American Transcendentalism Contra Contemporary Political Philosophy: Applications of Thomas Carlyle and Ralph Waldo Emerson to Liberal Democratic Capitalism, Platonism, Islamism, Technology, and the end of History

I construct Thomas Carlyle\u27s political philosophy in the contexts of twentieth-century and contemporary political philosophy by dialoging and contrasting Carlyle with the work of John Rawls, Alasdair MacIntyre, Jacques Ellul, and Sayyid Qutb, among others. I also focus my attention on Carlyle as a philosopher who is an intermediary between ancient Platonism and nineteenth-century American Transcendentalism. Carlyle\u27s Sartor Resartus is a Platonic text that provided a foundational inspiration for Ralph Waldo Emerson, Henry David Thoreau, and American Transcendentalism writ-large. Despite Carlyle being a chief source of inspiration for American Transcendentalism, his political theory did not inspire the development of a widely adopted political ideology to compete alongside other prominent twentieth-century ideologies such as liberalism, Marxism, fascism, and Islamism. It is in this context that Carlyle is also relevant in the philosophical inquiry of the end of history, or the ascertaining of the last stage of human political development. I argue that this is because Carlyle\u27s philosophical account of transcendentalism in Sartor Resartus can be constructed as post-liberalism, an ideology that reforms liberalism by seeking to stem its facilitation of increasing levels of economic inequality and increasing levels of political conflict on the bases of race, class, religion, etc. I apply Carlyle\u27s philosophy to build on literature that theorizes about post-liberalism by authors such as Patrick Deneen, John Milbank, and Adrian Pabst, who argue that liberalism is on a hazardous trajectory and there is a need to conceive of post-liberalism as an alternative to the trend of increasing authoritarianism

Not just death and ruins: the young and new beginnings in German 'rubble films'

The article looks at ‘Trümmerfilme’ from different zones of occupation and discusses the roles which the young were allocated on German post-war screens. While in all films under-age characters are central to negotiating the severe national crisis following the end of World War II and the defeat of the Nazi dictatorship, the analysis highlights emerging differences in the depiction of the young between films from the Soviet zone and the Western zones of occupation. Despite the general use of the young as figures of distraction from the adults’ involvement in Nazi crimes, children in films from the Soviet zone help to articulate a new national ideal based on collective, public productivity, while the young in films from the Western zones help to formulate the dangers inherited from the immediate past. These differences are reflected in the opposing depictions of the young as innocent in the East and feral in the West, as well as in the intergenerational relations resulting from this. While the children’s potential in the East replaces the parent generation, which is implicitly marked as guilty, the dangers posed by the young in the West strengthen the authority of the parents and the nuclear family model

Evaluation and optimization of medication related fall risk at a community hospital

Background: Falls occur commonly in older adults at a rate of 3-5 per 1000 beds in healthcare settings. They can results in increased length of stay, morbidity and mortality, and healthcare costs. Some risk factors include older age, environmental hazards and medications. Currently at BHM, patient’s risk for falling is assessed based on Morse Fall Scale (MFS), which does include drugs as part of its assessment. The purpose of this project is to integrate medication risk evaluation into our current fall assessment. Methodology: single-centered, retrospective, IRB-reviewed quality improvement project at BHM. We included patients over age 18 who fell with at least a minor injury (F2 level) in 2019. Our primary outcome was to determine prevalence of common high-fall-risk medications administered in patients who fell and our secondary outcome was to identify pharmacy-led interventions to decrease fall risk. Since MFS does not include medications as part of its score, we then evaluated each patient using a medication scoring system with point value of 1-3 for high-fall-risk medications (point value of 3 is assigned to high-fall-risk medications and point value of 1 is assigned to low fall risk medications). Any patient with a cumulative score of higher than 6 is recognized to be at high fall risk. Results: Primary outcome showed that cardiac agents, followed by opioids, and by benzodiazepines/sleep aids were the highest administered medications in our patients who fell. Based on those findings, we identified 29 opportunities where patient could have received lower doses and/or have had medication scheduling changes in order to reduce fall risk. We are proposing automatic dose adjustments similar to hydromorphone and zolpidem/temazepam protocols where pharmacists can reduce starting doses to lowest dose possible for drug naïve patients. In addition, we are proposing to have medication scoring system to be implemented into our software so pharmacists are notified if a patient is high risk for falls based on MFS score and medication score system. Conclusion: Pharmacists can play a huge role in reducing falls in inpatient settings. Based on our findings, some opportunities where pharmacists can intervene to reduce risk of falling include scheduling and automatic dose reductions with medications such as cardiac agents, opioids, and benzodiazepine/sleep aids

