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Prior research has shown that cancer risk varies by geography, but scan statistics methods for identifying cancer clusters in case-control studies have been limited in their ability to identify multiple clusters and adjust for participant-level risk factors. We develop a method to identify geographic patterns of breast cancer odds using the Wisconsin Women's Health Study, a series of 5 population-based case-control studies of female Wisconsin residents aged 20-79 enrolled in 1988-2004 (cases=16,076, controls=16,795). We create sets of potential clusters by overlaying a 1 km grid over each county-neighborhood and enumerating a series of overlapping circles. Using a two-step approach, we fit a penalized binomial regression model to the number of cases and trials in each grid cell, penalizing all potential clusters by the least absolute shrinkage and selection operator (Lasso). We use BIC to select the number of clusters, which are included in a participant-level logistic regression model. We identify 15 geographic clusters, resulting in 23 areas of unique geographic odds ratios. After adjustment for known risk factors, confidence intervals narrowed but breast cancer odds ratios did not meaningfully change; one additional hotspot was identified. By considering multiple overlapping spatial clusters simultaneously, we discern gradients of spatial odds across Wisconsin.

Background: Both shorter and longer telomeres in peripheral blood leukocyte (PBL) DNA have been associated with cancer risk. However, associations remain inconsistent across studies of the same cancer type. This study compares DNA preparation methods to determine telomere length from patients with colorectal cancer.Methods: We examined PBL relative telomere length (RTL) measured by quantitative PCR (qPCR) in 1,033 patients with colorectal cancer and 2,952 healthy controls. DNA was extracted with phenol/chloroform, PureGene, or QIAamp.Results: We observed differences in RTL depending on DNA extraction method (P < 0.001). Phenol/chloroform-extracted DNA had a mean RTL (T/S ratio) of 0.78 (range 0.01–6.54) compared with PureGene-extracted DNA (mean RTL of 0.75; range 0.00–12.33). DNA extracted by QIAamp yielded a mean RTL of 0.38 (range 0.02–3.69). We subsequently compared RTL measured by qPCR from an independent set of 20 colorectal cancer cases and 24 normal controls in PBL DNA extracted by each of the three extraction methods. The range of RTL measured by qPCR from QIAamp-extracted DNA (0.17–0.58) was less than from either PureGene or phenol/chloroform (ranges, 0.04–2.67 and 0.32–2.81, respectively).Conclusions: RTL measured by qPCR from QIAamp-extracted DNA was less than from either PureGene or phenol/chloroform (P < 0.001).Impact: Differences in DNA extraction method may contribute to the discrepancies between studies seeking to find an association between the risk of cancer or other diseases and RTL. Cancer Epidemiol Biomarkers Prev; 22(11); 2047–54. ©2013 AACR.

Background: The impact of screening mammography on breast cancer incidence is difficult to disentangle from cohort- and age-related effects on incidence.Methods: We developed an age–period–cohort model of ductal carcinoma in situ (DCIS) and invasive breast cancer incidence in U.S. females using cancer registry data. Five functions were included in the model to estimate stage-specific effects for age, premenopausal birth cohorts, postmenopausal birth cohorts, period (for all years of diagnosis), and a mammography period effect limited to women ages ≥40 years after 1982. Incidence with and without the mammography period effect was calculated.Results: More recent birth cohorts have elevated underlying risk compared with earlier cohorts for both pre- and postmenopausal women. Comparing models with and without the mammography period effect showed that overall breast cancer incidence would have been 23.1% lower in the absence of mammography in 2010 (95% confidence intervals, 18.8–27.4), including 14.7% (9.5–19.3) lower for invasive breast cancer and 54.5% (47.4–59.6) lower for DCIS. Incidence of distant-staged breast cancer in 2010 would have been 29.0% (13.1–48.1) greater in the absence of mammography screening.Conclusions: Mammography contributes to markedly elevated rates of DCIS and early-stage invasive cancers, but also contributes to substantial reductions in the incidence of metastatic breast cancer.Impact: Mammography is an important tool for reducing the burden of breast cancer, but future work is needed to identify risk factors accounting for increasing underlying incidence and to distinguish between indolent and potentially lethal early-stage breast cancers that are detected via mammography. Cancer Epidemiol Biomarkers Prev; 24(6); 905–12. ©2015 AACR.

Supplemental Tables S1-2. Supplemental Table S1. Case definitionsa for ductal carcinoma in situ (DCIS) and invasive breast cancer cases included in the age-period-cohort model, SEER Program and Connecticut Tumor Registry, 1935-2010. Supplemental Table S2. Rate ratios and 95% confidence intervals of breast cancer according to age, period and cohort.

Supplemental Movie. Observed and modeled overall breast cancer incidence rates for each of the 9 Surveillance, Epidemiology and End Results (SEER) registries, 1935-2010 by age and period (year of diagnosis). Includes rates per 100,000 women for DCIS and invasive breast cancer combined. Observed crude rates shown with circles. Modeled rates shown with solid lines.

PDF - 112KB, Supplemental Table 1: Cancer-Telomere length association studies. Supplemental Table 2: Validation Set: Differences in Peripheral Blood RTL by DNA Extraction Method (Southern Blots). Supplemental Table 3: Fixed Effects and Variance Estimates of relative telomere length (log T/S ratio) by Extraction Method (Southern Blots).

Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM).Two separate meta-analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021.A total of 30 and 15 studies were included in the first and second meta-analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09-1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15-1.30) and 1.20 (95% CI, 1.05-1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60-1.12) for metformin users compared with nonmetformin users.Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users.These two meta-analyses can inform decision-making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer.

BACKGROUND: Recent reports suggest that racial differences in breast cancer incidence rates have decreased. We examined whether these findings apply to breast cancer mortality while considering age, period, and cohort influences on both absolute and relative measures of breast cancer mortality. METHODS: Using publicly available datasets (CDC Wonder, Human Mortality Database), we developed an age-period-cohort model of breast cancer mortality and breast cancer deaths as a proportion of all deaths during 1968–2019 among all women and by five race/ethnicity groups with sufficient numbers for estimation: Hispanic (all races), American Indian/Alaska Native and Asian/Pacific Islanders (regardless of ethnicity), non-Hispanic Black, and non-Hispanic White. RESULTS: Initially increasing after 1968, age-adjusted breast cancer mortality rates have decreased among all racial/ethnic groups since 1988. The age-adjusted percent of all deaths due to breast cancer also has been declining for non-Hispanic White women since about 1990 while increasing or holding steady for other race/ethnic groups. In 2019, the age-adjusted percent of deaths due to breast cancer for women was highest for Asian/Pacific Islanders (5.6%) followed by non-Hispanic Black (4.5%), Hispanic (4.4%), non-Hispanic White (4.1%), and American Indian/Alaska Native women (2.6%). CONCLUSIONS: Breast cancer mortality disparities are now greater on both relative and absolute scales for non-Hispanic Black women, and using the relative scale for Asian/Pacific Islander and Hispanic women, compared with non-Hispanic White women for the first time in 50 years.

