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1.  Racial/ethnic disparities in hepatocellular carcinoma treatment and survival in California, 1988-2012 
World Journal of Gastroenterology  2016;22(38):8584-8595.
To describe racial/ethnic differences in treatment and survival among liver cancer patients in a population-based cancer registry.
Invasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White (White, n = 12710), Hispanic (n = 8500), Chinese (n = 2723), non-Hispanic Black (Black, n = 2609), Vietnamese (n = 2063), Filipino (n = 1479), Korean (n = 1099), Japanese (n = 658), American Indian/Alaskan Native (AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian (n = 233), South Asian (n = 190), Hawai`ian/Pacific Islander (n = 172), Thai (n = 95), and Other Asian (n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause mortality.
After adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio (OR) = 0.30, 95%CI: 0.17-0.53], Cambodian (OR = 0.65, 95%CI: 0.45-0.96), AIAN (OR = 0.66, 95%CI: 0.46-0.93), Black (OR = 0.76, 95%CI: 0.67-0.86), and Hispanic (OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese (OR = 1.58, 95%CI: 1.42-1.77), Koreans (OR = 1.45, 95%CI: 1.24-1.70), Japanese (OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese (OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio (HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians (HR = 1.35, 95%CI: 1.16-1.58), and Blacks (HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese (HR = 0.82, 95%CI: 0.77-0.86), Filipinos (HR = 0.84, 95%CI: 0.78-0.90), Vietnamese (HR = 0.85, 95%CI: 0.80-0.90), Koreans (HR = 0.90, 95%CI: 0.83-0.97), and Hispanics (HR = 0.91, 95%CI: 0.88-0.94); results were similar for all-cause mortality.
Disaggregated data revealed substantial racial/ethnic differences in liver cancer treatment and survival, demonstrating the need for development of targeted interventions to mitigate disparities.
PMCID: PMC5064040  PMID: 27784971
Disparities; Treatment; Survival; Liver cancer; Hepatocellular carcinoma
2.  Effect of herd size on subclinical infection of swine in Vietnam with influenza A viruses 
BMC Veterinary Research  2016;12:227.
Influenza A viruses of swine (IAV-S) cause acute and subclinical respiratory disease. To increase our understanding of the etiology of the subclinical form and thus help prevent the persistence of IAV-S in pig populations, we conducted active virologic surveillance in Vietnam, the second-largest pig-producing country in Asia, from February 2010 to December 2013.
From a total of 7034 nasal swabs collected from clinically healthy pigs at 250 farms and 10 slaughterhouses, we isolated 172 IAV-S from swine at the weaning and early-fattening stages. The isolation rate of IAV-S was significantly higher among pigs aged 3 weeks to 4.5 months than in older and younger animals. IAV-S were isolated from 16 large, corporate farms and 6 family-operated farms from among the 250 farms evaluated. Multivariate logistic regression analysis revealed that “having more than 1,000 pigs” was the most influential risk factor for IAV-S positivity. Farms affected by reassortant IAV-S had significantly larger pig populations than did those where A(H1N1)pdm09 viruses were isolated, thus suggesting that large, corporate farms serve as sites of reassortment events.
We demonstrate the asymptomatic circulation of IAV-S in the Vietnamese pig population. Raising a large number of pigs on a farm has the strongest impact on the incidence of subclinical IAV-S infection. Given that only some of the corporate farms surveyed were IAV-S positive, further active monitoring is necessary to identify additional risk factors important in subclinical infection of pigs with IAV-S in Vietnam.
Electronic supplementary material
The online version of this article (doi:10.1186/s12917-016-0844-z) contains supplementary material, which is available to authorized users.
PMCID: PMC5057248  PMID: 27724934
Active surveillance; Influenza A virus; Pig; Pig farm; Vietnam
3.  Cluster-Randomized Trial to Increase Hepatitis B Testing among Koreans in Los Angeles 
In the United States, Korean immigrants experience a disproportionately high burden of chronic hepatitis B (HBV) viral infection and associated liver cancer compared to the general population. However, despite clear clinical guidelines, HBV serologic testing among Koreans remains persistently sub-optimal.
We conducted a cluster-randomized trial to evaluate a church-based small group intervention to improve HBV testing among Koreans in Los Angeles. Fifty-two Korean churches, stratified by size (small, medium, large) and location (Koreatown versus other), were randomized to intervention or control conditions. Intervention church participants attended a single-session small-group discussion on liver cancer and HBV testing and control church participants attended a similar session on physical activity and nutrition. Outcome data consisted of self-reported HBV testing obtained via 6-month telephone follow-up interviews.
We recruited 1123 individuals, 18-64 years of age, across the 52 churches. Ninety-two percent of the sample attended the assigned intervention session and 86% completed the 6-month follow-up. Sample characteristics included: mean age 46 years, 65% female, 97% born in Korea, 69% completed some college, and 43% insured. In an intent-to-treat analysis, the intervention produced a statistically significant effect (OR = 4.9, p < .001), with 19% of intervention and 6% of control group participants reporting a HBV test.
Our intervention was successful in achieving a large and robust effect in a population at high risk of HBV infection and sequelae.
The intervention was fairly resource efficient and thus has high potential for replication in other high-risk Asian groups.
