Long-term protective effect of high-risk human papillomavirus testing in population-based cervical screening

We prospectively evaluated the 5-year predictive values of adding high-risk human papillomavirus (hrHPV) testing to cytology for the detection of ⩾cervical intraepithelial neoplasia (CIN)3 lesions in a population-based cohort of 2810 women. At baseline, nine (0.3%) women had prevalent lesions ⩾CIN3, all being hrHPV positive. After 5 years of follow-up, four (6.5%) of the 62 hrHPV-positive women with normal cytology developed lesions ⩾CIN3, vs only one (0.05%) of the 2175 hrHPV-negative women with normal cytology. High-risk human papillomavirus testing or combined screening revealed a much higher sensitivity, at the cost of a small decrease in specificity, and a higher negative predictive value for the detection of lesions ⩾CIN3 till the next screening round (5 years) than cytology alone

A new classification method using array Comparative Genome Hybridization data, based on the concept of Limited Jumping Emerging Patterns

<p>Abstract</p> <p>Background</p> <p>Classification using aCGH data is an important and insufficiently investigated problem in bioinformatics. In this paper we propose a new classification method of DNA copy number data based on the concept of limited Jumping Emerging Patterns. We present the comparison of our limJEPClassifier to SVM which is considered the most successful classifier in the case of high-throughput data.</p> <p>Results</p> <p>Our results revealed that the classification performance using limJEPClassifier is significantly higher than other methods. Furthermore, we show that application of the limited JEP's can significantly improve classification, when strongly unbalanced data are given.</p> <p>Conclusion</p> <p>Nowadays, aCGH has become a very important tool, used in research of cancer or genomic disorders. Therefore, improving classification of aCGH data can have a great impact on many medical issues such as the process of diagnosis and finding disease-related genes. The performed experiment shows that the application of Jumping Emerging Patterns can be effective in the classification of high-dimensional data, including these from aCGH experiments.</p

Reduced expression of tissue factor pathway inhibitor-2 contributes to apoptosis and angiogenesis in cervical cancer

<p>Abstract</p> <p>Background</p> <p>Tissue factor pathway inhibitor-2 (TFPI-2) is an extracellular matrix associated broad-spectrum Kunitz-type serine proteinase inhibitor. Recently, down regulation of TFPI-2 was suggested to be involved in tumor invasion and metastasis in some cancers.</p> <p>Methods</p> <p>This study involved 12 normal cervical squamous epithelia, 48 cervical intraepithelial neoplasia (CIN), and 68 cervical cancer. The expression of TFPI-2, Ki-67 and vascular endothelial growth factor (VEGF) were investigated by immunohistochemistry staining. The apoptolic index(AI) was determined with an in situ end-labeling assay(TUNEL). And the marker of CD34 staining was used as an indicator of microvessel density (MVD).</p> <p>Results</p> <p>TFPI-2 expression has a decreasing trend with the progression of cervical cancer and was significantly correlated with FIGO stage, lymph node metastasis and HPV infection. In addition, there were significant positive correlations between the grading of TFPI-2 expression and AI(P = 0.004). In contrast, the expression of TFPI-2 and VEGF or MVD was negatively correlated (both p < 0.001). However, we did not establish any significant correlation between Ki-67 and TFPI-2 expression in cervical cancer.</p> <p>Conclusions</p> <p>The results suggested that the expression of TFPI-2 had a decreasing trend with tumor progression of cervical cancer. There was a close association between the expression of TFPI-2 and tumor cell apoptosis and angiogenesis in patients with cervical cancer. TFPI-2 may play an inhibitive role during the development of cervical cancer.</p

Fast MCMC sampling for hidden markov models to determine copy number variations

<p>Abstract</p> <p>Background</p> <p>Hidden Markov Models (HMM) are often used for analyzing Comparative Genomic Hybridization (CGH) data to identify chromosomal aberrations or copy number variations by segmenting observation sequences. For efficiency reasons the parameters of a HMM are often estimated with maximum likelihood and a segmentation is obtained with the Viterbi algorithm. This introduces considerable uncertainty in the segmentation, which can be avoided with Bayesian approaches integrating out parameters using Markov Chain Monte Carlo (MCMC) sampling. While the advantages of Bayesian approaches have been clearly demonstrated, the likelihood based approaches are still preferred in practice for their lower running times; datasets coming from high-density arrays and next generation sequencing amplify these problems.</p> <p>Results</p> <p>We propose an approximate sampling technique, inspired by compression of discrete sequences in HMM computations and by <it>kd</it>-trees to leverage spatial relations between data points in typical data sets, to speed up the MCMC sampling.</p> <p>Conclusions</p> <p>We test our approximate sampling method on simulated and biological ArrayCGH datasets and high-density SNP arrays, and demonstrate a speed-up of 10 to 60 respectively 90 while achieving competitive results with the state-of-the art Bayesian approaches.</p> <p><it>Availability: </it>An implementation of our method will be made available as part of the open source GHMM library from <url>http://ghmm.org</url>.</p

Prevalence and consequences of patient safety incidents in general practice in the Netherlands: a retrospective medical record review study

