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Open Access Publications from the University of California

Scholarly Works (16 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2006)
This dissertation presents three studies using the event- related potential methodology (ERPs) that offer augmentative evidence for investigations of lexical properties during on-line auditory sentence comprehension. Because ERPs are sensitive to specific linguistic properties and have relatively fine-grained temporal resolution, the methodology can be brought to bear on significant issues in psycholinguistic inquiry that have yielded conflicting or inconclusive results. In particular, ERPs can differentiate between alternatives indistinguishable using behavioral methods. Experiment 1 examines whether the property of antecedent concreteness in available at the pronoun during co-reference resolution. Results suggest that antecedent concreteness is available relatively immediately at the pronoun in auditory sentences, supporting hypotheses that antecedents are reactivated at coreferent pronouns at a deep, conceptual level. Experiment 2 investigates the operation of aspectual coercion, in the case where an event that is typically interpreted as a point action event (e.g., "The light flashed at dawn") is "coerced" into a durative, iterative interpretation by an aspectually marked modifier (e.g., "The light flashed until dawn"). Consistent with linguistically motivated hypotheses, results indicate that aspectual coercion indeed may be a (primarily) semantic operation, manifesting as a lasting negative shift in the ERP in coercion conditions starting immediately when, or shortly after, coercion is licensed. Furthermore, a different effect is found when aspect is "coerced" in process verbs with a continuous but bounded sense (e.g., "The light glowed until dawn"). Experiment 3 examines the effects of phrase structure violations on the ERP. In this study, participants listened to grammatical and ungrammatical English and Jabberwocky sentences (comprised of semantically null nouns but English verbs and closed class words) to determine whether lexico-semantic influences of verbs properties (e.g., verb subcategorization rules) would be preserved even in language that contains meaningless (semantically null) arguments. Results indicate that phrase structure violations elicit a P600 effect in both English and Jabberwocky sentences, suggesting increased processing costs in the violation conditions. No LAN to violations was evident in either language for either violation type, contrary to what has been found with identical stimuli presented visually
    Cover page: Examination of lexical properties during auditory sentence processing using event-related potentials
    • Thesis
    • Peer Reviewed
    UC San Diego Electronic Theses and Dissertations (2023)

    Many viruses seek to manipulate the cellular environment during infection by seizing control over host post translational modifications (PTMs) by using viral E3-ubiquitin ligases, phosphatases, and kinases. Some viruses, including the genus of Alphaviruses, encode for a macrodomain, an enzymatic protein domain capable of reversing the PTM of ADP-ribosylation (ADPr). ADPr is found in a diverse range of host processes ranging from DNA damage and repair to protein quality control. When their macrodomains are disrupted, viruses lose infectious capacity, drawing attention to the importance of this modification. Identifying which host proteins are involved with this interaction could be key to understanding how these viruses are functioning and how they are manipulating the cell. The host factors at play are known as PARPs, which stands for poly-ADP-ribose-polymerases. Here, I have explored a number of these host PARPs and found novel ways in which they interact with alphaviruses to restrict viral replication. A number of PARPs are implicated in the interaction, most specifically those that either bear a macrodomain themselves, the macroPARPs of PARP9,14,and 15, or the Zinc Finger PARPS, PARP7,12, and 13. Further exploration of these PARPs, how they interact with both viral proteins and each other, is critical to fully understanding the role that ADP-ribosylation plays in restricting Alphavirus infection, as well as how alphaviruses are subverting that control.

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

      Two commercially-available solid-state sensors, both capable of measuring nitric oxide and oxygen content in the exhaust of diesel automotive systems, were utilized in the present study to determine their potential as an inexpensive alternative to traditional continuous emission monitoring systems for distributed generation (DG) deployments. In order to assess their performance and real-time measurement capabilities, an extensive data acquisition network was developed to compare signals against an established reference instrument (Horiba PG-350) over an extended period of six to eight months. An existing experimental testbed, a 60 kW Capstone Gas Turbine engine, was utilized as the representative DG system in this study, and an exhaust test section was designed and fabricated. Three sensors of the two commercial brands were selected to measure the deviation among individual signals. After the measurement period was conducted, it was found within a 99% confidence interval or greater, the NTK sensor performed better in three of five measured sensor characteristics, specifically with respect to LDL, Accuracy, and Lag-Time and Rise-Time. An emissions map was then generated using a statistically-designed study in order to find the operating parameters of the engine that produce the lowest nitric oxide and carbon monoxide emissions. Using these results, a control algorithm was developed and demonstrated, capable of incorporating the NTK sensor signals, to allow the engine to adjust its performance to reduce nitric oxide emissions in real-time and at all operating conditions.

