Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression.

Several studies have proposed that brain glutamate signaling abnormalities and glial pathology have a role in the etiology of major depressive disorder (MDD). These conclusions were primarily drawn from post-mortem studies in which forebrain brain regions were examined. The locus coeruleus (LC) is the primary source of extensive noradrenergic innervation of the forebrain and as such exerts a powerful regulatory role over cognitive and affective functions, which are dysregulated in MDD. Furthermore, altered noradrenergic neurotransmission is associated with depressive symptoms and is thought to have a role in the pathophysiology of MDD. In the present study we used laser-capture microdissection (LCM) to selectively harvest LC tissue from post-mortem brains of MDD patients, patients with bipolar disorder (BPD) and from psychiatrically normal subjects. Using microarray technology we examined global patterns of gene expression. Differential mRNA expression of select candidate genes was then interrogated using quantitative real-time PCR (qPCR) and in situ hybridization (ISH). Our findings reveal multiple signaling pathway alterations in the LC of MDD but not BPD subjects. These include glutamate signaling genes, SLC1A2, SLC1A3 and GLUL, growth factor genes FGFR3 and TrkB, and several genes exclusively expressed in astroglia. Our data extend previous findings of altered glutamate, astroglial and growth factor functions in MDD for the first time to the brainstem. These findings indicate that such alterations: (1) are unique to MDD and distinguishable from BPD, and (2) affect multiple brain regions, suggesting a whole-brain dysregulation of such functions

Pandemic influenza preparedness: an ethical framework to guide decision-making

BACKGROUND: Planning for the next pandemic influenza outbreak is underway in hospitals across the world. The global SARS experience has taught us that ethical frameworks to guide decision-making may help to reduce collateral damage and increase trust and solidarity within and between health care organisations. Good pandemic planning requires reflection on values because science alone cannot tell us how to prepare for a public health crisis. DISCUSSION: In this paper, we present an ethical framework for pandemic influenza planning. The ethical framework was developed with expertise from clinical, organisational and public health ethics and validated through a stakeholder engagement process. The ethical framework includes both substantive and procedural elements for ethical pandemic influenza planning. The incorporation of ethics into pandemic planning can be helped by senior hospital administrators sponsoring its use, by having stakeholders vet the framework, and by designing or identifying decision review processes. We discuss the merits and limits of an applied ethical framework for hospital decision-making, as well as the robustness of the framework. SUMMARY: The need for reflection on the ethical issues raised by the spectre of a pandemic influenza outbreak is great. Our efforts to address the normative aspects of pandemic planning in hospitals have generated interest from other hospitals and from the governmental sector. The framework will require re-evaluation and refinement and we hope that this paper will generate feedback on how to make it even more robust

Magnetized Domain Walls in the Deconfined Sakai-Sugimoto Model at Finite Baryon Density

The magnetized pure pion gradient ($\mathcal{5}\phi$) phase in the deconfined Sakai-Sugimoto model is explored at zero and finite temperature. We found that the temperature has very small effects on the phase. The thermodynamical properties of the phase shows that the excitations behave like a scalar solitonic free particles. By comparing the free energy of the pion gradient phase to the competing multiquark-pion gradient (MQ-$\mathcal{5}\phi$) phase, it becomes apparent that the pure pion gradient is less thermodynamically preferred than the MQ-$\mathcal{5}\phi$ phase. However, in the parameter space where the baryonic chemical potential is smaller than the onset value of the multiquark, the dominating magnetized nuclear matter is the pion gradient phase.Comment: 20 pages, 9 figure

A video life-world approach to consultation practice: The relevance of a socio-phenomenological approach

This article discusses the [development and] use of a video life-world schema to explore alternative orientations to the shared health consultation. It is anticipated that this schema can be used by practitioners and consumers alike to understand the dynamics of videoed health consultations, the role of the participants within it and the potential to consciously alter the outcome by altering behaviour during the process of interaction. The study examines health consultation participation and develops an interpretative method of analysis that includes image elicitation (via videos), phenomenology (to identify the components of the analytic framework), narrative (to depict the stories of interactions) and a reflexive mode (to develop shared meaning through a conceptual framework for analysis). The analytic framework is derived from a life-world conception of human mutual shared interaction which is presented here as a novel approach to understanding patient-centred care. The video materials used in this study were derived from consultations in a Walk-in Centre (WiC) in East London. The conceptual framework produced through the process of video analysis is comprised of different combinations of movement, knowledge and emotional conversations that are used to classify objective or engaged WiC health care interactions. The videoed interactions organise along an active or passive, facilitative or directive typical situation continuum illustrating different kinds of textual approaches to practice that are in tension or harmony. The schema demonstrates how practitioners and consumers interact to produce these outcomes and indicates the potential for both consumers and practitioners to be educated to develop practice dynamics that support patient-centred care and impact on health outcomes

