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Open Access Publications from the University of California

Scholarly Works (23 results)

  • Article
LBL Publications (1966)
    Cover page: DIMINUTION OF SENSITIVE TIME OF SPARK CHAMBERS
    • Article
    • Peer Reviewed
    UC Irvine Previously Published Works (2009)
    This prospective study (n=190) examined correlates of alcohol use from baseline data of a longitudinal trial conducted among moderate and heavy alcohol users receiving methadone maintenance therapy (MMT). The sample included MMT clients who were 18-55 years of age, and were receiving MMT from five large methadone maintenance clinics in the Los Angeles area. Half of the sample was heavy drinkers and nearly half (46%) reported heroin use. Using a structured questionnaire, correlates of heavy alcohol use included White and Hispanic ethnicity, and fair or poor physical health combined with older age (> or =50 years). We also found that MMT clients who were younger than 50 years, regardless of health status, were more likely to be heavy drinkers. Compared with moderate alcohol consumers, a greater number of heavy alcohol users also experienced recent victimization. To optimize MMT, alcohol screening should be part of routine assessment and alcohol treatment should be made available within MMT programs. Moreover, special consideration should be provided to the most vulnerable clients, such as the younger user, those with a long-term and current history of heavy drug use, and those victimized and reporting fair or poor health. In addition, promoting attention to general physical and mental health problems within MMT programs may be beneficial in enhancing health outcomes of this population.
      Cover page: Correlates of alcohol use among methadone-maintained adultsCreative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2018)
      Immune checkpoint inhibitors targeting the PD-1 pathway have greatly changed clinical management of metastatic urothelial carcinoma and metastatic renal cell carcinoma. However, response rates are low, and biomarkers are needed to predict for treatment response. Immunohistochemical quantification of PD-L1 was developed as a promising biomarker in early clinical trials, but many shortcomings of the four different assays (different antibodies, disparate cellular populations, and different thresholds of positivity) have limited its clinical utility. Further limitations include the use of archival specimens to measure this dynamic biomarker. Indeed, until PD-L1 testing is standardized and can consistently predict treatment outcome, the currently available PD-L1 assays are not clinically useful in urothelial and renal cell carcinoma. Other more promising biomarkers include tumor mutational burden, profiles of tumor infiltrating lymphocytes, molecular subtypes, and PD-L2. Potentially, a composite biomarker may be best but will need prospective testing to validate such a biomarker.
        Cover page: Biomarkers of immunotherapy in urothelial and renal cell carcinoma: PD-L1, tumor mutational burden, and beyond
        • Article
        • Peer Reviewed
        UC Santa Cruz Previously Published Works (2013)
        Stable-isotope ratios of carbon (13C/12C; δ13C) and nitrogen (15N/14N; δ15N) in animal tissues are analyzed to estimate animal foraging ecology because these ratios reflect those of an animal's diet. This reflection is generally indirect, as stable-isotope ratios change with trophic level. These differences, called discrimination factors (reported as Δ), vary considerably by species and tissue. Variations in discrimination factors used in stableisotope mixing models can lead to inaccurate estimates of diets. Therefore, determining accurate discrimination factors specific to species and tissue is important. We established the Δ13C and Δ15N values between diet and blood and feathers from chicks and juveniles of the California Condor (Gymnogyps californianus). Hatchlings were fed rats for 76-119 days, whereas juveniles were fed dairy calves for 64 days. The mean Δ13C and Δ15N values ( ± SD) between chick feathers and rat muscle were 0.4 ± 0.4‰ and 3.1 ± 0.2‰, respectively; those between chicks' whole blood and rat muscle were -0.7 ± 0.1‰ and 1.7 ± 0.1‰, respectively. The mean Δ13C and Δ15N values between juvenile condors' plasma and calf muscle were 0.9 ± 0.2‰ and 3.3 ± 0.7‰, respectively; those between juveniles' red blood cells and calf muscle were 0.3 ± 0.3‰ and 1.8 ± 0.1‰, respectively; and those between juveniles' whole blood and calf muscle were 0.3 ± 0.3‰ and 1.9 ± 0.2‰, respectively. We report the first discrimination factors for the Cathartidae (New World vultures), and our findings will have important applications in studies of the critically endangered California Condor's foraging ecology. © The Cooper Ornithological Society 2013.
          Cover page: Discrimination Factors for Stable Isotopes of Carbon and Nitrogen in Blood and Feathers from Chicks and Juveniles of the California Condor
          • Article
          • Peer Reviewed
          UC Irvine Previously Published Works (2009)
          This cross-sectional study (n = 190) examined correlates of hospitalization for physical health problems among methadone maintenance therapy (MMT) clients with a history of alcohol abuse. The study was derived from baseline data collected for a longitudinal trial assessing the effect of motivational interviewing among alcohol-abusing adults undergoing MMT. The sample included clients who were 18-55 years of age, abusing alcohol, and receiving MMT from five large methadone maintenance clinics in the Los Angeles area. A structured questionnaire was used to collect the data. Correlates of hospitalization in logistic regression analysis included lack of social support, recent victimization, age of first alcohol use, chronic severe pain in the previous 6 months, not having children, and ethnicity. Identification of hospitalization risk factors among alcohol-abusing MMT clients is a first step to developing risk-reducing interventions designed to lower hospitalization rates in this population.
            Cover page: Correlates of Hospitalization for Alcohol-Using Methadone-Maintained Persons With Physical Health ProblemsCreative Commons 'BY' version 4.0 license
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2021)
            Aim: To examine the prognostic value of the platelet-to-lymphocyte ratio (PLR) in the adjuvant renal cell carcinoma setting. Materials & methods: Patients received adjuvant sunitinib (50 mg/day; 4 weeks on/2 weeks off) or placebo. The primary end point was disease-free survival (DFS). Results: In 609 patients, DFS was similar for baseline PLR <140 versus ≥140 overall (median: 6.4 vs 5.9 years; hazard ratio: 0.9; 95% CI: 0.7-1.2). A ≥25% decrease in PLR at week 4 overall was associated with longer DFS versus no change (hazard ratio: 0.8; 95% CI: 0.6-1.0). Conclusion: Baseline PLR was not prognostic for DFS with adjuvant sunitinib treatment in patients with renal cell carcinoma. Clinical Trials Registration: NCT00375674 (ClinicalTrials.gov).
              Cover page: Exploratory analysis of the platelet-to-lymphocyte ratio prognostic value in the adjuvant renal cell cancer setting
              • Article
              • Peer Reviewed
              Faculty Publications (2012)

