Dose-response modeling of life shortening in a retrospective analysis of the combined data from the JANUS program at Argonne National Laboratory.

Life shortening was investigated in both sexes of the B6CF1 (C57BL/6 x BALB/c) mouse exposed to fission neutrons and 60Co gamma rays. Three basic exposure patterns for both neutrons and gamma rays were compared: single exposures, 24 equal once-weekly exposures, and 60 equal once-weekly exposures. Ten different dose-response models were fitted to the data for animals exposed to neutrons. The response variable used for all dose-response modeling was mean after-survival. A simple linear model adequately described the response to neutrons for females and males at doses less than or equal to 80 cGy. At higher neutron dose levels a linear-quadratic equation was required to describe the life-shortening response. An effect of exposure pattern was observed prior to the detection of curvature in the dose response for neutrons and emerged as a potentially significant factor at neutron doses in the range of 40-60 cGy. Augmentation of neutron injury with dose protraction was observed in both sexes and began at doses as low as 60 cGy. The life-shortening response for all animals exposed to gamma rays (22-1918 cGy) was linear and inversely dependent upon the protraction period (1 day, 24 weeks, 60 weeks). Depending on the exposure pattern used for the gamma-ray baseline, relative biological effectiveness (RBE) values ranged from 6 to 43. Augmentation, because it occurred only at higher levels of neutron exposure, had no influence on the estimation of RBEm.

Life shortening in mice exposed to fission neutrons and gamma rays. VIII. Exposures to continuous gamma radiation.

Data are presented on the mean aftersurvival of male B6CF1 mice exposed for 22 h per day, 5 days per week, to 60Co gamma radiation at dose rates of 1.36 to 12.64 x 10(-3) cGy/min for 23 weeks or 1.36 to 6.32 x 10(-3) cGy/min for 59 weeks. For deaths from all causes, linear dose-response curves were obtained with slopes (days of life lost/cGy) of 0.158 +/- 0.016 and 0.077 +/- 0.002 for 23- and 59-week exposures, respectively. These values were not significantly altered when the analysis was restricted to those mice dying with tumors (92% of the total) or to those presumably dying from tumors (82% of the total). Analysis of mortality rates showed that about 90% of the radiation-specific excess mortality was tumor related. The 59-week exposure series induced only a small increase in the number of days of life lost/cGy/weekly fraction over that induced by 23 weeks of irradiation, 4.53 +/- 0.15 compared to 3.64 +/- 0.36 days lost/cGy/weekly fraction. This lower than expected value for 59 weeks of exposure may signal the approach to the final linear, additive, injury term postulated from earlier studies at this laboratory with low-dose-rate, daily, duration-of-life 60Co gamma irradiation.

Life shortening in mice exposed to fission neutrons and gamma rays. VII. Effects of 60 once-weekly exposures.

A total of 6316 B6CF1 mice were exposed to 60 equal once-weekly doses of 0.85-MeV fission neutrons (0.033 to 0.67 cGy per weekly fraction) or 60Co gamma rays (1.67 to 10 cGy per weekly fraction) and were observed until they died. The mean aftersurvival times showed that the dose-response curves for both neutron and gamma-ray exposures were indistinguishable from linear over all doses except the highest neutron dose. The relative biological effectiveness (RBE) for neutrons, calculated as the ratio of the initial slopes of the dose-response curves, was about 20 for both males and females. Essentially the same value was obtained by a number of other analyses of the data. Virtually all of the radiation-specific excess mortality could be attributed to tumors; after decrementation of the population for nontumor deaths, the value of the RBE was not significantly changed.

Life shortening in mice exposed to fission neutrons and gamma rays. VI. Studies with the white-footed mouse, Peromyscus leucopus.

Some of the studies on late effects of neutron and gamma radiation previously carried out with the C57BL6 X BALB/c F1 hybrids of Mus musculus have been repeated with the white-footed mouse, Peromyscus leucopus, a cricetid rodent of a different subfamily, with differing physiological characteristics and a different spectrum of pathologies. Among the more important findings were the following: For both species, the life shortening per rad at low doses of either radiation was the same percentage of the life span. The limiting values of the relative biological effectiveness for life shortening from all causes of death were about the same for the two species, ranging from 8 to 16, depending on the method of calculation. Fractionated neutron exposures failed to produce significant life shortening in Peromyscus over that observed at single doses. Tumor-related deaths accounted for at least 70 to 75% of the radiation-specific excess mortality in Peromyscus.

Life shortening in mice exposed to fission neutrons and gamma rays. V. Further studies with single low doses.

Data are presented on the mean after survival of female B6CF1 mice exposed to single doses of neutrons (1 to 40 rad) or gamma rays (22.5, 45, and 90 rad). For gamma-ray exposures and for neutron exposures up to 10 rad, the dose-response curves are indistinguishable from linear; higher neutron doses produce significant departures and linearity. Consequently, in these data, an upper limit of the relative biological effectiveness (RBE) exists for life shortening from all causes of death after single neutron exposures; this value is 15.0 +/- 5.1. The RBE depends on the cause of death, ranging from 2 to 5 for lymphoreticular tumors to 23-24 for lung tumors.

Life shortening in mice exposed to fission neutrons and gamma rays. IV. Further studies with fractionated neutron exposures.

When mice were exposed to a total dose of 240 rad of fission neutrons divided into two, four, or six fractions given at 1-week intervals, more life shortening was observed than was seen after a single exposure. Maximum life shortening was observed with four fractions, although the value for six fractions was not significantly lower. Much of the augmentation effect was attributable to an increase in early deaths during the first 200-300 days after exposure, although differences persisted throughout the lifetime of the animals. The changes in life shortening were associated with changes in the distribution of causes of death; however, decrementation of the populations for any given specific cause of death failed to eliminate completely the differences in mean aftersurvival time.

Malaria along the southernmost fringe of its distribution in Africa: epidemiology and control.

After more than thirty years of malaria control in northern Transvaal with residual insecticides, malaria prevalence has been reduced to a low level. However, low-grade transmission of Plasmodium falciparum continues, with periodic focal outbreaks after abnormally high rainfall. From October 1973 to September 1976, the operational and epidemiological factors involved in this residual transmission were studied in over 17 000 people of an area of northern Transvaal. Incidence surveys based on the screening of fever cases revealed 42 autochthonous cases of malaria in 1974-75 and 10 cases in 1975-76. Parasite prevalence surveys were not sensitive enough to assess the malaria situation, and serological testing indicated different levels of infection according to the method used. One of the two principal vectors of malaria in Africa-Anopheles funestus Giles-was not detected in the project area, and the A. gambiae group (species A and B) was found in extremely low numbers, so that it could not have accounted for the low-grade transmission in the area. A recently discovered member of the A. funestus group somewhat resembling A. aruni Sobti, and a species hitherto undiscovered in the Transvaal, which is abundant in the area and is indistinguishable from A. flavicosta Edwards, may be involved. Both were found biting man-mostly outdoors during the four hours following dusk, when people frequently gather outside their houses and are thus vulnerable to mosquito bites.