Typology and Dynamics of Heavier Drinking Styles in Great Britain: 1978-2010.

AIMS: To identify a typology of heavier drinking styles in Great Britain and to identify socio-demographic trends in the typology over the period 1978-2010. METHODS: We applied multiple correspondence analysis and agglomerative hierarchical clustering to beverage-specific quantity-frequency measures of alcohol consumption in the repeated cross-sectional General Lifestyle Survey of Great Britain, 1978-2010. The cluster analysis focuses on the 60,043 adult respondents over this period reporting average drinking levels above the UK Government guidelines. We projected sex, age, income, education, socio-economic status and tobacco consumption variables onto the clusters to inspect socio-demographic trends in heavier drinking. RESULTS: We identified four stable clusters of heavier drinking: (a) high volume beer; (b) beer and spirit combination; (c) all beverage and (d) wine and spirit only. The socio-demographic characteristics of the clusters were distinct from both each other and the general population. However, all clusters had higher median incomes and higher smoking rates than the population. Increases in the prevalence of heavier drinking were driven by a 5-fold increase in the contribution of the female-dominated, wine and spirit only cluster. CONCLUSIONS: Recent changes in per capita alcohol consumption in Great Britain occurred within the context of a stable typology of heavier drinking styles and shifting socio-demographics. Identifying these trends is essential to better understand how drinking cultures develop over time and where potentially problematic drinking styles may emerge. Our findings suggest that careful attention to patterns and cultures of consumption is more important than relying on headline consumption data, for both understanding drinking behaviours and targeting interventions. SHORT SUMMARY: This analysis of alcohol consumption survey data identifies four styles of heavier drinking in Great Britain, which remain unchanged over the period 1978-2010. The socio-demographic characteristics of the drinking styles are distinct from both each other and the general population, with increased participation of female and older drinkers over time.

Macrophage Transactivation for Chemokine Production Identified as a Negative Regulator of Granulomatous Inflammation Using Agent-Based Modeling.

Cellular activation in trans by interferons, cytokines, and chemokines is a commonly recognized mechanism to amplify immune effector function and limit pathogen spread. However, an optimal host response also requires that collateral damage associated with inflammation is limited. This may be particularly so in the case of granulomatous inflammation, where an excessive number and/or excessively florid granulomas can have significant pathological consequences. Here, we have combined transcriptomics, agent-based modeling, and in vivo experimental approaches to study constraints on hepatic granuloma formation in a murine model of experimental leishmaniasis. We demonstrate that chemokine production by non-infected Kupffer cells in the Leishmania donovani-infected liver promotes competition with infected KCs for available iNKT cells, ultimately inhibiting the extent of granulomatous inflammation. We propose trans-activation for chemokine production as a novel broadly applicable mechanism that may operate early in infection to limit excessive focal inflammation.

Transition probabilities for four states of alcohol use in adolescence and young adulthood: what factors matter when?

BACKGROUND AND AIMS: Risky single-occasion drinking (RSOD) is a health threat, particularly at younger ages. The study aimed to quantify transition probabilities (TPs) between abstinence, use of alcohol, RSOD and frequent RSOD, and to understand how TPs are associated with key demographic factors. DESIGN: Cohort study (baseline, two follow-ups). A Markov model was fitted to estimate annual TPs and hazard ratios (HRs) for age, sex and socio-economic status (SES). SETTING: Adolescent and young adult general population of Munich (Germany) and surrounding areas. PARTICIPANTS: A total of 3021 people aged 14-25 years at baseline in 1995 followed-up in 1998/1999 (n = 2548) and 2003-2005 (n = 2210). MEASUREMENTS: Alcohol use, RSOD status, age, sex and SES (subjective financial situation) were assessed in a standardized interview. FINDINGS: The highest TPs (> 65%) were found for staying in the same drinking state. Higher age [hazard ratio (HR) for 1-year increase = 0.87, 95% confidence interval (CI) = 0.84-0.91], being female (HR = 0.30, 95% CI = 0.21-0.42), and a high SES (HR = 0.64, 95% CI = 0.43-0.97) were associated with a lower hazard to progress from use to RSOD. While age was associated predominantly with transitions between abstinence and alcohol use, sex was more relevant for transitions associated with RSOD and frequent RSOD. CONCLUSIONS: German adolescents and young adults tend to be stable in the drinking states of abstinence, use of alcohol, risky single-occasion drinking and frequent risky single-occasion drinking. Females are less likely to transition to riskier states and more likely to transition back from frequent risky single-occasion drinking, higher age is associated with lower hazard of transitioning and participants of higher socio-economic status are less likely to transition from 'use of alcohol' to 'risky single-occasion drinking'.

Functional complexity of the Leishmania granuloma and the potential of in silico modeling.

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.