Linguistic alignment and theory of mind impairments in schizophrenia patients' dialogic interactions

BACKGROUND: Impairments of contextual processing and theory of mind (ToM) have both been offered as accounts of the deviant language characterising formal thought disorder (FTD) in schizophrenia. This study investigated these processes in patients' dialogue. We predicted that FTD patients would show a decrement in linguistic alignment, associated with impaired ToM in dialogue. METHODS: Speech samples were elicited via participation in an interactive computer-based task and a semi-structured interview to assess contextual processing abilities and ToM skills in dialogue, respectively, and from an interactive card-sorting task to measure syntactic alignment. Degree of alignment in dialogue and the syntactic task, and evidence of ToM in (i) dialogue and (ii) a traditional ToM task were compared across schizophrenia patients with FTD (n = 21), non-FTD patients (n = 22) and healthy controls (n = 21). RESULTS: FTD patients showed less alignment than the other two groups in dialogue, and than healthy controls on the syntactic task. FTD patients showed poorer performance on the ToM task than the other two groups, but only compared to the healthy controls in dialogue. The FTD group's degree of alignment in dialogue was correlated with ToM performance in dialogue but not with the traditional ToM task or with syntactic alignment. CONCLUSIONS: In dialogue, FTD patients demonstrate an impairment in employing available contextual information to facilitate their own subsequent production, which is associated with a ToM deficit. These findings indicate that a contextual processing deficit impacts on exploiting representations via the production system impoverishing the ability to make predictions about upcoming utterances in dialogue

Spatial heterogeneity and peptide availability determine CTL killing efficiency in vivo

The rate at which a cytotoxic T lymphocyte (CTL) can survey for infected cells is a key ingredient of models of vertebrate immune responses to intracellular pathogens. Estimates have been obtained using in vivo cytotoxicity assays in which peptide-pulsed splenocytes are killed by CTL in the spleens of immunised mice. However the spleen is a heterogeneous environment and splenocytes comprise multiple cell types. Are some cell types intrinsically more susceptible to lysis than others? Quantitatively, what impacts are made by the spatial distribution of targets and effectors, and the level of peptide-MHC on the target cell surface? To address these questions we revisited the splenocyte killing assay, using CTL specific for an epitope of influenza virus. We found that at the cell population level T cell targets were killed more rapidly than B cells. Using modeling, quantitative imaging and in vitro killing assays we conclude that this difference in vivo likely reflects different migratory patterns of targets within the spleen and a heterogeneous distribution of CTL, with no detectable difference in the intrinsic susceptibilities of the two populations to lysis. Modeling of the stages involved in the detection and killing of peptide-pulsed targets in vitro revealed that peptide dose influenced the ability of CTL to form conjugates with targets but had no detectable effect on the probability that conjugation resulted in lysis, and that T cell targets took longer to lyse than B cells. We also infer that incomplete killing in vivo of cells pulsed with low doses of peptide may be due to a combination of heterogeneity in peptide uptake and the dissociation, but not internalisation, of peptide-MHC complexes. Our analyses demonstrate how population-averaged parameters in models of immune responses can be dissected to account for both spatial and cellular heterogeneity

Binary Fission, Telotroch Formation and Conjugation in Mantoscyphidia Jankowski, 1980 (Ciliophora: Peritrichia)

Mantoscyphidians occur in high numbers on the gills of South African Haliotis and limpet species. This provided the ideal opportunity to study asexual and sexual reproduction, for the first time in different African Mantoscyphidia Jankowski, 1985 populations. Descriptions of the reproductive processes found in scyphidiid peritrichs were until now, mostly based on line drawings. Scanning electronand light microscopy contributed uniquely, in providing detail information regarding binary fission, telotroch formation and conjugation. Mantoscyphidia spadiceae Botes, Basson and Van As, 2001 shed the most light on binary fission. Micronuclear division occurred first with the plane of fission already evident and macronuclear cleavage ended just before final separation took place. Fission is not complete until a small string of pellicle that joins the daughter cells finally separates. Information on telotroch development was gathered from M. branchi Van As, Basson and Van As, 1998 and M. spadiceae populations. Telotrochs were between 36.7 and 38.6% shorter than live, extended mantoscyphidians and their swimming action resembled mobiline peritrichs. Mantoscyphidia branchi populations also proved to be most useful for conjugation studies. Conjugation included three progamic nuclear divisions and preceded synkaryon formation and two metagamic nuclear divisions. The process required 24 hours to be completed

Sedentary time and markers of inflammation in people with newly diagnosed type 2 diabetes

This is the final version. Available on open access from Elsevier via the DOI in this recordBACKGROUND AND AIMS: We investigated whether objectively measured sedentary time was associated with markers of inflammation in adults with newly diagnosed type 2 diabetes. METHODS AND RESULTS: We studied 285 adults (184 men, 101 women, mean age 59.0 ± 9.7) who had been recruited to the Early ACTivity in Diabetes (Early ACTID) randomised controlled trial. C-reactive protein (CRP), adiponectin, soluble intracellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and accelerometer-determined sedentary time and moderate-vigorous physical activity (MVPA) were measured at baseline and after six-months. Linear regression analysis was used to investigate the independent cross-sectional and longitudinal associations of sedentary time with markers of inflammation. At baseline, associations between sedentary time and IL-6 were observed in men and women, an association that was attenuated following adjustment for waist circumference. After 6 months of follow-up, sedentary time was reduced by 0.4 ± 1.2 h per day in women, with the change in sedentary time predicting CRP at follow-up. Every hour decrease in sedentary time between baseline and six-months was associated with 24% (1, 48) lower CRP. No changes in sedentary time between baseline and 6 months were seen in men. CONCLUSIONS: Higher sedentary time is associated with IL-6 in men and women with type 2 diabetes, and reducing sedentary time is associated with improved levels of CRP in women. Interventions to reduce sedentary time may help to reduce inflammation in women with type 2 diabetes.National Institute for Health Research (NIHR

