Inter-laboratory study of human in vitro toxicogenomics-based tests as alternative methods for evaluating chemical carcinogenicity: a bioinformatics perspective.

The assessment of the carcinogenic potential of chemicals with alternative, human-based in vitro systems has become a major goal of toxicogenomics. The central read-out of these assays is the transcriptome, and while many studies exist that explored the gene expression responses of such systems, reports on robustness and reproducibility, when testing them independently in different laboratories, are still uncommon. Furthermore, there is limited knowledge about variability induced by the data analysis protocols. We have conducted an inter-laboratory study for testing chemical carcinogenicity evaluating two human in vitro assays: hepatoma-derived cells and hTERT-immortalized renal proximal tubule epithelial cells, representing liver and kidney as major target organs. Cellular systems were initially challenged with thirty compounds, genome-wide gene expression was measured with microarrays, and hazard classifiers were built from this training set. Subsequently, each system was independently established in three different laboratories, and gene expression measurements were conducted using anonymized compounds. Data analysis was performed independently by two separate groups applying different protocols for the assessment of inter-laboratory reproducibility and for the prediction of carcinogenic hazard. As a result, both workflows came to very similar conclusions with respect to (1) identification of experimental outliers, (2) overall assessment of robustness and inter-laboratory reproducibility and (3) re-classification of the unknown compounds to the respective toxicity classes. In summary, the developed bioinformatics workflows deliver accurate measures for inter-laboratory comparison studies, and the study can be used as guidance for validation of future carcinogenicity assays in order to implement testing of human in vitro alternatives to animal testing.

Investigating public perceptions of carbon dioxide utilisation (CDU) technology: a mixed methods study.

Carbon dioxide utilisation (CDU) technologies hold promise for helping to limit atmospheric releases of CO2 while generating saleable products. However, while there is growing investment in the research and development required to bring CDU to the market, to date there has been very little systematic research into public perceptions of the technology. The current research reports upon the findings of a series of six qualitative focus groups (and an associated questionnaire) held with members of the UK public in order to discuss the perceived benefits and risks of CDU technology. The findings reveal that public awareness of CDU is currently very low and that there is a desire to learn more about the technology. While our participants did, on average, appear to develop an overall positive attitude towards CDU, this attitude was tentative and was associated with a number of caveats. The implications for the findings in terms of the development of communication and broader strategies of public engagements are outlined.

Our experience using primary oral antibiotics in the management of orbital cellulitis in a tertiary referral centre.

AIMS/PURPOSE: Orbital cellulitis is conventionally managed by intravenous (i.v.) antibiotic therapy, followed by oral antibiotics once the infection shows signs of significant improvement. We report 4 years of experience using primary oral ciprofloxacin and clindamycin in cases of orbital cellulitis. Oral ciprofloxacin and clindamycin have a similar bioavailability to the i.v. preparations and provide an appropriate spectrum of antibiotic cover for the pathogens responsible for orbital cellulitis. METHODS: A retrospective review was performed that identified all patients with orbital cellulitis and treated with primary oral antibiotic therapy admitted to the Manchester Royal Eye Hospital between March 2003 and March 2007. Age, stage of disease, surgical intervention, hospital duration, and complications were obtained. A comparison was made with patients admitted to our unit with orbital cellulitis and treated with primary i.v. antibiotics between March 2000 and March 2003. RESULTS: Nineteen patients were included in the review for the period March 2003 to March 2007, which comprised of 7 children and 12 adults. Five patients required surgical intervention. All patients responded to the oral regimen, 18 patients had no change to their oral antibiotic therapy. Mean hospital stay was 4.4 days. There were no complications. DISCUSSION: Empirical oral ciprofloxacin and clindamycin combination may be as safe and effective as i.v. therapy in the management of orbital cellulitis. Oral treatment can offer the advantages of rapid delivery of the first antibiotic dose, fewer interruptions in treatment, and simplified delivery of medication particularly in children.

Donor-acceptor interactions in crystal engineering.

The molecular complex formed between 4-methyltolane and bis(4-N-methylpyridinium)ethyne ditriflate is reported. The X-ray crystal structure indicates that the crystalline superstructure consists of infinite zigzag ribbons of interlocked donor-acceptor complexes separated by triflate counterions.

Decompensation of a congenital retinal macrovessel with arteriovenous communications induced by repetitive rollercoaster rides.

PURPOSE: To describe a congenital retinal venous macrovessel that communicates with a cilioretinal artery and a retinal artery, and to report how this vascular anomaly decompensated as a result of repetitive rollercoaster rides. METHODS: Case report with serial fundus photography and fluorescein angiography. RESULTS: After a short period of intensive rollercoaster rides, a 19-year-old woman complained of reduced vision in one eye. Funduscopy and fluorescein angiography revealed a venous congenital retinal macrovessel with arteriovenous communications, and retinal exudation was visible at the termination of the anomalous vessel. Exudation resolved, and acuity recovered after a period of avoidance of rollercoaster rides. CONCLUSION: This case represents the first report of a retinal artery and a cilioretinal artery communicating with a congenital retinal macrovessel, and it suggests that such patients are at increased risk of retinal vascular decompensation if involved in activities associated with changes in g-forces, such as bungee jumping or rollercoaster rides.

Severe sclerokeratitis due to Pseudomonas aeruginosa in noncontact-lens wearers.

PURPOSE: To review the clinical presentation, treatment and outcome in four cases of severe anterior segment infection by Pseudomonas aeruginosa unrelated to contact lens wear. METHODS: Four cases presenting over an 18 month period were reviewed. RESULTS: The cases had variable presenting features and outcomes. Complications such as persistent infection, corneal thinning and phthisis bulbi were noted. Possible factors influencing adherence and tissue disruption are discussed. CONCLUSIONS: Suspicion of infection by P. aeruginosa and prompt isolation of the organism is needed early in the course of disease. Intensive and prolonged treatment with parenteral and topical antibiotics combined with judicious use of topical steroid gives the best chance of a favourable outcome.

Routine pre-oxygenation using a Hudson mask. A comparison with a conventional pre-oxygenation technique.

Two techniques of pre-oxygenation were studied by continuous analysis of respired gases using a mass spectrometer in 10 healthy volunteers. The first was a conventional technique as commonly used in anaesthesia with a Bain system and tightly-fitting anaesthetic face-mask and an oxygen flow of 8 l.min-1. The second technique also used a Bain system with an oxygen flow of 8 l.min-1, but with a Hudson mask attached. The mean fractional end-tidal oxygen concentrations after 3 min were 0.812 and 0.46 respectively for each of the pre-oxygenation techniques against 0.16 for subjects breathing air. This represents a considerable increase in pulmonary oxygen reserve for both techniques. The second technique is not an alternative to conventional pre-oxygenation for emergency anaesthesia, but is a useful and simple method that is acceptable to both patient and anaesthetist in routine cases.