Improving Weight of Evidence Approaches to Chemical Evaluations

Federal and other regulatory agencies often use or claim to use a weight of evidence (WoE) approach in chemical evaluation. Their approaches to the use of WoE, however, differ significantly, rely heavily on subjective professional judgment, and merit improvement. We review uses of WoE approaches in key articles in the peer‐reviewed scientific literature, and find significant variations. We find that a hypothesis‐based WoE approach, developed by Lorenz Rhomberg et al., can provide a stronger scientific basis for chemical assessment while improving transparency and preserving the appropriate scope of professional judgment. Their approach, while still evolving, relies on the explicit specification of the hypothesized basis for using the information at hand to infer the ability of an agent to cause human health impacts or, more broadly, affect other endpoints of concern. We describe and endorse such a hypothesis‐based WoE approach to chemical evaluation.     

Tracing ‘driver’ versus ‘modulator’ information flow throughout large-scale,task-related neural circuitry

Primary objective: To determine the relative uses of neural action potential (‘spike’) data versus local field potentials (LFPs) for modeling information flow through complex brain networks. Hypothesis: The common use of LFP data, which are continuous and therefore more mathematically suited for spectral information-flow modeling techniques such as Granger causality analysis, can lead to spurious inferences about whether a given brain area ‘drives’ the spiking in a downstream area. Experiment: We recorded spikes and LFPs from the forelimb motor cortex (M1) and the magnocellular red nucleus (mRN), which receives axon collaterals from M1 projection cells onto its distal dendrites, but not onto its perisomatic regions, as rats performed a skilled reaching task. Results and implications: As predicted, Granger causality analysis on the LFPs—which are mainly composed of vector-summed dendritic currents—produced results that if conventionally interpreted would suggest that the M1 cells drove spike firing in the mRN, whereas analyses of spiking in the two recorded regions revealed no significant correlations. These results suggest that mathematical models of information flow should treat the sampled dendritic activity as more likely to reflect intrinsic dendritic and input-related processing in neural networks, whereas spikes are more likely to provide information about the output of neural network processing.     

Reading Skills in Children with Multichannel Cochlear-lmplant Experience

Forty children with prelingual, profound deafness who received the Nucleus multichannel cochlear implant between the ages of 2 and 13 years participated in this study. The children had an average of 63.3 months (SD=24 months) of experience with their cochlear implants. A majority of the children used simultaneous communication and attended public-school programs at the time of testing. Reading achievement was assessed using the Paragraph Comprehension subtest of the Woodcock Reading Mastery Test-Revised, Form G (1987). This study compared the reading-achievement levels of this group of cochlear-implant users with the results of previous studies of children with profound hearing losses who did not have the benefit of cochlear implants. Results indicated that nearly one half of the children in this study were reading at or within 8 months of their grade level. The reading-grade quotient of .74 was calculated based upon the slope of the regression line for the plot of years in school and reading grade-level achieved. This finding indicates that using a cochlear implant has a positive effect on reading achievement level.     

Project agreements and government procurement

I discuss the recent proliferation of mandatory project labor agreements in government procurement, some of the ensuing litigation, and the effects of such agreements on contractors, workers, and the public.     

CEOs'Career Backgrounds and Corporate Long-Term Strategic Planning*

CEOs affect corporate outcomes along various dimensions, including the emphasis placed on long-term strategic planning. This study assesses the impact of CEOs’functional and industry specializations on R&D and capital spending in four manufacturing industries. We found only limited support for our position that CEOs with more professional-type careers are less willing than other CEOs to have their firms make long-term investments. “A critical theme of… the modem industrial enterprise is that creating and maintaining such capabilities is a continuing, long-term process–a process that requires sound, long-term perspectives from the decision makers responsible for the health and growth of their enterprise.” (Chandler 1991, p. 627)     

The analytic construction of D-optimal designs for the two-variable binary logistic regression model without interaction

Candidate locally D-optimal designs for the binary two-variable logistic model with no interaction, which comprise 3 and 4 support points lying in the first quadrant of the two-dimensional Euclidean space, were introduced by Haines et al. (D-optimal designs for logistic regression in two variables. In: Lopez-Fidalgo J, Rodrigez-Diaz JM, Torsney B, editors. MODA8 – advances in model-oriented designs and analysis. Heidelberg: Physica-Verlag; 2007. p. 91–98). The authors proved algebraically the global D-optimality of the 3-point design for the special case in which the intercept parameter is equal to?1.5434. However for other selected values of the intercept parameter, the global D-optimality of the proposed 3- and 4-point designs was only demonstrated numerically. In this paper, we provide analytical proofs of the D-optimality of these 3- and 4-point designs for all negative and zero intercept parameters of the binary two-variable logistic model with no interaction. The results are extended to the construction of D-optimal designs on a rectangular design space and illustrated by means of two examples of which one is a real example taken from the literature.     

To adjust or not to adjust for baseline when analyzing repeated binary responses? The case of complete data when treatment comparison at study end is of interest

The benefits of adjusting for baseline covariates are not as straightforward with repeated binary responses as with continuous response variables. Therefore, in this study, we compared different methods for analyzing repeated binary data through simulations when the outcome at the study endpoint is of interest. Methods compared included chi‐square, Fisher's exact test, covariate adjusted/unadjusted logistic regression (Adj.logit/Unadj.logit), covariate adjusted/unadjusted generalized estimating equations (Adj.GEE/Unadj.GEE), covariate adjusted/unadjusted generalized linear mixed model (Adj.GLMM/Unadj.GLMM). All these methods preserved the type I error close to the nominal level. Covariate adjusted methods improved power compared with the unadjusted methods because of the increased treatment effect estimates, especially when the correlation between the baseline and outcome was strong, even though there was an apparent increase in standard errors. Results of the Chi‐squared test were identical to those for the unadjusted logistic regression. Fisher's exact test was the most conservative test regarding the type I error rate and also with the lowest power. Without missing data, there was no gain in using a repeated measures approach over a simple logistic regression at the final time point. Analysis of results from five phase III diabetes trials of the same compound was consistent with the simulation findings. Therefore, covariate adjusted analysis is recommended for repeated binary data when the study endpoint is of interest. Copyright © 2015 John Wiley & Sons, Ltd.     

District Segregation,Race Legislation,and Black Enrollment in Charter Schools*

Objective. This article examines how segregation at the school level within districts and charter school legislation predict black enrollment levels at local charter schools. Methods. This study uses the Schools and Staffing Survey Charter School Data 1999–2000, Common Core of Data, and a unique data set of district test scores to estimate OLS regression models of black enrollment in charter schools on district racial segregation and race provisions in charter school legislation. Results. Findings suggest that segregated school districts, those districts where whites and blacks are more unevenly distributed among schools, have a larger percentage of blacks enrolled in local charter schools than districts where schools are integrated. In addition, charter schools in states that do not have a racial clause have a smaller percent of blacks in their charter schools. Conclusion. Findings suggest that black enrollment in charter schools is a function of district segregation and state policy.     

University-community partnerships in gerontological social work: building consensus around student learning

This article will demonstrate how schools of social work can collaborate with community agencies to provide a comprehensive and enriching educational experience for both student interns and participating agencies. An innovative partnership of a state school of social work with community agencies leading to a cutting-edge geriatric field education program is described. Case examples are used to illustrate the benefits of these partnerships, as well as challenges partners overcame in forging and sustaining partnerships. Necessary components of partnership development are detailed.