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Open Access Publications from the University of California
Cover page of Effective one-particle energies from generalized Kohn–Sham random phase approximation: A direct approach for computing and analyzing core ionization energies

Effective one-particle energies from generalized Kohn–Sham random phase approximation: A direct approach for computing and analyzing core ionization energies

(2019)

Generalized-Kohn-Sham (GKS) orbital energies obtained self-consistently from the random phase approximation energy functional with semicanonical projection (spRPA) were recently shown to rival the accuracy of GW quasiparticle energies for valence ionization potentials. Here we extend the scope of GKS-spRPA correlated one-particle energies from frontier-orbital ionization to core orbital ionization energies, which are notoriously difficult for GW and other response methods due to strong orbital relaxation effects. For a benchmark consisting of 15 1s core electron binding energies (CEBEs) of second-row elements, chemical shifts estimated from GKS-spRPA one-particle energies yield mean absolute deviations from experiment of 0.2 eV, which is significantly more accurate than standard GW and comparable to ∆ self-consistent field theory without semi-empirical adjustment of the energy functional. For small ammonia clusters and cytosine tautomers, GKS-spRPA based chemical shifts capture subtle variations in covalent and non-covalent bonding environments; GKS-spRPA 1s CEBEs for these systems agree with equation-of-motion coupled cluster singles and doubles and ADC(4) results within 0.2-0.3 eV. Two perturbative approximations to GKS-spRPA orbital energies, which reduce the scaling from O(N⁶) to O(N⁵) and O(N⁴) are introduced and tested. We illustrate the application of GKS-spRPA orbital energies to larger systems by using oxygen 1s CEBEs to probe solvation and packing effects in condensed phases of water. GKS-spRPA predicts a lowering of the oxygen 1s CEBE of approximately 1.6-1.7 eV in solid and liquid phases, consistent with liquid-jet XPS and gas phase cluster experiments. The results are rationalized by partitioning GKS-spRPA electron binding energies into static, relaxation, and correlation parts.

Cover page of Medication safety alert fatigue may be reduced via interaction design and clinical role tailoring: a systematic review.

Medication safety alert fatigue may be reduced via interaction design and clinical role tailoring: a systematic review.

(2019)

OBJECTIVE:Alert fatigue limits the effectiveness of medication safety alerts, a type of computerized clinical decision support (CDS). Researchers have suggested alternative interactive designs, as well as tailoring alerts to clinical roles. As examples, alerts may be tiered to convey risk, and certain alerts may be sent to pharmacists. We aimed to evaluate which variants elicit less alert fatigue. MATERIALS AND METHODS:We searched for articles published between 2007 and 2017 using the PubMed, Embase, CINAHL, and Cochrane databases. We included articles documenting peer-reviewed empirical research that described the interactive design of a CDS system, to which clinical role it was presented, and how often prescribers accepted the resultant advice. Next, we compared the acceptance rates of conventional CDS-presenting prescribers with interruptive modal dialogs (ie, "pop-ups")-with alternative designs, such as role-tailored alerts. RESULTS:Of 1011 articles returned by the search, we included 39. We found different methods for measuring acceptance rates; these produced incomparable results. The most common type of CDS-in which modals interrupted prescribers-was accepted the least often. Tiering by risk, providing shortcuts for common corrections, requiring a reason to override, and tailoring CDS to match the roles of pharmacists and prescribers were the most common alternatives. Only 1 alternative appeared to increase prescriber acceptance: role tailoring. Possible reasons include the importance of etiquette in delivering advice, the cognitive benefits of delegation, and the difficulties of computing "relevance." CONCLUSIONS:Alert fatigue may be mitigated by redesigning the interactive behavior of CDS and tailoring CDS to clinical roles. Further research is needed to develop alternative designs, and to standardize measurement methods to enable meta-analyses.

Cover page of Design and Outcomes of a Community Trial to Increase Pap Testing in Pacific Islander Women.

Design and Outcomes of a Community Trial to Increase Pap Testing in Pacific Islander Women.

