Susceptibility scoring in family-based association testing

BACKGROUND: Family-based association testing is an important part of genetic epidemiology. Tests are available to include multiple siblings, unaffected offspring, and to adjust for environmental covariates. We explore a susceptibility residual method of adjustment for covariates. RESULTS: Through simulation, we show that environmental adjustments that down-weight persons who are "destined" to be affected decrease the power to detect genetic association. We used the residual adjusted method on the Framingham Heart Study offspring data, provided for Genetic Analysis Workshop 13, and got mixed results. CONCLUSION: When the genetic effect and environmental effects are independent, a susceptibility residual method of adjustment for environmental covariates reduces the power of the association test. Further study is necessary to determine if residual adjustment is appropriate in more complex disease models

Analysis of gene × environment interactions in sibships using mixed models

BACKGROUND: Gene × environment models are widely used to assess genetic and environmental risks and their association with a phenotype of interest for many complex diseases. Mixed generalized linear models were used to assess gene × environment interactions with respect to systolic blood pressure on sibships adjusting for repeated measures and hierarchical nesting structures. A data set containing 410 sibships from the Framingham Heart Study offspring cohort (part of the Genetic Analysis Workshop 13 data) was used for all analyses. Three mixed gene × environment models, all adjusting for repeated measurement and varying levels of nesting, were compared for precision of estimates: 1) all sibships with adjustment for two levels of nesting (sibs within sibships and sibs within pedigrees), 2) all sibships with adjustment for one level of nesting (sibs within sibships), and 3) 100 data sets containing random draws of one sibship per extended pedigree adjusting for one level of nesting. RESULTS: The main effects were: gender, baseline age, body mass index (BMI), hypertensive treatment, cigarettes per day, grams of alcohol per day, and marker GATA48G07A. The interaction fixed effects were: baseline age by gender, baseline age by cigarettes per day, baseline age by hypertensive treatment, baseline age by BMI, hypertensive treatment by BMI, and baseline age by marker GATA48G07A. The estimates for all three nesting techniques were not widely discrepant, but precision of estimates and determination of significant effects did change with the change in adjustment for nesting. CONCLUSION: Our results show the importance of the adjustment for all levels of hierarchical nesting of sibs in the presence of repeated measures

North Dakota Economic-Demographic Assessment Model (NEDAM): Technical Description

This report describes the logic, structure, data bases, and operational procedures of the North Dakota model.Research Methods/ Statistical Methods,

The three-nucleon bound state using realistic potential models

The bound states of $^3$H and $^3$He have been calculated using the Argonne $v_{18}$ plus the Urbana three-nucleon potential. The isospin $T=3/2$ state have been included in the calculations as well as the $n$-$p$ mass difference. The $^3$H-$^3$He mass difference has been evaluated through the charge dependent terms explicitly included in the two-body potential. The calculations have been performed using two different methods: the solution of the Faddeev equations in momentum space and the expansion on the correlated hyperspherical harmonic basis. The results are in agreement within 0.1% and can be used as benchmark tests. Results for the CD-Bonn interaction are also presented. It is shown that the $^3$H and $^3$He binding energy difference can be predicted model independently.Comment: 5 pages REVTeX 4, 1 figures, 6 table

Data and safety monitoring in social behavioral intervention trials: the REACH II experience

Background Psychosocial and behavioral interventions trials targeting a broad range of complex social and behavioral problems such as smoking, obesity and family caregiving have proliferated in the past 30 years. At the same time the use of Data and Safety Monitoring Boards (DSMBs) to monitor the progress and quality of intervention trials and the safety of study participants has increased substantially. Most of the existing literature and guidelines for safety monitoring and reporting of adverse events focuses on medical interventions. Consequently, there is little guidance for investigators conducting social and behavior trials. Purpose This paper summarizes how issues associated with safety monitoring and adverse event reporting were handled in the Resources for Enhancing Alzheimer\u27s Caregiver Health (REACH II) program, a multi-site randomized clinical trial, funded by the National Institutes on Aging (NIA) and the National Institutes of Nursing Research (NINR), that tested the efficacy of a multicomponent social/behavioral intervention for caregivers of persons with Alzheimer\u27s disease. Methods A task force was formed to define adverse events for the trial and protocols for reporting and resolving events that occurred. The task force conducted a review of existing polices and protocols for data and safety monitoring and adverse event reporting and identified potential risks particular to the study population. An informal survey regarding data and safety monitoring procedures with investigators on psychosocial intervention trials was also conducted. Results Two categories of events were defined for both caregivers and patients; adverse events and safety alerts. A distinction was also made between events detected at baseline assessment and those detected post-randomization. Standardized protocols were also developed for the reporting and resolution of events that occurred and training of study personnel. Results from the informal survey indicated wide variability in practices for data safety and monitoring across psychosocial intervention trials. Conclusions Overall, the REACH II experience demonstrates that existing guidelines regarding safety monitoring and adverse event reporting pose unique challenges for social/behavioral intervention trials. Challenges encountered in the REACH II program included defining and classifying adverse events, defining resolution of adverse events and attributing causes for events that occurred. These challenges are highlighted and recommendations for addressing them in future studies are discussed

