IL-36α expression is elevated in ulcerative colitis and promotes colonic inflammation.

A role for the IL-36 family of cytokines has been identified in the pathogenesis of psoriasis. Although significant mechanistic overlap can exist between psoriasis and inflammatory bowel disease (IBD), to date there have been no reports investigating the IL-36 family in gastrointestinal inflammation. Here we demonstrate that expression levels of IL-36α are specifically elevated in the colonic mucosa of ulcerative colitis patients. This elevated expression is mirrored in the inflamed colonic mucosa of mice, wherein IL-36 receptor deficiency confirmed this pathway as a mediator of mucosal inflammation. Il36r-/- mice exhibited reduced disease severity in an acute DSS-induced model of colitis in association with decreased innate inflammatory cell infiltration to the colon lamina propria. Consistent with these data, infection with the enteropathogenic bacteria Citrobacter rodentium, resulted in reduced innate inflammatory cell recruitment and increased bacterial colonization in the colons of il36r-/- mice. Il36r-/- mice also exhibited altered T helper cell responses in this model, with enhanced Th17 and reduced Th1 responses, demonstrating that IL-36R signaling also regulates intestinal mucosal T-cell responses. These data identify a novel role for IL-36 signaling in colonic inflammation and indicate that the IL-36R pathway may represent a novel target for therapeutic intervention in IBD.

Survey of the reliability of carbon monoxide alarms deployed in domestic homes and efficacy of use by consumers.

Carbon monoxide (CO) alarms are extensively used in domestic premises in the UK to help protect against CO poisoning. Their expected lifetime has been increasing, and some current models now have a replacement period of more than 6 years under normal operation. However, concerns have been expressed as to the reliability of alarms over an extended period. In this study, 110 households with a CO alarm were surveyed, during which the alarm was uninstalled and replaced and a household survey questionnaire administered. Alarm reliability was assessed under laboratory conditions by testing conformity to the alarm condition gas tests in either the British (European) standard, BS EN 50291 for UK certified models, or the US standard, UL 2034 for US certified models. The questionnaire recorded the alarm make and model, its age, its location, whether it was correctly sited, and how often it was tested. General information on the property was also collected. Results of laboratory testing suggest that the reliability of the most common models of CO alarms used by UK consumers has improved over the last 7 years. However, findings from the household survey suggest that the way alarms are used in many homes may not maximize their ability to detect abnormal levels CO.

Evaluation of portable single-gas monitors for the detection of low levels of hydrogen sulfide and sulfur dioxide in petroleum industry environments.

Many portable single-gas monitors are used for the detection of low concentrations of hydrogen sulfide (H(2)S) and sulfur dioxide (SO(2)) in the workplace. With the recent lowering of the H(2)S and SO(2) ACGIH® threshold limit value (TLV®) the ability of these devices to selectively respond to these new lower levels is not well documented in petroleum industry environments, which often have potential interfering gases and vapors present as well as varying environmental conditions. Tests were carried out to measure the ability of various monitors with their respective sensors to correctly quantify and respond to H(2)S and SO(2) in a simulated petroleum industry environment. This included the identification of selected interference effects and estimation of the reliable lower limit of detection for real workplace environments. None of the H(2)S monitors responded at 0.1 times the new TLV (0.1 ppm), only some of them responded at the new TLV concentration (1 ppm), and all the monitors exposed to five times the new TLV (5 ppm) responded with reasonable accuracy. There was generally little effect of interferent gases and vapors on the H(2)S monitors. None of the SO(2) monitors responded at 0.1 and 1 times the new TLV (0.025 ppm and 0.25 ppm) concentrations, and all but one of them exposed to five times the new TLV (1.25 ppm) responded. There was much greater cross-sensitivity to interferents at the tested concentrations with the SO(2) monitors, which responded to six out of eight of the interferents tested. Results demonstrate that these monitors cannot reliably alarm and measure H(2)S or SO(2) concentrations at the new TLVs with an acceptable degree of accuracy. However, these monitors are designed to alarm as a safety device; these results do not change this important function.

