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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Article
Recent Work (2007)

A multi-year, cooperative program for the identification, prioritization and correction of fish passage at road- stream crossings (more than 4,000 sites on a land base of 24 million acres) sites has been developed and is being imple¬mented over the last five years.

A comprehensive assessment of fish passage, at road-stream crossings, was completed for all 17 of the National Forests in the states of Oregon and Washington. The assessment took 3 years to plan and complete. More than 5,100 crossings, representing 82% of all crossings on fish bearing streams, were evaluated in the field. Initial determinations were made to identify which crossings would pass all species and life stages of fish found in the respective streams. Juvenile coho salmon were used as the target species for evaluation and a matrix integrating a variety of crossing characteristics including crossing type, crossing structure gradient, outlet drop height, a ratio of crossing structure width to bank full width, etc. was utilized to categorize sites into three categories (passable, not passable and need further investigation). Results indicate that 68% of all road-stream crossings (bridges included) impair, to some degree, upstream passage for at least one species/life stage of fish. Considering only culvert crossing structures, about 90% are impassable. It is estimated that more than 3,000 miles of habitat for fish is affected. This represents about 15% of the total miles of fish bearing streams on National Forest System lands of the Pacific Northwest Region. The assess¬ment has provided the foundation for a more systematic and strategic approach to improve fish passage as part of the Regional Aquatic Restoration Program.

A cooperative process to prioritize river basins and treatment sites is being used to guide selection of sites for remedia¬tion. Regional design standards have been established for replacement crossings and 2 design assistance teams have been created to improve the effectiveness and cost efficiency of new structures. More than 250 sites have been treated over the last 5 years. Increasingly, cooperative funding is being used to increase the number of sites being treated.

A basic protocol for monitoring post treatment effectiveness is currently being revised to provide more quantitative results for post project monitoring. Additional research on the biological response of aquatic organisms, including non game and juvenile fish, during a full range of flows, is needed.

    Cover page: A Strategic Approach for the Identification and Correction of Fish Passage on National Forest Lands for the Pacific Northwest
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2014)
    State Medicaid programs and other state health agencies need to monitor and evaluate changes in health insurance coverage, access to care, financing, and the quality of health care delivery. The availability of new financial resources through the Patient Protection and Affordable Care Act is accompanied by raised expectations for such accountability. While state agencies often contract with universities on an ad hoc basis for specific policy projects, fourteen states have established formal state-university partnerships so that their analytic and technical needs can be addressed more readily. After a brief overview of these partnerships, this article provides examples of their projects, which most often affect Medicaid policy, including work on program eligibility, provider payments, and optional benefits. State-university partnerships are working on policy-relevant projects that influence decision making. Like the variation in Medicaid programs across the country, no two partnerships are alike. They thrive in a mix of structures, using different means of contracting, and with varied degrees of data access. All partnerships are interested in building a national network to share innovative practices and projects, spawn comparative policy studies across states, and support the development of new state-university partnerships.
      Cover page: Supporting the Needs of State Health Policy Makers Through University Partnerships
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2015)

      Background

      Evidence to guide primary prevention in adults aged 75 years or older is limited.

      Objective

      To project the population impact and cost-effectiveness of statin therapy in adults aged 75 years or older.

      Design

      Forecasting study using the Cardiovascular Disease Policy Model, a Markov model.

      Data sources

      Trial, cohort, and nationally representative data sources.

      Target population

      U.S. adults aged 75 to 94 years.

      Time horizon

      10 years.

      Perspective

      Health care system.

      Intervention

      Statins for primary prevention based on low-density lipoprotein cholesterol threshold of 4.91 mmol/L (190 mg/dL), 4.14 mmol/L (160 mg/dL), or 3.36 mmol/L (130 mg/dL); presence of diabetes; or 10-year risk score of at least 7.5%.

      Outcome measures

      Myocardial infarction (MI), coronary heart disease (CHD) death, disability-adjusted life-years, and costs.