PURPOSE: Physical activity is important for healthy cancer survivorship, yet many endometrial cancer survivors do not participate in recommended muscle-strengthening activity. The purpose of this study was to determine the feasibility of home-based muscle strengthening activity in endometrial cancer survivors. METHODS: Forty post-treatment endometrial cancer survivors were enrolled in a randomized trial, of twice-weekly home-based strength exercise versus wait-list control. The intervention included educational materials, exercise equipment (dumbbells, resistance bands), and support/feedback via video coaching sessions. Participants completed the exercises twice per week for 10 weeks, with a 5-week follow-up period. Feasibility was measured by program adherence, as well as safety of and satisfaction with the study. RESULTS: On average, participants were 60.9 years old (SD = 8.7), had a BMI of 39.9 kg/m(2) (SD = 15.2), and were 2.9 years (SD = 1.2) since diagnosis. The majority (83%) had stage I disease at diagnosis. Seventy-five percent adhered to the exercise prescription of twice/week, with 85% of participants missing fewer than 3 of the workouts. Forty percent of participants continued workouts during the 5-week follow-up. Participants were highly satisfied with intervention. No injuries or adverse everts occurred. CONCLUSION: This home-based program was feasible in endometrial cancer survivors. While adherence was measured, future research should focus on long-term maintenance of exercise and should explore progressions and modifications of exercises at a distance for various abilities. IMPLICATIONS FOR CANCER SURVIVORS: Muscle strengthening activities are recommended for all cancer survivors. This study shows that a home-based muscle strengthening exercise is feasible in endometrial cancer survivors.

Background: The evidence base regarding validity of wearable fitness trackers for assessment and/or modification of physical activity behavior is evolving. Accurate assessment of moderate- to vigorous-intensity physical activity (MVPA) is important for measuring adherence to physical activity guidelines in the United States and abroad. Therefore, this systematic review synthesizes the state of the validation literature regarding wearable trackers and MVPA.Methods: A systematic search of the PubMed, Scopus, SPORTDiscus, and Cochrane Library databases was conducted through October 2019 (PROSPERO registration number: CRD42018103808). Studies were eligible if they reported on the validity of MVPA and used devices from Fitbit, Apple, or Garmin released in 2012 or later or available on the market at the time of review. A meta-analysis was conducted on the correlation measures comparing wearables with the ActiGraph.Results: Twenty-two studies met the inclusion criteria; all used a Fitbit device; one included a Garmin model and no Apple-device studies were found. Moderate to high correlations (.7–.9) were found between MVPA from the wearable tracker versus criterion measure (ActiGraphn = 14). Considerable heterogeneity was seen with respect to the specific definition of MVPA for the criterion device, the statistical techniques used to assess validity, and the correlations between wearable trackers and ActiGraph across studies.Conclusions: There is a need for standardization of validation methods and reporting outcomes in individual studies to allow for comparability across the evidence base. Despite the different methods utilized within studies, nearly all concluded that wearable trackers are valid for measuring MVPA.

In regression analysis for spatio-temporal data, identifying clusters of spatial units over time in a regression coefficient could provide insight into the unique relationship between a response and covariates in certain subdomains of space and time windows relative to the background in other parts of the spatial domain and the time period of interest. In this article, we propose a varying coefficient regression method for spatial data repeatedly sampled over time, with heterogeneity in regression coefficients across both space and over time. In particular, we extend a varying coefficient regression model for spatial-only data to spatio-temporal data with flexible temporal patterns. We consider the detection of a potential cylindrical cluster of regression coefficients based on testing whether the regression coefficient is the same or not over the entire spatial domain for each time point. For multiple clusters, we develop a sequential identification approach. We assess the power and identification of known clusters via a simulation study. Our proposed methodology is illustrated by the analysis of a cancer mortality dataset in the Southeast of the U.S.

OBJECTIVES This pilot trial tested the effect of adding a multi-level, technology-based physical activity intervention module to a standard survivorship care plan for breast and colorectal cancer survivors. The objective of this analysis was to determine whether the physical activity module improved health-related quality of life, sleep, and factors key to lasting behavior change (eg, social support, self-efficacy). METHODS Breast and colorectal cancer survivors (n = 50) were enrolled alongside a support partner. Survivors were assigned to receive a standard survivorship care plan either alone or augmented by a 12-week multi-component physical activity module. The module included a Fitbit tracker (with the physical activity data integrated into the electronic health record for clinician review) and customized email feedback. Physical activity was measured using the ActiGraph GT3X+. Psychosocial outcomes included the SF-36, FACT, ISEL, PROMIS sleep measures, and physical activity beliefs. Data were analyzed using linear mixed modeling. RESULTS Cancer survivors were aged 54.4 ± 11.2 years and were 2.0 ± 1.5 years from diagnosis. Relative to comparison, the intervention was associated with moderate-to-large improvements in physical health (effect size: d = 0.39, 95% CI = 0.0, 0.78), mental health (d = 0.59, 95% CI = 0.19, 0.99), sleep impairment (d = 0.62, 95% CI = -1.02, -0.22), and exercise self-efficacy (d = 0.60, 95% CI = 0.20, 1.0). CONCLUSIONS The intervention delivered meaningful improvements in survivors' quality of life, social support, and sleep impairment. If replicated in a larger sample, adding a technology-supported physical activity module to survivorship care plans may be a practical strategy for supporting healthy survivorship. TRIAL REGISTRATION ClinicalTrials.gov#: NCT02677389.

