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Active school travel (walking, biking, scootering or skating to and from school) is declining in Wellington. This is concerning becauseactive forms of transport benefit children’s mental and physical health, as well as producing wider societal benefits such as lessnoise, reduced air pollution, lower congestion and fewer greenhouse gas emissions. This article explores the barriers to active schooltravel among primary school-aged children in Wellington, based on an anonymous online survey of parents. The results indicatethat the main barriers to active school travel are related to safety concerns, family schedule complexities, and the efficiency of othermodes of transport. Possible solutions include a walking school bus programme and more flexible working hours for parents, specifically during school drop-off and pick-up times.

Item does not contain fulltext 05 juli 2023

Methylation of host-cell deoxyribonucleic acid (DNA) has been proposed as a promising biomarker for triage of high-risk (hr) human papillomavirus (HPV) positive women at screening. Our study aims to validate recently identified host-cell DNA methylation markers for triage in an hrHPV-positive cohort derived from primary HPV-based cervical screening in The Netherlands. Methylation markers ASCL1, LHX8, ST6GALNAC5, GHSR, ZIC1 and SST were evaluated relative to the ACTB reference gene by multiplex quantitative methylation-specific PCR (qMSP) in clinician-collected cervical samples (n = 715) from hrHPV-positive women (age 29-60 years), who were enrolled in the Dutch IMPROVE screening trial (NTR5078). Primary clinical end-point was cervical intraepithelial neoplasia grade 3 (CIN3) or cancer (CIN3+). The single-marker and bi-marker methylation classifiers developed for CIN3 detection in a previous series of hrHPV-positive clinician-collected cervical samples were applied. The diagnostic accuracy was visualised using receiver operating characteristic (ROC) curves and assessed through area under the ROC curve (AUC). The performance of the methylation markers to detect CIN3+ was determined using the predefined threshold calibrated at 70% clinical specificity. Individual methylation makers showed good performance for CIN3+ detection, with highest AUC for ASCL1 (0.844) and LHX8 (0.830). Combined as a bi-marker panel with predefined threshold, ASCL1/LHX8 yielded a CIN3+ sensitivity of 76.9% (70/91; 95% CI 68.3-85.6%) at a specificity of 74.5% (465/624; 95% CI 71.1-77.9%). In conclusion, our study shows that the individual host-cell DNA methylation classifiers and the bi-marker panel ASCL1/LHX8 have clinical utility for the detection of CIN3+ in hrHPV-positive women invited for routine screening.

Orientadores: Jansle Vieira Rocha, Ramon Hanssen Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Engenharia Agrícola Resumo: Este estudo apresenta uma pesquisa sobre produtividade e monitoramento da cobertura de uso do solo, com foco na cana-de-açúcar, baseado em observações de sensoriamento remoto, coletadas por Synthetic Aperture Radar (SAR) e sensores ópticos. O estudo tem como objetivo fornecer novas discussões sobre técnicas e metodologias que permitem um monitoramento eficaz da produtividade da cana-de-açúcar e de sua expansão em larga escala ao longo do tempo. Este estudo faz parte de uma estrutura mais ampla de projetos de pesquisa, que possuem um objetivo geral de contribuir para uma sociedade de baseada na bioeconomia. O estado de São Paulo, Brasil, foi selecionado como área de estudo por ser uma das regiões mais importantes do mundo na produção de cana-de-açúcar, uma das culturas mais importantes para a produção de bioenergia. Como parte da pesquisa de monitoramento de produtividade, descrevemos detalhadamente os trabalhos de campo para a coleta de dados de cana de açúcar realizado em quatro áreas no estado de São de Paulo ao longo de um ano. Esses resultados são acompanhados de análises de qualidade das amostras, ilustrando sua confiabilidade das medições realizadas. Posteriormente, os dados de sensoriamento remoto de vários sensores ópticos e SAR (banda C e banda L) foram comparados com as medições realizadas em campo para desenvolver técnicas de monitoramento espacial da produtividade da cana de açúcar. Como parte da pesquisa de mapeamento, aplicamos uma adaptação do Modelo oculto de Markov para combinar dados SAR e observações ópticas. Uma atenção especial foi dada ao efeito da precipitação nas observações SAR e em certas condições da vegetação no desempenho do modelo. A pesquisa também discorre sobre as vantagens de se combinar dados SAR e observações ópticas. Posteriormente, foi demonstrada uma técnica que explora as flutuações do sinal SAR causadas por diferentes condições de umidade da superfície, a fim de melhorar a caracterização da vegetação. Finalmente, mostramos alguns exemplos de aplicações de nosso modelo no estado de São Paulo, desde os efeitos da seca em um reservatório de hidrelétrica, até mapas de ganhos e perdas de cobertura da terra ao longo de 15 anos no Estado Abstract: In this study, research on productivity and land cover monitoring is presented, with a focus on sugarcane, based on space-based remote sensing observations that were collected by Synthetic Aperture Radar (SAR) and optical sensors. The study aims to provide new insights into techniques and methodologies that allow for cost-efficient monitoring of sugarcane productivity and the wide-scale expansion of sugarcane over long time series. It is part of a wider framework of research projects, sharing the overarching goal to contribute to a biobased society. São Paulo state, Brazil, was selected as study area, primarily because it is one of the most prominent regions worldwide that hosts sugarcane, one of the most prominent crops for bio-energy production. As part of the productivity monitoring research we describe into detail the year-long sugarcane ground measurement campaign we conducted on four sugarcane fields in São Paulo state. These results are accompanied by detailed quality assessments, illustrating their reliability when collecting such measurements. Subsequently, remote sensing signals from various (C-band and L-band) SAR and optical satellites are compared to the ground reference measurements to develop space-based sugarcane productivity monitoring techniques. As part of the mapping research, we apply an adaptation of the Hidden Markov to combine SAR and optical observations. Special attention is paid to the effect of precipitation during SAR observations on and to certain vegetation conditions on the model¿s performance. The research also provides insights into the advantages when combining SAR and optical observations. Subsequently, a technique is demonstrated exploiting SAR signal fluctuations caused by varying surface wetness conditions in order to improve the characterization of vegetation. Finally, we show some examples of applications of our model in São Paulo state, from the effects of drought on a hydroelectric water reservoir to land cover gain and loss maps over 15 years in the state Doutorado Gestão de Sistemas na Agricultura e Desenvolvimento Rural Doutor em Engenharia Agrícola

Background: Radical cystectomy with pelvic lymph node dissection (PLND) and urinary diversion in patients with bladder cancer is known for its high risk of complications. Although open radical cystectomy (ORC) is regarded as the standard treatment, robot-assisted radical cystectomy (RARC) is increasingly used in practice, despite the fact that high-quality evidence comparing the effectiveness of both techniques is lacking.Objective: To study the effectiveness of RARC compared with that of ORC, in terms of 90 d complications (Clavien-Dindo), health-related quality of life (HRQOL), and clinical outcomes.Design, setting, and participants: A prospective comparative effectiveness study was conducted in 19 Dutch centres, expert in either ORC or RARC. Follow-up visits were scheduled at 30, 90, and 365 d.Intervention: Standard ORC or RARC with PLND, using a standardised perioperative protocol. Outcome measurements and statistical analysis: The primary outcome was any-grade complications after 90 d. Secondary outcomes included HRQOL, complications (minor, major, 30 d, and 365 d), and clinical outcomes. Differences were calculated as risk differences (RDs) between the groups with 95% confidence intervals (CIs), adjusted for potential baseline differences by means of propensity score–based inverse probability of treatment weighting.Results and limitations: Between March 2016 and November 2018, 348 patients were included (n = 168 for ORC, n = 180 for RARC). At 90 d, any-grade complication rates were 63% for ORC and 56% for RARC (RD –6.4%, 95% CI –17 to 4.5). Major complication rates were 15% for ORC and 16% for RARC (RD 0.9%, 95% CI –7.0 to 8.8). Total minor complication rates were 57% for ORC and 49% for RARC (RD –7.6%, 95% CI –19 to 3.6). Analyses showed no statistically significant differences in HRQOL between ORC and RARC. Some differences were found in the secondary outcomes in favour of either RARC or ORC. The major drawback inherent to the design comprises residual confounding.Conclusions: This multicentre comparative effectiveness study showed no statistically significant differences between ORC and RARC in terms of complications and HRQOL.Patient summary: This multicentre study did not show differences in overall complication rates, health-related quality of life, mortality, and clinical and oncological outcomes between open and robot-assisted radical cystectomy in bladder cancer patients.

