PEACE: Parallel Environment for Assembly and Clustering of Gene Expression.

We present PEACE, a stand-alone tool for high-throughput ab initio clustering of transcript fragment sequences produced by Next Generation or Sanger Sequencing technologies. It is freely available from www.peace-tools.org. Installed and managed through a downloadable user-friendly graphical user interface (GUI), PEACE can process large data sets of transcript fragments of length 50 bases or greater, grouping the fragments by gene associations with a sensitivity comparable to leading clustering tools. Once clustered, the user can employ the GUI's analysis functions, facilitating the easy collection of statistics and allowing them to single out specific clusters for more comprehensive study or assembly. Using a novel minimum spanning tree-based clustering method, PEACE is the equal of leading tools in the literature, with an interface making it accessible to any user. It produces results of quality virtually identical to those of the WCD tool when applied to Sanger sequences, significantly improved results over WCD and TGICL when applied to the products of Next Generation Sequencing Technology and significantly improved results over Cap3 in both cases. In short, PEACE provides an intuitive GUI and a feature-rich, parallel clustering engine that proves to be a valuable addition to the leading cDNA clustering tools.

Measuring cell proliferation in the rectal mucosa. comparing bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA) assays.

Cell proliferation in the human colorectum can be measured using bromodeoxyuridine (BrdU) or proliferating cell nuclear antigen (PCNA) assays. Using data from the National Cancer Institute's Polyp Prevention Trial, these two assays are compared using correlation coefficients and variance components analysis. Adjusting for fixed as well as for the random effects of between-biopsy and scoring variation, the estimated correlation is 0.46 for the log labeling index and 0.45 for log proliferative height. This is an estimate of the highest correlation that can be achieved by taking multiple biopsies scored by multiple scorers. For single biopsies, the estimated correlation is 0.16 and 0.10, respectively. There are significant differences between the variance components for the two assays. For example, for log labeling index, PCNA has a lower variation between biopsies than BrdU, but higher variation between scorings. When used in a clinical or epidemiological setting, it is important to take multiple biopsies at multiple time points.

Effect of training on adoption of cancer prevention nutrition-related activities by primary care practices: results of a randomized, controlled study.

OBJECTIVE: The National Cancer Institute (NCI) developed a manual to guide primary care practices in structuring their office environment and routine visits so as to enhance nutrition screening, advice/referral, and follow-up for cancer prevention. The adoption of the manual's recommendations by primary care practices was evaluated by examining two strategies: physician training on how to implement the manual's recommendations versus simple mailing of the manual. This article reports on the results of a randomized controlled trial to evaluate the effectiveness of these two strategies. DESIGN: A three-arm, randomized, controlled study. SETTING: Free-standing primary care physician practices in Pennsylvania and New Jersey. INTERVENTION: Each study practice was randomly assigned to one of three groups. The training group practices were invited to send one member from their practice of their choosing to a 3-hour "train-a-trainer" workshop, the manual-only-group practices were mailed the nutrition manual, and the control group practices received no intervention. For training group practices, training was provided in the four major components of the nutrition manual: how to organize the office environment to support cancer prevention nutrition-related activities; how to screen patient adherence to the NCI dietary guidelines; how to provide dietary advice/referral; and how to implement a patient follow-up system to support patients in making changes in their nutrition-related behaviors. MEASUREMENTS: The primary outcomes of the study were derived from two evaluation instruments. The observation instrument documented the tools and procedures recommended by the nutrition manual and adopted in patient charts and the office environment. The in-person structured interview evaluated the physician and staff's self-reported nutrition-related activities reflecting the nutrition manual's recommendations. Data from these two instruments were used to construct four adherence scores corresponding to the areas: office organization, nutrition screening, nutrition advice/referral, and patient follow-up. MAIN RESULTS: The adoption of the manual's recommendations was highest among the practices in the training group as reflected by their higher adherence scores. They organized their office ( P =.005) and screened their patients regarding their eating habits ( P =.046) significantly more closely to the recommendations of the nutrition manual than practices in the manual-only group. However, despite being the highest in compliance, the training group practices were only 54.9% adherent to the manual's recommendations regarding nutrition advice/referral, and 28.5% adherent to its recommendations on office organization, 23.5% adherent to its recommendations on nutrition screening, and 14.6% adherent to its patient follow-up recommendations. CONCLUSIONS: Primary care practices exposed to the nutrition manual in a training session adopted more of the manual's recommendations. Specifically, practices invited to training were more likely to perform nutrition screening and to structure their office environment to be conducive to providing nutrition-related services for cancer prevention. The impact of the training was moderate and not statistically significant for nutrition advice/referral or patient follow-up, which are important in achieving long-term dietary changes in patients. The overall low adherence scores to nutrition-related activities demonstrates that there is plenty of room for improvement among the practices in the training group.

An evaluation of rectal mucosal proliferation measure variability sources in the polyp prevention trial: can we detect informative differences among individuals' proliferation measures amid the noise?

We assessed components of total variability of bromodeoxyuridine (BrdUrd) and proliferating cell nuclear antigen (PCNA) assays of rectal mucosal proliferation in a subset of 390 participants from the U. S. National Cancer Institute's multicenter Polyp Prevention Trial. Biopsies were blindly double-scored by two technicians. For those participants for whom at least one evaluable biopsy was obtained, a mean of 2.0 and 2.6 biopsies, and 6.2 and 8.7 crypts/biopsy were evaluated, respectively, with the BrdUrd and PCNA assays. Factors such as clinical center, scorer, and month of biopsy collection significantly affected the observed values of the labeling index (LI) and proliferative height (PH). Therefore, it is essential to control or adjust for these variables in proliferation studies. Sources of random variation for LI and PH measures remaining after the aforementioned factors include between-participant variation and several sources of within-participant variation, including variation over time, between biopsies, and between multiple measurements on the same biopsy. Both LI and PH measurements exhibited substantial variability over time, between biopsies, and from reading-to-reading of the same biopsy. When other sources of variability have been accounted for, the PCNA LI seems to have little between-participant variation. This brings into question its utility as a marker in colorectal cancer studies. The PCNA PH showed significant between-participant variability and may hold some promise as a useful marker in colorectal cancer studies. Results for BrdUrd were less conclusive. The BrdUrd LI showed marginally significant between-participant variation, whereas the corresponding variation for PH was nonsignificant.

Register of dietary assessment calibration-validation studies: a status report.

A register of dietary assessment calibration-validation studies was created to improve communication between investigators, avoid duplication of effort, and identify gaps in knowledge. Calibration-validation studies were defined as investigations in which the participants completed at least two different dietary measurements. A questionnaire soliciting descriptive information about such studies was widely distributed. Completed questionnaires were received from October 1993 through September 1994 and the data from them were entered into a computer database. Preliminary individual reports were mailed to all contributors in September 1994 for revision or updating. Responses received by the end of October 1994 were incorporated into the database. A status report was published in December 1994. The report includes descriptions of 84 studies, 15 summary tables, and 6 reference indexes. Of the 84 studies included, 44 (52%) were conducted in North America, 35 (42%) in Europe, 2 (2%) in South America, 2 (2%) in Asia, and 1 (1%) in Australia. Sixty-three of the 84 studies (75%) used food-frequency questionnaires, 52 (62%) used food records, 35 (42%) used one or more dietary recalls, 11 (13%) used biological measures, and 8 (10%) used diet histories. Plans for maintaining and updating the register are being developed.