How the magnitude of clinical severity and recurrence risk affects reproductive decisions in adult males with different forms of progressive muscular dystrophy

A new antiretroviral drug (azidothymidine homodinucleotide, AZTp2AZT), designed for the protection of macrophages against retroviral infection, was evaluated in a murine retrovirus-induced immunodeficiency model of AIDS (MAIDS) alone and in combination with oral azidothymidine (AZT). C57BL/6 mice were infected with the retroviral complex LP-BM5 and treated for 3 months by weekly administrations of 15 nmol of AZTp2AZT encapsulated into autologous erythrocytes for macrophage protection. AZTp2AZT treatment was found to reduce lymphoadenopathy (48%), splenomegaly (26%), and BM5d proviral DNA content in lymph nodes, spleen, and brain of 37%, 40%, and 36%, respectively, compared with untreated animals. AZT administration in drinking water (0.25 mg/ml) was more effective than administration of AZTp2AZT encapsulated into erythrocytes in reducing lymphoadenopathy, splenomegaly, gammaglobulinemia, and proviral DNA content in lymph nodes, but it caused a reduction in erythrocyte count and hematocrit levels. Although combined treatments do not provide additive responses in the several parameters investigated, they were found to be much more effective in reducing the proviral DNA content in brain (67%) than were monotherapies. Furthermore, no apparent signs of hematotoxicity were observed. Thus, macrophage delivery of antiviral drugs may contribute to brain protection from retroviral infections by mechanisms other than those exerted by oral AZT administration.     

Where is the fault in fault trees?

When branches of a fault tree are pruned, their probabilities are not fully transferred to the "all other" branch. Three explanations for this underestimation of the "all other" probability were tested: availability, ambiguity, and credibility. In an experiment, the authors varied the credibility of a cover story and separately observed the generation of a fault's causes to isolate availability, and the categorization of causes to assess ambiguity. The results identify biased availability as a broad threat to the validity of likelihood estimates. Ambiguity adds to the problem whenever tree designers are unable to eliminate it from causes or categories. Finally, though Ss had clear expectations for what constitutes a credible fault tree, none of the "all other" underestimation could be traced to credibility factors. The discussion covers both underlying mechanisms and corrective techniques. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Elucidating the effects of reinforcement magnitude.

This article reviews the literature on magnitude of unconditioned reinforcement (including duration, volume, and percentage concentration methods of programming magnitude). Debate continues over whether manipulation of reinforcement magnitude influences behavior. Although some studies (particularly those involving choice contingencies) demonstrate magnitude effects, others do not. These contradictory findings are discussed here in terms of the necessary and sufficient conditions for producing a reinforcement magnitude effect. Also, the ability of various theories to account for various magnitude effects is discussed. It is suggested that future research take a more systematic direction, uncovering the necessary and sufficient conditions for producing an effect and expanding and testing theories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estimating the magnitude of experimental effects.

Discusses the increasing awareness that the mere statistical significance of an experimental effect is insufficient to warrant the conclusion that the effect is large and practically important. A number of related measures of the magnitude of experimental effects which can be applied to the results of a 1-way analysis of variance but not to the results of a more complicated design are available. The proper measure for a complex design depends on whether other factors are fixed or random, and the uncritical following of advice given in the literature can result in serious over- or underestimation of the magnitude of experimental effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Epidemiological determinants of the pattern and magnitude of the vCJD epidemic in Great Britain

Understanding the epidemiology and aetiology of new-variant Creutzfeldt-Jakob (vCJD) disease in humans has become increasingly important given the scientific evidence linking it to bovine spongiform encephalopathy (BSE) in cattle and hence the wide exposure of the population of Great Britain (GB) to potentially infectious tissue. The recent analysis undertaken to determine the risk to the population from dorsal route ganglia illustrated the danger in presenting point estimates rather than ranges of scenarios in the face of uncertainty. We present a mathematical template that relates the past pattern of the BSE epidemic in cattle to the future course of any vCJD epidemic in humans, and use extensive scenario analysis to explore the wide range of possible outcomes given the uncertainty in epidemiological determinants. We demonstrate that the average number of humans infected by one infectious bovine and the incubation period distribution are the two epidemiological factors that have the greatest impact on epidemic size and duration. Using the time-series of the BSE epidemic and the cases seen to date, we show that the minimum length of the incubation period is approximately nine years, and that at least 20% of the cases diagnosed to date were exposed prior to 1986. We also demonstrate that the current age distribution of vCJD cases can only arise if younger people were either exposed to a greater extent, more susceptible to infection, or have shorter incubation periods. Extensive scenario analyses show that given the information currently available, the very high degree of uncertainty in the future size of the epidemic will remain for the next 3-5 years. Furthermore, we demonstrate that this uncertainty is unlikely to be reduced by mass screening for late-stage infection.