The potential for bias in principal causal effect estimation when treatment received depends on a key covariate

Motivated by a potential-outcomes perspective, the idea of principal stratification has been widely recognized for its relevance in settings susceptible to posttreatment selection bias such as randomized clinical trials where treatment received can differ from treatment assigned. In one such setting, we address subtleties involved in inference for causal effects when using a key covariate to predict membership in latent principal strata. We show that when treatment received can differ from treatment assigned in both study arms, incorporating a stratum-predictive covariate can make estimates of the "complier average causal effect" (CACE) derive from observations in the two treatment arms with different covariate distributions. Adopting a Bayesian perspective and using Markov chain Monte Carlo for computation, we develop posterior checks that characterize the extent to which incorporating the pretreatment covariate endangers estimation of the CACE. We apply the method to analyze a clinical trial comparing two treatments for jaw fractures in which the study protocol allowed surgeons to overrule both possible randomized treatment assignments based on their clinical judgment and the data contained a key covariate (injury severity) predictive of treatment received.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS477 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Dissociating task difficulty from incongruence in face-voice emotion integration

In the everyday environment, affective information is conveyed by both the face and the voice. Studies have demonstrated that a concurrently presented voice can alter the way that an emotional face expression is perceived, and vice versa, leading to emotional conflict if the information in the two modalities is mismatched. Additionally, evidence suggests that incongruence of emotional valence activates cerebral networks involved in conflict monitoring and resolution. However, it is currently unclear whether this is due to task difficulty—that incongruent stimuli are harder to categorize—or simply to the detection of mismatching information in the two modalities. The aim of the present fMRI study was to examine the neurophysiological correlates of processing incongruent emotional information, independent of task difficulty. Subjects were scanned while judging the emotion of face-voice affective stimuli. Both the face and voice were parametrically morphed between anger and happiness and then paired in all audiovisual combinations, resulting in stimuli each defined by two separate values: the degree of incongruence between the face and voice, and the degree of clarity of the combined face-voice information. Due to the specific morphing procedure utilized, we hypothesized that the clarity value, rather than incongruence value, would better reflect task difficulty. Behavioral data revealed that participants integrated face and voice affective information, and that the clarity, as opposed to incongruence value correlated with categorization difficulty. Cerebrally, incongruence was more associated with activity in the superior temporal region, which emerged after task difficulty had been accounted for. Overall, our results suggest that activation in the superior temporal region in response to incongruent information cannot be explained simply by task difficulty, and may rather be due to detection of mismatching information between the two modalities

The Role of Pitch and Timbre in Voice Gender Categorization

Voice gender perception can be thought of as a mixture of low-level perceptual feature extraction and higher-level cognitive processes. Although it seems apparent that voice gender perception would rely on low-level pitch analysis, many lines of research suggest that this is not the case. Indeed, voice gender perception has been shown to rely on timbre perception and to be categorical, i.e., to depend on accessing a gender model or representation. Here, we used a unique combination of acoustic stimulus manipulation and mathematical modeling of human categorization performances to determine the relative contribution of pitch and timbre to this process. Contrary to the idea that voice gender perception relies on timber only, we demonstrate that voice gender categorization can be performed using pitch only but more importantly that pitch is used only when timber information is ambiguous (i.e., for more androgynous voices)

Comparative effectiveness trial comparing MyPlate to calorie counting for mostly low-income Latino primary care patients of a federally qualified community health center: study design, baseline characteristics.

