Anaesthetic impairment of immune function is mediated via GABA(A) receptors.

BACKGROUND: GABA(A) receptors are members of the Cys-loop family of neurotransmitter receptors, proteins which are responsible for fast synaptic transmission, and are the site of action of wide range of drugs. Recent work has shown that Cys-loop receptors are present on immune cells, but their physiological roles and the effects of drugs that modify their function in the innate immune system are currently unclear. We are interested in how and why anaesthetics increase infections in intensive care patients; a serious problem as more than 50% of patients with severe sepsis will die. As many anaesthetics act via GABA(A) receptors, the aim of this study was to determine if these receptors are present on immune cells, and could play a role in immunocompromising patients. PRINCIPAL FINDINGS: We demonstrate, using RT-PCR, that monocytes express GABA(A) receptors constructed of α1, α4, β2, γ1 and/or δ subunits. Whole cell patch clamp electrophysiological studies show that GABA can activate these receptors, resulting in the opening of a chloride-selective channel; activation is inhibited by the GABA(A) receptor antagonists bicuculline and picrotoxin, but not enhanced by the positive modulator diazepam. The anaesthetic drugs propofol and thiopental, which can act via GABA(A) receptors, impaired monocyte function in classic immunological chemotaxis and phagocytosis assays, an effect reversed by bicuculline and picrotoxin. SIGNIFICANCE: Our results show that functional GABA(A) receptors are present on monocytes with properties similar to CNS GABA(A) receptors. The functional data provide a possible explanation as to why chronic propofol and thiopental administration can increase the risk of infection in critically ill patients: their action on GABA(A) receptors inhibits normal monocyte behaviour. The data also suggest a potential solution: monocyte GABA(A) receptors are insensitive to diazepam, thus the use of benzodiazepines as an alternative anesthetising agent may be advantageous where infection is a life threatening problem.

Modelling cognitive impairment to improve universal access

The purpose of this study is to develop a model of cognitive impairment to help designers consider the range of issues which affect the lives of people living with such impairment. A series of interviews with experts of cognitive impairment was conducted to describe and assess the links between specific medical conditions, including learning disability, specific learning difficulties, autistic spectrum disorders, traumatic brain injury and schizophrenia, and the types of cognitive impairment associated with them. The results reveal some of the most prevalent and serious types of impairment, which - when transformed into design guidance - will help designers make mainstream products more inclusive also for people with cognitive impairment. © 2011 Springer-Verlag.

Adaptive modulation induced WDM impairment reduction in optical OFDM PONs

The transmission performance of multi-channel adaptively modulated optical OFDM (AMOOFDM) signals is numerically investigated, for the first time, in optical amplification- and chromatic dispersion compensation-free, intensity-modulation and direct-detection systems incorporating directly modulated DFB lasers (DMLs). It is shown that adaptive modulation not only reduces significantly the nonlinear WDM impairments induced by the effects of cross-phase modulation and four-wave mixing, but also compensates effectively for the DML-induced frequency chirp effect. In comparison with identical modulation, adaptive modulation improves the maximum achievable signal transmission capacity of a central channel by a factor of 1.3 and 3.6 for 40km and 80km SMFs, respectively, with corresponding dynamic input optical power ranges being extended by approximately 5dB. In addition, adaptive modulation also enables cross-channel complementary modulation format mapping, leading to an improved transmission capacity of the entire WDM system. Copyright © 2010 The authors.

A framework for studying cognitive impairment to inform inclusive design

Chapter 12 A Framework for Studying Cognitive Impairment to Inform Inclusive Design E. Jokisuu, PM Langdon and PJ Clarkson 12.1 Introduction Cognitive impairment is an exceptionally complicated phenomenon, for which no simple solutions ...

Simulating vision loss: What levels of impairment are actually represented?

Capability loss simulators give designers a brief experience of some of the functional effects of capability loss. They are an effective method of helping people to understand the impact of capability loss on product use. However, it is also important that designers know what levels of loss are being simulated and how they relate to the user population. The study in this paper tested the Cambridge Simulation Glasses with 25 participants to determine the effect of different numbers of glasses on a person's visual acuity. This data is also related to the glasses' use in usability assessment. A procedure is described for determining the number of simulator glasses with which the visual detail on a product is just visible. This paper then explains how to calculate the proportion of the UK population who would be unable to distinguish that detail.