Project description:A formal Mentorship Program within the Children's Oncology Group (COG) was established to pair young investigators (mentees) with established COG members (mentors). Despite the American Academy of Pediatrics policy statement promoting mentorship programs, there are no publications describing and evaluating national mentorship programs in pediatric subspecialties. In this study, a series of internal program evaluations were performed using surveys of both mentors and mentees. Responses were deidentified and analyzed to determine the utility of the program by both participant satisfaction and self-reported academic productivity. Results indicated that mentees were generally satisfied with the program. Mentor-mentee pairs that met at least quarterly demonstrated greater academic productivity than pairings that met less frequently. This formal mentorship program appeared to have subjective and objective utility for the development of academic pediatric subspecialists.
Project description:The Genetic Association Information Network (GAIN) Data Access Committee was established in June 2007 to provide prompt and fair access to data from six genome-wide association studies through the database of Genotypes and Phenotypes (dbGaP). Of 945 project requests received through 2011, 749 (79%) have been approved; median receipt-to-approval time decreased from 14 days in 2007 to 8 days in 2011. Over half (54%) of the proposed research uses were for GAIN-specific phenotypes; other uses were for method development (26%) and adding controls to other studies (17%). Eight data-management incidents, defined as compromises of any of the data-use conditions, occurred among nine approved users; most were procedural violations, and none violated participant confidentiality. Over 5 years of experience with GAIN data access has demonstrated substantial use of GAIN data by investigators from academic, nonprofit, and for-profit institutions with relatively few and contained policy violations. The availability of GAIN data has allowed for advances in both the understanding of the genetic underpinnings of mental-health disorders, diabetes, and psoriasis and the development and refinement of statistical methods for identifying genetic and environmental factors related to complex common diseases.
Project description:Over the past decades, outcomes for children with cancer have improved dramatically through serial clinical trials based in large measure on dose intensification of cytotoxic chemotherapy for children with high-risk malignancies. Progress made through such dose intensification, in general, is no longer yielding further improvements in outcome. With the revolution in sequencing technologies and rapid development of drugs that block specific proteins and pathways, there is now an opportunity to improve outcomes for pediatric cancer patients through mutation-based targeted therapeutic strategies. The Children's Oncology Group (COG), in partnership with the National Cancer Institute (NCI), is planning a trial entitled the COG-NCI Pediatric Molecular Analysis for Therapeutic Choice (Pediatric MATCH) protocol utilizing an umbrella design. This protocol will have centralized infrastructure and will consist of a biomarker profiling protocol and multiple single-arm phase II trials of targeted therapies. Pediatric patients with recurrent or refractory solid tumors, lymphomas, or histiocytoses with measurable disease will be eligible. The Pediatric MATCH Target and Agent Prioritization (TAP) committee includes membership representing COG disease committees, the Food and Drug Administration, and the NCI. The TAP Committee systematically reviewed target and agent pairs for inclusion in the Pediatric MATCH trial. Fifteen drug-target pairs were reviewed by the TAP Committee, with seven recommended for further development as initial arms of the Pediatric MATCH trial. The current evidence for availability, efficacy, and safety of targeted agents in children for each class of mutation considered for inclusion in the Pediatric MATCH trial is discussed in this review.
Project description:To explore the potential role of computed tomography (CT) texture analysis and an imaging biomarker in differentiating primary gastro-intestinal lymphoma (PGIL) from gastro-intestinal adenocarcinoma (GIAC). A total of 131 patients with surgical pathologically PGIL and GIAC were enrolled in this study. Histogram parameters of arterial and venous phases extracted from contrast enhanced modified discrete cosine transform (MDCT) images were compared between PGIL and GIAC by Mann-Whitney U tests. The optimal parameters for differentiating these two groups were obtained through receiver operating characteristic (ROC) curves and the area under the curve (AUC) was calculated. Compared with GIAC, in arterial phase, PGIL had statistically higher 5th, 10th percentiles (p = 0.003 and 0.011) and statistically lower entropy (p = 0.001). In the venous phase, PGIL had statistically lower mean, median, 75th, 90th, 95th percentiles, and entropy (p = 0.036, 0.029, 0.007, 0.001 and 0.001, respectively). For differentiating PGIL from GIAC, V-median + A-5th percentile was an optimal parameter for combined diagnosis (AUC = 0.746, p < 0.0001), and the corresponding sensitivity and specificity were 81.7 and 64.8%, respectively. CT texture analysis could be useful for differential diagnosis of PGIL and GIAC.
