Dietary glycemic load (GL), glycemic index (GI), and carbohydrate could be associated with breast cancer risk by influencing long-term blood glucose and insulin concentrations. We examined associations between GL, GI, and carbohydrate and incident breast cancer in 148,767 Women’s Heath Initiative (WHI) participants. Dietary variables were estimated from food frequency questionnaires administered at baseline. Self-reported breast cancers during follow-up were confirmed by medical records review. Cox proportional hazards regression modeled time to breast cancer within quintiles of GL, GI, and carbohydrate. There were 6,115 total breast cancers after a median follow-up of 8.0 yr. We observed no associations between GL, GI, or carbohydrate and total incident breast cancer, with hazard ratios and 95% confidence intervals for the highest vs. lowest quintiles of 1.08, 0.92–1.29 (P for trend = 0.27); 1.01, 0.91–1.12 (P = 0.74); and 0.95, 0.80–1.14 (P = 0.98), respectively. There was a trend toward significance for the positive association between GL and in situ cancers (1.40, 0.94–2.13; P = 0.07). Although there was no evidence of associations between GL, GI, or carbohydrate and total breast cancer risk in WHI participants, the suggestion of an association between GL and risk of in situ cancers requires further investigation.
To show how the variance of the measurement error (ME) associated with individual ancestry proportion estimates can be estimated, especially when the number of ancestral populations (k) is greater than 2.
We extend existing internal consistency measures to estimate the ME variance, and we compare these estimates with the ME variance estimated by use of the repeated measurement (RM) approach. Both approaches work by dividing the genotyped markers into subsets. We examine the effect of the number of subsets and of the allocation of markers to each subset on the performance of each approach. We used simulated data for all comparisons.
Independently of the value of k, the measures of internal reliability provided less biased and more precise estimates of the ME variance than did those obtained with the RM approach. Both methods tend to perform better when a large number of subsets of markers with similar sizes are considered.
Our results will facilitate the use of ME correction methods to address the ME problem in individual ancestry proportion estimates. Our method will improve the ability to control for type I error inflation and loss of power in association tests and other genomic research involving ancestry estimates.
Population stratification; admixture; type I error inflation; reliability; Cronbach’s alpha; measurement errors; measurement error variance
Quantitative polymerase chain reaction (qPCR) and pp65 antigenemia assays are used to monitor cytomegalovirus (CMV) infection in renal transplant recipients, but correlation of assays in a pediatric population has not been evaluated. Paired CMV real-time qPCR and pp65 antigenemia tests from 882 blood samples collected from 115 pediatric renal transplant recipients were analyzed in this retrospective cohort study for strength of association and clinical correlates.
The assays correlated well in detecting infection (κ = 0.61). Higher qPCR values were demonstrated with increasing levels of antigenemia (p < 0.01). Discordant test results were associated with antiviral treatment (OR 4.33, p < 0.01) and low-level viremia, with odds of concordance increasing at higher qPCR values (OR 3.67, p < 0.01), and no discordance occurring above 8500 genomic equivalents/mL. Among discordant samples, neither test preceded the other in detecting initial infection or in returning to negative while on treatment. Only 2 cases of disease occurred during the 2-year study period.
With strong agreement in the detection of CMV infection, either qPCR or pp65 antigenemia assays can be used effectively for monitoring pediatric renal transplant patients for both detection and resolution of infection.
Pediatrics; Kidney Transplantation; Cytomegalovirus Infections; Polymerase Chain Reaction; CMV pp65 Antigen
Introduction and Hypothesis
The goal of this study was to characterize associations between caffeine consumption and severity of urinary incontinence (UI) in US women. We hypothesized that moderate and high caffeine intake would be associated with UI in US women when controlling for other factors associated with UI.
