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

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

Substantial improvements not seen in health behaviors following corner store conversions in two Latino food swamps.

BackgroundThe effectiveness of food retail interventions is largely undetermined, yet substantial investments have been made to improve access to healthy foods in food deserts and swamps via grocery and corner store interventions. This study evaluated the effects of corner store conversions in East Los Angeles and Boyle Heights, California on perceived accessibility of healthy foods, perceptions of corner stores, store patronage, food purchasing, and eating behaviors.MethodsHousehold data (n = 1686) were collected at baseline and 12- to 24-months post-intervention among residents surrounding eight stores, three of which implemented a multi-faceted intervention and five of which were comparisons. Bivariate analyses and logistic and linear regressions were employed to assess differences in time, treatment, and the interaction between time and treatment to determine the effectiveness of this intervention.ResultsImprovements were found in perceived healthy food accessibility and perceptions of corner stores. No changes were found, however, in store patronage, purchasing, or consumption of fruits and vegetables.ConclusionsResults suggest limited effectiveness of food retail interventions on improving health behaviors. Future research should focus on other strategies to reduce community-level obesity

Cardiovascular Health: Associations with Race-ethnicity, Nativity, and Education in a Diverse, Population-based Sample of Californians

Purpose—This study examined how race-ethnicity, nativity, and education interact to influence disparities in cardiovascular (CV) health, a new concept defined by the American Heart Association (AHA). We assessed whether race-ethnicity and nativity disparities in CV health vary by education, and whether the foreign-born differ in CV health from their US-born race-ethnic counterparts with comparable education. Methods—We used data from the 2009 California Health Interview Survey to determine the prevalence of optimal CV health metrics (based on selected AHA guidelines) among adults ages 25 and over (n = 42,014). We examined the interaction between education and ethnicity-nativity, comparing predicted probabilities of each CV health measure between US-born and foreign-born Whites, Asians, and Latinos. Results—All groups were at high risk of suboptimal physical activity levels, fruit and vegetable and fast food consumption, and overweight/obesity. Those with higher education were generally better-off, except among Asians. Ethnicity-nativity differences were more pronounced among those with less than a college degree. The foreign-born exhibited both advantages anddisadvantages in CV health compared to their US-born counterparts that varied by ethnicitynativity. Conclusions—Education influences ethnicity-nativity disparities in CV health, with most raceethnic and nativity differences occurring among the less educated. Studies of nativity differences in CV health should stratify by education in order to adequately address SES differences

Depression prevalence in disadvantaged young black women

Research with Mexican Americans suggests that immigrants have lower rates of mental disorders than U. S.-born Mexican Americans. We examine the prevalence of depression, somatization, alcohol use and drug use among black American women, comparing rates of disorders among U. S.-born, Caribbean-born, and African-born subsamples.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41740/1/127_2005_Article_879.pd

Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle.

Migration through 3D constrictions can cause nuclear rupture and mislocalization of nuclear proteins, but damage to DNA remains uncertain, as does any effect on cell cycle. Here, myosin II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent block in cell cycle appears unaffected. Co-overexpression of multiple DNA repair factors or antioxidant inhibition of break formation also exert partial effects, independently of rupture. Combined treatments completely rescue cell cycle suppression by DNA damage, revealing a sigmoidal dependence of cell cycle on excess DNA damage. Migration through custom-etched pores yields the same damage threshold, with ∼4-µm pores causing intermediate levels of both damage and cell cycle suppression. High curvature imposed rapidly by pores or probes or else by small micronuclei consistently associates nuclear rupture with dilution of stiff lamin-B filaments, loss of repair factors, and entry from cytoplasm of chromatin-binding cGAS (cyclic GMP-AMP synthase). The cell cycle block caused by constricted migration is nonetheless reversible, with a potential for DNA misrepair and genome variation

Magnetic field - temperature phase diagram of quasi-two-dimensional organic superconductor lambda-(BETS)_2 GaCl_4 studied via thermal conductivity

