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Open Access Publications from the University of California

Scholarly Works (10 results)

  • Article
  • Peer Reviewed
Recent Work (2000)

We illustrate data analytic concerns that arise in the context of relating “genotype”, as represented by amino acid sequence, to phenotypes (outcomes). The present application examines whether peptides that bind to a particular major histocompatibility complex (MHC) class I molecule have characteristic amino acid sequences. However, the concerns identified and addressed are considerably more general. It is recognized that simple rules for predicting binding based solely on preferences for specific amino acids in certain (anchor) positions of the peptide’s amino acid sequence are generally inadequate and that binding is potentially influenced by all sequence positions as well as between-position interactions. The desire to elucidate these more complex prediction rules has spawned various modeling attempts, the shortcomings of which provide motivation for the methods adopted here. Because of (i) this need to model between-position interactions, (ii) amino acids constituting a highly (20) multilevel unordered categorical covariate, and (iii) there frequently being numerous such covariates (i.e. positions) comprising the sequence standard regression/classification techniques are problematic due to the proliferation of indicator variables required for encoding the sequence position covariates and attendant interactions. These difficulties have led to analyses based on (continuous) properties (e.g. molecular weights) of the amino acids. However, there is potential information loss in such an approach if the properties used are incomplete and/or do not capture the mechanism underlying association with the phenotype. Here we demonstrate that handling unordered categorical covariates with numerous levels and accompanying interactions can be done effectively using classification trees and recently devised bump-hunting methods. We further tackle the question of whether observed associations are attributable to amino acid properties as well as addressing the assessment and implications of between-position covariation.

    Cover page: Relating amino acid sequence to phenotype: Analysis of peptide binding data
    • Article
    • Peer Reviewed
    UC San Francisco Previously Published Works (2022)

    Purpose

    To develop and compare tumor-control probability (TCP) models for single-fraction stereotactic radiosurgery (SRS) for brain metastasis (BMs) with and without retreatment.

    Methods and materials

    We developed three different schemas to model TCP of BMs treated with linear accelerator-based SRS. Dose to 99% of each planning target volume (PTV D99) and 6-month local control were fit using linear-quadratic-linear (LQ-L) models based on equivalent-dose conversions in 2 Gy (EQD2). The M1 schema had separate LQ-L TCP models for initial dose (M1-initial) and retreatment dose (M1-retreat), and the M2 schema had an LQ-L model using the sum of 50% of the initial SRS dose plus the retreatment SRS dose. The M1-initial and M1-retreat schema modeled local control after first SRS to 48 lesions (patients = 22) and second SRS to 46 lesions (patients = 21). The M0 schema included a whole data set of 349 lesions (patients = 136) receiving first SRS (no retreatment and M1-initial).

    Results

    LQ-L models fitted the data well (χ2 = 0.059-0.525 and P = 0.999-1.000). For M0 and M1-retreat, the fitted models EQD250 and γ50 parameters were similar. The LQ-L fitted EQD250 was ∼8.0 Gy for M0 and M1-retreat, ∼24 Gy for M1-initial, and ∼19 Gy for M2. The model fitted γ50 was 0.1 Gy for M0, M1-retreat, and M2 and 0.5 for M1-initial. For the PTV D99 of 10 and 20 Gy, the steepest to shallowest dose-response or largest change in TCP, that is, TCP20Gy - TCP10Gy, was observed in M1-initial (0.49) and M2 (0.17). M0 and M1-retreat showed a similar change in TCP of 0.21.

