibiotics whereas 17.4% of patients received antibiotics that were not recommended. No patient received an antibiotic from the reserve group. Conclusion: the prevalence of antibiotic prescriptions in Tanzania is high and some antibiotics not recommended by the WHO are still prescribed. We recommend revision of the current Tanzania treatment guideline on antibiotics to reflect WHO recommendations, and further research to address local factors influencing antibiotic prescriptions is warranted

Roving Bandits? The Geographical Evolution of African Armed Conflicts

The fighting in some civil wars primarily takes place in a few stable locations, while the fighting in others moves substantially. We posit that rebel groups that do not primarily fight for a specific ethnic group, that receive outside military assistance, or that have relatively weak fighting capacity tend to fight in inconsistent locations. We develop new measures of conflict zone movement to test our hypotheses, based on shifts in the conflict polygons derived from the new Georeferenced Event Dataset (GED) developed by the Uppsala Conflict Data Program (UCDP). Our empirical results provide support for the suggested mechanisms. We find that groups which lack strong ethnic ties and sufficient military strength to compete with government forces in conventional warfare fight in more varied locations. These findings improve our understandings of and expectations for variations in the humanitarian footprint of armed conflicts, the interdependencies between rebel groups and local populations, and the dilemmas faced by government counterinsurgency efforts

Peacekeeping as Conflict Containment

A rich literature has developed focusing on the efficacy of peacekeeping operations (PKOs) in a temporal sense - asking whether the periods following a deployment are more peaceful or not. We know less about the efficacy of PKOs in a spatial sense. Can peacekeeping shape the geographic dispersion of particular episodes of violence? We posit that PKOs can contain conflict by decreasing the tactical advantage of mobility for the rebels, by obstructing the movement of armed actors, and by altering the ability for governments to seek and confront rebel actors. We investigate the observable implications using georeferenced conflict polygons from the Uppsala Conflict Data Program's (UCDP) Georeferenced Event Dataset (GED). Our findings confirm that PKOs tend to decrease movement in the conflict polygons, especially when robust forces are deployed and when rebel groups have strong ethnic ties. Our findings, on the one hand, imply that PKOs reduce the geographic scope of violence. On the other hand, PKOs may allow nonstate actors to gain strength and legitimacy and thus constitute an even greater future threat to the state whether some form of accord is not reached

Use of H19 Gene Regulatory Sequences in DNA-Based Therapy for Pancreatic Cancer

Pancreatic cancer is the eighth most common cause of death from cancer in the world, for which palliative treatments are not effective and frequently accompanied by severe side effects. We propose a DNA-based therapy for pancreatic cancer using a nonviral vector, expressing the diphtheria toxin A chain under the control of the H19 gene regulatory sequences. The H19 gene is an oncofetal RNA expressed during embryo development and in several types of cancer. We tested the expression of H19 gene in patients, and found that 65% of human pancreatic tumors analyzed showed moderated to strong expression of the gene. In vitro experiments showed that the vector was effective in reducing Luciferase protein activity on pancreatic carcinoma cell lines. In vivo experiment results revealed tumor growth arrest in different animal models for pancreatic cancer. Differences in tumor size between control and treated groups reached a 75% in the heterotopic model (P = .037) and 50% in the orthotopic model (P = .007). In addition, no visible metastases were found in the treated group of the orthotopic model. These results indicate that the treatment with the vector DTA-H19 might be a viable new therapeutic option for patients with unresectable pancreatic cancer

You Can?t Win If You Don?t Fight: The Role of Regime Type in Counterinsurgency Outbreaks and Outcomes

What effect, if any, does democracy have on outcomes of counterinsurgency wars? Previous studies have provided inconclusive answers mainly because of the challenges involved in testing the question empirically: First, insurgencies are not accidental and the anticipated outcomes also affect whether they break out in the first place. Second, regimes are non-random and their determinants can also affect insurgency incidence and its outcomes. Moreover, different aspects of democracy can have opposite effects on the government's chances of winning. I address these challenges by conducting a critical test to distinguish between different causal mechanisms. I find that domestic institutions that are associated with public goods provision make insurgency onsets less likely. I also show that once we control for this selection effect, domestic political institutions do not influence insurgency outcomes

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