End-to-End Joint Antenna Selection Strategy and Distributed Compress and Forward Strategy for Relay Channels

Multi-hop relay channels use multiple relay stages, each with multiple relay nodes, to facilitate communication between a source and destination. Previously, distributed space-time codes were proposed to maximize the achievable diversity-multiplexing tradeoff, however, they fail to achieve all the points of the optimal diversity-multiplexing tradeoff. In the presence of a low-rate feedback link from the destination to each relay stage and the source, this paper proposes an end-to-end antenna selection (EEAS) strategy as an alternative to distributed space-time codes. The EEAS strategy uses a subset of antennas of each relay stage for transmission of the source signal to the destination with amplify and forwarding at each relay stage. The subsets are chosen such that they maximize the end-to-end mutual information at the destination. The EEAS strategy achieves the corner points of the optimal diversity-multiplexing tradeoff (corresponding to maximum diversity gain and maximum multiplexing gain) and achieves better diversity gain at intermediate values of multiplexing gain, versus the best known distributed space-time coding strategies. A distributed compress and forward (CF) strategy is also proposed to achieve all points of the optimal diversity-multiplexing tradeoff for a two-hop relay channel with multiple relay nodes.Comment: Accepted for publication in the special issue on cooperative communication in the Eurasip Journal on Wireless Communication and Networkin

Epidemic space

The aim of this article is to highlight the importance of 'spatiality' in understanding the materialization of risk society and cultivation of risk sensibilities. More specifically it provides a cultural analysis of pathogen virulence (as a social phenomenon) by means of tracing and mapping the spatial flows that operate in the uncharted zones between the microphysics of infection and the macrophysics of epidemics. It will be argued that epidemic space consists of three types of forces: the vector, the index and the vortex. It will draw on Latour's Actor Network Theory to argue that epidemic space is geared towards instability when the vortex (of expanding associations and concerns) displaces the index (of finding a single cause)

Activation of peroxisome proliferator-activated receptors by chlorinated hydrocarbons and endogenous steroids.

Trichloroethylene (TCE) and related hydrocarbons constitute an important class of environmental pollutants whose adverse effects on liver, kidney, and other tissues may, in part, be mediated by peroxisome proliferator-activated receptors (PPARs), ligand-activated transcription factors belonging to the steroid receptor superfamily. Activation of PPAR induces a dramatic proliferation of peroxisomes in rodent hepatocytes and ultimately leads to hepatocellular carcinoma. To elucidate the role of PPAR in the pathophysiologic effects of TCE and its metabolites, it is important to understand the mechanisms whereby PPAR is activated both by TCE and endogenous peroxisome proliferators. The investigations summarized in this article a) help clarify the mechanism by which TCE and its metabolites induce peroxisome proliferation and b) explore the potential role of the adrenal steroid and anticarcinogen dehydroepiandrosterone 3beta-sulfate (DHEA-S) as an endogenous PPAR activator. Transient transfection studies have demonstrated that the TCE metabolites trichloroacetate and dichloroacetate both activate PPAR alpha, a major liver-expressed receptor isoform. TCE itself was inactive when tested over the same concentration range, suggesting that its acidic metabolites mediate the peroxisome proliferative potential of TCE. Although DHEA-S is an active peroxisome proliferator in vivo, this steroid does not stimulate trans-activation of PPAR alpha or of two other PPAR isoforms, gamma and delta/Nuc1, when evaluated in COS-1 cell transfection studies. To test whether PPAR alpha mediates peroxisomal gene induction by DHEA-S in intact animals, DHEA-S has been administered to mice lacking a functional PPAR alpha gene. DHEA-S was thus shown to markedly increase hepatic expression of two microsomal P4504A proteins associated with the peroxisomal proliferative response in wild-type mice. In contrast, DHEA-S did not induce these hepatic proteins in PPAR alpha-deficient mice. Thus, despite its unresponsiveness to steroidal peroxisome proliferators in transfection assays, PPAR alpha is an obligatory mediator of DHEA-S-stimulated hepatic peroxisomal gene induction. DHEA-S, or one of its metabolites, may thus serve as an important endogenous regulator of liver peroxisomal enzyme expression

The missions of medical schools: the pursuit of health in the service of society

Mission statements and role documents of medical schools in the United Kingdom, United States, Canada and Australia have been examined on their Internet Web sites and categorised in purpose, content and presentation. The format and content are highly variable, but there is a common vision of three integral roles, namely, education, advancement of knowledge and service to society. Other frequent themes include tradition and historical perspective, service for designated communities, and benchmarking to accreditation standards. Differences in content reflect variable interpretation of the notion of "mission", and local or national characteristics such as institutional affiliations, the types, levels and organisation of medical education, relationships with health systems, and extent of multi-professional education. Outcomes data and measures of medical school performance referenced to the institution's stated missions are rarely encountered. Mission documents placed on the Internet are in the public domain. These Web sites and documents and linked information constitute a valuable new resource for international exchange of approaches and ideas in medical education and generally in academic medicine. Routine inclusion of outcome or performance data could help to demonstrate the community roles and social accountability of medical schools This paper proposes that partial standardisation of these Web documents could enhance their value both internally and for external readers. A generic descriptive statement template is offered