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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2018)

Most breast cancer-related deaths are due to distant metastasis that occur years after successful tumor removal and treatment. Tumor metastasis is a multi-step process in which primary tumors lose cell polarity and undergo dissemination by Epithelial-Mesenchymal Transition (EMT). The disseminated tumor cells circulate throughout the body and often remain in a dormant state after reaching distant organs. Once the microenvironment becomes suitable, the cells undergo Mesenchymal-Epithelial Transition (MET) and exit dormancy, which results in macrometastases. Previous studies show that a transcription factor Twist1 plays a key role in inducing EMT and promoting tumor metastasis. However, the molecular mechanisms of metastasis are not well understood due to the lack of an in vivo mouse model that can monitor disseminated tumor cells. Therefore, we established a Twist1-inducible breast cancer mouse model that utilizes fluorescent markers to visualize and characterize disseminated tumor cells at various stages of metastasis.

    Cover page: Analysis of an Inducible-Twist1 Breast Cancer Mouse Model to Investigate Metastasis Dormancy
    • Article
    • Peer Reviewed
    InterActions: UCLA Journal of Education and Information Studies, Volume 2, Issue 1 (2006)

    According to Indigenous educational philosophy, in learning how to become a complete human being, an individual has to become aware of their own worth and role in contributing to the well being of their community. This philosophy resonates with critical pedagogy, an educational approach intended to transform the lives of individuals from oppressed populations. Yet it departs from critical pedagogy in its emphasis on service to community, rather than individual liberation. This article demonstrates how the Tribal Resource Institute in Business, Engineering, and Science (TRIBES), a summer program for Native students at the University of New Mexico, intersects with critical pedagogy and Indigenous education to restore Indigenous goals in education by encouraging its students to develop critical Indigenous consciousness and to make a commitment to their communities.

      Cover page: “I Came Here to Learn How to be a Leader”: An Intersection of Critical Pedagogy and Indigenous Education
      • Multimedia
      • Peer Reviewed
      UC Irvine Previously Published Works (2018)

      What is “Classic Theatre”? Why does the literary canon insist on Shakespeare, Chekhov, Sophocles, and Euripides while most students and nonacademics are discouraged from them? I'm writing this thesis to combat the idea that Classic plays have a selective audience. My thesis is a contemporary adaption of Euripides’s Classic Greek play Hippolytus, set in today’s United States. In my adaption I've focused on characters, setting, and three central themes: individual identity, family, and power. My play is 17 scenes long with an original cast of 7. The play will be performed as a table read on June 8th, 2018 at 8pm. The performance will be recorded, audio only, and added to the digital and physical archives.

       

      Cast (in order of appearance):