        Cover page: Development of Closed Loop Emissions Control for Use in Dispatchable, Distributed Generation Systems using a Low Cost, State-of-the-Art, Solid-State Nitric Oxide Sensor
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2023)
        Protein post-translational modifications (PTMs) are an important battleground in the evolutionary arms races that are waged between the host innate immune system and viruses. One such PTM, ADP-ribosylation, has recently emerged as an important mediator of host antiviral immunity. Important for the host-virus conflict over this PTM is the addition of ADP-ribose by PARP proteins and removal of ADP-ribose by macrodomain-containing proteins. Interestingly, several host proteins, known as macroPARPs, contain macrodomains as well as a PARP domain, and these proteins are both important for the host antiviral immune response and evolving under very strong positive (diversifying) evolutionary selection. In addition, several viruses, including alphaviruses and coronaviruses, encode one or more macrodomains. Despite the presence of the conserved macrodomain fold, the enzymatic activity of many of these proteins has not been characterized. Here, we perform evolutionary and functional analyses to characterize the activity of macroPARP and viral macrodomains. We trace the evolutionary history of macroPARPs in metazoans and show that PARP9 and PARP14 contain a single active macrodomain, whereas PARP15 contains none. Interestingly, we also reveal several independent losses of macrodomain enzymatic activity within mammalian PARP14, including in the bat, ungulate, and carnivore lineages. Similar to macroPARPs, coronaviruses contain up to three macrodomains, with only the first displaying catalytic activity. Intriguingly, we also reveal the recurrent loss of macrodomain activity within the alphavirus group of viruses, including enzymatic loss in insect-specific alphaviruses as well as independent enzymatic losses in two human-infecting viruses. Together, our evolutionary and functional data reveal an unexpected turnover in macrodomain activity in both host antiviral proteins and viral proteins.
          Cover page: Recurrent Loss of Macrodomain Activity in Host Immunity and Viral Proteins
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2022)

          Objective

          To assess longitudinal primary care organization participation patterns in large-scale reform programs and identify organizational characteristics associated with multiprogram participation.

          Data sources

          Secondary data analysis of national program participation data over an eight-year period (2009-2016).

          Study design

          We conducted a retrospective, observational study by creating a unique set of data linkages (including Medicare and Medicaid Meaningful Use and Medicare Shared Savings Program Accountable Care Organization (MSSP ACO) participation from CMS, Patient-Centered Medical Home (PCMH) participation from the National Committee for Quality Assurance, and organizational characteristics) to measure longitudinal participation and identify what types of organizations participate in one or more of these reform programs. We used multivariate models to identify organizational characteristics that differentiate those that participate in none, one, or two-to-three programs.

          Data extraction methods

          We used Medicare claims to identify organizations that delivered primary care services (n = 56 ,287) and then linked organizations to program participation data and characteristics.

          Principal findings

          No program achieved more than 50% participation across the 56,287 organizations in a given year, and participation levels flattened or decreased in later years. 36% of organizations did not participate in any program over the eight-year study period; 50% participated in one; 13% in two; and 1% in all three. 14.31% of organizations participated in five or more years of Meaningful Use while 3.84% of organizations participated in five years of the MSSP ACO Program and 0.64% participated in at least five years of PCMH. Larger organizations, those with younger providers, those with more primary care providers, and those with larger Medicare patient panels were more likely to participate in more programs.

