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

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

A Cross-Sectional Study of All Clinicians’ Conflict of Interest Disclosures to NHS Hospital Employers in England 2015-2016

Objective We set out to document how NHS trusts in the UK record and share disclosures of conflict of interest by their employees. Design Cross-sectional study of responses to a Freedom of Information Act request for Gifts and Hospitality Registers. Setting NHS Trusts (secondary/tertiary care organisations) in England. Participants 236 Trusts were contacted, of which 217 responded. Main outcome measures We assessed all disclosures for completeness and openness, scoring them for achieving each of five measures of transparency. Results 185 Trusts (78%) provided a register. 71 Trusts did not respond within the 28 day time limit required by the FoIA. Most COI registers were incomplete by design, and did not contain the information necessary to assess conflicts of interest. 126/185 (68%) did not record the names of recipients. 47/185 (25%) did not record the cash value of the gift or hospitality. Only 31/185 registers (16%) contained the names of recipients, the names of donors, and the cash amounts received. 18/185 (10%) contained none of: recipient name, donor name, and cash amount. Only 15 Trusts had their disclosure register publicly available online (6%). We generated a transparency index assessing whether each Trust met the following criteria: responded on time; provided a register; had a register with fields identifying donor, recipient, and cash amount; provided a register in a format that allowed further analysis; and had their register publicly available online. Mean attainment was 1.9/5; no NHS trust met all five criteria. Conclusion Overall, recording of employees’ conflicts of interest by NHS trusts is poor. None of the NHS Trusts in England met all transparency criteria. 19 did not respond to our FoIA requests, 51 did not provide a Gifts and Hospitality Register and only 31 of the registers provided contained enough information to assess employees’ conflicts of interest. Despite obligations on healthcare professionals to disclose conflicts of interest, and on organisations to record these, the current system for logging and tracking such disclosures is not functioning adequately. We propose a simple national template for reporting conflicts of interest, modelled on the US ‘Sunshine Act’

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

Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat

The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and brains were collected immediately following motor activity assays. Bifenthrin concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin exposure decreased motor activity from 20% to 70% in a dose-dependent manner at both time points. The relationship between motor activity data and administered dose, and blood and brain bifenthrin concentrations were described using a sigmoidal E max model. The relationships between motor activity and administered dose or blood concentrations were different between the 4- and 7-h time points. The relationship between motor activity and brain concentration was not significantly different between the two time points. These data suggest that momentary brain concentration of bifenthrin may be a more precise dose metric for predicting behavioral effects because the relationship between brain concentration and locomotor activity is independent of the time of exposure.Fil: Scollon, Edward J.. National Health And Environmental Effects Research Laboratory; Estados UnidosFil: Starr, James M.. United States Environmental Protection Agency; Estados UnidosFil: Crofton, Kevin M.. National Health And Environmental Effects Research Laboratory; Estados UnidosFil: Wolansky, Marcelo Javier. National Research Council; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: DeVito, Michael J.. National Health And Environmental Effects Research Laboratory; Estados UnidosFil: Hughes, Michael F.. National Health And Environmental Effects Research Laboratory; Estados Unido