Analysis of the potential of cancer cell lines to release tissue factor-containing microvesicles: correlation with tissue factor and PAR2 expression

BackgroundDespite the association of cancer-derived circulating tissue factor (TF)-containing microvesicles and hypercoagulable state, correlations with the incidence of thrombosis remain unclear.MethodsIn this study the upregulation of TF release upon activation of various cancer cell lines, and the correlation with TF and PAR2 expression and/or activity was examined. Microvesicle release was induced by PAR2 activation in seventeen cell lines and released microvesicle density, microvesicle-associated TF activity, and phoshpatidylserine-mediated activity were measured. The time-course for TF release was monitored over 90 min in each cell line. In addition, TF mRNA expression, cellular TF protein and cell-surface TF activities were quantified. Moreover, the relative expression of PAR2 mRNA and cellular protein were analysed. Any correlations between the above parameters were examined by determining the Pearson’s correlation coefficients.ResultsTF release as microvesicles peaked between 30–60 min post-activation in the majority of cell lines tested. The magnitude of the maximal TF release positively correlated with TF mRNA (c = 0.717; p

Population-based emergence of unfamiliar climates

Time of emergence, which characterizes when significant signals of climate change will emerge from existing variability, is a useful and increasingly common metric. However, a more useful metric for understanding future climate change in the context of past experience may be the ratio of climate signal to noise (S/N)—a measure of the amplitude of change expressed in terms of units of existing variability. Here, we present S/N projections in the context of emergent climates (termed ‘unusual’, ‘unfamiliar’ and ‘unknown’ by reference to an individual’s lifetime), highlighting sensitivity to future emissions scenarios and geographical and human groupings. We show how for large sections of the world’s population, and for several geopolitical international groupings, mitigation can delay the onset of ‘unknown’ or ‘unfamiliar’ climates by decades, and perhaps even beyond 2100. Our results demonstrate that the benefits of mitigation accumulate over several decades, a key metric of which is reducing S/N, or keeping climate as familiar as possible. A relationship is also identified between cumulative emissions and patterns of emergent climate signals. Timely mitigation will therefore provide the greatest benefits to those facing the earliest impacts, many of whom are alive now

Aquatic community response to volcanic eruptions on the Ecuadorian Andean flank: evidence from the palaeoecological record

Aquatic ecosystems in the tropical Andes are under increasing pressure from human modification of the landscape (deforestation and dams) and climatic change (increase of extreme events and 1.5 °C on average temperatures are projected for AD 2100). However, the resilience of these ecosystems to perturbations is poorly understood. Here we use a multi-proxy palaeoecological approach to assess the response of aquatic ecosystems to a major mechanism for natural disturbance, volcanic ash deposition. Specifically, we present data from two Neotropical lakes located on the eastern Andean flank of Ecuador. Laguna Pindo (1°27.132′S–78°04.847′W) is a tectonically formed closed basin surrounded by a dense mid-elevation forest, whereas Laguna Baños (0°19.328′S–78°09.175′W) is a glacially formed lake with an inflow and outflow in high Andean Páramo grasslands. In each lake we examined the dynamics of chironomids and other aquatic and semi-aquatic organisms to explore the effect of thick (> 5 cm) volcanic deposits on the aquatic communities in these two systems with different catchment features. In both lakes past volcanic ash deposition was evident from four large tephras dated to c.850 cal year BP (Pindo), and 4600, 3600 and 1500 cal year BP (Baños). Examination of the chironomid and aquatic assemblages before and after the ash depositions revealed no shift in composition at Pindo, but a major change at Baños occurred after the last event around 1500 cal year BP. Chironomids at Baños changed from an assemblage dominated by Pseudochironomus and Polypedilum nubifer-type to Cricotopus/Paratrichocladius type-II, and such a dominance lasted for approximately 380 years. We suggest that, despite potential changes in the water chemistry, the major effect on the chironomid community resulted from the thickness of the tephra being deposited, which acted to shallow the water body beyond a depth threshold. Changes in the aquatic flora and fauna at the base of the trophic chain can promote cascade effects that may deteriorate the ecosystem, especially when already influenced by human activities, such as deforestation and dams, which is frequent in the high Andes

