Stage managing bipolar disorder.

OBJECTIVES: Clinical staging is widespread in medicine - it informs prognosis, clinical course, and treatment, and assists individualized care. Staging places an individual on a probabilistic continuum of increasing potential disease severity, ranging from clinically at-risk or latency stage through first threshold episode of illness or recurrence, and, finally, to late or end-stage disease. The aim of the present paper was to examine and update the evidence regarding staging in bipolar disorder, and how this might inform targeted and individualized intervention approaches. METHODS: We provide a narrative review of the relevant information. RESULTS: In bipolar disorder, the validity of staging is informed by a range of findings that accompany illness progression, including neuroimaging data suggesting incremental volume loss, cognitive changes, and a declining likelihood of response to pharmacological and psychosocial treatments. Staging informs the adoption of a number of approaches, including the active promotion of both indicated prevention for at-risk individuals and early intervention strategies for newly diagnosed individuals, and the tailored implementation of treatments according to the stage of illness. CONCLUSIONS: The nature of bipolar disorder implies the presence of an active process of neuroprogression that is considered to be at least partly mediated by inflammation, oxidative stress, apoptosis, and changes in neurogenesis. It further supports the concept of neuroprotection, in that a diversity of agents have putative effects against these molecular targets. Clinically, staging suggests that the at-risk state or first episode is a period that requires particularly active and broad-based treatment, consistent with the hope that the temporal trajectory of the illness can be altered. Prompt treatment may be potentially neuroprotective and attenuate the neurostructural and neurocognitive changes that emerge with chronicity. Staging highlights the need for interventions at a service delivery level and implementing treatments at the earliest stage of illness possible

Trapped 6^{6}Li : A high T_c superfluid ?

We consider the effect of the indirect interaction due to the exchange of density fluctuations on the critical temperature of superfluid $^{6}$Li . We obtain the strong coupling equation giving this critical temperature. This equation is solved approximately by retaining the same set of diagrams as in the paramagnon model. We show that, near the instability threshold, the attractive interaction due to density fluctuations gives rise to a strong increase in the critical temperature, providing a clear signature of the existence of fluctuation induced interactions.Comment: 4 pages, revtex, 1 figur

Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial

While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of \u27antidepressant\u27 but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression

Theory of spin and charge fluctuations in the Hubbard model

A self-consistent theory of both spin and charge fluctuations in the Hubbard model is presented. It is in quantitative agreement with Monte Carlo data at least up to intermediate coupling $(U\sim 8t)$. It includes both short-wavelength quantum renormalization effects, and long-wavelength thermal fluctuations which can destroy long-range order in two dimensions. This last effect leads to a small energy scale, as often observed in high temperature superconductors. The theory is conserving, satisfies the Pauli principle and includes three-particle correlations necessary to account for the incipient Mott transition.Comment: J1K 2R1 10 pages, Revtex 3.0, 4 uuencoded postscript figures, report# CRPS-93-4

A comparison of incompressible limits for resistive plasmas

The constraint of incompressibility is often used to simplify the magnetohydrodynamic (MHD) description of linearized plasma dynamics because it does not affect the ideal MHD marginal stability point. In this paper two methods for introducing incompressibility are compared in a cylindrical plasma model: In the first method, the limit $\gamma \to \infty$ is taken, where $\gamma$ is the ratio of specific heats; in the second, an anisotropic mass tensor $\mathbf{\rho}$ is used, with the component parallel to the magnetic field taken to vanish, $\rho_{\parallel} \to 0$. Use of resistive MHD reveals the nature of these two limits because the Alfv\'en and slow magnetosonic continua of ideal MHD are converted to point spectra and moved into the complex plane. Both limits profoundly change the slow-magnetosonic spectrum, but only the second limit faithfully reproduces the resistive Alfv\'en spectrum and its wavemodes. In ideal MHD, the slow magnetosonic continuum degenerates to the Alfv\'en continuum in the first method, while it is moved to infinity by the second. The degeneracy in the first is broken by finite resistivity. For numerical and semi-analytical study of these models, we choose plasma equilibria which cast light on puzzling aspects of results found in earlier literature.Comment: 14 pages, 10 figure

Correlations, compressibility, and capacitance in double-quantum-well systems in the quantum Hall regime

In the quantum Hall regime, electronic correlations in double-layer two-dimensional electron systems are strong because the kinetic energy is quenched by Landau quantization. In this article we point out that these correlations are reflected in the way the partitioning of charge between the two-layers responds to a bias potential. We report on illustrative calculations based on an unrestricted Hartree-Fock approximation which allows for spontaneous inter-layer phase coherence. The possibility of studying inter-layer correlations by capacitive coupling to separately contacted two-dimensional layers is discussed in detail.Comment: RevTex style, 21 pages, 6 postscript figures in a separate file; Phys. Rev. B (in press

Overriding plate, mantle wedge, slab, and subslab contributions to seismic anisotropy beneath the northern Central Andean Plateau

The Central Andean Plateau, the second-highest plateau on Earth, overlies the subduction of the Nazca Plate beneath the central portion of South America. The origin of the high topography remains poorly understood, and this puzzle is intimately tied to unanswered questions about processes in the upper mantle, including possible removal of the overriding plate lithosphere and interaction with the flow field that results from the driving forces associated with subduction. Observations of seismic anisotropy can provide important constraints on mantle flow geometry in subduction systems. The interpretation of seismic anisotropy measurements in subduction settings can be challenging, however, because different parts of the subduction system may contribute, including the overriding plate, the mantle wedge above the slab, the slab itself, and the deep upper mantle beneath the slab. Here we present measurements of shear wave splitting for core phases (SKS, SKKS, PKS, and sSKS), local S, and source-side teleseismic S phases that sample the upper mantle beneath southern Peru and northern Bolivia, relying mostly on data from the CAUGHT experiment. We find evidence for seismic anisotropy within most portions of the subduction system, although the overriding plate itself likely makes only a small contribution to the observed delay times. Average fast orientations generally trend roughly trench-parallel to trench-oblique, contradicting predictions from the simplest two-dimensional flow models and olivine fabric scenarios. Our measurements suggest complex, layered anisotropy beneath the northern portion of the Central Andean Plateau, with significant departures from a two-dimensional mantle flow regime