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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

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.

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.

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

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.

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.

BackgroundActivity trackers are now ubiquitous in certain populations, with potential applications for health promotion and monitoring and chronic disease management. Understanding the accuracy of this technology is critical to the appropriate and productive use of wearables in health research. Although other peer-reviewed validations have examined other features (eg, steps and heart rate), no published studies to date have addressed the accuracy of automatic activity type detection and duration accuracy in wearable trackers. ObjectiveThe aim of this study was to examine the ability of 4 commercially available wearable activity trackers (Fitbits Flex 2, Fitbit Alta HR, Fitbit Charge 2, and Garmin Vívosmart HR), in a controlled setting, to correctly and automatically identify the type and duration of the physical activity being performed. MethodsA total of 8 activity types, including walking and running (on both a treadmill and outdoors), a run embedded in walking bouts, elliptical use, outdoor biking, and pool lap swimming, were tested by 28 to 34 healthy adult participants (69 total participants who participated in some to all activity types). Actual activity type and duration were recorded by study personnel and compared with tracker data using descriptive statistics and mean absolute percent error (MAPE). ResultsThe proportion of trials in which the activity type was correctly identified was 93% to 97% (depending on the tracker) for treadmill walking, 93% to 100% for treadmill running, 36% to 62% for treadmill running when preceded and followed by a walk, 97% to 100% for outdoor walking, 100% for outdoor running, 3% to 97% for using an elliptical, 44% to 97% for biking, and 87.5% for swimming. When activities were correctly identified, the MAPE of the detected duration versus the actual activity duration was between 7% and 7.9% for treadmill walking, 8.7% and 144.8% for treadmill running, 23.6% and 28.9% for treadmill running when preceded and followed by a walk, 4.9% and 11.8% for outdoor walking, 5.6% and 9.6% for outdoor running, 9.7% and 13% for using an elliptical, 9.5% and 17.7% for biking, and was 26.9% for swimming. ConclusionsIn a controlled setting, wearable activity trackers provide accurate recognition of the type of some common physical activities, especially outdoor walking and running and walking on a treadmill. The accuracy of measurement of activity duration varied considerably by activity type and tracker model and was poor for complex sets of activity, such as a run embedded within 2 walking segments.

Background. Since their inception in 2000, the Cancer Intervention and Surveillance Network (CISNET) breast cancer models have collaborated to use a nationally representative core of common input parameters to represent key components of breast cancer control in each model. Employment of common inputs permits greater ability to compare model output than when each model begins with different input parameters. The use of common inputs also enhances inferences about the results, and provides a range of reasonable results based on variations in model structure, assumptions, and methods of use of the input values. The common input data are updated for each analysis to ensure that they reflect the most current practice and knowledge about breast cancer. The common core of parameters includes population rates of births and deaths; age- and cohort-specific temporal rates of breast cancer incidence in the absence of screening and treatment; effects of risk factors on incidence trends; dissemination of plain film and digital mammography; screening test performance characteristics; stage or size distribution of screen-, interval-, and clinically- detected tumors by age; the joint distribution of ER/HER2 by age and stage; survival in the absence of screening and treatment by stage and molecular subtype; age-, stage-, and molecular subtype-specific therapy; dissemination and effectiveness of therapies over time; and competing non-breast cancer mortality. Method and Results. In this paper, we summarize the methods and results for the common input values presently used in the CISNET breast cancer models, note assumptions made because of unobservable phenomena and/or unavailable data, and highlight plans for the development of future parameters. Conclusion. These data are intended to enhance the transparency of the breast CISNET models.

PURPOSE. Women diagnosed with ductal carcinoma in situ (DCIS) often experience adverse changes in health-related behaviors following diagnosis. The impact of health behaviors on long-term quality of life (QoL) in DCIS survivors has not been investigated. METHODS. We examined the association of post-diagnosis body mass index (BMI), physical activity, alcohol, and smoking with QoL among 1,448 DCIS survivors aged 20–74 enrolled in the population-based Wisconsin in Situ Cohort from 1997–2006. Health behaviors and QoL were self-reported during biennial post-diagnosis interviews. Physical and mental QoL were measured using the validated SF-36 questionnaire. Generalized linear regression was used to determine the association between behaviors and QoL with adjustment for confounders. Lagged behavior variables were used to predict QoL during follow-up and avoid reverse causation. RESULTS. Women reported 3,536 QoL observations over an average 7.9 years of follow-up. Women maintaining a healthy BMI had on average a significantly higher summary measure score of physical QoL than obese women (normal vs. obese: β = 3.02; 2.18, 3.85). Physical QoL scores were also elevated among those who were physically active (5+ hours/week vs. none: β = 1.96; 0.72, 3.20), those consuming at least 7 drinks/week of alcohol (vs. none; β = 1.40; 0.39, 2.41), and non-smokers (vs. current smokers: β = 1.80; 0.89, 2.71). Summary measures of mental QoL were significantly higher among women who were moderately physically active (up to 2 hours/week vs. none: β = 1.11; 0.30, 1.92) and non-smokers (vs. current smokers: β = 1.49;0.45, 2.53). CONCLUSIONS. Our results demonstrate that maintaining healthy behaviors following DCIS treatment is associated with modest improvements in long-term QoL. These results inform interventions aimed at promoting healthy behaviors and optimizing QoL in DCIS survivors.

