KERNEL-PENALIZED REGRESSION FOR ANALYSIS OF MICROBIOME DATA.

The analysis of human microbiome data is often based on dimension-reduced graphical displays and clusterings derived from vectors of microbial abundances in each sample. Common to these ordination methods is the use of biologically motivated definitions of similarity. Principal coordinate analysis, in particular, is often performed using ecologically defined distances, allowing analyses to incorporate context-dependent, non-Euclidean structure. In this paper, we go beyond dimension-reduced ordination methods and describe a framework of high-dimensional regression models that extends these distance-based methods. In particular, we use kernel-based methods to show how to incorporate a variety of extrinsic information, such as phylogeny, into penalized regression models that estimate taxonspecific associations with a phenotype or clinical outcome. Further, we show how this regression framework can be used to address the compositional nature of multivariate predictors comprised of relative abundances; that is, vectors whose entries sum to a constant. We illustrate this approach with several simulations using data from two recent studies on gut and vaginal microbiomes. We conclude with an application to our own data, where we also incorporate a significance test for the estimated coefficients that represent associations between microbial abundance and a percent fat.

Stress Among Latinos: Does it Vary by Occupation and Agricultural Season?

OBJECTIVE: Stress is pervasive among Latino immigrants. We identified seasonal and occupational patterns in stress among rural Latino immigrants. METHODS: During three agricultural periods, farmworker and non-farmworker participants responded to a 24-item stress questionnaire (Snipes et al, 2007). We measured the associations of stress with occupation, with season, and occupation within season, adjusting for demographic variables. RESULTS: The highest levels of stress were observed in the pre-thinning season when pruning takes place among farmworkers. Stress is significantly higher in farmworkers compared with non-farmworkers only in the non-spray season when crops are dormant. Higher income was associated with decreased stress in the pre-thinning and thinning seasons when buds and small fruit are removed from orchards. CONCLUSIONS: Identification of strategies to reduce stress in Latino migrants is warranted. Although some sources of stress may be intractable, others may be amenable to intervention.

Nightshift work, chronotype, and genome-wide DNA methylation in blood.

Molecular mechanisms underlying the negative health effects of shift work are poorly understood, which remains a barrier to developing intervention strategies to protect the long-term health of shift workers. We evaluated genome-wide differences in DNA methylation (measured in blood) between 111 actively employed female nightshift and 86 actively employed female dayshift workers from the Seattle metropolitan area. We also explored the effect of chronotype (i.e., measure of preference for activity earlier or later in the day) on DNA methylation among 110 of the female nightshift workers and an additional group of 131 male nightshift workers. Methylation data were generated using the Illumina Infinium HumanMethylation450 BeadChip (450K) Array. After applying the latest methylation data processing methods, we compared methylation levels at 361,210 CpG loci between the groups using linear regression models adjusted for potential confounders and applied the false-discovery rate (FDR) ≤ 0.05 to account for multiple comparisons. No statistically significant associations at the genome-wide level were observed with shift work or chronotype, though based on raw P values and absolute effect sizes, there were suggestive associations in genes that have been previously linked with cancer (e.g., BACH2, JRK, RPS6KA2) and type-2 diabetes (e.g., KCNQ1). Given that our study was underpowered to detect moderate effects, examining these suggestive results in well-powered independent studies or in pooled data sets may improve our understanding of the pathways underlying the negative health effects of shift work and the influence of personal factors such as chronotype. Such an approach may help identify potential interventions that can be used to protect the long-term health of shift workers.

Enhancing Biospecimen Knowledge Among Health Care Providers and Representatives From Community Organizations.

