Reward learning as a potential target for pharmacological augmentation of cognitive remediation for schizophrenia: a roadmap for preclinical development.

RationaleImpaired cognitive abilities are a key characteristic of schizophrenia. Although currently approved pharmacological treatments have demonstrated efficacy for positive symptoms, to date no pharmacological treatments successfully reverse cognitive dysfunction in these patients. Cognitively-based interventions such as cognitive remediation (CR) and other psychosocial interventions however, may improve some of the cognitive and functional deficits of schizophrenia. Given that these treatments are time-consuming and labor-intensive, maximizing their effectiveness is a priority. Augmenting psychosocial interventions with pharmacological treatments may be a viable strategy for reducing the impact of cognitive deficits in patients with schizophrenia.ObjectiveWe propose a strategy to develop pharmacological treatments that can enhance the reward-related learning processes underlying successful skill-learning in psychosocial interventions. Specifically, we review clinical and preclinical evidence and paradigms that can be utilized to develop these pharmacological augmentation strategies. Prototypes for this approach include dopamine D1 receptor and α7 nicotinic acetylcholine receptor agonists as attractive targets to specifically enhance reward-related learning during CR.ConclusionThe approach outlined here could be used broadly to develop pharmacological augmentation strategies across a number of cognitive domains underlying successful psychosocial treatment

Perturbation theory for the effective diffusion constant in a medium of random scatterer

We develop perturbation theory and physically motivated resummations of the perturbation theory for the problem of a tracer particle diffusing in a random media. The random media contains point scatterers of density $\rho$ uniformly distributed through out the material. The tracer is a Langevin particle subjected to the quenched random force generated by the scatterers. Via our perturbative analysis we determine when the random potential can be approximated by a Gaussian random potential. We also develop a self-similar renormalisation group approach based on thinning out the scatterers, this scheme is similar to that used with success for diffusion in Gaussian random potentials and agrees with known exact results. To assess the accuracy of this approximation scheme its predictions are confronted with results obtained by numerical simulation.Comment: 22 pages, 6 figures, IOP (J. Phys. A. style

Effective diffusion constant in a two dimensional medium of charged point scatterers

We obtain exact results for the effective diffusion constant of a two dimensional Langevin tracer particle in the force field generated by charged point scatterers with quenched positions. We show that if the point scatterers have a screened Coulomb (Yukawa) potential and are uniformly and independently distributed then the effective diffusion constant obeys the Volgel-Fulcher-Tammann law where it vanishes. Exact results are also obtained for pure Coulomb scatterers frozen in an equilibrium configuration of the same temperature as that of the tracer.Comment: 9 pages IOP LaTex, no figure

Renormalization of Drift and Diffusivity in Random Gradient Flows

We investigate the relationship between the effective diffusivity and effective drift of a particle moving in a random medium. The velocity of the particle combines a white noise diffusion process with a local drift term that depends linearly on the gradient of a gaussian random field with homogeneous statistics. The theoretical analysis is confirmed by numerical simulation. For the purely isotropic case the simulation, which measures the effective drift directly in a constant gradient background field, confirms the result previously obtained theoretically, that the effective diffusivity and effective drift are renormalized by the same factor from their local values. For this isotropic case we provide an intuitive explanation, based on a {\it spatial} average of local drift, for the renormalization of the effective drift parameter relative to its local value. We also investigate situations in which the isotropy is broken by the tensorial relationship of the local drift to the gradient of the random field. We find that the numerical simulation confirms a relatively simple renormalization group calculation for the effective diffusivity and drift tensors.Comment: Latex 16 pages, 5 figures ep