US women participated in the 2005–2006 and 2007–2008 National Health and Nutrition Examination Survey (NHANES), a cross-sectional, nationally representative survey. Using the Incontinence Severity Index, UI was categorized as “any” and “moderate/severe”. Types of UI included stress, urge, mixed, and other. Food diaries were completed and average water (gm/day), total dietary moisture (gm/day), and caffeine (mg/day) intake were calculated into quartiles. Step-wise logistic regression models were constructed adjusting for: sociodemographics, chronic diseases, body mass index, self-rated health, depression, alcohol use, dietary water and moisture in take, and reproductive factors.
From the 4309 non-pregnant women (aged ≥20 years) who had complete UI and dietary data, UI prevalence for any UI was 41.0% and 16.5% for moderate/severe UI, with stress UI the most common UI type (36.6%). Women consumed a mean caffeine intake of 126.7 mg/day. After adjusting for multiple factors, caffeine in take in the highest quartile (≥204 mg/day) was associated with any UI (prevalence odds ratio (POR)1.47, 95% CI 1.07, 2.01), but not moderate/severe UI (POR 1.42, 95% CI 0.98, 2.07). Type of UI (stress, urgency, mixed) was not associated with caffeine intake.
Caffeine intake ≥204 mg/day was associated with any UI, but not moderate/severe UI, in US women.
urinary; incontinence; caffeine; intake; women
The purpose of this study was to assess the impact of body mass index (BMI) on tension-free vaginal tape (TVT) success rates, patient satisfaction, and complications one year following surgery.
Baseline and one-year post-surgery outcomes were abstracted, including Urogenital Distress Inventory (UDI-6) scores, Incontinence Impact Questionnaire (IIQ-7) scores, and patient satisfaction ratings. Multivariable logistic and linear regression analyses were performed to examine relationships between outcomes and BMI.
195 subjects with a mean age of 59.3 ±12.6 were included. There was significant improvement within each group (all p-values <0.01) in total UDI-6 and IIQ-7 scores from baseline to one year post-surgery; all groups had high patient satisfaction. No differences in improvement or complications rates were observed among the BMI cohorts (all p-values >0.05)
Differential counseling of overweight or obese women regarding outcomes of the TVT procedure is not supported by these results; longer follow-up is warranted.
obesity; outcomes; TVT sling; urinary incontinence
A distribution-free method to generate high-dimensional sequences of dependent variables with an autoregressive structure is presented. The quantile or fractile correlation (i.e., the moment correlation of the quantiles) is used as measure of dependence among a set of contiguous variables. The proposed algorithm breaks the sequence in small parts and avoids having to define one large correlation matrix for the entire high-dimensional sequence of variables. Simulations based on proteomics data are presented. Results suggest that negligible or no loss of fractile correlation occurs by splitting the generation of a sequence into small parts.
Distribution-free methods; Fractile correlations; High-dimensional data; Simulation
To determine the incidence of fecal incontinence (FI) in community-dwelling older adults and identify risk factors associated with incident FI.
Planned secondary analysis of a longitudinal, population-based cohort study.
Three rural and two urban Alabama counties (in-home assessments 2000–2005).
Stratified random sample of 1,000 Medicare beneficiaries: 25% African-American men, 25% white men, 25% African-American women, 25% white women, aged 65 and older. Eligible participants for this analysis were continent at baseline and community-dwelling 4 years later (n =557).
FI was defined as any loss of control of bowels occurring during the previous year. Independent variables were sociodemographics, Charlson comorbidity counts, self-reported bowel symptoms (chronic diarrhea and constipation), depression, and body mass index (BMI). Multivariable logistic regression models were constructed using incident FI as the dependent variable.
The incidence rate of FI at 4 years was 17% (95% confidence interval (CI) =13.7–20.1), with 6% developing FI at least monthly (95% CI =4.0–8.3). White women were more likely to have incident FI (22%) than African-American women (13%, P =.04); no racial differences were observed in men. Controlling for age, comorbidity count, and BMI, significant independent risk factors for incident FI in women were white race, depression, chronic diarrhea, and urinary incontinence (UI). UI was the only significant risk factor for incident FI in men.
