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Open Access Publications from the University of California

Scholarly Works (8 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2006)
    Cover page: Design considerations for 400 GHz InP/InGaAs Heterojunction Bipolar Transistors
    • Article
    • Peer Reviewed
    UCLA Previously Published Works (2010)
    To improve understanding about genetic and environmental influences on antisocial behavior (ASB), we tested the association of the 44-base pair polymorphism of the serotonin transporter gene (5-HTTLPR) and maltreatment using latent class analysis in 2,488 boys and girls from Wave 1 of the National Longitudinal Study of Adolescent Health. In boys, ASB was defined by three classes (Exclusive Covert, Mixed Covert and Overt, and No Problems) whereas in girls, ASB was defined by two classes (Exclusive Covert, No Problems). In boys, 5-HTTLPR and maltreatment were not significantly related to ASB. However, in girls, maltreatment, but not 5-HTTLPR, was significantly associated with ASB. A significant interaction between 5-HTTLPR and maltreatment was also observed, where maltreated girls homozygous for the short allele were 12 times more likely to be classified in the Exclusive Covert group than in the No Problems group. Structural differences in the latent structure of ASB at Wave 2 and Wave 3 prevented repeat LCA modeling. However, using counts of ASB, 5-HTTLPR, maltreatment, and its interaction were unrelated to overt and covert ASB at Wave 2 and only maltreatment was related to covert ASB at Wave 3. We discuss these findings within the context of sex differences in ASB and relevant models of gene-environment interplay across developmental periods.
      Cover page: Latent Class Analysis of Antisocial Behavior: Interaction of Serotonin Transporter Genotype and Maltreatment
      • Thesis
      • Peer Reviewed
      UCLA Electronic Theses and Dissertations (2013)

      Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset disorder characterized by developmentally-aberrant and impairing levels of inattention and/or hyperactivity-impulsivity (Diagnostic and Statistical Manual of Mental Disorders, 4th edition - Text Revision; American Psychiatric Association, 2000). ADHD affects approximately 8-12% of school-aged children worldwide (Froehlich et al., 2007), and prospectively predicts a wide range of negative outcomes, including academic failure, criminality, substance abuse, and neuropsychological impairment (Barkley & Fischer, 2010; Langley et al., 2010; Molina et al., 2009).

      Although there is consensus that ADHD is influenced by biological (e.g., genetics) and environmental factors (e.g., parenting) (Nigg, Nikolas, & Burt, 2010; Plomin, Owen, & McGuffin, 1994), relatively little research has directly assessed how biological and environmental factors interact in the development of ADHD and other forms of psychopathology (Moffitt, Caspi, & Rutter, 2006). Genetic influences on psychopathology are likely to depend on exposure to or the experience of varying environmental conditions such that some children exposed to environmental adversity (e.g., abuse, maladaptive parenting) develop psychopathology whereas others do not (i.e., gene x environment interaction; G×E ) (Waldman, 2007). The primary aim of this study is to investigate the interactive effects of several functional polymorphisms and their interaction with environmental factors that are known to influence ADHD and related phenotypes. My dissertation will interrogate these influences using multiple research designs (i.e., cross-sectional, longitudinal) and methods (i.e., rating scales, experimental manipulations), including a large prospective longitudinal study of unselected youth and an intensively characterized sample of school-age children with and without ADHD being followed prospectively.

        Cover page: Multi-Method Investigation of Gene-Environment Interplay and ADHD
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2016)
        Item response theory (IRT) was separately applied to parent- and teacher-rated symptoms of attention-deficit/hyperactivity disorder (ADHD) from a pooled sample of 526 six- to twelve-year-old children with and without ADHD. The dimensional structure ADHD was first examined using confirmatory factor analyses, including the bifactor model. A general ADHD factor and two group factors, representing inattentive and hyperactive/impulsive dimensions, optimally fit the data. Using the graded response model, we estimated discrimination and location parameters and information functions for all 18 symptoms of ADHD. Parent- and teacher-rated symptoms demonstrated adequate discrimination and location values, although these estimates varied substantially. For parent ratings, the test information curve peaked between -2 and +2 SD, suggesting that ADHD symptoms exhibited excellent overall reliability at measuring children in the low to moderate range of the general ADHD factor, but not in the extreme ranges. Similar results emerged for teacher ratings, in which the peak range of measurement precision was from -1.40 to 1.90 SD Several symptoms were comparatively more informative than others; for example, is often easily distracted ("Distracted") was the most informative parent- and teacher-rated symptom across the latent trait continuum. Clinical implications for the assessment of ADHD as well as relevant considerations for future revisions to diagnostic criteria are discussed.
          Cover page: Item Response Theory Analysis of ADHD Symptoms in Children With and Without ADHD
          • Article
          • Peer Reviewed
          UCLA Previously Published Works (2016)

          Context

          Although children with attention-deficit/hyperactivity disorder (ADHD) are at elevated risk for comorbid psychopathology, the clinical correlates of ADHD in girls are far less understood relative to boys, despite ADHD being one of the most common childhood disorders in girls.

