Victim of a Revolution: Nicholas Cresswell\u27s American Odyssey, 1774-1777

The diary of Nicholas Cresswell, a young Englishman who traveled in America from 1774-1777, has long been an important primary source on the American Revolution. Cresswell\u27s travels took him from the eastern seaboard (and Barbados) to Kentucky and Ohio, and from Williamsburg, Virginia to New York City. The people he met encompassed almost the entire political spectrum of the day, ranging from William Howe and Loyalist operatives such as John Connolly to grassroots patriot activists on the Committees of Public Safety and founding luminaries such as George Rogers Clark, Thomas Jefferson, and Patrick Henry. He rubbed shoulders with people from radically different social, ethnic, and cultural groups: prosperous merchants in Alexandria and Philadelphia; plantation elites and their slaves in Barbados, Maryland, and Virginia; struggling Scots-Irish pioneers on the frontier; peaceful Delaware Indians and Moravian converts; poor tenant farmers in Loudoun County, Virginia; and the wildly diverse inhabitants of British-occupied New York City, including naval captains and crews, redcoats and Hessians, Loyalist refugees, and the beggars and prostitutes that constituted the social dregs of a city under siege. Above all, he had adventures, described in vivid detail and with a wry humor. Despite the diary\u27s popularity as a cornucopia of useful quotations, historians have written almost nothing about Cresswell himself, nor have they examined his diary simply for its own sake. In order to make Cresswell\u27s fascinating record of his American journey more accessible, this work will take advantage of a new edition of the diary text to provide a detailed narrative retelling and restore chronological order to the story while also including necessary historical context and analysis. Cresswell did not remain politically neutral but instead acted decisively to support the British cause during the early years of the Revolutionary War, which he viewed as a grassroots insurrection sparked by the Intolerable Acts of 1774 and goaded on by the zealous Committees of Public Safety, without any broader philosophical or ideological justification. His experiences among the Delaware Indians on the western frontier caused a remarkable transformation in his attitude towards American Indians, and his descriptions of relationships with American women reveal important facts about eighteenth-century views of women, marriage, and sexuality. The diary of Nicholas Cresswell, often quoted but seldom read, can open a valuable window on the life of a remarkable individual and the remarkably ordinary people around him during the crucial early years of the American Revolution

An Assessment of H1N1 Influenza-Associated Acute Respiratory Distress Syndrome Severity after Adjustment for Treatment Characteristics

Pandemic influenza caused significant increases in healthcare utilization across several continents including the use of high-intensity rescue therapies like extracorporeal membrane oxygenation (ECMO) or high-frequency oscillatory ventilation (HFOV). The severity of illness observed with pandemic influenza in 2009 strained healthcare resources. Because lung injury in ARDS can be influenced by daily management and multiple organ failure, we performed a retrospective cohort study to understand the severity of H1N1 associated ARDS after adjustment for treatment. Sixty subjects were identified in our hospital with ARDS from “direct injury” within 24 hours of ICU admission over a three month period. Twenty-three subjects (38.3%) were positive for H1N1 within 72 hours of hospitalization. These cases of H1N1-associated ARDS were compared to non-H1N1 associated ARDS patients. Subjects with H1N1-associated ARDS were younger and more likely to have a higher body mass index (BMI), present more rapidly and have worse oxygenation. Severity of illness (SOFA score) was directly related to worse oxygenation. Management was similar between the two groups on the day of admission and subsequent five days with respect to tidal volumes used, fluid balance and transfusion practices. There was, however, more frequent use of “rescue” therapy like prone ventilation, HFOV or ECMO in H1N1 patients. First morning set tidal volumes and BMI were significantly associated with increased severity of lung injury (Lung injury score, LIS) at presentation and over time while prior prescription of statins was protective. After assessment of the effect of these co-interventions LIS was significantly higher in H1N1 patients. Patients with pandemic influenza-associated ARDS had higher LIS both at presentation and over the course of the first six days of treatment when compared to non-H1N1 associated ARDS controls. The difference in LIS persisted over the duration of observation in patients with H1N1 possibly explaining the increased duration of mechanical ventilation

Thrombospondin-1 Contributes to Mortality in Murine Sepsis through Effects on Innate Immunity