White individuals in the United States (US) have historically had disproportionate access to firearms. The real-life availability of firearms, including those most lethal, may still be greater among White populations, manifesting in the number of victims in shootings. We compared the severity of US mass public shootings since Columbine by race and/or ethnicity of the perpetrator using The Violence Project Database of Mass Shooters, assessing fatalities (minimum four), total victims, type, and legal status of guns used. We used data visualization and Quasi-Poisson regression of victims minus four - accounting for truncation at 4 fatalities - to assess fatality and total victim rates comparing Non-Hispanic (NH) White with NH Black shooters, using winsorization to account for outlier bias from the 2017 Las Vegas shooting. In 104 total mass public shootings until summer 2021, NH White shooters had higher median fatalities (6 [IQR 5-9] versus 5 [IQR 4-6]) and total victims (9 [IQR 6-19] versus 7 [IQR 5-12]) per incident. Confidence intervals of NH Black versus NH White fatalities rate ratios (RR) ranged from 0.17-1.15, and of total victim RRs from 0.15-1.04. White shooters were overrepresented in mass public shootings with the most victims, typically involving legally owned assault rifles. To better understand the consequences when firearms are readily available, including assault rifles, we need a database of all US gun violence. Our assessment of total victims beyond fatalities emphasizes the large number of US gun violence survivors and the need to understand their experiences to capture the full impact of gun violence.

Background: African ancestry is associated with a higher prevalence and greater severity of asthma than European ancestries, yet genetic studies of the most common locus associated with childhood-onset asthma, 17q12–21, in African Americans have been inconclusive. The aim of this study was to leverage both the phenotyping of the Children's Respiratory and Environmental Workgroup (CREW) birth cohort consortium, and the reduced linkage disequilibrium in African Americans, to fine map the 17q12–21 locus. Methods: We first did a genetic association study and meta-analysis using 17q12–21 tag single-nucleotide polymorphisms (SNPs) for childhood-onset asthma in 1613 European American and 870 African American children from the CREW consortium. Nine tag SNPs were selected based on linkage disequilibrium patterns at 17q12–21 and their association with asthma, considering the effect allele under an additive model (0, 1, or 2 effect alleles). Results were meta-analysed with publicly available summary data from the EVE consortium (on 4303 European American and 3034 African American individuals) for seven of the nine SNPs of interest. Subsequently, we tested for expression quantitative trait loci (eQTLs) among the SNPs associated with childhood-onset asthma and the expression of 17q12–21 genes in resting peripheral blood mononuclear cells (PBMCs) from 85 African American CREW children and in upper airway epithelial cells from 246 African American CREW children; and in lower airway epithelial cells from 44 European American and 72 African American adults from a case-control study of asthma genetic risk in Chicago (IL, USA). Findings: 17q12–21 SNPs were broadly associated with asthma in European Americans. Only two SNPs (rs2305480 in gasdermin-B [GSDMB] and rs8076131 in ORMDL sphingolipid biosynthesis regulator 3 [ORMDL3]) were associated with asthma in African Americans, at a Bonferroni-corrected threshold of p

Maternal depression is a risk factor for the development of problem behavior in children. Although food insecurity and housing instability are associated with adult depression and child behavior, how these economic factors mediate or moderate the relationship between maternal depression and child problem behavior is not understood. The purpose of this study was to determine whether food insecurity and housing instability are mediators and/or moderators of the relationship between maternal depression when children are age 3 and children's problem behaviors at age 9 and to determine whether these mechanisms differ by race/ethnicity. We used data from the Fragile Families and Child Wellbeing Study. Food insecurity and housing instability at age 5 were tested as potential mediators and moderators of the relationship between maternal depression status at age 3 and problem behavior at age 9. A path analysis confirmed our hypothesis that food insecurity and housing instability partially mediate the relationship between maternal depression when children are age 3 and problem behavior at age 9. However, housing instability was only a mediator for externalizing problem behavior and not internalizing problem behavior or overall problem behavior. Results of the moderation analysis suggest that neither food insecurity nor housing instability were moderators. None of the mechanisms explored differed by race/ethnicity. While our findings stress the continued need for interventions that address child food insecurity, they emphasize the importance of interventions that address maternal mental health throughout a child's life. Given the central role of maternal health in child development, additional efforts should be made to target maternal depression.

Introduction:Translating complex behavior change interventions into practice can be accompanied by a loss of fidelity and effectiveness. We present the evaluation of two sequential phases of implementation of a complex evidence-based community workshop to reduce falls, using the Replicating Effective Programs Framework. Between the two phases, workshop training and delivery were revised to improve fidelity with key elements.Methods:Stepping On program participants completed a questionnaire at baseline (phase 1: n = 361; phase 2: n = 2219) and 6 months post-workshop (phase 1: n = 232; phase 2: n = 1281). Phase 2 participants had an additional follow-up at 12 months (n = 883). Outcomes were the number of falls in the prior 6 months and the Falls Behavioral Scale (FaB) score.Results:Workshop participation in phase 1 was associated with a 6% reduction in falls (RR = 0.94, 95% CI 0.74–1.20) and a 0.14 improvement in FaB score (95% CI, 0.11– 0.18) at 6 months. Workshop participation in phase 2 was associated with a 38% reduction in falls (RR = 0.62, 95% CI 0.57–0.68) and a 0.16 improvement in FaB score (95% CI 0.14–0.18) at 6 months, and a 28% reduction in falls (RR = 0.72, 95% CI 0.65–0.80) and a 0.19 score improvement in FaB score (95% CI 0.17–0.21) at 12-month follow-up.Conclusions:Effectiveness can be maintained with widespread dissemination of a complex behavior change intervention if attention is paid to fidelity of key elements. An essential role for implementation science is to ensure effectiveness as programs transition from research to practice.

Purposeof Review This review highlights six “best practices” for cancer epidemiology coordinating centers to facilitate the success of a research consortium. Recent Findings Evidence from emerging literature regarding the Science of Team Science suggests that coordinating centers can more effectively foster collaborative cancer epidemiology research in consortia by (1) establishing collaboration as a shared goal at the start, (2) providing scientific expertise complementary to the research sites that adapts over the course of the project, (3) enacting anti-racist and inclusive approaches in all consortium decisions and activities, (4) fostering early-stage investigator career development, (5) engaging stakeholders including cancer survivors as peers, and (6) delivering reliable logistical support and technology tools with planned process evaluation so that researchers can collaboratively focus on the science. Summary By drawing on the Science of Team Science, coordinating centers can accelerate research progress and increase the impact of cancer epidemiology consortia.