The occurrence of new FI is common in men and women aged 65 and older, with a 17% incidence rate over 4 years. FI and UI may share common pathophysiologic mechanisms and need regular assessment in older adults.
fecal incontinence; incidence; urinary incontinence; African Americans; gender; functional bowel disorders; epidemiology
To characterize differences in health-related quality of life among women presenting for treatment of fecal incontinence.
Among 155 women presenting for treatment of fecal incontinence in a specialty clinic, validated questionnaires measured impact on quality of life (Modified Manchester Health Questionnaire) and severity (the Fecal Incontinence Severity Index). Bowel symptoms, including frequency, urgency, and stool consistency, were ascertained. Co-morbid diseases were self-reported. Linear regression models were constructed from significant univariate variables to examine differences seen in quality of life scores.
Average age was 58.7 ± 11.5 with no differences found in quality of life scores according to race, body mass index, or number of vaginal deliveries (p > 0.05). Younger age, increased urinary incontinence symptoms, prior cholecystectomy, prior hysterectomy, and severity of bowel symptoms correlated with a negative impact on quality of life in univariate analysis (p <0.05). Average severity scores were 30.5 ± 13.7 with moderate correlation seen with increasing severity and quality of life scores (R2= 0.60). After controlling for severity, women had increased quality of life scores with more bowel urgency (15 points, 95% CI 8.1, 21.2), harder stool consistency (10 points, 95% CI 3.8, 16.3), and prior hysterectomy (9 points, 95% CI 2.7, 15.4).
Bowel symptoms and having a prior hysterectomy had the greatest negative impact on quality of life in women seeking treatment for fecal incontinence. Targeting individualized treatments to improve bowel symptoms may improve quality of life for women with fecal incontinence.
fecal incontinence; women; quality of life; urinary incontinence; bowel symptoms
To examine the association between baseline bone mineral density (BMD) and radiographic damage at 3-year disease duration in a longitudinal cohort of African Americans (AAs) with recent-onset RA.
Participants (n=141) included AAs with < 2 years of disease duration. All patients underwent baseline BMD measurement (femoral neck and/or lumbar spine) using DXA. T-scores were calculated using AAs normative data. Patients were categorized as having osteopenia/osteoporosis (T score ≤ −1) or healthy. Hand/wrist radiographs, obtained at baseline and at 3-year disease duration, were scored using modified Sharp/van der Heijde method. The association between baseline BMD and total radiographic score at 3-year disease duration was examined using multivariable negative binomial regression.
At baseline, the mean age and disease duration were 52.4 years and 14.8 months respectively (85.1% women). Average total radiographic scores at baseline and 3-year disease duration were 2.4 and 5.7. In the final reduced multivariable model adjusting for age, gender, anti-cyclic citrullinated peptide antibody positivity, and the presence of radiographic damage at baseline, the total radiographic score at 3-years of disease duration in patients with osteopenia/osteoporosis at the femoral neck was twice that in patients with healthy bone density and the difference was statistically significant (p=0.0084). No association between lumbar spine osteopenia/osteoporosis and radiographic score was found.
These findings suggest that reduced generalized BMD may be a predictor of future radiographic damage and support the hypothesis that radiographic damage and reduced generalized BMD in RA patients may share a common pathogenic mechanism.