          Conclusions and relevance

          Primary care transformation via use of voluntary programs, each with their own participation requirements and approach to incentives, has failed to broadly engage primary care organizations. Those that have chosen to participate in multiple programs are likely those already providing high-quality care.
            Cover page: Longitudinal participation in delivery and payment reform programs among US Primary Care Organizations
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2021)
            The NLRP1 inflammasome is a multiprotein complex that is a potent activator of inflammation. Mouse NLRP1B can be activated through proteolytic cleavage by the bacterial Lethal Toxin (LeTx) protease, resulting in degradation of the N-terminal domains of NLRP1B and liberation of the bioactive C-terminal domain, which includes the caspase activation and recruitment domain (CARD). However, natural pathogen-derived effectors that can activate human NLRP1 have remained unknown. Here, we use an evolutionary model to identify several proteases from diverse picornaviruses that cleave human NLRP1 within a rapidly evolving region of the protein, leading to host-specific and virus-specific activation of the NLRP1 inflammasome. Our work demonstrates that NLRP1 acts as a 'tripwire' to recognize the enzymatic function of a wide range of viral proteases and suggests that host mimicry of viral polyprotein cleavage sites can be an evolutionary strategy to activate a robust inflammatory immune response.
              Cover page: Diverse viral proteases activate the NLRP1 inflammasome
              • Article
              • Peer Reviewed
              UC Berkeley Previously Published Works (2018)

              Objectives

              To evaluate whether greater experience and success with performance incentives among physician practices are related to increased participation in Medicare's voluntary value-based payment reforms.

              Data sources/study setting

              Publicly available data from Medicare's Physician Compare (n = 1,278; January 2012 to November 2013) and nationally representative physician practice data from the National Survey of Physician Organizations 3 (NSPO3; n = 907,538; 2013).

              Study design

              We used regression analysis to examine practice-level relationships between prior exposure to performance incentives and participation in key Medicare value-based payment reforms: accountable care organization (ACO) programs, the Physician Quality Reporting System ("Physician Compare"), and the Meaningful Use of Health Information Technology program ("Meaningful Use"). Prior experience and success with financial incentives were measured as (1) the percentage of practices' revenue from financial incentives for quality or efficiency; and (2) practices' exposure to public reporting of quality measures.

              Data collection/extraction methods

              We linked physician participation data from Medicare's Physician Compare to the NSPO3 survey.

              Principal findings

              There was wide variation in practices' exposure to performance incentives, with 64 percent exposed to financial incentives, 45 percent exposed to public reporting, and 2.2 percent of practice revenue coming from financial incentives. For each percentage-point increase in financial incentives, there was a 0.9 percentage-point increase in the probability of participating in ACOs (standard error [SE], 0.1, p < .001) and a 0.8 percentage-point increase in the probability of participating in Meaningful Use (SE, 0.1, p < .001), controlling for practice characteristics. Financial incentives were not associated with participation in Physician Compare. Among ACO participants, a 1 percentage-point increase in incentives was associated with a 0.7 percentage-point increase in the probability of being "very well" prepared to utilize cost and quality data (SE, 0.1, p < .001).

              Conclusions

              Physicians organizations' prior experience and success with performance incentives were related to participation in Medicare ACO arrangements and participation in the meaningful use criteria but not to participation in Physician Compare. We conclude that Medicare must complement financial incentives with additional efforts to address the needs of practices with less experience with such incentives to promote value-based payment on a broader scale.
                Cover page: Financial Incentives and Physician Practice Participation in Medicare's Value‐Based Reforms
                • Article
                • Peer Reviewed
                UC Berkeley Previously Published Works (2015)

                Background

                The accountable care organization (ACO) is a new organizational form to manage patients across the continuum of care. There are numerous questions about how ACOs should be optimally structured, including compensation arrangements with primary care physicians.

                Methods

                Using data from a national survey of physician practices, we compared primary care physicians' compensation between practices in ACOs and practices that varied in their financial risk for primary care costs using 3 groups: practices not participating in a Medicare ACO and with no substantial risk for primary care costs; practices not participating in an ACO but with substantial risk for primary care costs; and practices participating in an ACO regardless of their risk for primary care costs. We measured physicians' compensation as the percentage of compensation based on salary, productivity, clinical quality or patient experience, and other factors. Regression models estimated physician compensation as a function of ACO participation and risk for primary care costs while controlling for other practice characteristics.