PMCID: PMC4560609  PMID: 26104909
HBV Testing; Koreans; Randomized Trial
4.  A Social Network Family-Focused Intervention to Promote Smoking Cessation in Chinese and Vietnamese American Male Smokers: A Feasibility Study 
Nicotine & Tobacco Research  2015;17(8):1029-1038.
Smoking prevalence is high among limited English-proficient Chinese and Vietnamese American men, who are frequently unmotivated to quit and who underutilize smoking cessation resources. This study applied lay health worker outreach to leverage peer and family networks to promote smoking cessation among these men.
We integrated qualitative formative research findings and Social Network Theory to develop a social-network family-focused intervention. In a pilot single-group trial, 15 lay health workers recruited 96 dyads (N = 192, 75% Vietnamese) of Chinese or Vietnamese male daily smokers and their family members and delivered the intervention consisting of two small group education sessions and two individual telephone calls over 2 months.
At baseline, 42% of smokers were at precontemplation. At 3 months following the initiation of the intervention, 7-day and 30-day point prevalence smoking abstinence rates as reported by smokers and independently corroborated by family members were 30% and 24%, respectively. Utilization of smoking cessation resources (medication, quitline, physician’s advice) increased from 2% to 60% (P < .001). Findings showed high acceptability of the intervention as it facilitated learning about tobacco-related health risks and cessation resources, and communications between smokers and their families.
This novel social network family-focused intervention to promote smoking cessation among Chinese and Vietnamese smokers appears to be acceptable, feasible, and potentially efficacious. Findings warrant evaluation of long-term efficacy of the intervention in a larger scale randomized controlled trial.
PMCID: PMC4542845  PMID: 26180229
5.  Clade-level Spatial Modelling of HPAI H5N1 Dynamics in the Mekong Region Reveals New Patterns and Associations with Agro-Ecological Factors 
Scientific Reports  2016;6:30316.
The highly pathogenic avian influenza (HPAI) H5N1 virus has been circulating in Asia since 2003 and diversified into several genetic lineages, or clades. Although the spatial distribution of its outbreaks was extensively studied, differences in clades were never previously taken into account. We developed models to quantify associations over time and space between different HPAI H5N1 viruses from clade 1, 2.3.4 and 2.3.2 and agro-ecological factors. We found that the distribution of clades in the Mekong region from 2004 to 2013 was strongly regionalised, defining specific epidemiological zones, or epizones. Clade 1 became entrenched in the Mekong Delta and was not supplanted by newer clades, in association with a relatively higher presence of domestic ducks. In contrast, two new clades were introduced (2.3.4 and 2.3.2) in northern Viet Nam and were associated with higher chicken density and more intensive chicken production systems. We suggest that differences in poultry production systems in these different epizones may explain these associations, along with differences in introduction pressure from neighbouring countries. The different distribution patterns found at the clade level would not be otherwise apparent through analysis treating all outbreaks equally, which requires improved linking of disease outbreak records and genetic sequence data.
PMCID: PMC4958987  PMID: 27453195
6.  3D Mandibular Superimposition: Comparison of Regions of Reference for Voxel-Based Registration 
PLoS ONE  2016;11(6):e0157625.
The aim was to evaluate three regions of reference (Björk, Modified Björk and mandibular Body) for mandibular registration testing them in a patients’ CBCT sample.
Mandibular 3D volumetric label maps were built from CBCTs taken before (T1) and after treatment (T2) in a sample of 16 growing subjects and labeled with eight landmarks. Registrations of T1 and T2 images relative to the different regions of reference were performed, and 3D surface models were generated. Seven mandibular dimensions were measured separately for each time-point (T1 and T2) in relation to a stable reference structure (lingual cortical of symphysis), and the T2-T1 differences were calculated. These differences were compared to differences measured between the superimposed T2 (generated from different regions of reference: Björk, Modified Björk and Mandibular Body) over T1 surface models. ICC and the Bland-Altman method tested the agreement of the changes obtained by nonsuperimposition measurements from the patients’ sample, and changes between the overlapped surfaces after registration using the different regions of reference.
The Björk region of reference (or mask) did work properly only in 2 of 16 patients. Evaluating the two other masks (Modified Björk and Mandibular body) on patients’ scans registration, the concordance and agreement of the changes obtained from superimpositions (registered T2 over T1) compared to results obtained from non superimposed T1 and T2 separately, indicated that Mandibular Body mask displayed more consistent results.
The mandibular body mask (mandible without teeth, alveolar bone, rami and condyles) is a reliable reference for 3D regional registration.
PMCID: PMC4919005  PMID: 27336366
7.  Incorporating 3-dimensional models in online articles 
The aims of this article were to introduce the capability to view and interact with 3-dimensional (3D) surface models in online publications, and to describe how to prepare surface models for such online 3D visualizations.
Three-dimensional image analysis methods include image acquisition, construction of surface models, registration in a common coordinate system, visualization of overlays, and quantification of changes. Cone-beam computed tomography scans were acquired as volumetric images that can be visualized as 3D projected images or used to construct polygonal meshes or surfaces of specific anatomic structures of interest. The anatomic structures of interest in the scans can be labeled with color (3D volumetric label maps), and then the scans are registered in a common coordinate system using a target region as the reference. The registered 3D volumetric label maps can be saved in .obj, .ply, .stl, or .vtk file formats and used for overlays, quantification of differences in each of the 3 planes of space, or color-coded graphic displays of 3D surface distances.