BackgroundPrimary care-based behavior change obesity treatment has long featured the Calorie restriction (CC), portion control approach. By contrast, the MyPlate-based obesity treatment approach encourages eating more high-satiety/high-satiation foods and requires no calorie-counting. This report describes study methods of a comparative effectiveness trial of CC versus MyPlate. It also describes baseline findings involving demographic characteristics and their associations with primary outcome measures and covariates, including satiety/satiation, dietary quality and acculturation.MethodsA comparative effectiveness trial was designed to compare the CC approach (n = 130) versus a MyPlate-based approach (n = 131) to treating patient overweight. Intervenors were trained community health workers. The 11 intervention sessions included two in-home health education sessions, two group education sessions, and seven telephone coaching sessions. Questionnaire and anthropometric assessments occurred at baseline, 6- and 12 months; food frequency questionnaires were administered at baseline and 12 months. Participants were overweight adult primary care patients of a federally qualified health center in Long Beach, California. Two measures of satiety/satiation and one measure of post-meal hunger comprised the primary outcome measures. Secondary outcomes included weight, waist circumference, blood pressure, dietary quality, sugary beverage intake, water intake, fruit and vegetable fiber intake, mental health and health-related quality of life. Covariates included age, gender, nativity status (U.S.-born, not U.S.-born), race/ethnicity, education, and acculturation.AnalysisBaseline characteristics were compared using chi square tests. Associations between covariates and outcome measures were evaluated using multiple regression and logistic regression.ResultsTwo thousand eighty-six adult patients were screened, yielding 261 enrollees who were 86% Latino, 8% African American, 4% White and 2% Other. Women predominated (95%). Mean age was 42 years. Most (82%) were foreign-born; 74% chose the Spanish language option. Mean BMI was 33.3 kg/m2; mean weight was 82 kg; mean waist circumference was 102 cm. Mean blood pressure was 122/77 mm. Study arms on key baseline measures did not differ except on dietary quality and sugary beverage intake. Nativity status was significantly associated with dietary quality.ConclusionsThe two treatment arms were well-balanced demographically at baseline. Nativity status is inversely related to dietary quality.Trial registrationNCT02514889 , posted on 8/4/2015

DNA damage induces nuclear actin filament assembly by Formin-2 and Spire-1/2 that promotes efficient DNA repair

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in eLife 4 (2015): e07735, doi:10.7554/eLife.07735.Actin filaments assemble inside the nucleus in response to multiple cellular perturbations, including heat shock, protein misfolding, integrin engagement, and serum stimulation. We find that DNA damage also generates nuclear actin filaments—detectable by phalloidin and live-cell actin probes—with three characteristic morphologies: (i) long, nucleoplasmic filaments; (ii) short, nucleolus-associated filaments; and (iii) dense, nucleoplasmic clusters. This DNA damage-induced nuclear actin assembly requires two biologically and physically linked nucleation factors: Formin-2 and Spire-1/Spire-2. Formin-2 accumulates in the nucleus after DNA damage, and depletion of either Formin-2 or actin’s nuclear import factor, importin-9, increases the number of DNA double-strand breaks (DSBs), linking nuclear actin filaments to efficient DSB clearance. Nuclear actin filaments are also required for nuclear oxidation induced by acute genotoxic stress. Our results reveal a previously unknown role for nuclear actin filaments in DNA repair and identify the molecular mechanisms creating these nuclear filaments.Howard Hughes Medical Institute; National Institutes of Health, GM061010, GM079556, 5F31AG39147-2; National Science Foundatio

Intermittency and the Slow Approach to Kolmogorov Scaling

From a simple path integral involving a variable volatility in the velocity differences, we obtain velocity probability density functions with exponential tails, resembling those observed in fully developed turbulence. The model yields realistic scaling exponents and structure functions satisfying extended self-similarity. But there is an additional small scale dependence for quantities in the inertial range, which is linked to a slow approach to Kolmogorov (1941) scaling occurring in the large distance limit.Comment: 10 pages, 5 figures, minor changes to mirror version to appear in PR

