The New Monumental Era: Daniel Webster and the Commemoration of Compromise in the Age of Disunion, 1853-1865

Professional Paper 1: This professional paper is an in-depth analysis of a statue of Daniel Webster erected in Boston, Massachusetts, in 1859. Daniel Webster was a congressman for Massachusetts who became a controversial figure after he spoke in support of the Fugitive Slave Law as part of the Compromise of 1850. This paper analyzes the Daniel Webster statue and argues that the fractured politics of Union politicized public commemoration in the late antebellum period after the Compromise of 1850. This paper furthermore analyzes one of the first debates surrounding the public commemoration of a controversial historical actor with close ties to the perpetuation of American slavery. The Daniel Webster statue was part of a mass movement to commemorate and celebrate America’s past heroes from the revolutionary generation and the recent past. The monied aristocracy in Boston viewed the statue as an emblem of nationalist pride and unity in the months leading up to the war. Meanwhile, Garrisonian abolitionists contested the politics of commemoration and moral physical boundaries in antebellum American cities such as Boston. Southern politicians also debated the significance of the Webster state and engaged in rituals of the public commemoration. This professional paper is an important contribution to the historical scholarship on statues, memorials, and the politicization of memory. Furthermore, it encourages historians to analyze how memorials fit into the politics of union and democratic practices of the late antebellum period. Monuments and other forms of public commemoration are deeply connected to moral about the political economy of slavery. Professional Paper 2: This professional paper analyzes the history of the Virginian oyster industry over the course of the long nineteenth century. It argues that the Virginia state legislature debated and ultimately implemented protectionist economic policies aimed to guard the state from Northern exploitation. To make Virginia more commercially independent, policymakers determined that the taxation, policing, and strict regulation of state-owned oyster beds would facilitate the revenue necessary for industrial modernization. This essay adopts the oyster commodity as its focus to analyze the Southern political economy of the late antebellum period and postbellum period. This exploration of the oyster commodity reveals how sectionalism impacted the relationship between Southern agricultural goods and Northern businesses and consumers. This paper also argues that Virginia’s oyster industry and state regulations relied on the threatened use of violence. The Virginia oyster police shows that the American regulatory state in the nineteenth century not only relied on matters of property and law, but also state-sanctioned violence. This professional paper contributes to scholarship on Virginian and Southern history. It also engages with scholarship on the Southern political economy in the nineteenth century

Biomarkers and Cellular Biology in Perioperative Medicine.

Surgical procedures alter tissue integrity; are associated with pain and activation of the sympathetic nervous system; and sometimes, cause exposure to foreign materials used during the surgery or implanted perioperatively [...]

Adaptive Lerngraphen im Digitalen Klassenzimmer: Synchrones Distanzlernen mit ASYMPTOTE

Mit der COVID-19-Pandemie und dem plötzlich erforderlichen Distanzunterricht im Frühjahr 2020 wurden verschiedenste Defizite in der digitalen Schulbildung sichtbar. So sahen sich viele Lehrkräfte mit mangelnder technischer Ausstattung als auch der fehlenden technischen Ausbildung konfrontiert (Forsa, 2020). Des Weiteren konnten sie nur auf ein unzureichendes Angebot an digitalen Lernplattformen zurückgreifen und berichteten von einem vermehrten Einsatz von Reproduktionsaufgaben (Barlovits et al., 2021). Sprunghaft rückte die Nutzung und Entwicklung von digitalen Lernplattformen in den vergangenen Jahren sowohl in den öffentlichen als auch den politischen Fokus (WELT, 2020). In einer Bestandsaufnahme einiger bestehender Lernplattformen von Thurm und Graewert (2022) wurde allerdings deutlich, dass das volle Potential von digitalen Lernangeboten bei weitem nicht ausgenutzt wird und auch in der Qualität der Lernangebote teils gravierende Unterschiede bestehen. Thurm und Graewert (2022) fordern daher eine Weiterentwicklung der digitalen Lehr-/Lernumgebungen beziehungsweise eine Neuentwicklung dieser unter Berücksichtigung verschiedener Kriterien. Zu Letzteren gehören mitunter die Qualität der Aufgaben in Bezug auf mögliche Aufgabenformate, die Qualität der Diagnostik, die Adaptivität an die Lernenden, soziales Lernen in Form von Teamarbeit sowie Teamkommunikation und nicht zuletzt die Möglichkeiten der Eigenregulation. Mit dem Wissen um diese Anforderungen für digitale Lernplattformen stellen wir das Projekt ASYMPTOTE und das gleichnamige System für synchrones Distanzlernen vor

Sequential Surgical Procedures in Vascular Surgery Patients Are Associated With Perioperative Adverse Cardiac Events

