PAX-D:study protocol for a randomised placebo-controlled trial evaluating the efficacy and mechanism of pramipexole as add-on treatment for people with treatment resistant depression

Introduction: Clinical depression is usually treated in primary care with psychological therapies and antidepressant medication. However, when patients do not respond to at least two or more antidepressants within a depressive episode, they are considered to have treatment resistant depression (TRD). Previous small randomised controlled trials suggested that pramipexole, a dopamine D2/3 receptor agonist, may be effective for treating patients with unipolar and bipolar depression as it is known to influence motivational drive and reward processing. PAX-D will compare the effects of pramipexole versus placebo when added to current antidepressant medication for people with TRD. Additionally, PAX-D will investigate the mechanistic effect of pramipexole on reward sensitivity using a probabilistic decision-making task. Methods and analysis: PAX-D will assess effectiveness in the short- term (during the first 12 weeks) and in the longer-term (48 weeks) in patients with TRD from the UK. The primary outcome will be change in self-reported depressive symptoms from baseline to Week 12 post-randomisation measured using the QIDS-SR. Performance on the decision-making task will be measured at Week 0, Week 2, and Week 12. Secondary outcomes include anhedonia, anxiety, and health economic measures including quality of life, capability, wellbeing, and costs. PAX-D will also assess the adverse effects of pramipexole including impulse control difficulties. Discussion: Pramipexole is a promising augmentation agent for treatment resistant depression and may be a useful addition to existing treatment regimes. PAX-D will assess its effectiveness and test for a potential mechanism of action in patients with treatment resistant depression

Solutions of the steady-state Landau-Ginzburg equation in external driving fields

A steady state equation derived from the variation with respect to the order parameter M(x) of a Landau-Ginzburg free energy density of the form -- [special characters omitted] -- is considered, where h ≠ 0, C ≥ 0, D ≠ 0 is a second rank tensor. This is a generalization of prior work by Winternitz et al. [J.Phys. C 21 4931-4953 (1988)], who studied the case h = 0 and C = 0. Applied to a magnetic system, it describes the behaviour of the magnetization of a critical system in the presence of an external magnetic field h and near a structural phase transition. The Landau coefficients A, B, and C are weakly temperature dependent, but are considered constant near the transition temperature Ttr (the Curie point in magnetic systems), except for A α (T — Ttr). The gradient term allows for spatial inhomogeneities due to nearest neighbour interactions. Two cases are examined: C = 0 (B > 0) and C > 0 (B < 0) which correspond to second and first order phase transitions, respectively. The symmetries of the equation arc exploited by the symmetry reduction method to find exact solutions in terms of varied symmetry variables. These solutions are in the form of kinks, bumps, singular, periodic, and doubly periodic solutions. The physical interpretation of these results and other calculations (e.g. energy, susceptibility) based on these results is discussed

Network-Based Diffusion Analysis Reveals Cultural Transmission of Lobtail Feeding in Humpback Whales

We used network-based diffusion analysis to reveal the cultural spread of a naturally occurring foraging innovation, lobtail feeding, through a population of humpback whales (Megaptera novaeangliae) over a period of 27 years. Support for models with a social transmission component was 6 to 23 orders of magnitude greater than for models without. The spatial and temporal distribution of sand lance, a prey species, was also important in predicting the rate of acquisition. Our results, coupled with existing knowledge about song traditions, show that this species can maintain multiple independently evolving traditions in its populations. These insights strengthen the case that cetaceans represent a peak in the evolution of nonhuman culture, independent of the primate lineage

Network-Based Diffusion Analysis Reveals Cultural Transmission of Lobtail Feeding in Humpback Whales

We used network-based diffusion analysis to reveal the cultural spread of a naturally occurring foraging innovation, lobtail feeding, through a population of humpback whales (Megaptera novaeangliae) over a period of 27 years. Support for models with a social transmission component was 6 to 23 orders of magnitude greater than for models without. The spatial and temporal distribution of sand lance, a prey species, was also important in predicting the rate of acquisition. Our results, coupled with existing knowledge about song traditions, show that this species can maintain multiple independently evolving traditions in its populations. These insights strengthen the case that cetaceans represent a peak in the evolution of nonhuman culture, independent of the primate lineage