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Opioid receptors are widely distributed throughout the brain and play an essential role in modulating aspects of human mood, reward, and well-being. Accumulating evidence indicates the endogenous opioid system is dysregulated in depression and that pharmacological modulators of mu, delta, and kappa opioid receptors hold potential for the treatment of depression. Here we review animal and clinical data, highlighting evidence to support: dysregulation of the opioid system in depression, evidence for opioidergic modulation of behavioural processes and brain regions associated with depression, and evidence for opioidergic modulation in antidepressant responses. We evaluate clinical trials that have examined the safety and efficacy of opioidergic agents in depression and consider how the opioid system may be involved in the effects of other treatments, including ketamine, that are currently understood to exert antidepressant effects through non-opioidergic actions. Finally, we explore key neurochemical and molecular mechanisms underlying the potential therapeutic effects of opioid system engagement, that together provides a rationale for further investigation into this relevant target in the treatment of depression.

Technologies for measuring physiological parameters in vivo offer the possibility of the detection of disease and its progression due to the resulting changes in tissue pH, or temperature, etc.. Here, a compact hydrogel-based optical fibre pH sensor was fabricated, in which polymer microarrays were utilized for the high-throughput discovery of an optimal matrix for pH indicator immobilization. The fabricated hydrogel-based probe responded rapidly to pH changes and demonstrated a good linear correlation within the physiological pH range (from 5.5 to 8.0) with a precision of 0.10 pH units. This miniature probe was validated by measuring pH across a whole ovine lung and allowed discrimination of tumorous and normal tissue, thus offering the potential for the rapid and accurate observation of tissue pH changes.

We present a fourth-order accurate finite volume method for the solution of ideal magnetohydrodynamics (MHD). The numerical method combines high-order quadrature rules in the solution of semi-discrete formulations of hyperbolic conservation laws with the upwind constrained transport (UCT) framework to ensure that the divergence-free constraint of the magnetic field is satisfied. A novel implementation of UCT that uses the piecewise parabolic method (PPM) for the reconstruction of magnetic fields at cell corners in 2D is introduced. The resulting scheme can be expressed as the extension of the second-order accurate constrained transport (CT) Godunov-type scheme that is currently used in the Athena astrophysics code. After validating the base algorithm on a series of hydrodynamics test problems, we present the results of multidimensional MHD test problems which demonstrate formal fourth-order convergence for smooth problems, robustness for discontinuous problems, and improved accuracy relative to the second-order scheme., 42 pages, 22 figures, accepted for publication in J. Comp. Phys

The interstellar medium is heterogeneous with dense clouds amid an ambient medium. Radiation from young OB stars asymmetrically irradiate the dense clouds. Bertoldi (1989) developed analytic formulae to describe possible outcomes of these clouds when irradiated by hot, young stars. One of the critical parameters that determines the cloud’s fate is the number of photon mean free paths in the cloud. For the extreme cases where the cloud size is either much greater than or much less than one mean free path, the radiation transport should be well understood. However, as one transitions between these limits, the radiation transport is much more complex and is a challenge to solve with many of the current radiation transport models implemented in codes. We present the design of laboratory experiments that use a thermal source of x-rays to asymmetrically irradiate a low-density plastic foam sphere. The experiment will vary the density and hence the number of mean free paths of the sphere to study the radiation transport in different regimes. We have developed dimensionless parameters to relate the laboratory experiment to the astrophysical system and we show that we can perform the experiment in the same transport regime.

We provide an experimental study of the nonlinear optical effects which can be enhanced in order to produce visible supercontinua in photonic crystal fibers. We examine individual uniform fibers and discuss the physical origins of the resulting supercontinua. We then examine tapered supercontinuum fibers which exploit the advantages of our individual uniform fibers at different points along the length of the taper. We demonstrate reproducible control of taper shape.

Background: It is not known whether regional brain N-acetyl aspartate (NAA) changes in the progression from prodrome to chronic schizophrenia. We used effect size meta-analysis to determine which brain regions show the most robust reductions in NAA first episode and chronic schizophrenia as measured by proton magnetic resonance spectroscopy and to determine whether these changes are present in individuals at high risk of developing schizophrenia.Methods: We identified 131 articles, of which 97 met inclusion criteria. Data were separated by stage of illness (at risk, first episode schizophrenia, chronic schizophrenia) and by brain region. For each region, mean and SD of the NAA measure was extracted.Results: Significant reductions in NAA levels were found in frontal lobe, temporal lobe, and thalamus in both patient groups (effect size > .3; p Conclusions: These data suggest that schizophrenia is associated with loss of neuronal integrity in frontal and temporal cortices and in the thalamus and suggest that these changes in the frontal and temporal lobe might occur in the transition between the at-risk phase and the first episode.