In a personalized medicine environment, it is necessary to have access to a range of biospecimens to establish optimal plans for disease diagnosis and treatment for individual patients. Cancer research is especially dependent on biospecimens for determining ideal personalized treatment for patients. Unfortunately, the vast majority of biospecimens are collected from non-Hispanic White individuals; thus, minority representation is lacking. This has negative implications for comprehensive cancer treatment. The Geographic Management of Cancer Health Disparities Program (GMaP) Region 6 implemented a series of biospecimen education seminars adapted from the Biospecimen and Biobanking module of an existing Cancer Education and Training Program. Regional GMaP partners participated in a train-the-trainer webinar to familiarize themselves with the training materials. Participants trained by the trainers completed pre- and posttests to document changes in awareness, knowledge, and intention. Nine biospecimen education seminars were offered in 2013; 255 health care professionals and representatives from community organizations attended. Participants demonstrated a significant increase in knowledge, intention to donate samples, and intention to talk to patients about biospecimen sample donation. Representatives from community organizations had more improvement on knowledge scores than health care providers. Participation in a well-designed biospecimen education program may ameliorate some of the distrust of biomedical research experienced by racial/ethnic minorities and, in turn, increase needed minority representation in biospecimen collection.

Single-arm trial of the second version of an acceptance & commitment therapy smartphone application for smoking cessation.

BACKGROUND: The first randomized trial of a smartphone application (app) for adult smoking cessation (SmartQuit 1.0) revealed key features that predict cessation. These findings guided the revision of this Acceptance & Commitment Therapy (ACT)-based application (SmartQuit 2.0), which was primarily tested to examine participant receptivity, short-term cessation and reduction, and the relationship between program completion, smoking cessation and reduction. Secondarily, outcomes were descriptively compared with the SmartQuit1.0 trial. METHOD: Adult participants (78% female, 25% with high school or less education, 30% unemployed) were recruited into the single-arm pilot trial (N=99) of SmartQuit 2.0 with a two-month follow-up (85% retention). RESULTS: Regarding receptivity, 84% of participants were satisfied with SmartQuit 2.0 (vs. 59% for SmartQuit1.0), 73% would recommend it to a friend (vs. 48% for SmartQuit1.0), 81% found the ACT exercises useful for quitting (vs. 44% for SmartQuit1.0). At the 2-month follow-up, the quit rates were 21% for 7-day point prevalence (vs. 23% for SmartQuit1.0), 11% for 30-day point prevalence (vs. 13% for SmartQuit1.0), and 75% of participants reduced their smoking frequency (vs. 57% for SmartQuit1.0). Among program completers (24% of total sample), the quit rates were 33% for 7-day point prevalence, 28% for 30-day point prevalence, and 88% of participants reduced their smoking frequency. CONCLUSIONS: The revised app had high user receptivity, modest quit rates, and high smoking reduction rates. Program completion may be key to boosting the app's effectiveness.

The impact of medical tourism on colorectal screening among Korean Americans: A community-based cross-sectional study.

BACKGROUND: Colorectal cancer (CRC) remains the most commonly diagnosed cancer among Korean Americans (KAs) in part due to low screening rates. Recent studies suggest that some KA patients engage in medical tourism and receive medical care in their home country. The impact of medical tourism on CRC screening is unknown. The purpose of this paper was to 1) investigate the frequency of medical tourism, 2) examine the association between medical tourism and CRC screening, and 3) characterize KA patients who engage in medical tourism. METHODS: This is a community-based, cross-sectional study involving self-administered questionnaires conducted from August 2013 to October 2013. Data was collected on 193 KA patients, ages 50-75, residing in the Seattle metropolitan area. The outcome variable is up-to-date with CRC screening, defined as having had a stool test (Fecal Occult Blood Test or Fecal Immunochemical Test) within the past year or a colonoscopy within 10 years. Predictor variables are socio-demographics, health factors, acculturation, knowledge, financial concerns for medical care costs, and medical tourism. RESULTS: In multi-variate modeling, medical tourism was significantly related to being up-to-date with CRC screening. Participants who engaged in medical tourism had 8.91 (95% CI: 3.89-23.89) greater odds of being up-to-date with CRC screening compared to those who did not travel for healthcare. Factors associated with engaging in medical tourism were lack of insurance coverage (P = 0.008), higher levels of education (P = 0.003), not having a usual place of care (P = 0.002), older age at immigration (P = 0.009), shorter years-of-stay in the US (P = 0.003), and being less likely to speak English well (P = 0.03). CONCLUSIONS: This study identifies the impact of medical tourism on CRC screening and characteristics of KA patients who report engaging in medical tourism. Healthcare providers in the US should be aware of the customary nature of medical tourism among KAs and consider assessing medical tests done abroad when providing cancer care. TRIAL REGISTRATION: Not applicable.

