New strategies for human papillomavirus-based cervical screening.

Author manuscript; published in final edited form as: Womens Health (Lond Engl). 2013 September; 9(5):. doi:10.2217/whe.13.48Human papillomavirus testing has been shown to be far more sensitive and robust in detecting cervical intraepithelial neoplasia 2 and above (and cervical intraepithelial neoplasia 3 and above) for cervical screening than approaches based on either cytology or visual inspection; however, there are a number of issues that need to be overcome if it is to substantially reduce the morbidity and mortality associated with cervical cancer at the population level. The two main issues are coverage (increasing the number of women who participate in screening) and the management of women who test positive for high-risk human papillomavirus. This article will review the potential for vaginal self-collection to improve coverage and the options for triage of high-risk human papillomavirus-positive women in high-resource and low-resource settings

HPV16 L1 and L2 DNA methylation predicts high-grade cervical intraepithelial neoplasia in women with mildly abnormal cervical cytology

Cancer Research UK, Queen Mary University of London. Grant Number: project grant C8162/A4609 and programme grants C8162/A10406, C569/A10404 and C236/A1179

Routine cervical screening with primary HPV testing and cytology triage protocol in a randomised setting

The role of high-risk human papillomavirus (hrHPV) testing in primary cervical screening has not been established. We generated a randomised evaluation design ultimately to clarify whether primary hrHPV testing implemented into routine screening can bring increase in the programme effectiveness. The aim of the present report on first-year results was to assess the cross-sectional relative validity parameters for routine hrHPV screening, in comparison with conventional screening. An equal number of women invited to routine screening was randomly allocated to primary hrHPV screening (n=7060) and to cytological screening (n=7089). In the hrHPV screening arm, after a single positive hrHPV test result, the need of colposcopy referral was determined by a cytological triage test. Compared with the conventional arm, more colposcopy referrals were made in the hrHPV screening arm (relative risk 1.51, confidence interval 95% 1.03–2.22). Specificity of the primary screening with sole hrHPV test (91.5–92.1%) was much lower than that with the cytology triage (98.7–99.3%), which was not quite as specific as screening with conventional cytology (99.2–99.6%). Compared with conventional cytology, primary screening with hrHPV test results in increased cross-sectional relative sensitivity at the level of all positive lesions at the cost of substantial loss in specificity. With cytology triage, the specificity improves to the level of conventional cytology

Some Comments on the Entropy-Based Criteria for Piping

This paper is an extension of previous work which characterises soil behaviours using the grading entropy diagram. The present work looks at the piping process in granular soils, by considering some new data from flood-protection dikes. The piping process is divided into three parts here: particle movement at the micro scale to segregate free water; sand boil development (which is the initiation of the pipe), and pipe growth. In the first part of the process, which occurs during the rising flood, the increase in shear stress along the dike base may cause segregation of water into micro pipes if the subsoil in the dike base is relatively loose. This occurs at the maximum dike base shear stress level (ratio of shear stress and strength) zone which is close to the toe. In the second part of the process, the shear strain increment causes a sudden, asymmetric slide and cracking of the dike leading to the localized excess pore pressure, liquefaction and the formation of a sand boil. In the third part of the process, the soil erosion initiated through the sand boil continues, and the pipe grows. The piping in the Hungarian dikes often occurs in a two-layer system; where the base layer is coarser with higher permeability and the cover layer is finer with lower permeability. The new data presented here show that the soils ejected from the sand boils are generally silty sands and sands, which are prone to both erosion (on the basis of the entropy criterion) and liquefaction. They originate from the cover layer which is basically identical to the soil used in the Dutch backward erosion experiments

GMAP is an Atg8a-interacting protein that regulates Golgi turnover In Drosophila

Selective autophagy receptors and adapters contain short linear motifs called LIR motifs (LC3-interacting region), which are required for the interaction with the Atg8-family proteins. LIR motifs bind to the hydrophobic pockets of the LIR motif docking site (LDS) of the respective Atg8-family proteins. The physiological significance of LDS docking sites has not been clarified in vivo. Here, we show that Atg8a-LDS mutant Drosophila flies accumulate autophagy substrates and have reduced lifespan. Using quantitative proteomics to identify the proteins that accumulate in Atg8a-LDS mutants, we identify the cis-Golgi protein GMAP (Golgi microtubule-associated protein) as a LIR motif-containing protein that interacts with Atg8a. GMAP LIR mutant flies exhibit accumulation of Golgi markers and elongated Golgi morphology. Our data suggest that GMAP mediates the turnover of Golgi by selective autophagy to regulate its morphology and size via its LIR motif-mediated interaction with Atg8a