Abnormal vaginal discharge may be caused by bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis and/or aerobic vaginitis. For the development of a diagnostic algorithm, tree-based classification analysis was performed on symptoms, signs and bedside test results of 56 patients, and laboratory tests (culture, Nugent score, qPCRs) were compared. Amplicon sequencing of the 16S rRNA gene was used as reference test for bacterial vaginosis and aerobic vaginitis, culture for vulvovaginal candidiasis and qPCR for trichomoniasis. For bacterial vaginosis, the best diagnostic algorithm was to screen at the bedside with a pH and odour test and if positive, to confirm by qPCR (sensitivity 94%; specificity 97%) rather than Nugent score (sensitivity of 59%; specificity 97%; P = 0.031). The analysis for the other infections was less conclusive due to the low num -ber of patients with these infections. For bacterial vaginosis, the developed algorithm is sensitive, specific, and reduces the need for laboratory tests in 50% of the patients. (c) 2021 Elsevier Inc. All rights reserved.

DNA methylation is a well-known epigenetic modification that plays a crucial role in gene regulation, but genome-wide analysis of DNA methylation remains technically challenging and costly. DNA methylation-dependent restriction enzymes can be used to restrict CpG methylation analysis to methylated regions of the genome only, which significantly reduces the required sequencing depth and simplifies subsequent bioinformatics analysis. Unfortunately, this approach has been hampered by complete digestion of DNA in CpG methylation-dense regions, resulting in fragments that are too small for accurate mapping. Here, we show that the activity of DNA methylation-dependent enzyme, LpnPI, is blocked by a fragment size smaller than 32 bp. This unique property prevents complete digestion of methylation-dense DNA and allows accurate genome-wide analysis of CpG methylation at single-nucleotide resolution. Methylated DNA sequencing (MeD-seq) of LpnPI digested fragments revealed highly reproducible genome-wide CpG methylation profiles for >50% of all potentially methylated CpGs, at a sequencing depth less than one-tenth required for whole-genome bisulfite sequencing (WGBS). MeD-seq identified a high number of patient and tissue-specific differential methylated regions (DMRs) and revealed that patient-specific DMRs observed in both blood and buccal samples predict DNA methylation in other tissues and organs. We also observed highly variable DNA methylation at gene promoters on the inactive X Chromosome, indicating tissue-specific and interpatient-specific escape of X Chromosome inactivation. These findings highlight the potential of MeD-seq for high-throughput epigenetic profiling.

Synthetic aperture radar (SAR) acquisitions are mainly deemed suitable for mapping dynamic land-cover and land-use scenarios due to their timeliness and reliability. This particularly applies to Sentinel-1 imagery. Nevertheless, the accurate mapping of regions characterized by a mixture of crops and grasses can still represent a challenge. Radar time-series have to date mainly been exploited through backscatter intensities, whereas only fewer contributions have focused on analyzing the potential of interferometric information, intuitively enhanced by the short revisit. In this paper, we evaluate, as primary objective, the added value of short-temporal baseline coherences over a complex agricultural area in the São Paulo state, cultivated with heterogeneously (asynchronously) managed annual crops, grasses for pasture and sugarcane plantations. We also investigated the sensitivity of the radar information to the classification methods as well as to the data preparation and sampling practices. Two supervised machine learning methods—namely support vector machine (SVM) and random forest (RF)—were applied to the Sentinel-1 time-series at the pixel and field levels. The results highlight that an improvement of 10 percentage points (p.p.) in the classification accuracy can be achieved by using the coherence in addition to the backscatter intensity and by combining co-polarized (VV) and cross-polarized (VH) information. It is shown that the largest contribution in class discrimination is brought during winter, when dry vegetation and bare soils can be expected. One of the added values of coherence was indeed identified in the enhanced sensitivity to harvest events in a small but significant number of cases.

Objective To compare the sensitivity of high-risk human papillomavirus (hrHPV) and genotype detection in self-collected urine samples in the morning (U1), and later on (U2), brush-based self-samples (SS), and clinician-taken smears (CTS) for detecting cervical intraepithelial neoplasia grade 2+ (CIN2+) in a colposcopic referral population. Design Cross-sectional single-centre study. Setting A colposcopy clinic in Spain. Population A cohort of 113 women referred for colposcopy after an abnormal Pap smear. Methods Women undergoing colposcopy with biopsy for abnormal Pap smears were sent a device (Colli-Pee™, Novosanis, Wijnegem, Belgium) to collect U1 on the morning of colposcopy. U2, CTS, and SS (Evalyn brush™, Rovers Medical Devices B.V., Oss, the Netherlands) were also analysed. All samples were tested for HPV DNA using the analytically sensitive SPF10-DEIA-LiPA25 assay and the clinically validated GP5+/6+-EIA-LMNX. Main outcome measures Histologically confirmed CIN2+ and hrHPV positivity for 14 high-risk HPV types. Results Samples from 91 patients were analysed. All CIN3 cases (n = 6) tested positive for hrHPV in CTS, SS, U1, and U2 with both HPV assays. Sensitivity for CIN2+ with the SPF10 system was 100, 100, 95, and 100%, respectively. With the GP5+/6+ assay, sensitivity was 95% in all sample types. The sensitivities and specificities for both tests on each of the sample types did not significantly differ. There was 10–14% discordance on hrHPV genotype. Conclusions CIN2+ detection using HPV testing of U1 shows a sensitivity similar to that of CTS or brush-based SS, and is convenient. There was substantial to almost excellent agreement between all samples on genotype with both hrHPV assays. There was no advantage in testing U1 compared with U2 samples. Tweetable abstract Similar CIN2+ sensitivity for HPV testing in first-void urine, physician-taken smear and brush-based self-sample.

Abstract Background In January 2017, the Dutch cervical cancer screening programme transitioned from cytomorphological to primary high-risk HPV (hrHPV) DNA screening, including the introduction of self-sampling, for women aged between 30 and 60 years. The Netherlands was the first country to switch to hrHPV screening at the national level. We investigated the health impact of this transition by comparing performance indicators from the new hrHPV-based programme with the previous cytology-based programme. Methods We obtained data from the Dutch nationwide network and registry of histo- and cytopathology (PALGA) for 454,573 women eligible for screening in 2017 who participated in the hrHPV-based programme between 1 January 2017 and 30 June 2018 (maximum follow-up of almost 21 months) and for 483,146 women eligible for screening in 2015 who participated in the cytology-based programme between 1 January 2015 and 31 March 2016 (maximum follow-up of 40 months). We compared indicators of participation (participation rate), referral (screen positivity; referral rate) and detection (cervical intraepithelial neoplasia (CIN) detection; number of referrals per detected CIN lesion). Results Participation in the hrHPV-based programme was significantly lower than that in the cytology-based programme (61% vs 64%). Screen positivity and direct referral rates were significantly higher in the hrHPV-based programme (positivity rate: 5% vs 9%; referral rate: 1% vs 3%). CIN2+ detection increased from 11 to 14 per 1000 women screened. Overall, approximately 2.2 times more clinical irrelevant findings (i.e. ≤CIN1) were found in the hrHPV-based programme, compared with approximately 1·3 times more clinically relevant findings (i.e. CIN2+); this difference was mostly due to a national policy change recommending colposcopy, rather than observation, of hrHPV-positive, ASC-US/LSIL results in the hrHPV-based programme. Conclusions This is the first time that comprehensive results of nationwide implementation of hrHPV-based screening have been reported using high-quality data with a long follow-up. We have shown that both benefits and potential harms are higher in one screening round of a well-implemented hrHPV-based screening programme than in an established cytology-based programme. Lower participation in the new hrHPV programme may be due to factors such as invitation policy changes and the phased roll-out of the new programme. Our findings add further to evidence from trials and modelling studies on the effectiveness of hrHPV-based screening.

Additional file 1. Detailed description of methods for calculating results. Table A1. Age groupings used in analysis by programme type. Table A2. Calculation of the indicators shown in Figure 2 for participation, referral and detection within the new hrHPV-based screening programme, 2017 cohort. Table A3. Calculation of the indicators for participation, referral and detection in the old cytology-based screening programme, cohort 2015, and within the new hrHPV-based screening programme, 2017 cohort.