PURPOSE: Endometrial cancer is strongly linked to obesity and inactivity; however, increased physical activity has important benefits even in the absence of weight loss. Resistance (strength) training can deliver these benefits; yet few women participate in resistance exercise. The purpose of this study was to describe both physiological and functional changes following a home-based strength training intervention. METHODS: Forty post-treatment endometrial cancer survivors within 5 years of diagnosis were enrolled in a pilot randomized trial, comparing twice-weekly home-based strength exercise to wait list control. Participants conducted the exercises twice per week for 10 supervised weeks with 5 weeks of follow-up. Measures included DXA-measured lean mass, functional fitness assessments, blood biomarkers, and quality of life outcomes. RESULTS: On average, participants were 60.9 years old (SD = 8.7) with BMI of 39.9 kg/m(2) (SD = 15.2). At baseline, participants had 51.2% (SD = 6.0) body fat, which was not different between groups. Improvements were seen in the 30-s chair sit to stand (d = .99), the 30-s arm curl (d = .91), and the 8-ft up-and-go test (d = .63). No changes were measured for HbA1c or C-reactive protein. No changes were observed for flexibility (chair sit and reach, back scratch tests), 6-min walk test, maximum handgrip test, anxiety, depression, fatigue, or self-efficacy for exercise. CONCLUSIONS: Home-based muscle-strengthening exercise led to favorable and clinically relevant improvements in 3 of 7 physical function assessments. Physical function, body composition, blood biomarkers, and patient-reported outcomes were feasible to measure. These fitness improvements were observed over a relatively short time frame of 10 weeks.

BACKGROUND High adolescent gun-related mortality, gun violence, pro-gun policies, white supremacy, and the long-term socioeconomic and other effects of racial oppression are intricately linked in the United States. Racist prejudice depicts male individuals of color as more prone to criminality than white male individuals. We described long-term patterns of weapon carrying in US schools among non-Hispanic (NH) white, NH Black/African American, and Hispanic boys, hypothesizing that in contrast to racist stereotypes, boys of color did not bring weapons into schools more often than NH white boys in recent years. METHODS We conducted a time series analysis using 1993–2019 Youth Risk Behavior Surveillance System data comparing boys’ self-reported weapon carrying in a nationally representative sample of US high schools by race and/or ethnicity, age, and self-reported experience of safety and violence at school. RESULTS Weapon carrying in schools has declined among all boys. Comparing all schools, we found no significant differences in weapon carrying (4%–5%) by race and/or ethnicity in 2017 and 2019. Boys who reported experiencing violence or feeling unsafe at school were at least twice as likely to bring a weapon into school, and such negative experiences were more common among boys of color (8%–12%) than among NH white boys (4%–5%). In schools perceived as safer, NH white boys have been more likely to bring weapons into schools than NH Black/African American or Hispanic boys in the past 20 years. CONCLUSIONS Our findings contradict racist prejudice with regard to weapon carrying in schools, particularly in more favorable school environments. Making schools safer may reduce weapon carrying in schools where weapon carrying is most common.

BackgroundSchools are primary venues of influenza amplification with secondary spread to communities. We assessed K-12 student absenteeism monitoring as a means for early detection of influenza activity in the community.Materials and MethodsBetween September 2014 and March 2020, we conducted a prospective observational study of all-cause (a-TOT), illness-associated (a-I), and influenza-like illness–associated (a-ILI) absenteeism within the Oregon School District (OSD), Dane County, Wisconsin. Absenteeism was reported through the electronic student information system. Students were visited at home where pharyngeal specimens were collected for influenza RT-PCR testing. Surveillance of medically-attended laboratory-confirmed influenza (MAI) occurred in five primary care clinics in and adjoining OSD. Poisson general additive log linear regression models of daily counts of absenteeism and MAI were compared using correlation analysis.FindingsInfluenza was detected in 723 of 2,378 visited students, and in 1,327 of 4,903 MAI patients. Over six influenza seasons, a-ILI was significantly correlated with MAI in the community (r = 0.57; 95% CI: 0.53—0.63) with a one-day lead time and a-I was significantly correlated with MAI in the community (r = 0.49; 0.44-0.54) with a 10-day lead time, while a-TOT performed poorly (r = 0.27; 0.21—0.33), following MAI by six days.DiscussionSurveillance using cause-specific absenteeism was feasible and performed well over a study period marked by diverse presentations of seasonal influenza. Monitoring a-I and a-ILI can provide early warning of seasonal influenza in time for community mitigation efforts.

Physical activity (pre- and post-diagnosis) has been studied in prevention and survivorship contexts for endometrial cancer. However, the association of physical activity (PA) across the lifespan on mortality risk among endometrial cancer survivors is understudied. The study's objective was to identify the association of lifetime PA on mortality risk in endometrial cancer survivors.Seven hundred forty-five endometrial cancer survivors drawn from a population-based cancer registry (diagnosed between 1991 and 1994) reported the frequency (sessions/week) of moderate- and vigorous intensity physical activity (MVPA) at age 12, age 20, and 5 years pre-interview (post-diagnosis). Cox proportional hazards were used to estimate hazard ratios (HR) and 95% confidence intervals for the association between PA, all-cause, and cardiovascular disease mortality as assessed in 2016. MVPA was modeled using natural cubic splines.Diagnosis age, body mass index, and smoking (pack-years) were each positively associated with increased all-cause mortality risk. Those who did one session of MVPA 5 years pre-interview had a lower mortality risk (HR 0.61; 95% CI 0.41-0.92) compared to those with no MVPA. Those reporting one session of MVPA was similarly observed at age 12 (HR 0.95; 95% CI 0.86-1.06) and at age 20 (HR 0.87; 95% CI 0.65-1.16).Those who participated in PA, compared to those who did not, in the 5 years before diagnosis had a lower mortality risk. While PA was not independently protective against mortality risk at ages 12 or 20, PA is still important for endometrial cancer survivors for other non-mortality outcomes.