BACKGROUND:Thrombospondin-1 (TSP-1) is involved in many biological processes, including immune and tissue injury response, but its role in sepsis is unknown. Cell surface expression of TSP-1 on platelets is increased in sepsis and could activate the anti-inflammatory cytokine transforming growth factor beta (TGFβ1) affecting outcome. Because of these observations we sought to determine the importance of TSP-1 in sepsis. METHODOLOGY/PRINCIPAL FINDINGS:We performed studies on TSP-1 null and wild type (WT) C57BL/6J mice to determine the importance of TSP-1 in sepsis. We utilized the cecal ligation puncture (CLP) and intraperitoneal E. coli injection (i.p. E. coli) models of peritoneal sepsis. Additionally, bone-marrow-derived macrophages (BMMs) were used to determine phagocytic activity. TSP-1-/- animals experienced lower mortality than WT mice after CLP. Tissue and peritoneal lavage TGFβ1 levels were unchanged between animals of each genotype. In addition, there is no difference between the levels of major innate cytokines between the two groups of animals. PLF from WT mice contained a greater bacterial load than TSP-1-/- mice after CLP. The survival advantage for TSP-1-/- animals persisted when i.p. E. coli injections were performed. TSP-1-/- BMMs had increased phagocytic capacity compared to WT. CONCLUSIONS:TSP-1 deficiency was protective in two murine models of peritoneal sepsis, independent of TGFβ1 activation. Our studies suggest TSP-1 expression is associated with decreased phagocytosis and possibly bacterial clearance, leading to increased peritoneal inflammation and mortality in WT mice. These data support the contention that TSP-1 should be more fully explored in the human condition

A clinical procedures curriculum for undergraduate medical students: the eight-year history of a third-year immersive experience

Background: Procedural skills training is a critical component of medical education, but is often lacking in standard clinical curricula. We describe a unique immersive procedural skills curriculum for medical students, designed and taught primarily by emergency medicine faculty at The Ohio State University College of Medicine. Objectives: The primary educational objective of this program was to formally introduce medical students to clinical procedures thought to be important for success in residency. The immersion strategy (teaching numerous procedures over a 7-day period) was intended to complement the student's education on third-year core clinical clerkships. Program design: The course introduced 27 skills over 7 days. Teaching and learning methods included lecture, prereading, videos, task trainers, peer teaching, and procedures practice on cadavers. In year 4 of the program, a peer-team teaching model was adopted. We analyzed program evaluation data over time. Impact: Students valued the selection of procedures covered by the course and felt that it helped prepare them for residency (97%). The highest rated activities were the cadaver lab and the advanced cardiac life support (97 and 93% positive endorsement, respectively). Lectures were less well received (73% positive endorsement), but improved over time. The transition to peer-team teaching resulted in improved student ratings of course activities (p<0.001). Conclusion: A dedicated procedural skills curriculum successfully supplemented the training medical students received in the clinical setting. Students appreciated hands-on activities and practice. The peer-teaching model improved course evaluations by students, which implies that this was an effective teaching method for adult learners. This course was recently expanded and restructured to place the learning closer to the clinical settings in which skills are applied

Microvesicular caspase-1 mediates lymphocyte apoptosis in sepsis.

OBJECTIVE:Immune dysregulation during sepsis is poorly understood, however, lymphocyte apoptosis has been shown to correlate with poor outcomes in septic patients. The inflammasome, a molecular complex which includes caspase-1, is essential to the innate immune response to infection and also important in sepsis induced apoptosis. Our group has recently demonstrated that endotoxin-stimulated monocytes release microvesicles (MVs) containing caspase-1 that are capable of inducing apoptosis. We sought to determine if MVs containing caspase-1 are being released into the blood during human sepsis and induce apoptosis.. DESIGN:Single-center cohort study. MEASUREMENTS:50 critically ill patients were screened within 24 hours of admission to the intensive care unit and classified as either a septic or a critically ill control. Circulatory MVs were isolated and analyzed for the presence of caspase-1 and the ability to induce lymphocyte apoptosis. Patients remaining in the ICU for 48 hours had repeated measurement of caspase-1 activity on ICU day 3. MAIN RESULTS:Septic patients had higher microvesicular caspase-1 activity 0.05 (0.04, 0.07) AFU versus 0.0 AFU (0, 0.02) (p<0.001) on day 1 and this persisted on day 3, 0.12 (0.1, 0.2) versus 0.02 (0, 0.1) (p<0.001). MVs isolated from septic patients on day 1 were able to induce apoptosis in healthy donor lymphocytes compared with critically ill control patients (17.8±9.2% versus 4.3±2.6% apoptotic cells, p<0.001) and depletion of MVs greatly diminished this apoptotic signal. Inhibition of caspase-1 or the disruption of MV integrity abolished the ability to induce apoptosis. CONCLUSION:These findings suggest that microvesicular caspase-1 is important in the host response to sepsis, at least in part, via its ability to induce lymphocyte apoptosis. The ability of microvesicles to induce apoptosis requires active caspase-1 and intact microvesicles

Caspase-1 Regulates Escherichia coli Sepsis and Splenic B Cell Apoptosis Independently of Interleukin-1β and Interleukin-18

Rationale: Caspase-1 processes interleukin 1β (IL-1β) and IL-18 but may also contribute to apoptosis. In this context, caspase-1 knockout mice have been shown to be protected from endotoxin-induced mortality, whereas IL-1β knockout mice are not protected