Stigmatisation et VIH : tous concernés [Stigma and HIV: relevant for everyone]

Medical advances in the treatment of HIV over the last 35 years mean that people living with HIV (PLHIV) now have a life expectancy close to that of the general population. Further, when successfully treated, PLHIV cannot transmit the virus. Despite this, HIV-related stigma remains widespread, including within healthcare settings. Stigma is not a vague sociological notion but represents a real threat to public health, with repercussions for both PLHIV and HIV-negative individuals. Stigma has been shown to have a negative impact on HIV prevention, testing, access to health services, and on the healthcare management of PLHIV. Taking stigma into consideration is essential, both in meeting the medical and psycho-social needs of PLHIV and in order to effectively combat HIV/AIDS

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum

Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

Rationale Dopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus-response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood. Objectives We present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control. Methods The dietary intervention of acute dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the effects of reduced global dopamine function on action control. Participants were randomly assigned to either the APTD or placebo group (ns = 14) to allow for a between-subjects comparison of performance on a novel three-stage experimental paradigm. In the initial learning phase, participants learned to respond to different stimuli in order to gain rewarding outcomes. Subsequently, an outcome-devaluation test and a slips-of-action test were conducted to assess whether participants were able to flexibly adjust their behaviour to changes in the desirability of the outcomes. Results APTD did not prevent stimulus-response learning, nor did we find evidence for impaired response-outcome learning in the subsequent outcome-devaluation test. However, when goal-directed and habitual systems competed for control in the slips-of-action test, APTD tipped the balance towards habitual control. These findings were restricted to female volunteers. Conclusions We provide direct evidence that the balance between goal-directed and habitual control in humans is dopamine dependent. The results are discussed in light of gender differences in dopamine function and psychopathologies

Influence of Dopaminergically Mediated Reward on Somatosensory Decision-Making

This pharmacological fMRI study shows that during reward-based sensory decision-making, dopamine is crucially involved in reward-related modulation of human primary sensory cortex

Mapping anhedonia onto reinforcement learning: A behavioural meta-analysis

BACKGROUND: Depression is characterised partly by blunted reactions to reward. However, tasks probing this deficiency have not distinguished insensitivity to reward from insensitivity to the prediction errors for reward that determine learning and are putatively reported by the phasic activity of dopamine neurons. We attempted to disentangle these factors with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD), Bipolar Disorder (BPD) and a dopaminergic challenge. METHODS: Six behavioural datasets involving 392 experimental sessions were subjected to a model-based, Bayesian meta-analysis. Participants across all six studies performed a probabilistic reward task that used an asymmetric reinforcement schedule to assess reward learning. Healthy controls were tested under baseline conditions, stress or after receiving the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were evaluated. Reinforcement learning models isolated the contributions of variation in reward sensitivity and learning rate. RESULTS: MDD and anhedonia reduced reward sensitivity more than they affected the learning rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent with a mixed effect on reward sensitivity and learning rate. CONCLUSION: Reward-related learning reflected at least two partially separable contributions. The first related to phasic prediction error signalling, and was preferentially modulated by a low dose of the dopamine agonist pramipexole. The second related directly to reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered both components. Collectively, these findings highlight the contribution of model-based reinforcement learning meta-analysis for dissecting anhedonic behavior

Minnesota Agricultural Economist No. 568

The Wetlands and Drainage Controversy; Basic Economics of Farm Drainag