A Brief Community-Based Nutrition Education Intervention Combined With Food Baskets Can Increase Fruit and Vegetable Consumption Among Low-Income Latinos.

OBJECTIVE: To evaluate the impact of an 8-week community-based nutrition education program combined with food baskets on fruit and vegetable consumption (FVC) among Latinos. DESIGN: Pre-post intervention study assessing perceived barriers, knowledge, food efficacy, food outcomes, and FVC, using mixed methods (quantitative and qualitative). SETTING: Participants' recruitment and data collection took place in the Seattle Metropolitan area from September 2012 to July 2013. PARTICIPANTS: Participants' (n = 40) mean age was 37.8 (±10.5) years. Participants were mostly women, from Mexico, uninsured, low income, and overweight or obese. INTERVENTION: Nuestras Comidas was developed through the use of the Social Cognitive Theory and focused on increasing behavioral capability, food efficacy, food outcomes, and FVC. MAIN OUTCOME MEASURE: Dependent variables were knowledge, perceived barriers, food efficacy, food outcomes, and FVC. Independent variable was the intervention (pre-post). STATISTICAL ANALYSES: A McNemar exact test was computed for categorical variables and Wilcoxon signed-rank test and paired t test for continuous variables. Focus group data were analyzed by identifying common themes. RESULTS: Participation in the intervention was significantly associated with increased knowledge, food efficacy, and vegetable consumption. CONCLUSIONS AND IMPLICATIONS: A brief nutrition education intervention combined with food baskets can improve healthy eating among Latinos.

Get with the program: Adherence to a smartphone app for smoking cessation.

INTRODUCTION: Although engagement is generally predictive of positive outcomes in technology-based behavioral change interventions, engagement measures remain largely atheoretical and lack treatment-specificity. This study examines the extent to which adherence measures based on the underlying behavioral change theory of an Acceptance and Commitment Therapy (ACT) app for smoking cessation predict smoking outcomes, and user characteristics associated with adherence. METHODS: Study sample was adult daily smokers in a single arm pilot study (n=84). Using the app's log file data, we examined measures of adherence to four key components of the ACT behavior change model as predictors of smoking cessation and reduction. We also examined baseline user characteristics associated with adherence measures that predict smoking cessation. RESULTS: Fully adherent users (24%) were over four times more likely to quit smoking (OR=4.45; 95% CI=1.13, 17.45; p=0.032). Both an increase in tracking the number of urges passed (OR=1.02; 95% CI=1.00, 1.03; p=0.043) and ACT modules completed (OR=1.27; 95% CI=1.01, 1.60; p=0.042) predicted cessation. Lower baseline acceptance of cravings was associated with over four times higher odds of full adherence (OR=4.59; 95% CI=1.35, 15.54; p=0.014). CONCLUSIONS: Full adherence and use of specific ACT theory-based components of the app predicted quitting. Consistent with ACT theory, users with low acceptance were most likely to adhere to the app. Further research is needed on ways to promote app engagement.

Enterolignan-producing phenotypes are associated with increased gut microbial diversity and altered composition in premenopausal women in the United States.

BACKGROUND: Lignans in plant foods are metabolized by gut bacteria to the enterolignans, enterodiol (END) and enterolactone (ENL). Enterolignans have biologic activities important to the prevention of cancer and chronic diseases. We examined the composition of the gut microbial community (GMC) as a contributor to human enterolignan exposure. METHODS: We evaluated the association between the GMC in stool, urinary enterolignan excretion, and diet from a 3-day food record in 115 premenopausal (ages 40-45 years) women in the United States. Urinary enterolignans were measured using gas chromatography-mass spectroscopy. The GMC was evaluated using 454 pyrosequencing of the 16S rRNA gene. Sequences were aligned in SILVA (www.arb-silva.de). Operational taxonomic units were identified at 97% sequence similarity. Taxonomic classification was performed and alpha and beta diversity in relationship to ENL production were assessed. Multivariate analysis and regression were used to model the association between enterolignan excretion and the GMC. Bacteria associated with ENL production were identified using univariate analysis and ridge regression. RESULTS: After adjusting for dietary fiber intake and adiposity, we found a significant positive association between ENL excretion and either the GMC (P = 0.0007), or the diversity of the GMC (P = 0.01). The GMC associated with high ENL production was distinct (UNIFRAC, P < 0.003, MRPP) and enriched in Moryella spp., Acetanaerobacterium spp., Fastidiosipila spp., and Streptobacillus spp. CONCLUSION: Diversity and composition of the GMC are associated with increased human exposure to enterolignans. IMPACT: Differences in gut microbial diversity and composition explain variation in gut metabolic processes that affect environmental exposures and influence human health. Cancer Epidemiol Biomarkers Prev; 24(3); 546-54. ©2014 AACR.

