Knut M. Wittkowski

Inflammatory Role of Two Venom Components of Yellow Jackets (Vespula vulgaris): A Mast Cell Degranulating Peptide Mastoparan and Phospholipase A1

Background: Venom sac extract of yellow jackets Vespula vulgaris was toxic in mice when injected intraperitoneally but not toxic when injected subcutaneously. Necropsy showed the toxicity to be an inflammatory response. Methods: Venom peptide and protein fractions were tested to identify the inflammatory components. The active components were tested to establish whether they might function as adjuvant for venom protein-specific antibody response. Results: Venom toxicity required the synergistic action of two venom components, a mast cell degranulating peptide mastoparan and phospholipase A1. Both components stimulated prostaglandin E2 release from murine peritoneal cells and macrophages. Mastoparan showed a weak activity to enhance IgE and IgG1 responses to a yellow jacket venom protein Ves v 5 in BALB/c mice. It was not possible to assess the adjuvant activity of phospholipase A1 because of its suppression of Ves v 5-specific response. Melittin, a mast cell degranulating peptide from bee venom, was inactive as an adjuvant for Ves v 5-specific response. Conclusion: Yellow jacket venom contains two inflammatory components, mastoparan and phospholipase A1. Our findings suggest that mastoparan can function as a weak adjuvant for TH2 cell-associated antibody response.

The protective effect of condoms and nonoxynol-9 against HIV infection.

OBJECTIVES Whether or not spermicides can reduce the risk of human immunodeficiency virus (HIV) transmission remains an important question for the control of heterosexual HIV transmission. The authors provide estimates from a reanalysis of one of the few observational studies on the efficacy of condoms and spermicides, used separately and together, per vaginal contact. METHODS In this reanalysis, three different models were used to assess the efficacy of spermicides and condoms: linear (Pearl index), exponential (maximum likelihood), and monotonic (marginal likelihood). RESULTS Reported use of barrier methods among 27,432 contacts was as follows: condoms plus nonoxynol-9, 39%; condoms alone, 25%; nonoxynol-9 alone, 24%; and unprotected, 11%. Under all three models, the results indicate a strong protective effect for spermicidal suppositories. The Pearl index indicated that spermicide alone is apparently efficacious, but the efficacy per contact cannot be quantified with this approach. Maximum likelihood estimates for the efficacy of nonoxynol-9 alone and condoms (with or without nonoxynol-9) were 100% (95% confidence interval [CI95] = 43%, 100%) and 92% (95% CI95 = 79%, 100%), respectively. CONCLUSIONS The data from this observational study suggest that spermicides may be efficacious in reducing the risk of HIV transmission.

Friedman-type statistics and consistent multiple comparisons for unbalanced designs with missing data

Abstract A generalization of the Friedman test using the marginal likelihood principle (Kalbfleisch and Prentice 1973) is presented and its asymptotic power given. It allows use of a variety of score functions and handles ties and unbalanced designs. Some well-known statistics [including the tests of Kruskal and Wallis (1952), Prentice (1979), and Rinaman (1983)] are proven to be special cases, whereas others (e.g., Klotz 1980; Groggel and Skillings 1986; Rai 1987; Skillings and Mack 1981) are shown to be less appropriate. Multiple comparisons are considered under both the global hypothesis and alternatives. Evaluating non-centrality parameters under local shift alternatives, the procedures of Klotz (1980) and (for a special case) Skillings and Mack (1981) can be either anticonservative (showing differences that do not exist) or insensitive (ignoring differences that do exist), depending on the distribution of missing data. A new Scheffe-type procedure for arbitrarily missing data is presented and recomme...

A Statistically Valid Alternative to the TDT

Objective: To present an alternative linkage test to the transmission/disequilibrium test (TDT) which is conservative under the null hypothesis and generally more powerful under alternatives. Methods: The exact distribution of the TDT is examined under both the null hypothesis and relevant alternatives. The TDT is rewritten in an alternate form based on the contributions from each of the three relevant parental mating types. This makes it possible to show that a particular term in the estimate is an exact tie and thus to rewrite the estimate without this term and to replace the multinomial ‘variance estimate’ of Spielman et al. [Am J Hum Genet 1993;52:506–516] by the binomial variance. Results: The resulting test is shown to be a stratified McNemar test (SMN). The significance level attained by the SMN is shown to be conservative when compared to the asymptotic χ2 distribution, while the TDT often exceeds the nominal level α. Under alternatives, the proposed test is shown to be typically more powerful than the TDT. Conclusion: The properties of the TDT as a statistical test have never been fully investigated. The proposed test replaces the heuristically motivated TDT by a formally derived test, which is also computationally simple.

Building a Statistical Expert System with Knowledge Bases of Different Levels of Abstraction

Statistical analysis is predetermined by the way a (prospective) experiment is planned or data are collected in a (retrospective) study. The a-priori knowledge of observable, theoretical and hypothetical relations (WITTKOWSKI 1987) determines the semantically meaningful database activities and statistical analyses. For instance, relations between variables and types of observational units may be used to determine whether or not the meaning of a value depends on values of other variables. The models underlying the statistical methods are determined by theoretical knowledge on the sampling strategy of factors, scales, and constraints (WITTKOWSKI 1985). For confirmatory analyses, the primary goal (hypothesis) needs to be specified at the time the sample size is computed.

On the Use of Statistical Expert Systems for Supporting Quality Assurance in Analysis of Clinical Trials

Statistical analysis of clinical trials is predetermined by the study protocol. Because this knowledge cannot be represented in commercially available analysis systems (e.g. BMDP, P-STAT, SPSS, SAS), their application is susceptible to mistakes which are often overlooked. A knowledge based front end for the analysis of clinical trials is presented which consists of six layers corresponding to different levels of abstraction in the knowledge. It is demonstrated that this “expert system” can improve statistical analysis in that access to data and programs is facilitated, the probability of erroneous applications of analysis programs is reduced, and the user is assisted in interpreting both confirmatory and exploratory results. This approach leads also to improved standards for the analysis of clinical trials.