Increasing awareness of gynaecological cancer symptoms: a GP perspective.

In the UK there has been an effort, through the National Awareness and Early Diagnosis Initiative (NAEDI), to increase early stage diagnoses and ultimately cancer survival. Encouraging early symptom presentation through awareness-raising activities in primary care is one method to achieve this goal. Understanding GPs' views about this type of activity, however, is crucial prior to implementation

A Pair of Dopamine Neurons Target the D1-Like Dopamine Receptor DopR in the Central Complex to Promote Ethanol-Stimulated Locomotion in Drosophila

Dopamine is a mediator of the stimulant properties of drugs of abuse, including ethanol, in mammals and in the fruit fly Drosophila. The neural substrates for the stimulant actions of ethanol in flies are not known. We show that a subset of dopamine neurons and their targets, through the action of the D1-like dopamine receptor DopR, promote locomotor activation in response to acute ethanol exposure. A bilateral pair of dopaminergic neurons in the fly brain mediates the enhanced locomotor activity induced by ethanol exposure, and promotes locomotion when directly activated. These neurons project to the central complex ellipsoid body, a structure implicated in regulating motor behaviors. Ellipsoid body neurons are required for ethanol-induced locomotor activity and they express DopR. Elimination of DopR blunts the locomotor activating effects of ethanol, and this behavior can be restored by selective expression of DopR in the ellipsoid body. These data tie the activity of defined dopamine neurons to D1-like DopR-expressing neurons to form a neural circuit that governs acute responding to ethanol

Human place and response learning: navigation strategy selection, pupil size and gaze behavior.

In this study, we examined the cognitive processes and ocular behavior associated with on-going navigation strategy choice using a route learning paradigm that distinguishes between three different wayfinding strategies: an allocentric place strategy, and the egocentric associative cue and beacon response strategies. Participants approached intersections of a known route from a variety of directions, and were asked to indicate the direction in which the original route continued. Their responses in a subset of these test trials allowed the assessment of strategy choice over the course of six experimental blocks. The behavioral data revealed an initial maladaptive bias for a beacon response strategy, with shifts in favor of the optimal configuration place strategy occurring over the course of the experiment. Response time analysis suggests that the configuration strategy relied on spatial transformations applied to a viewpoint-dependent spatial representation, rather than direct access to an allocentric representation. Furthermore, pupillary measures reflected the employment of place and response strategies throughout the experiment, with increasing use of the more cognitively demanding configuration strategy associated with increases in pupil dilation. During test trials in which known intersections were approached from different directions, visual attention was directed to the landmark encoded during learning as well as the intended movement direction. Interestingly, the encoded landmark did not differ between the three navigation strategies, which is discussed in the context of initial strategy choice and the parallel acquisition of place and response knowledge

Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>The role of TNFα in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function.</p> <p>Methods</p> <p>This study used immunohistochemistry to investigate the expression of TNFα in the tumour islets and stroma with respect to survival in 133 patients with surgically resected NSCLC.</p> <p>Results</p> <p>TNFα expression was increased in the tumour islets of patients with above median survival (AMS) compared to those with below median survival (BMS)(p = 0.006), but similar in the stroma of both groups. Increasing tumour islet TNFα density was a favorable independent prognostic indicator (p = 0.048) while stromal TNFα density was an independent predictor of reduced survival (p = 0.007). Patients with high TNFα expression (upper tertile) had a significantly higher 5-year survival compared to patients in the lower tertile (43% versus 22%, p = 0.01). In patients with AMS, 100% of TNFα⁺cells were macrophages and mast cells, compared to only 28% in the islets and 50% in the stroma of BMS patients (p < 0.001).</p> <p>Conclusions</p> <p>The expression of TNFα in the tumour islets of patients with NSCLC is associated with improved survival suggesting a role in the host anti-tumour immunological response. The expression of TNFα by macrophages and mast cells is critical for this relationship.</p

Host-guest and guest-guest interactions between xylene isomers confined in the MIL-47(V) pore system

