Solid-state Marx based two-switch voltage modulator for the On-Line Isotope Mass Separator accelerator at the European Organization for Nuclear Research

A new circuit topology is proposed to replace the actual pulse transformer and thyratron based resonant modulator that supplies the 60 kV target potential for the ion acceleration of the On-Line Isotope Mass Separator accelerator, the stability of which is critical for the mass resolution downstream separator, at the European Organization for Nuclear Research. The improved modulator uses two solid-state switches working together, each one based on the Marx generator concept, operating as series and parallel switches, reducing the stress on the series stacked semiconductors, and also as auxiliary pulse generator in order to fulfill the target requirements. Preliminary results of a 10 kV prototype, using 1200 V insulated gate bipolar transistors and capacitors in the solid-state Marx circuits, ten stages each, with an electrical equivalent circuit of the target, are presented, demonstrating both the improved voltage stability and pulse flexibility potential wanted for this new modulator

Effect of diindolylmethane supplementation on low-grade cervical cytological abnormalities: double-blind, randomised, controlled trial

This work was supported by a Cancer Research UK project grant (C8162/A4609 project costs) and a programme grant (C8162/A10406)

Human papillomavirus prevalence in women attending routine cervical screening in South Wales, UK: a cross-sectional study

In this cross-sectional population-based study we determine human papillomavirus (HPV) prevalence in South Wales to provide comprehensive baseline data for future assessment of the impact of prophylactic HPV vaccination and to help inform future screening strategies. Liquid-based cytology samples from women attending routine cervical screening were collected (n=10 000: mean age 38 years, 93% cytology negative, and 64.8% from the 50% least deprived LSOA according to social deprivation score (SDS)). High-Risk (HR) and Low-Risk HPV screening was performed using HPV PCR-EIA with genotyping of HR positives and data correlated with age, SDS and cytology. Overall HPV prevalence was 13.5% (9.3% age standardised) and the most frequent HR types were HPV 16, 31, 18 and 58. In HR HPV-positive cases 42.4% had a single HR type and they were predominant in women with severe cytological abnormalities. Here, 66% of all HR HPV cases were in women aged 30 years of age or less and SDS had no significant effect on HPV status. HPV prevalence increased significantly with degree of dyskarosis from 7% in cytology negative samples to 80% in samples with severe cytological abnormalities (P-value <0.0001). Overall, 46% of HR HPV cases were positive for the two HR types targeted by the prophylactic vaccines (HPV 16 and HPV 18). The data presented represents the largest type-specific investigation of HPV prevalence in an unselected UK population

Cervical human papillomavirus infection and squamous intraepithelial lesions in rural Gambia, West Africa: viral sequence analysis and epidemiology

The development of effective strategies against cervical cancer in Africa requires accurate type specific data on human papillomavirus (HPV) prevalence, including determination of DNA sequences in order to maximise local vaccine efficacy. We have investigated cervical HPV infection and squamous intraepithelial lesions (SIL) in an unselected cohort of 1061 women in a rural Gambian community. Squamous intraepithelial lesions was diagnosed using cytology and histology, HPV was typed by PCR-ELISA of DNA extracts, which were also DNA sequenced. The prevalence of cervical HPV infection was 13% and SIL were observed in 7% of subjects. Human papillomavirus-16 was most prevalent and most strongly associated with SIL. Also common were HPV-18, -33, -58 and, notably, -35. Human papillomavirus DNA sequencing revealed HPV-16 samples to be exclusively African type 1 (Af1). Subjects of the Wolof ethnic group had a lower prevalence of HPV infection while subjects aged 25–44 years had a higher prevalence of cervical precancer than older or younger subjects. This first report of HPV prevalence in an unselected, unscreened rural population confirms high rates of SIL and HPV infection in West Africa. This study has implications for the vaccination of Gambian and other African populations in the prevention of cervical cancer

Cervical cancer screening service utilisation in UK.

This study investigates empirically how past screening behaviour, individual and household characteristics affect the current uptake of cervical cancer screening in UK. For the conceptual framework, we use a modified Grossman model which is extended for non-economic factors. A dynamic version of a random effects panel probit model with initial conditions is estimated on the balanced sub-sample of the data. The analysis sample is restricted to women of age 16 and older and grouped into different age categories with respect to the NHS Cervical Screening Programme (NHSCSP). As dataset a balanced panel data of 857 women with 11,998 observations from the British Household Panel Study (BHPS) for the period from 1992 to 2008 is used for the analysis. Results suggest show that previous screening uptake, age, partner status, employment status and a previous GP visit have a significant influence on the likelihood of the uptake of cervical cancer screening

Human papillomavirus type 16 L1/L2 DNA methylation shows weak association with cervical disease grade in young women

BackgroundPersistent infection with human papillomavirus (HPV) type 16 causes the majority of cervical cancers. Genital HPV infection is very common, but neoplastic progression is uncommon. There is an urgent need for biomarkers associated with cervical neoplasia, to enable triage of women who test positive for HPV.ObjectivesTo assess the ability of quantitative measurement of HPV16 DNA methylation to separate samples of different cytological and histological grades from young women, among whom rates of HPV infection are high.Study designDNA methylation was quantified by pyrosequencing of bisulphite converted DNA from liquid based cytology samples from 234 women (mean age 20.6 years) who tested positive for HPV16 and showed varying degrees of neoplasia. Methylation was assessed at CpGs in the HPV E2 and L1/L2 regions.ResultsThe performance of methylation-based classifiers was assessed by ROC curve analyses. The best combination of CpGs (5600 and 5609) achieved AUCs of 0.656 (95% CI = 0.520–0.792) for separation of cytologically normal and severely dyskaryotic samples, and 0.639 (95% CI = 0.547–0.731) for separation of samples with or without high-grade neoplasia (CIN2+/−).ConclusionsThe data are consistent with HPV L1/L2 methylation being a marker of the duration of infection in a specific host. Assessment of HPV DNA methylation is hence a promising biomarker to triage HPV-positive cytology samples, but may have limited utility in young women. Future studies assessing the likely utility of HPV DNA methylation as a potential triage biomarker must take account of women’s age