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By the conclusion of the eighteenth century, nearly 10% of all humans had been dis gured, crippled, or killed by smallpox Cosmetics had come into being as a result of a need to hide the scars of smallpox In the twentieth century alone, approximately 300 million people had perished from smallpox For comparison, all the wars of the twentieth century killed just one-third the number of humans as did smallpox Variolation, the practice of rubbing smallpox pustule exudate into a needle scratch on the arm, provided protection against variola virus, but at a cost of 2 deaths per 100 variolations Edward Jenner s cowpox vaccination gave smallpox prophylaxis with a dramatic decrease in iatrogenic disease and death and further set the stage for the eradication of smallpox, a hope once advanced both by Jenner himself as well as Thomas Jefferson.

Although ideally the age should be matched to the expected exposure period in terms of the stage of human development, this is not often done Young adult or adolescent animals that are still growing are preferred in almost all cases, and both sexes are routinely used Good animal care is critical at all times because toxicity has been shown to vary with diet, disease, and environmental factors Animals should be quarantined for some time before being admitted to the test area, their diet should be optimum for the test species, and the facility should be kept clean at all times Regular inspection by a veterinarian is essential, and any animals showing unusual symptoms not related to the treatment (eg, in controls or in low dose but not high dose animals) should be removed from the test and autopsied Results.

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discussion for the LRD case only However, an essentially identical procedure, estimator de nition, and properties hold in the self-similar case For other kinds of scaling also, magnitude parameters can be de ned and estimated in a similar way; however, this will not be discussed here We brie y summarize the results of Veitch and Abry [74, 75] for a twodimensional joint estimator ^ ; cf of long-range dependence One of the powerful a ^ ^ properties of a is that its statistics are entirely independent of the speci c form of the mother wavelet, depending on the coef cients of the linear regression and the amount of data nj at each scale It is this feature that allows an explicit expression for its variance to be obtained independently of the wavelet basis.

It is clear that ^ this property is shared by a vj yj , the unbiased estimator of the intercept a of the same linear regression de ning a (The coef cients vj are given by vj Sjj Sj j = s2 SSjj Sj2 , cf Eq (223)) From Eq (216) it is apparent j that whereas a is simply the slope in the logscale diagram, the magnitude parameter ^ cf is related to the intercept, being essentially proportional to 2a , a quantity that ^ ^ retains the wavelet independence advantages of a Unfortunately, 2a does not correspond exactly to cf but rather to the dimensionless quantity cf C a; c0 , and an attempt to isolate the former necessarily brings in a wavelet dependence.

Although the information required from subchronic tests varies somewhat from one regulatory agency to another, the requirements are basically similar (Table 215) For explanatory purposes the data obtained from these tests can be described as two types: that obtained from living animals during the course of the test and that obtained from animals sacri ced either during or at the end of the test period Many of the tests performed on living animals can be carried out rst before the test period begins to provide a baseline for comparison to subsequent measurement A satellite group of treated animals can be added to the test for evaluation of recovery For these animals the treated food would be removed at the end of the test period and they would be returned to the control diet for 21 to 28 days while the various end points are followed.

In spite of initial widespread opposition to a program of worldwide smallpox eradication, continued pressure by individuals such as Brock Chisholm of the World Health Organization (WHO), Victor Zhadnov of the Soviet Union, and Marcelino Candau of WHO, saw the worldwide eradication program eventually actualized and nanced Under the direction of Donald A Henderson from 1966, the WHO smallpox eradication campaign achieved its remarkable goal of worldwide eradication when the last case of smallpox was reported in Somalia in 1977 The yellow fever virus also has directed the course of human history1 This avivirus was introduced into the New World from Africa by means of the slave trade, which Europeans expanded to replace the human labor lost when smallpox and measles took their ghastly toll of Native American slaves.

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