Intercultural New Media Studies: The Next Frontier in intercultural Communication

New media (ICT\u27s) are transforming communication across cultures. Despite this revolution in cross cultural contact, communication researchers have largely ignored the impact of new media on intercultural communication. This groundbreaking article defines the parameters of a new field of inquiry called Intercultural New Media Studies (INMS), which explores the intersection between ICT\u27s and intercultural communication. Composed of two research areas—(1) new media and intercultural communication theory and (2) culture and new media—INMS investigates new digital theories of intercultural contact as well as refines and expands twentieth-century intercultural communication theories, examining their salience in a digital world. INMS promises to increase our understanding of intercultural communication in a new media age and is the next frontier in intercultural communication

A report on the health and social care listening event

The purpose of the Listening Event was to enable a wide range of people, including professionals working in statutory, voluntary and other organisations and members of the public, to ‘have a say’ about health and social care and what we as a University can do for and with these partners and the public. We particularly wanted to hear about key concerns of the University such as: • Strengthening community engagement and partnerships • Health and social care training we should be providing, for whom, and how this is delivered • Ideas relating to the University themes including media, use of space and buildings, human rights, social justice and security • Research topics we should be addressing However the main strength of the Listening Event approach is that topics for discussion are mostly led by participants who attend. On this occasion, the discussion topics were very much focused on the concerns of participants and lots of information and ideas were generated. The task now is for the event planning team to review the discussion notes and identify what can be addressed and how, in the short, medium and long term. This planning will be taking place over the Autumn in 2011, and any participants or readers of this report are more than welcome to get in touch to work with us or add their views. The purpose of this report is to record all discussion summaries for sharing amongst participants and others. It is important that participants especially get to read what others had said at the event. The report will lead to changes in University practices such as the content of some of our courses and new business ideas and relationships will also be explored. The event itself provided a useful means of public engagement that others may wish to adopt

Management of patients with biliary sphincter of Oddi disorder without sphincter of Oddi manometry

<p>Abstract</p> <p>Background</p> <p>The paucity of controlled data for the treatment of most biliary sphincter of Oddi disorder (SOD) types and the incomplete response to therapy seen in clinical practice and several trials has generated controversy as to the best course of management of these patients. In this observational study we aimed to assess the outcome of patients with biliary SOD managed without sphincter of Oddi manometry.</p> <p>Methods</p> <p>Fifty-nine patients with biliary SOD (14% type I, 51% type II, 35% type III) were prospectively enrolled. All patients with a dilated common bile duct were offered endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy whereas all others were offered medical treatment alone. Patients were followed up for a median of 15 months and were assessed clinically for response to treatment.</p> <p>Results</p> <p>At follow-up 15.3% of patients reported complete symptom resolution, 59.3% improvement, 22% unchanged symptoms, and 3.4% deterioration. Fifty-one percent experienced symptom resolution/improvement on medical treatment only, 12% after sphincterotomy, and 10% after both medical treatment/sphincterotomy. Twenty percent experienced at least one recurrence of symptoms after initial response to medical and/or endoscopic treatment. Fifty ERCP procedures were performed in 24 patients with an 18% complication rate (16% post-ERCP pancreatitis). The majority of complications occurred in the first ERCP these patients had. Most complications were mild and treated conservatively. Age, gender, comorbidity, SOD type, dilated common bile duct, presence of intact gallbladder, or opiate use were not related to the effect of treatment at the end of follow-up (p > 0.05 for all).</p> <p>Conclusions</p> <p>Patients with biliary SOD may be managed with a combination of endoscopic sphincterotomy (performed in those with dilated common bile duct) and medical therapy without manometry. The results of this approach with regards to symptomatic relief and ERCP complication rate are comparable to those previously published in the literature in cohorts of patients assessed by manometry.</p