Project description:Asiatic wild ass (Kulan, Equus hemionus) population range and numbers became severely reduced and a reintroduction project is currently aiming to re-establish a population in the Central Steppe of Kazakhstan. Pre-emptive deworming is often recommended for equid translocations but eliminating parasites prior to translocation could cause disruptions in a balanced host-parasite relationship, adding an additional stressor to an already stressful intervention involving capture, transport, and adaptation to a new environment. Following a disease risk assessment, we decided against pre-emptive deworming and focused on monitoring the first group of nine translocated kulan in a large acclimatization enclosure prior to release. Over the 5-month acclimatization period, we regularly collected fecal samples and analyzed the shedding intensity of gastro-intestinal parasite eggs, obtained time budgets through behavioral observations, and visually assessed body condition. We identified strongyles (Strongylinae and Cyathostominae) and pinworms (Oxyuris equi) in fecal samples. All individuals shed strongyle eggs and two of the nine individuals had higher shedding intensities, but rarely reached levels for which deworming is recommended. All kulan appeared healthy throughout the observation period, aggressive interactions were very rare, and time budgets were very similar and dominated by feeding. Our results suggest that in translocation projects where the risk of introducing new parasites is minimal, pre-emptive treatment in wild equids can be replaced with non-invasive monitoring during the acclimatization period. We acknowledge that the small number of kulan, the large size of the enclosure, and the low temperatures during the animals stay in the acclimatization enclosure may all have reduced infestation pressure.
Project description:Background: Data sharing is now a mandatory prerequisite for several major funders and journals, where researchers are obligated to deposit the data resulting from their studies in an openly accessible repository. Biomedical open data are now widely available in almost all disciplines, where researchers can freely access and reuse these data in new studies. We aim to study the BioLINCC datasets, number of publications that used BioLINCC open access data, and the impact of these publications through the citations they received. Methods: As of July 2019, there was a total of 194 datasets stored in BioLINCC repository and accessible through their portal. We requested the full list of publications that used these datasets from BioLINCC, and we also performed a supplementary PubMed search for other publications. We used Web of Science (WoS) to analyze the characteristics of publications and the citations they received, where WoS database index high quality articles. Results: 1,086 published articles used data from BioLINCC repository for 79 (40.72%) datasets, where 115 (59.28%) datasets didn't have any publications associated with it. Of the total publications, 987 (90.88%) articles were WoS indexed. The number of publications has steadily increased since 2002 and peaked in 2018 with a total number of 138 publications on that year. The 987 open data publications received a total of 34,181 citations up to 1 st October 2019. The average citation per item for the open data publications was 34.63. The total number of citations received by open data publications per year has increased from only 2 citations in 2002, peaking in 2018 with 2361 citations. Conclusion: Majority of BioLINCC datasets were not used in secondary publications. Despite that, the datasets used for secondary publications yielded publications in WoS indexed journals and are receiving an increasing number of citations.
Project description:Clinical trials data from National Cancer Institute (NCI)-funded cooperative oncology group trials could be enhanced by merging with external data sources. Merging without direct patient identifiers would provide additional patient privacy protections. We sought to develop and validate a matching algorithm that uses only indirect patient identifiers.We merged the data from two Phase III Children's Oncology Group (COG) trials for de novo acute myeloid leukemia (AML) with the Pediatric Health Information Systems (PHIS). We developed a stepwise matching algorithm that used indirect identifiers including treatment site, gender, birth year, birth month, enrollment year and enrollment month. Results from the stepwise algorithm were compared against the direct merge method that used date of birth, treatment site, and gender. The indirect merge algorithm was developed on AAML0531 and validated on AAML1031.Of 415 patients enrolled on the AAML0531 trial at PHIS centers, we successfully matched 378 (91.1%) patients using the indirect stepwise algorithm. Comparison to the direct merge result suggested that 362 (95.7%) matches identified by the indirect merge algorithm were concordant with the direct merge result. When validating the indirect stepwise algorithm using the AAML1031 trial, we successfully matched 157 out of 165 patients (95.2%) and 150 (95.5%) of the indirectly merged matches were concordant with the directly merged matches.These data demonstrate that patients enrolled on COG clinical trials can be successfully merged with PHIS administrative data using a stepwise algorithm based on indirect patient identifiers. The merged data sets can be used as a platform for comparative effectiveness and cost effectiveness studies.
Project description:Background and aims: Dysregulation of intestinal epithelial cells performance associates with an array of pathologies whose onset mechanisms are incompletely understood. The aim of the present study was to provide a map of gene expresssion patterns along the human healthy adult gastro-intestinal tract and to implement a new procedure for microarray data noise filtering that would allow their use as a reference when screening for pathological deviations, such as inflammatory bowel disease (IBD). Methods: Gene expression profiles in antrum, duodenum, jejunum, ileum and transverse colon biopsies were measured with the Affymetrix U133A array and principal component analysis was used to identify region-selective biomarkers. These data were intersected with highly variable genes from a public dataset of gene expression in the ileal and colonic healthy regions of UC and Crohn’s disease patients. Moreover, gene sets covering gut functions not entirely accounted for by the available public tools were constructed to monitor their expression along the GI tract. Results: 166 genes were found to be responsible for distinguishing the five regions considered. Fourteen had never been described in the GI tract, including a semaphorin probably implicated in pathogen invasion, and six other novel genes. Similar analysis of the IBD datasets revealed that samples stratify based on disease rather than on the intestinal region. This withstanding, eleven genes were identified as possible early predictors of Crohn’s and/or UC in ileum and/or colon. These include CLCA4 and SLC26A2, both implicated in ion transport. Conclusions: This novel approach, validated by retrieving known gene profiles, allowed the identification of promising new leads both in health and IBD state. Keywords: gastro-intestinal tract comparison