Evidence for cross-protection but not type-replacement over the 11 years after human papillomavirus vaccine introduction

Examination of cross-protection and type replacement after human papillomavirus (HPV) vaccine introduction is essential to guide vaccination recommendations and policies. The aims of this study were to examine trends in non-vaccine-type HPV: 1) genetically related to vaccine types (to assess for cross-protection) and 2) genetically unrelated to vaccine types (to assess for type replacement), among young women 13-26 years of age during the 11 years after HPV vaccine introduction. Participants were recruited from a hospital-based teen health center and a community health department for four cross-sectional surveillance studies between 2006 and 2017. Participants completed a survey that assessed sociodemographic characteristics and behaviors, and cervicovaginal swabs were collected and tested for 36 HPV genotypes. We determined changes in proportions of non-vaccine-type HPV prevalence and conducted logistic regression to determine the odds of infection across the surveillance studies, propensity-score adjusted to control for selection bias. Analyses were stratified by vaccination status. Among vaccinated women who received only the 4-valent vaccine (n = 1,540), the adjusted prevalence of HPV types genetically related to HPV16 decreased significantly by 45.8% (adjusted odds ratio [AOR] = 0.48, 95% confidence interval [CI] = 0.31-0.74) from 2006-2017, demonstrating evidence of cross-protection. The adjusted prevalence of HPV types genetically related to HPV18 did not change significantly (14.2% decrease, AOR = 0.83, 95% CI = 0.56-1.21). The adjusted prevalence of HPV types genetically unrelated to vaccine types did not change significantly (4.2% increase, AOR = 1.09, CI = 0.80-1.48), demonstrating no evidence of type replacement. Further studies are needed to monitor for cross-protection and possible type replacement after introduction of the 9-valent HPV vaccine

Epidemiology of Any and Vaccine-Type Anogenital Human Papillomavirus Among 13-26-Year-Old Young Men After HPV Vaccine Introduction

PURPOSE: The aims of this study were to determine prevalence of and factors associated with any human papillomavirus (HPV) and vaccine-type HPV among young men after vaccine introduction, stratified by vaccination status. METHODS: Young men were recruited from clinical sites from 2013 to 2015, completed a survey, and were tested for 36 anogenital HPV types. We determined factors associated with ≥1 HPV type among all participants, and vaccine-type HPV (HPV6, 11, 16, and/or 18) among all, vaccinated and unvaccinated participants, using multivariable regression. RESULTS: Mean age was 21.5 years and 26% had received at least one HPV vaccine dose. HPV prevalence was lower in vaccinated versus unvaccinated young men (50.5% vs. 62.6%, p = .03). HPV positivity was discordant by anogenital site. At both sites, 59.4% were positive for ≥1 HPV type and 26.0% for ≥1 4-valent vaccine type. In multivariable logistic regression, factors associated with ≥1 HPV type among all participants were frequency of oral sex (odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.00-3.24), recent smoking (OR = 1.84, CI = 1.17-2.90), and sexually transmitted infection history (OR = 1.56, CI = 1.02-2.38). Factors associated with vaccine-type HPV among all participants were white versus black race (OR = 1.91, CI = 1.10-3.34) and gonorrhea history (OR = 2.52, CI = 1.45-4.38); among vaccinated participants were private versus Medicaid insurance (OR = 5.6, CI = 1.46-20.4) and private versus no insurance (OR = 15.9, CI = 3.06-83.3); and among unvaccinated participants was gonorrhea history (OR = 1.83, CI = 1.03-3.24). CONCLUSIONS: Anogenital HPV prevalence was high and vaccination rates low among young men 2-4 years after vaccine introduction, underscoring the urgency of increasing vaccination rates and vaccinating according to national guidelines

Change in hematologic indices over time in pediatric inflammatory bowel disease treated with azathioprine

Azathioprine leads to changes in mean corpuscular volume (MCV) and white blood cell (WBC) indices reflecting efficacy or toxicity. Understanding the interactions between bone marrow stem cells and azathioprine could highlight abnormal response patterns as forerunners for hematologic malig-nancies. This study gives a statistical description of factors influencing the relationship between MCV and WBC in children with inflammatory bowel disease treated with azathioprine. We found that leukopenia preceded macro¬cytosis. Macrocytosis is therefore not a good predictor of leukopenia. Further studies will be necessary to determine the subgroup of patients at increased risk of malignancies based on bone marrow response