Whitetail Deer Carrying Capacity at a Georgia Barrier Island

Whitetail deer (Odocoileus virginianus) populations of several islands along the Georgia coast have appeared to be in declining health for the past 10 years. Several explanations for this phenomenon have been proposed; however, several researchers have alluded to the over-population of the species. We calculated the carrying capacity of the Skidaway Island State Park (SISP), a portion of Skidaway Island located near the coastal City of Savannah. By determining the amount of biomass produced by several habitats located within the park, and knowing the hectares of these habitats, the total amount of biomass was calculated. Using the caloric requirements of the whitetail deer found at various regions of the continental United States, we determined the sustainable carrying capacity of a healthy deer population within the park. We calculated that approximately 11.5 deer can be annually sustained on the vegetative biomass produced by the Skidaway Island State Park (SISP)

Visualization of actin filaments and monomers in somatic cell nuclei

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 24 (2013): 982-994, doi:10.1091/mbc.E12-09-0685.In addition to its long-studied presence in the cytoplasm, actin is also found in the nuclei of eukaryotic cells. The function and form (monomer, filament, or noncanonical oligomer) of nuclear actin are hotly debated, and its localization and dynamics are largely unknown. To determine the distribution of nuclear actin in live somatic cells and evaluate its potential functions, we constructed and validated fluorescent nuclear actin probes. Monomeric actin probes concentrate in nuclear speckles, suggesting an interaction of monomers with RNA-processing factors. Filamentous actin probes recognize discrete structures with submicron lengths that are excluded from chromatin-rich regions. In time-lapse movies, these actin filament structures exhibit one of two types of mobility: 1) diffusive, with an average diffusion coefficient of 0.06–0.08 μm2/s, or (2) subdiffusive, with a mobility coefficient of 0.015 μm2/s. Individual filament trajectories exhibit features of particles moving within a viscoelastic mesh. The small size of nuclear actin filaments is inconsistent with a role in micron-scale intranuclear transport, and their localization suggests that they do not participate directly in chromatin-based processes. Our results instead suggest that actin filaments form part of a large, viscoelastic structure in the nucleoplasm and may act as scaffolds that help organize nuclear contents.This bulk of this work was supported by a grant from the National Institutes of Health to R.D.M. (5R01GM061010-12). Additional support was provided by National Institutes of Health Grant R01 CA096840 (E.H.B.), a National Science Foundation Predoctoral Fellowship (B.B.), a National Institutes of Health Ruth L. Kirschstein Predoctoral Fellowship (B.B.), and a Genentech Fellowship (B.C.)

On the value of the Kullback-Leibler divergence for cost-effective spectral imaging of plants by optimal selection of wavebands

The practical value of a criterion based on statistical information theory is demonstrated for the selection of optimal wavelength and bandwidth of low-cost lighting systems in plant imaging applications. Kullback–Leibler divergence is applied to the problem of spectral band reduction from hyperspectral imaging. The results are illustrated on various plant imaging problems and show similar results to the one obtained with state-of-the-art criteria. A specific interest of the proposed approach is to offer the possibility to integrate technological constraints in the optimization of the spectral bands selected

Transitions and Probes in Turbulent Helium

Previous analysis of a Paris turbulence experiment \cite{zoc94,tab95} shows a transition at the Taylor Reynolds number \rel \approx 700. Here correlation function data is analyzed which gives further evidence for this transition. It is seen in both the power spectrum and in structure function measurements. Two possible explanations may be offered for this observed transition: that it is intrinsic to the turbulence flow in this closed box experiment or that it is an effect of a change in the flow around the anemometer. We particularly examine a pair of ``probe effects''. The first is a thermal boundary layer which does exist about the probe and does limit the probe response, particularly at high frequencies. Arguments based on simulations of the response and upon observations of dissipation suggests that this effect is only crucial beyond \rel\approx 2000. The second effect is produced by vortex shedding behind the probe. This has been seen to produce a large modification in some of the power spectra for large \rel. It might also complicate the interpretation of the experimental results. However, there seems to be a remaining range of data for \rel < 1300 uncomplicated by these effects, and which are thus suggestive of an intrinsic transition.Comment: uuencoded .ps files. submitted to PRE. 12 figures are sent upon request to jane wang ([email protected]