The unexplained nature of reading.

The effects of properties of words on their reading aloud response times (RTs) are 1 major source of evidence about the reading process. The precision with which such RTs could potentially be predicted by word properties is critical to evaluate our understanding of reading but is often underestimated due to contamination from individual differences. We estimated this precision without such contamination individually for 4 people who each read 2,820 words 50 times each. These estimates were compared to the precision achieved by a 31-variable regression model that outperforms current cognitive models on variance-explained criteria. Most (around 2/3) of the meaningful (non-first-phoneme, non-noise) word-level variance remained unexplained by this model. Considerable empirical and theoretical-computational effort has been expended on this area of psychology, but the high level of systematic variance remaining unexplained suggests doubts regarding contemporary accounts of the details of the mechanisms of reading at the level of the word. Future assessment of models can take advantage of the availability of our precise participant-level database

A complete characterization of phase space measurements

We characterize all the phase space measurements for a non-relativistic particle.Comment: 11 pages, latex, no figures, iopart styl

Letters in words are read simultaneously, not in left-to-right sequence

The identification of individual letters is necessary for reading words in alphabetic script (Pelli, Farell, & Moore, 2003). Sequential models of letter processing (Whitney, 2001) in reading words posit an initial left-to-right sequence of letter processing (in left-to-right languages, such as English), each letter taking 10–25 ms to process before the next is processed. In contrast, simultaneous models of letter processing (e.g., Tydgat & Grainger, 2009) in reading words posit that information about the identity of each letter starts to be extracted at the same time point, regardless of horizontal position. Here we show that people reading four-letter words do not extract identity information for any letter from an 18 ms display of the word, but some information about all four letters is available from 24 ms of display. Our results indicate that a left-to-right sequence of attention across letters is not used in establishing the cognitive representation of words. Instead, all letters are processed simultaneously

Comparison of the diagnostic yield and outcomes between standard 8 h capsule endoscopy and the new 12 h capsule endoscopy for investigating small bowel pathology

AIM: To evaluate the completion rate and diagnostic yield of the PillCam SB2-ex in comparison to the PillCam SB2. METHODS: Two hundred cases using the 8-h PillCam SB2 were retrospectively compared to 200 cases using the 12 h PillCam SB2-ex at a tertiary academic center. Endoscopically placed capsules were excluded from the study. Demographic information, indications for capsule endoscopy, capsule type, study length, completion of exam, clinically significant findings, timestamp of most distant finding, and significant findings beyond 8 h were recorded. RESULTS: The 8 and 12 h capsule groups were well matched respectively for both age (70.90 +/- 14.19 vs 71.93 +/- 13.80, P = 0.46) and gender (45.5% vs 48% male, P = 0.69). The most common indications for the procedure in both groups were anemia and obscure gastrointestinal bleeding. PillCam SB2-ex had a significantly higher completion rate than PillCam SB2 (88% vs 79.5%, P = 0.03). Overall, the diagnostic yield was greater for the 8 h capsule (48.5% for SB2 vs 35% for SB2-ex, P = 0.01). In 4/70 (5.7%) of abnormal SB2-ex exams the clinically significant finding was noted in the small bowel beyond the 8 h mark. CONCLUSION: In our study, we found the PillCam SB2-ex to have a significantly increased completion rate, though without any improvement in diagnostic yield compared to the PillCam SB2

Comparison of the Use of a Physiologically Based Pharmacokinetic Model and a Classical Pharmacokinetic Model for Dioxin Exposure Assessments

In epidemiologic studies, exposure assessments of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) assume a fixed elimination rate. Recent data suggest a dose-dependent elimination rate for TCDD. A physiologically based pharmacokinetic (PBPK) model, which uses a body-burden–dependent elimination rate, was developed previously in rodents to describe the pharmacokinetics of TCDD and has been extrapolated to human exposure for this study. Optimizations were performed using data from a random selection of veterans from the Ranch Hand cohort and data from a human volunteer who was exposed to TCDD. Assessment of this PBPK model used additional data from the Ranch Hand cohort and a clinical report of two women exposed to TCDD. This PBPK model suggests that previous exposure assessments may have significantly underestimated peak blood concentrations, resulting in potential exposure misclassifications. Application of a PBPK model that incorporates an inducible elimination of TCDD may improve the exposure assessments in epidemiologic studies of TCDD

