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The modi ed Dietz formula is named for its creator and is best described as a quick and relatively accurate approximation of the return for a portfolio over a discrete period of time. It adjusts for cash ows coming into and going out of a portfolio by adjusting the cash ow amounts based on the actual amount of time that the assets were invested in the portfolio. In addition, it can incorporate as many cash ows as needed. Formula 4.7 (Modi ed Dietz Return) EMV BMV Cont + Dist MDR = BMV + (NTWCF)



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&nH& = (H2 8 W ( H 2 8 H d T = H2HT 8 HnH: = (212) 8 (n1,) = 2n(Z2 8 In) = 2nz2,. This constructionof Hadamard matrices is referred to as the Sylvester construction. By this construction, Hadamard matrices of sizes 1, 2, 4 , 8, 16, 32, etc., exist. However, unless a Hadamard matrix of size 6 exists, for example, then this construction cannot be used to construct a Hadamard matrix of size 12. As the following theorem indicates, there is no Hadamard matrix of size 6.





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The regulatory background for validation is stated in various GMPs, which all have requirements for control of the environment. An extract is listed in Table 19.3. The type, size, and complexity of the BMS will determine how dif cult it is to demonstrate that the BMS environment is under control. The FDA has issued a large number of warning letters regarding BMS systems. Extracts from some of these can be seen in Table 19.4. The key word here is control over the environment. As mentioned in an earlier chapter, it is easier to see how the FDA handles deviations than how the EU does. The reason for this is the US Freedom of Information Act, which requires the US authorities to be open with the public. The FDA web page (www.fda.gov) lists all of the warning letters issued to pharmaceutical companies. The EU does not have the same openness, and it is rare to nd information on inspections and ndings.

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Before we go into each section and the underlying factors in detail, I will explain what each of the column headings mean. If you refer to Exhibit 12.4, you will see that the model s summary report has seven columns. Column 1 (#) highlights the number of each speci c factor. Column 2 (Section/Factors) lists the names for each of the six broad sections and each of the 30 factors. Column 3 (% Breakout Variable) represents each factor s percentage contribution to the score in its respective section. Column 4 (Maximum Points Variable) lists the maximum number of points allotted to each section and individual factor. Column 5 (Manager Score 0 to 5) lists the grade we give to each individual factor, from 0 (low) to 5 (high). Column 6 (Scaled Score). In order to keep the model s maximum total score to 100, we need to scale the individual factors and sections because the sum of all the individual factors when they are unscaled actually exceeds 100 (30 factors with a maximum score of 5 each would result in a possible maximum score of 150. This is done by adding the scores for all the factors in a given section and dividing that gure by the total possible score and then multiplying the result by the maximum points available for the section. For example, the scaled score for the rst section (Investment Professionals) was calculated as follows: Scaled Score = where

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