Summary Background Although the risk of human papillomavirus (HPV) infection is greatest in young women, women older than 25 years remain at risk. We present data from the VIVIANE study of the HPV 16/18 AS04-adjuvanted vaccine in adult women after 7 years of follow-up. Methods In this phase 3, double-blind, randomised controlled trial, healthy women older than 25 years were enrolled (age stratified: 26–35 years, 36–45 years, and ≥46 years). Up to 15% in each age stratum had a history of HPV infection or disease. Women were randomly assigned (1:1) to receive HPV 16/18 vaccine or aluminium hydroxide control, with an internet-based system. The primary endpoint was vaccine efficacy against 6-month persistent infection or cervical intraepithelial neoplasia grade 1 or greater (CIN1+) associated with HPV 16/18. We did analyses in the according-to-protocol cohort for efficacy and total vaccinated cohort. Data for the combined primary endpoint in the according-to-protocol cohort for efficacy were considered significant when the lower limit of the 96·2% CI around the point estimate was greater than 30%. For all other endpoints and cohorts, data were considered significant when the lower limit of the 96·2% CI was greater than 0%. This study is registered with ClinicalTrials.gov, number NCT00294047. Findings The first participant was enrolled on Feb 16, 2006, and the last study visit took place on Jan 29, 2014. 4407 women were in the according-to-protocol cohort for efficacy (n=2209 vaccine, n=2198 control) and 5747 women in the total vaccinated cohort (n=2877 vaccine, n=2870 control). At month 84, in women seronegative for the corresponding HPV type in the according-to-protocol cohort for efficacy, vaccine efficacy against 6-month persistent infection or CIN1+ associated with HPV 16/18 was significant in all age groups combined (90·5%, 96·2% CI 78·6–96·5). Vaccine efficacy against HPV 16/18-related cytological abnormalities (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) and CIN1+ was also significant. We also noted significant cross-protective efficacy against 6-month persistent infection with HPV 31 (65·8%, 96·2% CI 24·9–85·8) and HPV 45 (70·7%, 96·2% CI 34·2–88·4). In the total vaccinated cohort, vaccine efficacy against CIN1+ irrespective of HPV was significant (22·9%, 96·2% CI 4·8–37·7). Serious adverse events related to vaccination occurred in five (0·2%) of 2877 women in the vaccine group and eight (0·3%) of 2870 women in the control group. Interpretation In women older than 25 years, the HPV 16/18 vaccine continues to protect against infections, cytological abnormalities, and lesions associated with HPV 16/18 and CIN1+ irrespective of HPV type, and infection with non-vaccine types HPV 31 and HPV 45 over 7 years of follow-up. Funding GlaxoSmithKline Biologicals SA.

We investigated HPV in adenocarcinoma presenting and managed as cervical adenocarcinoma (CADC) at 7 major representative regional cancer centres across China. From 1,051 CADC cases diagnosed locally in 2005-2010, 881 had available paraffin embedded tissue. Initial review excluded 154 cases as other diagnoses or inappropriate specimens. In 718 eligible cases consensus panel pathology diagnosis was made using an algorithm incorporating p16 and progesterone receptor immunohistochemistry (IHC). Classification of cervical adenocarcinoma categories was subject to substantial pathological disagreement. High-risk human papillomaviruses (HR-HPV) DNA was studied by the sensitive SPF10 PCR-DEIA-LiPA25 version 1 for L1 genes and type-specific HR-HPV E6/7 gene PCR's. HR-HPV prevalence in whole tissue samples in eligible tested CADC was 74.5%: 100.0% in neuro-endocrine carcinoma (NEC), 82.2% in classical cervical adenocarcinoma (ADC-CX), 40.0% in adenocarcinoma-not otherwise specified (ADC-NOS), and 33.3% in endometrioid adenocarcinoma (ADC-ENDO). Higher mean age at diagnosis correlated with histological categories showing low HPV prevalence (Linear regression: β=-13.794, P

In order to make effective decisions on sustainable development, it is essential for sugarcane-producing countries to take into account sugarcane acreage and sugarcane production dynamics. The availability of sugarcane biophysical data along the growth season is key to an effective mapping of such dynamics, especially to tune agronomic models and to cross-validate indirect satellite measurements. Here, we introduce a dataset comprising 3,500 sugarcane observations collected from October 2014 until October 2015 at four fields in the São Paulo state (Brazil). The campaign included both non-destructive measurements of plant biometrics and destructive biomass weighing procedures. The acquisition plan was designed to maximize cost-effectiveness and minimize field-invasiveness, hence the non-destructive measurements outnumber the destructive ones. To compensate for such imbalance, a method to convert the measured biometrics into biomass estimates, based on the empirical adjustment of allometric models, is proposed. In addition, the paper addresses the precisions associated to the ground measurements and derived metrics. The presented growth dynamics and associated precisions can be adopted when designing new sugarcane measurement campaigns.

A hospital-based multicenter, retrospective study was conducted to compare the distribution of human papillomavirus (HPV) in squamous cell carcinoma (SCC) and cervical adenocarcinoma (CADC) in China.Paraffin-embedded tissue blocks diagnosed as SCC and CADC across China were collected, as well as the total number of diagnosed invasive cervical cancer of the 9 selected centers. DNA enzyme immunoassay, reverse hybridization, and multiplex type-specific polymerase chain reaction were used for HPV genotyping.The ratios of CADC to SCC were increasing from 2005 to 2010, in parallel with HPV prevalence in CADC. In 630 patients with SCC (mean ± SD age, 45.40 ± 10.30) and 718 patients with CADC (mean ± SD age, 46.09 ± 10.59) recruited, HPV prevalence rates were 97.6% and 74.5%, respectively. Human papillomavirus viral load for SCC is significantly higher than that for CADC. Most common HPV types distributed in SCC and CADC were HPV-16 (78.5%, 75.1%-81.6%; 47.1%, 42.9%-51.3%), HPV-18 (8.0%, 6.1%-10.4%; 41.1%, 37.0%-45.3%), HPV-52 (2.3%, 1.4%-3.8%; 5.6%, 4.0%-7.9%), and HPV-45 (1.1%, 0.6%-2.3%; 3.9%, 2.6%-5.9%). Different diagnostic mean ± SD age for HPV-16/HPV-18 versus other high-risk HPV types were observed: SCC (44.5 ± 9.94 vs 51.0 ± 10.83, p.05) and CADC (44.1 ± 9.44 vs 47.4 ± 10.41, p = .006). For HPV-negative cases, mean ± SD age was 46.1 ± 10.73 in SCC and 50.3 ± 11.85 in CADC, which were older than the positive (45.4 ± 10.31, 44.5 ± 9.64). HPV-16 and HPV-18 were the most frequent HPV types in both histological types, and HPV-18 was more frequent in CADC than in SCC.Human papillomavirus infection was identified more often in SCC than in CADC. Women with HPV-associated cancers, especially HPV-16/HPV-18, were of a younger age at diagnosis when compared with non-HPV-associated cancers.

Reliable and timely mapping of crop growth conditions and of their water resources is considered a prioritary application in light of the abrupt climate changes. With this view, the paper presents a novel approach that makes use of dense C-Band time-series for the timely estimation of crop growth stages and for the detection of changes in crop water conditions, especially related to precipitation and irrigation events. Aided by vegetation indexes extracted from Landsat and Sentinel-2 imagery, the proposed Sentinel-l centered method exploits both temporal patterns of crop growth and spatial patterns of water anomalies to enhance its classification robustness.

SAR as an active remote sensing technique is capable of providing insights into the physical features of agricultural vegetation. However, the noisy nature of SAR signals makes the direct conversion to effective productivity metrics challenging. This study sheds light on the effect of gaps present in a sugarcane field on L-band and C-band SAR signals and demonstrates the variability of this effect with changing spatial averaging windows, changing precipitation conditions and changing vegetation height.

Human Papillomavirus (HPV) is reported in 60-100% of cervical adenocarcinoma (CADC) globally. We investigated this relationship in a hospital-based survey in China. 718 CADC samples from nine Chinese regions were analysed. Expert pathologists reviewed cases with p16 and progesterone receptor immunostaining. Cases were tested for HPV using whole-tissue sections (WTS) and laser-capture microdissection. All cases were HPV-tested by L1 based broad-spectrum SPF10 -DEIA-LiPA25 PCR. Negative cases were tested for DNA adequacy and with E6 oncogene, type-specific HPV PCRs. Using WTS-PCR CADC showed overall 75% HPV-positivity (33-100% for different histological types). LCM-PCR showed that none of minimal deviation or serous CADC, and

It is generally assumed that virtually all cervical squamous cell carcinomas are associated with persistent infection by high-risk human papillomavirus (HPV), although it is well known that unusual variants of cervical adenocarcinoma are mostly HPV negative. We report a case of a well-differentiated cervical squamous cell carcinoma in a 54-yr-old woman, the morphologic features of which suggested a non-HPV-related neoplasm. The tumor was p16 negative. HPV was also negative by 2 methods, including the highly sensitive SPF-10 system. Further study of additional cases is needed to establish the etiological and pathogenetic factors that underlie very rare non-HPV-related cervical squamous cell carcinoma.