All registered 3D surface models in this study were saved in .vtk file format and loaded in the Elsevier 3D viewer. In this study, we describe possible ways to visualize the surface models constructed from cone-beam computed tomography images using 2D and 3D figures. The 3D surface models are available in the article’s online version for viewing and downloading using the reader’s software of choice. These 3D graphic displays are represented in the print version as 2D snapshots. Overlays and color-coded distance maps can be displayed using the reader’s software of choice, allowing graphic assessment of the location and direction of changes or morphologic differences relative to the structure of reference. The interpretation of 3D overlays and quantitative color-coded maps requires basic knowledge of 3D image analysis.
When submitting manuscripts, authors can now upload 3D models that will allow readers to interact with or download them. Such interaction with 3D models in online articles now will give readers and authors better understanding and visualization of the results.
PMCID: PMC4418234  PMID: 25925649
8.  The global antigenic diversity of swine influenza A viruses 
eLife  null;5:e12217.
Swine influenza presents a substantial disease burden for pig populations worldwide and poses a potential pandemic threat to humans. There is considerable diversity in both H1 and H3 influenza viruses circulating in swine due to the frequent introductions of viruses from humans and birds coupled with geographic segregation of global swine populations. Much of this diversity is characterized genetically but the antigenic diversity of these viruses is poorly understood. Critically, the antigenic diversity shapes the risk profile of swine influenza viruses in terms of their epizootic and pandemic potential. Here, using the most comprehensive set of swine influenza virus antigenic data compiled to date, we quantify the antigenic diversity of swine influenza viruses on a multi-continental scale. The substantial antigenic diversity of recently circulating viruses in different parts of the world adds complexity to the risk profiles for the movement of swine and the potential for swine-derived infections in humans.
eLife digest
Influenza viruses, commonly called flu, infect millions of people and animals every year and occasionally causes pandemics in humans. The immune system can neutralise flu viruses by recognising the proteins on the virus surface, generically referred to as antigens. These antigens change as flu viruses evolve to escape detection by the immune system. These changes tend to be relatively small such that exposure to one flu virus generates immunity that is still effective against other related flu viruses. However, over time, the accumulation of these small changes can result in larger differences such that prior infections no longer provide protection against the new virus.
Influenza A viruses infect a wide variety of birds and mammals. Viruses can also transmit from one species to another, which may result in the introduction of viruses with antigens that are new to the recipient species and which have the potential to cause substantial outbreaks. Pig flu viruses have long been considered to be a potential risk for human pandemic viruses and were the source of the 2009 pandemic H1N1 virus. Importantly, humans often transmit flu viruses to pigs. Understanding the dynamics and consequences of this two-way transmission is important for designing effective strategies to detect and respond to new strains of flu.
Influenza A viruses of the H1 and H3 subtypes circulate widely in pigs. However, it was poorly understood how closely related swine and human viruses circulating in different regions were to one another and how much the antigens varied between the different viruses.
Lewis, Russell et al. have now analysed the antigenic variation of hundreds of H1 and H3 viruses from pigs on multiple continents. The antigenic diversity of recent swine flu viruses resembles the diversity of H1 and H3 viruses observed in humans over the last 40 years. A key factor driving the diversity of the H1 and H3 viruses in pigs is the frequent introduction of human viruses to pigs. In contrast, only one flu virus from a bird had contributed to the observed antigenic diversity in pigs in a substantial way.
Once in pigs, human-derived flu viruses continue to evolve their antigens. This results in a tremendous diversity of flu viruses that can be transmitted to other pigs and also to humans. These flu viruses could pose a serious risk to public health because they are no longer similar to the current human flu strains. These findings have important implications not only for developing flu vaccines for pigs but also for informing the development of more-effective surveillance and disease-control strategies to prevent the spread of new flu variants.
PMCID: PMC4846380  PMID: 27113719
influenza; swine; human; pandemic; Virus
9.  Computational schemes for the prediction and annotation of enhancers from epigenomic assays 
Identifying and annotating distal regulatory enhancers is critical to understand the mechanisms that control gene expression and cell-type-specific activities. Next-generation sequencing techniques have provided us an exciting toolkit of genome-wide assays that can be used to predict and annotate enhancers. However, each assay comes with its own specific set of analytical needs if enhancer prediction is to be optimal. Furthermore, integration of multiple genome-wide assays allows for different genomic features to be combined, and can improve predictive performance. Herein, we review the genome-wide assays and analysis schemes that are used to predict and annotate enhancers. In particular, we focus on three key computational topics: predicting enhancer locations, determining the cell-type-specific activity of enhancers, and linking enhancers to their target genes.
PMCID: PMC4778972  PMID: 25461775
Enhancer prediction; Epigenomics; Enhancer–gene linking; Enhancer activity; Epigenetics
10.  Assessment of HBV Preventive Services in a Medically Underserved Asian and Pacific Islander Population Using Provider and Patient Data 
Hepatitis B (HBV) represents a significant health disparity among medically underserved Asian and Hawaiian/Pacific Islander (API) populations. Studies evaluating adherence to HBV screening and vaccination guidelines in this population are limited.
The purpose of this study was to evaluate HBV screening and vaccination practices using both provider self-report and patient records.