              Endangered species recovery programs seek to restore populations to self-sustaining levels. Nonetheless, many recovering species require continuing management to compensate for persistent threats in their environment. Judging true recovery in the face of this management is often difficult, impeding thorough analysis of the success of conservation programs. We illustrate these challenges with a multidisciplinary study of one of the world's rarest birds-the California condor (Gymnogyps californianus). California condors were brought to the brink of extinction, in part, because of lead poisoning, and lead poisoning remains a significant threat today. We evaluated individual lead-related health effects, the efficacy of current efforts to prevent lead-caused deaths, and the consequences of any reduction in currently intensive management actions. Our results show that condors in California remain chronically exposed to harmful levels of lead; 30% of the annual blood samples collected from condors indicate lead exposure (blood lead ≥ 200 ng/mL) that causes significant subclinical health effects, measured as >60% inhibition of the heme biosynthetic enzyme δ-aminolevulinic acid dehydratase. Furthermore, each year, ∼20% of free-flying birds have blood lead levels (≥450 ng/mL) that indicate the need for clinical intervention to avert morbidity and mortality. Lead isotopic analysis shows that lead-based ammunition is the principle source of lead poisoning in condors. Finally, population models based on condor demographic data show that the condor's apparent recovery is solely because of intensive ongoing management, with the only hope of achieving true recovery dependent on the elimination or substantial reduction of lead poisoning rates.

                Cover page: Lead poisoning and the deceptive recovery of the critically endangered California condor.
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2016)
                Oncogenic transformation may reprogram tumor metabolism and render cancer cells addicted to extracellular nutrients. Deprivation of these nutrients may therefore represent a therapeutic opportunity, but predicting which nutrients cancer cells become addicted remains difficult. Here, we performed a nutrigenetic screen to determine the phenotypes of isogenic pairs of clear cell renal cancer cells (ccRCC), with or without VHL, upon the deprivation of individual amino acids. We found that cystine deprivation triggered rapid programmed necrosis in VHL-deficient cell lines and primary ccRCC tumor cells, but not in VHL-restored counterparts. Blocking cystine uptake significantly delayed xenograft growth of ccRCC. Importantly, cystine deprivation triggered similar metabolic changes regardless of VHL status, suggesting that metabolic responses alone are not sufficient to explain the observed distinct fates of VHL-deficient and restored cells. Instead, we found that increased levels of TNFα associated with VHL loss forced VHL-deficient cells to rely on intact RIPK1 to inhibit apoptosis. However, the preexisting elevation in TNFα expression rendered VHL-deficient cells susceptible to necrosis triggered by cystine deprivation. We further determined that reciprocal amplification of the Src-p38 (MAPK14)-Noxa (PMAIP1) signaling and TNFα-RIP1/3 (RIPK1/RIPK3)-MLKL necrosis pathways potentiated cystine-deprived necrosis. Together, our findings reveal that cystine deprivation in VHL-deficient RCCs presents an attractive therapeutic opportunity that may bypass the apoptosis-evading mechanisms characteristic of drug-resistant tumor cells. Cancer Res; 76(7); 1892-903. ©2016 AACR.
                  Cover page: Cystine Deprivation Triggers Programmed Necrosis in VHL-Deficient Renal Cell Carcinomas.
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2020)