    Conclusions

    The model-fitted parameters predicted the recurrent BMs required a higher threshold dose and had a steeper dose-response for first SRS versus second SRS and M0. Alternatively, the recurrent BMs required ∼2 Gy higher predicted PTV D99 dose for first SRS to achieve the same TCP of 0.75 compared with second SRS and M0. Further investigations on larger patient cohorts are needed for validating our findings in predictive modeling of recurrent BMs.
      Creative Commons 'BY' version 4.0 license
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2024)
      Radiotherapy, a crucial technique in cancer therapy, has traditionally relied on the premise of largely unchanging patient anatomy during the treatment course and encompassing uncertainties by target margins. This review introduces adaptive radiotherapy (ART), a notable innovation that addresses anatomy changes and optimizes the therapeutic ratio. ART utilizes advanced imaging techniques such as CT, MRI, and PET to modify the treatment plan based on observed anatomical changes and even biological changes during the course of treatment. The narrative review provides a comprehensive guide on ART for healthcare professionals and trainees in radiation oncology and anyone else interested in the topic. The incorporation of artificial intelligence in ART has played a crucial role in improving effectiveness, particularly in contour segmentation, treatment planning, and quality assurance. This has expedited the process to render online ART feasible, lowered the burden for radiation oncology practitioners, and enhanced the precision of dynamically personalized treatment. Current technical and clinical progress on ART is discussed in this review, highlighting the ongoing development of imaging technologies and AI and emphasizing their contribution to enhancing the applicability and effectiveness of ART.
        Cover page: Adaptive Radiotherapy: Next-Generation Radiotherapy.
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2021)
        Sales data in China indicate that slim cigarette consumption has increased dramatically over the last few years. This study examined who smoked slim cigarettes and the reasons for adopting these new products. A survey of an online panel from 19 Chinese cities was conducted from October 2018 to April 2019 with 20,055 members aged 16 and older. Among the 31.7% [95% confidence interval (CI) = 30.1-33.4] of panel members who reported currently smoking, 37.7% (95% CI = 34.8-40.5) smoked slim cigarettes. Among smokers, women were significantly more likely to smoke slim cigarettes than men [56.5% (95% CI = 50.8-62.2) vs. 35.5% (95% CI = 32.8-38.1)]. Smokers with a bachelor's degree were more likely to smoke slim cigarettes than those without [41.3% (95% CI = 38.1-44.4) vs. 33.1% (95% CI = 30.0-36.1)]. Most slim cigarette smokers were dual smokers [77.7% (95% CI = 75.3-80.1)], smoking both regular and slim cigarettes. Among dual smokers, 97.5% (95% CI = 96.7-98.3) started smoking regular cigarettes before slim cigarettes. Of the many reasons given for smoking slim cigarettes, 37.0% (95% CI = 34.3-39.7) directly related to harm reduction with another 10.1% (95% CI = 8.4-11.7) reporting their reason as wanting "to reduce consumption of regular cigarettes," a plausible indication of harm reduction. These findings suggest strong interest in harm reduction among the current Chinese smoking population and that the popularity of slim cigarettes is likely to increase, with the more educated as the early adopters. Given the absence of any evidence that these products actually reduce harm, it is urgent that the public health community be on high alert in order to avoid repeating the sad history of low-tar cigarettes, when a supposed harm-reduction product misled the field of tobacco control.
          • Article
          • Peer Reviewed
          UC Santa Barbara Previously Published Works (2013)
          Mineralogical, chemical, and Li and Nd isotopic compositions of two drill cores (8-9m deep) through bauxites developed on the Miocene Columbia River Basalts document the changes associated with basalt weathering, provide insights into the processes involved, and allow us to examine the overall influence of chemical weathering on juvenile (basaltic) crust. Gibbsite, hematite, ±kaolinite, halloysite, goethite, and maghemite are the weathering products in the bauxites. Quartz is observed near the tops of the cores and its abundance decreases progressively with depth; no quartz is observed below five meters depth in either core. Most major and trace elements, including "mobile" and some "immobile" elements are severely depleted in the bauxites. Niobium is less mobile relative to the rare earth elements, thus chemical weathering attenuates the negative Nb anomaly in the continental crust. Li and Nd are strongly depleted relative to fresh basalt, and both increase systematically towards the surface in the quartz-bearing samples while δ7Li and εNd values decrease systematically towards the surface in these same samples. Both Li and Nd were likely lost from the bauxites through leaching. The systematic enrichment of Li, Nd, and quartz, as well as the less radiogenic Nd isotopic composition at the tops of both profiles reflects 20-60wt.% addition of an eolian component to the soils. The eolian dust is unlikely to have experienced significant post-depositional weathering due to the relatively high Li contents near the tops of the profiles, and, therefore, the low δ7Li and εNd values suggest that the dust came from an old, weathered region of the continent. Our results demonstrate that lithium isotopes are sensitive tracers of chemical weathering, particularly in extreme weathering settings, and support the hypothesis that chemical weathering influences the mass and composition of the continental crust. © 2013 Elsevier Ltd.
            Cover page: Influence of chemical weathering on the composition of the continental crust: Insights from Li and Nd isotopes in bauxite profiles developed on Columbia River Basalts
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2021)

            Background

            California Proposition 56 increased cigarette excise tax by $2 per pack with equivalent increases on non-cigarette tobacco products. We estimated the changes in cigarette price, cigarette use, and non-cigarette use following the implementation of Proposition 56 in California in 2017.

