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Open Access Publications from the University of California

Scholarly Works (11 results)

  • Thesis
  • Peer Reviewed
UC Berkeley Electronic Theses and Dissertations (2014)

Microbes occur in extraordinary abundance and diversity in vertebrates, and a growing body of work, particularly on humans and mice, has highlighted the pervasive role that microbiota may play in host physiology and health. Yet factors underlying the assembly of microbiota and the potential for microbiota to mediate host fitness in free-living vertebrate populations remain understudied. Investigating host-microbial interactions in natural systems is necessary to understand the extent to which ecologically relevant levels of environmental heterogeneity shape host-microbial relationships and to gain insight into the role that microbiota may play in the ecology and evolution of non-model host taxa. The neonatal vertebrate life stage is of particular interest during which substantial physiological development occurs and through which the initial microbial colonization can have longlasting effects on metabolic programming. To better understand mechanisms underlying microbial variation and associations with host condition during early periods of vertebrate development, this study characterized the gut microbiota of nestlings and their mothers in a natural population of Western Bluebirds Sialia mexicana. A novel method based on solid phase reversible immobilization beads was developed to extract metagenomic DNA from minimally invasive avian fecal and swab specimens. Illumina sequence analysis of bacterial 16S rRNA amplicons was performed on oral, cloacal, and fecal samples collected longitudinally from nestlings throughout the nestling period across multiple nests and over three consecutive breeding seasons (2011-2013). Environmental selection appeared to drive variation in microbiota across gut sites within individuals as well as between nests among individuals. Ambient temperature and sampling year correlated substantially with variation in the gut microbiota. In contrast, surprisingly no association was recovered between host age and alpha diversity, and increased similarity of microbiota across gut sites with host age was observed. Also unexpectedly, shared nest environment and geographical distance were weak predictors of microbial similarity among individuals. Variation in the gut microbiota significantly associated with morphological metrics of nestling growth, even after accounting for the influence of several temporal and environmental variables known to mediate nestling development. However, gut microbiota comprised a less robust predictor of nestling morphology than host age, sampling year, and ambient temperature. Furthermore, perturbation in the form of a viral immune challenge caused measurable shifts in the bacterial gut microbiota, which has previously been undocumented, but no measured effect of the immune challenge was observed on morphological metrics. These data inform intriguing hypotheses for future research on the drivers of avian host-microbial associations and the extent to which microbiota may impact host growth in natural systems. Discerning how microbiota may generate phenotypic or fitness differences among vertebrate host organisms is essential to understanding the evolution and maintenance of biodiversity.