                  Purpose

                  In the S-TRAC trial, adjuvant sunitinib improved disease-free survival (DFS) compared with placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence. This post hoc exploratory analysis investigated the neutrophil-to-lymphocyte ratio (NLR) for predictive and prognostic significance in the RCC adjuvant setting.

                  Experimental design

                  Kaplan-Meier estimates and Cox proportional analyses were performed on baseline NLR and change from baseline at week 4 to assess their association with DFS. Univariate P values were two-sided and based on an unstratified log-rank test.

                  Results

                  609 of 615 patients had baseline NLR values; 574 patients had baseline and week 4 values. Sunitinib-treated patients with baseline NLR <3 had longer DFS versus placebo (7.1 vs. 4.7; HR, 0.71; P = 0.02). For baseline NLR ≥3, DFS was similar regardless of treatment (sunitinib 6.8 vs. placebo not reached; HR, 1.03; P = 0.91). A ≥25% NLR decrease at week 4 was associated with longer DFS versus no change (6.8 vs. 5.3 years; HR, 0.71; P = 0.01). A greater proportion of sunitinib-treated patients had ≥25% NLR decrease at week 4 (71.2%) versus placebo (17.4%). Patients with ≥25% NLR decrease at week 4 received a higher median cumulative sunitinib dose (10,137.5 mg) versus no change (8,168.8 mg) or ≥25% increase (6,712.5 mg).

                  Conclusions

                  In the postnephrectomy high-risk RCC patient cohort, low baseline NLR may help identify those most suitable for adjuvant sunitinib. A ≥25% NLR decrease at week 4 may be an early indicator of those most likely to tolerate treatment and derive DFS benefit.
                    Cover page: Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor of Disease-free Survival in Postnephrectomy High-risk Locoregional Renal Cell Carcinoma: Analysis of the S-TRAC Trial
                    • Article
                    • Peer Reviewed
                    UC Irvine Previously Published Works (2010)

                    Background

                    Methadone-maintained (MM) clients who engage in excessive alcohol use are at high risk for HIV and hepatitis B virus (HBV) infection. Nurse-led hepatitis health promotion (HHP) may be one strategy to decrease alcohol use in this population.

                    Objective

                    To evaluate the impact of nurse-led HHP, delivered by nurses compared to motivational interviewing (MI), delivered by trained therapists in group sessions or one-on-one on reduction of alcohol use.

                    Methods

                    A three-arm randomized, controlled trial, conducted with 256 MM adults attending one of five MM outpatient clinics in the Los Angeles area. Within each site, moderate-to-heavy alcohol-using MM participants were randomized into one of three conditions: (1) nurse-led hepatitis health promotion group sessions (n=87); (2) MI delivered in group sessions (MI-group; n=79), or (3) MI delivered one-on-one sessions (MI-single, n=90).

                    Results

                    Self-reported alcohol use was reduced from a median of 90 drinks/month at baseline to 60 drinks/month at 6-month follow-up. A Wilcoxon sign-rank test indicated a significant reduction in alcohol use in the total sample (p<.05). In multiple logistic regression analysis controlling for alcohol consumption at baseline and other covariates, no differences by condition were found.

                    Discussion

                    As compared to two programs delivered by MI specialists, a culturally-sensitive and easy to implement nurse-led HHP program produced similar reductions in alcohol use over 6 months. Employing nurse-led programs may allow cost savings for treatment programs as well as a greater integration of alcohol reduction counseling along with a more comprehensive focus on general health-related issues than previously conducted.
                      Cover page: Effect of motivational interviewing on reduction of alcohol useCreative Commons 'BY' version 4.0 license
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