Purpose To assess the association between geographic access to mammography facilities and women's mammography utilization frequency. Methods Using data from the population-based 1995–2007 Wisconsin Women's Health study, we used proportional odds and logistic regression to test whether driving times to mammography facilities and the number of mammography facilities within 10 km of women's homes were associated with mammography frequency among women aged 50–74 years and whether associations differed between Rural-Urban Commuting Areas and income and education groups. Results We found evidence for nonlinear relationships between geographic access and mammography utilization (nonlinear effects of driving times and facility density, P -values .01 and .005, respectively). Having at least one nearby mammography facility was associated with greater mammography frequency among urban women (1 vs. 0 facilities, odds ratio 1.26, 95% confidence interval, 1.09–1.47), with similar effects among rural women. Adding more facilities had decreasing marginal effects. Long driving times tended to be associated with lower mammography frequency. We found no effect modification by income, education, or urbanicity. In rural settings, mammography nonuse was higher, facility density smaller, and driving times to facilities were longer. Conclusions Having at least one mammography facility near one's home may increase mammography utilization, with decreasing effects per each additional facility.

We tested the hypothesis that large areas of small hard drusen (diameter &lt, 63 µm) and intermediate drusen (diameter 63–124 µm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least two consecutive visits spaced five years apart over a 20-year period were included. A 6-level severity scale, including no drusen, four levels of increasing area (from minimal (&lt, 2596 µm²) to large (&gt, 9086 µm²)) of only small hard drusen, and intermediate drusen, was used. The five-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (p &lt, 0.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (p &lt, 0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.

Purpose To compare overall colorectal cancer (CRC) screening rates for patients who were eligible and due for CRC screening and who were with and without insurance coverage for computed tomographic (CT) colonography for CRC screening. Materials and Methods The institutional review board approved this retrospective cohort study, with a waiver of consent. This study used longitudinal electronic health record data from 2005 through 2010 for patients managed by one of the largest multispecialty physician groups in the United States. It included 33 177 patients under age 65 who were eligible and due for CRC screening and managed by the participating health system. Stratified Cox regression models provided propensity-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between CT colonography coverage and CRC screening. Results After adjustment, patients who had insurance coverage for CT colonography and were due for CRC screening had a 48% greater likelihood of being screened for CRC by any method compared with those without coverage who were due for CRC screening (HR, 1.48; 95% CI: 1.41, 1.55). Similarly, patients with CT colonography coverage had a greater likelihood of being screened with CT colonography (HR, 8.35; 95% CI: 7.11, 9.82) and with colonoscopy (HR, 1.38; 95% CI: 1.31, 1.45) but not with fecal occult blood test (HR, 1.00; 95% CI: 0.91, 1.10) than those without such insurance coverage. Conclusion Insurance coverage of CT colonography for CRC screening was associated with a greater likelihood of a patient being screened and a greater likelihood of being screened with a test that helps both to detect cancer and prevent cancer from developing (CT colonography or colonoscopy).

Rationale: We have previously reported that early rhinovirus (RV) wheezing illnesses are the most robust predictor of asthma development at age 6 years in high-risk children in the Childhood Origins of ASThma (COAST) birth cohort study. We sought to assess the role of etiology and frequency of wheezing illnesses in asthma risk from ages 6 to 13 years. Methods: A total of 259 children were followed prospectively to age 6 years, and 217 were followed to age 13 years. A generalized additive logistic regression model (GAM) of asthma was fit for asthma diagnosed at ages 6, 8, 11, 13 years, with smooth terms for number of RV wheezing illnesses, number of non-RV wheezing illnesses, and their interaction. In the absence of significant interaction the main effect p-values are reported. Results: The number of RV wheezing episodes in early childhood was significantly associated with asthma at all ages (6 years: p

Background Early life rhinovirus (RV) wheezing illnesses and aeroallergen sensitization increase the risk of asthma at school age. Whether these remain risk factors for the persistence of asthma out to adolescence is not established. Objective We sought to define the relationships among specific viral illnesses and the type and timing of aeroallergen sensitization with the persistence of asthma into adolescence. Methods A total of 217 children were followed prospectively from birth to age 13 years. The etiology and timing of viral wheezing illnesses during the first 3 years of life were assessed along with patterns of allergen sensitization. The associations between viral wheezing illnesses, presence and pattern of aeroallergen sensitization, and asthma diagnosis at age 13 years were evaluated. Results When adjusted for all viral etiologies, wheezing with RV (odds ratio = 3.3; 95% CI, 1.5-7.1), but not respiratory syncytial virus (odds ratio = 1.0; 95% CI, 0.4-2.3), was associated with asthma at age 13 years. Age of aeroallergen sensitization also influenced asthma risk; 65% of children sensitized by age 1 year had asthma at age 13 years, compared with 40% of children not sensitized at age 1 year but sensitized by age 5 years, and 17% of children not sensitized at age 5 years. Early life aeroallergen sensitization and RV wheezing had additive effects on asthma risk at adolescence. Conclusions In a high-risk birth cohort, the persistence of asthma at age 13 years was most strongly associated with outpatient wheezing illnesses with RV and aeroallergen sensitization in early life.