                Results

                Physicians in ACO and non-ACO practices with no substantial risk for costs on average received nearly one-half of their compensation from salary, slightly less from productivity, and about 5% from quality and other factors. Physicians not in ACOs but with substantial risk for primary care costs received two-thirds of their compensation from salary, nearly one-third from productivity, and slightly more than 1% from quality and other factors. Participation in ACOs was associated with significantly higher physician compensation for quality; however, participation was not significantly associated with compensation from salary, whereas financial risk was associated with much greater compensation from salary.

                Conclusion

                Although practices in ACOs provide higher compensation for quality, compared with practices at large, they provide a similar mix of compensation based on productivity and salary. Incentives for ACOs may not be sufficiently strong to encourage practices to change physician compensation policies for better patient experience, improved population health, and lower per capita costs.
                  Cover page: Salary and Quality Compensation for Physician Practices Participating in Accountable Care Organizations
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2014)

                  Objective

                  To provide the first nationally based information on physician practice involvement in ACOs.

                  Data sources/study setting

                  Primary data from the third National Survey of Physician Organizations (January 2012-May 2013).

                  Study design

                  We conducted a 40-minute phone survey in a sample of physician practices. A nationally representative sample of practices was surveyed in order to provide estimates of organizational characteristics, care management processes, ACO participation, and related variables for four major chronic illnesses.

                  Data collection/extraction methods

                  We evaluated the associations between ACO participation, organizational characteristics, and a 25-point index of patient-centered medical home processes.

                  Principal findings

                  We found that 23.7 percent of physician practices (n = 280) reported joining an ACO; 15.7 percent (n = 186) were planning to become involved within the next 12 months and 60.6 percent (n = 717) reported no involvement and no plans to become involved. Larger practices, those receiving patients from an IPA and/or PHO, those that were physician-owned versus hospital/health system-owned, those located in New England, and those with greater patient-centered medical home (PCMH) care management processes were more likely to have joined an ACO.

                  Conclusions

                  Physician practices that are currently participating in ACOs appear to be relatively large, or to be members of an IPA or PHO, are less likely to be hospital-owned and are more likely to use more care management processes than nonparticipating practices.
                    Cover page: Physician Practice Participation in Accountable Care Organizations: The Emergence of the Unicorn
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2015)
                    OBJECTIVE. The purpose of this study is to evaluate the per-patient diagnostic performance of an abbreviated gadoxetic acid-enhanced MRI protocol for hepatocellular carcinoma (HCC) surveillance. MATERIALS AND METHODS. A retrospective review identified 298 consecutive patients at risk for HCC enrolled in a gadoxetic acid-enhanced MRI-based HCC surveillance program. For each patient, the first gadoxetic acid-enhanced MRI was analyzed. To simulate an abbreviated protocol, two readers independently read two image sets per patient: set 1 consisted of T1-weighted 20-minute hepatobiliary phase and T2-weighted single-shot fast spin-echo (SSFSE) images; set 2 included diffusion-weighted imaging (DWI) and images from set 1. Image sets were scored as positive or negative according to the presence of at least one nodule 10 mm or larger that met the predetermined criteria. Agreement was assessed using Cohen kappa statistics. A composite reference standard was used to determine the diagnostic performance of each image set for each reader. RESULTS. Interreader agreement was substantial for both image sets (κ = 0.72 for both) and intrareader agreement was excellent (κ = 0.97-0.99). Reader performance for image set 1 was sensitivity of 85.7% for reader A and 79.6% for reader B, specificity of 91.2% for reader A and 95.2% for reader B, and negative predictive value of 97.0% for reader A and 96.0% for reader B. Reader performance for image set 2 was nearly identical, with only one of 298 examinations scored differently on image set 2 compared with set 1. CONCLUSION. An abbreviated MRI protocol consisting of T2-weighted SSFSE and gadoxetic acid-enhanced hepatobiliary phase has high negative predictive value and may be an acceptable method for HCC surveillance. The inclusion of a DWI sequence did not significantly alter the diagnostic performance of the abbreviated protocol.
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