      Chorus (m/f) : Emma Dorn, Miguel Lopez, Shannon O’Connor

      Natalie “Nat” Johanne (f) : Eileen Sanchez

      Phoebe Pratt (f) : Desiree Nguyen

      Hayden Wilson (m) : Stewart Wilson

      Theodore “Theo” Pratt (m) : Matt Caballero

      Winter 2018-Spring 2018

      • 1 supplemental PDF
      • Article
      • Peer Reviewed
      UC Irvine Previously Published Works (2014)
      AIMS: While etiology behind the observed acceleration of ischemic heart disease in postmenopausal women is poorly understood, collective scientific data suggest cardioprotective effects of the endogenous female sex hormone, estrogen. We have previously shown that 17β-estradiol (E2) protects cardiomyocytes exposed to hypoxia-reoxygenation (H/R) by inhibiting p38α - p53 signaling in apoptosis and activating pro-survival p38β mitogen activated protein kinase (p38β MAPK), leading to suppression of reactive oxygen species (ROS) post H/R. However, little is known about the mechanism behind the antioxidant actions of E2-dependent p38β. The aim of this study is to determine whether the cytoprotection by estrogen involves regulation of manganese superoxide dismutase (MnSOD), a major mitochondrial ROS scavenging enzyme, via cardiac p38β. METHODS AND RESULTS: We identified mitochondrial p38β by immunocytochemistry and by immunoblotting in mitochondria isolated from neonatal cardiomyocytes of Sprague-Dawley rats. E2 facilitated the mitochondrial localization of the active form of the kinase, phosphorylated p38β (p-p38β). E2 also reduced the H/R-induced mitochondrial membrane potential decline, augmented the MnSOD activity and suppressed anion superoxide generation, while the dismutase protein expression remained unaltered. Co-immunoprecipitation studies showed physical association between MnSOD and p38β. p38β phosphorylated MnSOD in an E2-dependent manner in in-vitro kinase assays. CONCLUSION: This work demonstrates for the first time a mitochondrial pool of active p38β and E2-mediated phosphorylation of MnSOD by the kinase. The results shed light on the mechanism behind the cytoprotective actions of E2 in cardiomyocytes under oxidative stress.
        Cover page: Mitochondrial p38β and manganese superoxide dismutase interaction mediated by estrogen in cardiomyocytes.
        • Article
        • Peer Reviewed
        UC Irvine Previously Published Works (2014)
          Cover page: Mitochondrial p38β and Manganese Superoxide Dismutase Interaction Mediated by Estrogen in CardiomyocytesCreative Commons 'BY' version 4.0 license
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2024)
          BACKGROUND: Patients hospitalized with COVID-19 can clinically deteriorate after a period of initial stability, making optimal timing of discharge a clinical and operational challenge. OBJECTIVE: To determine risks for post-discharge readmission and death among patients hospitalized with COVID-19. DESIGN: Multicenter retrospective observational cohort study, 2020-2021, with 30-day follow-up. PARTICIPANTS: Adults admitted for care of COVID-19 respiratory disease between March 2, 2020, and February 11, 2021, to one of 180 US hospitals affiliated with the HCA Healthcare system. MAIN MEASURES: Readmission to or death at an HCA hospital within 30 days of discharge was assessed. The area under the receiver operating characteristic curve (AUC) was calculated using an internal validation set (33% of the HCA cohort), and external validation was performed using similar data from six academic centers associated with a hospital medicine research network (HOMERuN). KEY RESULTS: The final HCA cohort included 62,195 patients (mean age 61.9 years, 51.9% male), of whom 4704 (7.6%) were readmitted or died within 30 days of discharge. Independent risk factors for death or readmission included fever within 72 h of discharge; tachypnea, tachycardia, or lack of improvement in oxygen requirement in the last 24 h; lymphopenia or thrombocytopenia at the time of discharge; being ≤ 7 days since first positive test for SARS-CoV-2; HOSPITAL readmission risk score ≥ 5; and several comorbidities. Inpatient treatment with remdesivir or anticoagulation were associated with lower odds. The models AUC for the internal validation set was 0.73 (95% CI 0.71-0.74) and 0.66 (95% CI 0.64 to 0.67) for the external validation set. CONCLUSIONS: This large retrospective study identified several factors associated with post-discharge readmission or death in models which performed with good discrimination. Patients 7 or fewer days since test positivity and who demonstrate potentially reversible risk factors may benefit from delaying discharge until those risk factors resolve.
            Cover page: Analysis of Clinical Criteria for Discharge Among Patients Hospitalized for COVID-19: Development and Validation of a Risk Prediction Model.
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2020)

            Importance

            Although intensive care unit (ICU) adaptations to the coronavirus disease of 2019 (COVID-19) pandemic have received substantial attention , most patients hospitalized with COVID-19 have been in general medical units.

            Objective

            To characterize inpatient adaptations to care for non-ICU COVID-19 patients.

            Design

            Cross-sectional survey.

            Setting

            A network of 72 hospital medicine groups at US academic centers.

            Main outcome measures

            COVID-19 testing, approaches to personal protective equipment (PPE), and features of respiratory isolation units (RIUs).

            Results

            Fifty-one of 72 sites responded (71%) between April 3 and April 5, 2020. At the time of our survey, only 15 (30%) reported COVID-19 test results being available in less than 6 hours. Half of sites with PPE data available reported PPE stockpiles of 2 weeks or less. Nearly all sites (90%) reported implementation of RIUs. RIUs primarily utilized attending physicians, with few incorporating residents and none incorporating students. Isolation and room-entry policies focused on grouping care activities and utilizing technology (such as video visits) to communicate with and evaluate patients. The vast majority of sites reported decreases in frequency of in-room encounters across provider or team types. Forty-six percent of respondents reported initially unrecognized non-COVID-19 diagnoses in patients admitted for COVID-19 evaluation; a similar number reported delayed identification of COVID-19 in patients admitted for other reasons.