Purpose Studies of quality of life (QoL) are scarce among survivors of ductal carcinoma in situ (DCIS). The objective of this study was to assess long-term QoL in DCIS survivors in relation to age at diagnosis, time since diagnosis, and treatments received. Methods We assessed physical and mental measures of health-related QoL in 1,604 patients with DCIS diagnosed in 1997 to 2006 with up to four follow-up interviews. We further compared baseline QoL to 1,055 control patients without DCIS. QoL was measured using the validated Medical Outcomes Study Short Form 36 Health Status Survey questionnaire. Among patients with DCIS, we examined trends in QoL over time since diagnosis using generalized linear regression models, adjusting for confounders. We tested for effect modification by surgical treatment choice, post-treatment endocrine therapy use, and age at diagnosis. Results Both physical and mental measures of QoL among DCIS survivors at fewer than 2 years after diagnosis were comparable to controls. Mental measures of QoL among patients with DCIS declined at ≥ 10 years after diagnosis and were significantly lower than at less than 2 years after diagnosis (47.4 v 52.0; P < .01). In the first 5 years after a DCIS diagnosis, mental QoL was significantly higher among women diagnosed at ages 50 to 74 years compared with those diagnosed at ages 28 to 49 years, although this difference was not sustained in later time periods. Conclusion QoL after a DCIS diagnosis was generally comparable to that of women of similar age without a personal history of DCIS. Our findings suggest that DCIS survivors, and particularly those diagnosed at a younger age, may benefit from support for mental QoL.

A minority of women with urinary incontinence (UI) and even fewer with fecal incontinence (FI) report having discussed it with a health care provider in the past year. Thus our aim was to evaluate whether the use of an electronic pelvic floor assessment questionnaire (ePAQ-PF) improves communication about incontinence in primary care.Women 40 years and older who were scheduled for an annual wellness physical at an internal medicine clinic between August 2007 and August 2008 were randomized to complete the ePAQ-PF prior to (n = 145) or after (n = 139) their visit. Clinicians of women in the intervention group received the ePAQ-PF report prior to the visit. Outcome measures from clinic note abstraction included mention of UI (primary) and FI. Participant-reported outcome measures included discussion of UI and FI and initiator of discussion.Discussions of UI was more common in the intervention group than the control group: (27% vs. 19%; odds ratio [OR], 1.6 95% confidence interval [95%CI] 0.9-2.8, particularly for women over 60 (33% vs. 12%; OR 3.8, 95%CI 1.2-11.8) and for women with UI (42% vs. 25%; OR 2.2, 95%CI 1.1-4.1). The intervention primarily led to an increase in clinician-initiated UI discussions which were more common in the intervention group (18% vs. 4%, OR 4.8, 95%CI 1.9-12.0) Participants in the intervention group more frequently reported discussion of FI (14% vs. 6%; OR 2.5, 95%CI 1.1-6.0) which was clinician initiated in over half the cases (9% vs. 3%; OR 3.5, 95%CI 1.1-11.0).Use of the ePAQ-PF prior to clinic visits increases discussion of UI and FI, particularly clinician-initiated discussion. These findings suggest that such instruments may increase the detection and treatment of this often "silent" affliction.

Objectives The University of Wisconsin Population Health Institute has published the County Health Rankings since 2010. These rankings use population-based data to highlight health outcomes and the multiple determinants of these outcomes and to encourage in-depth health assessment for all United States counties. A significant methodological limitation, however, is the uncertainty of rank estimates, particularly for small counties. To address this challenge, we explore the use of longitudinal and pooled outcome data in hierarchical Bayesian models to generate county ranks with greater precision. Methods In our models we used pooled outcome data for three measure groups: (1) Poor physical and poor mental health days; (2) percent of births with low birth weight and fair or poor health prevalence; and (3) age-specific mortality rates for nine age groups. We used the fixed and random effects components of these models to generate posterior samples of rates for each measure. We also used time-series data in longitudinal random effects models for age-specific mortality. Based on the posterior samples from these models, we estimate ranks and rank quartiles for each measure, as well as the probability of a county ranking in its assigned quartile. Rank quartile probabilities for univariate, joint outcome, and/or longitudinal models were compared to assess improvements in rank precision. Results The joint outcome model for poor physical and poor mental health days resulted in improved rank precision, as did the longitudinal model for age-specific mortality rates. Rank precision for low birth weight births and fair/poor health prevalence based on the univariate and joint outcome models were equivalent. Conclusion Incorporating longitudinal or pooled outcome data may improve rank certainty, depending on characteristics of the measures selected. For measures with different determinants, joint modeling neither improved nor degraded rank precision. This approach suggests a simple way to use existing information to improve the precision of small-area measures of population health.

In order to better understand how family caregiving may contribute to poor health outcomes, this study sought to determine (1) if and to what extent caregiving characteristics were associated with caregiver strain and health-related quality of life (HRQoL), and (2) whether caregiver strain mediated this association. Data were from the 2008–2010 Survey of the Health of Wisconsin, a representative sample of Wisconsin adults aged 21–74 years. Participants completed questionnaires about their caregiving, sociodemographics, and HRQoL; 264 caregivers were identified. Staged generalized additive models assessed the associations among caregiving characteristics, caregiver strain, and HRQoL; survey weights were applied to account for the complex sampling design. More hours per week of care and greater duration of caregiving were associated with higher levels of strain. Greater caregiver strain was in turn associated with worse mental HRQoL. However, most caregiving characteristics were not directly associated with mental or physical HRQoL. The findings suggest a chains-of-risk model in which caregiving may increase strain, which may in turn adversely influence mental HRQoL. Using this perspective to refine interventions may improve our ability to support caregivers on practice and policy levels.

