Dopamine, affordance and active inference.

The role of dopamine in behaviour and decision-making is often cast in terms of reinforcement learning and optimal decision theory. Here, we present an alternative view that frames the physiology of dopamine in terms of Bayes-optimal behaviour. In this account, dopamine controls the precision or salience of (external or internal) cues that engender action. In other words, dopamine balances bottom-up sensory information and top-down prior beliefs when making hierarchical inferences (predictions) about cues that have affordance. In this paper, we focus on the consequences of changing tonic levels of dopamine firing using simulations of cued sequential movements. Crucially, the predictions driving movements are based upon a hierarchical generative model that infers the context in which movements are made. This means that we can confuse agents by changing the context (order) in which cues are presented. These simulations provide a (Bayes-optimal) model of contextual uncertainty and set switching that can be quantified in terms of behavioural and electrophysiological responses. Furthermore, one can simulate dopaminergic lesions (by changing the precision of prediction errors) to produce pathological behaviours that are reminiscent of those seen in neurological disorders such as Parkinson's disease. We use these simulations to demonstrate how a single functional role for dopamine at the synaptic level can manifest in different ways at the behavioural level

Vaccination against helminth parasite infections

Helminth parasites infect over one fourth of the human population and are highly prevalent in livestock worldwide. In model systems, parasites are strongly immunomodulatory, but the immune system can be driven to expel them by prior vaccination. However, no vaccines are currently available for human use. Recent advances in vaccination with recombinant helminth antigens have been successful against cestode infections of livestock and new vaccines are being tested against nematode parasites of animals. Numerous vaccine antigens are being defined for a wide range of helminth parasite species, but greater understanding is needed to define the mechanisms of vaccine-induced immunity, to lay a rational platform for new vaccines and their optimal design. With human trials underway for hookworm and schistosomiasis vaccines, a greater integration between veterinary and human studies will highlight the common molecular and mechanistic pathways, and accelerate progress towards reducing the global health burden of helminth infection

Precision Electroweak Measurements on the Z resonance.

We report on the final electroweak measurements performed with data taken at the Z resonance by the experiments operating at the electron–positron colliders SLC and LEP. The data consist of 17 million Z decays accumulated by the ALEPH, DELPHI, L3 and OPAL experiments at LEP, and 600 thousand Z decays by the SLD experiment using a polarised beam at SLC. The measurements include cross-sections, forward–backward asymmetries and polarised asymmetries. The mass and width of the Z boson, mZ and ΓZ, and its couplings to fermions, for example the ρ parameter and the effective electroweak mixing angle for leptons, are precisely measured: The number of light neutrino species is determined to be 2.9840±0.0082, in agreement with the three observed generations of fundamental fermions. The results are compared to the predictions of the Standard Model (SM). At the Z-pole, electroweak radiative corrections beyond the running of the QED and QCD coupling constants are observed with a significance of five standard deviations, and in agreement with the Standard Model. Of the many Z-pole measurements, the forward–backward asymmetry in b-quark production shows the largest difference with respect to its SM expectation, at the level of 2.8 standard deviations. Through radiative corrections evaluated in the framework of the Standard Model, the Z-pole data are also used to predict the mass of the top quark, , and the mass of the W boson, . These indirect constraints are compared to the direct measurements, providing a stringent test of the SM. Using in addition the direct measurements of mt and mW, the mass of the as yet unobserved SM Higgs boson is predicted with a relative uncertainty of about 50% and found to be less than at 95% confidence level