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Open Access Publications from the University of California

Scholarly Works (11 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2020)

Additive manufacturing (AM) has matured significantly over the past decade and become a highly attractive tool for reducing manufacturing complexity and removing traditional design constraints. This is particularly desirable for rocket combustion devices which often feature hundreds of individual parts with precise tolerances. The degree to which AM can be used to improve combustion device performance, however, has been less rigorously explored. In this work, hydraulic performance impacts associated with and enabled by AM are assessed for a liquid bi-propellant swirl coaxial injector. Specifically, a single-element liquid oxygen/kerosene injector based on a canonical design was manufactured from inconel using Direct Metal Laser Sintering at two different coaxial recess depths. Cold-flow testing for the as-manufactured baseline injector found a reduction in the designed discharge coefficients, which is primarily attributed to increased surface roughness inherent in the AM process. Quantifying this difference provides data for tuning surface roughness effects in Computational Fluid Dynamics (CFD) models, which may be used to inform the design stage. In addition, CFD simulations were leveraged to identify hydraulic losses in the baseline design and redesign a more hydraulically efficient injector geometry utilizing reductions in dramatic flow constrictions. For the modified injector geometry, computational results predict a 19% and 8% increase in the fuel and oxidizer discharge coefficients, respectively, as well as an 18% increase in angular momentum relative to the baseline. These results in addition to recommendations made for minimizing frictional losses that resulted from the printing process demonstrate how AM and analysis-driven design may be utilized to develop a more hydraulically efficient liquid rocket engine injector, thus highlighting a pathway to higher thrust-to-weight ratio propulsion systems and increased launch vehicle payload capacity. This work was presented in part at the 2019 AIAA Propulsion and Energy Conference.

    Cover page: Minimizing hydraulic losses in additively-manufactured swirl coaxial rocket injectors via analysis-driven design methods
    • Article
    • Peer Reviewed
    UC Santa Cruz Previously Published Works (2020)
    This article identifies diverse rationales to call for anticipatory governance of solar geoengineering, in light of a climate crisis. In focusing on governance rationales, we step back from proliferating debates in the literature on how, when, whom, and where to govern, to address the important prior question of why govern solar geoengineering in the first place: to restrict or enable its further consideration? We link these opposing rationales to contrasting underlying visions of a future impacted by climate change. These visions see the future as either more or less threatening, depending upon whether it includes the possible future use of solar geoengineering. Our analysis links these contrasting visions and governance rationales to existing governance proposals in the literature. In doing so, we illustrate why some proposals differ so significantly, while also showing that similar-sounding proposals may emanate from quite distinct rationales and thus advance different ends, depending upon how they are designed in practice.
      Cover page: Anticipatory governance of solar geoengineering: conflicting visions of the future and their links to governance proposals.
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2021)
      Background Currently, there is limited research on the prognostic value of NT-proBNP (N-terminal pro-B-type natriuretic peptide) as a biomarker in COVID-19. We proposed the a priori hypothesis that an elevated NT-proBNP concentration at admission is associated with increased in-hospital mortality. Methods and Results In this prospective, observational cohort study of the American Heart Association's COVID-19 Cardiovascular Disease Registry, 4675 patients hospitalized with COVID-19 were divided into normal and elevated NT-proBNP cohorts by standard age-adjusted heart failure thresholds, as well as separated by quintiles. Patients with elevated NT-proBNP (n=1344; 28.7%) were older, with more cardiovascular risk factors, and had a significantly higher rate of in-hospital mortality (37% versus 16%; P<0.001) and shorter median time to death (7 versus 9 days; P<0.001) than those with normal values. Analysis by quintile of NT-proBNP revealed a steep graded relationship with mortality (7.1%-40.2%; P<0.001). NT-proBNP was also associated with major adverse cardiac events, intensive care unit admission, intubation, shock, and cardiac arrest (P<0.001 for each). In subgroup analyses, NT-proBNP, but not prior heart failure, was associated with increased risk of in-hospital mortality. Adjusting for cardiovascular risk factors with presenting vital signs, an elevated NT-proBNP was associated with 2-fold higher adjusted odds of death (adjusted odds ratio [OR], 2.23; 95% CI, 1.80-2.76), and the log-transformed NT-proBNP with other biomarkers projected a 21% increased risk of death for each 2-fold increase (adjusted OR, 1.21; 95% CI, 1.08-1.34). Conclusions Elevated NT-proBNP levels on admission for COVID-19 are associated with an increased risk of in-hospital mortality and other complications in patients with and without heart failure.