Continuum Derrida Approach to Drift and Diffusivity in Random Media

By means of rather general arguments, based on an approach due to Derrida that makes use of samples of finite size, we analyse the effective diffusivity and drift tensors in certain types of random medium in which the motion of the particles is controlled by molecular diffusion and a local flow field with known statistical properties. The power of the Derrida method is that it uses the equilibrium probability distribution, that exists for each {\em finite} sample, to compute asymptotic behaviour at large times in the {\em infinite} medium. In certain cases, where this equilibrium situation is associated with a vanishing microcurrent, our results demonstrate the equality of the renormalization processes for the effective drift and diffusivity tensors. This establishes, for those cases, a Ward identity previously verified only to two-loop order in perturbation theory in certain models. The technique can be applied also to media in which the diffusivity exhibits spatial fluctuations. We derive a simple relationship between the effective diffusivity in this case and that for an associated gradient drift problem that provides an interesting constraint on previously conjectured results.Comment: 18 pages, Latex, DAMTP-96-8

Applications of the ER-2 meteorological measurement system

The NASA ER-2 aircraft is used as a platform for high altitude atmospheric missions. The Meteorological Measurement System (MMS) was developed specifically for atmospheric research to provide accurate high resolution measurements of pressure, temperature, and the 3-D wind vector with a sampling rate of 5/s. The MMS consist of three subsystems: (1) an air motion sensing system to measure the velocity of the air with respect to the aircraft; (2) a high resolution inertial navigation system (INS) to measure the velocity of the aircraft with respect to the earth; and (3) a data acquisition system to sample, process, and record the measurement quantities. MMS data have been used extensively by ER-2 investigators in elucidating the polar ozone chemistry. Herein, applications on atmospheric dynamics are emphasized. Large scale (polar vortex, potential vorticity, model atmosphere), mesoscale (gravity waves, mountain waves) and microscale (heat fluxes) atmospheric phenomena are investigated and discussed

Human resource inequalities at the base of India's public health care system

This paper examines the extent of inequalities in human resource provision at India's Heath Sub-Centres (HSC) - first level of service provision in the public health system. ‘Within state' inequality explained about 71% and ‘between state’ inequality explained the remaining 29% of the overall inter-HSC inequality. The Northern states had a lower health worker share relative to the extent of their HSC provision. Contextual factors that contributed to ‘between’ and ‘within’ district inequalities were the percentages of villages connected with all-weather roads and having primary schools. Analysis demonstrates a policy and programming need to address ‘within State’ inequalities as a priority

Imaging Polarimeter Arrays for Near-Millimeter Waves

An integrated-circuit antenna array has been developed that images both polarization and intensity. The array consists of a row of antennas that lean alternately left and right, creating two interlaced sub-arrays that respond to different polarizations. The arrays and the bismuth bolometer detectors are made by a photoresist shadowing technique that requires only one photolithographic mask. The array has measured polarization at a wavelength of 800 µm with an absolute accuracy of 0.8° and a relative precision of 7 arc min. and has demonstrated nearly diffraction-Iimited resolutiort of a 20° step in polarization

Visibility Representations of Boxes in 2.5 Dimensions

We initiate the study of 2.5D box visibility representations (2.5D-BR) where vertices are mapped to 3D boxes having the bottom face in the plane $z=0$ and edges are unobstructed lines of sight parallel to the $x$- or $y$-axis. We prove that: $(i)$ Every complete bipartite graph admits a 2.5D-BR; $(ii)$ The complete graph $K_n$ admits a 2.5D-BR if and only if $n \leq 19$; $(iii)$ Every graph with pathwidth at most $7$ admits a 2.5D-BR, which can be computed in linear time. We then turn our attention to 2.5D grid box representations (2.5D-GBR) which are 2.5D-BRs such that the bottom face of every box is a unit square at integer coordinates. We show that an $n$-vertex graph that admits a 2.5D-GBR has at most $4n - 6 \sqrt{n}$ edges and this bound is tight. Finally, we prove that deciding whether a given graph $G$ admits a 2.5D-GBR with a given footprint is NP-complete. The footprint of a 2.5D-BR $\Gamma$ is the set of bottom faces of the boxes in $\Gamma$.Comment: Appears in the Proceedings of the 24th International Symposium on Graph Drawing and Network Visualization (GD 2016