Purpose To evaluate the relationship of retinal layer thickness with age and age-related macular degeneration (AMD) in the Carotenoids in Age-Related Eye Disease Study 2. Methods Total retinal thickness within the macular area, and individual layer thickness was determined for CAREDS2 participants (n = 906 eyes, 473 women) from the Women's Health Initiative using Heidelberg optical coherence tomography (OCT). Mean measurements within the OCT grid were compared across age tertiles (69–78, 78–83, and 83–101 years) and AMD outcomes. Results Mean retinal thickness in the central circle, inner ring, and outer ring were 277 ± 34 µm, 326 ± 20 µm, and 282 ± 15 µm, respectively. Thickness did not vary by age in the central circle, but decreased with age in the inner and outer circles (P ≤ 0.004). Specifically, ganglion cell (GCL), inner plexiform, and outer nuclear (ONL) layer thickness decreased with age (P ≤ 0.003). Age-adjusted retinal thickness in all three circles did not vary by AMD outcomes (486 without AMD and 413 with AMD). However, individual layers showed changes with GCL and photoreceptor thinning and retinal pigment epithelial thicknening in eyes with late AMD. After controlling for age and AMD, higher ONL thickness was associated with better visual acuity. Conclusions In this cohort of older women, a decrease in perifoveal thickness was associated with increasing age, particularly in the inner retinal layers. Variabilty in thickness in AMD eyes was primarily due to outer retinal layers. Among all retinal layers, the ONL plays an important role in preserving visual acuity. Translational Relevance The study provides a deeper understanding of age related changes to the retinal layers and their effect on visual loss.

Purpose To examine the relationships of retinal vessel geometric characteristics (RVGCs) to the incidence and progression of diabetic retinopathy (DR). Design Observational, prospective cohort study. Participants Nine hundred ninety-six persons with type 1 diabetes mellitus (T1DM) and 1370 persons with type 2 diabetes mellitus (T2DM) seen at a baseline examination who were eligible for follow-up examinations at subsequent 5-year intervals. A total of 3846 person-interval data from these follow-up examinations are the basis for the analyses. Methods Diabetic retinopathy and macular edema were assessed by grading of 30° stereoscopic color fundus photographs. Retinal vessel geometric characteristics were assessed using the Singapore I Vessel Assessment program from a digitized copy of 1 of the field 1 fundus photographs obtained at baseline and follow-up. Main Outcome Measures The 5-year incidence of any DR, progression of DR, and incidence of proliferative diabetic retinopathy (PDR) and clinically significant macular edema (CSME) in right eyes. Results Incident DR occurred in 45%, progression in 32%, PDR in 10%, and CSME in 5%. While adjusting for glycated hemoglobin, duration of diabetes, and other factors, retinal arteriolar simple tortuosity was associated significantly with the incidence of any DR (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01–1.35). Retinal venular branching angle was associated significantly with progression of DR (OR, 1.18; 95% CI, 1.03–1.36), retinal venular curvature tortuosity was associated significantly with the incidence of PDR (OR, 1.15; 95% CI, 1.01–1.30), and retinal venular branching angle (OR, 1.41; 95% CI, 1.10–1.82) was associated significantly with the incidence of CSME. There were no significant associations of other RVGCs with any of the DR outcomes in the full multivariate model. Inclusion of all possible RVGCs did not improve the predictive value of the models that already included retinal vessel diameter and baseline DR severity level. Conclusions Retinal vessel geometric characteristics of the retinal venules were associated with progression of DR; however, most of the RVGCs measured from digitized fundus photographs added little to the assessment of risk of incidence and progression of DR when other risk factors were considered in T1DM and T2DM.

Spatial and spatio-temporal cluster detection are important tools in public health and many other areas of application. Cluster detection can be approached as a multiple testing problem, typically using a space and time scan statistic. We recast the spatial and spatio-temporal cluster detection problem in a high-dimensional data analytical framework with Poisson or quasi-Poisson regression with the Lasso penalty. We adopt a fast and computationally-efficient method using a novel sparse matrix representation of the effects of potential clusters. The number of clusters and tuning parameters are selected based on (quasi-)information criteria. We evaluate the performance of our proposed method including the false positive detection rate and power using a simulation study. Application of the method is illustrated using breast cancer incidence data from three prefectures in Japan.

Rationale: Rhinovirus (RV) C can cause asymptomatic infection and respiratory illnesses ranging from the common cold to severe wheezing. Objectives: To identify how age and other individual-level factors are associated with susceptibility to RV-C illnesses. Methods: Longitudinal data from the COAST (Childhood Origins of Asthma) birth cohort study were analyzed to determine relationships between age and RV-C infections. Neutralizing antibodies specific for RV-A and RV-C (three types each) were determined using a novel PCR-based assay. Data were pooled from 14 study cohorts in the United States, Finland, and Australia, and mixed-effects logistic regression was used to identify factors related to the proportion of RV-C versus RV-A detection. Measurements and Main Results: In COAST, RV-A and RV-C infections were similarly common in infancy, whereas RV-C was detected much less often than RV-A during both respiratory illnesses and scheduled surveillance visits (P

Background Studies indicate that the nasal microbiome may correlate strongly with the presence or future risk of childhood asthma. Objectives In this study, we tested whether developmental trajectories of the nasopharyngeal microbiome in early life and the composition of the microbiome during illnesses were related to risk of childhood asthma. Methods Children participating in the Childhood Origins of Asthma study (n=285) provided nasopharyngeal mucus samples in the first two years of life, during routine healthy study visits (2, 4, 6, 9, 12, 18 and 24 months of age) and episodes of respiratory illnesses, which were analyzed for respiratory viruses and bacteria. We identified developmental trajectories of early-life microbiome composition, as well as predominant bacteria during respiratory illnesses, and correlated these with presence of asthma at 6, 8, 11, 13 and 18 years of age. Results Of the four microbiome trajectories identified, a Staphylococcus-dominant microbiome in the first 6 months of life was associated with increased risk of recurrent wheezing by age 3 years and asthma that persisted throughout childhood. In addition, this trajectory was associated with the early onset of allergic sensitization. During wheezing illnesses, detection of rhinoviruses and predominance of Moraxella were associated with asthma that persisted throughout later childhood. Conclusion In infancy, the developmental composition of the microbiome during healthy periods and the predominant microbes during acute wheezing illnesses are both associated with the subsequent risk of developing persistent childhood asthma. Clinical Implication Identifying factors that promote early colonization with S. aureus may lead to future interventional studies to prevent childhood asthma., Capsule summary: In a birth cohort study, early colonization of the upper airway with Staphylococcus aureus and detection of rhinoviruses and Moraxella catarrhalis during illnesses were associated with subsequent childhood asthma.

