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

Einstein gravity from ANEC correlators

We study correlation functions with multiple averaged null energy (ANEC) operators in conformal field theories. For large $N$ CFTs with a large gap to higher spin operators, we show that the OPE between a local operator and the ANEC can be recast as a particularly simple differential operator acting on the local operator. This operator is simple enough that we can resum it and obtain the finite distance OPE. Under the large $N$ - large gap assumptions, the vanishing of the commutator of ANEC operators tightly constrains the OPE coefficients of the theory. An important example of this phenomenon is the conclusion that $a=c$ in $d=4$. This implies that the bulk dual of such a CFT is semi-classical Einstein-gravity with minimally coupled matter.Comment: 32 pages + appendices, 6 figures; v2:typos corrected and a comment added in introductio

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

Ascorbic acid is a regulator of the intracellular cAMP concentration: Old molecule, new functions?

AbstractRecently, using an animal model of Charcot-Marie-Tooth human disorder, we showed that ascorbic acid (AA) represses PMP22 gene expression by acting on intracellular cAMP concentrations. In this work, we present kinetics data on the inhibitory effect of AA upon adenylate cyclase activity. The data show that this molecule acts as a competitive inhibitor of the enzyme, a finding that opens new pharmacological avenues

N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake.

BACKGROUND: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown. METHODS: We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation. Rats then received daily saline or NAC (60 mg/kg, intraperitoneal) treatment and were tested under a progressive ratio and several consecutive sessions in which lever presses were punished by mild electric foot shocks. RESULTS: NAC increased the sensitivity to punishment in LgA rats only, thereby promoting abstinence. Following the cessation of punishment, NAC-treated LgA rats failed to recover fully their prepunishment cocaine intake levels and resumed cocaine SA at a lower rate than short access and vehicle-treated LgA rats. However, NAC altered neither the escalation of SA nor the motivation for cocaine. At the neurobiological level, NAC reversed cocaine-induced decreases in the glutamate type 1 transporter observed in both the nucleus accumbens and the dorsolateral striatum. NAC also increased the expression of Zif268 in the nucleus accumbens and dorsolateral striatum of LgA rats. CONCLUSIONS: Our results indicate that NAC contributes to the restoration of control over cocaine SA following adverse consequences, an effect associated with plasticity mechanisms in both the ventral and dorsolateral striatum.This research was supported by a French Institute of Health and Medical Research Avenir and an ANR12 SAMA00201 Grant (to DB) as well as a Newton Trust/Cambridge University Grant (to DB). BJE and JEM are supported by a Medical Research Council (G9536855, G0701500) Grant to BJE and by a joint award from the Medical Research Council and Wellcome Trust in support of the Behavioral and Clinical Neuroscience Institute at Cambridge University

De la vaccination du Porc contre la fièvre aphteuse

Belin Marcel. De la vaccination du Porc contre la fièvre aphteuse. In: Bulletin de l'Académie Vétérinaire de France tome 101 n°6, 1948. pp. 279-280

Structural effects of anomalous current densities on manganese hexacyanoferrate for Li-ion batteries

A battery management system (BMS) plays a pivotal role in providing optimal performance of lithium-ion batteries (LIBs). However, the eventual malfunction of the BMS may lead to safety hazards or reduce the remaining useful life of LIBs. Manganese hexacyanoferrate (MnHCF) was employed as the positive electrode material in a Li-ion half-cell and subjected to five cycles at high current densities (10 A gMnHCF−1) and to discharge at 0.1 A gMnHCF−1, instead of classical charge/discharge cycling with initial positive polarization at 0.01 A gMnHCF−1, to simulate a current sensor malfunctioning and to evaluate the electrochemical and structural effects on MnHCF. The operando set of spectra at the Mn and Fe K-edges was further analyzed through multivariate curve resolution analysis with an alternating least squares algorithm (MCR–ALS) and extended X-ray absorption fine structure (EXAFS) spectroscopy to investigate the structural modifications arising during cycling after the applied electrochemical protocol. The coulombic efficiency in the first cycle was dramatically affected; however, the local structural environment around each photo absorber recovered during charging. The identification of an additional spectral contribution in the electrochemical process was achieved through MCR-ALS analysis, and the Mn-local asymmetry was thoroughly explored via EXAFS analysis