The porous MIL-47 material shows a selective adsorption behavior for para-, ortho-, and meta-isomers of xylenes, making the material a serious candidate for separation applications. The origin of the selectivity lies in the differences in interactions (energetic) and confining (entropic). This paper investigates the xylene-framework interactions and the xylene-xylene interactions with quantum mechanical calculations, using a dispersion-corrected density functional and periodic boundary conditions to describe the crystal. First, the strength and geometrical characteristics of the optimal xylene-xylene interactions are quantified by studying the pure and mixed pairs in gas phase. An extended set of initial structures is created and optimized to sample as many relative orientations and distances as possible. Next, the pairs are brought in the pores of MIL-47. The interaction with the terephthalic linkers and other xylenes increases the stacking energy in gas phase (-31.7 kJ/mol per pair) by roughly a factor four in the fully loaded state (-58.3 kJ/mol per xylene). Our decomposition of the adsorption energy shows various trends in the contributing xylene-xylene interactions. The absence of a significant difference in energetics between the isomers indicates that entropic effects must be mainly responsible for the separation behavior

Declining mortality following acute myocardial infarction in the Department of Veterans Affairs Health Care System

<p>Abstract</p> <p>Background</p> <p>Mortality from acute myocardial infarction (AMI) is declining worldwide. We sought to determine if mortality in the Veterans Health Administration (VHA) has also been declining.</p> <p>Methods</p> <p>We calculated 30-day mortality rates between 2004 and 2006 using data from the VHA External Peer Review Program (EPRP), which entails detailed abstraction of records of all patients with AMI. To compare trends within VHA with other systems of care, we estimated relative mortality rates between 2000 and 2005 for all males 65 years and older with a primary diagnosis of AMI using administrative data from the VHA Patient Treatment File and the Medicare Provider Analysis and Review (MedPAR) files.</p> <p>Results</p> <p>Using EPRP data on 11,609 patients, we observed a statistically significant decline in adjusted 30-day mortality following AMI in VHA from 16.3% in 2004 to 13.9% in 2006, a relative decrease of 15% and a decrease in the odds of dying of 10% per year (p = .011). Similar declines were found for in-hospital and 90-day mortality.</p> <p>Based on administrative data on 27,494 VHA patients age 65 years and older and 789,400 Medicare patients, 30-day mortality following AMI declined from 16.0% during 2000-2001 to 15.7% during 2004-June 2005 in VHA and from 16.7% to 15.5% in private sector hospitals. After adjusting for patient characteristics and hospital effects, the overall relative odds of death were similar for VHA and Medicare (odds ratio 1.02, 95% C.I. 0.96-1.08).</p> <p>Conclusion</p> <p>Mortality following AMI within VHA has declined significantly since 2003 at a rate that parallels that in Medicare-funded hospitals.</p

Ecological Determinants of Highly Pathogenic Avian Influenza (H5N1) Outbreaks in Bangladesh

BACKGROUND: The agro-ecology and poultry husbandry of the south Asian and south-east Asian countries share common features, however, with noticeable differences. Hence, the ecological determinants associated with risk of highly pathogenic avian influenza (HPAI-H5N1) outbreaks are expected to differ between Bangladesh and e.g., Thailand and Vietnam. The primary aim of the current study was to establish ecological determinants associated with the risk of HPAI-H5N1 outbreaks at subdistrict level in Bangladesh. The secondary aim was to explore the performance of two different statistical modeling approaches for unmeasured spatially correlated variation. METHODOLOGY/PRINCIPAL FINDINGS: An ecological study at subdistrict level in Bangladesh was performed with 138 subdistricts with HPAI-H5N1 outbreaks during 2007-2008, and 326 subdistricts with no outbreaks. The association between ecological determinants and HPAI-H5N1 outbreaks was examined using a generalized linear mixed model. Spatial clustering of the ecological data was modeled using 1) an intrinsic conditional autoregressive (ICAR) model at subdistrict level considering their first order neighbors, and 2) a multilevel (ML) model with subdistricts nested within districts. Ecological determinants significantly associated with risk of HPAI-H5N1 outbreaks at subdistrict level were migratory birds' staging areas, river network, household density, literacy rate, poultry density, live bird markets, and highway network. Predictive risk maps were derived based on the resulting models. The resulting models indicate that the ML model absorbed some of the covariate effect of the ICAR model because of the neighbor structure implied in the two different models. CONCLUSIONS/SIGNIFICANCE: The study identified a new set of ecological determinants related to river networks, migratory birds' staging areas and literacy rate in addition to already known risk factors, and clarified that the generalized concept of free grazing duck and duck-rice cultivation interacted ecology are not significant determinants for Bangladesh. These findings will refine current understanding of the HPAI-H5N1 epidemiology in Bangladesh

