Sequential effects of propofol on functional brain activation induced by auditory language processing: an event‐related functional magnetic resonance imaging study

Background. We have investigated the effect of propofol on language processing using event‐related functional magnetic resonance imaging (MRI). Methods. Twelve healthy male volunteers underwent MRI scanning at a magnetic field strength of 3 Tesla while performing an auditory language processing task. Functional images were acquired from the perisylvian cortical regions that are associated with auditory and language processing. The experiment consisted of three blocks: awake state (block 1), induction of anaesthesia with 3 mg kg-1 propofol (block 2), and maintenance of anaesthesia with 3 mg kg-1 h-1 propofol (block 3). During each block normal sentences and pseudo‐word sentences were presented in random order. The subjects were instructed to press a button to indicate whether a sentence was made up of pseudo‐words or not. All subjects stopped responding during block two. The data collected before and after the subjects stopped responding during this block were analyzed separately. In addition, propofol plasma concentrations were measured and the effect‐site concentrations of propofol were calculated. Results. During wakefulness, language processing induced brain activation in a widely distributed temporofrontal network. Immediately after unresponsiveness, activation disappeared in frontal areas but persisted in both temporal lobes (block 2 second half, propofol effect‐site concentration: 1.51 µg ml-1). No activation differences related to the task were observed during block 3 (propofol effect‐site concentration: 4.35 µg ml-1). Conclusion. Our findings suggest sequential effects of propofol on auditory language processing networks. Brain activation firstly declines in the frontal lobe before it disappears in the temporal lobe. Br J Anaesth 2004; 92: 641-5

Comment on ``Protective measurements of the wave function of a single squeezed harmonic-oscillator state''

Alter and Yamamoto [Phys. Rev. A 53, R2911 (1996)] claimed to consider ``protective measurements'' [Phys. Lett. A 178, 38 (1993)] which we have recently introduced. We show that the measurements discussed by Alter and Yamamoto ``are not'' the protective measurements we proposed. Therefore, their results are irrelevant to the nature of protective measurements.Comment: 2 pages LaTe

PANIC: the new panoramic NIR camera for Calar Alto

PANIC is a wide-field NIR camera, which is currently under development for the Calar Alto observatory (CAHA) in Spain. It uses a mosaic of four Hawaii-2RG detectors and covers the spectral range from 0.8-2.5 micron(z to K-band). The field-of-view is 30x30 arcmin. This instrument can be used at the 2.2m telescope (0.45arcsec/pixel, 0.5x0.5 degree FOV) and at the 3.5m telescope (0.23arcsec/pixel, 0.25x0.25 degree FOV). The operating temperature is about 77K, achieved by liquid Nitrogen cooling. The cryogenic optics has three flat folding mirrors with diameters up to 282 mm and nine lenses with diameters between 130 mm and 255 mm. A compact filter unit can carry up to 19 filters distributed over four filter wheels. Narrow band (1%) filters can be used. The instrument has a diameter of 1.1 m and it is about 1 m long. The weight limit of 400 kg at the 2.2m telescope requires a light-weight cryostat design. The aluminium vacuum vessel and radiation shield have wall thicknesses of only 6 mm and 3 mm respectively.Comment: This paper has been presented in the SPIE of Astronomical Telescopes and Instrumentation 2008 in Marseille (France