        Cover page: N‐Terminal Pro‐B‐Type Natriuretic Peptide as a Biomarker for the Severity and Outcomes With COVID‐19 in a Nationwide Hospitalized Cohort
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2019)
        Background Cardiovascular intensive care units ( CICUs ) have evolved from coronary care wards into distinct units for critically ill patients with primary cardiac diseases, often suffering from illnesses that cross multiple disciplines. Mounting evidence has demonstrated improved survival with the incorporation of dedicated CICU providers with expertise in critical care medicine ( CCM ). This is the first study to systematically survey dual certified physicians in order to assess the relevance of CCM training to contemporary CICU care. Methods and Results Utilizing American Board of Internal Medicine data through 2014, 397 eligible physicians had obtained initial certification in both cardiovascular disease and CCM . A survey to delineate the role of critical care training in the CICU was provided to these physicians. Among those surveyed, 120 physicians (30%) responded. Dual certified physicians reported frequent use of their CCM skills in the CICU , highlighting ventilator management, multiorgan dysfunction management, end-of-life care, and airway management. The majority (85%) cited these skills as the reason CCM training should be prioritized by future CICU providers. Few (17%) agreed that general cardiology fellowship alone is currently sufficient to care for patients in the modern CICU . Furthermore, there was a consensus that there is an unmet need for cardiologists trained in CCM (70%) and that CICU s should adopt a level system similar to trauma centers (61%). Conclusions Citing specific skills acquired during CCM training, dual certified critical care cardiologists reported that their additional critical care experience was necessary in their practice to effectively deliver care in the modern CICU .
          Cover page: Role of Critical Care Medicine Training in the Cardiovascular Intensive Care Unit: Survey Responses From Dual Certified Critical Care Cardiologists.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2023)
          BACKGROUND: Little is known about the prevalence and post-surgical outcomes associated with cardiac intensive care unit (CICU) therapeutics among CICU patients referred for cardiac surgery. OBJECTIVES: The purpose of this study was to investigate the clinical characteristics and outcomes of CICU patients referred for cardiac surgery from the intensive care unit. METHODS: We analyzed characteristics and outcomes of CICU admissions referred from the CICU for cardiac surgery during 2017 to 2020 across 29 centers. The primary outcome was in-hospital mortality. RESULTS: Among 10,321 CICU admissions, 887 (8.6%) underwent cardiac surgery, including 406 (46%) coronary artery bypass graftings, 201 (23%) transplants or ventricular assist devices, 171 (19%) valve surgeries, and 109 (12%) other procedures. Common indications for CICU admission included shock (33.5%) and respiratory insufficiency (24.9%). Preoperative CICU therapies included vasoactive therapy in 52.2%, mechanical circulatory support in 35.9%, renal replacement in 8.2%, mechanical ventilation in 35.7%, and 17.5% with high-flow nasal cannula or noninvasive positive pressure ventilation. In-hospital mortality was 11.7% among all CICU admissions and 9.1% among patients treated with cardiac surgery. After multivariable adjustment, pre-op mechanical circulatory support and renal replacement therapy were associated with mortality, while respiratory support and vasoactive therapy were not. CONCLUSIONS: Nearly 1 in 12 contemporary CICU patients receive cardiac surgery. Despite high preoperative disease severity, CICU admissions undergoing cardiac surgery had a comparable mortality rate to CICU patients overall; highlighting the ability of clinicians to select higher acuity patients with a reasonable perioperative risk.
            Cover page: Presentation and Outcomes of Patients With Preoperative Critical Illness Undergoing Cardiac Surgery.
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2021)
            CD8+ T cells are key mediators of antiviral and antitumor immunity. The isolation and study of Ag-specific CD8+ T cells, as well as mapping of their MHC restriction, has practical importance to the study of disease and the development of therapeutics. Unfortunately, most experimental approaches are cumbersome, owing to the highly variable and donor-specific nature of MHC-bound peptide/TCR interactions. Here we present a novel system for rapid identification and characterization of Ag-specific CD8+ T cells, particularly well suited for samples with limited primary cells. Cells are stimulated ex vivo with Ag of interest, followed by live cell sorting based on surface-trapped TNF-α. We take advantage of major advances in single-cell sequencing to generate full-length sequence data from the paired TCR α- and β-chains from these Ag-specific cells. The paired TCR chains are cloned into retroviral vectors and used to transduce donor CD8+ T cells. These TCR transductants provide a virtually unlimited experimental reagent, which can be used for further characterization, such as minimal epitope mapping or identification of MHC restriction, without depleting primary cells. We validated this system using CMV-specific CD8+ T cells from rhesus macaques, characterizing an immunodominant Mamu-A1*002:01-restricted epitope. We further demonstrated the utility of this system by mapping a novel HLA-A*68:02-restricted HIV Gag epitope from an HIV-infected donor. Collectively, these data validate a new strategy to rapidly identify novel Ags and characterize Ag-specific CD8+ T cells, with applications ranging from the study of infectious disease to immunotherapeutics and precision medicine.
              Cover page: Identification and Characterization of Antigen-Specific CD8+ T Cells Using Surface-Trapped TNF-α and Single-Cell Sequencing.
