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The Impact of Dietary Iron Restriction on Sickling Kinetics and Hemolysis in A Transgenic Model of Sickle Cell Disease
No full textSickle cell disease (SCD) is caused by polymerization of deoxy-hemoglobin-S (HbS) within the red blood cell (RBC). HbS polymerization is a concentration-dependent process. I hypothesized that dietary iron restriction would decrease the concentration of HbS in the RBC, resulting in delayed sickling, and decreased organ injury.To test this hypothesis, I studied male and female transgenic mice that express the human gamma, alpha and beta globin-S genes (SCD mice). To induce iron deficiency, mice were fed an iron-restricted diet (0-3 ppm iron) introduced at weaning. For comparison, parallel cohorts were fed an iron-sufficient diet (39 ppm iron) or an iron-abundant diet (821 ppm iron) also introduced at weaning. After 2, 4, or 6 months on the diets, mice were euthanized to collect blood and harvest tissues. Iron availability was determined by measuring plasma ferritin and hepcidin using ELISA kits. RBC and reticulocyte parameters were measured by an automated hematology analyzer. Hemoglobin composition was quantified by ion-exchange chromatography. Hb-O2 affinity was measured by sickling assay and HEMOX-Analyzer. RBC sickling was measured as the half-life of cells remaining round after exposure to 3% oxygen. Hemolysis was evaluated by measuring the absorbance of plasma heme, and the concentration of the heme and hemoglobin scavengers hemopexin and haptoglobin by ELISA. To examine tissues, animals were first perfused PBS. Organs were weighed to determine organ/body mass indices. Liver, spleen, and kidneys were preserved in formalin and embedded in paraffin for sectioning. Sections were stained with Prussian blue to determine iron deposition and stained with hematoxylin and eosin for histologic analysis by a veterinary pathologist. Histologic evidence of hepatic necrosis was reported as either present or absent.Dietary iron restriction caused depletion of iron stores as evidenced by lower plasma ferritin levels and suppression of the negative iron regulator hepcidin in both male and female SCD mice. RBC and reticulocyte parameters were unaffected by dietary iron restriction, though sex differences and age-related changes were observed. Fetal hemoglobin (HbF) levels were less than 1% and were unchanged by dietary iron restriction, though HbF levels were higher in females over time. Dietary iron restriction increased hemoglobin oxygen affinity in the first cohort, but this finding was not confirmed in a second cohort. The half-life of round cells under conditions of 3% oxygen was increased in SCD mice after 4 or 6 months of dietary iron restriction, but not after 2 months. The plasma heme concentration was decreased by the dietary iron-restriction at 4 and 6 months in the first cohort but was unchanged in the second cohort. Liver mass indices were decreased in mice fed the iron-restricted diet, and dietary iron restriction reduced the incidence of hepatic necrosis in the females by half.Dietary iron restriction was effective at depleting iron stores and suppressing the negative regulator of iron uptake, hepcidin. Nevertheless, the concentration of hemoglobin S, and many other RBC parameters, remained constant despite a clear impact of diet on iron stores and regulation. The physiologic effects of iron restriction showed important sex-specific differences: male SCD mice developed increased hemoglobin oxygen affinity and a longer round cell half-life after six months of iron restriction; whereas female SCD mice were protected against hepatic necrosis without similar improvements in sickling. My work demonstrates that iron restriction can improve sickling through changes in hemoglobin oxygen affinity, rather than through changes in hemoglobin-S concentration, as hypothesized. Furthermore, I have demonstrated for the first time that iron restriction is protective against hepatic necrosis, without changes in ex vivo sickling. This raises the possibly that protection is conferred instead through sex-specific increases in hepatic iron recycling. Together, the results in this thesis show that iron restriction can modulate the severity of sickle cell disease through both erythrocytic and non-erythrocytic pathways – a key conclusion that will inform clinical studies of iron restriction in patients with sickle cell disease.Health sciencesHematology, Iron Deficiency Anemia, Red Blood Cell, Sickle Cell DiseaseBiologyDegree Awarded: Ph.D. Biology. The Catholic University of Americ
Andrea Echeverria Interview, May 19, 2020
No full textAndrea Echeverria discusses the impact of COVID on her life. She shares that she has started teaching online, and that her four-year-old son has stopped going to school. This means that she can spend more time with him, and is surviving thanks to increased interactions with family and friends in Chile and Columbia. She has also been playing games online for the first time, and meditating everyday. Thinking about new stories and research projects, and looking for a new home, has also kept her going. Andrea reflects on how this crisis has led her to realize how fragile economic and social structures are, and how everything is so connected right now. This video is part of the Humanities Truck's From Me To You: A Covid-19 Oral History Project. https://humanitiestruck.com/frommetoyou