The efficacy of the human papillomavirus type 16 (HPV-16)/HPV-18 AS04-adjuvanted vaccine against cervical infections with HPV in the Pa pilloma Tri al against C ancer i n Young A dults (PATRICIA) was evaluated using a combination of the broad-spectrum L1-based SPF 10 PCR-DNA enzyme immunoassay (DEIA)/line probe assay (LiPA 25 ) system with type-specific PCRs for HPV-16 and -18. Broad-spectrum PCR assays may underestimate the presence of HPV genotypes present at relatively low concentrations in multiple infections, due to competition between genotypes. Therefore, samples were retrospectively reanalyzed using a testing algorithm incorporating the SPF 10 PCR-DEIA/LiPA 25 plus a novel E6-based multiplex type-specific PCR and reverse hybridization assay (MPTS12 RHA), which permits detection of a panel of nine oncogenic HPV genotypes (types 16, 18, 31, 33, 35, 45, 52, 58, and 59). For the vaccine against HPV types 16 and 18, there was no major impact on estimates of vaccine efficacy (VE) for incident or 6-month or 12-month persistent infections when the MPTS12 RHA was included in the testing algorithm versus estimates with the protocol-specified algorithm. However, the alternative testing algorithm showed greater sensitivity than the protocol-specified algorithm for detection of some nonvaccine oncogenic HPV types. More cases were gained in the control group than in the vaccine group, leading to higher point estimates of VE for 6-month and 12-month persistent infections for the nonvaccine oncogenic types included in the MPTS12 RHA assay (types 31, 33, 35, 45, 52, 58, and 59). This post hoc analysis indicates that the per-protocol testing algorithm used in PATRICIA underestimated the VE against some nonvaccine oncogenic HPV types and that the choice of the HPV DNA testing methodology is important for the evaluation of VE in clinical trials. (This study has been registered at ClinicalTrials.gov under registration no. NCT00122681.)

The goal of our study was to provide comprehensive data on the worldwide human papillomavirus (HPV) genotype distribution in patients with invasive cervical adenocarcinoma in correlation with histologic tumor subtypes, geographical location, patients' age, and duration of sample storage. Paraffin-embedded samples of 760 cervical adenocarcinoma cases were collected worldwide. A three-level pathology review of cases was performed to obtain consensus histologic diagnoses and 682 cases were determined to be eligible for further analysis. HPV DNA detection and genotyping was performed using SPF-10/DEIA/LiPA(25) system (version 1). Classic cervical adenocarcinoma accounted for 83.1% of cases, while rare histological variants accounted for a few percent of cases individually. HPV positivity varied significantly between the different histologic tumor subtypes. Classic cervical adenocarcinoma showed high HPV positivity (71.8%), while other adenocarcinoma types had significantly lower HPV prevalence (endometrioid 27.3%, serous 25%, clear cell 20%, not otherwise specified 13.9%, and minimal deviation 8.3%). In all, 91.8% of HPV-positive tumors showed the presence of a single viral type and in 7% of cases multiple viral types were detected. Three HPV genotypes, HPV 16, 18, and 45, dominated in all adenocarcinomas and together accounted for 94.1% of HPV-positive tumors. HPV16 was the most common and found in 50.9% of HPV-positive cases, followed by HPV18 (31.6%) and HPV45 (11.6%). HPV prevalence varied depending on geographical region, patient age, and sample storage time. Tumors from older patients and tumor samples with longer storage time showed lower HPV prevalence. Our results indicate that HPV vaccines may prevent up to 82.5% (HPV16/18) and up to 95.3% (9-valent vaccine) of HPV-positive cervical adenocarcinomas, mostly the classic type. HPV testing and vaccination will not provide full coverage for a very small subset of classical adenocarcinomas and most of the rare tumor variants such as clear cell, serous, endometrioid, and minimal deviation.

Multi-temporal and multi-sensor solutions are essential to increase timeliness and reliability of land monitoring systems. This paper advocates the exploitation of the temporal contextual information provided by temporally dense SAR and optical data series series through the use of a Hidden Markov model (HMM)-based approach. An efficient strategy to incorporate the C-Band SAR data into the HMM framework, relying so far on Landsat, will be debated and assessed over a dynamic agricultural scenario, i.e. characterized by high temporal and spatial diversity in cropping practices. The site is located in the state of Sao Paulo (Brazil), where recent ground surveying activities has been conducted.

Behandeling door middel van elektrochirurgische transurethrale resectie van de prostaat (TURP) is de gouden standaard voor de behandeling van lower urinary tract symptoms (LUTS) door benigne prostaathyperplasie (BPH). Als alternatief wordt fotoselectieve vaporisatie van de prostaat (PVP) toegepast. In deze studie worden de resultaten gemeld van de behandeling met de 120 W High Performance System (HPS) GreenLight Laser, waarbij ook een subgroep patienten met een prostaat > 80 ml wordt geanalyseerd. 221 patienten met LUTS op basis van BPH ondergingen laservaporisatie. De operatiekarakteristieken zijn beschreven. De uitgangssituatie voor de operatie is bepaald met de International Prostate Symptom Score (IPSS) en de Quality of Life (QoL) score, uroflowmetrie, residumeting, meting van het prostaatvolume en een PSAtest. Postoperatief zijn opnieuw IPSS-score, flowmetrie en residu bepaald (na zes weken, en na zes en 18 maanden). Zes maanden postoperatief zijn tevens het prostaatvolume en de PSA bepaald. Prostaten van 80 ml of meer werden ook als subgroep nagekeken. De gemiddelde leeftijd was 69 jaar (44-97). Operatiekarakteristieken: gemiddelde opnameduur twee dagen (range 1-12), gemiddelde OK-duur 61 minuten (range 19- 180), gemiddelde lasertijd 31 minuten (range 6-124), gemiddeld energieverbruik 197 kJ (range 0,2-692). Na 18 maanden was de IPSS gemiddeld 14,2 punten afgenomen ten opzichte van de preoperatieve waarde. De Qmax na 18 maanden was 19 ml/sec (9,4-39). Operatiekarakteristieken grote prostaten: gemiddelde opnameduur twee dagen (range 2-5), gemiddelde OK-duur 96 minuten (range 35-180), gemiddelde lasertijd 56 minuten (range 6-114), gemiddeld energieverbruik 361 kJ (range 61-692). Postoperatieve resultaten waren gelijkwaardig aan die van de gehele groep. Behandeling met de GreenLight Laser lijkt ook na 18 maanden effectief bij LUTS op basis van BPH, ook bij grote prostaten.

Objective This retrospective registry-based study aimed to assess the human papillomavirus (HPV)-type distribution in primary and recurrent high-grade cervical intraepithelial neoplasia (CIN2+), and to discriminate pre-existing from newly-acquired infections. Methods Cervical specimens from 58 women (median age (Q1–Q3): 37.6 (31.7–44.9)) who underwent primary (1998–2003) and repeat conizations were confirmed as CIN2+ during expert pathology review. HPV testing was performed using PCR MP-TS123 Luminex for 16 HPV types. Molecular HPV16 E6 and HPV18 LCR DNA sequencing was performed on specimens with persistent HPV16/18. Results All 58 paired cones were HPV positive; 49 had CIN3+ in the primary cone. Forty-seven (95.9%) women with primary CIN3+ and recurrent CIN2+ had persistent high-risk ( hr ) HPV infection, of which 74.5% were HPV16/18. Two women had probable newly-acquired HPV16/52/56 and HPV39 infections. One woman with persistent HPV52 also had a probable new HPV16 E6 variant in the recurrent CIN2+. Median time delay (Q1–Q3) between conizations was 2.0years (1.1–4.0), being shorter for women older than 40years: 2.6years (1.1–3.7) than for women younger than 40years: 6.0years (2.0–8.7). Primary conization histology revealed CIN3, cervical adenocarcinoma in situ and microinvasive carcinomas in 43 (87.8%), 5 (10.2%) and 1 (2.0%) women, respectively. Primary HPV16- and HPV18-infected CIN3+ had a shorter delay between conizations: 1.8years (1.2–4.4) and 2.2years (0.4–NE), respectively, compared to HPV33-: 3.8years (3.3–7.8) or other HPV type-infected: 8.2years (6.0–NE) CIN3+. Conclusions Routine post-conization hr- HPV DNA testing together with cervical cytology may provide a better prediction for potential recurrent disease. Further, primary prevention through adolescent vaccination may prevent CIN2+ and its recurrence.

In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ≥ 21 years with lesions clinically suggestive of ICC. Histopathological diagnosis of ICC was determined by light microscopy examination of hematoxylin and eosin stained sections of paraffin-embedded cervical specimens; samples with a confirmed histopathological diagnosis underwent HPV DNA testing by polymerase chain reaction. HPV-positive specimens were typed by reverse hybridization line probe assay. Between October 2007 and March 2010, cervical specimens from 659 women were collected (167 in Ghana, 192 in Nigeria and 300 in South Africa); 570 cases were histologically confirmed as ICC. The tumor type was identified in 551/570 women with ICC; squamous cell carcinoma was observed in 476/570 (83.5%) cases. The HPV-positivity rate in ICC cases was 90.4% (515/570). In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%) and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV-positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45 and 35 were the most common HPV types in sub-Saharan African women with ICC and HPV infections were more common in HIV-positive women.

