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SUMMARY.-In two separate experiments benzopyrene has been painted regularly on the backs of mice at difference dose levels.It has been shown that the incidence rate of both tumours and infiltrating carcinomas can be taken as proportional to d2(t W)k where t is time from first application, w and k are constants independent of dose, and d is the applied dose.IT has been suggested that when a constant repetitive dose of carcinogen is applied to a target area the incidence rate of tumours with time is approximately proportional to (t W) k-I where t is time under insult and w and k are constants (Pike, 1966).It has also been pointed out that this hypothesis could most easily be tested by reference to animal experimentation, but that it was not easy to find details of experiments that included sufficient numbers of animals for statistical evaluation (Cook, Doll and Fellingham, 1969).Accepting this hypothesis, it still remains to be shown how the tumour incidence rate at any fixed time depends on the carcinogenic insult applied. The multistage model of the cancer process (Armitage and Doll, 1954) postulates that if the carcinogen affects X rate-determining stages of the process, then increasing the dose by a factor C will increase the tumour incidence rate by a factor Cm.Two large separate experiments were carried out at the T.R.C. Laboratories, Harrogate, and the Batelle Institute, Geneva, using benzopyrene applied at 4 different dose levels to the shaved backs of mice.. The data from these experiments was used to investigate the above hv-potheses. MATERIALS AND METHODSBenzopyrene (B.P.) For the experiment in Harrogate 3,4-benzo(a)pyrene was obtained from the Koch-Light Laboratories, Colnbrook, England, whereas for that in Geneva it was obtained from Fluka Limited, Buchs SG, Switzerland.Mice and details of treatment (1) For the Harrogate experiment female albino mice of a specific pathogenfree strain were obtained from the Pharmaceuticals Division, Imperial Chemical Industries Ltd., at 4-6 weeks of age, a month before first treatment.

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Risk strati cation is required to set an exercise prescription for cardiac rehabilitation, but an optimal scheme for congenital heart disease (CHD) is unknown. We piloted a system based on hemodynamic rather than anatomic factors: Function, Oxygen level, Rhythm, Complex/Coronary anatomy, and Elevated load (FORCE). Feasibility, e cacy, and safety of the FORCE tool were evaluated.Methods: Patients <22 years old participating in the Cardiac Fitness Program at Boston Children's Hospital between 02/2017 and 12/2021 were retrospectively analyzed. Assigned FORCE levels, anatomy, adverse events, tness and exercise test data were collected.Results: Of 63 attempts at FORCE classi cation, 62 (98%) were successfully classi ed while one with restrictive cardiomyopathy was not. Thirty-nine (62%) were FORCE 1, 16 (25%) were FORCE 2, and 7 (11%) were FORCE 3. Almost half of FORCE 1 patients had simple or complex CHD and the majority of FORCE 2 patients had single ventricle CHD. FORCE 3 patients were more likely to have serious arrhythmias or cardiomyopathy than those in FORCE 1 or 2 (p<0.001). Postural orthostatic tachycardia syndrome patients appeared in FORCE 1 only. No adverse events occurred over 958 total sessions. The total number of tness sessions/participant was similar across FORCE levels. Conclusion: It was feasible to risk stratify patients with CHD using a clinical FORCE tool. The tool was effective in categorizing patients and simple to use. No adverse events occurred with tness training over nearly 1,000 exercise training sessions. Adding diastolic dysfunction to the original model may add utility.