      Results of base-case analysis

      All adults aged 75 years or older in the National Health and Nutrition Examination Survey have a 10-year risk score greater than 7.5%. If statins had no effect on functional limitation or cognitive impairment, all primary prevention strategies would prevent MIs and CHD deaths and be cost-effective. Treatment of all adults aged 75 to 94 years would result in 8 million additional users and prevent 105 000 (4.3%) incident MIs and 68 000 (2.3%) CHD deaths at an incremental cost per disability-adjusted life-year of $25 200.

      Results of sensitivity analysis

      An increased relative risk for functional limitation or mild cognitive impairment of 1.10 to 1.29 could offset the cardiovascular benefits.

      Limitation

      Limited trial evidence targeting primary prevention in adults aged 75 years or older.

      Conclusion

      At effectiveness similar to that in trials, statins are projected to be cost-effective for primary prevention; however, even a small increase in geriatric-specific adverse effects could offset the cardiovascular benefit. Improved data on the potential benefits and harms of statins are needed to inform decision making.

      Primary funding source

      American Heart Association Western States Affiliate, National Institute on Aging, and the National Institute for Diabetes on Digestive and Kidney Diseases.
        Cover page: Cost-effectiveness and population impact of statins for primary prevention in adults aged 75 years or older in the United States.
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2017)

        Background

        Statins are effective in the primary prevention of atherosclerotic cardiovascular disease. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline expands recommended statin use, but its cost-effectiveness has not been compared with other guidelines.

        Methods

        We used the Cardiovascular Disease Policy Model to estimate the cost-effectiveness of the ACC/AHA guideline relative to current use, Adult Treatment Panel III guidelines, and universal statin use in all men 45 to 74 years of age and women 55 to 74 years of age over a 10-year horizon from 2016 to 2025. Sensitivity analyses varied costs, risks, and benefits. Main outcomes were incremental cost-effectiveness ratios and numbers needed to treat for 10 years per quality-adjusted life-year gained.

        Results

        Each approach produces substantial benefits and net cost savings relative to the status quo. Full adherence to the Adult Treatment Panel III guideline would result in 8.8 million more statin users than the status quo, at a number needed to treat for 10 years per quality-adjusted life-year gained of 35. The ACC/AHA guideline would potentially result in up to 12.3 million more statin users than the Adult Treatment Panel III guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 68. Moderate-intensity statin use in all men 45 to 74 years of age and women 55 to 74 years of age would result in 28.9 million more statin users than the ACC/AHA guideline, with a marginal number needed to treat for 10 years per quality-adjusted life-year gained of 108. In all cases, benefits would be greater in men than women. Results vary moderately with different risk thresholds for instituting statins and statin toxicity estimates but depend greatly on the disutility caused by daily medication use (pill burden).

        Conclusions

        At a population level, the ACC/AHA guideline for expanded statin use for primary prevention is projected to treat more people, to save more lives, and to cost less compared with Adult Treatment Panel III in both men and women. Whether individuals benefit from long-term statin use for primary prevention depends more on the disutility associated with pill burden than their degree of cardiovascular risk.
          Cover page: Evaluating the Impact and Cost-Effectiveness of Statin Use Guidelines for Primary Prevention of Coronary Heart Disease and Stroke.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2017)

          Introduction

          In Argentina, the national guidelines for lipid control emphasize the use of relatively inexpensive low- or moderate-potency statins by patients at high risk (>20 %) of a cardiovascular event. The objective of this study was to compare the impact and costs of the current national CVD prevention guidelines with regard to morbidity and mortality in Argentina with the impact and costs of three strategies that incorporate high-potency statins.

          Methods

          We used the CVD Policy Model-Argentina to model the proposed interventions. This model is a national-scale, state-transition (Markov) computer simulation model of the CVD incidence, prevalence, mortality, and costs in adults 35-84 years of age. We modeled three scenarios: scenario 1 lowers the risk threshold for treatment to >10 % according the Framingham Risk Score (FRS); scenario 2 intensifies statin potency under current treatment thresholds; and scenario 3 combines both scenarios by lowering the treatment threshold to ≥10 % FRS and intensifying statin potency.