            Methods

            Seven waves of Tobacco Use Supplements to the Current Population Survey (TUS-CPS) 2011-2019 data were used to obtain state-level aggregate self-reported outcomes, including cigarette price per pack, current and daily cigarette use, cigarette consumption per day, and current and daily use of non-cigarette tobacco products (hookah, pipe, cigar, and smokeless tobacco). A modified version of a synthetic control method was used to create a "synthetic" California that best resembled pre-policy sociodemographic characteristics and outcome trends in California while correcting time-invariant pre-policy differences. Various sensitivity analyses were also conducted.

            Results

            The implementation of Proposition 56 was associated with an increase in self-reported cigarette price per pack in California ($1.844, 95%CI: $0.153, $3.534; p = 0.032). No evidence suggested that Proposition 56 was associated with the changes in the prevalence of current or daily cigarette use, cigarette consumption per day, or the prevalence of current or daily use of non-cigarette tobacco products.

            Conclusion

            Most of the cigarette tax increase following Proposition 56 in California was passed on to consumers. There is a lack of evidence that the implementation of Proposition 56 was associated with the changes in the use of cigarettes and other tobacco products such as hookah, pipe, cigar, and smokeless tobacco.
              Cover page: Tobacco price and use following California Proposition 56 tobacco tax increase
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2019)
              BEAGLE is a high-performance likelihood-calculation library for phylogenetic inference. The BEAGLE library defines a simple, but flexible, application programming interface (API), and includes a collection of efficient implementations for calculation under a variety of evolutionary models on different hardware devices. The library has been integrated into recent versions of popular phylogenetics software packages including BEAST and MrBayes and has been widely used across a diverse range of evolutionary studies. Here, we present BEAGLE 3 with new parallel implementations, increased performance for challenging data sets, improved scalability, and better usability. We have added new OpenCL and central processing unit-threaded implementations to the library, allowing the effective utilization of a wider range of modern hardware. Further, we have extended the API and library to support concurrent computation of independent partial likelihood arrays, for increased performance of nucleotide-model analyses with greater flexibility of data partitioning. For better scalability and usability, we have improved how phylogenetic software packages use BEAGLE in multi-GPU (graphics processing unit) and cluster environments, and introduced an automated method to select the fastest device given the data set, evolutionary model, and hardware. For application developers who wish to integrate the library, we also have developed an online tutorial. To evaluate the effect of the improvements, we ran a variety of benchmarks on state-of-the-art hardware. For a partitioned exemplar analysis, we observe run-time performance improvements as high as 5.9-fold over our previous GPU implementation. BEAGLE 3 is free, open-source software licensed under the Lesser GPL and available at https://beagle-dev.github.io.
                Cover page: BEAGLE 3: Improved Performance, Scaling, and Usability for a High-Performance Computing Library for Statistical Phylogenetics
                • Article
                • Peer Reviewed
                UC Irvine Previously Published Works (2011)
                  Cover page: Organization of a US County System for Acute Stroke CareCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2012)
                  Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software.
                    Cover page: BEAGLE: An Application Programming Interface and High-Performance Computing Library for Statistical Phylogenetics
                    • Article
                    • Peer Reviewed
                    ICTS Publications (2012)
                    BACKGROUND AND PURPOSE

                    Organized systems of care have the potential to improve acute stroke care delivery. The current report describes the experience of implementing a countywide system of spoke-and-hub Stroke Neurology Receiving Centers (SNRC) that incorporated several comprehensive stroke center recommendations.

                    METHODS

                    Observational study of patients with suspected stroke <5 hours duration transported by Emergency Medical System personnel to an SNRC during the first year of this system.

                    RESULTS

                    A total of 1,360 patients with suspected stroke were evaluated at 9 hub SNRCs, of which 553 (40.7%) had a discharge diagnosis of ischemic stroke. Of these 553, intravenous (IV) tPA was given to 110 patients (19.9% of ischemic strokes). Care at the 6 neurointerventional-ready SNRC was a major focus, where 25.1% (99/395) of the patients with ischemic stroke received acute IV or intraarterial reperfusion therapy, and where provision of such therapies was less common with milder stroke, higher age, and Hispanic origin. The door-to-needle time for IV tPA met the <60 minute target in only 25% of patients and was 37% longer (p=0.0001) when SNRCs were neurointerventional-ready.

                    CONCLUSIONS

                    A stroke system that incorporates features of comprehensive stroke centers can be effectively implemented, and with substantial rates of acute reperfusion therapy administration. Experiences potentially useful to broader implementation of comprehensive stroke centers are considered.

                      Cover page: Organization of a U.S. County System for Comprehensive Acute Stroke Care
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