Understanding Impaired Immunity to Bacterial Pathogens Post-Bone Marrow Transplantation

Respiratory tract infections (RTI) are major causes of morbidity and mortality, with lower respiratory infections alone being the fourth major cause of death in the world, taking the life of over 3 million individuals in 2016 (World Health Organization (WHO), 2018). Bacterial infections are a major cause of RTI. In this dissertation we focused on a subject group who is at high risk of developing severe illness due to opportunistic bacterial infections, hematopoietic stem cell transplant (HSCT) patients. HSCT utilizes stem cells derived from bone marrow, umbilical cord blood, or peripheral blood of patients themselves (autologous) or matched donors (allogeneic) to treat or cure a variety of hematological and inherited disorders. This procedure has become standard of care with more than 18,000 HSCTs performed every year in the United States alone. Unfortunately, patients that undergo HSCT (both autologous and allogeneic) are immunosuppressed and remain so even after stem cell engraftment, making them susceptible to infections by a wide array of opportunistic pathogens. Pseudomonas aeruginosa is an opportunistic Gram-negative bacterium that can cause life-threatening complications in HSCT patients and has recently been identified by the WHO as a critical pathogen for which new therapeutic strategies are needed. In the lung of immunosuppressed individuals, P. aeruginosa can cause lethal organ injury mainly by stimulating alveolar macrophages to secrete high levels of Interleukin-1β (IL-1β). IL-1β is a potent pro-inflammatory cytokine that is mainly activated by the serine protease caspase-1, but can be activated by caspase-8. Here, we aimed to understand the reasons behind the success of P. aeruginosa infections in HSCT subjects with the use of murine bone marrow transplantation (BMT) model. We identified that high levels of prostaglandin E2 (PGE2), a cyclooxygenase (COX) lipid metabolite with hormone-like characteristics and found at elevated levels in HSCT patients, induces exacerbated levels of IL-1β in HSCT subjects leading to severe lung injury post-P. aeruginosa infection. We identified that the PGE2-mediated increase in IL-1β is dependent on adenyl cyclase (AC) activation by EP2 and/or EP4 receptor stimulation which leads to activation of the transcription factor CREB. We hypothesized that reducing the levels of PGE2 in BMT mice can reduce IL-1β-mediated acute lung injury and improve outcome. In accordance with our hypothesis, we were able to decrease IL-1β levels, improve bacterial killing, and reduce lung injury by treating HSCT mice with indomethacin, a non-selective inhibitor of the two isoforms of COX (COX1 & COX2), post-P. aeruginosa infection. Additionally, we showed how PGE2 production impaired neutrophil extracellular trap (NETs), an important antimicrobial pathway, release post-HSCT in human and mouse neutrophils which could implicate immunosuppression to multiple microbes including bacterial pathogens. Our findings suggest new therapeutic strategies aimed at blocking PGE2 production or signaling may have positive impacts against bacterial infections in HSCT subjects. The appendix of this dissertation contains an additional chapter looking at influenza-induced immunosuppression of lung innate immunity and describes a novel role for toll like receptor 9 signaling in regulating secondary bacterial infection post-influenza.PHDImmunologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/147671/1/martingj_1.pd

High Temperature Electrochemical Engineering and Clean Energy Systems

Global power demand is projected to more than double by 2050 and meeting this increased power demand will require maintaining or increasing power output from all existing energy sources while adding a large amount of new capacity. The power sources that have the greatest opportunity to fulfill this demand gap over this time period are clean energy sources including solar and nuclear power. One of the areas of expertise that SRNL has been applying to help with a variety of clean energy technologies is in high temperature electrochemistry. Savannah River National Laboratory (SRNL) in collaboration with industrial and university partners has used high temperature electrochemical engineering to make improvements in solar power, nuclear fuel reprocessing, and fusion energy technologies. This article describes how high temperature electrochemistry has been applied at SRNL to mitigate corrosion in high temperature CSP systems, develop novel methods of nuclear fuel processing, and recover tritium in fusion energy technologies

Alternativas de formación educativa en San Basilio de Palenque para los practicantes de la medicina tradicional

El presente proyecto busca darle reconocimiento a la población de palenque en sus prácticas de salud ancestrales, y al mismo tiempo trata de dar una solución a esta situación sanitaria y legal que aqueja a esta población, con el fin de proporcionar los recursos gubernamentales necesarios para el mejoramiento del ámbito de la medicina de este territorio.Nos proponemos de manera práctica e inmediata brindarles más participación en el ámbito de la medicina científica a los “curanderos” como son denominados en palenque de tal forma que articulando estos dos tipos de medicina, puedan resultar muchos beneficios tanto a la sociedad palenquera como a las demás civilizaciones mediante la medicina moderna o científica