          Results

          Scenario 1 would translate into 1400 fewer MIs and 500 fewer CHD deaths every year, a 3 % and 2 % reduction, respectively. Scenario 2 would lead to 2000 fewer MIs and 1000 fewer CHD deaths every year. Scenario 3 would result in the greatest reduction in MIs and CHD deaths, with 3400 fewer MIs and 1400 fewer CHD deaths every year, which translates to a 7 % and 6 % reduction, respectively. All scenarios were cost-effective if the cost of a high-potency statin pill was under US$0.25.

          Conclusion

          Incorporating those individuals with greater than 10 % cardiovascular risk and the use of high-potency statins into Argentina's national lipid guidelines could result in fewer CHD deaths and events at a reasonable cost.
            • Article
            • Peer Reviewed
            UC Santa Cruz Previously Published Works (2020)
            Structural variants (SVs) remain challenging to represent and study relative to point mutations despite their demonstrated importance. We show that variation graphs, as implemented in the vg toolkit, provide an effective means for leveraging SV catalogs for short-read SV genotyping experiments. We benchmark vg against state-of-the-art SV genotypers using three sequence-resolved SV catalogs generated by recent long-read sequencing studies. In addition, we use assemblies from 12 yeast strains to show that graphs constructed directly from aligned de novo assemblies improve genotyping compared to graphs built from intermediate SV catalogs in the VCF format.
              Cover page: Genotyping structural variants in pangenome graphs using the vg toolkit
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2022)

              Objective

              Chronic pancreatitis (CP) is a potentially fatal disease of the exocrine pancreas, with no specific or effective approved therapies. Due to difficulty in accessing pancreas tissues, little is known about local immune responses or pathogenesis in human CP. We sought to characterise pancreatic immune responses using tissues derived from patients with different aetiologies of CP and non-CP organ donors in order to identify key signalling molecules associated with human CP.

              Design

              We performed single-cell level cellular indexing of transcriptomes and epitopes by sequencing and T-cell receptor (TCR) sequencing of pancreatic immune cells isolated from organ donors, hereditary and idiopathic patients with CP who underwent total pancreatectomy. We validated gene expression data by performing flow cytometry and functional assays in a second patient with CP cohort.

              Results

              Deep single-cell sequencing revealed distinct immune characteristics and significantly enriched CCR6+ CD4+ T cells in hereditary compared with idiopathic CP. In hereditary CP, a reduction in T-cell clonality was observed due to the increased CD4+ T (Th) cells that replaced tissue-resident CD8+ T cells. Shared TCR clonotype analysis among T-cell lineages also unveiled unique interactions between CCR6+ Th and Th1 subsets, and TCR clustering analysis showed unique common antigen binding motifs in hereditary CP. In addition, we observed a significant upregulation of the CCR6 ligand (CCL20) expression among monocytes in hereditary CP as compared with those in idiopathic CP. The functional significance of CCR6 expression in CD4+ T cells was confirmed by flow cytometry and chemotaxis assay.

              Conclusion

              Single-cell sequencing with pancreatic immune cells in human CP highlights pancreas-specific immune crosstalk through the CCR6-CCL20 axis, a signalling pathway that might be leveraged as a potential future target in human hereditary CP.
                Cover page: Single-cell sequencing unveils distinct immune microenvironments with CCR6-CCL20 crosstalk in human chronic pancreatitis
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2016)

                Background

                Antiretroviral therapy scale-up in Sub-Saharan Africa has created a growing, aging HIV-positive population at risk for non-communicable diseases such as hypertension. However, the prevalence and risk factors for hypertension in this population remain incompletely understood.

                Methods

                We measured blood pressure and collected demographic data on over 65,000 adults attending multi-disease community health campaigns in 20 rural Ugandan communities (SEARCH Study: NCT01864603). Our objectives were to determine (i) whether HIV is an independent risk factor for hypertension, and (ii) awareness and control of hypertension in HIV-positive adults and the overall population.