School-age effects of the newborn individualized developmental care and assessment program for preterm infants with intrauterine growth restriction: preliminary findings

Background: The experience in the newborn intensive care nursery results in premature infants’ neurobehavioral and neurophysiological dysfunction and poorer brain structure. Preterms with severe intrauterine growth restriction are doubly jeopardized given their compromised brains. The Newborn Individualized Developmental Care and Assessment Program improved outcome at early school-age for preterms with appropriate intrauterine growth. It also showed effectiveness to nine months for preterms with intrauterine growth restriction. The current study tested effectiveness into school-age for preterms with intrauterine growth restriction regarding executive function (EF), electrophysiology (EEG) and neurostructure (MRI). Methods: Twenty-three 9-year-old former growth-restricted preterms, randomized at birth to standard care (14 controls) or to the Newborn Individualized Developmental Care and Assessment Program (9 experimentals) were assessed with standardized measures of cognition, achievement, executive function, electroencephalography, and magnetic resonance imaging. The participating children were comparable to those lost to follow-up, and the controls to the experimentals, in terms of newborn background health and demographics. All outcome measures were corrected for mother’s intelligence. Analysis techniques included two-group analysis of variance and stepwise discriminate analysis for the outcome measures, Wilks’ lambda and jackknifed classification to ascertain two-group classification success per and across domains; canonical correlation analysis to explore relationships among neuropsychological, electrophysiological and neurostructural domains at school-age, and from the newborn period to school-age. Results: Controls and experimentals were comparable in age at testing, anthropometric and health parameters, and in cognitive and achievement scores. Experimentals scored better in executive function, spectral coherence, and cerebellar volumes. Furthermore, executive function, spectral coherence and brain structural measures discriminated controls from experimentals. Executive function correlated with coherence and brain structure measures, and with newborn-period neurobehavioral assessment. Conclusion: The intervention in the intensive care nursery improved executive function as well as spectral coherence between occipital and frontal as well as parietal regions. The experimentals’ cerebella were significantly larger than the controls’. These results, while preliminary, point to the possibility of long-term brain improvement even of intrauterine growth compromised preterms if individualized intervention begins with admission to the NICU and extends throughout transition home. Larger sample replications are required in order to confirm these results

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Bose-Einstein condensation as symmetry breaking in compact curved spacetimes

We examine Bose-Einstein condensation as a form of symmetry breaking in the specific model of the Einstein static universe. We show that symmetry breaking never occursin the sense that the chemical potential $\mu$ never reaches its critical value.This leads us to some statements about spaces of finite volume in general. In an appendix we clarify the relationship between the standard statistical mechanical approaches and the field theory method using zeta functions.Comment: Revtex, 25 pages, 3 figures, uses EPSF.sty. To be published in Phys. Rev.

Deterministic and stochastic descriptions of gene expression dynamics

A key goal of systems biology is the predictive mathematical description of gene regulatory circuits. Different approaches are used such as deterministic and stochastic models, models that describe cell growth and division explicitly or implicitly etc. Here we consider simple systems of unregulated (constitutive) gene expression and compare different mathematical descriptions systematically to obtain insight into the errors that are introduced by various common approximations such as describing cell growth and division by an effective protein degradation term. In particular, we show that the population average of protein content of a cell exhibits a subtle dependence on the dynamics of growth and division, the specific model for volume growth and the age structure of the population. Nevertheless, the error made by models with implicit cell growth and division is quite small. Furthermore, we compare various models that are partially stochastic to investigate the impact of different sources of (intrinsic) noise. This comparison indicates that different sources of noise (protein synthesis, partitioning in cell division) contribute comparable amounts of noise if protein synthesis is not or only weakly bursty. If protein synthesis is very bursty, the burstiness is the dominant noise source, independent of other details of the model. Finally, we discuss two sources of extrinsic noise: cell-to-cell variations in protein content due to cells being at different stages in the division cycles, which we show to be small (for the protein concentration and, surprisingly, also for the protein copy number per cell) and fluctuations in the growth rate, which can have a significant impact.Comment: 23 pages, 5 figures; Journal of Statistical physics (2012

Bose-Einstein condensation for interacting scalar fields in curved spacetime

We consider the model of self-interacting complex scalar fields with a rigid gauge invariance under an arbitrary gauge group $G$. In order to analyze the phenomenon of Bose-Einstein condensation finite temperature and the possibility of a finite background charge is included. Different approaches to derive the relevant high-temperature behaviour of the theory are presented.Comment: 28 pages, LaTe