Word predictability depends on parafoveal preview validity in Chinese reading

Research with alphabetic scripts shows that providing an invalid parafoveal preview eliminates or diminishes effects of contextual predictability on word identification, revealing that such effects depend on the interplay between top-down contextual expectations and bottom-up perceptual information. Whether similar effects are observed in character-based scripts like Chinese is unknown. However, such knowledge would extend our understanding of contextual prediction in different writing systems. Accordingly, we conducted an eye movement experiment using the boundary paradigm to assess contextual predictability effects on the processing of target words with valid and invalid parafoveal previews. Interactions between predictability and preview validity were observed in early reading times but not word-skipping for targets. This suggests an interplay between top-down and bottom-up processes drives contextual processing in Chinese reading, but that word-skipping is not strongly mediated by contextual expectations in this script. We consider these findings in relation to differences between alphabetic and non-alphabetic writing systems

The assertive cardiac care trial: A randomised controlled trial of a coproduced assertive cardiac care intervention to reduce absolute cardiovascular disease risk in people with severe mental illness in the primary care setting

BACKGROUND: Cardiovascular disease (CVD) accounts for 40% of the excess mortality identified in people with severe mental illness (SMI). Modifiable CVD risk factors are higher and can be exacerbated by the cardiometabolic impact of psychotropic medications. People with SMI frequently attend primary care presenting a valuable opportunity for early identification, prevention and management of cardiovascular health. The ACCT Healthy Hearts Study will test a coproduced, nurse-led intervention delivered with general practitioners to reduce absolute CVD risk (ACVDR) at 12 months compared with an active control group. METHODS/DESIGN: ACCT is a two group (intervention/active control) individually randomised (1:1) controlled trial (RCT). Assessments will be completed baseline (pre-randomisation), 6 months, and 12 months. The primary outcome is 5-year ACVDR measured at 12 months. Secondary outcomes include 6-month ACVDR; and blood pressure, lipids, HbA1c, BMI, quality of life, physical activity, motivation to change health behaviour, medication adherence, alcohol use and hospitalisation at 6 and 12 months. Linear mixed-effects regression will estimate mean difference between groups for primary and secondary continuous outcomes. Economic cost-consequences analysis will be conducted using quality of life and health resource use information and routinely collected government health service use and medication data. A parallel process evaluation will investigate implementation of the intervention, uptake and outcomes. DISCUSSION: ACCT will deliver a coproduced and person-centred, guideline level cardiovascular primary care intervention to a high need population with SMI. If successful, the intervention could lead to the reduction of the mortality gap and increase opportunities for meaningful social and economic participation. Trial registration ANZCTR Trial number: ACTRN12619001112156

Novel CCL21-Vault Nanocapsule Intratumoral Delivery Inhibits Lung Cancer Growth

Based on our preclinical findings, we are assessing the efficacy of intratumoral injection of dendritic cells (DC) transduced with an adenoviral vector expressing the secondary lymphoid chemokine (CCL21) gene (Ad-CCL21-DC) in a phase I trial in advanced non-small cell lung cancer (NSCLC). While this approach shows immune enhancement, the preparation of autologous DC for CCL21 genetic modification is cumbersome, expensive and time consuming. We are evaluating a non-DC based approach which utilizes vault nanoparticles for intratumoral CCL21 delivery to mediate antitumor activity in lung cancer.Here we describe that vault nanocapsule platform for CCL21 delivery elicits antitumor activity with inhibition of lung cancer growth. Vault nanocapsule packaged CCL21 (CCL21-vaults) demonstrated functional activity in chemotactic and antigen presenting activity assays. Recombinant vaults impacted chemotactic migration of T cells and this effect was predominantly CCL21 dependent as CCL21 neutralization abrogated the CCL21 mediated enhancement in chemotaxis. Intratumoral administration of CCL21-vaults in mice bearing lung cancer enhanced leukocytic infiltrates (CXCR3(+)T, CCR7(+)T, IFNγ(+)T lymphocytes, DEC205(+) DC), inhibited lung cancer tumor growth and reduced the frequencies of immune suppressive cells [myeloid derived suppressor cells (MDSC), T regulatory cells (Treg), IL-10 T cells]. CCL21-vaults induced systemic antitumor responses by augmenting splenic T cell lytic activity against parental tumor cells.This study demonstrates that the vault nanocapsule can efficiently deliver CCL21 to sustain antitumor activity and inhibit lung cancer growth. The vault nanocapsule can serve as an "off the shelf" approach to deliver antitumor cytokines to treat a broad range of malignancies

The assertive cardiac care trial: a randomised controlled trial of a coproduced assertive cardiac care intervention to reduce absolute cardiovascular disease risk in people with severe mental illness in the primary care setting

Background: Cardiovascular disease (CVD) accounts for 40% of the excess mortality identified in people with severe mental illness (SMI). Modifiable CVD risk factors are higher and can be exacerbated by the cardiometabolic impact of psychotropic medications. People with SMI frequently attend primary care presenting a valuable opportunity for early identification, prevention and management of cardiovascular health. The ACCT Healthy Hearts Study will test a coproduced, nurse-led intervention delivered with general practitioners to reduce absolute CVD risk (ACVDR) at 12 months compared with an active control group. Methods/design: ACCT is a two group (intervention/active control) individually randomised (1:1) controlled trial (RCT). Assessments will be completed baseline (pre-randomisation), 6 months, and 12 months. The primary outcome is 5-year ACVDR measured at 12 months. Secondary outcomes include 6-month ACVDR; and blood pressure, lipids, HbA1c, BMI, quality of life, physical activity, motivation to change health behaviour, medication adherence, alcohol use and hospitalisation at 6 and 12 months. Linear mixed-effects regression will estimate mean difference between groups for primary and secondary continuous outcomes. Economic cost-consequences analysis will be conducted using quality of life and health resource use information and routinely collected government health service use and medication data. A parallel process evaluation will investigate implementation of the intervention, uptake and outcomes. Discussion: ACCT will deliver a coproduced and person-centred, guideline level cardiovascular primary care intervention to a high need population with SMI. If successful, the intervention could lead to the reduction of the mortality gap and increase opportunities for meaningful social and economic participation

