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exists in the Southern Hemisphere Kurland s studies indicate that there is a threefold increase in prevalence and a vefold gradient in mortality rate between New Orleans (30 degrees north latitude), on the one hand, and Boston (42 degrees north) and Winnipeg (50 degrees north) on the other In Japan there is a similar though less distinct geographic gradient (the prevalence of MS there is much lower than in corresponding latitudes of North America and northern Europe) The increasing risk of developing MS with increasing latitude has been con rmed by J B Barlow and Kurtzke and associates The latter studied a series of unprecedented size (5305 undoubted cases of MS and matched controls) They showed also that in the United States, African Americans are at lower risk than whites at all latitudes, but both races show the same south-to-north gradient in risk, probably indicating the importance of an environmental factor regardless of race Supporting this view are the descriptions, by Kurtzke and Hyllested, of an epidemic of MS in the Faroe Islands of the North Atlantic They found a much higher than expected incidence of the disease, occurring as three separate outbreaks of decreasing extent between the years 1943 and 1973 (It should be pointed out that the largest outbreak consisted of only 21 cases) It was their contention, con rmed by Poskanzer, that the disease was due possibly to an unidenti ed infection introduced by British troops who occupied the islands in large numbers in the years immediately preceding the outbreak Kurtzke and colleagues have also described a similar postwar epidemic in Iceland Several studies indicate that persons who migrate from a highrisk to a low-risk zone carry with them at least part of the risk of their country of origin, even though the disease may not become apparent until 20 years after migration Such a pattern has been demonstrated in both South Africa and Israel Dean determined that the prevalence of MS in native-born white South Africans was 3 to 11 per 100,000, whereas the rate in immigrants from northern Europe was about 50 per 100,000, only slightly less than among the nonimmigrating natives of those countries The data of Dean and Kurtzke indicate further that in persons who had immigrated before the age of 15, the risk was similar to that of native-born South Africans; whereas in persons who had immigrated after that age, the risk was similar to that of their birthplace Alter and colleagues found that in the descendants of European immigrants born in Israel, the risk of MS was low, similar to that of other nativeborn Israelis, whereas among recent immigrants the incidence in each national group approached that of the land of birth Again, the critical age of immigration appeared to be about 15 years These epidemiologic studies and others have shown that MS is associated with particular localities rather than with a particular ethnic group in those localities and again implicate environmental factors in the genesis of the disease Also, a familial aggregation of MS is now well established About 15 percent of MS patients have an affected relative, with the highest risk of concurrence being observed in the patient s siblings (Ebers, 1983) In a large population-based study carried out in British Columbia by Sadovnick and colleagues, it was found that almost 20 percent of index cases had an affected relative, again with the highest risk in siblings In a subsequent study, Sadovnick and colleagues sought to determine the degree of heritability of MS by comparing the risk of disease in the half-sibs (one biologic parent in common) of affected individuals with the risk in full sibs; the risk for full sibs was two to three times greater than for half-sibs and they interpreted these results as largely genetic in basis The case for heritability is supported by studies of twins in.

$ perl -pibak -e "print" *

.

In contrastto this approach, now retain the second-derivative we term by substituting derivative[recallEq (427)]: the following forward-difference approximation the second of

As we already know, this puts a notional loop around the single print statement to iterate through the files on the command line In fact, the loop is slightly more complex, and more correctly actually looks like this: