Longitudinal Beta-Binomial Modeling using GEE for Over-Dispersed Binomial Data

Longitudinal binomial data are frequently generated from multiple questionnaires and assessments in various scientific settings for which the binomial data are often overdispersed. The standard generalized linear mixed effects model may result in severe underestimation of standard errors of estimated regression parameters in such cases and hence potentially bias the statistical inference. In this paper, we propose a longitudinal beta-binomial model for overdispersed binomial data and estimate the regression parameters under a probit model using the generalized estimating equation method. A hybrid algorithm of the Fisher scoring and the method of moments is implemented for computing the method. Extensive simulation studies are conducted to justify the validity of the proposed method. Finally, the proposed method is applied to analyze functional impairment in subjects who are at risk of Huntington disease from a multisite observational study of prodromal Huntington disease

A formal test of linguistic and genetic coevolution in native Central and South America

This paper investigates a mechanism of linguistic and genetic coevolution in Native Central and South America. This mechanism proposes that a process of population fissions, expansions into new territories, and isolation of ancestral and descendant groups will produce congruent language and gene trees. To evaluate this population fissions mechanism, we collected published mtDNA sequences for 1,381 individuals from 17 Native Central and South American populations. We then tested the hypothesis that three well-known language classifications also represented the genetic structure of these populations. We rejected the hypothesis for each language classification. Our tests revealed linguistic and genetic correspondence in several shallow branches common to each classification, but no linguistic and genetic correspondence in the deeper branches contained in two of the language classifications. We discuss the possible causes for the lack of congruence between linguistic and genetic structure in the region, and describe alternative mechanisms of linguistic and genetic correspondence and their predictions. Am J Phys Anthropol, 2007. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55923/1/20542_ftp.pd

Emergency Medical Operations at Kennedy Space Center in Support of Space Shuttle

The unique environment of the Kennedy Space Center includes a wide variety of industrial processes culminating in launch and spaceflight. Many are potentially hazardous to the work force and the astronauts. Technology, planning, training, and quality control are utilized to prevent contingencies and expedite response should a contingency occur

Strong exchange and magnetic blocking in N 2 32 -radical-bridged lanthanide complexes

Single-molecule magnets approach the ultimate size limit for spin-based devices. These complexes can retain spin information over long periods of time at low temperature, suggesting possible applications in high-density information storage, quantum computing and spintronics. Notably, the success of most such applications hinges upon raising the inherent molecular spin-inversion barrier. Although recent advances have shown the viability of lanthanide-containing complexes in generating large barriers, weak or non-existent magnetic exchange coupling allows fast relaxation pathways that mitigate the full potential of these species. Here, we show that the diffuse spin of an N 2 32 radical bridge can lead to exceptionally strong magnetic exchange in dinuclear Ln(III) (Ln 5 Gd, Dy) complexes. The Gd(III) congener exhibits the strongest magnetic coupling yet observed for that ion, while incorporation of the high-anisotropy Dy(III) ion gives rise to a molecule with a record magnetic blocking temperature of 8.3 K at a sweep rate of 0.08 T s 21

Turbine Powered Simulator Calibration and Testing for Hybrid Wing Body Powered Airframe Integration

Propulsion airframe integration testing on a 5.75% scale hybrid wing body model us- ing turbine powered simulators was completed at the National Full-Scale Aerodynamics Complex 40- by 80-foot test section. Four rear control surface con gurations including a no control surface de ection con guration were tested with the turbine powered simulator units to investigate how the jet exhaust in uenced the control surface performance as re- lated to the resultant forces and moments on the model. Compared to ow-through nacelle testing on the same hybrid wing body model, the control surface e ectiveness was found to increase with the turbine powered simulator units operating. This was true for pitching moment, lift, and drag although pitching moment was the parameter of greatest interest for this project. With the turbine powered simulator units operating, the model pitching moment was seen to increase when compared to the ow-through nacelle con guration indicating that the center elevon and vertical tail control authority increased with the jet exhaust from the turbine powered simulator units

Dose-finding study of a 90-day contraceptive vaginal ring releasing estradiol and segesterone acetate.

ObjectiveTo evaluate serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200 mcg/day and segesterone acetate (SA) 200 mcg/day to identify a dose that avoids hypoestrogenism.Study designWe conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥40 pg/mL). In an optional 2-cycle extension substudy, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information.ResultsSixty-five participants enrolled in E2 75 (n = 22), 100 (n = 21), and 200 (n = 22) mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100 mcg/day groups were <40 pg/mL. In the 200 mcg/day group, median E2 concentrations peaked on days 4-5 of CVR use at 194 pg/mL (range 114-312 pg/mL) and remained >40 pg/mL throughout 30 days; E2 concentrations were 37 pg/mL (range 28-62 pg/mL) on days 88-90 (n = 11). Among the E2 200 mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0-16) and three (range 0-19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days.ConclusionsEstradiol concentrations with rings releasing E2 200 mcg/day and SA 200 mcg/day avoid hypoestrogenism over 30-day use.ImplicationsA 90-day contraceptive vaginal ring releasing estradiol 200 mcg/day and segesterone acetate 200 mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation

Applying the Huntington’s Disease Integrated Staging System (HD-ISS) to Observational Studies

Background: The Huntington’s Disease Integrated Staging System (HD-ISS) has four stages that characterize disease progression. Classification is based on CAG length as a marker of Huntington’s disease (Stage 0), striatum atrophy as a biomarker of pathogenesis (Stage 1), motor or cognitive deficits as HD signs and symptoms (Stage 2), and functional decline (Stage 3). One issue for implementation is the possibility that not all variables are measured in every study, and another issue is that the stages are broad and may benefit from progression subgrouping./ Objective: Impute stages of the HD-ISS for observational studies in which missing data precludes direct stage classification, and then define progression subgroups within stages./ Methods: A machine learning algorithm was used to impute stages. Agreement of the imputed stages with the observed stages was evaluated using graphical methods and propensity score matching. Subgroups were defined based on descriptive statistics and optimal cut-point analysis./ Results: There was good overall agreement between the observed stages and the imputed stages, but the algorithm tended to over-assign Stage 0 and under-assign Stage 1 for individuals who were early in progression./ Conclusion: There is evidence that the imputed stages can be treated similarly to the observed stages for large-scale analyses. When imaging data are not available, imputation can be avoided by collapsing the first two stages using the categories of Stage≤1, Stage 2, and Stage 3. Progression subgroups defined within a stage can help to identify groups of more homogeneous individuals.

Agile software development in an earned value world: a survival guide

Agile methodologies are current best practice in software development. They are favored for, among other reasons, preventing premature optimization by taking a somewhat short-term focus, and allowing frequent replans/reprioritizations of upcoming development work based on recent results and current backlog. At the same time, funding agencies prescribe earned value management accounting for large projects which, these days, inevitably include substantial software components. Earned Value approaches emphasize a more comprehensive and typically longer-range plan, and tend to characterize frequent replans and reprioritizations as indicative of problems. Here we describe the planning, execution and reporting framework used by the LSST Data Management team, that navigates these opposite tensions

Childhood Sexual Abuse and Early Timing of Puberty

AbstractPurposeThe purpose was to examine whether the timing of puberty, indexed by breast development and pubic hair development, was earlier for sexually abused females compared with a matched comparison group of nonabused females, controlling for key alternative confounds.MethodsA cohort of sexually abused females and matched comparisons was followed longitudinally at mean ages 11 through 20 years. Sexually abused participants (N = 84) were referred by protective services. Comparison participants (N = 89) were recruited to be comparable in terms of age, ethnicity, income level, family constellation, zip codes, and nonsexual trauma histories. Stage of puberty was indexed at each assessment by nurse and participant ratings of breast and pubic hair development using Tanner staging—the gold standard for assessing pubertal onset and development. Cumulative logit mixed models were used to estimate the association between sexual abuse status and the likelihood of transitioning from earlier to later Tanner stage categories controlling for covariates and potential confounds.ResultsSexual abuse was associated with earlier pubertal onset: 8 months earlier for breasts (odds ratio: 3.06, 95% CI: 1.11–8.49) and 12 months earlier for pubic hair (odds ratio: 3.49, 95% CI: 1.34–9.12). Alternative explanations including ethnicity, obesity, and biological father absence did not eradicate these findings.ConclusionsThis study confirms an association between exposure to childhood sexual abuse and earlier pubertal onset. Results highlight the possibility that, due to this early onset, sexual abuse survivors may be at increased risk for psychosocial difficulties, menstrual and fertility problems, and even reproductive cancers due to prolonged exposure to sex hormones

Phenotype Characterization of HD Intermediate Alleles in PREDICT-HD

BACKGROUND: Huntington disease (HD) is a neurodegenerative disease caused by a CAG repeat expansion on chromosome 4. Pathology is associated with CAG repeat length. Prior studies examining people in the intermediate allele (IA) range found subtle differences in motor, cognitive, and behavioral domains compared to controls. OBJECTIVE: The purpose of this study was to examine baseline and longitudinal differences in motor, cognitive, behavioral, functional, and imaging outcomes between persons with CAG repeats in three ranges: normal (≤26), intermediate (27-35), and reduced penetrance (36-39). METHODS: We examined longitudinal data from 389 participants in three allele groups: 280 normal controls (NC), 21 intermediate allele [IA], and 88 reduced penetrance [RP]. We used linear mixed models to identify differences in baseline and longitudinal outcomes between groups. Three models were tested: 1) no baseline or longitudinal differences; 2) baseline differences but no longitudinal differences; and 3) baseline and longitudinal differences. RESULTS: Model 1 was the best fitting model for most outcome variables. Models 2 and 3 were best fitting for some of the variables. We found baseline and longitudinal trends of declining performance across increasing CAG repeat length groups, but no significant differences between the NC and IA groups. CONCLUSION: We did not find evidence to support differences in the IA group compared to the NC group. These findings are limited by a small IA sample size