The Creation of a Critical Care Admission Pressure Injury Prevention Cart to Reduce Hospital-Acquired Pressure Injuries

The goal of this process improvement initiative is to reduce hospital-acquired pressure injuries related to Covid-19 with Critical Care patients. Critically ill and ventilated patients require prone position therapy and prolonged ventilator times place the patient at risk for hospital acquired conditions and pressure injuries. The Critical Care team created a Critical Care Admission Pressure Injury Prevention Cart that contains preventative dressings for all pressure areas at risk. The Critical Care Admission Pressure Injury Prevention Cart has significantly reduced the pressure injury rate. With the emergence of the pandemic and additional surges, pressure injuries continued to be on the rise due to prone position therapy. The Critical Care team worked with the system and developed prone position protocols, which included preventative dressings for all areas at risk. Prior to the implementation of the admission cart, Critical Care ended fiscal year 2022, quarter one, with fifty-three hospital acquired pressure injuries. Last December and early January 2022 there was another surge of Covid-19. The Critical Care team implemented the admission cart in January 2022. From January 2022 through September 2022, there has been an 98% reduction. The cart has been successful for Critical Care, and Baptist Hospital implemented the cart in all high acuity areas. This cart was a multidisciplinary practice, which consists of nursing, the wound and skin team, respiratory care, and leadership working together towards the goal of patient safety and pressure injury prevention

Análisis de seguridad y productividad del suministro de energía eléctrica en el sistema eléctrico de Nicaragua en el periodo comprendido desde el año 2010 hasta el 2018

El propósito de este estudio fue el de estudiar la seguridad y productividad del suministro de energía eléctrica en el sistema eléctrico de Nicaragua en el periodo desde el año 2010 hasta el 2018 utilizando el Indicador Stirling, indicador margen de reserva, indicador pérdida del mayor generador, el indicador de concentración de mercado y herramienta metodológica de análisis envolvente de datos (DEA) y los índices de Malmquist. Se estudió el comportamiento del sector energético de Nicaragua, en el periodo 2005 – 2013. Como resultado del indicador Stirling se obtuvo, que Nicaragua en estos momentos cuenta con seguridad en el sistema eléctrico, Del indicador margen de reserva se obtuvo como resultado, que el nivel de seguridad desde el punto de evaluación de este indicador el sistema cuenta con la suficiente seguridad como para no incurrir en afectaciones a los consumidores finales, Como resultado del indicador pérdida del mayor generador (LU), concluye en que se posee un sistema seguro. Por otra parte, El índice de concentración de mercado mostro que Nicaragua no posee un mercado energético competitivo. En la evaluación de productividad del uso de recursos energéticos se encontró que solo el uso de biomasa presenta un ritmo promedio anual de crecimiento de productividad

A revised Plio-Pleistocene age model and paleoceanography of the northeastern Caribbean Sea: IODP Site U1396 off Montserrat, Lesser Antilles

Site U1396 was piston cored as a part of Integrated Ocean Drilling Project Expedition 340 to establish a long record for Lesser Antilles volcanism. A ~150 m sediment succession was recovered from three holes on a bathymetric high ~33 km southwest of Montserrat. A series of shipboard and newly-generated chronostratigraphic tools (biostratigraphy, magnetostratigraphy, astrochronology, and stable isotope chemostratigraphy) were employed to generate an integrated age model. Two possible chronostratigraphic interpretations for the Brunhes chron are presented, with hypotheses to explain the discrepancies seen between this study and Wall-Palmer et al. (2014). The recent Wade et al. (2011) planktic foraminiferal biostratigraphic calibration is tested, revealing good agreement between primary datums observed at Site U1396 and calibrated ages, but significant mismatches for some secondary datums. Sedimentation rates are calculated, both including and excluding the contribution of discrete volcanic sediment layers within the succession. Rates are found to be ‘pulsed’ or highly variable within the Pliocene interval, declining through the 1.5-2.4 Ma interval, and then lower through the Pleistocene. Different explanations for the trends in the sedimentation rates are discussed, including orbitally-forced biogenic production spikes, elevated contributions of cryptotephra (dispersed ash), and changes in bottom water sources and flow rates with increased winnowing in the area of Site U1396 into the Pleistocene

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results