Purpose The reproductive windows between age at menarche and age at first birth (standardized age at first birth) and from menarche to menopause (reproductive lifespan) may interact with genetic variants in association with breast cancer risk. Methods We assessed this hypothesis in 6131 breast cancer cases and 7274 controls who participated in the population-based Collaborative Breast Cancer Study. Risk factor information was collected through telephone interviews, and DNA samples were collected on a subsample ( N = 1484 cases, 1307 controls) to genotype for 13 genome-wide association study-identified loci. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated, and P values for the interaction between reproductive windows and genotypes were obtained by adding cross-product terms to statistical models. Results For standardized age at first birth, the OR was 1.52 (CI, 1.36–1.71) comparing the highest quintile with the lowest quintile. Carrier status for rs10941679 (5p12) and rs10483813 ( RAD51B ) appeared to modify this relationship ( P = .04 and P = .02, respectively). For reproductive lifespan, the OR comparing the highest quintile with the lowest quintiles was 1.62 (CI, 1.35–1.95). No interactions were detected between genotype and reproductive lifespan (all P > .05). All results were similar regardless of ductal versus lobular breast cancer subtype. Conclusions Our results suggest that the reproductive windows are associated with breast cancer risk and that associations may vary by genetic variants.

Falling is a serious hazard for older veterans that may lead to severe injury, loss of independence, and death. While the American Geriatrics Society (AGS) provides guidelines to screen individuals at risk for falls, the guidelines may be less successful with specific subgroups of patients. In a veteran sample, we examined whether the Timed Up and Go (TUG) test, including a modified version, the TUG-Cognition, effectively detected potential fallers whose risk was associated with cognitive deficits. Specifically, we sought to determine whether TUG tasks and AGS criteria were differentially associated with executive dysfunction, whether the TUG tasks identified potential fallers outside of those recognized by AGS criteria, and whether these tasks distinguished groups of fallers. Participants included 120 mostly male patients referred to the Memory Assessment Clinic because of cognitive impairment. TUG-Cognition scores were strongly associated with executive dysfunction and differed systematically between fallers grouped by number of falls. These findings suggest that the TUG-Cognition shows promise in identifying fallers whose risk is related to or compounded by cognitive impairment. Future research should study the predictive validity of these measures by following patients prospectively.

Informal caregivers play a critical role in the care of individuals who are aging or have disabilities and are at increased risk for poor health outcomes. This study sought to determine whether and to what extent: (1) global stress and health-related quality of life (HRQoL) differed between caregivers and non-caregivers; (2) global stress mediated the relationship between caregiving status and HRQoL; and (3) caregiver strain (i.e., stress attributable to caregiving) was associated with worse HRQoL after accounting for global stress.Cross-sectional data were from the 2008-2010 Survey of the Health of Wisconsin, a representative sample of adults aged 21-74 years. Participants (n = 1,364) completed questionnaires about caregiving status, sociodemographics, global stress, and HRQoL. Staged generalized additive models assessed the impact of caregiving on HRQoL and the role of caregiver strain and global stress in this relationship.In the last 12 months, 17.2% of the sample reported caregiving. Caregivers reported worse mental HRQoL than non-caregivers (β -1.88, p = 0.02); global stress mediated this relationship (p0.01). Caregivers with the highest levels of strain reported worse mental and physical HRQoL (β -7.12, p0.01), and caregivers with the lowest levels of strain reported better mental HRQoL (β 2.06, p = 0.01) than non-caregivers; these associations were attenuated by global stress (p0.01).Global stress, rather than caregiving per se, contributes to poor HRQoL among caregivers, above and beyond the effect of caregiving strain. Screening, monitoring, and reducing stress in multiple life domains presents an opportunity to improve HRQoL outcomes for caregivers.

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.

Isometric progressive resistance oropharyngeal (I-PRO) therapy improves swallowing function; however, current devices utilize a single sensor that provides limited information or are prohibitively expensive. This single-subject study presents results of I-PRO therapy, detraining, and maintenance using the 5-sensor Madison Oral Strengthening Therapeutic (MOST) device combined with upper esophageal sphincter (UES) dilatation.A 56-year-old female nurse who was 27 months post stroke and subsequent to traditional behavioral interventions and UES dilatations presented limited to gastrostomy tube intake only and expectorating all saliva. She completed 8 weeks of I-PRO therapy, 5 weeks of detraining, and 9 weeks of I-PRO maintenance (reduced frequency) followed by a third UES dilatation post intervention. Data included diet inventory, lingual pressures (MOST), lingual volume (magnetic resonance imaging), postswallow residue (videofluoroscopy), UES and pharyngeal pressures (high-resolution manometry), and quality of life (QOL).Findings after 8 weeks of I-PRO therapy were progression to general oral diet, 15 lb weight gain, increased isometric pressures (Δ ≯16 kPa) with transference to swallowing pressures, increased lingual volume (8.3%), reduced pharyngeal wall residue (P = .03), increased pharyngeal pressures (Δ ≯ 43 mm Hg) and increased UES opening (nadir) pressures (Δ ≯ 9 mm Hg) with improved temporopressure coordination across the pharynx, and improved QOL. After detraining, decreased isometric pressures and reduced UES opening were noted. After I-PRO maintenance, isometric anterior lingual pressures returned to levels noted after the 8 weeks of intervention.I-PRO therapy, facilitated by the MOST device combined with instrumental UES dilatation, improved swallow safety, increased oropharyngeal intake, and facilitated UES opening while enriching QOL.