Background An increase in incidence of cervical adenocarcinoma (CADC) has been reported in many countries, including Korea. However, few studies describe human papillomavirus (HPV) type distribution among CADC in Asia. Objective and methods This was a retrospective, hospital-based observational study between 2005 and 2010 to estimate the overall prevalence and distribution of HPV types among CDAC in Korean women. The study used hematoxylin & eosin and immunohistochemical staining (for the two biomarkers p16 and progesterone receptor [PR]) to diagnose and subtype CADC samples. HPV DNA was amplified by polymerase chain reaction (PCR) and HPV genotypes were identified using reverse hybridization. Results Of 196 cases submitted, 89.3% of the cases were confirmed as CADC. The mean age at diagnosis was 47.1 (standard deviation [SD] 11.9) years. No statistically significant differences in mean age at diagnosis by histological subtype were found. HPV DNA was detected in 90.3% (177/196) of CADC. HPV-18 was the most prevalent type (54.2%), followed by HPV-16 (44.1%) and HPV-45 (3.4%). Infection with any high-risk HPV type was identified in 97.7% of HPV-DNA-positive CADC. The biomarker p16 was positive in 92% of CADC cases and PR was positive in 19.6% of CADC. Conclusion HPV DNA was found in the large majority of CADC in Korean women, with HPV-18 being the most common type followed by HPV-16 and HPV-45. This study is among the first in Asia to specifically report HPV type distribution in CADC. This information will help inform policy decisions concerning HPV vaccination for the prevention of CADC.

During the 2014–2015 sugarcane growth season in Sao Paulo, Brazil, a considerable dataset was acquired consisting of space-based remote sensing images from radar and optical sensors, together with intensive ground measurements. In this work, images from the Sentinel-1, Radarsat-2 and Landsat-8 satellites are used to test the effectiveness of satellite-based indicators in sugarcane growth monitoring. A two-fold hypothesis testing is applied, in order to find statistically significant emerging hot spots and cold spots, both in space and time. Especially the comparison of results from the radar and optical sensors gives an insight into the difference in capability of these sensors to detect spatial and temporal patterns and trends.

The paper debates a novel approach for land cover (LC) mapping based on the Hidden Markov Model. The proposed methodology is aimed to address both the urgent demand of off-line (or historic) LC information retrieval and of near-real time LC monitoring. The discrete-time model employs short steps of 16 days, that conveniently fits the Landsat revisit time while providing a continuous and temporally dense representation of the land cover dynamics. Two temporal pattern typologies were identified and modeled within the proposed Markov chain architecture: a seasonal and synchrounous behavior which can be associated to the observables of LC classes such as forest and grasses, and a highly asynchronous behaviour, which characterizes the crop observables. The first typology is addressed by introducing time-dependency in state output probabilities, whereas the latter is rendered through a sequence of (sub-class) states interlinked by means of a ‘left-right’ based model. Such model inherently incorporates crop growth tracking functionalities as an added value. In this paper the methodology has been tailored to Sao Paulo state (Brazil) scenario, showing overall accuracy above 80% on the test sample. A particular emphasis is attributed to the identification of sugarcane plantations, that are indeed responsible for major land use changes.

In 20-40% of cervical intra-epithelial neoplasia (CIN) and in 4-8% of cervical carcinoma tissue specimens, multiple HPV genotypes have been detected. Whole tissue section (WTS) PCR does not determine how the individual types relate causally to complex and multiple CIN. Our objective was to determine whether laser capture micro-dissection (LCM) with HPV PCR genotyping (LCM-PCR) could accurately recover type-specific HPV DNA from epithelial cells in individual areas of CIN and normal epithelium, and whether one or more viruses are present in one lesion. For that, histologically selected samples of CIN and normal epithelium were isolated by LCM and analysed by the SPF(10) PCR/LiPA(25) (version 1) HPV genotyping system for 25 HPV genotypes. HPV genotypes detected in 756 areas of CIN (grade 1, 2 or 3) by LCM-PCR were compared with results obtained by WTS-PCR in 60 cases (74 biopsies). We showed that when a single HPV type is detected by WTS-PCR, that type was almost always (94%; 29/31) recovered by LCM-PCR from CIN. When multiple HPV types were present by WTS-PCR, their distribution within histological sections could be mapped by LCM-PCR. Association of a single HPV type with a discrete area of CIN was found for 93% (372/399) of LCM fragments analysed by PCR. We found colliding CIN lesions associated with separate HPV types and only 62% (61/99) of HPV types detected by WTS-PCR were found in CIN by LCM-PCR. Therefore, the LCM-PCR technique was found very accurate for high-resolution HPV genotyping and for assigning an individual HPV type to an area of CIN. At LCM level, in cervical biopsy sections with multiple HPV infections, the relation between HPV types and CIN lesions is often complex. Almost every HPV type found in CIN by LCM-PCR is associated with a biological separate independent CIN lesion-one virus, one lesion.

In this study, a terrain classification algorithm is presented that was derived from various properties of the returned full waveform signals collected from the Ice, Cloud and land elevation Satellite ICESat mission. Such an algorithm would be beneficial for current and future studies of the cryosphere, particularly Greenland and Antarctica, by helping to identify changes in the large scale surface properties over time. The algorithm developed was validated over a test region in the Dry Valleys of Antarctica, where the terrain is well known and regularly monitored. The new classification algorithm distinguishes between four different types of terrain: snow, rock, ice and water. A description of the decision tree behind the algorithm will be provided, along with the results from the validation site. Over this test site, the algorithm achieved an overall classification accuracy of 74%.

Prophylactic vaccination against HPV 16 and 18 has the potential for effective prevention of high-grade precancer (cervical intraepithelial neoplasia [CIN)] 2/3) and ICC caused by these viruses (globally 50 and 70%, respectively) when employed in women prior to starting sexual activity. To provide data for decisions on HPV vaccination in China, we determined HPV type-distribution in ICC and CIN 2/3 from women of different regions within China. A multicenter study was conducted by randomized sampling of paraffin blocks of 664 ICC (630 squamous cell carcinoma [SCC]; 34 adenocarcinoma [ADC]), 569 CIN 2/3 cases from seven regions of China. Histological diagnosis was confirmed in 1,233 cases by consensus review. HPV DNA was detected using the SPF10 LiPA25 version 1 assay. HPV prevalence was 97.6% in SCC, 85.3% in adenocarcinoma, and 98.9% in CIN 2/3. HPV 16 (76.7%) and HPV 18 (7.8%) were the most common, together accounting for 84.5% of SCC, followed by HPV 31 (3.2%), HPV 52 (2.2%), and HPV 58 (2.2%). HPV positivity in SCC did not differ notably by region. However, SCC cases from womenor=34 years had higher HPV 16 positivity than women over 50 years, among whom HPV 52, 58, and 39 were more common. HPV 16 and 18 were under-represented, whereas HPV 31, 52, and 58 were over-represented in CIN2/3 compared to SCC. The potential impact of vaccines against oncogenic HPV types 16 and 18 is estimated to be high (84.5%) against total SCC. These data are critical for China's future evaluation of the cost-effectiveness of current cervical cancer vaccines and of HPV-based screening guidelines.

Classification of high-risk HPV types for cervical cancer screening depends on epidemiological studies defining HPV type-specific risk. The genotyping tests that are used, are however, not uniform with regard to type-specific detection rates making comparisons between different studies difficult. To overcome the lack of a “gold standard” four tests were evaluated crosswise using 824 cervical smears pretested by HC2. The tests evaluated were the L1-PCR-based assays PGMY09/11 LBA, HPV DNA Chip and SPF LiPA and an E1 consensus PCR followed by cycle sequencing (E1-PCR). A subset of 265 samples was tested in addition with the GP5+/6+ reverse line blot assay. Differences were noted in the sensitivity and range for specific HPV types, e.g. with detection rates for HPV53 ranging from 2.3% to 11.6%. HPV16 was the most prevalent type detected by all tests except for the SPF-10 LiPa, which detected HPV31 more often. Kappa values calculated ranged from poor (k = 0.20) to intermediate (k = 0.54) for HPV positivity, but were higher for high-risk type positivity (k = 0.31–0.61) and best for recognition of HPV16 (k = 0.53–0.72). The analytical sensitivity of the tests ranged between 15% and 97% for individual types and specificity was highly dependent on which test system was used as “gold standard” for the analysis. The results of histology were used for calculation of clinical sensitivity and specificity. E1-PCR, PGMY09/11 LBA and SPF-10 LiPA had a high clinical sensitivity (>95%) for the detection of cervical intraepithelial neoplasia 2 or higher, whereas the HPV DNA Chip reached only 84.1%. J. Med. Virol. 80: 1264–1274, 2008. © 2008 Wiley-Liss, Inc.