The alpha-particle based on modern nuclear forces

The Faddeev-Yakubovsky equations for the alpha-particle are solved. Accurate results are obtained for several modern NN interaction models, which include charge-symmetry breaking effects in the NN force, nucleon mass dependences as well as the Coulomb interaction. These models are augmented by three-nucleon forces of different types and adjusted to the 3N binding energy. Our results are close to the experimental binding energy with a slight overbinding. Thus there is only little room left for the contribution of possible 4N interactions to the alpha-particle binding energy. We also discuss model dependences of the binding energies and the wave functions.Comment: 22 pages REVTeX 4, 12 figures, table with TM parameters added, typos corrected, version as published in PR

Pharmacy Data for Tuberculosis Surveillance and Assessment of Patient Management

Pharmacy data help locate tuberculosis cases and assess their management

Racial differences in serum prostate-specific antigen (PSA) doubling time, histopathological variables and long-term PSA recurrence between African-American and white American men undergoing radical prostatectomy for clinically localized prostate cancer

To determine if there are significant differences in biochemical characteristics, biopsy variables, histopathological data, and rates of prostate-specific antigen (PSA) recurrence between African-American (AA) and white American (WA) men undergoing radical prostatectomy (RP), as AA men are twice as likely to die from prostate cancer than their white counterparts. PATIENTS AND METHODS We established a cohort of 1058 patients (402 AA, 646 WA) who had RP and were followed for PSA recurrence. Age, race, serum PSA, biopsy Gleason score, clinical stage, pathological stage, and PSA recurrence data were available for the cohort. The chi-square test of proportions and t -tests were used to assess basic associations with race, and log-rank tests and Cox regression models for time to PSA recurrence. Forward stepwise variable selection was used to assess the effect on the risk of PSA recurrence for race, adjusted by the other variables added one at a time. RESULTS The AA men had higher baseline PSA levels, more high-grade prostatic intraepithelial neoplasia (HGPIN) in the biopsy, and more HGPIN in the pathology specimen than WA men. The AA men also had a shorter mean (sd) PSA doubling time before RP, at 4.2 (4.7) vs 5.2 (5.9) years. However, race was not an independent predictor of PSA recurrence ( P  = 0.225). Important predictors for PSA recurrence in a multivariable model were biopsy HGPIN ( P  < 0.014), unilateral vs bilateral cancer ( P  < 0.006), pathology Gleason score and positive margin status (both P  < 0.001). CONCLUSIONS This study indicates that while there are racial differences in baseline serum PSA and incidence of HGPIN, race is not an independent risk factor for PSA recurrence. Rather, other variables such as pathology Gleason score, bilateral cancers, HGPIN and margin positivity are independently associated with PSA recurrence. The PSA doubling time after recurrence may also be important, leading to the increased mortality of AA men with prostate cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74706/1/j.1464-410X.2005.05561.x.pd

Induced pseudoscalar coupling of the proton weak interaction

The induced pseudoscalar coupling $g_p$ is the least well known of the weak coupling constants of the proton's charged--current interaction. Its size is dictated by chiral symmetry arguments, and its measurement represents an important test of quantum chromodynamics at low energies. During the past decade a large body of new data relevant to the coupling $g_p$ has been accumulated. This data includes measurements of radiative and non radiative muon capture on targets ranging from hydrogen and few--nucleon systems to complex nuclei. Herein the authors review the theoretical underpinnings of $g_p$, the experimental studies of $g_p$, and the procedures and uncertainties in extracting the coupling from data. Current puzzles are highlighted and future opportunities are discussed.Comment: 58 pages, Latex, Revtex4, prepared for Reviews of Modern Physic

Mammal responses to global changes in human activity vary by trophic group and landscape

Wildlife must adapt to human presence to survive in the Anthropocene, so it is critical to understand species responses to humans in different contexts. We used camera trapping as a lens to view mammal responses to changes in human activity during the COVID-19 pandemic. Across 163 species sampled in 102 projects around the world, changes in the amount and timing of animal activity varied widely. Under higher human activity, mammals were less active in undeveloped areas but unexpectedly more active in developed areas while exhibiting greater nocturnality. Carnivores were most sensitive, showing the strongest decreases in activity and greatest increases in nocturnality. Wildlife managers must consider how habituation and uneven sensitivity across species may cause fundamental differences in human–wildlife interactions along gradients of human influence.Peer reviewe