In human and canine visceral leishmaniasis and in various experimental models of this disease, host resistance is strongly linked to efficient granuloma development. However, it is unknown exactly how the granuloma microenvironment executes an effective antileishmanial response. Recent studies, including using advanced imaging techniques, have improved our understanding of granuloma biology at the cellular level, highlighting heterogeneity in granuloma development and function, and hinting at complex cellular, temporal, and spatial dynamics. In this mini-review, we discuss the factors involved in the formation and function of Leishmania donovani-induced hepatic granulomas, as well as their importance in protecting against inflammation-associated tissue damage and the generation of immunity to rechallenge. Finally, we discuss the role that computational, agent-based models may play in answering outstanding questions within the field.

This paper presents a new real-world application of evolutionary computation: identifying parameterisations of a theory-driven model that can reproduce alcohol consumption dynamics observed in a population over time. Population alcohol consumption is a complex system, with multiple interactions between economic and social factors and drinking behaviours, the nature and importance of which are not well-understood. Prediction of time trends in consumption is therefore difficult, but essential for robust estimation of future changes in health-related consequences of drinking and for appraising the impact of interventions aimed at changing alcohol use in society. The paper describes a microsimulation approach in which an attitude-behaviour model, Theory of Planned Behaviour, is used to describe the frequency of drinking by individuals. Consumption dynamics in the simulation are driven by changes in the social roles of individuals over time (parenthood, partnership, and paid labour). An evolutionary optimizer is used to identify parameterisations of the Theory that can describe the observed changes in drinking frequency. Niching is incorporated to enable multiple possible parameterisations to be identified, each of which can accurately recreate history but potentially encode quite different future trends. The approach is demonstrated using evidence from the 1979-1985 birth cohort in England between 2003 and 2010.

SUMMARY We conducted a retrospective cohort study assessing the association between diabetes mellitus (DM) and immune recovery in HIV-infected adults. Immune reconstitution after initiating antiretroviral therapy was more rapid in DM patients (120.4 cells/year) compared to non-DM patients (94.2 cells/year, p < 0.023). Metformin use was associated with improved CD4 recovery (p= 0.034).

These findings suggest a complex interrelation among traditional host factors and treatment-related metabolic changes in the pathogenesis of DM inpatients receiving ART. Notably, pre-ART weight, particularly if >70 kg, is associated with the diagnosis of diabetes in HIV-infected patients in Botswana.