The paper debates a novel approach for sugarcane identification and characterization based on multi-spectral and multi-temporal profile matching. A parametric model aimed at identifying sugarcane among pasture/grasses/shrubs, annual crops and forest is proposed. Differently from other supervised and unsupervised classification techniques, the discussed profile-based parametric model accounts for variability in growth date, that becomes valuable information to be extracted, rather than simply a nuisance parameter, and delivers an effective extrapolation of the cane vigor. The approach is then applied to Landsat 5 TM and ERS/ENVISAT SAR time-series over the Orindiuva area attaining preliminary promising although perfectible results.

We investigated HPV in adenocarcinoma presenting and managed as cervical adenocarcinoma (CADC) at seven major representative regional cancer centres across China. From 1,051 CADC cases diagnosed locally in 2005-2010, 881 had available paraffin embedded tissue. Initial review excluded 154 cases as other diagnoses or inappropriate specimens. In 718 eligible cases consensus panel pathology diagnosis was made using an algorithm incorporating p16 and progesterone receptor immunohistochemistry (IHC). Classification of cervical adenocarcinoma categories was subject to substantial pathological disagreement. High-risk human papillomaviruses (HR-HPV) DNA was studied by the sensitive SPF10 PCR-DEIA-LiPA25 version 1 for L1 genes and type-specific HR-HPV E6/7 gene PCR's. HR-HPV prevalence in whole tissue samples in eligible tested CADC was 74.5%: 100.0% in neuro-endocrine carcinoma (NEC), 82.2% in classical cervical adenocarcinoma (ADC-CX), 40.0% in adenocarcinoma-not otherwise specified (ADC-NOS) and 33.3% in endometrioid adenocarcinoma (ADC-ENDO). Higher mean age at diagnosis correlated with histological categories showing low HPV prevalence (Linear regression: β= -13.794, p 0.001). HPV-16 and 18 were associated with early development of CADC and a lower mean age correlated with carcinogenic risk of associated HPV (β = -0.1829, p 0.001). HPV-16 or HPV-18 was found in 88.2% of all HPV positive cases including multiple-infections. HPV-18 was the commonest HPV type in NEC (58.3%), ASC (40.2%) and ADC-CX (40.9%). The proportion of HPV-unrelated CADC and in different final histological categories varied geographically and by age. Although HPV negativity was predominantly associated with special categories of CADC, some HPV-negative usual adenocarcinomas indistinguishable by adjudicated microscopic diagnosis from ADC-CX were found and varied in frequency across China.

Human Papillomavirus (HPV) is reported in 60-100% of cervical adenocarcinoma (CADC) globally. We investigated this relationship in a hospital-based survey in China. 718 CADC samples from nine Chinese regions were analysed. Expert pathologists reviewed cases with p16 and progesterone receptor immunostaining. Cases were tested for HPV using whole-tissue sections (WTS) and laser-capture microdissection. All cases were HPV-tested by L1 based broad-spectrum SPF10 -DEIA-LiPA25 PCR. Negative cases were tested for DNA adequacy and with E6 oncogene, type-specific HPV PCRs. Using WTS-PCR CADC showed overall 75% HPV-positivity (33-100% for different histological types). LCM-PCR showed that none of minimal deviation or serous CADC, and10% of all clear cell and endometrioid CADC were HPV-positive in tumour cells. Usual and adenosquamous CADC showed a single HPV genotype in 60 and 78% cases. In some cases, HPV was found in adjacent cervix but not in tumour. HPV 16, 18 and 45 accounted for 90% of HPV in tumour cells. Patients with HPV-positive tumours were on average 6 years younger and presented at a lower clinicopathological stage as compared to patients with HPV-negative cancers. CADC is diverse pathologically and in HPV status. Special histopathological tumor subtypes may develop through different cellular and molecular pathways. Between 20 and 40% usual and adenosquamous types, in particular these diagnosed in older women and at advanced FIGO stages, are not driven by oncogenic HPV. In these cases HPV may not be involved in carcinogenisis or maybe lost during tumour progression.

Two commercial HPV tests target the same 65 bp fragment of the human papillomavirus genome (designated SPF10): the original HPV SPF10 PCR-DEIA-LiPA25 system, version 1, (LiPA25) and the INNO-LiPA HPV Genotyping Extra (INNO-LiPA). The original SPF10 LiPA25 system was designed to have high analytical sensitivity and applied in HPV vaccine and epidemiology studies worldwide. But due to apparent similarities, this test can be easily confused with INNO-LiPA, a more recent assay of which the intended use, i.e., epidemiological or clinical, is currently unclear. The aim was to compare the analytical sensitivity of SPF10 LiPA25 to that of INNO-LiPA on the level of general HPV detection and genotyping. HPV testing by both assays was performed on the same DNA isolated from cervical swab (n = 365) and biopsy (n = 42) specimens. In cervical swabs, SPF10 LiPA25 and INNO-LiPA identified 35.3% and 29.3% multiple infections, 52.6% and 51.5% single infections, and no HPV type in 12.1% and 19.2%, respectively. Genotyping results were 64.7% identical, 26.0% compatible and 9.3% discordant between both methods. SPF10 LiPA25 detected significantly more genotypes (p < 0.001). The higher analytical sensitivity of SPF10 LiPA25 was confirmed by the MPTS123 genotyping assay. HPV positivity by the general probes in SPF10 DEIA was significantly higher (87.9%) than by those on INNO-LiPA (77.0%) (kappa = 0.592, p < 0.001). In cervical biopsies, SPF10 LiPA25 and INNO-LiPA identified 21.4% and 9.5% multiple types, 76.2% and 81.0% single types, and no type in 2.4% and 9.5%, respectively. Between both tests, the identification of genotypes was 76.3% identical, 14.3% compatible and 9.5% discordant. Overall, significantly more genotypes were detected by SPF10 LiPA25 (kappa = 0.853, p = 0.022). HPV positivity was higher by the SPF10 DEIA (97.6%) than by the INNO-LiPA strip (92.9%). These results demonstrate that SPF10 LiPA25 is more suitable for HPV genotyping in epidemiologic and vaccine-related studies, due to its higher analytical sensitivity.

Objective To study diagnostic and therapeutic strategies, outcomes, and follow-up in a large series of women with adenocarcinoma in situ (AIS) of the uterine cervix and investigate if human papillomavirus (HPV) typing among women with negative cytology reports would have helped with early AIS detection. Materials and Methods Records of 132 AIS cases diagnosed between 1989 and 2012 were retrieved. Clinical and pathological data were reviewed and analyzed. Results Mean age at diagnosis was 37 years. Seventy-two percent (n = 95) of all patients were asymptomatic; diagnosis was established using cytology and biopsy. Primary treatment for 124 patents was cold knife cone or loop electrosurgical excision procedure (LEEP). Positive margins were found in 18% of those women treated with CKC versus 40% in those treated with LEEP. The mean follow-up time was 62 months (range, 2-217 months; median, 46 months). Three recurrences were found after conservative treatment in 86 patients. High-risk HPV (hrHPV) positivity was detected in 115 (96%) of 120 patients, with HPV-18 being the most commonly occurring subtype (51%). Conclusions There is a small risk of relapse after conservative therapy with cold knife cone or LEEP when resection margins are negative in women with AIS. Patients should be given the options of hysterectomy or conservative therapy with strict follow-up.

The t(12;22) creates an MN1-TEL fusion gene leading to acute myeloid leukemia. The fusion partner TEL (ETV6) is a member of the ETS family of transcription factors. The nature of the other fusion partner, MN1, has not been investigated in detail until now. We recently described that MN1 activates the transcription activity of the moloney sarcoma virus long terminal repeat, indicating that this protein itself may act as a transcription factor. We show here that MN1 comprises multiple transcription activating domains. A search for a bound DNA sequence revealed that MN1 has affinity for retinoic acid responsive elements. A DR5 retinoic acid responsive element was observed in the LTR. The combination of MN1 and ligand-activated retinoic acid receptor leads to a synergistic induction of expression directed by the LTR. Cotransfection of MN1 with RAC3 or p300, known coactivators of retinoic acid receptors, leads to a further synergistic induction of transcription. In addition, the effect of MN1 can be inhibited by the wild-type adenovirus ElA protein that inhibits p300 function, but not by an E1A mutant lacking the p300-binding site. GAL4-MN1-mediated transcription can be enhanced directly by RAC3 and p300. Taken together, our results indicate that MN1 is a transcription coactivator rather than a sequence-specific transcription factor, and that it may stimulate RAR/RXR-mediated transcription through interaction with p160 and p300.