As genome-wide association studies expand beyond populations of European ancestry, the role of admixture will become increasingly important in the continued discovery and fine-mapping of variation influencing complex traits. Although admixture is commonly viewed as a confounding influence in association studies, approaches such as admixture mapping have demonstrated its ability to highlight disease susceptibility regions of the genome. In this study, we illustrate a powerful two-stage testing strategy designed to uncover trait-associated single nucleotide polymorphisms in the presence of ancestral allele frequency differentiation. In the first stage, we conduct an association scan by using predicted genotypic values based on regional admixture estimates. We then select a subset of promising markers for inclusion in a second-stage analysis, where association is tested between the observed genotype and the phenotype conditional on the predicted genotype. We prove that, under the null hypothesis, the test statistics used in each stage are orthogonal and asymptotically independent. Using simulated data designed to mimic African-American populations in the case of a quantitative trait, we show that our two-stage procedure maintains appropriate control of the family wise error rate and has higher power under realistic effect sizes than the one-stage testing procedure in which all markers are tested for association simultaneously with control of admixture. We apply the proposed procedure to a study of height in 201 African-Americans genotyped at 108 ancestry informative markers. The two-stage procedure identified two statistically significant markers rs1985080 (PTHB1/BBS9) and rs952718 (ABCA12). PTHB1/BBS9 is downregulated by parathyroid hormone in osteoblastic cells and is thought to be involved in parathyroid hormone action in bones and may play a role in height. ABCA12 is a member of the superfamily of ATP-binding cassette transporters and its potential involvement in height is unclear.
two-stage; structured association testing; admixture mapping; regional admixture estimate; genome-wide association studies
Associations between dietary glycemic load (GL) and cardiovascular disease (CVD) risk factors, including plasma lipoprotein/lipid levels, blood pressure (BP), and glucose metabolism factors, in the Women's Health Initiative Observational Study were examined.
A random sample of 878 Observational Study participants (postmenopausal women age 50 to 79 years) with baseline blood measures (647 White, 104 Black, 127 Hispanic) was included. Dietary GL was estimated from baseline food frequency questionnaires, which assessed dietary intake over the previous three months. At the baseline visit, participants completed demographic and health habit questionnaires, fasting blood samples were collected, anthropometric measurements were completed, and BP was assessed.
In all participants combined, GL was inversely associated with high-density lipoprotein (HDL) cholesterol (P for trend = 0.004) and positively associated with log10-transformed triglycerides (P = 0.008). While there were no statistically significant interactions of race/ethnicity with associations between GL and CVD risk factors, stratified results were suggestive, showing that GL was positively associated with total cholesterol (P = 0.018) and low-density lipoprotein (LDL) cholesterol (P = 0.038) in Hispanics. In Whites, there was a trend of reduced HDL cholesterol with higher GL (P = 0.003), while GL was positively associated with log10-transformed triglycerides (P = 0.015). Associations between GL and HDL cholesterol and GL and triglycerides also varied by BMI, although the interactions were not statistically significant.
Among these generally healthy postmenopausal women, GL was associated with HDL cholesterol and triglycerides. Suggestive effects of race/ethnicity and BMI on these associations need to be confirmed in larger studies.
Glycemic load; Glycemic index; Carbohydrate; Cardiovascular disease; Women's Health Initiative
As genome-wide association studies expand beyond populations of European ancestry, the role of admixture will become increasingly important in the continued discovery and fine-mapping of variation influencing complex traits. Although admixture is commonly viewed as a confounding influence in association studies, approaches such as admixture mapping have demonstrated its ability to highlight disease susceptibility regions of the genome. In this study, we illustrate a powerful two-stage testing strategy designed to uncover trait-associated single nucleotide polymorphisms in the presence of ancestral allele frequency differentiation. In the first stage, we conduct an association scan by using predicted genotypic values based on regional admixture estimates. We then select a subset of promising markers for inclusion in a second-stage analysis, where association is tested between the observed genotype and the phenotype conditional on the predicted genotype. We prove that, under the null hypothesis, the test statistics used in each stage are orthogonal and asymptotically independent. Using simulated data designed to mimic African-American populations in the case of a quantitative trait, we show that our two-stage procedure maintains appropriate control of the family wise error rate and has higher power under realistic effect sizes than the one-stage testing procedure in which all markers are tested for association simultaneously with control of admixture. We apply the proposed procedure to a study of height in 201 African-Americans genotyped at 108 ancestry informative markers. The two-stage procedure identified two statistically significant markers rs1985080 (PTHB1/BBS9) and rs952718 (ABCA12). PTHB1/BBS9 is downregulated by parathyroid hormone in osteoblastic cells and is thought to be involved in parathyroid hormone action in bones and may play a role in height. ABCA12 is a member of the superfamily of ATP binding cassette transporters and its potential involvement in height is unclear.