OBJECTIVES: We examined the association of exposure to maternal depression during year 2 of a child’s life with future child problem behavior. We conducted a secondary analysis to investigate whether race/ethnicity is a moderator of this relationship. METHODS: We used Fragile Families and Child Well-Being Study data (age 3 N=3288 and 49% Black, 26% Hispanic, 22% non-Hispanic White; age 5 N=3001 and 51% Black, 25% Hispanic, 21% non-Hispanic White; age 9 N=3630 and 50% Black, 25% Hispanic, 21% non-Hispanic White) and ordinal logistic regression to model problem behavior at ages 3, 5, and 9 on maternal depression status during year 2. RESULTS: At age 9, children whose mother was depressed during year 2 were significantly more likely to have higher internalizing (AOR=1.92, 95% CI: 1.42,2.61) and externalizing (AOR=1.65, 95% CI: 1.10,2.48) problem behavior scores. In our secondary analysis, race/ethnicity did not have moderating effects, potentially due to a limitation of the data that required use of maternal self-reported race/ethnicity as a proxy for child race/ethnicity. Conclusions for Practice: Exposure to maternal depression after the prenatal and perinatal periods may have a negative association with children’s behavioral development through age 9. Interventions that directly target maternal depression during this time should be developed. Additional research is needed to further elucidate the role of race/ethnicity in the relationship between maternal depression and child problem behavior.

Objectives We aimed to estimate the association between Medicaid unbundling of payment for long-acting reversible contraceptives (LARC) from the global delivery fee and immediate postpartum (IPP) LARC provision, in a state outside a select group of early-adopters. We also examine the potential moderating roles of hospital academic affiliation and Catholic status on the association between unbundling and IPP LARC provision. Methods We used a pre–post design to examine the association between unbundling and IPP LARC provision. We observed Medicaid-covered childbirth deliveries in Wisconsin hospitals between January 2016 and December 2017 (n = 45,200) in the State Inpatient Database from the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project. We conducted multivariate regressions using generalized linear mixed models. Results From 2016 to 2017, IPP LARC provision increased from 0.28% to 0.44% of deliveries (p = .003). In our adjusted model, IPP LARC provision was 1.55 times more likely in the post–period versus the pre-period (95% confidence interval, 1.12–2.13). Both before and after unbundling, IPP LARC provision was significantly more common in academic versus nonacademic settings and was exceedingly rare in Catholic institutions. Conclusions In contrast with many early adopting states, in this later adopting state, Wisconsin Medicaid's unbundling of LARC from the global fee did not meaningfully change the rates of IPP LARC provision. These results indicate that delivery hospital characteristics are strong correlates of access to IPP LARC and suggest the need for interventions—perhaps outside of the inpatient setting—to ensure that patients can access desired contraceptive methods promptly postpartum.

Bicycles are a source of transportation, recreation, and exercise throughout the world. Bicycling is associated with both health and environmental benefits but also poses a risk of injury. The use of bicycle helmets has been shown to reduce morbidity and mortality associated with cycling. It is unknown if helmet use differs across Wisconsin geographic areas and sociodemographic groups.Data were obtained from the Survey of the Health of Wisconsin (SHOW). Bicycle use and helmet use frequency were determined from a self-administered questionnaire that contained questions specific to preventative health behaviors. Descriptive statistics summarized overall bicycle ridership. Chi-square and Student t tests were performed to assess relationships between bicycle and helmet use across geographic categories and sociodemographic groups.Differences between sex, race or ethnicity, and education level were found to be associated with bicycle ridership and the frequency of helmet use. Men were significantly more likely to report riding a bicycle and never wearing a helmet. Individuals from urban communities reported always wearing a helmet more often than rural communities. Higher education levels were associated with higher levels of bicycle and helmet use. Race or ethnicity was not associated with bicycle ridership but was associated with differences in helmet use frequency.Nearly half of those who ride bicycles in Wisconsin report never wearing a helmet. Since bicycle ridership and helmet use were found to be associated with a number of sociodemographic characteristics, any solution should consider the role of equity when attempting to increase ridership or helmet use.

PURPOSE: Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer. METHODS: Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n = 5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses. RESULTS: In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5 kg/m(2) difference in BMI = 0.85, 95% CI 0.75–0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI ≥ 35 kg/m(2) vs. 18.5–24.9 kg/m(2) = 4.74, 95% CI 1.78–12.59). CONCLUSIONS: Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

It is fairly common to rank different geographic units, e.g. counties in the USA, based on health indices. In a typical application, point estimates of the health indices are obtained for each county, and the indices are then simply ranked as if they were known constants. Several authors have considered optimal rank estimators under squared error loss on the rank scale as a default method for general purpose ranking, e.g. situations where ranking units across the full spectrum of performance (low, medium, high) is important. While computationally convenient, squared error loss on the rank scale may not represent the true inferential goals of rank consumers. We construct alternative loss functions based on three components: (1) the inferential goal (rank position or pairwise comparisons), (2) the scale (original, log-transformed or rank) and (3) the (positional or pairwise) loss function (0/1, squared error or absolute error). We can obtain optimal ranks for loss functions based on rank positions and nearly optimal ranks for loss functions based on pairwise comparisons paired with highest posterior density (HPD) credible intervals. We compare inferences produced by the various ranking methods, both optimal and heuristic, using low birth weight data for counties in the Midwestern United States, from 2006 to 2012.

Objective. Breast cancer simulation models must take changing mortality rates into account to evaluate the potential impact of cancer control interventions. We estimated mortality rates due to breast cancer and all other causes combined to determine their impact on overall mortality by year, age, and birth cohort. Methods. Based on mortality rates from publicly available datasets, an age-period-cohort model was used to estimate the proportion of deaths due to breast cancer for US women aged 0 to 119 years, with birth years 1900 to 2000. Breast cancer mortality was calculated as all-cause mortality multiplied by the proportion of deaths due to breast cancer; other-cause mortality was the difference between all-cause and breast cancer mortality. Results. Breast cancer and other-cause mortality rates were higher for older ages and birth cohorts. The percent of deaths due to breast cancer increased across birth cohorts from 1900 to 1940 then decreased. Among 50-year-old women, in the 1920 birth cohort, 52 (9.9%) of 100,000 deaths (95% CI, 9.8% to 10.1%) were attributed to breast cancer whereas 476 of 100,000 were due to other causes; in the 1960 birth cohort, 22 (8.5%) of 100,000 deaths (95% CI, 8.3% to 8.7%) were attributed to breast cancer with 242 of 100,000 deaths due to other causes. The percentage of all deaths due to breast cancer was highest (4.1% to 12.9%) for women in their 40s and 50s for all birth cohorts. Conclusions. This study offers evidence that advances in breast cancer screening and treatment have reduced breast cancer mortality for women across the age spectrum, and provides estimates of age-, year- and birth cohort-specific competing mortality rates for simulation models. Other-cause mortality estimates are important in these models because most women die from causes other than breast cancer.