In this study, space remote sensing data and crop specific information from the ESA-led AgriSAR 2009 campaign are used for studying the profiles of C-band SAR backscatter signals and multispectral-based leaf area index (LAI) over the growth period of canola, pea and wheat. In addition, the correlations between radar backscatter parameters and the crop yields were analyzed, based on extracted statistics of temporal profiles. The results show that the HV backscatter and LAI are correlated differently before and after LAI peak. In addition, the coefficient of determination between peakrelated statistics from polarimetric indicator profiles and yield for pea fields can reach up to 0.68, and for canola and wheat up to 0.47 and 0.5, respectively. HV backscatter and coherence between HH and VV are most.

Cervical glandular neoplasias (CGN) present a challenge for cervical cancer prevention due to their complex histopathology and difficulties in detecting preinvasive stages with current screening practices. Reports of human papillomavirus (HPV) prevalence and type‐distribution in CGN vary, providing uncertain evidence to support prophylactic vaccination and HPV screening. This study [108288/108290] assessed HPV prevalence and type‐distribution in women diagnosed with cervical adenocarcinoma in situ (AIS, N = 49), adenosquamous carcinoma (ASC, N = 104), and various adenocarcinoma subtypes (ADC, N = 461) from 17 European countries, using centralised pathology review and sensitive HPV testing. The highest HPV‐positivity rates were observed in AIS (93.9%), ASC (85.6%), and usual‐type ADC (90.4%), with much lower rates in rarer ADC subtypes (clear‐cell: 27.6%; serous: 30.4%; endometrioid: 12.9%; gastric‐type: 0%). The most common HPV types were restricted to HPV16/18/45, accounting for 98.3% of all HPV‐positive ADC. There were variations in HPV prevalence and ADC type‐distribution by country. Age at diagnosis differed by ADC subtype, with usual‐type diagnosed in younger women (median: 43 years) compared to rarer subtypes (medians between 57 and 66 years). Moreover, HPV‐positive ADC cases were younger than HPV‐negative ADC. The six years difference in median age for women with AIS compared to those with usual‐type ADC suggests that cytological screening for AIS may be suboptimal. Since the great majority of CGN are HPV16/18/45‐positive, the incorporation of prophylactic vaccination and HPV testing in cervical cancer screening are important prevention strategies. Our results suggest that special attention should be given to certain rarer ADC subtypes as most appear to be unrelated to HPV., What's new? Cervical cancer occurs in several different types; while Pap smears do a fine job of preventing one type, they fall short when it comes to another. Cervical adenocarcinoma (ADC) can look very different from case to case, and is more difficult to identify. This study characterized the HPV subtypes most commonly associated with ADC. Most commonly found were HPV 16, 18, and 45; thus, many of these cancers could be prevented by vaccination. The rarer subtypes of ADC had less of a link to HPV infection, and these cancers warrant special attention to develop better screening tools.

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Background Cervical cancer ranks second among all cancers reported in Sri Lankan women. This study assessed the prevalence and type-distribution of human papillomavirus (HPV) among Sri Lankan women with invasive cervical cancer (ICC) and pre-cancerous lesions. Methods 114 women aged 21 years and above, hospitalized in the National Cancer Institute, Sri Lanka with a diagnosis of ICC or cervical intraepithelial neoplasia (CIN) 2/3 were prospectively enrolled between October 2009 and September 2010 (110430/NCT01221987). The cervical biopsy or excision specimens collected during routine clinical procedures were subjected to histopathological review. DNA was extracted from samples with a confirmed histological diagnosis and was amplified using polymerase chain reaction and HPV DNA was detected using Enzyme Immuno Assay. HPV positive samples were typed using reverse hybridization Line Probe Assay. Results Of the cervical samples collected, 93.0% (106/114) had a histologically confirmed diagnosis of either ICC (98/106) or CIN 2/3 (8/106). Among all ICC cases, squamous cell carcinoma was diagnosed in the majority of women (81.6% [80/98]). HPV prevalence among ICC cases was 84.7% (83/98). The HPV types most commonly detected in ICC cases with single HPV infection (98.8% [82/83]) were HPV-16 (67.3%) and HPV-18 (9.2%). Infection with multiple HPV types was recorded in a single case (co-infection of HPV-16 and HPV-59). Conclusions HPV was prevalent in most women with ICC in Sri Lanka; HPV-16 and HPV-18 were the predominantly detected HPV types. An effective prophylactic vaccine against the most prevalent HPV types may help to reduce the burden of ICC disease.

Background and objectives Since July 1 1999, four laboratories in the Netherlands have been routinely screening plasma minipools for the release of labile blood components utilizing hepatitis C virus nucleic acid amplification technology (HCV NAT). This report describes the performance evaluation of the HCV NAT method and the quality control results obtained during 6 months of routine screening. Materials and methods Plasma minipools of 48 donations were prepared on a Tecan Genesis robot. HCV RNA was isolated from 2 ml of plasma by using the NucliSens Extractor and amplified and detected with the Cobas HCV Amplicor 2.0 test system. For validation of the test system the laboratories used viral quality control (VQC) reagents of CLB. Results Initial robustness experiments demonstrated consistent detection of PeliSpy HCV RNA samples of 140 genome equivalents/ml (geq/ml) in each station of the installed Nuclisens Extractors. Further 'stress' tests with a highly viraemic sample of approximately 5 x 10(6) geq/ml did not contaminate negative samples processed on all Extractor stations in subsequent runs. In the validation period prior to July 1999, 1021 pools were tested with the following performance characteristics: 0.1%, initially false reactive; 0.89%, failure of internal control detection; 0.97%, no eluate generated by the Extractor; and 100% reactivity of the PeliSpy 140 geq/ml control in 176 Extractor runs and a 98% reactivity rate of the PeliSpy 38 geq/ml control in 102 test runs. By testing the PeliCheck HCV RNA genotype 1 dilution panels 49 times, an overall 95% detection limit of 30 geq/ml ( approximately 8 IU/ml) and a 50% detection limit of 5 geq/ml was found by the four laboratories. In the first 6 months of routine screening, the minimum requirement for invalid results (2%) was exceeded with some batches of silica and NucliSens Extractor cartridges. From November 1999 to February 2000, the manufacturer (Organon Teknika) improved the protocol for silica absorption of the Nuclisens Extractor -- the cartridge design as well as the software of the Extractor. During the next 6 months of observation in 2000, the percentages of false initial reactives and invalids were 0.05% and 1.4%, respectively, in 8962 pools tested. Of these invalid results, 0.74% and 0.66% were caused by Extractor failure and negative internal control signals, respectively. The PeliSpy HCV RNA 'stop or go' run control of 140 geq/ml was 100% reactive, but invalid in 16/1375 (1.2%) of cases. The PeliSpy run control of 38 geq/ml for monitoring sensitivity of reagent batches was reactive in 95% of 123 samples tested. Conclusions Each of the four HCV NAT laboratories in the Netherlands have achieved similar detection limits that are well below the sensitivity requirements of the regulatory bodies. After improvement of the NucliSens Extractor procedure, the robustness of the test system has proved to be acceptable for routine screening and timely release of all labile blood components.

The neurofibromatosis Type 2 tumor suppressor gene is implicated in the hereditary tumor syndrome NF2, hallmarked by bilateral vestibular schwannomas, meningiomas, and ocular non-neoplastic features. The gene product has characteristics of a membrane cytoskeleton-linking protein but the mechanism of tumor suppression by the NF2 protein remains to be elucidated. The NF2 gene is widely expressed in mouse and rat tissues. In humans, most of the expression data have accumulated through Northern blot analysis, RT-PCR and, more recently, Western blot analysis, providing information on whole tissues and organs rather than on specific cell types. We report here an extensive survey of NF2 gene expression in human tissues using a combination of mRNA in situ hybridization (mRNA ISH) and immunohistochemistry (IH) with a panel of monoclonal antibodies (MAbs) supplemented by tissue immunoprecipitation experiments with affinity-purified polyclonal antibodies. Expression was observed in many different cell types, most of which appear functionally normal in individuals affected by NF2. Surprisingly, expression could not be consistently documented in Schwann cells and arachnoidal cells by IH or by mRNA ISH in formalin-fixed tissue. However, consistent immunostaining of Schwann cells was seen in frozen sections. (J Histochem Cytochem 47:1471-1479, 1999)