two-stage; structured association testing; admixture mapping; regional admixture estimate; genome-wide association studies
Questions remain regarding the utility of self-reported ethnicity (SRE) in genetic and epidemiologic research. It is not clear whether conditioning on SRE provides adequate protection from inflated type I error rates due to population stratification and admixture. We address this question using data obtained from the Multi-Ethnic Study of Atherosclerosis (MESA), which enrolled individuals from 4 self-reported ethnic groups. We compare the agreement between SRE and genetic based measures of ancestry (GBMA), and conduct simulation studies based on observed MESA data to evaluate the performance of each measure under various conditions.
Four clusters are identified using 96 ancestry informative markers. Three of these clusters are well delineated, but 30% of the self-reported Hispanic-Americans are misclassified. We also found that MESA SRE provides type I error rates that are consistent with the nominal levels. More extensive simulations revealed that this finding is likely due to the multi-ethnic nature of the MESA. Finally, we describe situations where SRE may perform as well as a GBMA in controlling the effect of population stratification and admixture in association tests.
The performance of SRE as a control variable in genetic association tests is more nuanced than previously thought, and may have more value than it is currently credited with, especially when smaller replication studies are being considered in multi-ethnic samples.
To determine incidence and predictors of incident urinary incontinence over 3 years in community-dwelling older adults.
MATERIALS & METHODS
A population-based, prospective cohort study was conducted with a random sample of Medicare beneficiaries, stratified to be 50% African American, 50% men, and 50% rural. In-home baseline assessment included standardized questionnaires and short physical performance battery. Three annual follow-up interviews were conducted by telephone. Incontinence was defined as any degree of incontinence occurring at least once a month in the past 6 months.
Participants were 490 women and 496 men, age 65 to 106 years (mean=75 years). Prevalence of incontinence at baseline was 41% in women and 27% in men. Three-year incidence of incontinence was 29% (84/290) in women and 24% (86/363) in men. There were no differences by race in prevalent or incident incontinence. In multivariable logistic regression models for women, significant independent baseline predictors of new incontinence included: stroke (OR 3.4, p=.011), incontinence < monthly (OR 3.3, p=.001), past or current post-menopausal estrogen (OR 2.3, p<.006), slower time to stand from a chair 5 times (OR 1.3, p<.045), and higher Geriatric Depression Scale Score (OR 1.2, p=.016). For men, significant independent baseline predictors of new incontinence included: incontinence < monthly (OR 4.2, p<.001) and lower score on the composite Physical Performance Score (OR 1.2, p<.001).
Prevalence of incontinence among community-dwelling older adults was high with an additional 29% of women and 24% of men reporting incident incontinence over 3 years of follow-up. Infrequent incontinence is a strong risk factor for developing at least monthly incontinence in both men and women.