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Evolution of a Bacterial Regulon Controlling Virulence and Mg2+ Homeostasis

Related organisms typically rely on orthologous regulatory proteins to respond to a given signal. However, the extent to which (or even if) the targets of shared regulatory proteins are maintained across species has remained largely unknown. This question is of particular significance in bacteria due to the widespread effects of horizontal gene transfer. Here, we address this question by investigating the regulons controlled by the DNA-binding PhoP protein, which governs virulence and Mg2+ homeostasis in several bacterial species. We establish that the ancestral PhoP protein directs largely different gene sets in ten analyzed species of the family Enterobacteriaceae, reflecting both regulation of species-specific targets and transcriptional rewiring of shared genes. The two targets directly activated by PhoP in all ten species (the most distant of which diverged >200 million years ago), and coding for the most conserved proteins are the phoPQ operon itself and the lipoprotein-encoding slyB gene, which decreases PhoP protein activity. The Mg2+-responsive PhoP protein dictates expression of Mg2+ transporters and of enzymes that modify Mg2+-binding sites in the cell envelope in most analyzed species. In contrast to the core PhoP regulon, which determines the amount of active PhoP and copes with the low Mg2+ stress, the variable members of the regulon contribute species-specific traits, a property shared with regulons controlled by dissimilar regulatory proteins and responding to different signals

Evolution of a Bacterial Regulon Controlling Virulence and Mg2+ Homeostasis

Related organisms typically rely on orthologous regulatory proteins to respond to a given signal. However, the extent to which (or even if) the targets of shared regulatory proteins are maintained across species has remained largely unknown. This question is of particular significance in bacteria due to the widespread effects of horizontal gene transfer. Here, we address this question by investigating the regulons controlled by the DNA-binding PhoP protein, which governs virulence and Mg2+ homeostasis in several bacterial species. We establish that the ancestral PhoP protein directs largely different gene sets in ten analyzed species of the family Enterobacteriaceae, reflecting both regulation of species-specific targets and transcriptional rewiring of shared genes. The two targets directly activated by PhoP in all ten species (the most distant of which diverged >200 million years ago), and coding for the most conserved proteins are the phoPQ operon itself and the lipoprotein-encoding slyB gene, which decreases PhoP protein activity. The Mg2+-responsive PhoP protein dictates expression of Mg2+ transporters and of enzymes that modify Mg2+-binding sites in the cell envelope in most analyzed species. In contrast to the core PhoP regulon, which determines the amount of active PhoP and copes with the low Mg2+ stress, the variable members of the regulon contribute species-specific traits, a property shared with regulons controlled by dissimilar regulatory proteins and responding to different signals

HIV-induced immune activation - pathogenesis and clinical relevance. Summary of a workshop organised by the German AIDs Society (DAIG e.v.) and the ICH Hamburg, Hamburg, Germany, November 22, 2008

This manuscript is communicated by the German AIDS Society (DAIG) http://www.daignet.de. It summarizes a series of presentations and discussions during a workshop on immune activation due to HIV infection. The workshop was held on November 22nd 2008 in Hamburg, Germany. It was organized by the ICH Hamburg under the auspices of the German AIDS Society (DAIG e.V.)

Diabetes self-management arrangements in Europe: a realist review to facilitate a project implemented in six countries

Background: Self-management of long term conditions can promote quality of life whilst delivering benefits to the financing of health care systems. However, rarely are the meso-level influences, likely to be of direct relevance to these desired outcomes, systematically explored. No specific international guidelines exist suggesting the features of the most appropriate structure and organisation of health care systems within which to situate self-management approaches and practices. This review aimed to identify the quantitative literature with regard to diabetes self-management arrangements currently in place within the health care systems of six countries (The United Kingdom, The Netherlands, Norway, Spain, Bulgaria, and Greece) and explore how these are integrated into the broader health care and welfare systems in each country. Methods: The methodology for a realist review was followed. Publications of interest dating from 2000 to 2013 were identified through appropriate MeSH terms by a systematic search in six bibliographic databases. A search diary was maintained and the studies were assessed for their quality and risk of bias. Results: Following the multi-step search strategy, 56 studies were included in the final review (the majority from the UK) reporting design methods and findings on 21 interventions and programmes for diabetes and chronic disease self-management. Most (11/21, 52%) of the interventions were designed to fit within the context of primary care. The majority (11/21, 52%) highlighted behavioural change as an important goal. Finally, some (5/21, 24%) referred explicitly to Internet-based tools. Conclusions: This review is based on results which are derived from a total of at least 5,500 individuals residing in the six participating countries. It indicates a policy shift towards patient-centred self-management of diabetes in a primary care context. The professional role of diabetes specialist nurses, the need for multidisciplinary approaches and a focus on patient education emerge as fundamental principles in the design of relevant programmes. Socio-economic circumstances are relevant to the capacity to self-manage and suggest that any gains and progress will be hard to maintain during economic austerity. This realist review should be interpreted within the wider context of a whole systems approach regarding self-care support and chronic illness management