From a mathematical perspective, radiation hydrodynamics can be thought of as a system of hyperbolic balance laws with dual multiscale behavior (multiscale behavior associated with the hyperbolic wave speeds as well as multiscale behavior associated with source term relaxation). With this outlook in mind, this paper presents a hybrid Godunov method for one-dimensional radiation hydrodynamics that is uniformly well behaved from the photon free streaming (hyperbolic) limit through the weak equilibrium diffusion (parabolic) limit and to the strong equilibrium diffusion (hyperbolic) limit. Moreover, one finds that the technique preserves certain asymptotic limits. The method incorporates a backward Euler upwinding scheme for the radiation energy density and flux as well as a modified Godunov scheme for the material density, momentum density, and energy density. The backward Euler upwinding scheme is first-order accurate and uses an implicit HLLE flux function to temporally advance the radiation components according to the material flow scale. The modified Godunov scheme is second-order accurate and directly couples stiff source term effects to the hyperbolic structure of the system of balance laws. This Godunov technique is composed of a predictor step that is based on Duhamel's principle and a corrector step that is based on Picard iteration. The Godunov scheme is explicit on the material flow scale but is unsplit and fully couples matter and radiation without invoking a diffusion-type approximation for radiation hydrodynamics. This technique derives from earlier work by Miniati & Colella 2007. Numerical tests demonstrate that the method is stable, robust, and accurate across various parameter regimes., accepted for publication in Journal of Computational Physics; 61 pages, 15 figures, 11 tables

We describe a numerical algorithm based on Godunov methods for integrating the equations of compressible magnetohydrodynamics (MHD) in multidimensions. It combines a simple, dimensionally-unsplit integration method with the constrained transport (CT) discretization of the induction equation to enforce the divergence-free constraint. We present the results of a series of fully three-dimensional tests which indicate the method is second-order accurate for smooth solutions in all MHD wave families, and captures shocks, contact and rotational discontinuities well. However, it is also more diffusive than other more complex unsplit integrators combined with CT. Thus, the primary advantage of the method is its simplicity. It does not require a characteristic tracing step to construct interface values for the Riemann solver, it is straightforward to extend with additional physics, and it is suitable for use with nested and adaptive meshes. The method is implemented as one of two dimensionally unsplit MHD integrators in the Athena code, which is freely available for download from the web.

We present a single step, second-order accurate Godunov scheme for ideal MHD which is an extension of the method described by Gardiner & Stone (2005) to three dimensions. This algorithm combines the corner transport upwind (CTU) method of Colella for multidimensional integration, and the constrained transport (CT) algorithm for preserving the divergence-free constraint on the magnetic field. We describe the calculation of the PPM interface states for 3D ideal MHD which must include multidimensional ``MHD source terms'' and naturally respect the balance implicit in these terms by the ${\bf\nabla\cdot B}=0$ condition. We compare two different forms for the CTU integration algorithm which require either 6- or 12-solutions of the Riemann problem per cell per time-step, and present a detailed description of the 6-solve algorithm. Finally, we present solutions for test problems to demonstrate the accuracy and robustness of the algorithm., Extended version of the paper accepted for publication in JCP

We describe a single step, second-order accurate Godunov scheme for ideal MHD based on combining the piecewise parabolic method (PPM) for performing spatial reconstruction, the corner transport upwind (CTU) method of Colella for multidimensional integration, and the constrained transport (CT) algorithm for preserving the divergence-free constraint on the magnetic field. We adopt the most compact form of CT, which requires the field be represented by area-averages at cell faces. We demonstrate that the fluxes of the area-averaged field used by CT can be made consistent with the fluxes of the volume-averaged field returned by a Riemann solver if they obey certain simple relationships. We use these relationships to derive new algorithms for constructing the CT fluxes at grid cell corners which reduce exactly to the equivalent one-dimensional solver for plane-parallel, grid-aligned flow. We show that the PPM reconstruction algorithm must include multidimensional terms for MHD, and we describe a number of important extensions that must be made to CTU in order for it to be used for MHD with CT. We present the results of a variety of test problems to demonstrate the method is accurate and robust., 45 pages, 13 figures, accepted for publication in J. Comp. Phys., More information on Athena can be found at http://www.astro.princeton.edu/~jstone/athena.html