Urinary Incontinence; Epidemiology; Incidence; African Americans
Chronic insulin resistance contributes to subclinical inflammation, thrombosis/impaired fibrinolysis, and dyslipidemia. The effect of dietary carbohydrate, specifically of glycemic index (GI) and glycemic load (GL), on established and emerging coronary heart disease (CHD) risk factors has not been elucidated fully. We conducted a randomized, cross-over feeding study of matched diets differing only in GI and GL in 24 overweight or obese but otherwise healthy men to investigate the effects on insulin sensitivity, inflammation, thrombosis/fibrinolysis, lipoproteins/lipids, and body composition. All meals for the high- and low-GI/GL diets were prepared in a metabolic kitchen. Each participant consumed both diets in random order for 4 weeks each, with a 4-week wash-out period in between. Each participant underwent a frequently-sampled intravenous glucose tolerance test for assessment of insulin sensitivity; blood sampling for the measurement of inflammatory markers, coagulation factors, and lipoproteins/lipids; and dual-energy x-ray absorptiometry for assessment of body composition at the beginning and end of each dietary period. There were no statistically significant differences in glucose metabolism factors, inflammatory markers, or coagulation factors following 4 weeks on the high- and low-GI/GL diets. The high-GI/GL diet resulted in a slightly greater reduction in fat mass and a slightly greater increase in lean mass compared to the low-GI/GL diet. The high-GI/GL diet resulted in significant, but unexpected, reductions in total and LDL cholesterol, while HDL cholesterol concentration was significantly reduced on the high-GI/GL diet compared to the low-GI/GL diet. Overall, high- and low-GI/GL diets of 4-weeks duration had no consistent effects on CHD risk factors in this group of overweight/obese men.
The obesity epidemic is a global issue and shows no signs of abating, while the cause of this epidemic remains unclear. Marketing practices of energy-dense foods and institutionally-driven declines in physical activity are the alleged perpetrators for the epidemic, despite a lack of solid evidence to demonstrate their causal role. While both may contribute to obesity, we call attention to their unquestioned dominance in program funding and public efforts to reduce obesity, and propose several alternative putative contributors that would benefit from equal consideration and attention. Evidence for microorganisms, epigenetics, increasing maternal age, greater fecundity among people with higher adiposity, assortative mating, sleep debt, endocrine disruptors, pharmaceutical iatrogenesis, reduction in variability of ambient temperatures, and intrauterine and intergenerational effects, as contributing factors to the obesity epidemic are reviewed herein. While the evidence is strong for some contributors such as pharmaceutical-induced weight gain, it is still emerging for other reviewed factors. Considering the role of such putative etiological factors of obesity may lead to comprehensive, cause specific, and effective strategies for prevention and treatment of this global epidemic.
With the advent of powerful computers, simulation studies are becoming an important tool in statistical methodology research. However, computer simulations of a specific process are only as good as our understanding of the underlying mechanisms. An attractive supplement to simulations is the use of plasmode datasets. Plasmodes are data sets that are generated by natural biologic processes, under experimental conditions that allow some aspect of the truth to be known. The benefit of the plasmode approach is that the data are generated through completely natural processes, thus circumventing the common concern of the realism and accuracy of computer simulated data. The estimation of admixture, or the proportion of an individual’s genome that originates from different founding populations, is a particularly difficult research endeavor that is well suited to the use of plasmodes. Current methods have been tested with simulations of complex populations where the underlying mechanisms such as the rate and distribution of recombination are not well understood. To demonstrate the utility of this method data derived from mouse crosses is used to evaluate the effectiveness of several admixture estimation methodologies. Each cross shares a common founding population so that the ancestry proportion for each individual is known, allowing for the comparison of true and estimated individual admixture values. Analysis shows that the different estimation methodologies (Structure, AdmixMap and FRAPPE) examined all perform well with simple datasets. However, the performance of the estimation methodologies varied greatly when applied to a plasmode consisting of three founding populations. The results of these examples illustrate the utility of plasmodes in the evaluation of statistical genetics methodologies.
Admixture; ancestry; simulation; plasmode; population structure
To describe how women with fecal incontinence (FI) respond to combined pharmacologic therapy and pelvic floor muscle exercises (PFME).
Validated questionnaires (Fecal Incontinence Severity Index and Modified Manchester Health Questionnaire) were mailed to 80 women who received combined therapy for FI and had complete baseline assessments. Regression models were constructed to identify predictors of change in questionnaire scores.
