Issues in Qualitative and Quantitative Risk Analysis for Developmental Toxicology1

The qualitative and quantitative evaluation of risk in developmental toxicology has been discussed in several recent publications.(^1–3) A number of issues still are to be resolved in this area. The qualitative evaluation and interpretation of end points in developmental toxicology depends on an understanding of the biological events leading to the end points observed, the relationships among end points, and their relationship to dose and to maternal toxicity. The interpretation of these end points is also affected by the statistical power of the experiments used for detecting the various end points observed. The quantitative risk assessment attempts to estimate human risk for developmental toxicity as a function of dose. The current approach is to apply safety (uncertainty) factors to die no observed effect level (NOEL). An alternative presented and discussed here is to model the experimental data and apply a safety factor to an estimated risk level to achieve an “acceptable” level of risk. In cases where the dose-response curves upward, this approach provides a conservative estimate of risk. This procedure does not preclude the existence of a threshold dose. More research is needed to develop appropriate dose-response models that can provide better estimates for low-dose extrapolation of developmental effects.     

The benefits of a nap during prolonged work and wakefulness

Prolonged work scenarios with demands for sustained performance are increasingly common. Because sleep loss inevitably compromises functioning in such situations, napping has been proposed as a countermeasure. The optimal timing of the nap relative to its benefits for performance and mood is not known, however. To address this issue, 41 healthy adults were permitted a two-hour nap at one of five times during a 56-hour period of intermittent work, with no other sleep. Naps were placed 12 hours apart, near the circadian peak (P) or trough (T), and were preceded by 6(P), 18(T), 30(P), 42(T), or 54(P) hours of wakefulness. Work test bouts occurred every few hours and consisted of a variety of psychomotor and cognitive tasks as well as mood scales completed at the beginning, middle and end of each bout. A total of eight performance and 24 mood parameters were derived from the bouts and compared between groups at all test points prior to and following the naps. An estimate of the extent to which each nap condition differed from the control (P54) condition was derived by totalling the proportion of test points that yielded statistically significant results relative to the total number of tests conducted both before and after naps.

Although all performance and most mood parameters displayed a circadian-modulated deterioration as the protocol progressed, a nap appeared to attentuate the extent of this change in all performance parameters but not in mood parameters. Overall, the timing of the nap across days and within the circadian cycle was irrelevant to its effect on performance, suggesting that it diminished the intrusion of sleepiness into behavioural functioning, even though subjects were phenomenally unaware of this benefit.     

Estimation and Extrapolation of Tumor Probabilities from a Mouse Bioassay with Survival/Sacrifice Components

A nonparametric estimator of the probability distribution of time-to-tumor is incorporated into an algorithm for calculating linearly extrapolated dosage limits from an animal carcino-genesis bioassay. The procedure is illustrated with tumor data from a mouse bioassay with 2-acetylaminofluorene. Extrapolated dosage limits for an excess risk of 10^-6 differ by only a factor of 2 across the six replicates of the experiment.     

Power: A Conceptual Framework*

Symbolic interactionism lacks a coherent conception of power. This paper defines power in a manner consistent with the interactionist perspective. Power is conceptualized as a collective transaction characterized by a division of labor, movement toward a common end, and flexible coordination between opponents. Power is distinguished from other types of collective transactions by asymmetrical interaction, a conflict of interests between opponents, and the intentional production of compliance. Some implications of considering power as a collective transaction are then examined.     

Price vs. revenue stabilization through a buffer stock: Which is more financially feasible for LDCs?

Optimal control theory is used to analyze the implications of the adoption of price and LDC export revenue stabilization objectives by an international buffer stock for cocoa. The results obtained for the period 1956–76 suggest that the stabilization of either price or revenue at systematic trend would reduce the instability of both variables from that during the sample period. Although the stabilization of revenues at systematic trend decreases their average level, the stabilization of price has the opposite effect. Because of this, it may be financially feasible for the LDCs to provide the necessary resources for a price-stabilizing buffer stock.     

Assessing Intimacy: The Pair Inventory*

PAIR, acronym for Personal Assessment of Intimacy in Relationships, was developed as a tool for educators, researchers and therapists. PAIR provides systematic information on five types of intimacy: emotional, social, sexual, intellectual and recreational. Individuals, married or unmarried, describe their relationship in terms of how they currently perceive it (perceived) and how they would like it to be (expected). PAIR can be used with couples in marital therapy and enrichment groups.