Thalamic neurochemical abnormalities may underlie psychotic symptoms and auditory event-related potential (ERP) abnormalities in schizophrenia. We investigated this hypothesis in subjects at risk of psychosis using magnetic resonance spectroscopy and electroencephalography (EEG). Reduced thalamic glutamate plus glutamine and N-acetyl aspartate levels were associated with abnormal frontal ERPs, supporting a thalamic basis for filtering impairments. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Studying the multidimensional, time-dependent and/or highly nonlinear dynamics of astrophysical plasmas usually requires numerical methods, however, developing accurate and robust algorithms for compressible MHD and/or radiation MHD is still an active area of research. Recent advances in the development of numerical algorithms are described, and results from applications of the methods to the study of a variety of problems in astrophysics is discussed.

Magnetic fields are important components of many astrophysical systems. These systems are studied with numerical simulations of the equations of magnetohydrodynamics (MHD). We briefly review the MHD assumptions, some of the numerical approaches currently in use, and some of the problems to which MHD codes are being applied. We describe in detail the Method of Characteristics-Constrained Transport scheme. This is a time-explicit, operator split, nonconservative technique that uses information propagated along Alfven characteristics to compute electromagnetic forces at intermediate time levels for the induction equation and for the Lorentz force. The advantages and difficulties with this scheme are investigated with a series of test problems.

We describe a hybrid scheme for cosmological simulations that incorporates a Lagrangean particle-mesh (PM) algorithm to follow the collisionless matter with the higher order accurate piecewise parabolic method (PPM) to solve the equations of gas dynamics. Both components interact through the gravitational potential, which requires the solution of Poisson's equation, here done by Fourier transforms. Due to the vast range of conditions that occur in cosmological flows (pressure differences of up to fourteen orders of magnitude), a number of additions and modifications to PPM were required to produce accurate results. These are described, as are a suite of cosmological tests.

We present the results of axisymmetric time-dependent hydrodynamic calculations of line-driven winds from accretion disks in active galactic nuclei (AGN). We assume the disk is flat, Keplerian, geometrically thin, and optically thick, radiating according to the α-disk prescription. The central engine of the AGN is a source of both ionizing X-rays and wind-driving ultraviolet (UV) photons. To calculate the radiation force, we take into account radiation from the disk and the central engine. The gas temperature and ionization state in the wind are calculated self-consistently from the photoionization and heating rate of the central engine. We find that a disk accreting onto a 10 8 M ⊙ yr −1 black hole at the rate of 1.8 M ⊙ yr −1 can launch a wind at ∼ 10 16 cm from the central engine. The X-rays from the central object are significantly attenuated by the disk atmosphere so they cannot prevent the local disk radiation from pushing matter away from the disk. However in the supersonic portion of the flow high above the disk, the X-rays can overionize the gas and decrease the wind terminal velocity. For a reasonable X-ray opacity, e.g., κ X = 40 g −1 cm 2 , the disk wind can be accelerated by the central UV radiation to velocities of up to 15000 km s −1 at a distance of ∼ 10 17 cm from the central engine. The covering factor of the disk wind is ∼ 0.2. The wind is unsteady and consists of an opaque, slow vertical flow near the disk that is bounded on the polar side by a high-velocity, stream. A typical column density through the fast stream is a few 10 23 cm −2 so the stream is optically thin to the UV radiation. This low column density is precisely why gas can be accelerated to high velocities. The fast stream contributes nearly 100% to the total wind mass loss rate of 0.5 M ⊙ yr −1 .

We describe the use of upwind monotonic interpolation methods for the solution of the time-dependent radiative transfer equation in both optically thin and thick media. These methods, originally developed to solve Eulerian advection problems in hydrodynamics, have the ability to propagate sharp features in the flow with very little numerical diffusion. We consider the implementation of both explicit and implicit versions of the method. The explicit version is able to keep radiation fronts resolved to only a few zones wide when higher order interpolation methods are used. Although traditional implementations of the implicit version suffer from large numerical diffusion, we describe an implicit method which considerably reduces this diffusion.

Unlike other patients requiring nutritional support, injured patients are usually in good health premorbidly. Nutritional therapy in the traumatized patient is designed to prevent the deterioration of body cell mass and to treat specific complications as they occur.

Although most individuals contain enough reserve to support the processes of metabolism and healing for extended periods, severe trauma and sepsis may be associated with an energy crisis. The authors discuss methods of assessing the need for nutritional support and of instituting support.