Patients at elevated cardiovascular risk are prone to perioperative cardiovascular complications, like myocardial injury after non-cardiac surgery (MINS). We have demonstrated in a mouse model of atherosclerosis that perioperative stress leads to an increase in plaque volume and higher plaque vulnerability. Regulatory T cells (Tregs) play a pivotal role in development and destabilization of atherosclerotic plaques. For this exploratory post-hoc analysis we identified 40 patients recruited into a prospective perioperative biomarker study, who within the inclusion period underwent sequential open vascular surgery. On the basis of protein markers measured in the biomarker study, we evaluated the perioperative inflammatory response in patients' plasma before and after index surgery as well as before and after a second surgical procedure. We also analyzed available immunohistochemistry samples to describe plaque vulnerability in patients who underwent bilateral carotid endarterectomy (CEA) in two subsequent surgical procedures. Finally, we assessed if MINS was associated with sequential surgery. The inflammatory response of both surgeries was characterized by postoperative increases of interleukin-6,−10, Pentraxin 3 and C-reactive protein with no clear-cut difference between the two time points of surgery. Plaques from CEA extracted during the second surgery contained less Tregs, as measured by Foxp3 staining, than plaques from the first intervention. The 2nd surgical procedure was associated with MINS. In conclusion, we provide descriptive evidence that sequential surgical procedures involve repeat inflammation, and we hypothesize that elevated rates of cardiovascular complications after the second procedure could be related to reduced levels of intraplaque Tregs, a finding that deserves confirmatory testing and mechanistic exploration in future populations

Intravenous Sphingosylphosphorylcholine Protects Ischemic and Postischemic Myocardial Tissue in a Mouse Model of Myocardial Ischemia/Reperfusion Injury

HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P3 was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P3-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P3 receptor

Acute perioperative-stress-induced increase of atherosclerotic plaque volume and vulnerability to rupture in apolipoprotein-E-deficient mice is amenable to statin treatment and IL-6 inhibition

Myocardial infarction and stroke are frequent after surgical procedures and consume a considerable amount of benefit of surgical therapy. Perioperative stress, induced by surgery, is composed of hemodynamic and inflammatory reactions. The effects of perioperative stress on atherosclerotic plaques are ill-defined. Murine models to investigate the influence of perioperative stress on plaque stability and rupture are not available. We developed a model to investigate the influence of perioperative stress on plaque growth and stability by exposing apolipoprotein-E-deficient mice, fed a high cholesterol diet for 7 weeks, to a double hit consisting of 30 min of laparotomy combined with a substantial blood loss (approximately 20% of total blood volume; 400 µl). The innominate artery was harvested 72 h after the intervention. Control groups were sham and baseline controls. Interleukin-6 (IL-6) and serum amyloid A (SAA) plasma levels were determined. Plaque load, vascular smooth muscle cell (VSMC) and macrophage content were quantified. Plaque stability was assessed using the Stary score and frequency of signs of plaque rupture were assessed. High-dose atorvastatin (80 mg/kg body weight/day) was administered for 6 days starting 3 days prior to the double hit. A single dose of an IL-6-neutralizing antibody or the fusion protein gp130-Fc selectively targeting IL-6 trans-signaling was subcutaneously injected. IL-6 plasma levels increased, peaking at 6 h after the intervention. SAA levels peaked at 24 h (n=4, P<0.01). Plaque volume increased significantly with the double hit compared to sham (n=8, P<0.01). More plaques were scored as complex or bearing signs of rupture after the double hit compared to sham (n=5-8, P<0.05). Relative VSMC and macrophage content remained unchanged. IL-6-inhibition or atorvastatin, but not blocking of IL-6 trans-signaling, significantly decreased plaque volume and complexity (n=8, P<0.01). Using this model, researchers will be able to further investigate the pathophysiology of perioperative plaque stability, which can result in myocardial infarction, and, additionally, to test potential protective strategies

Measurement of dissociation rate of biomolecular complexes using CE

Fluorescence anisotropy (FA), non-equilibrium CE of equilibrium mixtures (NECEEM) and high-speed CE were evaluated for measuring dissociation kinetics of peptide–protein binding systems. Fyn-SH3-SH2, a protein construct consisting of the src homology 2 (SH2) and 3 (SH3) domain of the protein Fyn, and a fluorescein-labeled phosphopeptide were used as a model system. All three methods gave comparable half-life of∼53 s for Fyn-SH3-SH2:peptide complex. Achieving satisfactory results by NECEEM required columns over 30 cm long. When using Fyn-SH2-SH3 tagged with glutathione S -transferase (GST) as the binding protein, both FA and NECEEM assays gave evidence of two complexes forming with the peptide, yet neither method allowed accurate measurement of dissociation rates for both complexes because of a lack of resolution. High-speed CE, with a 7 s separation time, enabled separation of both complexes and allowed determination of dissociation rate of both complexes independently. The two complexes had half-lives of 22.0±2.7 and 58.8±6.1 s, respectively. Concentration studies revealed that the GST-Fyn-SH3-SH2 protein formed a dimer so that complexes had binding ratios of 2:1 (protein-to-peptide ratio) and 2:2. Our results demonstrate that although all methods are suitable for 1:1 binding systems, high-speed CE is unique in allowing multiple complexes to be resolved simultaneously. This property allows determination of binding kinetics of complicated systems and makes the technique useful for discovering novel affinity interactions.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/61861/1/457_ftp.pd