(2019)

BACKGROUND:Pap tests remain an essential cervical cancer detection method in the U.S., yet they are underutilized among Pacific Islanders (PIs) who experience elevated cervical cancer incidence and mortality. This study describes the design, methods, participants, and outcomes of a multi-year (2010-2016), community-based randomized intervention trial in southern California. Based upon strong collectivistic norms, the trial tested the efficacy of a unique social support intervention targeting Chamorro, Samoan and Tongan women and their male husbands/partners. METHODS:A single-session educational intervention was designed and tailored for ethnic- and gender-specific groups to increase men's social support for their female wives/partners to receive a Pap test, and for women to receive a Pap test. The comparison group received pre-existing brochures on Pap testing (for women) or general men's health (for men). Pre-test and six-month follow-up data were analyzed. RESULTS:Intervention and comparison groups were mostly equivalent on pre-test demographics and outcome variables. Intervention women who were not compliant with Pap screening recommendations at pre-test were significantly more likely to have scheduled and received a Pap test at six-month follow-up. However, six-month follow-up results indicated no intervention effect on changes in women's Pap testing knowledge, fatalistic attitudes, or perceived social support from their male partner. CONCLUSIONS:Ethnic- and gender-tailored community interventions can successfully increase Pap test behaviors for PI women, although more research is needed on the specific pathways leading to behavior change. IMPACT:Collaborative community-based interventions lead to increases in women's cancer prevention and early detection for Pacific Islander and other collectivistic communities.

Cover page of Neuroimaging Biomarkers for Alzheimer's Disease.

Neuroimaging Biomarkers for Alzheimer's Disease.

(2019)

Currently, over five million Americans suffer with Alzheimer's disease (AD). In the absence of a cure, this number could increase to 13.8 million by 2050. A critical goal of biomedical research is to establish indicators of AD during the preclinical stage (i.e. biomarkers) allowing for early diagnosis and intervention. Numerous advances have been made in developing biomarkers for AD using neuroimaging approaches. These approaches offer tremendous versatility in terms of targeting distinct age-related and pathophysiological mechanisms such as structural decline (e.g. volumetry, cortical thinning), functional decline (e.g. fMRI activity, network correlations), connectivity decline (e.g. diffusion anisotropy), and pathological aggregates (e.g. amyloid and tau PET). In this review, we survey the state of the literature on neuroimaging approaches to developing novel biomarkers for the amnestic form of AD, with an emphasis on combining approaches into multimodal biomarkers. We also discuss emerging methods including imaging epigenetics, neuroinflammation, and synaptic integrity using PET tracers. Finally, we review the complementary information that neuroimaging biomarkers provide, which highlights the potential utility of composite biomarkers as suitable outcome measures for proof-of-concept clinical trials with experimental therapeutics.

Cover page of Phylogenetic conservation of bacterial responses to soil nitrogen addition across continents.

Phylogenetic conservation of bacterial responses to soil nitrogen addition across continents.

(2019)

Soil microbial communities are intricately linked to ecosystem functioning such as nutrient cycling; therefore, a predictive understanding of how these communities respond to environmental changes is of great interest. Here, we test whether phylogenetic information can predict the response of bacterial taxa to nitrogen (N) addition. We analyze the composition of soil bacterial communities in 13 field experiments across 5 continents and find that the N response of bacteria is phylogenetically conserved at each location. Remarkably, the phylogenetic pattern of N responses is similar when merging data across locations. Thus, we can identify bacterial clades - the size of which are highly variable across the bacterial tree - that respond consistently to N addition across locations. Our findings suggest that a phylogenetic approach may be useful in predicting shifts in microbial community composition in the face of other environmental changes.

Cover page of Mechanisms and competition of halide substitution and hydrolysis in reactions of N2O5 with seawater.

Mechanisms and competition of halide substitution and hydrolysis in reactions of N2O5 with seawater.

(2019)

SN2-type halide substitution and hydrolysis are two of the most ubiquitous reactions in chemistry. The interplay between these processes is fundamental in atmospheric chemistry through reactions of N2O5 and seawater. N2O5 plays a major role in regulating levels of O3, OH, NO x , and CH4. While the reactions of N2O5 and seawater are of central importance, little is known about their mechanisms. Of interest is the activation of Cl in seawater by the formation of gaseous ClNO2, which occurs despite the fact that hydrolysis (to HNO3) is energetically more favorable. We determine key features of the reaction landscape that account for this behavior in a theoretical study of the cluster N2O5/Cl-/H2O. This was carried out using ab initio molecular dynamics to determine reaction pathways, structures, and time scales. While hydrolysis of N2O5 occurs in the absence of Cl-, results here reveal that a low-lying pathway featuring halide substitution intermediates enhances hydrolysis.