Response rate was 69%. Mean age was 59 ± 12 years. All women were taught PFME with digital palpation and 87% of the women received medications. FI severity scores and quality of life (QOL) improved from baseline to follow-up (p < .001 and p = .02, respectively). A fair/normal external anal sphincter (EAS) contraction resulted in greater improvements in FI severity (13 points, p=0.006) and QOL scores (22 points, p<0.001).
FI severity and QOL improved after combination therapies and a fair/normal EAS contraction predicted greater improvement.
Treating fecal incontinence in women with combination therapy including pelvic floor muscle exercises and medications improved fecal incontinence symptom severity and health-related quality of life.
Fecal Incontinence; Treatment Outcomes; Quality of Life; Behavioral Medicine
Sub-Saharan Africa is disproportionately burdened by intestinal helminth and human immunodeficiency virus (HIV)-1 infection. Recent evidence suggests detrimental immunologic effects from concomitant infection with the two pathogens. Few studies, however, have assessed the prevalence of and predictors for intestinal helminth infection among HIV-1–infected adults in urban African settings where HIV infection rates are highest. We collected and analyzed sociodemographic and parasitologic data from 297 HIV-1–infected adults (mean age = 31.1 years, 69% female) living in Lusaka, Zambia to assess the prevalence and associated predictors of helminth infection. We found at least one type of intestinal helminth in 24.9% of HIV-infected adults. Thirty-nine (52.7%) were infected with Ascaris lumbricoides, and 29 (39.2%) were infected with hookworm. More than 80% were light-intensity infections. A recent visit to a rural area, food shortage, and prior history of helminth infection were significant predictors of current helminth status. The high helminth prevalence and potential for adverse interactions between helminths and HIV suggests that helminth diagnosis and treatment should be part of routine HIV care.
Infection with intestinal helminths may stimulate dysfunctional immune responses in human immunodeficiency virus (HIV)–infected persons. Studies have yielded conflicting results regarding the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA.
We conducted a prospective study of 54 HIV-1– and helminth-coinfected and 57 HIV-1–infected, helminth-uninfected asymptomatic adults living in Lusaka, Zambia, to assess the impact of antihelminthic treatment on plasma concentrations of HIV-1 RNA.
Median baseline viral load was 0.33 log10 copies/mL lower in the helminth-infected group than in the uninfected group. Mean viral load between pretreatment and posttreatment visits increased in the helminth-infected (mean, 4.23 vs. 4.29 log10 copies/mL; P = .6) and helminth-uninfected (mean, 4.39 vs. 4.52 log10 copies/mL; P = .2) groups. Helminth-infected participants with high pretreatment viral loads had a mean 0.25-log10 copies/mL decrease after treatment (P = .3), and helminth-uninfected participants had a mean 0.02-log10 copies/mL decrease (P = .8).
We did not find an overall association between treatment of intestinal helminth infections and reduction in viral load in coinfected adults. Future studies may need to focus on adults with intense helminth infections who live in rural areas or on adults or children who harbor higher helminth burdens and plasma concentrations of HIV-1 RNA.
Investigators are actively testing interventions intended to increase lifespan and wish to test whether the interventions increase maximum lifespan. Based on the fact that one cannot be assured of observing population maximum lifespans in finite samples, in previous work, we constructed and validated several tests of difference in the upper parts of lifespan distributions between a treatment group and a control group by testing whether the probabilities that observations are above some threshold defining 'old' or being in the tail of the survival distribution are equal in the two groups. However, a limitation of these tests is that they do not consider how much above the threshold any particular observation is.
In this article we propose new methods which improve upon our previous tests by considering not only whether an observation is above some threshold, but also the magnitudes by which observations exceed the threshold.
Simulations show that the new methods control type I error rates quite well and that the power of the new methods is usually higher than that of the tests we previously proposed. In illustrative analyses of two real datasets involving rodents, when setting the threshold equal to 110 (100) weeks for the first (second) datasets, the new methods detected differences in 'maximum lifespan' between groups at nominal alpha levels of 0.01 (0.05) for the first (second) datasets and provided more significant results than competitor tests.