The University of Wisconsin Breast Cancer Epidemiology Simulation Model (UWBCS), also referred to as Model W, is a discrete-event microsimulation model that uses a systems engineering approach to replicate breast cancer epidemiology in the US over time. This population-based model simulates the lifetimes of individual women through 4 main model components: breast cancer natural history, detection, treatment, and mortality. A key feature of the UWBCS is that, in addition to specifying a population distribution in tumor growth rates, the model allows for heterogeneity in tumor behavior, with some tumors having limited malignant potential (i.e., would never become fatal in a woman’s lifetime if left untreated) and some tumors being very aggressive based on metastatic spread early in their onset. The model is calibrated to Surveillance, Epidemiology, and End Results (SEER) breast cancer incidence and mortality data from 1975 to 2010, and cross-validated against data from the Wisconsin cancer reporting system. The UWBCS model generates detailed outputs including underlying disease states and observed clinical outcomes by age and calendar year, as well as costs, resource usage, and quality of life associated with screening and treatment. The UWBCS has been recently updated to account for differences in breast cancer detection, treatment, and survival by molecular subtypes (defined by ER/HER2 status), to reflect the recent advances in screening and treatment, and to consider a range of breast cancer risk factors, including breast density, race, body-mass-index, and the use of postmenopausal hormone therapy. Therefore, the model can evaluate novel screening strategies, such as risk-based screening, and can assess breast cancer outcomes by breast cancer molecular subtype. In this article, we describe the most up-to-date version of the UWBCS.

Due to limitations in the ability to identify non-progressive disease, ductal carcinoma in situ (DCIS) is usually managed similarly to localized invasive breast cancer. We used simulation modeling to evaluate the potential impact of a hypothetical test that identifies non-progressive DCIS. A discrete-event model simulated a cohort of U.S. women undergoing digital screening mammography. All women diagnosed with DCIS underwent the hypothetical DCIS prognostic test. Women with test results indicating progressive DCIS received standard breast cancer treatment and a decrement to quality of life corresponding to the treatment. If the DCIS test indicated non-progressive DCIS, no treatment was received and women continued routine annual surveillance mammography. A range of test performance characteristics and prevalence of non-progressive disease were simulated. Analysis compared discounted quality-adjusted life years (QALYs) and costs for test scenarios to base-case scenarios without the test. Compared to the base case, a perfect prognostic test resulted in a 40% decrease in treatment costs, from $13,321 to $8005 USD per DCIS case. A perfect test produced 0.04 additional QALYs (16 days) for women diagnosed with DCIS, added to the base case of 5.88 QALYs per DCIS case. The results were sensitive to the performance characteristics of the prognostic test, the proportion of DCIS cases that were non-progressive in the model, and the frequency of mammography screening in the population. A prognostic test that identifies non-progressive DCIS would substantially reduce treatment costs but result in only modest improvements in quality of life when averaged over all DCIS cases.

Purpose To determine if skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation endproducts and oxidative stress in skin is associated with AMD. Methods SIF was measured with the SCOUT DS skin fluorescence spectrometer in a cross-sectional cohort study of 969 persons aged 68 to 102 years from the 1181 who participated in the 25-year follow-up examination in the Beaver Dam Eye Study (BDES) in 2014 to 2016. The SCOUT DS skin fluorescence spectrometer uses five light-emitting diodes, centered at 375 nm to 456 nm. AMD was assessed by grading of digital color 45° stereoscopic fundus photographs of the macula using the Wisconsin Age-Related Maculopathy grading scheme. Analyses included logistic regression with generalized estimating equations to account for correlation between the eyes of a person. Results There were data for 1827 eyes for analyses. Early AMD was present in 22% and late AMD in 4% of the eyes. While adjusting for age, sex, smoking status, and history of cardiovascular disease, there were no significant associations of any SIF measure with any AMD or exudative AMD. SIF01 (odds ratio per 1 SD difference on the log scale, 95% confidence interval) (1.66, 1.00-2.74, P = 0.05) and SIF03 (1.81, 1.16-2.81, P = 0.008) were associated with geographic atrophy. Conclusions There was a suggestive relationship of two SIF measures, SIF01 and SIF03, using different correction factors from the excitation centered at 375 nm, with the prevalence of geographic atrophy in the BDES. Longitudinal follow-up is indicated to assess a temporal relationship.

Funding has been provided by a USDA Cooperative State Research, Education and Extension Service (CSREES) McIntire-Stennis project. We thank the School of Natural Resources and Agricultural Sciences, University of Alaska Fairbanks, for the development and maintenance of the Cooperative Alaska Forest Inventory, and thank the Global Forest Biodiversity Initiative (GFBI) for establishing data-sharing protocols and standards for international collaborative research projects. We also thank Thomas Malone for his insights on Alaska boreal forest.

Popular approaches to spatial cluster detection, such as the spatial scan statistic, are defined in terms of the responses. Here, we consider a varying-coefficient regression and spatial clusters in the regression coefficients. For varying-coefficient regression, such as the geographically weighted regression, different regression coefficients are obtained for different spatial units. It is often of interest to the practitioners to identify clusters of spatial units with distinct patterns in a regression coefficient, but there is no formal statistical methodology for that. Rather, cluster identification is often ad-hoc such as by eyeballing the map of fitted regression coefficients and discerning patterns. In this paper, we develop new methodology for spatial cluster detection in the regression setting based on hypotheses testing. We evaluate our methods in terms of power and coverages for true clusters via simulation studies. For illustration, our methodology is applied to a cancer mortality dataset. Copyright © 2016 John Wiley & Sons, Ltd.