Background Prediction of subsequent school-age asthma during the preschool years has proven challenging. Objective To confirm in a post hoc analysis the predictive ability of the modified Asthma Predictive Index (mAPI) in a high-risk cohort and a theoretical unselected population. We also tested a potential mAPI modification with a 2-wheezing episode requirement (m 2 API) in the same populations. Methods Subjects (n = 289) with a family history of allergy and/or asthma were used to predict asthma at age 6, 8, and 11 years with the use of characteristics collected during the first 3 years of life. The mAPI and the m 2 API were tested for predictive value. Results For the mAPI and m 2 API, school-age asthma prediction improved from 1 to 3 years of age. The mAPI had high predictive value after a positive test (positive likelihood ratio ranging from 4.9 to 55) for asthma development at years 6, 8, and 11. Lowering the number of wheezing episodes to 2 (m 2 API) lowered the predictive value after a positive test (positive likelihood ratio ranging from 1.91 to 13.1) without meaningfully improving the predictive value of a negative test. Posttest probabilities for a positive mAPI reached 72% and 90% in unselected and high-risk populations, respectively. Conclusions In a high-risk cohort, a positive mAPI greatly increased future asthma probability (eg, 30% pretest probability to 90% posttest probability) and is a preferred predictive test to the m 2 API. With its more favorable positive posttest probability, the mAPI can aid clinical decision making in assessing future asthma risk for preschool-age children.

Context Aspirin is widely used for relief of pain and for cardioprotective effects. Its use is of concern to ophthalmologists when ocular surgery is being considered and also in the presence of age-related macular degeneration (AMD). Objective To examine the association of regular aspirin use with incidence of AMD. Design, Setting, and Participants The Beaver Dam Eye Study, a longitudinal population-based study of age-related eye diseases conducted in Wisconsin. Examinations were performed every 5 years over a 20-year period (1988-1990 through 2008-2010). Study participants (N = 4926) were aged 43 to 86 years at the baseline examination. At subsequent examinations, participants were asked if they had regularly used aspirin at least twice a week for more than 3 months. Main Outcome Measure Incidence of early AMD, late AMD, and 2 subtypes of late AMD (neovascular AMD and pure geographic atrophy), assessed in retinal photographs according to the Wisconsin Age-Related Maculopathy Grading System. Results The mean duration of follow-up was 14.8 years. There were 512 incident cases of early AMD (of 6243 person-visits at risk) and 117 incident cases of late AMD (of 8621 person-visits at risk) over the course of the study. Regular aspirin use 10 years prior to retinal examination was associated with late AMD (hazard ratio [HR], 1.63 [95% CI, 1.01-2.63]; P = .05), with estimated incidence of 1.76% (95% CI, 1.17%-2.64%) in regular users and 1.03% (95% CI, 0.70%-1.51%) in nonusers. For subtypes of late AMD, regular aspirin use 10 years prior to retinal examination was significantly associated with neovascular AMD (HR, 2.20 [95% CI, 1.20-4.15]; P = .01) but not pure geographic atrophy (HR, 0.66 [95% CI, 0.25-1.95]; P = .45). Aspirin use 5 years (HR, 0.86 [95% CI, 0.71-1.05]; P = .13) or 10 years (HR, 0.86 [95% CI, 0.65-1.13]; P = .28) prior to retinal examination was not associated with incident early AMD. Conclusions Among an adult cohort, aspirin use 5 years prior to observed incidence was not associated with incident early or late AMD. However, regular aspirin use 10 years prior was associated with a small but statistically significant increase in the risk of incident late and neovascular AMD.

Human rhinoviruses (HRVs) consist of approximately 160 types that cause a wide range of clinical outcomes, including asymptomatic infections, common colds, and severe lower respiratory illnesses.To identify factors that influence the severity of HRV illnesses.HRV species and types were determined in 1,445 nasal lavages that were prospectively collected from 209 infants participating in a birth cohort who had at least one HRV infection. Questionnaires were used during each illness to identify moderate to severe illnesses (MSI).Altogether, 670 HRV infections were identified, and 519 of them were solitary infections (only one HRV type). These 519 viruses belonged to 93 different types of three species: 49 A, 9 B, and 35 C types. HRV-A (odds ratio, 8.2) and HRV-C (odds ratio, 7.6) were more likely to cause MSI compared with HRV-B. In addition, HRV infections were 5- to 10-fold more likely to cause MSI in the winter months (P0.0001) compared with summer, in contrast to peak seasonal prevalence in spring and fall. When significant differences in host susceptibility to MSI (P = 0.004) were considered, strain-specific rates of HRV MSI ranged from less than 1% to more than 20%.Factors related to HRV species and type, season, and host susceptibility determine the risk of more severe HRV illness in infancy. These findings suggest that anti-HRV strategies should focus on HRV-A and -C species and identify the need for additional studies to determine mechanisms for seasonal increases of HRV severity, independent of viral prevalence, in cold weather months.