The new methods not only have good performance in controlling the type I error rates but also improve the power compared with the tests we previously proposed.
This article describes the evaluation of a comprehensive school-based asthma management program in an inner-city, largely African-American school system. All 54 elementary schools (combined enrollment 13,247 students) from a single urban school system participated in this study. Schools were randomly divided between immediate and delayed intervention programs. The intervention consisted of 3 separate educational programs (for school faculty/staff, students with asthma, and peers without asthma) and medical management for the children with asthma (including an Individual Asthma Action Plan, medications, and peakflow meters). Children with asthma were identified using a case detection program and 736 were enrolled into the intervention study. No significant differences were observed in school absences, grade point average, emergency room visits, or hospitalizations between the immediate and delayed intervention groups. Significant increases in knowledge were observed in the immediate intervention group. This study of a school-based asthma management education and medical intervention program did not show any differences between the intervention and control groups on morbidity outcomes. Our experience leads us to believe that such measures are difficult to impact and are not always reliable. Future researchers should be aware of the problems associated with using such measures. In addition, connecting children with a regular source of health care in this population was difficult. More intensive methods of medical management, such as school-based health centers or supervised asthma therapy, might prove more effective in inner-city schools.
This paper describes an asthma screening procedure developed to identify children with asthma for an intervention study. Students were classified into three categories based on questionnaire responses (previous asthma, suspected asthma, and no evidence of asthma). Those classified as suspected asthma by questionnaire underwent further testing including spirometry and exercise challenge. Using the questionnaire alone, the measured asthma prevalence was 32%; the addition of spirometry and step testing reduced this estimate to 9.89%. The diagnosis of asthma was confirmed in 96% of children who saw the study physician. This screening procedure can identify school children with suspected undiagnosed asthma.
Asthma; Screening; Schools; Children; Spriometry
Individual genetic admixture estimates, determined both across the genome and at specific genomic regions, have been proposed for use in identifying specific genomic regions harboring loci influencing phenotypes in regional admixture mapping (RAM). Estimates of individual ancestry can be used in structured association tests (SAT) to reduce confounding induced by various forms of population substructure. Although presented as two distinct approaches, we provide a conceptual framework in which both RAM and SAT are special cases of a more general linear model. We clarify which variables are sufficient to condition upon in order to prevent spurious associations and also provide a simple closed form “semiparametric” method of evaluating the reliability of individual admixture estimates. An estimate of the reliability of individual admixture estimates is required to make an inherent errors-in-variables problem tractable. Casting RAM and SAT methods as a general linear model offers enormous flexibility enabling application to a rich set of phenotypes, populations, covariates, and situations, including interaction terms and multilocus models. This approach should allow far wider use of RAM and SAT, often using standard software, in addressing admixture as either a confounder of association studies or a tool for finding loci influencing complex phenotypes in species as diverse as plants, humans, and nonhuman animals.
In recent years, scientific efforts to find genes influencing disease and health-related traits have sought to capitalize on the unique genetic characteristics of admixed populations. Admixture can refer to the event of two or more genetically diverse populations intermating and producing an admixed population. Admixture creates the potential for efficient identification of trait-influencing genes. However, genetic association studies using admixed populations are also prone to incorrectly concluding that a gene is linked and associated with a trait even when it is not. Several researchers have produced promising statistical methodologies for genetic association studies within admixed populations. In this paper, the authors show how these statistical methods can be unified in a broadly applicable regression framework and discuss which variables should be included in the regression models for valid testing. Because the variables required in this regression framework can only be measured with error, the authors show the consequences of these measurement errors and present measurement error correction methods applicable to this problem. By recasting the statistical methods for genetic association studies within admixed populations as regression models, a broader range of modeling and hypothesis testing becomes available.