Use of a Physiologically Based Pharmacokinetic Model for Rats to Study the Influence of Body Fat Mass and Induction of CYP1A2 on the Pharmacokinetics of TCDD

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly lipophilic chemical that distributes into adipose tissue, especially at low doses. However, at high doses TCDD sequesters in liver because it induces cytochrome P450 1A2 (CYP1A2) that binds TCDD. A physiologically based pharmacokinetic (PBPK) model was developed that included an inducible elimination rate of TCDD in the Sprague-Dawley rat. Objectives of this work were to characterize the influence of induction of CYP1A2 and adipose tissue mass fraction on the terminal elimination half-life (t(1/2)) of TCDD using this PBPK model. When the model assumes a fixed elimination of TCDD, t(1/2) increases with dose, due to hepatic sequestration. Because experimental data indicate that the t(1/2) of TCDD decreases with dose, the model was modified to include an inducible elimination rate. The PBPK model was then used to compare the t(1/2) after an increase of adipose tissue mass fraction from 6.9 to 70%. The model suggests that at low exposures, increasing adipose tissue mass increases the terminal t(1/2). However, at higher exposures, as CYP1A2 is induced, the relationship between adipose tissue mass and t(1/2) reaches a plateau. This demonstrates that an inducible elimination rate is needed in a PBPK model in order to describe the pharmacokinetics of TCDD. At low exposures these models are more sensitive to parameters related to partitioning into adipose tissue

Thyroid-Hormone–Disrupting Chemicals: Evidence for Dose-Dependent Additivity or Synergism

Endocrine disruption from environmental contaminants has been linked to a broad spectrum of adverse outcomes. One concern about endocrine-disrupting xenobiotics is the potential for additive or synergistic (i.e., greater-than-additive) effects of mixtures. A short-term dosing model to examine the effects of environmental mixtures on thyroid homeostasis has been developed. Prototypic thyroid-disrupting chemicals (TDCs) such as dioxins, polychlorinated biphenyls (PCBs), and poly-brominated diphenyl ethers have been shown to alter thyroid hormone homeostasis in this model primarily by up-regulating hepatic catabolism of thyroid hormones via at least two mechanisms. Our present effort tested the hypothesis that a mixture of TDCs will affect serum total thyroxine (T(4)) concentrations in a dose-additive manner. Young female Long-Evans rats were dosed via gavage with 18 different polyyhalogenated aromatic hydrocarbons [2 dioxins, 4 dibenzofurans, and 12 PCBs, including dioxin-like and non-dioxin-like PCBs] for 4 consecutive days. Serum total T(4) was measured via radioimmunoassay in samples collected 24 hr after the last dose. Extensive dose–response functions (based on seven to nine doses per chemical) were determined for individual chemicals. A mixture was custom synthesized with the ratio of chemicals based on environmental concentrations. Serial dilutions of this mixture ranged from approximately background levels to 100-fold greater than background human daily intakes. Six serial dilutions of the mixture were tested in the same 4-day assay. Doses of individual chemicals that were associated with a 30% TH decrease from control (ED(30)), as well as predicted mixture outcomes were calculated using a flexible single-chemical-required method applicable to chemicals with differing dose thresholds and maximum-effect asymptotes. The single-chemical data were modeled without and with the mixture data to determine, respectively, the expected mixture response (the additivity model) and the experimentally observed mixture response (the empirical model). A likelihood-ratio test revealed statistically significant departure from dose additivity. There was no deviation from additivity at the lowest doses of the mixture, but there was a greater-than-additive effect at the three highest mixtures doses. At high doses the additivity model underpredicted the empirical effects by 2- to 3-fold. These are the first results to suggest dose-dependent additivity and synergism in TDCs that may act via different mechanisms in a complex mixture. The results imply that cumulative risk approaches be considered when assessing the risk of exposure to chemical mixtures that contain TDCs