Defining responses to therapy and study outcomes in clinical trials of invasive fungal diseases: Mycoses Study Group and European Organization for Research and Treatment of Cancer consensus criteria.

Invasive fungal diseases (IFDs) have become major causes of morbidity and mortality among highly immunocompromised patients. Authoritative consensus criteria to diagnose IFD have been useful in establishing eligibility criteria for antifungal trials. There is an important need for generation of consensus definitions of outcomes of IFD that will form a standard for evaluating treatment success and failure in clinical trials. Therefore, an expert international panel consisting of the Mycoses Study Group and the European Organization for Research and Treatment of Cancer was convened to propose guidelines for assessing treatment responses in clinical trials of IFDs and for defining study outcomes. Major fungal diseases that are discussed include invasive disease due to Candida species, Aspergillus species and other molds, Cryptococcus neoformans, Histoplasma capsulatum, and Coccidioides immitis. We also discuss potential pitfalls in assessing outcome, such as conflicting clinical, radiological, and/or mycological data and gaps in knowledge.

The timing and interval of mate encounter affects investment during mating

The benefits obtained from mating are usually condition-dependent, favouring the evolution of flexible investment during copulation, for instance, in terms of invested time, energy, or sperm. Flexible investment strategies are predicted to depend on the likelihood of acquiring alternative mates and therefore they should depend on the timing of mate encounter. However, scarce experimental evidence for this hypothesis exists. Here we manipulated the time delay until first mating and the interval between first and second mating in the polygynandrous common lizard, Zootoca vivipara. We determined treatment effects on fertilisation success and copulation duration, the latter being a proxy for investment in mating and for quantity of transferred sperm. The duration of the second copulation decreased with increasing inter-mating interval and depended on the fertilisation success of first mates. The former provides evidence for time-dependent investment strategies, most likely resulting from the progression of the female's reproductive cycle. Fertilisation success of first mates increased with increasing inter-mating interval and was higher when females were closer to ovulation, showing that flexible investment strategies significantly affected male reproductive success. This points to fertilisation assurance, which may mitigate negative effects of low population density on reproductive success, e.g. Allee effects.