Evaluation of Four-Factor Prothrombin Complex Concentrate Dosing Strategies for the Reversal of Bleeding Associated with Apixaban or Rivaroxaban

In clinical practice, 4F-PCC is commonly used off-label as a non-specific reversal agent for factor Xa inhibitors apixaban and rivaroxaban. While the hemostatic effectiveness of 4F-PCC in patients taking apixaban and rivaroxaban has been studied in the literature, the optimal dose remains unclear. This was a multicenter, retrospective observational study designed to evaluate the hemostatic effectiveness and safety of 4F-PCC dosed at 2000 units, 35 units/kg, and 50 units/kg for the reversal of bleeding associated with apixaban or rivaroxaban. The primary outcome was hemostatic effectiveness as defined by the Internal Society of Thrombosis and Hemostasis and secondary outcomes were rates of all-cause in-hospital mortality and thrombosis at 30 days or discharge. Out of 278 patients who received 4F-PCC for reversal of bleeding associated with apixaban or rivaroxaban, 72 patients were included in the final analysis. The 2000-unit, 35 unit/kg, and 50 unit/kg dosing strategies were used in 12, 36, and 24 patients, respectively. Hemostatic effectiveness was achieved in 86%, 67%, and 70% of intracerebral hemorrhages (p = 0.762) and 60%, 71%, 86% of gastrointestinal hemorrhages (p = 0.422). Neither dosing strategy was associated with a statistically significantly higher rate of hemostatic effectiveness nor lower rates of all-cause mortality or thrombosis

Modificación post-síntesis de macrogeles y nanogeles :control del grado de entrecruzamiento, estructura y funcionalización