Response of electrochemical oxygen sensors to inert gas-air and carbon dioxide-air mixtures: measurements and mathematical modelling.

Electrochemical oxygen gas sensors are widely used for monitoring the state of inertisation of flammable atmospheres and to warn of asphyxiation risks. It is well established but not widely known by users of such oxygen sensors that the response of the sensor is affected by the nature of the diluent gas responsible for the decrease in ambient oxygen concentration. The present work investigates the response of electrochemical sensors, with either acid or alkaline electrolytes, to gas mixtures comprising air with enhanced levels of nitrogen, carbon dioxide, argon or helium. The measurements indicate that both types of sensors over-read the oxygen concentrations when atmospheres contain high levels of helium. Sensors with alkaline electrolytes are also shown to underestimate the severity of the hazard in atmospheres containing high levels of carbon dioxide. This deviation is greater for alkaline electrolyte sensors compared to acid electrolyte sensors. A Computational Fluid Dynamics (CFD) model is developed to predict the response of an alkaline electrolyte, electrochemical gas sensor. Differences between predicted and measured sensor responses are less than 10% in relative terms for nearly all of the gas mixtures tested, and in many cases less than 5%. Extending the model to simulate responses of sensors with acid electrolytes would be straightforward.

A review of video exposure monitoring as an occupational hygiene tool.

This study reviews use of video exposure monitoring (VEM, also known as PIMEX) as an occupational hygiene tool since its inception in the mid-1980s. VEM involves the combination of real-time monitoring instruments, usually for gases/vapours and dust, with video of the worker's activities. VEM is an established method used by practitioners in different countries. The technical aspects of these VEM systems are described, then applications of VEM are discussed, focussing on task analysis, training (risk communication), encouraging worker participation in and motivation for improvements in the workplace environment and occupational hygiene research. The experiences from these applications are used to illustrate how exposure visualization with video can act as a catalyst, initiating a change process in the workplace. Finally, the role of VEM as a workplace improvement tool, now and in the future, is discussed.

Performance testing of three portable, direct-reading dust monitors.

Three portable direct-reading dust monitors were tested in a recirculating dust tunnel and a calm air dust chamber against a range of industrial dusts with different size distributions to investigate sources of variation in their responses. Responses were found to be linear compared to reference gravimetric respirable samplers over a range of concentrations for a particular particle size distribution. Their calibration factors were dependant on particle size, particle composition and air velocity. If particle size and air velocity do not change significantly then the calibration factor can be applied to the monitor readings to give an accurate measure of dust concentration. The DataRam and HAM, factory calibrated against respirable dust concentration, were found to agree closely, whereas the Microdust gave higher readings, having been factory calibrated against total suspended particulate concentration. The calibration of the DataRam was significantly altered by either contamination of the optics with dust or by cleaning the optics. This was not observed with either the Microdust or HAM, since both monitors include a reference calibration element.

Monitoring exposure to solvent vapour in the workplace using a video-visualization technique.

A video-visualization technique, using a combination of a fast-response, direct-reading, personal gas monitor (photo-ionization detector) and synchronized video monitoring (with a standard camcorder), has been applied to assess exposure to solvents in various industries. The objective is to understand how short-term peaks occur and how they can be controlled to minimise both short-term exposure and their contribution to long-term exposure. The technique was employed to identify peaks associated with work activities and their contribution to total exposure arising from use of tetrachloroethene in a dry cleaning establishment. The exposure and video data are simultaneously displayed on computer and the information is disseminated on CD (and video), forming the basis of a detailed occupational hygiene assessment or training material.

The insulin-like growth factor-I receptor is regulated by CD28 and protects activated T cells from apoptosis.

Co-stimulatory signals through the CD28 receptor enhance the survival of T cells that have their antigen receptor (TCR) engaged. Here we show that stimulation through the CD28 receptor in the absence of TCR engagement with either an anti-CD28 cross-linking antibody or the CD80 ligand transiently increases expression of the insulin-like growth factor-I receptor (IGF-IR) on T cells. Antibodies that block signaling through the IGF-IR decrease the survival of T cells activated through the TCR and CD28 in the presence of IL-2 by more than 50%, and also enhance susceptibility to Fas-induced apoptosis. CD28 stimulation increases IGF-IR expression on Jurkat cells, and exogenously added IGF-I can protect these cells from Fas-induced apoptosis. We conclude that CD28-mediated enhancement of IGF-IR expression provides activated T cells with essential survival signals that are independent of survival mediated by IL-2 and Bcl-xl.