NT-proBNP or Self-Reported Functional Capacity in Estimating Risk of Cardiovascular Events After Noncardiac Surgery

ImportanceNearly 16 million surgical procedures are conducted in North America yearly, and postoperative cardiovascular events are frequent. Guidelines suggest functional capacity or B-type natriuretic peptides (BNP) to guide perioperative management. Data comparing the performance of these approaches are scarce.ObjectiveTo compare the addition of either N-terminal pro-BNP (NT-proBNP) or self-reported functional capacity to clinical scores to estimate the risk of major adverse cardiac events (MACE).Design, Setting, and ParticipantsThis cohort study included patients undergoing inpatient, elective, noncardiac surgery at 25 tertiary care hospitals in Europe between June 2017 and April 2020. Analysis was conducted in January 2023. Eligible patients were either aged 45 years or older with a Revised Cardiac Risk Index (RCRI) of 2 or higher or a National Surgical Quality Improvement Program, Risk Calculator for Myocardial Infarction and Cardiac (NSQIP MICA) above 1%, or they were aged 65 years or older and underwent intermediate or high-risk procedures.ExposuresPreoperative NT-proBNP and the following self-reported measures of functional capacity were the exposures: (1) questionnaire-estimated metabolic equivalents (METs), (2) ability to climb 1 floor, and (3) level of regular physical activity.Main Outcome and MeasuresMACE was defined as a composite end point of in-hospital cardiovascular mortality, cardiac arrest, myocardial infarction, stroke, and congestive heart failure requiring transfer to a higher unit of care.ResultsA total of 3731 eligible patients undergoing noncardiac surgery were analyzed; 3597 patients had complete data (1258 women [35.0%]; 1463 (40.7%) aged 75 years or older; 86 [2.4%] experienced a MACE). Discrimination of NT-proBNP or functional capacity measures added to clinical scores did not significantly differ (Area under the receiver operating curve: RCRI, age, and 4MET, 0.704; 95% CI, 0.646-0.763; RCRI, age, and 4MET plus floor climbing, 0.702; 95% CI, 0.645-0.760; RCRI, age, and 4MET plus physical activity, 0.724; 95% CI, 0.672-0.775; RCRI, age, and 4MET plus NT-proBNP, 0.736; 95% CI, 0.682-0.790). Benefit analysis favored NT-proBNP at a threshold of 5% or below, ie, if true positives were valued 20 times or more compared with false positives. The findings were similar for NSQIP MICA as baseline clinical scores.Conclusions and relevanceIn this cohort study of nearly 3600 patients with elevated cardiovascular risk undergoing noncardiac surgery, there was no conclusive evidence of a difference between a NT-proBNP–based and a self-reported functional capacity–based estimate of MACE risk.Trial RegistrationClinicalTrials.gov Identifier: NCT0301693

Biomarker-guided intervention to prevent acute kidney injury after major surgery (BigpAK-2 trial): study protocol for an international, prospective, randomised controlled multicentre trial

IntroductionPrevious studies demonstrated that the implementation of the Kidney Disease Improving Global Outcomes (KDIGO) guideline-based bundle, consisting of different supportive measures in patients at high risk for acute kidney injury (AKI), might reduce rate and severity of AKI after surgery. However, the effects of the care bundle in broader population of patients undergoing surgery require confirmation.Methods and analysisThe BigpAK-2 trial is an international, randomised, controlled, multicentre trial. The trial aims to enrol 1302 patients undergoing major surgery who are subsequently admitted to the intensive care or high dependency unit and are at high-risk for postoperative AKI as identified by urinary biomarkers (tissue inhibitor of metalloproteinases 2*insulin like growth factor binding protein 7 (TIMP-2)*IGFBP7)). Eligible patients will be randomised to receive either standard of care (control) or a KDIGO-based AKI care bundle (intervention). The primary endpoint is the incidence of moderate or severe AKI (stage 2 or 3) within 72 hours after surgery, according to the KDIGO 2012 criteria. Secondary endpoints include adherence to the KDIGO care bundle, occurrence and severity of any stage of AKI, change in biomarker values during 12 hours after initial measurement of (TIMP-2)*(IGFBP7), number of free days of mechanical ventilation and vasopressors, need for renal replacement therapy (RRT), duration of RRT, renal recovery, 30-day and 60-day mortality, intensive care unit length-of-stay and hospital length-of-stay and major adverse kidney events. An add-on study will investigate blood and urine samples from recruited patients for immunological functions and kidney damage.Ethics and disseminationThe BigpAK-2 trial was approved by the Ethics Committee of the Medical Faculty of the University of Münster and subsequently by the corresponding Ethics Committee of the participating sites. A study amendment was approved subsequently. In the UK, the trial was adopted as an NIHR portfolio study. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and will guide patient care and further research.Trial registration numberNCT04647396