Contains fulltext : 97252.pdf (publisher's version ) (Open Access)BACKGROUND: Patient safety can be at stake in both hospital and general practice settings. While severe patient safety incidents have been described, quantitative studies in large samples of patients in general practice are rare. This study aimed to assess patient safety in general practice, and to show areas where potential improvements could be implemented. METHODS: We conducted a retrospective review of patient records in Dutch general practice. A random sample of 1,000 patients from 20 general practices was obtained. The number of patient safety incidents that occurred in a one-year period, their perceived underlying causes, and impact on patients' health were recorded. RESULTS: We identified 211 patient safety incidents across a period of one year (95% CI: 185 until 241). A variety of types of incidents, perceived causes and consequences were found. A total of 58 patient safety incidents affected patients; seven were associated with hospital admission; none resulted in permanent disability or death. CONCLUSIONS: Although this large audit of medical records in general practices identified many patient safety incidents, only a few had a major impact on patients' health. Improving patient safety in this low-risk environment poses specific challenges, given the high numbers of patients and contacts in general practice

Estimation of Parent Specific DNA Copy Number in Tumors using High-Density Genotyping Arrays

Chromosomal gains and losses comprise an important type of genetic change in tumors, and can now be assayed using microarray hybridization-based experiments. Most current statistical models for DNA copy number estimate total copy number, which do not distinguish between the underlying quantities of the two inherited chromosomes. This latter information, sometimes called parent specific copy number, is important for identifying allele-specific amplifications and deletions, for quantifying normal cell contamination, and for giving a more complete molecular portrait of the tumor. We propose a stochastic segmentation model for parent-specific DNA copy number in tumor samples, and give an estimation procedure that is computationally efficient and can be applied to data from the current high density genotyping platforms. The proposed method does not require matched normal samples, and can estimate the unknown genotypes simultaneously with the parent specific copy number. The new method is used to analyze 223 glioblastoma samples from the Cancer Genome Atlas (TCGA) project, giving a more comprehensive summary of the copy number events in these samples. Detailed case studies on these samples reveal the additional insights that can be gained from an allele-specific copy number analysis, such as the quantification of fractional gains and losses, the identification of copy neutral loss of heterozygosity, and the characterization of regions of simultaneous changes of both inherited chromosomes

Germline Variation Controls the Architecture of Somatic Alterations in Tumors

Studies have suggested that somatic events in tumors can depend on an individual's constitutional genotype. We used squamous cell carcinomas (SCC) of the skin, which arise in high multiplicity in organ transplant recipients, as a model to compare the pattern of somatic alterations within and across individuals. Specifically, we performed array comparative genomic hybridization on 104 tumors from 25 unrelated individuals who each had three or more independently arisen SCCs and compared the profiles occurring within patients to profiles of tumors across a larger set of 135 patients. In general, chromosomal aberrations in SCCs were more similar within than across individuals (two-sided exact-test p-value ), consistent with the notion that the genetic background was affecting the pattern of somatic changes. To further test this possibility, we performed allele-specific imbalance studies using microsatellite markers mapping to 14 frequently aberrant regions of multiple independent tumors from 65 patients. We identified nine loci which show evidence of preferential allelic imbalance. One of these loci, 8q24, corresponded to a region in which multiple single nucleotide polymorphisms have been associated with increased cancer risk in genome-wide association studies (GWAS). We tested three implicated variants and identified one, rs13281615, with evidence of allele-specific imbalance (p-value = 0.012). The finding of an independently identified cancer susceptibility allele with allele-specific imbalance in a genomic region affected by recurrent DNA copy number changes suggest that it may also harbor risk alleles for SCC. Together these data provide strong evidence that the genetic background is a key driver of somatic events in cancer, opening an opportunity to expand this approach to identify cancer risk alleles

Patient safety culture measurement in general practice. Clinimetric properties of 'SCOPE'

<p>Abstract</p> <p>Background</p> <p>A supportive patient safety culture is considered to be an essential condition for improving patient safety. Assessing the current safety culture in general practice may be a first step to target improvements. To that end, we studied internal consistency and construct validity of a safety culture questionnaire for general practice (SCOPE) which was derived from a comparable questionnaire for hospitals (Dutch-HSOPS).</p> <p>Methods</p> <p>The survey was conducted among caregivers of Dutch general practice as part of an ongoing quality accreditation process using a 46 item questionnaire. We conducted factor analyses and studied validity by calculating correlations between the subscales and testing the hypothesis that respondents' <it>patient safety grade </it>of their practices correlated with their scores on the questionnaire.</p> <p>Results</p> <p>Of 72 practices 294 respondents completed the questionnaire. Eight factors were identified concerning <it>handover and teamwork, support and fellowship, communication openness, feedback and learning from error, intention to report events, adequate procedures and staffing, overall perceptions of patient safety </it>and <it>expectations and actions of managers</it>. Cronbach's alpha of the factors rated between 0.64 and 0.85. The subscales intercorrelated moderately, except for the factor about intention to report events. Respondents who graded patient safety highly scored significantly higher on the questionnaire than those who did not.</p> <p>Conclusions</p> <p>The SCOPE questionnaire seems an appropriate instrument to assess patient safety culture in general practice. The clinimetric properties of the SCOPE are promising, but future research should confirm the factor structure and construct of the SCOPE and delineate its responsiveness to changes in safety culture over time.</p