Medical records for 20,574 API adults were reviewed retrospectively and primary care providers were surveyed to evaluate rates and adherence to HBV screening and vaccination guidelines.
The study included primary care providers and their adult API patients in the San Francisco safety-net healthcare system.
Main Measures
Patient, practice, and provider factors, as well as HBV screening and vaccination practices, were assessed using provider survey constructs and patient laboratory and clinical data. Generalized linear mixed models and multivariate logistic regression analyses were used to identify factors associated with recommended HBV screening and vaccination.
Key Results
The mean age of patients was 52 years, and 63.4 % of patients were female. Only 61.5 % underwent HBV testing, and 47.4 % of HBV-susceptible patients were vaccinated. Of 148 (44.8 %) responding providers, most were knowledgeable and had a favorable attitude towards screening, but 43.2 % were unfamiliar with HBV guidelines. HBV screening was positively associated with favorable provider attitude score (OR per unit 1.80, 95 % CI 1.18–2.74) and negatively associated with female patient sex (OR 0.82, 95 % CI 0.73–0.92), a higher number of clinic patients per week (OR per 20 patients 0.46, 95 % CI 0.28–0.76), and provider barrier score (OR per unit 0.45, 95 % CI 0.24–0.87). HBV vaccination was negatively associated with provider barrier score (OR per unit 0.48, 95 % CI 0.25–0.91).
Rates of HBV screening and vaccination of API patients in this safety-net system are suboptimal, and provider factors play a significant role. Efforts to cultivate positive attitudes among providers and expand healthcare system resources to reduce provider barriers to HBV care are warranted.
PMCID: PMC4284271  PMID: 25324148
HBV screening; HBV vaccination; HBV prevention; Safety net; Asians
11.  Disruption of Germination and Seedling Development in Brassica napus by Mutations Causing Severe Seed Hormonal Imbalance 
The Brassica napus (oilseed rape) accession 1012-98 shows a disturbed germination phenotype that was thought to be associated with its lack of testa pigmentation and thin seed coat. Here, we demonstrate that the disturbed germination and seedling development are actually due to independent mutations that disrupt the balance of hormone metabolites and their regulators in the seeds. High-throughput UPLC-MS/MS hormone profiling of seeds and seedlings before and after germination revealed that 1012-98 has a severely disturbed hormone balance with extremely atypical, excessive quantities of auxin and ABA metabolites. The resulting hypersensitivity to abscisic acid (ABA) and a corresponding increase in dormancy often results in death of the embryo after imbibition or high frequencies of disturbed, often lethal developmental phenotypes, resembling Arabidopsis mutants for the auxin regulatory factor gene ARF10 or the auxin-overproducing transgenic line iaaM-OX. Molecular cloning of Brassica ARF10 orthologs revealed four loci in normal B. napus, two derived from the Brassica A genome and two from the C genome. On the other hand, the phenotypic mutant 1012-98 exhibited amplification of C-genome BnaC.ARF10 copy number along with a chimeric allele originating from recombination between homeologous A and C genome loci which lead to minor increase of Bna.ARF10 transcription on the critical timepoint for seed germination, the indirect regulator of ABI3, the germinative inhibitor. Bna.GH3.5 expression was upregulated to conjugate free auxin to IAA-asp between 2 and 6 DAS. Functional amino acid changes were also found in important DNA binding domains of one BnaC.ARF10 locus, suggesting that regulatory changes in Bna.ARF10 are collectively responsible for the observed phenotpyes in 1012-98. To our knowledge, this study is the first to report disruption of germination and seedling development in Brassica napus caused by the crosstalk of auxin-ABA and the corresponding regulators Bna.ARF10 and Bna.GH3.5.
PMCID: PMC4791391  PMID: 27014334
Brassica napus; oilseed rape; seeds; hormones; germination; vigor
12.  Emergence of Highly Pathogenic Avian Influenza A(H5N1) Virus PB1-F2 Variants and Their Virulence in BALB/c Mice 
Journal of Virology  2015;89(11):5835-5846.
Influenza A viruses (IAVs) express the PB1-F2 protein from an alternate reading frame within the PB1 gene segment. The roles of PB1-F2 are not well understood but appear to involve modulation of host cell responses. As shown in previous studies, we find that PB1-F2 proteins of mammalian IAVs frequently have premature stop codons that are expected to cause truncations of the protein, whereas avian IAVs usually express a full-length 90-amino-acid PB1-F2. However, in contrast to other avian IAVs, recent isolates of highly pathogenic H5N1 influenza viruses had a high proportion of PB1-F2 truncations (15% since 2010; 61% of isolates in 2013) due to several independent mutations that have persisted and expanded in circulating viruses. One natural H5N1 IAV containing a mutated PB1-F2 start codon (i.e., lacking ATG) was 1,000-fold more virulent for BALB/c mice than a closely related H5N1 containing intact PB1-F2. In vitro, we detected expression of an in-frame protein (C-terminal PB1-F2) from downstream ATGs in PB1-F2 plasmids lacking the well-conserved ATG start codon. Transient expression of full-length PB1-F2, truncated (24-amino-acid) PB1-F2, and PB1-F2 lacking the initiating ATG in mammalian and avian cells had no effect on cell apoptosis or interferon expression in human lung epithelial cells. Full-length and C-terminal PB1-F2 mutants colocalized with mitochondria in A549 cells. Close monitoring of alterations of PB1-F2 and their frequency in contemporary avian H5N1 viruses should continue, as such changes may be markers for mammalian virulence.
