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A nal aspect of the estimation problem is determination of measures of dispersion for the estimates that can be used for inference An asymptotic variance matrix based on the Fisher information matrix shown below for the parameters = ( , , 2 ) can be used to provide measures of dispersion for the estimates of , , and 2 : 1 2L (99) [I ( )] 1 = E For problems involving a small number of observations, we can use analytical expressions for the theoretical information matrix presented in Anselin (1988) This approach is computationally impossible when dealing with large problems involving thousands of observations The expressions used to calculate terms in the information matrix involve operating on very large matrices that would take a great deal of computer memory and computing time.

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Traditional medical liability doctrines seek to establish that the plaintiffs were in fact injured, usually meaning that they sustained some physical harm as a result of the medical intervention But in addition to adverse reactions, drugs also have the ability to create genetic harm, a modi cation of the germ cells that damage one s progeny or leave one s progeny more susceptible to disease Medical liability law s traditional response to increased risk of disease is best illustrated by the manner in which courts reacted to the increased intergenerational risks of various forms of cancer associated with DES The California Supreme Court ruled that the daughters of women who had taken DES to prevent miscarriages could not hold the manufacturers liable under product liability doctrine because DES injured them in utero (Brown v Superior Court, 1988).

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In these cases we can evaluate the numerical Hessian matrix using the maximum likelihood estimates of , , and 2 and our sparse matrix representation of the likelihood Given the ability to evaluate the likelihood function rapidly, numerical methods can be used to compute approximations to the gradients shown in (99) 933 Trade-offs between Speed and Numerical Accuracy There are trade-offs between numerical accuracy and speed in a number of the operations required to solve the estimation problem First, one can ignore the.

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The plaintiff-daughters increased risk of cancer and other reproductive abnormalities meant that more medical monitoring and procedures to prevent malignancies as well as some actual cancers were not the legal responsibility of the manufacturers of DES In formulating a rule for prescription drugs that set them apart from general product liability doctrines, the court noted that the manufacturer had a duty to properly prepare the drug and warn of its dangerous propensities that were either known or reasonably scienti cally knowable at the time of manufacture (Brown v Superior Court, 1988) This latter duty has been characterized as one arising out of negligence, whereas the plaintiff s proposed product liability theory has been called a theory of strict liability or liability without fault In their action based in strict liability, the plaintiff sought a ruling that the drug was defectively designed because it created the risk of intergenerational harm.

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