Objectives: Our goal was to “reverse translate” the human response to surgical sepsis into the mouse by modifying a widely adopted murine intra-abdominal sepsis model to engender a phenotype that conforms to current sepsis definitions and follows the most recent expert recommendations for animal preclinical sepsis research. Furthermore, we aimed to create a model that allows the study of aging on the long-term host response to sepsis. Design: Experimental study. Setting: Research laboratory. Subjects: Young (3–5 mo) and old (18–22 mo) C57BL/6j mice. Interventions: Mice received no intervention or were subjected to polymicrobial sepsis with cecal ligation and puncture followed by fluid resuscitation, analgesia, and antibiotics. Subsets of mice received daily chronic stress after cecal ligation and puncture for 14 days. Additionally, modifications were made to ensure that “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” recommendations were followed. Measurements and Main Results: Old mice exhibited increased mortality following both cecal ligation and puncture and cecal ligation and puncture + daily chronic stress when compared with young mice. Old mice developed marked hepatic and/or renal dysfunction, supported by elevations in plasma aspartate aminotransferase, blood urea nitrogen, and creatinine, 8 and 24 hours following cecal ligation and puncture. Similar to human sepsis, old mice demonstrated low-grade systemic inflammation 14 days after cecal ligation and puncture + daily chronic stress and evidence of immunosuppression, as determined by increased serum concentrations of multiple pro- and anti-inflammatory cytokines and chemokines when compared with young septic mice. In addition, old mice demonstrated expansion of myeloid-derived suppressor cell populations and sustained weight loss following cecal ligation and puncture + daily chronic stress, again similar to the human condition. Conclusions: The results indicate that this murine cecal ligation and puncture + daily chronic stress model of surgical sepsis in old mice adhered to current Minimum Quality Threshold in Pre-Clinical Sepsis Studies guidelines and met Sepsis-3 criteria. In addition, it effectively created a state of persistent inflammation, immunosuppression, and weight loss, thought to be a key aspect of chronic sepsis pathobiology and increasingly more prevalent after human sepsis.

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A memory manager that does not move objects may suffer from memory fragmentation. Compaction is an efficient, and sometimes inevitable, mechanism for reducing fragmentation. A Mark-Sweep garbage collector must occasionally execute a compaction, usually while the application is suspended. Compaction during pause time can have detrimental effects for interactive applications that require guarantees for maximal pause time. This work presents a method for reducing the pause time created by compaction at a negligible throughput hit. The solution is most suitable when added to a Mark-Sweep garbage collector.Compaction normally consists of two major activities: the moving of objects and the update of all the objects' references to the new locations. We present a method for executing the reference updates concurrently, thus eliminating a substantial portion of the pause time hit. To reduce the time for moving objects in each compaction, we use the existing technique of incremental compaction, but select the optimal area to compact. Selecting the area is done after executing the mark and sweep phases, and is based on their results.We implemented our compaction on top of the IBM J9 JVM V2.2, and present measurements of its effect on pause time, throughput, and mutator utilization. We show that our compaction is indeed an efficient fragmentation reduction tool, and that it improves the performance of a few of the benchmarks we used, with very little increase in the pause time (typically far below the cost of the mark phase).