Professionalism and Brutality: The Viennese Police and the Public in Extraordinary Times, 1918–1955
No full textUsing the Vienna Police Directorate as a case study, this dissertation illuminates the relationship between Nazism, the Holocaust, and twentieth-century ideals of professional policing. To do so, it takes a longer view and examine the Vienna Police Directorate under four regimes: the Austrian First Republic, the Austrofascist dictatorship, Nazi Austria, and Allied-occupied Austria. I primarily focus on the decisions, policies, and attitudes of Viennese policemen, but also pay close attention to the perspective of those whom they policed. Oral histories, memoirs, court testimonies, and newspapers reveal that many Viennese had strong opinions and memorable interactions with policemen. My inclusion and prioritization of their stories reflects my goal, inspired by Saul Friedländer’s work on the Holocaust, of writing an “integrated history” of the Vienna Police Directorate that understands interactions between the police and the public as causal. In the midst of instability and regime change, professionalism became the metric by which both the Vienna Police Directorate and the Viennese public judged police conduct. Police claimed authority based on their status as neutral professionals, while the public accused the police of brutality and bias. These discourses shaped the Viennese-police relationship throughout the 1918 to 1955 period, transcending Austria’s democratic, dictatorial and Nazi regimes. My dissertation thus calls into question standard associations between police professionalism, brutality, politicization, and democracy.European historyHistoryAustria, Holocaust, Nazi Germany, Policing, Vienna, Vienna Police DirectorateHistoryDegree Awarded: Ph.D. History. American Universit
Quantum Chemistry and Kinetics Theory - Solving Mysteries of Chemical Mechanisms
No full textA presentation that was delivered in the Fifth University Research Day at the Catholic University of America in 2020
Limits to the Effectiveness of Foreign Aid: Conflicts, Debt Overhangs, and Epidemics
No full textThis dissertation examines how conflicts, debt overhangs, and epidemics can impact the effectiveness of foreign aid with respect to economic growth. The literature has been mixed on whether aid, proxied by official development assistance (ODA), has been effective in promoting growth. These three factors are used to assess whether the impact of aid is estimated properly because they are excluded in aid effectiveness studies. This dissertation uses system-GMM to determine whether the inclusion of these factors affect the coefficient of ODA. The findings provide some evidence that including conflicts, debt overhangs, and epidemic would result in a more robust analysis on the impact of foreign aid on GDP growth per capita. Conflicts and debt overhangs are found to have a negative impact on the effectiveness of aid on growth. These findings build on existing research that suggests the impact of foreign aid is small. The results of this dissertation have not only implications on better understanding the effectiveness of aid but also on the provision of aid.EconomicsInternational relationsConflicts, Debt, Epidemics, Foreign Aid, Foreign aid effectiveness, GrowthEconomicsDegree Awarded: Ph.D. Economics. American Universit
Immigration: Through a Child Psychological Lens {Poster}
No full textA presentation that was delivered in the Fifth University Research Day at the Catholic University of America in 2020
Macroeconomic Effects of 9/11 on the Economies of the United States, China, and Afghanistan
No full textA presentation that was delivered in the Fifth University Research Day at the Catholic University of America in 2020.This research was collaborated with Allison Kirby, Cameron Dunn, Sofia Cabrera, Cameron Ballar
Making Waves with V-Commerce
No full textA presentation that was delivered in the Fifth University Research Day at the Catholic University of America in 2020
Passing the Baton: An analysis of executive leadership transitions in small and mid-sized nonprofit organizations
No full textThis study examines how and why leadership transitions fail. The nonprofit sector has examined this topic for more than three decades, but research shows that small and mid-sized arts organizations remain unprepared for the inevitable leadership transitions of the future. Building on existing literature, consultants and nonprofit professionals weigh in on the intricacies of transitions in today’s nonprofit environment, how for-profit practices translate to the nonprofit sector, and best practices for involving other stakeholders in the process. Together, these findings suggest that a shift in attitude is needed in the nonprofit sector for organizations to approach these situations with appropriate care and secure the adequate financial resources.Arts managementExecutive, Nonprofit, Succession, TransitionPerforming ArtsDegree Awarded: M.A. Performing Arts. American Universit