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    Response to the Letter to the Editor

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    This paper has attracted interest around the world from the media (both TV and newspapers). In addition, we have received letters, emails and telephone calls. One of our favorites was a voicemail message asking us to return a call to Australia at which point we would learn who really killed JFK. We welcome the opportunity to respond to the letter to the editor from Mr. Fiorentino. Mr. Fiorentino claims that our ``statement relating to the likelihood of a second assassin based on the premise of three or more separate bullets is demonstrably false.'' In response we would like to simply quote from page 327 of Gerald Posner's book Case Closed, one of the most well known works supporting the single assassin theory: ``If Connally was hit by another bullet, it had to be fired from a second shooter, since the Warren Commission's own reconstructions showed that Oswald could not have operated the bolt and refired in 1.4 seconds.'' Mr. Fiorentino also claims that the ``second fatal flaw is the use of a rather uncomplicated formula based on Bayes Theorem.'' Let EE denote the evidence and TT denote the theory that there were just two bullets (and hence a single shooter). We used Bayes Theorem to hypothetically calculate P(TE)P(T|E) from P(ET)P(E|T) and the prior probability P(T)P(T). In order to make P(TE)P(T|E) ten times more likely than P(TˉE)P(\bar{T}|E), the ratio of the prior probabilities [i.e., P(T)/P(Tˉ)P(T) / P(\bar{T})] would have to be greater than 15. Thus, we again conclude that this casts serious doubt on Dr. Guinn's conclusion that the evidence supported just two bullets. Sadly, this is far from the first time that probability has been misunderstood and/or misapplied in a case of public interest. A notable British example is the Clark case. See Nobles and Schiff (2005) for details. Finally, we welcome and, in fact, encourage members of the scientific community to provide alternative analyses of the data.Comment: Published in at http://dx.doi.org/10.1214/07-AOAS154 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Environmental and genetic influences on neurocognitive development: the importance of multiple methodologies and time-dependent intervention

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    Genetic mutations and environmental factors dynamically influence gene expression and developmental trajectories at the neural, cognitive, and behavioral levels. The examples in this article cover different periods of neurocognitive development—early childhood, adolescence, and adulthood—and focus on studies in which researchers have used a variety of methodologies to illustrate the early effects of socioeconomic status and stress on brain function, as well as how allelic differences explain why some individuals respond to intervention and others do not. These studies highlight how similar behaviors can be driven by different underlying neural processes and show how a neurocomputational model of early development can account for neurodevelopmental syndromes, such as autism spectrum disorders, with novel implications for intervention. Finally, these studies illustrate the importance of the timing of environmental and genetic factors on development, consistent with our view that phenotypes are emergent, not predetermined

    Detecting Alterations in Pulmonary Airway Development with Airway-by-Airway Comparison

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    Neonatal and postnatal exposures to air pollutants have adverse effects on lung development resulting in airway structure changes. Usually, generation-averaged analysis of airway geometric parameters is employed to differentiate between pulmonary airway trees. However, this method is limited, especially for monopodial branching trees such as in rat airways, because both quite proximal and less proximal airways that have very different structure and function may be in the same generation. To avoid limitations inherent in generation averaging, we developed a method that compares two trees airway-by-airway using micro CT image data from rat lungs. This computerized technique (1) identifies the geometry and architecture of the conducting airways from CT images, (2) extracts the main tree, (3) associates paired airways from the two different trees, and (4) develops summary statistics on the degree of similarity between populations of animals. By comparing the trees airway-by-airway, we found that the variance in airway length of the group exposed to diffusion flame particles (DFP) is significantly larger than the group raised in filtered air (FA). This method also found that rotation angle of the DFP group is significantly larger than FA, which is not as certain in the generation-based analysis. We suggest that airway-by-airway analysis complements generation-based averaging for detecting airway alterations
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