An innovative strategy to reach the underserved for colorectal cancer screening.

Hispanics are an underserved population in terms of colorectal cancer (CRC). CRC is the second leading cause of cancer incidence among Hispanic men and women, and Hispanics have lower screening rates than non-Hispanic whites. The overall purpose of this project was to provide CRC information, education, and fecal occult blood test (FOBT) kits to Hispanics in a rural three-county region of Washington State. We held a series of 47 community health fair events that incorporated the use of a giant inflatable, walk-through colon model with physical depictions of healthy tissue, polyps, and CRC. We used a pre/post-design to look for changes in familiarity with CRC before and after walking through the colon among adults aged 18 and older (n = 947). McNemar's test analysis indicated significant differences in the distribution of the percentage of correct participant responses to CRC-related questions from pre- to post-test after an educational tour of the colon. Results from logistic regression analysis identified multiple participant characteristics associated with self-reported likelihood of being screened for CRC in 3 months following post-test. We distributed 300 free FOBT kits to be analyzed at no charge to the end user and to attendees aged 50 and older who toured the inflatable colon; 226 FOBT kits (75.3%) were returned for analysis. The use of the inflatable colon was an innovative way to attract people to learn about CRC and CRC screening modalities. Furthermore, the response to our distribution of FOBT kits indicates that if given the opportunity for education and access to services, this underserved population will comply with CRC screening.

Increasing cervical cancer screening in the United States-Mexico border region.

PURPOSE: Hispanic women living on the United States-México border experience health disparities, are less likely to access cervical cancer screening services, and have a higher rate of cervical cancer incidence compared to women living in nonborder areas. Here we investigate the effects of an intervention delivered by community health workers (CHWs, known as lay health educators or Promotores de Salud in Spanish) on rates of cervical cancer screening in Hispanic women who were out of compliance with recommended screening guidelines. METHODS: Hispanic women out of compliance with screening guidelines, attending clinics in southern New Mexico, were identified using medical record review. All eligible women were offered the intervention. The study was conducted between 2009 and 2011, and data were analyzed in 2012. Setting/participants--162 Hispanic women, resident in New Mexico border counties, aged 29-80 years, who had not had a Pap test within the past 3 years. Intervention--a CHW-led, culturally appropriate, computerized education intervention. Main outcome measures--the percentage of women who underwent cervical cancer screening within 12 months of receiving the intervention. Change in knowledge of, and attitudes toward cervical cancer and screening as assessed by a baseline and follow-up questionnaire. RESULTS: 76.5% of women had a Pap test after the intervention. Women displayed increased knowledge about cervical cancer screening and about HPV. CONCLUSIONS: A culturally appropriate promotora-led intervention is successful in increasing cervical cancer screening in at-risk Hispanic women on the United States-México border.

Diabetes prevention in Hispanics: report from a randomized controlled trial.