Information regarding the development and progression of age-related macular degeneration (AMD) has emerged from clinical and epidemiological studies.1–11 This has resulted in the development of severity scales ranging from no lesions through the most severe lesions (neovascular AMD and/or geographic atrophy).6,12–14 Most scales use size, type and area of drusen and retinal pigment epithelium (RPE) pigmentary abnormalities to define intermediate severity levels. While most epidemiological studies have investigated incidence and progression of AMD, few studies have examined regression and associated protective factors.2,5,9,11 In the Chesapeake Bay Waterman Study, large soft drusen disappeared in 34% of eyes over a 5-year follow-up.2 In the Melton Mowbray study, 20% of soft drusen regressed over a 7-year period.9 It is unclear what factors are associated with regression or how AMD transitions through various stages. Previous studies show that the Y402H polymorphism in the Complement Factor H (CFH) gene on chromosome 1q is strongly associated with AMD,15–18 suggesting a role for innate immunity and inflammation in AMD pathogenesis. Most studies have examined relationships of the Y402H polymorphism to incidence of early or progression to late AMD but few have considered progression through various stages of AMD or regression of AMD.19–22 Multi-state models (MSMs) can be used to gain greater insight into this relationship. We use MSMs to model transitions from the state at a study visit to the state at a subsequent visit.23–27 In practice, disease states are observed at intermittent study visits, and exact transition times are not observed; even when the exact date of death is known, the AMD state at death is unknown.28–31 Additionally, observations are frequently censored. For example, at the end of follow-up, subjects are known to be alive but their AMD state at that time is unknown. In this paper, we use MSMs to examine the effects of age, sex and the Y402H variant in the CFH gene on incidence, progression and regression of AMD as well as mortality in the population-based Beaver Dam Eye Study (BDES).

To the Editor: When sampling frames differ for cases and controls in a population based study, there are several analytical options to increase study validity. One is to exclude cases not found in the sampling frame for controls. Another, when the case sampling frame is nearly complete, is to link cases to the sampling frame for controls in order to obtain the information needed to model coverage propensity scores.1 Propensity scores have been used to address selection bias due to non-response and treatment-selection,2, 3 but we have found no studies that used propensity scores to address selection bias due to inadequate sampling frame coverage. We describe such an application here. Our analyses use data from the Wisconsin Women’s Health Study. Cases were women with incident invasive breast cancer reported to Wisconsin’s mandatory cancer registry. Controls were identified using a master file of licensed drivers who consented to have their private information released by the Wisconsin Department of Transportation. An estimated 68% of Wisconsin women with valid driver’s licenses provided this consent in 2008.4 Case eligibility was limited to women with a Wisconsin driver’s license (verified by self-report). We calculated odds ratio (OR) estimates of breast cancer risk using 3 established methods to correct selection bias, and compared these with published estimates.5, 6 The 3 methods were (1) excluding cases not in the control sampling frame, (2) applying propensity scores as weights, and (3) using quintiles of propensity scores to stratify analyses. We calculated standard errors of OR estimates to compare their precision. Additional details, including study inclusion criteria, are described elsewhere.4 The 2,988 breast cancer cases were linked to the driver’s license file to determine whether cases matched a record from the master-file of drivers (sampling frame for controls).4, 7 Propensity scores for inclusion in the sampling frame were calculated using logistic regression of 24 potential confounding factors ascertained through interviews with participants. The Table shows results of applying the 3 correction methods to a re-analysis of antidepressant medications and breast cancer risk.6 Of the 3 methods, stratifying by quintile of propensity score produced odds ratio3 with the best precision. Weighting, stratification and exclusion produced odds ratio3 with a similar degree of bias correction. However, the odds ratio3 changed only slightly after applying any of the correction methods. Similar results were found in another re-analysis of breast cancer risk, that one in relation to reproductive factors.4 Historically, the standard procedure in epidemiologic case-control studies has been to exclude cases that could not have been approached to serve as controls.8 This procedure assumes that factors that predict inclusion in the control sampling frame are similar for cases and potential controls. The two propensity-score-based methods implemented here also require this assumption and in addition, require correct model specification for propensity score estimation. The advantage of the propensity score methods is that they preserve the study base by allowing all cases to be used. Selection bias caused by incomplete sampling-frame coverage is frequently overlooked. In this study we linked the case and control sampling frames to demonstrate the use of propensity scores to adjust for selection bias due to incomplete study-base coverage of the sampling frames.

Background Viral illnesses are important factors in both asthma inception and exacerbations, and allergic sensitization in early life further enhances asthma risk through unclear mechanisms. Cellular damage caused by infection or allergen inhalation increases ATP levels in the airways with subsequent purinergic receptor activation. The purinergic receptor P2X 7 can enhance airway leukocyte recruitment to the airways, and P2X 7 knockout mice display a reduced asthma-like phenotype. Objective Based on the P2X 7 knockout mouse, we hypothesized that children with low P2X 7 function would have decreased rates of asthma. Methods We used a functional assay to determine P2X 7 pore-producing capacity in whole-blood samples in a birth cohort at high risk for asthma development. The P2X 7 assay was validated with known loss-of-function alleles in human subjects. P2X 7 pore status categorization was used to assess asthma and allergy status in the cohort. Results Attenuated P2X 7 function was associated with lower asthma rates at ages 6 and 8 years, and the greatest effects were observed in boys. Children with asthma at age 11 years who had low P2X 7 capacity had less severe disease in the previous year. Attenuated P2X 7 function was also associated with sensitization to fewer aeroallergens. Conclusion P2X 7 functional capacity is associated with asthma risk or disease severity, and these relationships appear to be age related.