                Results

                Hypertension prevalence was 14% overall, and 11% among HIV-positive individuals. 79% of patients were previously undiagnosed, 85% were not taking medication, and 50% of patients on medication had uncontrolled blood pressure. Multivariate predictors of hypertension included older age, male gender, higher BMI, lack of education, alcohol use, and residence in Eastern Uganda. HIV-negative status was independently associated with higher odds of hypertension (OR 1.2, 95% CI: 1.1-1.4). Viral suppression of HIV did not significantly predict hypertension among HIV-positives.

                Significance

                The burden of hypertension is substantial and inadequately controlled, both in HIV-positive persons and overall. Universal HIV screening programs could provide counseling, testing, and treatment for hypertension in Sub-Saharan Africa.
                  Cover page: Population-Based Assessment of Hypertension Epidemiology and Risk Factors among HIV-Positive and General Populations in Rural Uganda
                  • Article
                  • Peer Reviewed
                  UC San Francisco Previously Published Works (2020)

                  Background

                  Hypertension (HTN) is the single leading risk factor for human mortality worldwide, and more prevalent in sub-Saharan Africa than any other region [1]-although resources for HTN screening, treatment, and control are few. Most regional pilot studies to leverage HIV programs for HTN control have achieved blood pressure control in half of participants or fewer [2,3,4]. But this control gap may be due to inconsistent delivery of services, rather than ineffective underlying interventions.

                  Methods

                  We sought to evaluate the consistency of HTN program delivery within the SEARCH study (NCT01864603) among 95,000 adults in 32 rural communities in Uganda and Kenya from 2013-2016. To achieve this objective, we designed and performed a fidelity evaluation of the step-by-step process (cascade) of HTN care within SEARCH, calculating rates of HTN screening, linkage to care, and follow-up care. We evaluated SEARCH's assessment of each participant's HTN status against measured blood pressure and HTN history.

                  Findings

                  SEARCH completed blood pressure screens on 91% of participants. SEARCH HTN screening was 91% sensitive and over 99% specific for HTN relative to measured blood pressure and patient history. 92% of participants screened HTN+ received clinic appointments, and 42% of persons with HTN linked to subsequent care. At follow-up, 82% of SEARCH clinic participants received blood pressure checks; 75% received medication appropriate for their blood pressure; 66% remained in care; and 46% had normal blood pressure at their most recent visit.

                  Conclusion

                  The SEARCH study's consistency in delivering screening and treatment services for HTN was generally high, but SEARCH could improve effectiveness in linking patients to care and achieving HTN control. Its model for implementing population-scale HTN testing and care through an existing HIV test-and-treat program-and protocol for evaluating the intervention's stepwise fidelity and care outcomes-may be adapted, strengthened, and scaled up for use across multiple resource-limited settings.
                    Cover page: Hypertension testing and treatment in Uganda and Kenya through the SEARCH study: An implementation fidelity and outcome evaluation
                    • Article
                    • Peer Reviewed
                    LBL Publications (2020)
                    Linking genomic variation to phenotypical traits remains a major challenge in evolutionary genetics. In this study, we use phylogenomic strategies to investigate a distinctive trait among mammals: the development of masculinizing ovotestes in female moles. By combining a chromosome-scale genome assembly of the Iberian mole, Talpa occidentalis, with transcriptomic, epigenetic, and chromatin interaction datasets, we identify rearrangements altering the regulatory landscape of genes with distinct gonadal expression patterns. These include a tandem triplication involving CYP17A1, a gene controlling androgen synthesis, and an intrachromosomal inversion involving the pro-testicular growth factor gene FGF9, which is heterochronically expressed in mole ovotestes. Transgenic mice with a knock-in mole CYP17A1 enhancer or overexpressing FGF9 showed phenotypes recapitulating mole sexual features. Our results highlight how integrative genomic approaches can reveal the phenotypic impact of noncoding sequence changes.
                      Cover page: The mole genome reveals regulatory rearrangements associated with adaptive intersexuality
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