Low-risk human papillomaviruses (LR-HPVs) have been associated occasionally with clinically and pathologically unusual anogenital malignancies. The relation between clinicopathologic features and any pathogenetic role of LR-HPV remains unclear. From a global study of 13,328 anogenital carcinomas, we identified 57 cases in which whole-tissue polymerase chain reaction using SPF10-LiPA25 showed single LR-HPV infection. In 43/46 (93.5%) available carcinomas, multiple polymerase chain reaction assays confirmed single detection of HPV6, 11, 42, 44, or 70 DNA. In 75% (n=32) of these, LR-HPV DNA was confirmed in tumor cells by laser capture microdissection. In 2 cases, including 1 adenocarcinoma, viral DNA was only found outside the tumor. All anogenital tumors with confirmed HPV6/11 showed a distinctive range of papillary, warty or warty-basaloid, squamous, or transitional histology with patchy or negative p16 expression. HPV6-associated cervical tumors occurred at a low median age. HPV42/70 was associated with typical squamous cell carcinoma showing diffuse p16 staining like high-risk HPV-related malignancies. HPV44 was found in malignant cells in 1 case. Viral taxonomy and theoretical analysis show that HPV6/11 belong to a different genus from HPV42/70 with E6/E7 gene products that would not bind pRb or p53, whereas HPV42/70 could bind pRb. Our data support the causal involvement of LR-HPVs in the carcinogenesis of

In sub-Saharan Africa, invasive cervical cancer (ICC) incidence and mortality are among the highest in the world. This cross-sectional epidemiological study assessed human papillomavirus (HPV) prevalence and type distribution in women with ICC in Ghana, Nigeria, and South Africa. Cervical biopsy specimens were obtained from women aged ≥ 21 years with lesions clinically suggestive of ICC. Histopathological diagnosis of ICC was determined by light microscopy examination of hematoxylin and eosin stained sections of paraffin-embedded cervical specimens; samples with a confirmed histopathological diagnosis underwent HPV DNA testing by polymerase chain reaction. HPV-positive specimens were typed by reverse hybridization line probe assay. Between October 2007 and March 2010, cervical specimens from 659 women were collected (167 in Ghana, 192 in Nigeria and 300 in South Africa); 570 cases were histologically confirmed as ICC. The tumor type was identified in 551/570 women with ICC; squamous cell carcinoma was observed in 476/570 (83.5%) cases. The HPV-positivity rate in ICC cases was 90.4% (515/570). In ICC cases with single HPV infection (447/515 [86.8%]), the most commonly detected HPV types were HPV16 (51.2%), HPV18 (17.2%), HPV35 (8.7%), HPV45 (7.4%), HPV33 (4.0%) and HPV52 (2.2%). The prevalence of single and multiple HPV infections seemed higher among HIV-positive women and HPV type distribution appeared to differ according to tumor type and HIV status. In conclusion, HPV16, 18, 45 and 35 were the most common HPV types in sub-Saharan African women with ICC and HPV infections were more common in HIV-positive women.

ObjectiveIndependent, prospective, multicenter, hospital-based cross-sectional studies were conducted across 5 countries in Asia, namely, Malaysia, Vietnam, Singapore, South Korea, and the Philippines. The objectives of these studies were to evaluate the prevalence of human papillomavirus (HPV) types (high risk and others including coinfections) in women with invasive cervical cancer (ICC) and high-grade precancerous lesions.MethodsWomen older than 21 years with a histologic diagnosis of ICC and cervical intraepithelial neoplasia [CIN 2 or 3 and adenocarcinoma in situ (AIS)] were enrolled. Cervical specimens were reviewed by histopathologists to confirm the presence of ICC or CIN 2/3/AIS lesion and tested with short PCR fragment10-DNA enzyme immunoassay-line probe assay for 14 oncogenic HPV types and 11 non-oncogenic HPV types. The prevalence of HPV 16, HPV 18, and other high-risk HPV types in ICC [including squamous cell carcinoma (SCC) and adenocarcinoma/adenosquamous carcinoma (ADC/ASC)] and CIN 2/3/AIS was estimated.ResultsIn the 5 Asian countries, diagnosis of ICC was confirmed in 500 women [SCC (n = 392) and ADC/ASC (n = 108)], and CIN 2/3/AIS, in 411 women. Human papillomavirus DNA was detected in 93.8% to 97.0% (84.5% for the Philippines) of confirmed ICC cases [94.0%–98.7% of SCC; 87.0%–94.3% (50.0% for the Philippines) of ADC/ASC] and in 93.7% to 100.0% of CIN 2/3/AIS. The most common types observed among ICC cases were HPV 16 (36.8%–61.3%), HPV 18 (12.9%–35.4%), HPV 52 (5.4%–10.3%), and HPV 45 (1.5%–17.2%), whereas among CIN 2/3/AIS cases, HPV 16 (29.7%–46.6%) was the most commonly observed type followed by HPV 52 (17.0%–66.7%) and HPV 58 (8.6%–16.0%).ConclusionsThis article presents the data on the HPV prevalence, HPV type distribution, and their role in cervical carcinogenesis in 5 Asian countries. These data are of relevance to public health authorities for evaluating the existing and future cervical cancer prevention strategies including HPV-DNA testing–based screening and HPV vaccination in these Asian populations.

In view of the immunosuppressive action of glucocorticoids (GCs), the activation of the hypothalamo-pituitary-adrenal axis in patients with sepsis or septic shock is paradoxical. At the same time, administration of GCs to these patients is not clearly beneficial. We investigated the role of GCs in severe illness by measuring the sensitivity of peripheral blood mononuclear leukocytes to GCs in a mitogen-stimulated lymphocyte proliferation assay. In addition, we studied the role of interleukin-2 and several other cytokines in this system. Cells from patients with sepsis or septic shock (n = 15) were more sensitive to the antiproliferative action of GCs than were cells from normal controls (IC50 6.7 +/- 2.1 nmol/L for patients vs. 19.5 +/- 2.5 nmol/L for controls; P0.01). This increased sensitivity of the peripheral mononuclear cells to dexamethasone during the period of sepsis normalized during the ensuing period of clinical recovery of these patients. Dexamethasone inhibited the production of interleukin-2 in the mitogen-stimulated cells. Addition of interleukin-2 antagonized the suppressive effects of dexamethasone in a dose-dependent manner, both in cells from controls and in cells from patients with sepsis. To a lesser extent, the combination of interleukin-1, interleukin-6, and tumor necrosis factor-alpha also counteracted the effects of dexamethasone. In conclusion, our results suggest that not only the activity of the hypothalamo-pituitary-adrenal axis but also the sensitivity to GCs is regulated during sepsis and septic shock. Generally there is an increased sensitivity to GCs, which might help to protect the organism as a whole through supportive effects on metabolism and vasculature. This hypersensitivity is counteracted, possibly at the site of inflammation, by high local concentrations of cytokines. This would enable an adequate local response of the immune system in the presence of elevated cortisol levels. In view of the increased sensitivity of peripheral leukocytes to GCs, treatment of these patients with high doses of GCs may not be beneficial or may even be harmful.

Objective A study was undertaken to assess the distribution of high-risk HPV-genotypes in high-grade cervical intraepithelial neoplastic lesions in Danish women. Design Observational, cross-sectional. Setting Danish data from a multi-centre study undertaken in 13 European countries. Population 290 archived fixed biopsies with high-grade cervical lesions from the Departments of Pathology at the University Hospitals in Hvidovre and Odense, Denmark. Methods Relevant histological samples were anonymized and shipped to a central laboratory for histopathology review and PCR-testing for HPV-DNA. A standardised HPV-test methodology was utilised to enable comparison of HPV-genotype distribution. Results Of 290 Danish cervical samples, 276 were evaluated as histologically adequate and all of these were HPV-positive (HPV +). Of the HPV + samples 77.9% were diagnosed with a single HPV-type, with cervical intraepithelial neoplasia (CIN)3 diagnosed in 82.3% and CIN2, CIN2/3, adenocarcinoma in situ (AIS) and AIS + other high-grade lesion diagnosed in the remaining 17.7%. The most prevalent HPV-types were: HPV16 (54.0%), HPV33 (13.5%), HPV31 (10.7%), HPV18 (7.9%) and HPV52 (4.7%). Of the HPV + samples, 21.4% were diagnosed with multiple HPV-types, with CIN3 diagnosed in 79.6% and CIN2, CIN2/3, AIS and AIS + other high-grade lesion diagnosed in the remaining 20.4%. The most prevalent HPV-types were: HPV16 (49.2%), HPV31 (30.5%), HPV52 (27.1%), HPV51 (20.3%), HPV18 (16.9%), HPV33 (13.6%), HPV45 (11.9%), with 0.7% unknown types. Conclusions HPV16 and HPV18 were detected in approximately 75% of high-grade intraepithelial cervical lesions in a Danish population (single or multiple infections); these two genotypes are considered causative in at least 61.9% of the high-grade intraepithelial lesions (single infection).