New correlation consistent basis sets for the second-row atoms (Al–Ar) to be used with the neon-core correlation consistent effective core potentials (ccECPs) have been developed. The basis sets, ...denoted cc-pV(n+d)Z-ccECP (n = D, T, Q), include the “tight”-d functions that are known to be important for second-row elements. Sets augmented with additional diffuse functions are also reported. Effective core polarization potentials (CPPs) to account for the effect of core–valence correlation have been adjusted for the same elements, and two different forms of the CPP cutoff function have been analyzed. The accuracy of both the basis sets and the CPPs is assessed through benchmark calculations at the coupled-cluster level of theory for atomic and molecular properties. Agreement with all-electron results is much improved relative to the basis sets that originally accompanied the ccECPs; moreover, the combination of cc-pV(n+d)Z-ccECP and CPPs is found to be a computationally efficient and accurate alternative to including core electrons in the correlation treatment.
SummaryThe penetration characteristics of five modern wood coatings (three waterborne, one high solid and one solvent borne) into pine sapwood, spruce and dark red meranti have been systematically ...compared. The degree of coating penetration is mainly determined by the ability of the coating to flow into wood capillaries. Binder type, pigmentation, solid matter content and drying speed appeared to influence this ability. In softwoods the following different coating penetration routes are observed: the flow into open ends of longitudinal early-and latewood tracheids, the flow into ray cells and the transport from rays through the cross-field into longitudinal tracheids adjacent to rays. The possibility for the coating to follow the latter route is strongly influenced by the existing type of cross field pitting and to a lesser degree by the pigmentation of the paint. Clear differences between pine and spruce have been found with respect to the flow into ray parenchym and ray tracheids. The flow into open ends of longitudinal tracheids is strongly influenced by the grain angle of tracheids. Penetration into dark red meranti is mainly limited to vessels and rays. Tylose membranes can prevent the complete filling of vessels. The impact on penetration of the removal of extractives and of sanding of the surface has also been studied but appears to be of only minor importance.
The aim was to evaluate the cross-sectional and long-term triage performance of FAM19A4/miR124-2 methylation analysis in human papillomavirus (HPV)-based cervical screening.
We conducted a post hoc ...analysis within a Dutch population-based HPV-positive study cohort of women aged 30–60 years (n = 979). Cross-sectional cervical intraepithelial neoplasia (CIN) 3+ sensitivity, specificity, positive predictive value and negative predictive value as well as cumulative CIN3+ or cervical cancer risks after 9 and 14 years were compared for three baseline triage strategies: (1) cytology, (2) FAM19A4/miR124-2 methylation analysis and (3) combined FAM19A4/miR124-2 methylation with cytology.
CIN3+ sensitivity of FAM19A4/miR124-2 methylation analysis was similar to that of cytology (71.3% vs 76.0%, ratio 0.94, 95% CI 0.84 to 1.05), at a lower specificity (78.3% vs 87.0%, ratio 0.90, 95% CI 0.86 to 0.94). Combining FAM19A4/miR124-2 methylation analysis with cytology resulted in a CIN3+ sensitivity of 84.6% (95% CI 78.3 to 90.8) at a specificity of 69.6% (95% CI 66.5 to 72.7). Similar 9- and 14-year CIN3+ risks for baseline cytology-negative women and baseline FAM19A4/miR124-2 methylation-negative women were observed, with risk differences of –0.42% (95% CI –2.1 to 1.4) and –0.07% (95% CI –1.9 to 1.9), respectively. The 14-year cumulative cervical cancer incidence was significantly lower for methylation-negative women compared to cytology-negative women (risk difference 0.98%, 95% CI 0.26 to 2.0).
FAM19A4/miR124-2 methylation analysis has a good triage performance on baseline screening samples, with a cross-sectional CIN3+ sensitivity and long-term triage-negative CIN3+ risk equalling cytology triage. Therefore, FAM19A4/miR124-2 methylation analysis appears to be a good and objective alternative to cytology in triage scenarios in HPV-based cervical screening.