Law, Market Building and Public Health in the European Union

European Union (EU) law is based upon a liberalising imperative, the goal of which is to construct a single market between member states. Yet the EU is no ordinary trade pact, incorporating as it does a range of supranational political institutions and common policies in a range of areas beyond simple market building. Scholars have nevertheless noted a distinction between ‘positive’ integration (the formulation of common policies applying to all member states) and ‘negative’ integration (the removal of national-level regulations acting as barriers to market integration). In the context of debates about the implications of trade law and corporate activity for health, this article poses three related questions. First, to what extent does EU law afford corporations opportunities to challenge national-level health regulations? Second, to what extent do EU legal and political processes provide opportunities for positive pro-health supranational regulation, including that which might offset the effects of negative liberalising integration? Third, how do EU market-building processes differ from those of more narrowly-drawn trade agreements and organisations in their implications for health? We analyse and compare two recent sets of health-related legal proceedings under EU law, the first of which challenges legislation passed by the Scottish Government to introduce minimum unit pricing for alcohol, and the second of which addresses the legality of specific aspects of the EU’s 2014 Tobacco Products Directive. We find, first, that EU law offers ample opportunities for corporations to challenge national health regulations; second, that there is significant scope for pro-health supranational regulations, but that these must be couched in the language of facilitating the single market, and are dependent on the political commitment of key policy actors; and, third, that this (limited) scope for pro-health supranational regulation distinguishes EU legal and political processes from those of other trade agreements and organisations

OnabotulinumtoxinA muscle injection patterns in adult spasticity: a systematic literature review

BACKGROUND: OnabotulinumtoxinA has demonstrated significant benefit in adult focal spasticity. This study reviews the injection patterns (i.e., muscle distribution, dosing) of onabotulinumtoxinA for treatment of adult spasticity, as reported in published studies. METHODS: A systematic review of clinical trials and observational studies published between 1990 and 2011 reporting data on muscles injected with onabotulinumtoxinA in adult patients treated for any cause of spasticity. RESULTS: 28 randomized, 5 nonrandomized, and 37 single-arm studies evaluating 2,163 adult patients were included. The most frequently injected upper-limb muscles were flexor carpi radialis (64.0% of patients), flexor carpi ulnaris (59.1%), flexor digitorum superficialis (57.2%), flexor digitorum profundus (52.5%), and biceps brachii (38.8%). The most frequently injected lower-limb muscles were the gastrocnemius (66.1% of patients), soleus (54.7%), and tibialis posterior (50.5%). The overall dose range reported was 5–200 U for upper-limb muscles and 10–400 U for lower-limb muscles. CONCLUSIONS: The reviewed evidence indicates that the muscles most frequently injected with onabotulinumtoxinA in adults with spasticity were the wrist, elbow, and finger flexors and the ankle plantar flexors. OnabotulinumtoxinA was injected over a broad range of doses per muscle among the studies included in this review, but individual practitioners should be mindful of local regulatory approvals and regulations

Chronic HCV Infection Affects the NK Cell Phenotype in the Blood More than in the Liver

Although epidemiological and functional studies have implicated NK cells in protection and early clearance of HCV, the mechanism by which they may contribute to viral control is poorly understood, particularly at the site of infection, the liver. We hypothesized that a unique immunophenotypic/functional NK cell signature exists in the liver that may provide insights into the contribution of NK cells to viral control. Intrahepatic and blood NK cells were profiled from chronically infected HCV-positive and HCV-negative individuals. Baseline expression of activating and inhibitory receptors was assessed, as well as functional responses following stimulation through classic NK cell pathways. Independent of HCV infection, the liver was enriched for the immunoregulatory CD56bright NK cell population, which produced less IFNγ and CD107a but comparable levels of MIP1β, and was immunophenotypically distinct from their blood counterparts. This profile was mostly unaltered in chronic HCV infection, though different expression levels of NKp46 and NKG2D were associated with different grades of fibrosis. In contrast to the liver, chronic HCV infection associated with an enrichment of CD161lowperforinhigh NK cells in the blood correlated with increased AST and 2B4 expression. However, the association of relatively discrete changes in the NK cell phenotype in the liver with the fibrosis stage nevertheless suggests an important role for the NK response. Overall these data suggest that tissue localization has a more pervasive effect on NK cells than the presence of chronic viral infection, during which these cells might be mostly attuned to limiting immunopathology. It will be important to characterize NK cells during early HCV infection, when they should have a critical role in limiting infection

Neutralizing antibody response during acute and chronic hepatitis C virus infection