          Objective

          To meta-analytically summarize rates of comorbid internalizing (anxiety, depression) and externalizing (oppositional defiant disorder [ODD], conduct disorder [CD]) psychopathology among girls with and without ADHD.

          Data sources

          Literature searches (PubMed, Google Scholar) identified published studies examining comorbid psychopathology in girls with and without ADHD.

          Study selection

          Eighteen studies (1997 participants) met inclusion criteria and had sufficient data for the meta-analysis.

          Data extraction

          Odds ratios for each comorbid disorder were calculated from available data. Demographic (eg, age, race/ethnicity) and study characteristics (eg, referral source, diagnostic method) were also coded.

          Results

          Compared with girls without ADHD, girls with ADHD were significantly more likely to meet Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for each comorbid disorder assessed. Relative odds were higher for externalizing (ODD: 5.6×; CD: 9.4×) relative to internalizing disorders (anxiety: 3.2×; depression: 4.2×). Meta-regression revealed larger effect sizes of ADHD on anxiety for studies using multiple diagnostic methods, featuring younger children, and including clinic-referred (versus community-referred) girls; the effect of ADHD on ODD varied based on diagnostic informant.

          Limitations

          Findings were derived from cross-sectional studies, precluding causal inferences.

          Conclusions

          Girls with ADHD frequently exhibit comorbid externalizing and internalizing disorders. We discuss future research priorities and consider intervention implications for ADHD and comorbid psychopathology in girls.
            Cover page: Patterns of Comorbidity Among Girls With ADHD: A Meta-analysis
            • Article
            • Peer Reviewed
            UC Davis Previously Published Works (2022)
            Aim: We investigated the effect of ataluren plus standard of care (SoC) on age at loss of ambulation (LoA) and respiratory decline in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD) versus patients with DMD on SoC alone. Patients & methods: Study 019 was a long-term Phase III study of ataluren safety in nmDMD patients with a history of ataluren exposure. Propensity score matching identified Study 019 and CINRG DNHS patients similar in disease progression predictors. Results & conclusion: Ataluren plus SoC was associated with a 2.2-year delay in age at LoA (p = 0.0006), and a 3.0-year delay in decline of predicted forced vital capacity to <60% in nonambulatory patients (p = 0.0004), versus SoC. Ataluren plus SoC delays disease progression and benefits ambulatory and nonambulatory patients with nmDMD. ClinicalTrials.gov registration: NCT01557400.
              Cover page: Ataluren delays loss of ambulation and respiratory decline in nonsense mutation Duchenne muscular dystrophy patients.
              • Article
              • Peer Reviewed
              LBL Publications (2022)
              Processed foods often include food additives such as xanthan gum, a complex polysaccharide with unique rheological properties, that has established widespread use as a stabilizer and thickening agent. Xanthan gums chemical structure is distinct from those of host and dietary polysaccharides that are more commonly expected to transit the gastrointestinal tract, and little is known about its direct interaction with the gut microbiota, which plays a central role in digestion of other dietary fibre polysaccharides. Here we show that the ability to digest xanthan gum is common in human gut microbiomes from industrialized countries and appears contingent on a single uncultured bacterium in the family Ruminococcaceae. Our data reveal that this primary degrader cleaves the xanthan gum backbone before processing the released oligosaccharides using additional enzymes. Some individuals harbour Bacteroides intestinalis that is incapable of consuming polymeric xanthan gum but grows on oligosaccharide products generated by the Ruminococcaceae. Feeding xanthan gum to germfree mice colonized with a human microbiota containing the uncultured Ruminococcaceae supports the idea that the additive xanthan gum can drive expansion of the primary degrader Ruminococcaceae, along with exogenously introduced B. intestinalis. Our work demonstrates the existence of a potential xanthan gum food chain involving at least two members of different phyla of gut bacteria and provides an initial framework for understanding how widespread consumption of a recently introduced food additive influences human microbiomes.
                Cover page: Mechanistic insights into consumption of the food additive xanthan gum by the human gut microbiota.
                • Article
                • Peer Reviewed
                UC Davis Previously Published Works (2021)
                Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi-signaling networks across cells and cell types, with important implications to understand and treat diseases such as cancer. These technologies are, however, limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organized the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry dataset, covering 36 markers in over 4,000 conditions totaling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time-course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data.
                  Cover page: Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd
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