In view of possible type replacement upon introduction of human papillomavirus (HPV) vaccination, we aimed to explore patterns of type-specific clustering across populations with various background ...infection risks. A total of 3,874 women from 3 cross-sectional studies in the Netherlands (in 2007–2009) provided vaginal self-samples, which were tested for 25 HPV genotypes by a sensitive molecular assay (SPF10 line probe assay, DDL Diagnostic Laboratory, Voorburg, the Netherlands). The number of concurrent HPV infections per woman was studied by Poisson regression. Associations between HPV types were investigated by generalized estimating equation analyses. The prevalence of any HPV type was 14% in a population-based study, 54% in a chlamydia screening intervention study, and 73% in a study among attendees of sexually transmitted infection clinics. Overall, multiple HPV infections were detected in 26% of the women. The number of concurrent HPV infections conformed to an overdispersed Poisson distribution, even after correction for known risk factors. Types differed significantly in their tendencies to be involved in coinfections, but no evidence for particular type-type interactions was found. Moreover, the strongest associations were observed in the lowest-risk population and vice versa.We found no indications of pairwise interactions, but our findings do suggest that clustering differs among HPV types and varies across risk groups.
Abstract Cervical cancer incidence and mortality in Poland is among the highest in Europe. To investigate infection with different human papillomaviruses (HPV) in Warsaw, Poland, we obtained cervical ...cell specimens from 834 women aged 18–59 years from the general population, and 88 cervical cancers. DNA of 44 HPV types was detected using a GP5+/6+-based PCR assay. HPV prevalence was 16.6% in the general female population, being highest (24.2%) in women aged 25–34 years, notably among unmarried women (37.3%). HPV prevalence fell to 8.6% at ages 55–59. High-risk HPV prevalence was 11.3%, with HPV16 being the most common type (3.7%). All but one cervical cancer were high-risk HPV-positive, although the importance of HPV16 (73%) was much greater, and multiple infections fewer (1%), than among HPV-positive women in the general female population. In summary, we report a relatively high burden of HPV infection in Warsaw, Poland, where 79% of cervical cancers are theoretically preventable by HPV16/18 vaccines.
We followed 353 women referred with abnormal cervical cytology in a non-intervention cohort study. In 91 pregnant women we compared high-risk human papilloma virus rates in the subsequent trimesters ...and postpartum in comparison to 262 non-pregnant women. High-risk human papilloma virus clearance was compared with 179 high-risk human papilloma virus positive non-pregnant women. Our main questions were: (1) do high-risk human papilloma virus rates change during pregnancy?; and (2) is there any difference between high-risk human papilloma virus clearance in pregnant and non-pregnant women? Women were monitored 3-4 monthly by cytology, colposcopy, and high-risk human papilloma virus testing. The median follow-up time was 33 months (range 3-74). Non-pregnant women showed prevalence rates of high-risk human papilloma virus of 64, 57, 53, and 50%, respectively, in four subsequent 3-months periods since the start of the study. These high-risk human papilloma virus rates were higher than in the three trimesters of pregnancy, and during the first 3 months postpartum, i.e. 50, 44, 45, and 31%, respectively. Postpartum only, this difference was statistically significant (P=0.004). Paired comparisons of high-risk human papilloma virus prevalence rates of the different trimesters with the postpartum rate showed (McNemar test) decreased rates: first trimester: 18% (P=0.02), second trimester: 13% (P=0.02) and third trimester: 23% (P<0.005). Such a phenomenon was not found in non-pregnant women. Pregnant women showed a trend for increased high-risk human papilloma virus clearance during the third trimester and postpartum compared to non-pregnant women (hazard ratios 3.3 (0.8-13.7) and 4.6 (1.6-12.8), respectively). These results suggest a lowered immune-response against human papilloma virus during the first two trimesters of pregnancy with a catch-up postpartum.
