Inserting innovations in-service

Military platforms have exceptionally long lifecycles and given the state of defense budgets there is a significant trend in sustaining the operational capability of legacy platforms for much greater periods than originally designed. In the context of through-life management, one of the key questions is how to manage the flow of technology for platform modernization during the in-service phase of the lifecycle? Inserting technological innovations in-service is achieved through technology insertion processes. Technology insertion is the pre-eminent activity for both maintaining and enhancing the functional capability of a platform especially given the likely changes in future military operations, the pace of change in technology and with the increasing focus on lifecycle cost reduction. This chapter provides an introduction to technology insertion together with an overview of the key issues that practitioners are faced with. As an aid to planning technology insertion projects, a decision-support framework is presented. © 2010 Springer-Verlag Berlin Heidelberg.

Cecum lymph node dendritic cells harbor slow-growing bacteria phenotypically tolerant to antibiotic treatment.

In vivo, antibiotics are often much less efficient than ex vivo and relapses can occur. The reasons for poor in vivo activity are still not completely understood. We have studied the fluoroquinolone antibiotic ciprofloxacin in an animal model for complicated Salmonellosis. High-dose ciprofloxacin treatment efficiently reduced pathogen loads in feces and most organs. However, the cecum draining lymph node (cLN), the gut tissue, and the spleen retained surviving bacteria. In cLN, approximately 10%-20% of the bacteria remained viable. These phenotypically tolerant bacteria lodged mostly within CD103⁺CX₃CR1⁻CD11c⁺ dendritic cells, remained genetically susceptible to ciprofloxacin, were sufficient to reinitiate infection after the end of the therapy, and displayed an extremely slow growth rate, as shown by mathematical analysis of infections with mixed inocula and segregative plasmid experiments. The slow growth was sufficient to explain recalcitrance to antibiotics treatment. Therefore, slow-growing antibiotic-tolerant bacteria lodged within dendritic cells can explain poor in vivo antibiotic activity and relapse. Administration of LPS or CpG, known elicitors of innate immune defense, reduced the loads of tolerant bacteria. Thus, manipulating innate immunity may augment the in vivo activity of antibiotics.