Cover page of Znf703 is a novel RA target in the neural plate border.

Znf703 is a novel RA target in the neural plate border.

(2019)

Znf703 is an RAR- and Wnt-inducible transcription factor that exhibits a complex expression pattern in the developing embryo: Znf703 mRNA is found in the early circumblastoporal ring, then later throughout the neural plate and its border, and subsequently in the mid/hindbrain and somites. We show that Znf703 has a different and separable function in early mesoderm versus neural crest and placode development. Independent of its early knockdown phenotype on Gdf3 and Wnt8, Znf703 disrupts patterning of distinct neural crest migratory streams normally delineated by Sox10, Twist, and Foxd3 and inhibits otocyst formation and otic expression of Sox10 and Eya1. Furthermore, Znf703 promotes massive overgrowth of SOX2+ cells, disrupting the SoxB1 balance at the neural plate border. Despite prominent expression in other neural plate border-derived cranial and sensory domains, Znf703 is selectively absent from the otocyst, suggesting that Znf703 must be specifically cleared or down-regulated for proper otic development. We show that mutation of the putative Groucho-repression domain does not ameliorate Znf703 effects on mesoderm, neural crest, and placodes. We instead provide evidence that Znf703 requires the Buttonhead domain for transcriptional repression.

Cover page of A breast cancer case-control study of polybrominated diphenyl ether (PBDE) serum levels among California women.

A breast cancer case-control study of polybrominated diphenyl ether (PBDE) serum levels among California women.

(2019)

PURPOSE:Polybrominated diphenyl ethers (PBDEs) are among the most persistent and pervasive global environmental contaminants. Their toxic and endocrine-disrupting properties have made them a focus of concern for breast cancer. Our objective was to evaluate the risk of breast cancer associated with serum PBDE levels in a case-control study nested within the California Teachers Study. METHODS:Participants were 902 women with invasive breast cancer (cases) and 936 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed between 2011 and 2015. Blood samples were collected from cases an average of 35 months after diagnosis. PBDEs were measured in serum using automated solid phase extraction and gas chromatography/high resolution mass spectrometry. Statistical analyses were restricted to the three congeners with detection frequencies ≥75%: 2,2',4,4'-tetrabromodiphenyl ether (BDE-47), 2,2',4,4',6-pentabromodiphenyl ether (BDE-100), and 2,2',4,4',5,5'-hexabromodiphenyl ether (BDE-153). Unconditional logistic regression was used to estimate multivariable-adjusted odds ratios (ORs) and their 95% confidence intervals (CI) for each BDE congener, adjusting for serum lipids and other potential confounders. RESULTS:The OR for each of the three BDE congeners was close to unity with a CI that included one. Analyses stratified by menopausal status, tumor hormone responsiveness, BMI, and changes in body weight yielded similarly null results. CONCLUSIONS:Our findings provide no evidence that serum levels of BDE-47, BDE-100 or BDE-153 are associated with breast cancer risk. These results should be interpreted in the context of study limitations which include the reliance on PBDE measurements that may not represent pre-diagnostic, early-life or chronic exposures and a lack of information on genetic polymorphisms and other factors which may affect endogenous estrogen levels.

Cover page of Cell lineage and communication network inference via optimization for single-cell transcriptomics.

Cell lineage and communication network inference via optimization for single-cell transcriptomics.

(2019)

The use of single-cell transcriptomics has become a major approach to delineate cell subpopulations and the transitions between them. While various computational tools using different mathematical methods have been developed to infer clusters, marker genes, and cell lineage, none yet integrate these within a mathematical framework to perform multiple tasks coherently. Such coherence is critical for the inference of cell-cell communication, a major remaining challenge. Here, we present similarity matrix-based optimization for single-cell data analysis (SoptSC), in which unsupervised clustering, pseudotemporal ordering, lineage inference, and marker gene identification are inferred via a structured cell-to-cell similarity matrix. SoptSC then predicts cell-cell communication networks, enabling reconstruction of complex cell lineages that include feedback or feedforward interactions. Application of SoptSC to early embryonic development, epidermal regeneration, and hematopoiesis demonstrates robust identification of subpopulations, lineage relationships, and pseudotime, and prediction of pathway-specific cell communication patterns regulating processes of development and differentiation.