Proportion of infiltrating IgG-binding immune cells predict for tumour hypoxia

Macrophages can account for up to 50% of tumour mass and secrete many angiogenic factors. Furthermore, tumour hypoxia is thought to play a major role in the activation of macrophages and the regulation of angiogenesis. In this paper, we demonstrate a strong correlation between hypoxia and the recruitment of immune cells binding to IgG in 8 experimental tumours. We provide evidence that IgG binding immune cells in 3 tumour lines are predominately composed of macrophages. Reduced oxygenation may act as a stimulus for recruitment of immune cells to the tumour mass, and the detection of either IgG-positive host cells or macrophages may offer an alternative method for monitoring tumour hypoxia. © 2001 Cancer Research Campaign http://www.bjcancer.co

What lies beneath? The role of informal and hidden networks in the management of crises

Crisis management research traditionally focuses on the role of formal communication networks in the escalation and management of organisational crises. Here, we consider instead informal and unobservable networks. The paper explores how hidden informal exchanges can impact upon organisational decision-making and performance, particularly around inter-agency working, as knowledge distributed across organisations and shared between organisations is often shared through informal means and not captured effectively through the formal decision-making processes. Early warnings and weak signals about potential risks and crises are therefore often missed. We consider the implications of these dynamics in terms of crisis avoidance and crisis management

Science and Technology Studies in Policy: the UK Synthetic Biology Roadmap

In this paper, we reflect on our experience as Science and Technology Studies (STS) researchers who were members of the working group that produced A Synthetic Biology Roadmap for the UK in 2012. We explore how this initiative sought to govern an uncertain future, and describe how it was successfully used to mobilize public funds for synthetic biology from the UK government. We discuss our attempts to incorporate the insights and sensibilities of STS into the policy process, and why we chose to use the concept of Responsible Research and Innovation (RRI) to do so. We analyze how the roadmapping process, and the final report, narrowed and transformed our contributions to the Roadmap. We show how difficult it is for STS researchers to influence policy when our ideas challenge deeply entrenched pervasive assumptions, framings and narratives about how technological innovation necessarily leads to economic progress, about public reticence as a roadblock to that progress, and about the supposed separation between science and society. We end by reflecting on the constraints under which we were operating from the outset, and on the challenges for STS in policy

The vulnerability of public spaces: challenges for UK hospitals under the 'new' terrorist threat

This article considers the challenges for hospitals in the United Kingdom that arise from the threats of mass-casualty terrorism. Whilst much has been written about the role of health care as a rescuer in terrorist attacks and other mass-casualty crises, little has been written about health care as a victim within a mass-emergency setting. Yet, health care is a key component of any nation's contingency planning and an erosion of its capabilities would have a significant impact on the generation of a wider crisis following a mass-casualty event. This article seeks to highlight the nature of the challenges facing elements of UK health care, with a focus on hospitals both as essential contingency responders under the United Kingdom's civil contingencies legislation and as potential victims of terrorism. It seeks to explore the potential gaps that exist between the task demands facing hospitals and the vulnerabilities that exist within them

The Laboratory-Based Intermountain Validated Exacerbation (LIVE) Score Identifies Chronic Obstructive Pulmonary Disease Patients at High Mortality Risk.

Background: Identifying COPD patients at high risk for mortality or healthcare utilization remains a challenge. A robust system for identifying high-risk COPD patients using Electronic Health Record (EHR) data would empower targeting interventions aimed at ensuring guideline compliance and multimorbidity management. The purpose of this study was to empirically derive, validate, and characterize subgroups of COPD patients based on routinely collected clinical data widely available within the EHR. Methods: Cluster analysis was used in 5,006 patients with COPD at Intermountain to identify clusters based on a large collection of clinical variables. Recursive Partitioning (RP) was then used to determine a preferred tree that assigned patients to clusters based on a parsimonious variable subset. The mortality, COPD exacerbations, and comorbidity profile of the identified groups were examined. The findings were validated in an independent Intermountain cohort and in external cohorts from the United States Veterans Affairs (VA) and University of Chicago Medicine systems. Measurements and Main Results: The RP algorithm identified five LIVE Scores based on laboratory values: albumin, creatinine, chloride, potassium, and hemoglobin. The groups were characterized by increasing risk of mortality. The lowest risk, LIVE Score 5 had 8% 4-year mortality vs. 56% in the highest risk LIVE Score 1 (p < 0.001). These findings were validated in the VA cohort (n = 83,134), an expanded Intermountain cohort (n = 48,871) and in the University of Chicago system (n = 3,236). Higher mortality groups also had higher COPD exacerbation rates and comorbidity rates. Conclusions: In large clinical datasets across different organizations, the LIVE Score utilizes existing laboratory data for COPD patients, and may be used to stratify risk for mortality and COPD exacerbations

Risk, precaution and science: towards a more constructive policy debate. Talking point on the precautionary principle

Few issues in contemporary risk policy are as momentous or contentious as the precautionary principle. Since it first emerged in German environmental policy, it has been championed by environmentalists and consumer protection groups, and resisted by the industries they oppose (Raffensperger & Tickner, 1999). Various versions of the principle now proliferate across different national and international jurisdictions and policy areas (Fisher, 2002). From a guiding theme in European Commission (EC) environmental policy, it has become a general principle of EC law (CEC, 2000; Vos & Wendler, 2006). Its influence has extended from the regulation of environmental, technological and health risks to the wider governance of science, innovation and trade (O'Riordan & Cameron, 1994)

Some distorted thoughts about ketamine as a psychedelic and a novel hypothesis based on NMDA receptor-mediated synaptic plasticity.

Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA receptor-mediated excitation of GABAergic interneurons can result in glutamatergic overactivity. Thirdly, limbic cortical disinhibition may indirectly enhance dopaminergic and serotonergic activity. Fourthly, inhibition of NMDA receptor mediated synaptic plasticity, such as short-term potentiation (STP) and long-term potentiation (LTP), could lead to distorted memories. Here, for the first time, we compared quantitatively the effects of ketamine on STP and LTP. We report that ketamine inhibits STP in a double sigmoidal fashion with low (40 nM) and high (5.6 μM) IC50 values. In contrast, ketamine inhibits LTP in a single sigmoidal manner (IC50 value ∼ 15 μM). A GluN2D-subunit preferring NMDA receptor antagonist, UBP145, has a similar pharmacological profile. We propose that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'

A study of long-term potentiation in transgenic mice over-expressing mutant forms of both amyloid precursor protein and presenilin-1

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.Abstract Synaptic transmission and long-term potentiation (LTP) in the CA1 region of hippocampal slices have been studied during ageing of a double transgenic mouse strain relevant to early-onset familial Alzheimer's disease (AD). This strain, which over-expresses both the 695 amino acid isoform of human amyloid precursor protein (APP) with K670N and M671L mutations and presenilin 1 with the A246E mutation, has accelerated amyloidosis and plaque formation. There was a decrease in synaptic transmission in both wildtype and transgenic mice between 2 and 9 months of age. However, preparing slices from 14 month old animals in kynurenic acid (1 mM) counteracted this age-related deficit. Basal transmission and paired-pulse facilitation was similar between the two groups at all ages (2, 6, 9 and 14 months) tested. Similarly, at all ages LTP, induced either by theta burst stimulation or by multiple tetani, was normal. These data show that a prolonged, substantially elevated level of Aβ are not sufficient to cause deficits in the induction or expression of LTP in the CA1 hippocampal region.Published versio