Little is known about the role of Abs in determining the outcome of hepatitis C virus (HCV) infection. By using infectious retroviral pseudotypes bearing HCV glycoproteins, we measured neutralizing Ab (nAb) responses during acute and chronic HCV infection. In seven acutely infected health care workers, only two developed a nAb response that failed to associate with viral clearance. In contrast, the majority of chronically infected patients had nAbs. To determine the kinetics of strain-specific and crossreactive nAb emergence, we studied patient H, the source of the prototype genotype 1a H77 HCV strain. An early weak nAb response, specific for the autologous virus, was detected at seroconversion. However, neutralization of heterologous viruses was detected only between 33 and 111 weeks of infection. We also examined the development of nAbs in 10 chimpanzees infected with H77 clonal virus. No nAb responses were detected in three animals that cleared virus, whereas strain-specific nAbs were detected in six of the seven chronically infected animals after approximately 50 weeks of infection. The delayed appearance of high titer crossreactive nAbs in chronically infected patients suggests that selective mechanism(s) may operate to prevent the appearance of these Abs during acute infection. The long-term persistence of these nAbs in chronically infected patients may regulate viral replication

Exploring leadership in multi-sectoral partnerships

This article explores some critical aspects of leadership in the context of multi-sectoral partnerships. It focuses on leadership in practice and asks the question, `How do managers experience and perceive leadership in such partnerships?' The study contributes to the debate on whether leadership in a multi-sectoral partnership context differs from that within a single organization. It is based on the accounts of practising managers working in complex partnerships. The article highlights a number of leadership challenges faced by those working in multi-sectoral partnerships. Partnership practitioners were clear that leadership in partnerships was more complex than in single organizations. However, it was more difficult for them to agree a consensus on the essential nature of leadership in partnership. We suggest that a first-, second- and third-person approach might be a way of better interpreting leadership in the context of partnerships

A Novel Unsupervised Method to Identify Genes Important in the Anti-viral Response: Application to Interferon/Ribavirin in Hepatitis C Patients

Background: Treating hepatitis C with interferon/ribavirin results in a varied response in terms of decrease in viral titer and ultimate outcome. Marked responders have a sharp decline in viral titer within a few days of treatment initiation, whereas in other patients there is no effect on the virus (poor responders). Previous studies have shown that combination therapy modifies expression of hundreds of genes in vitro and in vivo. However, identifying which, if any, of these genes have a role in viral clearance remains challenging. Aims: The goal of this paper is to link viral levels with gene expression and thereby identify genes that may be responsible for early decrease in viral titer. Methods: Microarrays were performed on RNA isolated from PBMC of patients undergoing interferon/ribavirin therapy. Samples were collected at pre-treatment (day 0), and 1, 2, 7, 14 and 28 days after initiating treatment. A novel method was applied to identify genes that are linked to a decrease in viral titer during interferon/ribavirin treatment. The method uses the relationship between inter-patient gene expression based proximities and inter-patient viral titer based proximities to define the association between microarray gene expression measurements of each gene and viral-titer measurements. Results: We detected 36 unique genes whose expressions provide a clustering of patients that resembles viral titer based clustering of patients. These genes include IRF7, MX1, OASL and OAS2, viperin and many ISG's of unknown function. Conclusion: The genes identified by this method appear to play a major role in the reduction of hepatitis C virus during the early phase of treatment. The method has broad utility and can be used to analyze response to any group of factors influencing biological outcome such as antiviral drugs or anti-cancer agents where microarray data are available. © 2007 Brodsky et al

Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli

The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN). By comparing this network with measured gene expression data one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with less changes in their expression pattern have a higher fraction of feed-forward loop motifs and a lower fraction of small RNA targets within them. Our study implies that the TRN consists of several scales of regulatory organization: 1) subnets with more varying gene expression controlled by both transcription factors and post-transcriptional RNA regulation, and 2) subnets with less varying gene expression having more feed-forward loops and less post-transcriptional RNA regulation.Comment: 14 pages, 8 figures, to be published in PLoS Computational Biolog