Identifying and Characterizing Alternative Molecular Markers for the Symbiotic and Free-Living Dinoflagellate Genus Symbiodinium

Dinoflagellates in the genus Symbiodinium are best known as endosymbionts of corals and other invertebrate as well as protist hosts, but also exist free-living in coastal environments. Despite their importance in marine ecosystems, less than 10 loci have been used to explore phylogenetic relationships in this group, and only the multi-copy nuclear ribosomal Internal Transcribed Spacer (ITS) regions 1 and 2 have been used to characterize fine-scale genetic diversity within the nine clades (A–I) that comprise the genus. Here, we describe a three-step molecular approach focused on 1) identifying new candidate genes for phylogenetic analysis of Symbiodinium spp., 2) characterizing the phylogenetic relationship of these candidate genes from DNA samples spanning eight Symbiodinium clades (A–H), and 3) conducting in-depth phylogenetic analyses of candidate genes displaying genetic divergences equal or higher than those within the ITS-2 of Symbiodinium clade C. To this end, we used bioinformatics tools and reciprocal comparisons to identify homologous genes from 55,551 cDNA sequences representing two Symbiodinium and six additional dinoflagellate EST libraries. Of the 84 candidate genes identified, 7 Symbiodinium genes (elf2, coI, coIII, cob, calmodulin, rad24, and actin) were characterized by sequencing 23 DNA samples spanning eight Symbiodinium clades (A–H). Four genes displaying higher rates of genetic divergences than ITS-2 within clade C were selected for in-depth phylogenetic analyses, which revealed that calmodulin has limited taxonomic utility but that coI, rad24, and actin behave predictably with respect to Symbiodinium lineage C and are potential candidates as new markers for this group. The approach for targeting candidate genes described here can serve as a model for future studies aimed at identifying and testing new phylogenetically informative genes for taxa where transcriptomic and genomics data are available

Buffered memory: a hypothesis for the maintenance of functional, virus-specific CD8(+) T cells during cytomegalovirus infection.

Chronic infections have been a major topic of investigation in recent years, but the mechanisms that dictate whether or not a pathogen is successfully controlled are incompletely understood. Cytomegalovirus (CMV) is a herpesvirus that establishes a persistent infection in the majority of people in the world. Like other herpesviruses, CMV is well controlled by an effective immune response and induces little, if any, pathology in healthy individuals. However, controlling CMV requires continuous immune surveillance, and thus, CMV is a significant cause of morbidity and death in immune-compromised individuals. T cells in particular play an important role in controlling CMV and both CD4(+) and CD8(+) CMV-specific T cells are essential. These virus-specific T cells persist in exceptionally large numbers during the infection, traffic into peripheral tissues and remain functional, making CMV an attractive vaccine vector for driving CMV-like T cell responses against recombinant antigens of choice. However, the mechanisms by which these T cells persist and differentiate while remaining functional are still poorly understood, and we have no means to promote their development in immune-compromised patients at risk for CMV disease. In this review, I will briefly summarize our current knowledge of CMV-specific CD8(+) T cells and propose a mechanism that may explain their maintenance and preservation of function during chronic infection