To examine factors influencing primary care provider (PCP) adoption of CT colonography (CTC) for colorectal cancer (CRC) screening. We performed a retrospective cohort study linking electronic health record (EHR) data with PCP survey data. Patients were eligible for inclusion if they were not up-to-date with CRC screening and if they had CTC insurance coverage in the year prior to survey administration. PCPs were included if they had at least one eligible patient in their panel and completed the survey (final sample N = 95 PCPs; N = 6245 patients). Survey data included perceptions of CRC screening by any method, as well as CTC specifically. Multivariate logistic regression estimated odds ratios and 95% confidence intervals for PCP and clinic predictors of CRC screening by any method and screening with CTC. Substantial variation in CTC use was seen among PCPs and clinics (range 0–16% of CRC screening). Predictors of higher CTC use were PCP perceptions that CTC is effective in reducing CRC mortality, higher number of perceived advantages to screening with CTC, and Internal Medicine specialty. Factors not associated with CTC use were PCP perceptions of less organizational capacity to meet demand for colonoscopy, number of perceived disadvantages to screening with CTC, PCP age and gender, and clinic factors. Significant variation in PCP adoption of CTC exists. PCP perceptions of CTC and specialty practice were related to CTC adoption. Strategies to increase PCP adoption of CTC for CRC screening should include emphasis on the effectiveness and advantages of CTC.

Background: Air emissions from concentrated animal feeding operations (CAFO) have been associated with respiratory and allergic symptoms among farm workers, primarily on swine farms. Despite the increasing prevalence of CAFOs, few studies have assessed respiratory health implications among residents living near CAFOs and few have looked at the health impacts of dairy CAFOs. Objectives: The goal of this study was to examine objective and subjective measures of respiratory and allergic health among rural residents living near dairy CAFOs in a general population living in the Upper Midwest of the United States. Methods: Data were from the 2008–2016 Survey of the Health of Wisconsin (SHOW) cohort (n = 5338), a representative, population based sample of rural adults (age 18+). The association between distance to the nearest CAFO and the prevalence of self-reported physician-diagnosed allergies, asthma, episodes of asthma in the last 12 months, and asthma medication use was examined using logistic regression, adjusting for covariates and sampling design. Similarly, the association between distance to the nearest CAFO and lung function, measured using spirometry, was examined using multivariate linear regression. Restricted cubic splines accounted for nonlinear relationships between distance to the nearest CAFO and the aforementioned outcomes. Results: Living 1.5 miles from a CAFO was associated with increased odds of self-reported nasal allergies (OR = 2.08; 95% CI: 1.38, 3.14), lung allergies (OR = 2.72; 95% CI: 1.59, 4.66), asthma (OR = 2.67; 95% CI: 1.39, 5.13), asthma medication (OR = 3.31; 95% CI: 1.65 6.62), and uncontrolled asthma, reported as an asthma episode in last 12 months (OR = 2.34; 95% CI: 1.11, 4.92) when compared to living 5 miles from a CAFO. Predicted FEV1 was 7.72% (95% CI: −14.63, −0.81) lower at a residential distance 1.5 miles from a CAFO when compared with a residence distance of 3 miles from a CAFO. Conclusions: Results suggest CAFOs may be an important source of adverse air quality associated with reduced respiratory and allergic health among rural residents living in close proximity to a CAFO. Keywords: Air pollution, Concentrated animal feeding operation, Lung function, Allergies, Asthma

IntroductionApproximately 25%–35% of the 1991 Gulf War Veteran population report symptoms consistent with Gulf War Illness (GWI), a chronic, multi-symptom illness characterised by fatigue, pain, irritable bowel syndrome and problems with cognitive function. GWI is a disabling problem for Gulf War Veterans, and there remains a critical need to identify innovative, novel therapies.Gut microbiota perturbation plays a key role in the symptomatology of other chronic multi-symptom illnesses, including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Given similarities between ME/CFS and GWI and the presence of gastrointestinal disorders in GWI patients, Veterans with GWI may also have gut abnormalities like those seen with ME/CFS. In this longitudinal cohort study, we are comparing the diversity (structure) and the metagenomes (function) of the gut microbiome between Gulf War Veterans with and without GWI. If we find differences in Veterans with GWI, the microbiome could be a target for therapeutic intervention to alleviate GWI symptoms.Methods and analysisParticipants answer questions about diet, exercise and lifestyle factors. Participants also complete a questionnaire (based on the Kansas case definition of GWI) regarding their medical history and symptoms; we use this questionnaire to group participants into GWI versus healthy control cohorts. We plan to enrol 52 deployed Gulf War Veterans: 26 with GWI and 26 healthy controls. Participants provide stool and saliva samples weekly for an 8-week period for microbiome analyses. Participants also provide blood samples at the beginning and end of this period, which we will use to compare measures of inflammation markers between the groups.Ethics and disseminationThe protocol was approved by the University of Wisconsin-Madison Health Sciences Institutional Review Board and the William S. Middleton Memorial Veterans Hospital Research and Development Committee. Results of this study will be submitted for publication in a peer-reviewed journal.

Epidemiologic and cross-sectional studies suggest that early life farming and animal exposures are associated with major health benefits, influencing immune development and modifying the subsequent risk of allergic diseases, including asthma. The Wisconsin Infant Study Cohort (WISC) study was established in central Wisconsin to test the hypothesis that early life animal farm exposures are associated with distinct innate immune cell maturation trajectories, decreased allergen sensitization and reduced respiratory viral illness burden during the first 2 years of life. Beginning in 2013, a total of 240 families have been enrolled, 16,522 biospecimens have been collected, and 4098 questionnaires have been administered and entered into a secure database. Study endpoints include nasal respiratory virus identification and respiratory illness burden score, allergic sensitization, expression of allergic disease, and anti-viral immune response maturation and profiles. The WISC study prospective design, broad biospecimen collections, and unique US rural community will provide insights into the role of environmental exposures on early life immune maturation profiles associated with protection from allergic sensitization and significant respiratory viral disease burden. The WISC study findings will ultimately inform development of new strategies to promote resistance to severe respiratory viral illnesses and design primary prevention approaches for allergic diseases for all infants. Electronic supplementary material The online version of this article (10.1186/s13104-019-4448-0) contains supplementary material, which is available to authorized users.