            Conclusion

            The COVID-19 pandemic has required medical wards to rapidly adapt with expanding use of RIUs and use of technology emerging as critical approaches. Reports of unrecognized or delayed diagnoses highlight how such adaptations may produce potential adverse effects on care.
              Cover page: Hospital Ward Adaptation During the COVID‐19 Pandemic: A National Survey of Academic Medical Centers
              • Article
              • Peer Reviewed
              UC San Francisco Previously Published Works (2023)
              BACKGROUND: Few hospitals have built surveillance for diagnostic errors into usual care or used comparative quantitative and qualitative data to understand their diagnostic processes and implement interventions designed to reduce these errors. OBJECTIVES: To build surveillance for diagnostic errors into usual care, benchmark diagnostic performance across sites, pilot test interventions, and evaluate the programs impact on diagnostic error rates. METHODS AND ANALYSIS: Achieving diagnostic excellence through prevention and teamwork (ADEPT) is a multicenter, real-world quality and safety program utilizing interrupted time-series techniques to evaluate outcomes. Study subjects will be a randomly sampled population of medical patients hospitalized at 16 US hospitals who died, were transferred to intensive care, or had a rapid response during the hospitalization. Surveillance for diagnostic errors will occur on 10 events per month per site using a previously established two-person adjudication process. Concurrent reviews of patients who had a qualifying event in the previous week will allow for surveys of clinicians to better understand contributors to diagnostic error, or conversely, examples of diagnostic excellence, which cannot be gleaned from medical record review alone. With guidance from national experts in quality and safety, sites will report and benchmark diagnostic error rates, share lessons regarding underlying causes, and design, implement, and pilot test interventions using both Safety I and Safety II approaches aimed at patients, providers, and health systems. Safety II approaches will focus on cases where diagnostic error did not occur, applying theories of how people and systems are able to succeed under varying conditions. The primary outcome will be the number of diagnostic errors per patient, using segmented multivariable regression to evaluate change in y-intercept and change in slope after initiation of the program. ETHICS AND DISSEMINATION: The study has been approved by the University of California, San Francisco Institutional Review Board (IRB), which is serving as the single IRB. Intervention toolkits and study findings will be disseminated through partners including Vizient, The Joint Commission, and Press-Ganey, and through national meetings, scientific journals, and publications aimed at the general public.
                Cover page: Achieving diagnostic excellence through prevention and teamwork (ADEPT) study protocol: A multicenter, prospective quality and safety program to improve diagnostic processes in medical inpatients.
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2020)

                Background

                Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is unknown.

                Methods

                The US HIPEC Collaborative (2000-2017) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. The analysis was stratified by noninvasive appendiceal neoplasm versus invasive appendiceal/colorectal adenocarcinoma. The POCs were grouped into infectious, cardiopulmonary, thromboembolic, and intestinal dysmotility. The primary outcomes were overall survival (OS) and recurrence-free survival (RFS).

                Results

                Of the 1304 patients, 33% had noninvasive appendiceal neoplasm (n = 426), and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the noninvasive appendiceal cohort, POCs were identified in 55% of the patients (n = 233). The 3-year OS and RFS did not differ between the patients who experienced a complication and those who did not (OS, 94% vs 94%, p = 0.26; RFS, 68% vs 60%, p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased 3-year OS (59% vs 74%; p < 0.001) and RFS (32% vs 42%; p < 0.001). Infectious POCs were the most common (35%; n = 196). In Multivariable analysis accounting for gender, peritoneal cancer index (PCI), and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared with no complication (hazard ratio [HR] 2.08; p < 0.01) or other types of complications (HR, 1.6; p < 0.01). Similarly, infectious POCs were independently associated with worse RFS (HR 1.61; p < 0.01).

                Conclusion

                Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease such as noninvasive appendiceal neoplasm, and this association is largely driven by infectious complications. The exact mechanism is unknown, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious postoperative complications.
                  Cover page: Implications of Postoperative Complications for Survival After Cytoreductive Surgery and HIPEC: A Multi-Institutional Analysis of the US HIPEC Collaborative
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2023)

                  Background

                  The COVID-19 pandemic required clinicians to care for a disease with evolving characteristics while also adhering to care changes (e.g., physical distancing practices) that might lead to diagnostic errors (DEs).

                  Objective

                  To determine the frequency of DEs and their causes among patients hospitalized under investigation (PUI) for COVID-19.

                  Design

                  Retrospective cohort.

                  Setting

                  Eight medical centers affiliated with the Hospital Medicine ReEngineering Network (HOMERuN).

                  Target population

                  Adults hospitalized under investigation (PUI) for COVID-19 infection between February and July 2020.

                  Measurements

                  We randomly selected up to 8 cases per site per month for review, with each case reviewed by two clinicians to determine whether a DE (defined as a missed or delayed diagnosis) occurred, and whether any diagnostic process faults took place. We used bivariable statistics to compare patients with and without DE and multivariable models to determine which process faults or patient factors were associated with DEs.

                  Results

                  Two hundred and fifty-seven patient charts underwent review, of which 36 (14%) had a diagnostic error. Patients with and without DE were statistically similar in terms of socioeconomic factors, comorbidities, risk factors for COVID-19, and COVID-19 test turnaround time and eventual positivity. Most common diagnostic process faults contributing to DE were problems with clinical assessment, testing choices, history taking, and physical examination (all p < 0.01). Diagnostic process faults associated with policies and procedures related to COVID-19 were not associated with DE risk. Fourteen patients (35.9% of patients with errors and 5.4% overall) suffered harm or death due to diagnostic error.

                  Limitations

                  Results are limited by available documentation and do not capture communication between providers and patients.

                  Conclusion

                  Among PUI patients, DEs were common and not associated with pandemic-related care changes, suggesting the importance of more general diagnostic process gaps in error propagation.
                    Cover page: Prevalence and Causes of Diagnostic Errors in Hospitalized Patients Under Investigation for COVID-19
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