Clinical and translational science
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Epigenetic influences, such as DNA methylation, histone acetylation, and up-regulation/down-regulation of genes by microRNAs, change the genetic makeup of an individual without affecting DNA base-pair sequences. Indeed, epigenetic changes play an integral role in the progression from normal esophageal mucosa to Barrett's esophagus to esophageal adenocarcinoma via dysplasia-metaplasia-neoplasia sequence. Many genes involved in esophageal adenocarcinoma display hypermethylation, leading to their down-regulation. ⋯ However, microRNAs can target up to hundreds of genes, making it difficult to correlate directly with a given phenotype of the disease. Esophageal adenocarcinoma progressing from premalignant condition of Barrett's esophagus carries an extremely poor prognosis. Risk stratification for patients based on their epigenetic profiles may be useful in providing more targeted and directed treatment to patients.
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The number of clinical research training programs has increased over the past 5-10 years, but few studies have quantitatively evaluated the effectiveness of these programs. The goal of this study was to evaluate the clinical and translational research training program at the University of Cincinnati by comparing the number of National Institutes of Health grants awarded to pediatric fellows who graduated from the MS degree program between 1995 and 2013 versus fellows who did not pursue an MS degree. ⋯ In multivariable analysis, MS alumni were more than three times as likely to have received at least one grant than were non-MS fellows (OR = 3.5, 95% CI [1.7-7.2]; C-statistic = 0.71) and MS alumni were more likely to obtain at least one K-series (OR = 4.1, 95% CI [1.6-10.2]; C-statistic = 0.74), M-series (OR = 11.8, 95% CI [3.4-41.4]; C-statistic = 0.81), or R-series (OR = 10.1, 95% CI [2.4-42.8]; C-statistic = 0.74) grant than were non-MS fellows. These findings suggest that graduate training in clinical and translational research prepares graduates for the highly competitive field of clinical and translational research.
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To identify and disseminate the organizational characteristics of "top performing" National Institute of Health (NIH) Clinical and Translational Science Awards (CTSA) institutions in regards to career development, using the number of new K awards received per year to rank institutions and comparing these with non-CTSA institutions. ⋯ The CTSA network of institutions is committed to developing the next generation of physician scientists in order to meet the pressing health needs of society. Educators and evaluators within this network may need to provide training to junior investigators beyond the traditional KL2 programs in order to advance their career development as physician scientists and clinical translational researchers.
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A number of commentaries have suggested that large studies are more reliable than smaller studies and there is a growing interest in the analysis of "big data" that integrates information from many thousands of persons and/or different data sources. We consider a variety of biases that are likely in the era of big data, including sampling error, measurement error, multiple comparisons errors, aggregation error, and errors associated with the systematic exclusion of information. Using examples from epidemiology, health services research, studies on determinants of health, and clinical trials, we conclude that it is necessary to exercise greater caution to be sure that big sample size does not lead to big inferential errors. Despite the advantages of big studies, large sample size can magnify the bias associated with error resulting from sampling or study design.
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Training translational scientists is a priority of the Clinical and Translational Science Award (CTSA) consortium. ⋯ The CTSA program contributes substantially to training the next generation of translational investigators. One-third of child health investigators obtained subsequent NIH awards in the short follow-up period demonstrating success of the CTSA CDA programs. Child health investigators are represented variably across the consortium. Pediatric institutions can partner with the CTSA program to further support training child health investigators.