Grading immunohistochemical markers p16INK4a and HPV E4 identifies productive and transforming lesions caused by low- and high-risk HPV within high-grade anal squamous intraepithelial lesions

Objectives: Because current guidelines recognise high-grade anal squamous intraepithelial lesions (HSILs) and low-grade SILs (LSILs), and recommend treatment of all HSILs although not all progress to cancer, this study aims to distinguish transforming and productive HSILs by grading immunohistochemical (IHC) biomarkers p16INK 4a (p16) and E4 in low-risk human papillomavirus (lrHPV) and high-risk (hr)HPV-associated SILs as a potential basis for more selective treatment. Methods: Immunostaining for p16 and HPV E4 was performed and graded in 183 biopsies from 108 HIV-positive men who have sex with men. The causative HPV genotype of the worst lesion was identified using the HPV SPF10-PCR-DEIA-LiPA25 version 1 system, with laser capture microdissection for multiple infections. The worst lesions were scored for p16 (0–4) to identify activity of the hrHPV E7 gene, and panHPV E4 (0–2) to mark HPV production and life cycle completion. Results: There were 37 normal biopsies, 60 LSILs and 86 HSILs, with 85% of LSILs caused by lrHPV and 93% of HSILs by hrHPV. No normal biopsy showed E4, but 43% of LSILs and 37% of HSILs were E4 positive. No differences in E4 positivity rates were found between lrHPV and hrHPV lesions. Most of the lesions caused by lrHPV (90%) showed very extensive patchy p16 staining; p16 grade in HSILs was variable, with frequency of productive HPV infection dropping with increasing p16 grade. Conclusions: Combined p16/E4 IHC identifies productive and nonproductive HSILs associated with hrHPV within the group of HSILs defined by the Lower Anogenital Squamous Terminology recommendations. This opens the possibility of investigating selective treatment of advanced transforming HSILs caused by hrHPV, and a ‘wait and see’ policy for productive HSILs. What's already known about this topic?. For preventing anal cancer in high-risk populations, all patients with high-grade squamous intraepithelial lesions (HSILs) are treated, even though this group of lesions is heterogeneous, the histology is variable and regression is frequent. What does this study add?. By adding human papillomavirus (HPV) E4 immunohistochemistry to p16 INK4a (p16), and grading expression of both markers, different biomarker expression patterns that reflect the heterogeneity of HSILs can be identified. Moreover, p16/E4 staining can separate high-risk HPV-associated HSILs into productive and more advanced transforming lesions, providing a potential basis for selective treatment

Automated measurements of out-of-plane, ultrasonic elastic stiffnesses in paper

"August, 1988.""This manuscript is based on results obtained in IPC research and has been submitted for consideration for publication in the Journal of Pulp and Paper Science.

Using neoprene-faced, PVDF transducers to couple ultrasound into solids

"January, 1988.""This paper is based on IPC Project 3467 and has been submitted for consideration for publication in the Journal of the American Acoustical Society.

Neurotensin and bombesin, a relationship between their effects on body temperature and locomotor activity?

Neurotensin and bombesin have been tested for their effects on body temperature and locomotor activity in an open field. Both peptides induce hypothermia and suppress ambulation and rearing. The time curves of the hypothermic effects of both peptides appear to be rather similar, although bombesin is a more potent hypothermic agent than neurotensin. The time curves of the effects on locomotor activity appear to be quite different. The suppressive effect of neurotensin on locomotor activity is relatively short lasting and reaches its maximum at approximately 32 minutes. The effect of bombesin follows a different time curve and shows two peaks, suggesting that two different mechanisms are involved in the suppressive action of bombesin on locomotor activity. Calculation of the correlation coefficients between the effects of neurotensin and of bombesin on body temperature and on locomotor activity (ambulation) suggest that a causal relationship between these two effects is not likely, in particular for neurotensin

Safety of extending screening intervals beyond five years in cervical screening programmes with testing for high risk human papillomavirus: 14 year follow-up of population based randomised cohort in the Netherlands

OBJECTIVES To provide an early risk assessment of extending screening intervals beyond five years for a human papillomavirus (HPV) based cervical screening programme in the Netherlands. DESIGN 14 year follow-up of a population based randomised cohort from the POBASCAM randomised trial. SETTING Organised cervical screening in the Netherlands, based on a programme of three screening rounds (each round done every five years). PARTICIPANTS 43 339 women aged 29-61 years with a negative HPV and/or negative cytology test participating in the POBASCAM trial. INTERVENTIONS Women randomly assigned to HPV and cytology co-testing (intervention) or cytology testing only (control), and managed accordingly. MAIN OUTCOME MEASURES Cumulative incidence of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 or worse (CIN3+). Associations with age were expressed as incidence rate ratios. In HPV positive women, reductions in CIN3+ incidence after negative cytology, HPV type 16/18 genotyping, and/or repeat cytology were estimated. RESULTS The cumulative incidence of cervical cancer (0.09%) and CIN3+ (0.56%) among HPV negative women in the intervention group after three rounds of screening were similar to the cumulative among women with negative cytology in the control group after two rounds (0.09% and 0.69%, respectively). Cervical cancer and CIN3+ risk ratios were 0.97 (95% confidence interval 0.41 to 2.31, P=0.95) and 0.82 (0.62 to 1.09, P=0.17), respectively. CIN3+ incidence was 72.2% (95% confidence interval 61.6% to 79.9%, Pfive years) should be implemented with risk stratification

Using a robot based instrument to measure the in-plane ultrasonic velocities of paper

"September, 1988.""Portions of this work were used by BMP as partial fulfillment of the requirements for the Master of Science degree at The Institute of Paper Chemistry. This paper has been submitted for consideration for publication in Tappi Journal.

Automatic determination of ultrasound velocities in planar materials

"June, 1986.

Corrigendum: Sediments as a Source of Iron, Manganese, Cobalt and Nickel to Continental Shelf Waters (Louisiana, Gulf of Mexico)(Front. Mar. Sci., (2022), 9, (811953), 10.3389/fmars.2022.811953)

In the original article, the support by the Netherlands Initiative Changing Oceans Program(NICO) was not mentioned in the acknowledgments. The corrected Acknowledgments are shown below: “We thank the captain, crew, technicians, (co-)chief scientists D. Rush and Z. Erdem and all other scientists aboard R/V Pelagia during cruise 64PE434 of the Netherlands Initiative Changing Oceans Program (NICO) in March 2018, for their assistance. We also thank H. de Waard, C. Mulder, M. Séguret, and A. van Dijk for analytical assistance in Utrecht.” The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been update