Tesis (Doctor en Ciencias Químicas) - - Universidad Nacional de Córdoba. Facultad de Ciencias Químicas, 2019La actual, es considerada la generación de los materiales inteligentes. Éstos se caracterizan por ser capaces de sensar estímulos en su entorno, o su propio estado, y responder cambiando sus propiedades físico-químicas, de manera predecible y funcional. En los últimos años, el alto grado de desarrollo en este área ha generado la necesidad de sintetizar polímeros de alta complejidad que exhiben funcionalidades y propiedades distintivas. Como estrategia para alcanzar dicha complejidad, se recurre a los criterios de diseño y técnicas de control a nivel molecular desarrolladas en la Química Orgánica, que permiten la preparación de polímeros bien definidos y materiales nanoestructurados. Entre los materiales inteligentes más desarrollados en los últimos años, están los hidrogeles (HGs). Estos son redes poliméricas entrecruzadas, que tienen la capacidad de absorber y retener grandes cantidades de agua o fluidos biológicos. Poseen propiedades particularmente excepcionales, que los han colocado en la mira del desarrollo científico en el área de materiales. La versatilidad química de los hidrogeles, por ser un material polimérico; sus propiedades mecánicas; sus propiedades de hinchamiento; su porosidad; la presencia de una interfaz líquido-sólido en su interior; y su similitud con tejidos biológicos, son algunas de las características que proponen el uso de estos materiales en un creciente número de aplicaciones, principalmente en el área de biomedicina. La aplicación de los hidrogeles en entornos complejos como los biológicos, realizando funciones altamente específicas, requiere de la optimización de las propiedades mecánicas, propiedades de hinchamiento y funcionalidad química de los materiales. Por lo tanto, es necesario superar las barreras impuestas por los métodos tradicionales de síntesis de hidrogeles para lograr estructuras más controladas y funcionales tanto en la macro como en la micro o nanoescala. En este contexto, se ubica el presente trabajo de tesis doctoral titulado: “MODIFICACIÓN POST-SÍNTESIS DE MACROGELES Y NANOGELES: control del grado de entrecruzamiento, estructura y funcionalización”. Este trabajo tiene como objetivo principal el estudio y 2 desarrollo de metodologías de síntesis de hidrogeles y nanogeles (NGs) por polimerización radicalaria, que permitan su modificación post-síntesis, para el control de la morfología, propiedades mecánicas, propiedades de hinchamiento y funcionalidad química de los materiales. Durante el transcurso de esta tesis, se estudiaron y desarrollaron estrategias de síntesis radicalaria de hidrogeles que fueron útiles para controlar las propiedades mencionadas. Estas estrategias permitieron superar, en etapas post-síntesis, dificultades y limitaciones impuestas por las metodologías de síntesis radicalaria tradicionales de hidrogeles y nanogeles. En particular, se estudió la utilización del agente entrecruzante (+)-N,N'- dialiltartradiamida (DAT) en presencia o ausencia de N,N'-metilenbis(acrilamida) (BIS), para la síntesis radicalaria de hidrogeles (HGs) y nanogeles (NGs) basados en diferentes monómeros vinílicos derivados de la acrilamida o metacrilamida. La presencia de un grupo funcional (GF) diol vecinal en DAT permitió la modificación post-síntesis de los HGs y NGs, por tratamiento con soluciones de periodato de sodio. Estas reacciones se llevaron a cabo en solución acuosa, a tiempos cortos y temperatura ambiente. La modificación post-síntesis generó cambios en el grado de entrecruzamiento de HGs y NGs, por clivaje de los entrecruzamientos debidos a DAT, modificando sus propiedades de hinchamiento, propiedades mecánicas, morfología y funcionalidad química. Además, la oxidación de los dioles vecinales sensibles a periodato, permitió obtener GF α-oxo-aldehídos en los materiales sintetizados. Este GF es de alto valor sintético por su participación en reacciones (bio)ortogonales principalmente frente a aminas y α-nucleófilos como hidrazidas y alcoxilaminas. Los α-oxo-aldehídos son frecuentemente obtenidos en péptidos y proteínas para su utilización en bioconjugación, pero tienen muy escasos antecedentes en materiales sintéticos y no se encuentran reportes de su obtención en hidrogeles blandos. Posteriormente, se ensayó la reactividad de este GF con aminas e hidrazidas, en diferentes condiciones de reacción. Como soporte de los estudios realizados y sus resultados, esta tesis se organizó de la siguiente manera: 3 En el Capítulo 1, se introducen conceptos sobre la naturaleza de los hidrogeles, sus características principales y su continuo desarrollo en la elaboración de materiales funcionales. Se describen sus actuales aplicaciones en desarrollo y los desafíos que presentan, principalmente en el control de sus propiedades por limitaciones en las metodologías de síntesis. En el Capítulo 2 se presentan los objetivos generales y específicos de este estudio. En los siguientes Capítulos (3, 4, 5) se muestran los resultados obtenidos en la síntesis y modificación post-síntesis de (macro)hidrogeles con creciente complejidad sintética. Posteriormente, en el Capítulo 6, las metodologías desarrolladas en HGs se aplicaron a la síntesis de NGs termosensibles. La necesidad de control del tamaño, la polidispersidad y la estructura en estos sistemas, impone un mayor número de limitaciones a la obtención de productos por síntesis directa. Por lo tanto, la metodología desarrollada es una herramienta de utilidad para la síntesis y modificación post-síntesis de nanogeles. Posteriormente, y como prueba de concepto, se exploraron tres diferentes aplicaciones basadas en los nanogeles termosensibles sintetizados: la encapsulación de proteínas para su liberación controlada; el desarrollo de nanogeles termosensibles con doxorrubicina, un fármaco anticancerígeno, inmovilizado mediante enlaces covalentes pH sensibles para su liberación controlada; y la obtención de nanogeles huecos (nanocápsulas) basados en poli(N-isopropilacrilamida) (p-NIPAm). En el Capítulo 7 se presentan las conclusiones generales del trabajo de tesis y sus posibles proyecciones. En el Capítulo 8 se encuentra un Anexo con algunas figuras no incluidas en el cuerpo de la tesis. Este trabajo de tesis fue realizado en el Laboratorio de Materiales Poliméricos (LaMaP) de la Facultad de Ciencias Químicas de la Universidad Nacional de Córdoba, en colaboración con el grupo de investigación del Profesor Marcelo Calderón de la Freie Universität Berlín, Alemania. La metodología desarrollada y los resultados obtenidos en esta tesis conforman una nueva herramienta para el desarrollo de materiales funcionales, que podrían ser aplicadas en cualquiera de las actuales líneas de investigación de LaMaP: desde la producción de (nano)dispositivos para la liberación controlada de fármacos, al desarrollo de actuadores blandos (soft actuators), la modificación de superficies, el anclaje de biomoléculas en soportes cromatográficos, entre otras.202