Primary testing for human papillomavirus (HPV) in cervical screening requires triage to differentiate women with transient infection from those with persistent infection who require more intensive ...management given their risk for cervical (pre)cancer. In this study, the clinical performance of a novel methylation marker FAM19A4 for the triage of high-risk (hr)HPV-positive women was evaluated. Using a training-validation set approach, we analyzed a FAM19A4 quantitative methylation-specific PCR (qMSP). The training set comprised hrHPV-positive cervical scrapes of 43 women with cervical intraepithelial neoplasia grade 3 or worse (CIN3+) and 135 women with ≤CIN1. The validation set comprised hrHPV-positive cervical scrapes of 52 women with CIN2+, including 33 CIN3+, 19 CIN2, and 166 women with ≤CIN1. The methylation threshold of FAM19A4 qMSP that gave rise to CIN3+ specificity of 70% in the training set was applied in the validation set. This resulted in CIN3+ sensitivity of 75.8% 95% confidence interval (CI), 61.1-90.4 at 67.0% (95% CI, 60.3-73.8) specificity. Next, the validated qMSP was applied to an independent series of hrHPV-positive cervical scrapes of 22 women with cervical cancer, 29 with advanced CIN2/3 i.e., women with a known preceding hrHPV infection (PHI) lasting ≥5 years as proxy of longer duration of lesion existence, and 19 with early CIN2/3 (i.e., PHI <5 years). All carcinomas (22/22) and advanced CIN2/3 lesions (29/29) were FAM19A4 methylation-positive, compared with 42.1% (8/19; 95% CI, 19.9-64.3) of early CIN2/3 lesions. In conclusion, FAM19A4 is an attractive triage marker for hrHPV-positive women, with a high reassurance for the detection of cervical carcinoma and advanced CIN2/3 lesions.
Thermal Diels-Alder reactions of chiral 9-methoxyethyl and 9-hydroxyethyl anthracene have been investigated both experimentally and computationally with a range of N-substituted maleimides. Whereas ...cycloadditions with 9-methoxyethyl anthracene proceeded with almost complete diastereselectivity, those with 1-anthracene-9-yl-ethanol resulted in essentially no diastereoselectivity. Subsequent regio- and stereoselective transformations with reducing agents and carbon nucleophiles demonstrated the synthetic utility of this methodology, which was applied to the enantioselective synthesis of pyrrolo2,1-aisoquinolines and an attempted synthesis of the alkaloid crispine A. Computational studies supported the proposed hypotheses for the stereoselectivity observed in the transformations described.
Summary Background Tests for the DNA of high-risk types of human papillomavirus (HPV) have a higher sensitivity for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) than does cytological ...testing, but the necessity of such testing in cervical screening has been debated. Our aim was to determine whether the effectiveness of cervical screening improves when HPV DNA testing is implemented. Methods Women aged 29–56 years who were participating in the regular cervical screening programme in the Netherlands were randomly assigned to combined cytological and HPV DNA testing or to conventional cytological testing only. After 5 years, combined cytological and HPV DNA testing were done in both groups. The primary outcome measure was the number of CIN3+ lesions detected. Analyses were done by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN20781131. Findings 8575 women in the intervention group and 8580 in the control group were recruited, followed up for sufficient time (≥6·5 years), and met eligibility criteria for our analyses. More CIN3+ lesions were detected at baseline in the intervention group than in the control group (68/8575 vs 40/8580, 70% increase, 95% CI 15–151; p=0·007). The number of CIN3+ lesions detected in the subsequent round was lower in the intervention group than in the control group (24/8413 vs 54/8456, 55% decrease, 95% CI 28–72; p=0·001). The number of CIN3+ lesions over the two rounds did not differ between groups. Interpretation The implementation of HPV DNA testing in cervical screening leads to earlier detection of CIN3+ lesions. Earlier detection of such lesions could permit an extension of the screening interval.
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