IMPORTANCE Although most avian influenza viruses are harmless for humans, some (such as highly pathogenic H5N1 avian influenza viruses) are capable of infecting humans and causing severe disease with a high mortality rate. A number of risk factors potentially associated with adaptation to mammalian infection have been noted. Here we demonstrate that the protein PB1-F2 is frequently truncated in recent isolates of highly pathogenic H5N1 viruses. Truncation of PB1-F2 has been proposed to act as an adaptation to mammalian infection. We show that some forms of truncation of PB1-F2 may be associated with increased virulence in mammals. Our data support the assessment of PB1-F2 truncations for genomic surveillance of influenza viruses.
PMCID: PMC4442455  PMID: 25787281
13.  Chitinase 3–like–1 and its receptors in Hermansky-Pudlak syndrome–associated lung disease 
The Journal of Clinical Investigation  2015;125(8):3178-3192.
Hermansky-Pudlak syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in patients with subtypes HPS-1 and HPS-4, which both result from defects in biogenesis of lysosome-related organelle complex 3 (BLOC-3). The prototypic chitinase-like protein chitinase 3–like–1 (CHI3L1) plays a protective role in the lung by ameliorating cell death and stimulating fibroproliferative repair. Here, we demonstrated that circulating CHI3L1 levels are higher in HPS patients with pulmonary fibrosis compared with those who remain fibrosis free, and that these levels associate with disease severity. Using murine HPS models, we also determined that these animals have a defect in the ability of CHI3L1 to inhibit epithelial apoptosis but exhibit exaggerated CHI3L1-driven fibroproliferation, which together promote HPS fibrosis. These divergent responses resulted from differences in the trafficking and effector functions of two CHI3L1 receptors. Specifically, the enhanced sensitivity to apoptosis was due to abnormal localization of IL-13Rα2 as a consequence of dysfunctional BLOC-3–dependent membrane trafficking. In contrast, the fibrosis was due to interactions between CHI3L1 and the receptor CRTH2, which trafficked normally in BLOC-3 mutant HPS. These data demonstrate that CHI3L1-dependent pathways exacerbate pulmonary fibrosis and suggest CHI3L1 as a potential biomarker for pulmonary fibrosis progression and severity in HPS.
PMCID: PMC4563747  PMID: 26121745
14.  3D Osteoarthritic Changes in TMJ Condylar Morphology Correlates with Specific Systemic and Local Biomarkers of Disease 
To assess 3D morphological variations and local and systemic biomarker profiles in subjects with a diagnosis of temporomandibular joint osteoarthritis (TMJ OA).
Twenty-eight patients with long-term TMJ OA (39.9 ± 16 years), 12 patients at initial diagnosis of OA (47.4 ± 16.1 years), and 12 healthy controls (41.8 ± 12.2 years) were recruited. All patients were female and had cone beam CT scans taken. TMJ arthrocentesis and venipuncture were performed on 12 OA and 12 age-matched healthy controls. Serum and synovial fluid levels of 50 biomarkers of arthritic inflammation were quantified by protein microarrays. Shape Analysis MANCOVA tested statistical correlations between biomarker levels and variations in condylar morphology.
Compared with healthy controls, the OA average condyle was significantly smaller in all dimensions except its anterior surface, with areas indicative of bone resorption along the articular surface, particularly in the lateral pole. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were significantly correlated with bone apposition of the condylar anterior surface. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFβb1, IFNγg, TNFαa, IL-1αa, and IL-6 were significantly correlated with flattening of the lateral pole. Expression levels of ANG were significantly correlated with the articular morphology in healthy controls.
Bone resorption at the articular surface, particularly at the lateral pole was statistically significant at initial diagnosis of TMJ OA. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were correlated with bone apposition. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFβ1, IFNγ, TNFα, IL-1α, and IL-6 were correlated with bone resorption.
PMCID: PMC4185299  PMID: 25278075
Imaging biomarkers; protein biomarkers; image analysis
15.  Validation of Osteoarthritis synthetic defect database via non-rigid registration 
Temporomandibular joint (TMJ) disorders are a group of conditions that cause pain and dysfunction in the jaw joint and the muscles controlling jaw movement. However, diagnosis and treatment of these conditions remain controversial. To date, there is no single sign, symptom, or test that can clearly diagnose early stages of osteoarthritis (OA). Instead, the diagnosis is based on a consideration of several factors, including radiological evaluation. The current radiological diagnosis scores of TMJ pathology are subject to misdiagnosis. We believe these scores are limited by the acquisition procedures, such as oblique cuts of the CT and head positioning errors, and can lead to incorrect diagnoses of flattening of the head of the condyle, formation of osteophytes, or condylar pitting. This study consists of creating and validating a methodological framework to simulate defects in CBCT scans of known location and size, in order to create synthetic TMJ OA database. User-generated defects were created using a non-rigid deformation protocol in CBCT. All segmentation evaluation, surface distances and linear distances from the user-generated to the simulated defects showed our methodological framework to be very precise and within a voxel (0.5 mm) of magnitude. A TMJ OA synthetic database will be created next, and evaluated by expert radiologists, and this will serve to evaluate how sensitive the current radiological diagnosis tools are.