INTRODUCTION: Hispanics are at increased risk of developing type 2 diabetes. Lifestyle interventions are effective in preventing diabetes and restoring glucose regulation. METHODS: We recruited Hispanic men and women (N = 320) who were residents of the Lower Yakima Valley, Washington, aged 18 years or older with hemoglobin A1c (HbA1c) levels higher than 6% to a parallel 2-arm randomized-controlled trial conducted from 2008 through 2012. The trial compared participants in the intervention arm, who received an immediate educational curriculum (n = 166), to participants in the control arm, who received a delayed educational curriculum (n = 154). The home-based curriculum consisted of 5 sessions led by community health workers and was designed to inform participants about diabetes, diabetes treatment, and healthy dietary and physical activity behaviors. Participants were randomly assigned to the intervention and control arms, and analysts were blinded as to participant arm. We evaluated intervention effects on HbA1c levels; frequency (times per week) of fruit and vegetable consumption; and frequency (times per week) of mild, moderate, and strenuous leisure-time physical activity. At baseline, 3 months, and 6 months after randomization, participants completed a questionnaire and provided a blood sample. Analysts were blinded to intervention arm. RESULTS: The immediate intervention group (-0.64% [standard error (SE) 0.10]) showed a significant improvement in HbA1c scores (-37.5%, P = .04) compared with the delayed intervention group (-0.44%, P = .14). No significant changes were seen for dietary end points or changes in physical activity. We did observe a trend of greater increases in frequency of moderate and vigorous physical activity and a smaller increase in mild physical activity in the immediate intervention group than in the delayed intervention group. CONCLUSION: This home-based intervention delivered by CHWs was associated with a clinically and statistically significant reduction in HbA1c levels in Hispanic adults with HbA1c levels higher than 6%.

Premenopausal vasomotor symptoms in an ethnically diverse population.

OBJECTIVE: The prevalence of vasomotor symptoms (VMS) among women aged 45 years or older who report regular menses has not been described well. Variability by race/ethnicity is expected. METHODS: A cross-sectional analysis of Group Health enrollees was performed among women ages 45-56 y with regular and no skipped menses, and not taking hormones. Data were collected from electronic databases and mailed surveys, including a soy food questionnaire. Associations between race/ethnicity and VMS (ever/never; past 2 wk) were assessed using generalized linear models, controlling for age and body mass index. The prevalence of headache and joint pain, and VMS associations within race by soy intake were explored. RESULTS: A total of 1,513 premenopausal women with a mean age of 48.5 years responded to the survey; 75% were white. Native American women were most likely to report ever having VMS (66.7%), followed by black (61.4%), white (58.3%), Hawaiian/Pacific Islander (45.5%), mixed-ethnicity (42.1%), Vietnamese (40.0%), Filipino (38.9%, P < 0.05), Japanese (35.9%, P < 0.01), East Indian (31.3%, P < 0.05), Chinese (29.0%, P < 0.001), and other Asian (25.6%, P < 0.001) women, as compared with white women. Hispanic women were less likely to have VMS (41.7%) than non-Hispanic white women (58.8%, P < 0.001). Among white women, but not among other women, soy intake was associated with VMS (P = 0.03). CONCLUSIONS: Among a diverse population of premenopausal women, VMS prevalence is high at 55%. Asian (vs white) and Hispanic (vs non-Hispanic white) women are less likely to report ever having VMS, a pattern similar to that observed during the menopausal transition and early postmenopause in our studies. White women with more VMS seem to include more soy in their diet.

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium.

OBJECTIVE: To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. DESIGN: Pooled analyses of 20 prospective cohorts in Asia, including data from 835,082 east Asians and 289,815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. SETTING: General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). PARTICIPANTS: 1,124,897 men and women (mean age 53.4 years at baseline). MAIN OUTCOME MEASURES: Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. RESULTS: 49,184 cardiovascular deaths (40,791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). CONCLUSIONS: Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

mcaGUI: microbial community analysis R-Graphical User Interface (GUI).

UNLABELLED: Microbial communities have an important role in natural ecosystems and have an impact on animal and human health. Intuitive graphic and analytical tools that can facilitate the study of these communities are in short supply. This article introduces Microbial Community Analysis GUI, a graphical user interface (GUI) for the R-programming language (R Development Core Team, 2010). With this application, researchers can input aligned and clustered sequence data to create custom abundance tables and perform analyses specific to their needs. This GUI provides a flexible modular platform, expandable to include other statistical tools for microbial community analysis in the future. AVAILABILITY: The mcaGUI package and source are freely available as part of Bionconductor at http://www.bioconductor.org/packages/release/bioc/html/mcaGUI.html