Computer-aided video exposure monitoring.

A computer-aided video exposure monitoring system was used to record exposure information. The system comprised a handheld camcorder, portable video cassette recorder, radio-telemetry transmitter/receiver, and handheld or notebook computers for remote data logging, photoionization gas/vapor detectors (PIDs), and a personal aerosol monitor. The following workplaces were surveyed using the system: dry cleaning establishments--monitoring tetrachoroethylene in the air and in breath; printing works--monitoring white spirit type solvent; tire manufacturing factory--monitoring rubber fume; and a slate quarry--monitoring respirable dust and quartz. The system based on the handheld computer, in particular, simplified the data acquisition process compared with earlier systems in use by our laboratory. The equipment is more compact and easier to operate, and allows more accurate calibration of the instrument reading on the video image. Although a variety of data display formats are possible, the best format for videos intended for educational and training purposes was the review-preview chart superimposed on the video image of the work process. Recommendations for reducing exposure by engineering or by modifying work practice were possible through use of the video exposure system in the dry cleaning and tire manufacturing applications. The slate quarry work illustrated how the technique can be used to test ventilation configurations quickly to see their effect on the worker's personal exposure.

Cross-validatory selection of test and validation sets in multivariate calibration and neural networks as applied to spectroscopy.

Cross-validated and non-cross-validated regression models using principal component regression (PCR), partial least squares (PLS) and artificial neural networks (ANN) have been used to relate the concentrations of polycyclic aromatic hydrocarbon pollutants to the electronic absorption spectra of coal tar pitch volatiles. The different trends in the cross-validated and non-cross-validated results are discussed as well as a method for the production of a true cross-validated neural network regression model. It is shown that the methods must be compared through the errors produced in the validation sets as well as those given for the final model. Various methods for calculation of errors are described and compared. The separation of training, validation and test sets into fully independent groups is emphasized. PLS outperforms PCR using all indicators. ANNs are inferior to multivariate techniques for individual compounds but are reasonably effective in predicting the sum of PAHs in the mixture set.

Structure-activity relationships for skin sensitization potential: development of structural alerts for use in knowledge-based toxicity prediction systems.

The development of qualitative structure-activity relationships for the prediction of skin sensitization potential, based on structural alerts (substructures associated with a toxicological mechanism), and suitable for incorporation as rules into a knowledge-based system is described. The structure dependence of the skin sensitization mechanism may be largely defined in terms of the presence or metabolic/nonmetabolic formation of protein reactive functional groups on the test compound and by the physicochemical requirements of significant skin penetration. The proposed structural alerts were tested on a data set of diverse chemicals. The results showed that the alerts have potential as preliminary indicators of skin sensitization potential for a wide range of low molecular weight chemicals.

Neural network classification of mutagens using structural fragment data.

A neural network was applied to a large, structurally heterogeneous data set of mutagens and non-mutagens to investigate structure-property relationships. Substructural data comprising a total of 1280 fragments were used as inputs. The training of the back-propagation networks was directed by an algorithm which selected an optimal subset of fragments in order to maximize their discriminating power, and a good predictive network. The system comprised three programs: the first used a keyfile of 100 fragments to generate training and test files, the second was the network itself and a procedure for ranking the effectiveness of these fragments and the third randomly replaced the lowest fragments. This cycle was then repeated. After running on a 386/33 PC several networks produced approximately 11% failures in the test set and 6% in the training set. By simplifying the output of the hidden layer it was possible to describe the hidden layer states in terms of clusters of mutagens and non-mutagens. Some of these clusters were structurally homogeneous and contained known mutagenic and non-mutagenic structural classes. This analysis provided a useful means of demonstrating how the network was classifying the data.