This report identifies a radius dual-energy X-ray absorptiometry (DXA) confounder and technical approach to avoid this inaccuracy. Initially, a precision study revealed substantial differences (p0.001) in radius bone mineral density (BMD) least significant change ranging from 0.038 to 0.073g/cm(2) between 3 technologists that each performed assessments in 30 men and 30 women. Subsequently, visual examination of all 360 forearm DXA images, including bone, soft tissue, neutral, and air point-typing was performed. Errors in automated "soft tissue" identification were observed; compared with the manufacturer's ideal depiction, suboptimal soft tissue point-typing was present in 30/360 scans (8.3%) involving 27 individuals. These point-typing deviations appeared to result from inclusion of forearm positioner slots at the scan field edges or clothing covering the forearm. Twenty-four individuals had a paired scan appropriately point-typed, thus allowing evaluation of the effect on BMD measurement. In those with incorrect point-typing associated with positioner slots, the mean one-third radius BMD was ∼7% higher. In conclusion, positioner slots at the edges of the distal scan field can lead to automated soft tissue identification inaccuracies and consequent erroneous one-third radius BMD measurement. DXA technologists should avoid slot inclusion in forearm scans and evaluate point-typing as part of routine analysis.

Background: Increasing numbers of individuals are choosing to opt out of population-based sampling frames due to privacy concerns. This is especially a problem in the selection of controls for case–control studies, as the cases often arise from relatively complete population-based registries, whereas control selection requires a sampling frame. If opt out is also related to risk factors, bias can arise. Methods: We linked breast cancer cases who reported having a valid driver's license from the 2004–2008 Wisconsin women's health study (N = 2,988) with a master list of licensed drivers from the Wisconsin Department of Transportation (WDOT). This master list excludes Wisconsin drivers that requested their information not be sold by the state. Multivariate-adjusted selection probability ratios (SPR) were calculated to estimate potential bias when using this driver's license sampling frame to select controls. Results: A total of 962 cases (32%) had opted out of the WDOT sampling frame. Cases age Conclusions: Our results indicate the potential for selection bias due to differential opt out between various demographic and behavioral subgroups of controls. As selection bias may differ by exposure and study base, the assessment of potential bias needs to be ongoing. Impact: SPRs can be used to predict the direction of bias when cases and controls stem from different sampling frames in population-based case–control studies. Cancer Epidemiol Biomarkers Prev; 21(6); 881–6. ©2012 AACR.

Background Asthma is a complex disease characterized by sex-specific differences in incidence, prevalence, and severity, but little is known about the molecular basis of these sex-based differences. Objective To investigate the genetic architecture of sex differences in asthma risk, we evaluated (1) associations between polymorphisms in the IFNG gene and childhood-onset asthma in combined and sex-specific samples and (2) interactions between polymorphisms and sex on asthma risk. Methods Main and sex-interaction effects of IFNG genetic diversity on asthma risk and IFN-γ levels were examined in a birth cohort of children at high risk for asthma and allergic diseases. Replication of the genetic association was assessed in an independent sample of asthma cases. Results Significant genotype-sex interactions on asthma were observed for 2 IFNG single nucleotide polymorphisms, rs2069727 and rs2430561, which were in strong linkage disequilibrium with each other. In contrast, none of the 10 IFNG single nucleotide polymorphisms showed significant main effects on asthma. The observed genotype-sex interaction on asthma was characterized by nonadditivity; that is, heterozygous boys had the highest risk for asthma, and heterozygous girls had the lowest risk. The interaction effect was robust to other asthma risk factors but was limited to children who experienced wheezing illnesses with viral infections during the first 3 years of life. Genotype-sex interactions were also observed in the IFN-γ response to LPS in the first year of life. Finally, the sex-interaction effect was replicated in an independent population of childhood asthma cases. Conclusions These results provide insight into the genetic basis of sex differences in asthma and highlight the potential importance of interactions among sex, genotype, and environmental factors in asthma pathogenesis.

This study examined the impact of childhood activity limitations on family financial burden in the U.S. We used ten complete panels (1996–2006) of the Medical Expenditure Panel Survey (MEPS) to evaluate the burden of out-of-pocket healthcare expenditures for 17,857 families with children aged 0–17 years. Multivariate generalized linear models were used to examine the relationship between childhood activity limitation status and both absolute and relative financial burden. Families of children with limitations had higher absolute out-of-pocket healthcare expenditures than families of children without limitations ($594.36 higher; p

Purpose The purpose of this study was to test the hypothesis that eating a meal reduces tongue strength and endurance in healthy old and young adults. It was predicted that older adults would show greater declines in tongue endurance while demonstrating higher perceived effort, longer meal durations, and clinical signs of swallowing difficulty. Method Twenty-two healthy adults were enrolled into 2 groups (ages 20–35 years and ages 65–82 years; 5 males and 6 females each). Maximum tongue strength (P max ) and endurance (duration 50% of P max could be maintained) were measured twice at baseline and once postmeal. Subjects consumed half of a bagel with peanut butter, carrot sticks, and milk between measures. Results All subjects demonstrated reduced tongue strength and endurance postmeal. Young adults showed a greater decline in anterior tongue endurance compared with older adults ( p = .05). There was no evidence that changes in tongue strength, perceived effort, or meal duration varied by age or gender. The 3 oldest subjects reported the highest effort and displayed signs of difficulty swallowing while dining. Conclusions Young and old adults demonstrated reduced tongue strength and endurance after dining, but younger subjects showed greater declines in anterior tongue endurance, whereas older adults exhibited signs of swallowing difficulty.