    Cover page: Determinants and Implications of Variation in the Avian Gut Microbiota
    • Article
    • Peer Reviewed
    UC Berkeley Previously Published Works (2017)
    Determining the ecosystem function of high-order predators is critical for evaluation of food web interactions. Insectivorous birds are abundant predators in many ecosystems yet because they forage upon small taxa, it remains largely unknown whether birds are providing ecosystem services in the form of pest control or disservices by preying upon predaceous arthropod species. We extracted DNA from noninvasive fecal samples of adult and nestling Western Bluebirds (Sialia mexicana) in California vineyards. Using universal arthropod-specific primers, we sequenced prey items via massively parallel sequencing on the Illumina MiSeq platform. Bluebirds consumed a broad diet comprising 66 unique arthropod species from 6 orders and 28 families. Aedes sp. (mosquitoes: Culicidae), a previously unknown prey, was the most common item recovered, occurring in 49.5% of the fecal samples. Ectoparasitic bird blowfly (Protocalliphora) DNA was found in 7% of adult and 11% of nestling samples, presenting clear evidence of active feeding by the avian hosts on adult or larval ectoparasites. Herbivorous insects, primarily from the orders Hemiptera and Lepidoptera, represented over half (56%) of the prey items in bluebird diets. Intraguild predation (consumption of predator or parasitoid arthropods) represented only 3% of adult and nestling dietary items. Diets of adults were significantly different from nestlings as were diets from birds sampled in different vineyard blocks. Sex, date, number of young, and individual bird (based on resampled individuals) were all insignificant factors that did not explain diet variability. Nestling age was a significant factor in explaining a small amount of the variability in dietary components. In addition, our analysis of subsampling larger fecal samples and processing them independently revealed highly dissimilar results in all 10 trials and we recommend avoiding this common methodology. Molecular scatology offers powerfully informative techniques that can reveal the ecosystem function and services provided by abundant yet cryptic avian foragers.
      Cover page: Molecular scatology and high-throughput sequencing reveal predominately herbivorous insects in the diets of adult and nestling Western Bluebirds (Sialia mexicana) in California vineyards
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2023)
      COVID-19 testing is an important risk mitigation strategy for COVID-19 prevention in school settings, where the virus continues to pose a public health challenge for in-person learning. Socially vulnerable school communities with the highest proportion of low-income, minority, and non-English speaking families have the least testing access despite shouldering a disproportionate burden of COVID-19 morbidity and mortality. Through the Safer at School Early Alert (SASEA) program, we investigated community perceptions of testing in San Diego County schools, with a focus on barriers and facilitators from the perspective of socially vulnerable parents and school staff. Using a mixed-methods approach, we administered a community survey and conducted focus group discussions (FGDs) with staff and parents from SASEA-affiliated schools and childcares. We recruited 299 survey respondents and 42 FGD participants. Protecting one's family (96.6%) and protecting one's community (96.6%) were marked as key motivators to testing uptake. School staff in particular reported that the reassurance of a negative status mitigated concerns about COVID-19 infection in schools. Participants expressed that COVID-19-related stigma, loss of income as a result of isolation/quarantine requirements, and lack of multilingual materials were the most significant barriers to testing. Our findings suggest that the testing barriers faced by school community members are predominantly structural. Testing uptake efforts must provide support and resources to manage the social and financial consequences of testing while continuously communicating its benefits. There is a clear need to continue to incorporate testing as a strategy to maintain school safety and facilitate access for vulnerable community members.
        Cover page: Barriers and facilitators to COVID-19 testing among staff and parents from San Diego schools.
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2023)
        BACKGROUND: Case investigation and contact tracing (CI/CT) are important public health tools to interrupt COVID-19 transmission. Our study aims to understand how parents and school staff perceive COVID-19 CI/CT. METHODS: Using a mixed methods approach, we distributed a community survey and conducted 15 focus group discussions (FGDs) in English and Spanish between December 2020 and March 2021 with 20 parents and 22 staff from schools in San Diego County ZIP Codes with COVID-19 rates in the top quintile as of August 2020. RESULTS: One in 4 survey respondents reported that they would be reluctant to participate in CI/CT. FGDs revealed themes of mistrust in government authorities, overburdened institutions, unfamiliarity with CI/CT, and uncertainty about its reliability. School community members emphasized that parents trust schools to be involved in CI/CT efforts, but schools are overwhelmed with this added responsibility. CONCLUSIONS: Investing in schools as community hubs is necessary so they can become important partners in prevention and mitigation in public health.
          Cover page: Challenges of COVID-19 Case Investigation and Contact Tracing in School Settings: An Initial Investigation.
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2024)
          BACKGROUND: MGMT (O 6 -methylguanine-DNA methyltransferase) promoter methylation is a commonly assessed prognostic marker in glioblastoma (GBM). Epigenetic silencing of the MGMT gene by promoter methylation is associated with greater overall and progression free survival with alkylating agent regimens. To date, there is marked heterogeneity in how MGMT promoter methylation is tested and which CpG sites are interrogated. METHODS: To further elucidate which MGMT promoter CpG sites are of greatest interest, we performed comprehensive searches in PubMed, Web of Science, and Embase and reviewed 2,925 article abstracts. We followed the GRADE scoring system to assess risk of bias and the quality of the studies we included. RESULTS: We included articles on adult glioblastoma that examined significant sites or regions within MGMT promoter for the outcomes: overall survival, progression free survival, and/or MGMT expression. We excluded systemic reviews and articles on lower grade glioma. fifteen articles met inclusion criteria with variable overlap in laboratory and statistical methods employed, as well as CpG sites interrogated. Pyrosequencing or BeadChip arrays were the most popular methods utilized, and CpG sites between CpGs 70-90 were most frequently investigated. Overall, there was moderate concordance between the CpG sites that the studies reported to be highly predictive of prognosis. Combinations or means of sites between CpGs 73-89 were associated with improved OS and PFS. Six studies identified CpG sites associated with prognosis that were closer to the transcription start site: CpGs 8, 19, 22, 25, 27, 32,38, and CpG sites 21-37, as well as low methylation level of the enhancer regions. CONCLUSION: The following systematic review details a comprehensive investigation of the current literature and highlights several potential key CpG sites that demonstrate significant association with OS, PFS, and MGMT expression. However, the relationship between extent of MGMT promoter methylation and survival may be non-linear and could be influenced by potential CpG hotspots, the extent of methylation at each CpG site, and MGMT enhancer methylation status. There were several limitations within the studies such as smaller sample sizes, variance between methylation testing methods, and differences in the various statistical methods to test for association to outcome. Further studies of high impact CpG sites in MGMT methylation is warranted.
            Cover page: A systematic review of high impact CpG sites and regions for MGMT methylation in glioblastoma [A systematic review of MGMT methylation in GBM].
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2024)
            BACKGROUND: Institutional mistrust has weakened COVID-19 mitigation efforts. Assessing to what extent institutional mistrust impacts parental decision making is important in formulating structural efforts for improving future pandemic response. We hypothesized that institutional mistrust is associated with lower parental endorsement for COVID-19 vaccination. METHODS: We distributed an online survey among parents from schools in areas with high levels of social vulnerability relative to the rest of San Diego County. We defined vaccination endorsement as having a child aged 5 years or older who received at least one COVID-19 vaccine dose or being very likely to vaccinate their child aged 6 months-4 years when eligible. Institutional mistrust reflected the level of confidence in institutions using an aggregate score from 11 to 44. We built a multivariable logistic regression model with potential confounding variables. FINDINGS: Out of 290 parents in our sample, most were female (87.6%), reported their child as Hispanic/Latino (73.4%), and expressed vaccination endorsement (52.1%). For every one-point increase in mistrust score, there was an 8% reduction in the likelihood of participants endorsing vaccination for their child. Other statistically significant correlates that were positively associated with vaccination endorsement included parent vaccination status, child age, parent age, and Hispanic/Latino ethnicity. CONCLUSION: Our study further demonstrates how institutional mistrust hinders public response during health emergencies. Our findings also highlight the importance of building confidence in institutions and its downstream effects on pandemic preparedness and public health. One way that institutions can improve their relationship with constituents is through building genuine partnerships with trusted community figures.
              Cover page: Assessing the impact of institutional mistrust on parental endorsement for COVID-19 vaccination among school communities in San Diego County, California.
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2020)