Anomalies and the chiral magnetic effect in the Sakai-Sugimoto model

In the chiral magnetic effect an imbalance in the number of left- and right-handed quarks gives rise to an electromagnetic current parallel to the magnetic field produced in noncentral heavy-ion collisions. The chiral imbalance may be induced by topologically nontrivial gluon configurations via the QCD axial anomaly, while the resulting electromagnetic current itself is a consequence of the QED anomaly. In the Sakai-Sugimoto model, which in a certain limit is dual to large-N_c QCD, we discuss the proper implementation of the QED axial anomaly, the (ambiguous) definition of chiral currents, and the calculation of the chiral magnetic effect. We show that this model correctly contains the so-called consistent anomaly, but requires the introduction of a (holographic) finite counterterm to yield the correct covariant anomaly. Introducing net chirality through an axial chemical potential, we find a nonvanishing vector current only before including this counterterm. This seems to imply the absence of the chiral magnetic effect in this model. On the other hand, for a conventional quark chemical potential and large magnetic field, which is of interest in the physics of compact stars, we obtain a nontrivial result for the axial current that is in agreement with previous calculations and known exact results for QCD.Comment: 35 pages, 4 figures, v2: added comments about frequency-dependent conductivity at the end of section 4; references added; version to appear in JHE

Holographic chiral magnetic spiral

We study the ground state of baryonic/axial matter at zero temperature chiral-symmetry broken phase under a large magnetic field, in the framework of holographic QCD by Sakai-Sugimoto. Our study is motivated by a recent proposal of chiral magnetic spiral phase that has been argued to be favored against previously studied phase of homogeneous distribution of axial/baryonic currents in terms of meson super-currents dictated by triangle anomalies in QCD. Our results provide an existence proof of chiral magnetic spiral in strong coupling regime via holography, at least for large axial chemical potentials, whereas we don't find the phenomenon in the case of purely baryonic chemical potential.Comment: 24 pages, 15 figure

Cognitive reserve in granulin-related frontotemporal dementia: from preclinical to clinical stages

OBJECTIVE Consistent with the cognitive reserve hypothesis, higher education and occupation attainments may help persons with neurodegenerative dementias to better withstand neuropathology before developing cognitive impairment. We tested here the cognitive reserve hypothesis in patients with frontotemporal dementia (FTD), with or without pathogenetic granulin mutations (GRN+ and GRN-), and in presymptomatic GRN mutation carriers (aGRN+). METHODS Education and occupation attainments were assessed and combined to define Reserve Index (RI) in 32 FTD patients, i.e. 12 GRN+ and 20 GRN-, and in 17 aGRN+. Changes in functional connectivity were estimated by resting state fMRI, focusing on the salience network (SN), executive network (EN) and bilateral frontoparietal networks (FPNs). Cognitive status was measured by FTD-modified Clinical Dementia Rating Scale. RESULTS In FTD patients higher level of premorbid cognitive reserve was associated with reduced connectivity within the SN and the EN. EN was more involved in FTD patients without GRN mutations, while SN was more affected in GRN pathology. In aGRN+, cognitive reserve was associated with reduced SN. CONCLUSIONS This study suggests that cognitive reserve modulates functional connectivity in patients with FTD, even in monogenic disease. In GRN inherited FTD, cognitive reserve mechanisms operate even in presymptomatic to clinical stages

Chiral Symmetry Breaking and External Fields in the Kuperstein-Sonnenschein Model

A novel holographic model of chiral symmetry breaking has been proposed by Kuperstein and Sonnenschein by embedding non-supersymmetric probe D7 and anti-D7 branes in the Klebanov-Witten background. We study the dynamics of the probe flavours in this model in the presence of finite temperature and a constant electromagnetic field. In keeping with the weakly coupled field theory intuition, we find the magnetic field promotes spontaneous breaking of chiral symmetry whereas the electric field restores it. The former effect is universally known as the "magnetic catalysis" in chiral symmetry breaking. In the presence of an electric field such a condensation is inhibited and a current flows. Thus we are faced with a steady-state situation rather than a system in equilibrium. We conjecture a definition of thermodynamic free energy for this steady-state phase and using this proposal we study the detailed phase structure when both electric and magnetic fields are present in two representative configurations: mutually perpendicular and parallel.Comment: 50 pages, multiple figures, minor typo fixed, references adde

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population