              • Article
              • Peer Reviewed
              UC Davis Previously Published Works (2023)
              Rhesus cytomegalovirus-based (RhCMV-based) vaccine vectors induce immune responses that protect ~60% of rhesus macaques (RMs) from SIVmac239 challenge. This efficacy depends on induction of effector memory-based (EM-biased) CD8+ T cells recognizing SIV peptides presented by major histocompatibility complex-E (MHC-E) instead of MHC-Ia. The phenotype, durability, and efficacy of RhCMV/SIV-elicited cellular immune responses were maintained when vector spread was severely reduced by deleting the antihost intrinsic immunity factor phosphoprotein 71 (pp71). Here, we examined the impact of an even more stringent attenuation strategy on vector-induced immune protection against SIV. Fusion of the FK506-binding protein (FKBP) degradation domain to Rh108, the orthologue of the essential human CMV (HCMV) late gene transcription factor UL79, generated RhCMV/SIV vectors that conditionally replicate only when the FK506 analog Shield-1 is present. Despite lacking in vivo dissemination and reduced innate and B cell responses to vaccination, Rh108-deficient 68-1 RhCMV/SIV vectors elicited high-frequency, durable, EM-biased, SIV-specific T cell responses in RhCMV-seropositive RMs at doses of ≥ 1 × 106 PFU. Strikingly, elicited CD8+ T cells exclusively targeted MHC-Ia-restricted epitopes and failed to protect against SIVmac239 challenge. Thus, Rh108-dependent late gene expression is required for both induction of MHC-E-restricted T cells and protection against SIV.
                Cover page: Late gene expression-deficient cytomegalovirus vectors elicit conventional T cells that do not protect against SIV
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2023)
                AIMS: Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS. METHODS AND RESULTS: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018-2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th-75th percentile, 1.6-2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66-86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate. CONCLUSION: In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion.
                  Cover page: Prognostic significance of haemodynamic parameters in patients with cardiogenic shock.
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2022)
                  AIMS: The aims of the Critical Care Cardiology Trials Network (CCCTN) are to develop a registry to investigate the epidemiology of cardiac critical illness and to establish a multicentre research network to conduct randomised clinical trials (RCTs) in patients with cardiac critical illness. METHODS AND RESULTS: The CCCTN was founded in 2017 with 16 centres and has grown to a research network of over 40 academic and clinical centres in the United States and Canada. Each centre enters data for consecutive cardiac intensive care unit (CICU) admissions for at least 2 months of each calendar year. More than 20 000 unique CICU admissions are now included in the CCCTN Registry. To date, scientific observations from the CCCTN Registry include description of variations in care, the epidemiology and outcomes of all CICU patients, as well as subsets of patients with specific disease states, such as shock, heart failure, renal dysfunction, and respiratory failure. The CCCTN has also characterised utilization patterns, including use of mechanical circulatory support in response to changes in the heart transplantation allocation system, and the use and impact of multidisciplinary shock teams. Over years of multicentre collaboration, the CCCTN has established a robust research network to facilitate multicentre registry-based randomised trials in patients with cardiac critical illness. CONCLUSION: The CCCTN is a large, prospective registry dedicated to describing processes-of-care and expanding clinical knowledge in cardiac critical illness. The CCCTN will serve as an investigational platform from which to conduct randomised controlled trials in this important patient population.
                    Cover page: Critical Care Cardiology Trials Network (CCCTN): a cohort profile.
                    • Article
                    • Peer Reviewed
                    UC San Francisco Previously Published Works (2023)
                    BACKGROUND: The appropriate use of pulmonary artery catheters (PACs) in critically ill cardiac patients remains debated. OBJECTIVES: The authors aimed to characterize the current use of PACs in cardiac intensive care units (CICUs) with attention to patient-level and institutional factors influencing their application and explore the association with in-hospital mortality. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of CICUs in North America. Between 2017 and 2021, participating centers contributed annual 2-month snapshots of consecutive CICU admissions. Admission diagnoses, clinical and demographic data, use of PACs, and in-hospital mortality were captured. RESULTS: Among 13,618 admissions at 34 sites, 3,827 were diagnosed with shock, with 2,583 of cardiogenic etiology. The use of mechanical circulatory support and heart failure were the patient-level factors most strongly associated with a greater likelihood of the use of a PAC (OR: 5.99 [95% CI: 5.15-6.98]; P < 0.001 and OR: 3.33 [95% CI: 2.91-3.81]; P < 0.001, respectively). The proportion of shock admissions with a PAC varied significantly by study center ranging from 8% to 73%. In analyses adjusted for factors associated with their placement, PAC use was associated with lower mortality in all shock patients admitted to a CICU (OR: 0.79 [95% CI: 0.66-0.96]; P = 0.017). CONCLUSIONS: There is wide variation in the use of PACs that is not fully explained by patient level-factors and appears driven in part by institutional tendency. PAC use was associated with higher survival in cardiac patients with shock presenting to CICUs. Randomized trials are needed to guide the appropriate use of PACs in cardiac critical care.
                      Cover page: Pulmonary Artery Catheter Use&nbsp;and&nbsp;Mortality in the Cardiac&nbsp;Intensive&nbsp;Care Unit.
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