Imine bonding self-repair hydrogels after periodate-triggered breakage of their cross-links

The development of new materials with smart properties is currently expanding the development of new technologies. Therefore, the design of materials with novel sensitivities and smart behavior is important for the development of smart systems with automated responsivity. We have recently reported the synthesis of hydrogels, cross-linked by N,N´-diallyltartardiamide (DAT). The covalent DAT-crosslinking points have vicinal diols which can be easily cleaved with periodate, generating changes in the hydrogel properties, as well as generating valuable α-oxo-aldehyde functional groups useful for further chemical modification. Based on those findings, we envisioned that a self-healable hydrogel could be obtained by incorporation of primary amino functional groups, from 2-aminoethyl methacrylate hydrochloride (AEMA), coexisting with DAT into the same network. Herein, α-oxo-aldehyde groups generated after the reaction with periodate would arise in the immediate environment of amine groups to form imine cross-links. For this purpose, DAT-crosslinked hydrogels were synthesized and carefully characterized. The cleavage of DAT-crosslinks with periodate promoted changes in the mechanical and swelling properties of the materials. As expected, a self-healing behavior was observed, based on the spontaneous formation of imine covalent bonds. In addition, we surprisingly found a combination of fast vicinal diols cleavage and a low speed self-crosslinking reaction by imine formation. Consequently, it was found a time-window in which a periodate-treated polymer was obtained in a transient liquid state, which can be exploited to choose the final shape of the material, before automated gelling. The singular properties attained on these hydrogels could be useful for developing sensors, actuators, among other smart systems.Fil: Wolfel Sánchez, Alexis. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Alvarez Igarzabal, Cecilia Ines. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Romero, Marcelo Ricardo. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentin

Evaluation of clinical outcomes of 4-factor prothrombin complex concentrate versus andexanet alfa in the treatment of intracerebral hemorrhage

Purpose: Oral anticoagulants account for up to 20% of intracerebral hemorrhages (ICH) with one-year mortality estimated as high as 54%. Several studies have examined the use of 4-Factor prothrombin complex concentrate (4F-PCC) and andexanet alfa in the treatment of factor Xa associated ICH. High cost burden, lack of clinical outcomes, and risk of thromboembolic events continues to be a major dilemma behind product selection at many healthcare systems. The purpose of this project is to compare clinical outcomes between 4F-PCC and andexanet alfa in the management of patients with ICH secondary to apixaban and rivaroxaban at Baptist Hospital of Miami (BHM). Methodology: This single-center, performance improvement project was a retrospective chart review conducted for all patients admitted to BHM between August 1, 2018 and March 30, 2020. Patients were included if they received either 4F-PCC or andexanet alfa for the management of ICH induced by apixaban and rivaroxaban. The primary outcome of this project compared bleeding expansion at 24 and 48 hours among these two groups as defined by a brain computed tomography (CT) scan. Secondary outcomes included dose of reversal agent used, time to reversal agent administration in relation to the last direct oral anticoagulant (DOAC) dose, thromboembolic events within 30 days, hospital length of stay, mortality rate, and discharge status. Nominal data was presented as means and percentages. Baseline demographics and characteristics as well as primary and secondary outcomes were compared using the Fisher Exact test and Student’s T-test with p-values less than 0.05 considered statistically significant. Results: Overall, 62 patients were screened for inclusion and exclusion criteria. Of these, 19 patients were included and evaluated for primary and secondary outcomes. Eligible patients were divided into group I (andexanet alfa, n=7) and group II (4F-PCC, n=12). Several baseline demographics and patient characteristics were noted to be similar between these two groups, but not statistically significant. In reference to the primary outcome, patients in group I had 0% expansion of bleeds whereas group II patients had a 30% expansion of bleed, all non-surgical SDH (p=0.52). The average dose of 4F-PCC was 30 units/kg while 86% of the patients received low dose andexanet alfa. Administration of andexanet alfa and 4F-PCC in relation to the last DOAC dose was an average of 13 hours for both groups (p=0.91). The average hospital length of stay was 13 days for both groups (p=0.98). The incidence of thromboembolic events was noted to be 25% in group I while no thromboembolic events were noted in group II (p=0.26). Overall, there was a 14% mortality rate in group I versus 25% in group II (p=0.50). Conclusion: This study demonstrates clinical significant results relating to the efficacy and safety concerns of andexanet alfa and 4F-PCC in the management of ICH. As the results suggested, andexanet alfa treated patients had 0% expansion of bleed at 24 and 48 hours versus 30% in 4F-PCC treated patients (p=0.52), all non-surgical SDH. Moreover, the percent decrease in volume for the bleeding expansion was greater for andexanet alfa in the ICH arm, (52% vs 19%). Lastly, andexanet alfa treated patients had 0% thromboembolic rates versus 25% in 4F-PCC treated patients (p=0.26) with an overall mortality rate of 14% versus 25% respectively (p=0.50)