              Introduction

              The HIV epidemic in Tijuana, Mexico is concentrated in key populations, including people who inject drugs (PWID). However, HIV interventions among PWID are minimal, and federal funding was provided for compulsory abstinence programmes associated with HIV and overdose. Alternatively, opioid agonist therapy reduces overdose, reincarceration, HIV, while improving antiretroviral therapy (ART) outcomes. We assessed potential impact and synergies of scaled-up integrated ART and opioid agonist therapy, compared to scale-up of each separately, and potential harms of compulsory abstinence programmes on HIV and fatal overdose among PWID in Tijuana.

              Methods

              We developed a dynamic model of HIV transmission and overdose among PWID in Tijuana. We simulated scale-up of opioid agonist therapy from zero to 40% coverage among PWID. We evaluated synergistic benefits of an integrated harm reduction and ART scale-up strategy (40% opioid agonist therapy coverage and 10-fold ART recruitment), compared to scale-up of each intervention alone or no scale-up of low coverage ART and no harm reduction). We additionally simulated compulsory abstinence programmes (associated with 14% higher risk of receptive syringe sharing and 76% higher odds of overdose) among PWID.

              Results

              Without intervention, HIV incidence among PWID could increase from 0.72 per 100 person-years (PY) in 2020 to 0.92 per 100 PY in 2030. Over ten years, opioid agonist therapy scale-up could avert 31% (95% uncertainty interval (UI): 18%, 46%) and 22% (95% UI: 10%, 28%) new HIV infections and fatal overdoses, respectively, with the majority of HIV impact from the direct effect on HIV transmission due to low ART coverage. Integrating opioid agonist therapy and ART scale-up provided synergistic benefits, with opioid agonist therapy effects on ART recruitment/retention averting 9% more new infections compared to ART scale-up alone. The intervention strategy could avert 48% (95% UI: 26%, 68%) of new HIV infections and one-fifth of fatal overdoses over ten years. Conversely, compulsory abstinence programmes could increase HIV and overdoses.