PMCID: PMC4518713  PMID: 26236073
non-rigid registration; TMJ OA; validation studies; diagnosis evaluation
16.  Efficient Identification of Low-Income Asian American Women at High Risk for Hepatitis B 
Hepatitis B disproportionately affects Asian Americans. Because outreach to promote testing and vaccination can be intensive and costly, we assessed the feasibility of an efficient strategy to identify Asian Americans at risk. Prior research with California’s statewide toll-free phone service where low-income women call for free cancer screening found 50% of English- and Spanish-speaking callers were willing to participate in a study on health topics other than cancer screening. The current study ascertained whether Asian Americans could be recruited. Among 200 eligible callers, 50% agreed to take part (95% confidence interval 43%–57%), a rate comparable to our previous study. Subsequent qualitative interviews revealed that receptivity to recruitment was due to trust in the phone service and women’s need for health services and information. This was a relatively low-intensity intervention in that, on average, only five minutes additional call time was required to identify women at risk and provide a brief educational message. Underserved women from diverse backgrounds may be reached in large numbers through existing communication channels.
PMCID: PMC4497776  PMID: 24185165
Outreach; mixed methods; cost; low income; hepatitis B; Asian; research participation
17.  Notes on Metaphire multitheca (Chen, 1938) (Oligochaeta, Megascolecidae) recorded from Vietnam, with descriptions of two new species 
ZooKeys  2015;127-136.
The paper deals with Pheretima multitheca multitheca Chen, 1938 recorded from Vietnam (non Pheretima multitheca Chen, 1938 now in Metaphire from Hainan Island). As a result, a new species, Amynthas erroneous sp. n., is revealed from materials which were previously misidentified as Pheretima multitheca multitheca. The new species is obviously distinguished from other Amynthas species by multiple spermathecal pores lateroventral in intersegments 5/6/7/8/9, and presence of two pairs of crescentic genital markings in xviii. In addition, another new species, Amynthas nhonmontis sp. n., is described and easily recognized by multiple spermathecal pores ventral in intersegments 5/6/7/8 and three pairs of genital markings in xvii, xix and xx.
PMCID: PMC4467186  PMID: 26085799
Annelida; Pheretima; Amynthas; earthworm; new species; taxonomy
18.  Use of shape correspondence analysis to quantify skeletal changes associated with bone-anchored Class III correction 
The Angle orthodontist  2013;84(2):329-336.
To evaluate the three-dimensional (3D) skeletal changes in the mandibles of Class III patients treated with bone-anchored maxillary protraction using shape correspondence analysis.
Material and Method
Twenty-five consecutive patients with skeletal Class III who were between the ages of 9 and 13 years (mean age, 11.10 ± 1.1 years) were treated using Class III intermaxillary elastics and bilateral miniplates (two in the infrazygomatic crests of the maxilla and two in the anterior mandible). Cone-beam computed tomography (CBCT) was performed for each patient before initial loading (T1) and at 1 year out (T2). From the CBCT scans, 3D models were generated, registered on the anterior cranial base, and analyzed using 3D linear distances and vectors between corresponding point-based surfaces.
Bone-anchored traction produced anteroposterior and vertical skeletal changes in the mandible. The novel application of Shape correspondence analysis showed vectors of mean (± standard deviation) distal displacement of the posterior ramus of 3.6 ± 1.4 mm, while the chin displaced backward by 0.5 ± 3.92 mm. The lower border of the mandible at the menton region was displaced downward by 2.6 ± 1.2 mm, and the lower border at the gonial region moved downward by 3.6 ± 1.4 mm. There was a downward and backward displacement around the gonial region with a mean closure of the gonial angle by 2.1°. The condyles were displaced distally by a mean of 2.6 ± 1.5 mm, and there were three distinct patterns for displacement: 44% backward, 40% backward and downward, and 16% backward and upward.
This treatment approach induces favorable control of the mandibular growth pattern and can be used to treat patients with components of mandibular prognathism.
PMCID: PMC4394197  PMID: 23886012
Skeletal anchorage; Class III; Growth modification; Bone anchor; 3-D
19.  In Vivo Force Decay of Niti Closed Coil Springs 
Nickel-titanium (NiTi) closed coil springs are purported to deliver constant forces over extended ranges of activation and working times. In vivo studies supporting this claim are limited. The objective of this study is to evaluate changes in force decay properties of NiTi closed coil springs after clinical use.
Pseudoelastic force-deflection curves for 30 NiTi coil springs (used intra-orally) and 15 matched laboratory control springs (simulated intra-oral conditions - artificial saliva, 37°C) were tested pre- and post-retrieval via Dynamic Mechanical Analysis (DMA) and the Instron machine, respectively, to evaluate amount of force loss and hysteresis change following 4, 8, or 12 weeks of working time (n=10 per group). Effect of the oral environment and clinical use on force properties were evaluated by comparing in vivo and in vitro data.
The springs studied showed a statistically significant decrease in force (~12%) following 4 weeks of clinical use (p<0.01), with a further significant decrease (~7%) from 4–8 weeks (p=0.03) and force levels appearing to remain steady thereafter. Clinical space closure at an average rate of 0.91mm per month was still observed despite this decrease in force. In vivo and in vitro force loss data were not statistically different.