Chaste: an open source C++ library for computational physiology and biology

Chaste - Cancer, Heart And Soft Tissue Environment - is an open source C++ library for the computational simulation of mathematical models developed for physiology and biology. Code development has been driven by two initial applications: cardiac electrophysiology and cancer development. A large number of cardiac electrophysiology studies have been enabled and performed, including high performance computational investigations of defibrillation on realistic human cardiac geometries. New models for the initiation and growth of tumours have been developed. In particular, cell-based simulations have provided novel insight into the role of stem cells in the colorectal crypt. Chaste is constantly evolving and is now being applied to a far wider range of problems. The code provides modules for handling common scientific computing components, such as meshes and solvers for ordinary and partial differential equations (ODEs/PDEs). Re-use of these components avoids the need for researchers to "re-invent the wheel" with each new project, accelerating the rate of progress in new applications. Chaste is developed using industrially-derived techniques, in particular test-driven development, to ensure code quality, re-use and reliability. In this article we provide examples that illustrate the types of problems Chaste can be used to solve, which can be run on a desktop computer. We highlight some scientific studies that have used or are using Chaste, and the insights they have provided. The source code, both for specific releases and the development version, is available to download under an open source Berkeley Software Distribution (BSD) licence at http://www.cs.ox.ac.uk/chaste, together with details of a mailing list and links to documentation and tutorials

Regulation of Anthrax Toxin-Specific Antibody Titers by Natural Killer T Cell-Derived IL-4 and IFNγ

Activation of Natural Killer-like T cells (NKT) with the CD1d ligand α-GC leads to enhanced production of anthrax toxin protective Ag (PA)-neutralizing Abs, yet the underlying mechanism for this adjuvant effect is not known. In the current study we examined the role of Th1 and Th2 type responses in NKT-mediated enhancement of antibody responses to PA. First, the contribution of IL-4 and IFNγ to the production of PA-specific toxin-neutralizing Abs was examined. By immunizing C57Bl/6 controls IL-4−/− mice and IFNγ−/− mice and performing passive serum transfer experiments, it was observed that sera containing PA-specific IgG1, IgG2b and IgG2c neutralized toxin in vitro and conferred protection in vivo. Sera containing IgG2b and IgG2c neutralized toxin in vitro but were not sufficient for protection in vivo. Sera containing IgG1 and IgG2b neutralized toxin in vitro and conferred protection in vivo. IgG1 therefore emerged as a good correlate of protection. Next, C57Bl/6 mice were immunized with PA alone or PA plus a Th2-skewing α-GC derivative known as OCH. Neutralizing PA-specific IgG1 responses were modestly enhanced by OCH in C57Bl/6 mice. Conversely, IgG2b and IgG2c were considerably enhanced in PA/OCH-immunized IL-4−/− mice but did not confer protection. Finally, bone marrow chimeras were generated such that NKT cells were unable to express IL-4 or IFNγ. NKT-derived IL-4 was required for OCH-enhanced primary IgG1 responses but not recall responses. NKT-derived IL-4 and IFNγ also influenced primary and recall IgG2b and IgG2c titers. These data suggest targeted skewing of the Th2 response by α-GC derivatives can be exploited to optimize anthrax vaccination

How residents and interns utilise and perceive the personal digital assistant and UpToDate

<p>Abstract</p> <p>Background</p> <p>In this era of evidence-based medicine, doctors are increasingly using information technology to acquire medical knowledge. This study evaluates how residents and interns utilise and perceive the personal digital assistant (PDA) and the online resource UpToDate.</p> <p>Methods</p> <p>This is a questionnaire survey of all residents and interns in a tertiary teaching hospital.</p> <p>Results</p> <p>Out of 168 doctors, 134 (79.8%) responded to the questionnaire. Only 54 doctors (40.3%) owned a PDA. Although these owners perceived that the PDA was most useful for providing drug information, followed by medical references, scheduling and medical calculators, the majority of them did not actually have medical software applications downloaded on their PDAs. The greatest concerns highlighted for the PDA were the fear of loss and breakage, and the preference for working with desktop computers and paper. Meanwhile, only 76 doctors (56.7%) used UpToDate, even though the hospital had an institutional subscription for it. Although 93.4% of these users would recommend UpToDate to a colleague, only 57.9% stated that the use of UpToDate had led to a change in their management of patients.</p> <p>Conclusion</p> <p>Although UpToDate and various PDA software applications were deemed useful by some of the residents and interns in our study, both digital tools were under-utilised. More should be done to facilitate the use of medical software applications on PDAs, to promote awareness of tools for evidence-based medicine such as UpToDate, and to facilitate the application of evidence-based medicine in daily clinical practice.</p