              Conclusions

              Integrating ART with opioid agonist therapy could provide synergistic benefits and prevent HIV and overdoses among PWID in Tijuana, whereas compulsory abstinence programmes could cause harm. Policymakers should consider the benefits of integrating harm reduction and HIV services for PWID.
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2023)
                Rapid identification and isolation/quarantine of COVID-19 cases or close contacts, respectively, is a vital tool to support safe, in-person learning. However, safe isolation or quarantine for a young child also necessitates home confinement for at least one adult caregiver, as well as rapid learning material development by the teacher to minimize learning loss. The purpose of this study is to better understand barriers and supports to student home confinement. We conducted a mixed-methods study using focus group discussions and a self-administered online survey with parents and staff members from 12 elementary schools and childcare sites across San Diego County serving low-income and socially vulnerable families. Focus group participants reported that mental distress and loneliness, learning loss, childcare, food, income loss, and overcrowded housing were major barriers related to home confinement. The experiences described by FGD participants were prevalent in a concurrent community survey: 25% of participants reported that isolation would be extremely difficult for a household member who tested positive or was exposed to COVID-19, and 20% were extremely concerned about learning loss while in isolation or quarantine. Our findings suggest that there are serious structural impediments to safely completing the entire recommended course of isolation or quarantine, and that the potential for isolation or quarantine may also lead to increased hesitancy to access diagnostic testing.
                  Cover page: “It’s hard for everyone” systemic barriers to home confinement to prevent community spread of COVID-19
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2023)

                  Background

                  Needle and syringe programs (NSPs) are effective at preventing HIV and hepatitis C virus (HCV) among people who inject drugs (PWID), yet global coverage is low, partly because governments lack data on the cost and cost-effectiveness of NSP in their countries to plan and fund their responses. We conducted a global systematic review of unit costs of NSP provision to inform estimation of cost drivers and extrapolated costs to other countries.

                  Methods

                  We conducted a systematic review to extract data on the cost per syringe distributed and its cost drivers. We estimated the impact of country-level and program-level variables on the cost per syringe distributed using linear mixed-effects models. These models were used to predict unit costs of NSP provision, with the best performing model used to extrapolate the cost per syringe distributed for 137 countries. The total cost for a comprehensive NSP (200 syringes per PWID/year) was also estimated for 68 countries with PWID population size estimates.

                  Results

                  We identified 55 estimates of the unit cost per syringe distributed from 14 countries. Unit costs were extrapolated for 137 countries, ranging from $0.08 to $20.77 (2020 USD) per syringe distributed. The total estimated spend for a high-coverage, comprehensive NSP across 68 countries with PWID size estimates is $5 035 902 000 for 10 887 500 PWID, 2.1-times higher than current spend.

                  Conclusion

                  Our review identified cost estimates from high-income, upper-middle-income, and lower-middle-income countries. Regression models may be useful for estimating NSP costs in countries without data to inform HIV/HCV prevention programming and policy.
                    Creative Commons 'BY-NC-ND' version 4.0 license
                    • Article
                    UC San Diego Previously Published Works (2023)
                    BACKGROUND: Schools are high-risk settings for SARS-CoV-2 transmission, but necessary for children's educational and social-emotional wellbeing. Previous research suggests that wastewater monitoring can detect SARS-CoV-2 infections in controlled residential settings with high levels of accuracy. However, its effective accuracy, cost, and feasibility in non-residential community settings is unknown. METHODS: The objective of this study was to determine the effectiveness and accuracy of community-based passive wastewater and surface (environmental) surveillance to detect SARS-CoV-2 infection in neighborhood schools compared to weekly diagnostic (PCR) testing. We implemented an environmental surveillance system in nine elementary schools with 1700 regularly present staff and students in southern California. The system was validated from November 2020 - March 2021. FINDINGS: In 447 data collection days across the nine sites 89 individuals tested positive for COVID-19, and SARS-CoV-2 was detected in 374 surface samples and 133 wastewater samples. Ninety-three percent of identified cases were associated with an environmental sample (95% CI: 88% - 98%); 67% were associated with a positive wastewater sample (95% CI: 57% - 77%), and 40% were associated with a positive surface sample (95% CI: 29% - 52%). The techniques we utilized allowed for near-complete genomic sequencing of wastewater and surface samples. INTERPRETATION: Passive environmental surveillance can detect the presence of COVID-19 cases in non-residential community school settings with a high degree of accuracy. FUNDING: County of San Diego, Health and Human Services Agency, National Institutes of Health, National Science Foundation, Centers for Disease Control.
                      Cover page: Wastewater and surface monitoring to detect COVID-19 in elementary school settings: The Safer at School Early Alert project
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