Bernard Altshuler

Statistical Measures of the Lower Limit of Detection of a Radioactivity Counter

AbstractThe lower limit of detection of a counter is best expressed statistically in terms of two minimal activities determined by the maximal acceptable risks of making a Type I error (of concluding there is sample activity when there is none) and a Type II error (of concluding there is no activity

Theory for the measurement of competing risks in animal experiments

Abstract The problem of competing risks in animal assay is to evaluate biological activity leading to a specific end point which is one of a set of mutually exclusiveend points. Just one assumption is made: the chance of observing a specific end point is continuous in time. The concept of equal-age replacement is introduced to construct a set of independent nonhomogeneous Poisson processes whose mean value functions are the integrals of the conditional event rates which are taken to represent cumulative specific activities. Only in an experiment which guarantees a minimum number of animals at risk at a fixed time can a measurement be made which is independent of complementary risks. In such an experiment the sum of the reciprocals of the numbers of animals at risk at the times of observation of a specific end point is an unbiased measurement of its cumulative activity.

ESTIMATION OF LUNG TISSUE DOSE FROM THE INHALATION OF RADON AND DAUGHTERS

AbstractThe radon hazard is presumed to be lung cancer induced by alpha irradiation of basal cells in the bronchial epithelium. The effective dose is calculated by a relatively complete analysis which includes (1) the distribution of atmospheric activity by size and daughter, (2) the prediction of a

DEPOSITION OF AEROSOLS IN THE HUMAN RESPIRATORY TRACT DURING BREATH HOLDING

Abstract The anatomical character of both the conducting airways and of the functional gas exchange region exerts an important influence on rates of deposition of inhaled aerosol. In the present studies an attempt is made to use the rate of deposition of aerosol particles in the respiratory tract during breath-holding as an index of the effective lumen diameters of the respiratory branches. During breath-holding for periods up to about 30 sec, the ratio of exhaled to inhaled aerosol decreases exponentially with time; this was observed for all subjects at particle sizes from about 0×15 to 1×0 micron. Calculations of lumen diameter based on these observations yielded estimates which are consistent with those obtained by microscopic measurements on human lungs.

The Dose-Response Relationships of Beta-Ray-Induced Skin Tumors in the Rat'

Single doses of beta radiation ranging from 230 to 10000 rads were applied to 35-cm² skin areas on the backs of young male rats. The resultant dose-tumor incidence curves were highly nonlinear: the incidence of tumors of all types increased abruptly at about 2000 rads, reached a peak at about 4000 rads, and declined at higher doses. The sharp upturn in tumor formation occurred at doses which prcduced mild to moderate skin damage, while markedly pilocidal doses had a suppressing effect on the formation of adnexal tumors. There was a shifting distribution of tumor types with respect to dose: the hair follicle and sebaceous tumors predominated at the intermediate levels, whereas epidermoid carcinomas were more common at doses which produced very severe skin damage. The appearance time of tumors seemed to have little dose dependence in contrast to the magnitude of tumor incidence. The frequency distribution of tumors on individual rats was found to conform fairly well to a calculated Poisson distribution, suggesting that the presence of some tumors on the irradiated skin dces not markedly affect the formation of others. (auth)

REGIONAL AEROSOL DEPOSITION IN THE HUMAN RESPIRATORY TRACT

Abstract Regional deposition of aerosol in the human respiratory tract is estimated from experiments in which aerosol concentration and respiratory flow were measured continuously during individual breaths and from a theoretical analogy with a tubular continuous filter bed model of the respiratory tract. Since the volume of anatomic dead space is uncertain, regional distinction is made by selected boundary volumes which separate the upper tract of the selected volume from the more distal lower tract. The central feature of the estimation procedure is the determination of a combined upper tract penetration, for inspiration, pause, and expiration, derived from expired aerosol concentration corrected for aerosol mixing. The estimations indicate the particle size for maximum alveolar deposition is greater than 2 μ, equivalent diameter of a unit density sphere. This result is consistent with the calculations of Findeisen, Landahl, and Beeckmans and higher than the 1 μ value of Brown et al.

Calculation of regional deposition of aerosol in the respiratory tract

The removal of air-borne particles in the respiratory tract is treated to enable regional deposition to be inferred from measurement of expired aerosol as well as predicted from theory of the primary removal processes. The analysis uses the analogy of a continuous tubular filter-bed and includes consideration of respiratory pauses and the mechanical mixing of gas flow. Derived equations relate regional deposition, distribution of aerosol in the expired air, and efficiency of removal at different depths in the respiratory tract.

Exchangeable Sodium, Body Potassium, and Body Water in Previously Edematous Cardiac Patients: Evidence for Osmotic Inactivation of Cation

Measurements have been made of total exchangeable sodium, total body potassium, and total body water in a group of 13 previously edematous patients with heart disease, and in 20 “control” patients. The data show that while both groups have the same quantity of water as the per cent of bodyweight and the same body potassium concentration, the cardiac group has an excess of exchangeable sodium when compared with the “controls.” Since the excess sodium in the cardiac group cannot be attributed to the loss of potassium or the accumulation of water, the results of these studies are taken as evidence that osmotic inactivation of a considerable amount of some cation, probably sodium, has taken place. It is suggested that a likely site for cation binding is in the polyanionic constituents of the connective tissues.

TISSUE REACTIONS AND DOSE RELATIONSHIPS IN RATS FOLLOWING INTRAPULMONARY BETA RADIATION.

Squamous cell carcinomas of bronchial origin have been produced in lungs of rats exposed to the beta radiation of lo6Ru and 32P sources. Utilizing intrabronchial pellets implanted by surgical techniques, the spacial relationships of the emitting pellet to the bronchial origin of tumor has been defined, permitting dose in rads to the target tissue to be directly calculated. Previously reported experiments with electroplated lo6Ru sources have shown a rad dose-related incidence of tumor yield. These doses based on time of death with cancer rather than time of initiation of malignant change included some “wasted” radiation. Serial sacrifice experiments with rats exposed to 5 pc lo6Ru sources have demonstrated earlier finding of cancer providing for minimum estimates of the period of “wasted” radiation. Spontaneous deaths in the serial sacrifice pool have confirmed the cancer incidences of previous experiments at the 5 pc level. A hollow plastic pellet has been devised for the examination of dose rate effect on tumor induction with the use of isotopes of varying half-life. An initial experiment with Phosphorus32 delivering doses of lo3, lo4, lo5 rads has resulted in a yield of tumors at these levels comparable to the yield from the same dose in rads delivered by lo6Ru pellets. Thus, within these limits, there has been no dose-rate dependence for tumor yield.

Benign and Malignant Tumor Induction in Mouse Skin

Carcinogenesis has often been assumed to be a multistage disease where a single cell progresses from normal to cancer in discrete sequential stages1,2,3. There is statistical support for the existence of such stages in the shape of functions that describe the dependence of cancer yield on dose and time. Biological evidence in favor of the multistage theory is derived from chromosomally marked clones seen in exacerbations of myeloid leukemia and in the progressive acquisition of automony seen in certain types of tumors, especially, hormone dependent tumors4,5.