Some extensions in continuous models for immunological correlates of protection.

BACKGROUND: A scaled logit model has previously been proposed to quantify the relationship between an immunological assay and protection from disease, and has been applied in a number of settings. The probability of disease was modelled as a function of the probability of exposure, which was assumed to be fixed, and of protection, which was assumed to increase smoothly with the value of the assay. METHODS: Some extensions are here investigated. Alternative functions to represent the protection curve are explored, applications to case-cohort designs are evaluated, and approaches to variance estimation compared. The steepness of the protection curve must sometimes be bounded to achieve convergence and methods for doing so are outlined. Criteria for evaluating the fit of models are proposed and approaches to assessing the utility of results suggested. Models are evaluated by application to sixteen datasets from vaccine clinical trials. RESULTS: Alternative protection curve functions improved model evaluation criteria for every dataset. Standard errors based on the observed information were found to be unreliable; bootstrap estimates of precision were to be preferred. In most instances, case-cohort designs resulted in little loss of precision. Some results achieved suggested measures for utility. CONCLUSIONS: The original scaled logit model can be improved upon. Evaluation criteria permit well-fitting models and useful results to be identified. The proposed methods provide a comprehensive set of tools for quantifying the relationship between immunological assays and protection from disease.

Effect of cooling rates and temperatures on quality and safety of quahog clams (Mercenaria mercenaria).

The model ordinance in the National Shellfish Sanitation Program's Guide for the Control of Molluscan Shellfish was initially established for oysters; however, the clam industry also follows the protocol. Rapid cooling during periods when the growing waters exceed 80 °F (26.7 °C) results in cold shock, which causes unacceptable mortalities in clams. The clam industry was looking for a procedure to lower the clams to the standard temperature while minimizing shell shock mortalities during the warm summer months. Three tempering treatments were examined, and total aerobic plate counts (APCs) and most-probable-number (MPN) counts of Vibrio, V. parahaemolyticus, and fecal coliforms were enumerated. In treatment 1 (control), clams were harvested, held for 5 h at 90 °F (32.2 °C), and then moved to 45 °F (7.2 °C) for storage. In treatment 2, clams were harvested and held for 5 h at 90 °F (32.2 °C), followed by 12 h at 65 °F (18.3 °C) and 12 h at 55 °F (12.8 °C), and then were moved to 45 °F (7.2 °C) for long-term storage. In treatment 3, clams were harvested and held for 5 h at 90 °F (32.2 °C), followed by 24 h at 55 °F (12.8 °C) before being moved to 45 °F (7.2 °C) for long-term storage. Three replicate trials were performed with triplicate analyses during late June through early to mid-August. The current National Shellfish Sanitation Program standard is treatment 1; it contained statistically (P ≤ 0.05) higher total APCs than treatments 2 and 3 throughout the 21-day storage period. APCs ranged from 2.3 × 10(4) immediately after harvest to 2.7 × 10(6), 1.6 × 10(5), and 4.8 × 10(5) for treatments 1, 2, and 3, respectively, after 14 days of storage. A statistical analysis showed that treatments 2 and 3 had significantly lower total MPN per gram Vibrio than treatment 1 on day 7 but were equal to treatment 1 on days 1 and 14. MPN per gram for V. parahaemolyticus was statistically lower in treatments 2 and 3 than in treatment 1 on storage days 1 and 7. However, on day 14, treatment 3 was significantly lower than treatments 1 and 2. There was no statistical difference for fecal coliforms. The greatest mortality occurred in treatment 1 (87.4%), followed by treatment 2 (83.3%) and treatment 3 (66.0%). The outcome of this research clearly shows that treatments 2 and 3 can cool clams to a temperature of 45 °F (7.2 °C) without compromising quality or safety and can reduce the number of dead clams introduced into the marketplace.