The spatial scan statistic is a widely applied tool for cluster detection. The spatial scan statistic evaluates the significance of a series of potential circular clusters using Monte Carlo simulation to account for the multiplicity of comparisons. In most settings, the extent of the multiplicity problem varies across the study region. For example, urban areas typically have many overlapping clusters, while rural areas have few. The spatial scan statistic does not account for these local variations in the multiplicity problem. We propose two new spatially-varying multiplicity adjustments for spatial cluster detection, one based on a nested Bonferroni adjustment and one based on local averaging. Geographic variations in power for the spatial scan statistic and the two new statistics are explored through simulation studies, and the methods are applied to both the well-known New York leukemia data and data from a case–control study of breast cancer in Wisconsin.

International audience; Climate changes are altering patterns of temperature and precipitation, potentially affecting regions of malaria transmission. We show that areas of the Amazon Basin with few wetlands show a variable relationship between precipitation and malaria, while areas with extensive wetlands show a negative relationship with malaria incidence.

Normal esophageal bolus transport in asymptomatic healthy older adults has not been well defined,potentiallyleading to ambiguity in differentiating esophageal swallowing patterns of dysphagic and healthy individuals. This pilot study of 24 young (45–64 years) and old (65+years) men and women was designed to assess radiographic esophageal bolus movement patterns in healthy adults using videofluoroscopic recording. Healthy, asymptomatic adults underwent videofluoroscopic esophagram to evaluate for the presence of ineffective esophageal clearance, namely, intraesophageal stasis and intraesophageal reflux. Intraesophageal stasis and intraesophageal reflux were visualized radiographically in these normal subjects. Intraesophageal stasis occurred significantly more frequently with semisolid (96%) compared with liquid (16%) barium, suggesting that a variety of barium consistencies, as opposed to only the traditional fluids, would better define the spectrum of esophageal transport. Intraesophageal reflux was observed more frequently in older males than in their younger counterparts. The rates of intraesophageal stasis and intraesophageal reflux were potentially high given that successive bolus presentations were spaced 10 seconds apart. These findings suggest a need for a more comprehensive definition regarding the range of normal esophageal bolus transport to (a) prevent misdiagnosis of dysphagia and (b) to enhance generalization to functional eating, which involves solid foods in addition to liquids.

Virus-induced wheezing episodes in infancy often precede the development of asthma. Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood.To define the relationship between specific viral illnesses and early childhood asthma development.A total of 259 children were followed prospectively from birth to 6 years of age. The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using nasal lavage, culture, and multiplex reverse transcriptase-polymerase chain reaction. The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed.Viral etiologies were identified in 90% of wheezing illnesses. From birth to age 3 years, wheezing with respiratory syncytial virus (RSV) (odds ratio [OR], 2.6), rhinovirus (RV) (OR, 9.8), or both RV and RSV (OR , 10) was associated with increased asthma risk at age 6 years. In Year 1, both RV wheezing (OR, 2.8) and aeroallergen sensitization (OR, 3.6) independently increased asthma risk at age 6 years. By age 3 years, wheezing with RV (OR, 25.6) was more strongly associated with asthma at age 6 years than aeroallergen sensitization (OR, 3.4). Nearly 90% (26 of 30) of children who wheezed with RV in Year 3 had asthma at 6 years of age.Among outpatient viral wheezing illnesses in infancy and early childhood, those caused by RV infections are the most significant predictors of the subsequent development of asthma at age 6 years in a high-risk birth cohort.

OBJECTIVES: Telomeres are nucleoprotein structures that cap the end of chromosomes and shorten with sequential cell divisions in normal aging. Short telomeres are also implicated in the incidence of many cancers, but the evidence is not conclusive for colorectal cancer (CRC). Therefore, the aim of this study was to assess the association of CRC and telomere length. METHODS: In this case–control study, we measured relative telomere length from peripheral blood leukocytes (PBLs) DNA with quantitative PCR in 598 CRC patients and 2,212 healthy controls. RESULTS: Multivariate analysis indicated that telomere length was associated with risk for CRC, and this association varied in an age-related manner; younger individuals (≤50 years of age) with longer telomeres (80–99 percentiles) had a 2–6 times higher risk of CRC, while older individuals (>50 years of age) with shortened telomeres (1–10 percentiles) had 2–12 times the risk for CRC. The risk for CRC varies with extremes in telomere length in an age-associated manner. CONCLUSIONS: Younger individuals with longer telomeres or older individuals with shorter telomeres are at higher risk for CRC. These findings indicate that the association of PBL telomere length varies according to the age of cancer onset and that CRC is likely associated with at minimum two different mechanisms of telomere dynamics.