Edinburgh, United Kingdom
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Cuschieri K.,Specialist Virology Center | Brewster D.H.,Scottish Cancer Registry | Williams A.R.W.,Royal Inf Irmary of Edinburgh | Millan D.,Glasgow Royal Inf Irmary | And 6 more authors.
British Journal of Cancer | Year: 2010

Background/metho:This study evaluated human papillomavirus (HPV) type prevalence in 370 Scottish invasive cervical cancers (ICCs) using HPV genotyping and HPV mRNA detection.Results:HPV 16 and/or 18 was detected in 72% of cancers overall and in 82% of HPV-positive cancers. HPV 45 and 16 were the most frequently transcribed types.Conclusion:A significant reduction in ICC in Scotland should be achieved through the HPV immunisation programme. © 2010 Cancer Research UK All rights reserved.


Barber T.J.,Medical Research Council Clinical Trials Unit | Barber T.J.,Chelsea and Westminster Hospital | Barber T.J.,Mortimer Market Center | Harrison L.,Medical Research Council Clinical Trials Unit | And 102 more authors.
Journal of Antimicrobial Chemotherapy | Year: 2012

Background: Selection of protease mutations on antiretroviral therapy (ART) including a ritonavir-boosted protease inhibitor (PI) has been reported infrequently. Scarce data exist from long-term cohorts on resistance incidence or mutational patterns emerging to different PIs. Methods: We studied UK patients receiving lopinavir/ritonavir as their first PI, either while naive to ART or having previously received non-PI-based ART. Virological failure was defined as viral load ≥400 copies/mL after previous suppression <400 copies/mL, or failure to achieve <400 copies/mL during the first 6 months. pol sequences whilst failing lopinavir or within 30 days after stopping were analysed. Major and minor mutations (IAS-USA 2008-after exclusion of polymorphisms) were considered. Predicted susceptibility was determined using the Stanford HIVdb algorithm. Results: Three thousand and fifty-six patients were followed for a median (IQR) of 14 (6-30) months, of whom 811 (27%) experienced virological failure. Of these, resistance test results were available on 291 (36%). One or more protease mutations were detected in 32 (11%) patients; the most frequent were I54V (n = 12), M46I (n = 11), V82A (n = 7) and L76V (n = 3). No association with viral subtype was evident. Many patients retained virus predicted to be susceptible to lopinavir (14, 44%), tipranavir (26, 81%) and darunavir (27, 84%). Conclusions: This study reflects the experience of patients in routine care. Selection of protease gene mutations by lopinavir/ritonavir occurred at a much higher rate than in clinical trials. The mutations observed showed only partial overlap with those previously identified by structural chemistry models, serial cell culture passage and genotype-phenotype analyses. There remained a low degree of predicted cross-resistance to other widely used PIs. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.


Castro H.,Medical Research Council Clinical Trials Unit | Pillay D.,University College London | Cane P.,Public Health England | Asboe D.,Chelsea and Westminster Hospital | And 56 more authors.
Journal of Infectious Diseases | Year: 2013

There are few data on the persistence of individual human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) mutations in the absence of selective drug pressure. We studied 313 patients in whom TDR mutations were detected at their first resistance test and who had a subsequent test performed while ART-naive. The rate at which mutations became undetectable was estimated using exponential regression accounting for interval censoring. Most thymidine analogue mutations (TAMs) and T215 revertants (but not T215F/Y) were found to be highly stable, with NNRTI and PI mutations being relatively less persistent. Our estimates are important for informing HIV transmission models. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.


Gormley M.,Heriot - Watt University | Templeton K.E.,Specialist Virology Center | Kelly D.A.,Heriot - Watt University | Hardie A.,Specialist Virology Center
Building Services Engineering Research and Technology | Year: 2014

A potential cross-transmission route, first identified in the spread of the SARs virus in South East Asia, in which infection was spread by virus-laden aerosolised droplets entering habitable space via defective water traps is investigated. The main aim of this work was to detect norovirus in wastewater from the collection drain in a hospital Building Drainage System and attempt to trace it in the BDS vent airflow. The methodology employed polymerase chain reaction tests on waste water samples and indicated strong positives for the norovirus GII strain from the collection drain, corresponding to an outbreak in the building, confirming that the BDS is contaminated in such circumstances and poses a threat. Pathogens were not detected in the BDS vertical stack airflows; however, the methodology employed to collect samples from the airflow was considered ineffective requiring further research. An average temperature of 24.3 was recorded, together with an average humidity of 96.6%. This research also confirmed that inside the building drainage stack, air flow movement occurs in both the 'up' and 'down' direction. Thus, aerosolised pathogens could travel from the contaminated horizontal collection drains upwards and enter wards via defective traps or little used showers, sinks, baths and sluices.Practical application: The detection of norovirus from raw, unprocessed samples taken from the collection drain of a hospital complex highlights the need for caution in dealing with these large contaminated systems. The obvious area affected by these findings is in the awareness by building managers and facilities managers that this contamination exists and that all appropriate measures are taken to minimise infection spread due to normal o&m operations. While it was not possible to detect the virus in the airflow itself, it is considered significant that the identification of the direction and magnitude of these airflows confirms that building drainage stacks could act as conduits for the transmission of aerosolised pathogen-laden water droplets. This research suggests that there is a need for a secure and verifiable seal between the building drainage/sewer network and habitable space within a building to minimize the likelihood of any potential cross-contamination and consequent risk to human health. © 2013 The Chartered Institution of Building Services Engineers.

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