NiTi closed coil springs do not deliver constant forces when used intra-orally, but they still allow for space closure rates of ~1mm/month.
PMCID: PMC3979479  PMID: 24703289
20.  Exploring a Culturally Relevant Model of Cancer Prevention Involving Traditional Chinese Medicine Providers in a Chinese American Community 
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in all racial and ethnic groups. Although CRC screening is very cost-effective, screening rates are low among most ethnic groups, including Asian Americans. Given the high use of traditional Chinese medicine (TCM) among Chinese Americans one potentially useful approach to promote CRC screening in these communities could involve TCM providers in outreach efforts.
A two-phase study was conducted. The perceived suitability of TCM providers in CRC prevention was explored in Phase 1. Guided by Phase 1 findings, in Phase 2, a 38-page integrative educational flipchart was developed and tested. Focus groups and observations were conducted with TCM providers (acupuncturists and herbalists) and with limited English proficient Chinese American immigrants living in San Francisco, California.
In Phase 1, the role of TCM providers as CRC screening educators was deemed acceptable by both providers and community members, although some providers had reservations about engaging in CRC outreach activities due to lack of expertise. The majority of providers were not aware of regular CRC screening as a preventive measure, and most were not up-to-date in their own screening. In Phase 2, the integrative CRC education flipchart was perceived as culturally appropriate based on stakeholder input and feedback.
This study shows that TCM providers have the potential to be a valuable and culturally appropriate community resource for providing information on CRC screening. It suggests a potential role for traditional healers as change agents in the immigrant community health network.
PMCID: PMC4374358  PMID: 25821531
Chinese American; Colorectal Cancer; Preventive Screening; Public Health Education; Integrative Medicine
21.  Healthy Colon, Healthy Life 
Colorectal cancer (CRC) screening rates are increasing, but they are still low, particularly in ethnic minority groups. In many resource-poor settings, fecal occult blood test (FOBT) is the main screening option.
Culturally tailored telephone counseling by community health advisors employed by a community-based organization, culturally tailored brochures, and customized FOBT kits.
RCT. Participants were randomized to (1) basic intervention: culturally tailored brochure plus FOBT kit (n=765); (2) enhanced intervention: brochure, FOBT plus telephone counseling (n=768); or (3) usual care (n=256).
Latino and Vietnamese primary care patients at a large public hospital.
Main outcome measures
Self-reported receipt of FOBT or any CRC screening at 1-year follow-up.
1358 individuals (718 Latinos and 640 Vietnamese) completed the follow-up survey. Self-reported FOBT screening rates increased by 7.8 % in the control group, by 15.1 % in the brochure group, and by 25.1 % in the brochure/telephone counseling group (p<0.01 for differences between each intervention and usual care and for the difference between brochure/telephone counseling and brochure alone). For any CRC screening, rates increased by 4.1 % in the usual care group, by 11.9 % in the FOBT/brochure group, and by 21.4 % in the brochure/telephone counseling group (p<0.01 for differences between each intervention and usual care and for the difference between the basic and the enhanced intervention).
An intervention that included culturally tailored brochures and tailored telephone counseling increased CRC screening in Latinos and the Vietnamese. Brochure and telephone counseling together had the greatest impact. Future research should address replication and dissemination of this model for Latinos and Vietnamese in other communities, and adaptation of the model for other groups.
PMCID: PMC4282133  PMID: 20547275
22.  Breast Cancer Screening Among Vietnamese Americans 
Vietnamese-American women underutilize breast cancer screening.
An RCT was conducted comparing the effect of lay health workers (LHWs) and media education (ME) to ME alone on breast cancer screening among these women.
Conducted in California from 2004 to 2007, the study included 1100 Vietnamese-American women aged ≥40 years who were recruited through LHW social networks. Data were analyzed from 2007 to 2009.
Both groups received targeted ME. The intervention group received two LHW educational sessions and two telephone calls.
Main outcome measures
Change in self-reported receipt of mammography ever, mammography within 2 years, clinical breast examination (CBE) ever, or CBE within 2 years.
The LHW+ME group increased receipt of mammography ever and mammography in the past 2 years (84.1% to 91.6% and 64.7% to 82.1%, p<0.001) while the ME group did not. Both ME (73.1% to 79.0%, p<0.001) and LHW+ME (68.1% to 85.5%, p<0.001) groups increased receipt of CBE ever, but the LHW+ME group had a significantly greater increase. The results were similar for CBE within 2 years. In multivariate analyses, LHW+ME was significantly more effective than ME for all four outcomes, with ORs of 3.62 (95% CI=1.35, 9.76) for mammography ever; 3.14 (95% CI=1.98, 5.01) for mammography within 2 years; 2.94 (95% CI=1.63, 5.30) for CBE ever; and 3.04 (95% CI=2.11, 4.37) for CBE within 2 years.
Increased breast cancer screening by LHWs among Vietnamese-American women. Future research should focus on how LHWs work and whether LHW outreach can be disseminated to other ethnic groups.
PMCID: PMC4282142  PMID: 19765502
23.  Hepatitis B Management in Vulnerable Populations: Gaps in Disease Monitoring and Opportunities for Improved Care 
Hepatitis B (HBV) is prevalent in certain US populations and regular HBV disease monitoring is critical to reducing associated morbidity and mortality. Adherence to established HBV monitoring guidelines among primary care providers is unknown.