A Test-Negative Design with Additional Population Controls Can Be Used to Rapidly Study Causes of the SARS-CoV-2 Epidemic.

Testing of symptomatic persons for infection with severe acute respiratory syndrome coronavirus-2 is occurring worldwide. We propose two types of case-control studies that can be carried out jointly in test settings for symptomatic persons. The first, the test-negative case-control design (TND) is the easiest to implement; it only requires collecting information about potential risk factors for Coronavirus Disease 2019 (COVID-19) from the tested symptomatic persons. The second, standard case-control studies with population controls, requires the collection of data on one or more population controls for each person who is tested in the test facilities, so that test-positives and test-negatives can each be compared with population controls. The TND will detect differences in risk factors between symptomatic persons who have COVID-19 (test-positives) and those who have other respiratory infections (test-negatives). However, risk factors with effect sizes of equal magnitude for both COVID-19 and other respiratory infections will not be identified by the TND. Therefore, we discuss how to add population controls to compare with the test-positives and the test-negatives, yielding two additional case-control studies. We describe two options for population control groups: one composed of accompanying persons to the test facilities, the other drawn from existing country-wide healthcare databases. We also describe other possibilities for population controls. Combining the TND with population controls yields a triangulation approach that distinguishes between exposures that are risk factors for both COVID-19 and other respiratory infections, and exposures that are risk factors for just COVID-19. This combined design can be applied to future epidemics, but also to study causes of nonepidemic disease

Unraveling the gallol-driven assembly mechanism of thermoreversible supramolecular hydrogels inspired by ascidians

Polyphenols-based supramolecular hydrogels have recently attracted much attention as smart materials for applications in several technologies. Although great advances have been made in this field, there is a challenging need for creating new versatile materials that combine synthesis simplicity and suitable functional properties. In this work, inspired by the hydrogen bonding ability of pyrogallol-bearing proteins found in ascidians, we explored a small gallol analog, gallic acid (GA), as a dynamic crosslinker of poly(vinyl alcohol) (PVA). The fundamentals of the supramolecular assembly mechanism of PVA/GA hydrogels are studied for understanding the final properties of the obtained thermo-reversible hydrogels. The polymer deacetylation degree was a key factor to control the gelation kinetics, morphology, and properties of the supramolecular materials. Furthermore, the intercalation of GA molecules between PVA chains produced polymer crystals with a new spatial arrangement, modifying the elastic modulus of the supramolecular network and increasing its stability in water. With remarkable fast gelation ability, ascidian-inspired PVA-GA hydrogels may provide a promising platform for a wide range of biomedical applications including topical drug delivery of therapeutic proteins, wearable electronic devices, and 3D printing.Fil: Wolfel Sánchez, Alexis. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Euti, Esteban. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Picchio, Matías Luis. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Romero, Marcelo Ricardo. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Galván Josa, Víctor Martín. Universidad Nacional de Córdoba. Facultad de Matemática, Astronomía y Física; ArgentinaFil: Martinelli, Marisa. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Minari, Roque Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Desarrollo Tecnológico para la Industria Química. Universidad Nacional del Litoral. Instituto de Desarrollo Tecnológico para la Industria Química; ArgentinaFil: Alvarez Igarzabal, Cecilia Ines. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; Argentin