Playing Offense: A Deeper Look into the Motivations and Significance of Sulla's March on Rome

In 88 BCE, Roman general Lucius Cornelius Sulla marched on his own city for the first time in the Roman Republic’s history to procure for himself political control that had been awarded to Gaius Marius. This paper examines not only the impact of this decision, but also some of the most important motivations behind it that help to shape the march’s significance. Specifically, narratives of Appian, Plutarch, and Velleius Paterculus, that describe this event, in conjunction with commentary from modern historian Allen M. Ward, are presented to illustrate that Sulla’s march on Rome was politically significant in that it set a precedent of violence against the state as a means to attain military command. However, it was not necessarily novel on its own: in fact, it was shaped by the Marian military reforms, Sulla's personal struggle for power in a rivalry with Marius, and the ongoing popular revolt against Roman authority during the Italian War

Mechanical and Biologic Impact of Dynamic Loading on Bovine and Human Models of Osteoarthritis

Both dexamethasone (Dex) and Insulin-like growth factor 1 (IGF-1) have shown promise as disease-modifying therapeutics for osteoarthritis (OA), a disease characterized by cartilage degradation. Additionally, dynamic loading has been demonstrated to affect chondrocyte metabolic activity, with mechanical stimuli acting as a therapeutic at specific amplitudes and frequencies. The goal of this thesis was to investigate the potential of these therapeutics and loading to be synergistic in preventing post-traumatic osteoarthritis (PTOA) disease initiation (e.g., after a traumatic joint injury) and in ameliorating progression of OA. We hypothesized that Dex and IGF-1 could help to maintain the mechanical properties and biochemical composition of cartilage in human osteochondral tissues when treated with exogenous inflammatory cytokines. Bovine knee cartilage and human ankle cartilage-bone explants were used in vitro with a cytokine challenged to mimic an OA disease state. A load-controlled dynamic loading protocol was modeled after a physiologically relevant rehabilitation program and was tested in healthy tissue to optimize the applied stress magnitude and loading duration. The optimized protocol was then used for 7 days duration (at 0.33 Hz, 40% duty cycle for 1 hour per day) +/- Dex and IGF-1 to evaluate biochemical changes on the protein and gene expression levels. Stress-relaxation testing was utilized to calculate mechanical properties of human cartilage, both before and after one 1-hour loading session, at baseline and after treatment with cytokines and Dex. It was found that a load-controlled protocol could mimic exercise with total strain in a physiologically relevant range. Loading after 7 days also increased the effects of Dex and IGF-1 on cell viability, and further increased GAG biosynthesis and decreased GAG loss seen with Dex alone. Notably, in human tissue there was donor-to-donor variability in this response to both loading on its own, and to Dex/IGF-1 with and without loading. While Dex preserved cell viability and decreased GAG loss and NO release from cartilage explants treated with cytokines, Dex did not alter mechanical properties (before or after loading) after 10 days. However, there was variation in these values between donor age groups at baseline. Taken together, these results suggest that a rehabilitative loading therapy in combination with Dex/IGF-1 could enhance certain disease-modifying effects of each of the two drugs, and that inherent tissue variability (between patients) could contribute to individual variation in responses and thus emphasize the need for a personalized medicine approach.S.M

The role of resting myocardial blood flow and myocardial blood flow reserve as a predictor of major adverse cardiovascular outcomes.

Cardiac perfusion PET is increasingly used to assess ischemia and cardiovascular risk and can also provide quantitative myocardial blood flow (MBF) and flow reserve (MBFR) values. These have been shown to be prognostic biomarkers of adverse outcomes, yet MBF and MBFR quantification remains underutilized in clinical settings. We compare MBFR to traditional cardiovascular risk factors in a large and diverse clinical population (60% African-American, 35.3% Caucasian) to rank its relative contribution to cardiovascular outcomes. Major adverse cardiovascular events (MACE), including unstable angina, non-ST and ST-elevation myocardial infarction, stroke, and death, were assessed for consecutive patients who underwent rest-dipyridamole stress 82Rb PET cardiac imaging from 2012-2015 at the Hospital of the University of Pennsylvania (n = 1283, mean follow-up 2.3 years). Resting MBF (1.1 ± 0.4 ml/min/g) was associated with adverse cardiovascular outcomes. MBFR (2.1 ± 0.8) was independently and inversely associated with MACE. Furthermore, MBFR was more strongly associated with MACE than both traditional cardiovascular risk factors and the presence of perfusion defects in regression analysis. Decision tree analysis identified MBFR as superior to established cardiovascular risk factors in predicting outcomes. Incorporating resting MBF and MBFR in CAD assessment may improve clinical decision making