To evaluate HBV disease monitoring patterns and factors associated with adherence to HBV management guidelines in the primary care setting.
Primary providers within the San Francisco safety net healthcare system were surveyed for HBV management practices, knowledge, attitudes, and barriers to HBV care. Medical records from 1,727 HBV-infected patients were also reviewed retrospectively.
Of 148 (45%) responding providers, 79% reported ALT and 44% reported HBV viral load testing every 6–12 months. Most providers were knowledgeable about HBV but 43% were unfamiliar with HBV management guidelines. Patient characteristics included: mean age 51 years; 54% male; 67% Asian. Within the past year, 75% had ALT; 24% viral load; 21% HBeAg tested, and 40% of at-risk patients had abdominal imaging for HCC. Provider familiarity with guidelines (OR 1.02, 95%CI 1.00–1.03), Asian patient race (OR 4.18, 95%CI 2.40–7.27), and patient age were associated with recommended HBV monitoring. Provider HBV knowledge and attitudes were positively associated, while provider age and perceived barriers were negatively associated with HCC surveillance.
Comprehensive HBV disease monitoring including HCC screening with imaging were suboptimal. While familiarity with AASLD guidelines and patient factors were associated with HBV monitoring, only provider and practice factors were associated with HCC surveillance. These findings highlight the importance of targeted provider education to improve HBV care.
PMCID: PMC3947196  PMID: 24052195
Hepatitis B; Hepatocellular carcinoma; Primary care; Provider education; Practice guidelines; Health disparities
24.  Three-dimensional treatment outcomes in Class II patients treated with the Herbst appliance: A pilot study 
The aims of this study were to analyze 3-dimensional skeletal changes in subjects with Class II malocclusion treated with the Herbst appliance and to compare these changes with treated Class II controls using 3-dimensional superimposition techniques.
Seven consecutive Herbst patients and 7 Class II controls treated with Class II elastics who met the inclusion criteria had cone-beam computed tomographs taken before treatment, and either after Herbst removal or at posttreatment for the control subjects. Three-dimensional models were generated from the cone-beam computed tomography images, registered on the anterior cranial bases, and analyzed using color maps and point-to-point measurements.
The Herbst patients demonstrated anterior translation of the glenoid fossae and condyles (right anterior fossa, 1.69 ± 0.62 mm; left anterior fossa, 1.43 ± 0.71 mm; right anterior condyle, 1.20 ± 0.41 mm; left anterior condyle, 1.29 ± 0.57 mm), whereas posterior displacement predominated in the controls (right anterior fossa, −1.51 ± 0.68 mm; left anterior fossa, −1.31 ± 0.61 mm; right anterior condyle, −1.20 ± 0.41 mm; left anterior condyle, −1.29 ± 0.57 mm; P <0.001). There was more anterior projection of B-point in the Herbst patients (2.62 ± 1.08 mm vs 1.49 ± 0.79 mm; P <0.05). Anterior displacement of A-point was more predominant in the controls when compared with the Herbst patients (1.20 ± 0.53 mm vs −1.22 ± 0.43 mm; P <0.001).
Class II patients treated with the Herbst appliance demonstrated anterior displacement of the condyles and glenoid fossae along with maxillary restraint when compared with the treated Class II controls; this might result in more anterior mandibular projection.
PMCID: PMC3999969  PMID: 24286905
25.  Using appropriate body mass index cut points for overweight and obesity among Asian Americans 
Preventive medicine  2014;65:1-6.
Asian Americans have low prevalence of overweight/obesity based on standard BMI cut points yet have higher rates of diabetes. We examined the prevalence of overweight/obesity, using lower BMI cut points recommended by the World Health Organization (WHO) for Asians, and diabetes in Asian American subgroups in California.
Secondary analysis of the 2009 adult California Health Interview Survey (n = 45,946) of non-Hispanic Whites (NHW), African Americans, Hispanics and Asians (Vietnamese, Chinese, Korean, Filipino, South Asian and Japanese). WHO Asian BMI cut points (overweight = 23–27.5 kg/m2; obese ≥ 27.5 kg/m2) were used for Asian subgroups. Standard BMI cut points (overweight = 25–29.9 kg/m2; obese ≥ 30 kg/m2) were applied for other groups.
Among Asian subgroups, overweight/obesity was highest among Filipinos (78.6%), which was higher than NHWs (p < 0.001) but similar to African Americans and Hispanics. Compared to NHW, diabetes prevalence was higher for Vietnamese, Koreans, Filipinos and South Asians with BMI = 23–24.9 kg/m2 and Koreans, Filipinos and Japanese with BMI = 27.5–29.9 kg/m2, the ranges WHO recommends as overweight or obese for Asians but not for other groups.
Filipinos should be a priority population for overweight/obesity screening. Filipinos, Vietnamese, Korean, South Asians and Japanese have higher diabetes prevalence at lower BMI cut points. WHO Asian BMI cut points may have clinical utility to identify at-risk Asian Americans.
PMCID: PMC4217157  PMID: 24736092
Obesity; Overweight; Type 2 diabetes mellitus; Asian Americans; Minority health

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