The thermal conductivity kappa of the quasi-two-dimensional (Q2D) organic superconductor lambda-(BETS)_2 GaCl_4 was studied in the magnetic field H applied parallel to the Q2D plane. The phase diagram determined from this bulk measurement shows notable dependence on the sample quality. In dirty samples the upper critical field H_{c2} is consistent with the Pauli paramagnetic limiting, and a sharp change is observed in kappa(H) at H_{c2 parallel}. In contrast in clean samples H_{c2}(T) shows no saturation towards low temperatures and the feature in kappa(H) is replaced by two slope changes reminiscent of second-order transitions. The peculiarity was observed below ~ 0.33T_c and disappeared on field inclination to the plane when the orbital suppression of superconductivity became dominant. This behavior is consistent with the formation of a superconducting state with spatially modulated order parameter in clean samples.Comment: 10 pages, 8 figures, new figure (Fig.5) and references added, title change

Observation of an Excited Bc+ State

Using pp collision data corresponding to an integrated luminosity of 8.5 fb-1 recorded by the LHCb experiment at center-of-mass energies of s=7, 8, and 13 TeV, the observation of an excited Bc+ state in the Bc+π+π- invariant-mass spectrum is reported. The observed peak has a mass of 6841.2±0.6(stat)±0.1(syst)±0.8(Bc+) MeV/c2, where the last uncertainty is due to the limited knowledge of the Bc+ mass. It is consistent with expectations of the Bc∗(2S31)+ state reconstructed without the low-energy photon from the Bc∗(1S31)+→Bc+γ decay following Bc∗(2S31)+→Bc∗(1S31)+π+π-. A second state is seen with a global (local) statistical significance of 2.2σ (3.2σ) and a mass of 6872.1±1.3(stat)±0.1(syst)±0.8(Bc+) MeV/c2, and is consistent with the Bc(2S10)+ state. These mass measurements are the most precise to date

Actin binding to WH2 domains regulates nuclear import of the multifunctional actin regulator JMY

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Molecular Biology of the Cell 23 (2012): 853-863, doi:10.1091/mbc.E11-12-0992.Junction-mediating and regulatory protein (JMY) is a regulator of both transcription and actin filament assembly. In response to DNA damage, JMY accumulates in the nucleus and promotes p53-dependent apoptosis. JMY's actin-regulatory activity relies on a cluster of three actin-binding Wiskott–Aldrich syndrome protein homology 2 (WH2) domains that nucleate filaments directly and also promote nucleation activity of the Arp2/3 complex. In addition to these activities, we find that the WH2 cluster overlaps an atypical, bipartite nuclear localization sequence (NLS) and controls JMY's subcellular localization. Actin monomers bound to the WH2 domains block binding of importins to the NLS and prevent nuclear import of JMY. Mutations that impair actin binding, or cellular perturbations that induce actin filament assembly and decrease the concentration of monomeric actin in the cytoplasm, cause JMY to accumulate in the nucleus. DNA damage induces both cytoplasmic actin polymerization and nuclear import of JMY, and we find that damage-induced nuclear localization of JMY requires both the WH2/NLS region and importin β. On the basis of our results, we propose that actin assembly regulates nuclear import of JMY in response to DNA damage.This work was supported by grants from the National Institutes of Health, an American Heart Association Predoctoral Fellowship (J.B.Z.), the Robert Day Allen Fellowship Fund (J.B.Z.), and a National Science Foundation Predoctoral Fellowship (B.B.)

Reward-Related Dorsal Striatal Activity Differences between Former and Current Cocaine Dependent Individuals during an Interactive Competitive Game

Cocaine addiction is characterized by impulsivity, impaired social relationships, and abnormal mesocorticolimbic reward processing, but their interrelationships relative to stages of cocaine addiction are unclear. We assessed blood-oxygenation-level dependent (BOLD) signal in ventral and dorsal striatum during functional magnetic resonance imaging (fMRI) in current (CCD; n = 30) and former (FCD; n = 28) cocaine dependent subjects as well as healthy control (HC; n = 31) subjects while playing an interactive competitive Domino game involving risk-taking and reward/punishment processing. Out-of-scanner impulsivity-related measures were also collected. Although both FCD and CCD subjects scored significantly higher on impulsivity-related measures than did HC subjects, only FCD subjects had differences in striatal activation, specifically showing hypoactivation during their response to gains versus losses in right dorsal caudate, a brain region linked to habituation, cocaine craving and addiction maintenance. Right caudate activity in FCD subjects also correlated negatively with impulsivity-related measures of self-reported compulsivity and sensitivity to reward. These findings suggest that remitted cocaine dependence is associated with striatal dysfunction during social reward processing in a manner linked to compulsivity and reward sensitivity measures. Future research should investigate the extent to which such differences might reflect underlying vulnerabilities linked to cocaine-using propensities (e.g., relapses)