Impact of the Image Gently® Campaign on Computerized Tomography Use for Evaluation of Pediatric Nephrolithiasis.

PURPOSE: The Image Gently® campaign was launched by several radiological societies in 2007 to promote safe imaging in children. A goal of the campaign was to reduce ionizing radiation exposure in children. Given the recurrent nature of kidney stones, affected children are at risk for unnecessary ionizing radiation exposure from computerized tomography. We sought to determine whether the Image Gently campaign led to a decrease in the use of computerized tomography for evaluating children with nephrolithiasis. We hypothesized that the campaign was the primary cause of a reduction in the use of computerized tomography. MATERIALS AND METHODS: We analyzed medical claims data from 2001 to 2015 identifying children with nephrolithiasis covered by the same commercial insurance provider. Using a difference in differences design, we estimated changes in computerized tomography use after the campaign started among patients less than 18 years old compared to a control group age 18 years or older with nephrolithiasis. RESULTS: We identified 12,734 children and 787,720 adults diagnosed with nephrolithiasis. Before 2007 quarterly rates of computerized tomography use during a stone episode (per 1,000 patients) were increasing at a parallel rate in children and adults (5.1 in children vs 7.2 in adults, p = 0.123). After the Image Gently campaign started the use of computerized tomography decreased in both groups but at a slightly higher rate in adults (difference in differences 2.96, 95% CI 0.00 to 5.91, p = 0.050). CONCLUSIONS: Although there has been a reduction in the use of computerized tomography among children with nephrolithiasis, given a similar trend seen in adults this change cannot be primarily attributed to the Image Gently campaign.

Noncanonical secondary structure stabilizes mitochondrial tRNA(Ser(UCN)) by reducing the entropic cost of tertiary folding.

Mammalian mitochondrial tRNA(Ser(UCN)) (mt-tRNA(Ser)) and pyrrolysine tRNA (tRNA(Pyl)) fold to near-canonical three-dimensional structures despite having noncanonical secondary structures with shortened interhelical loops that disrupt the conserved tRNA tertiary interaction network. How these noncanonical tRNAs compensate for their loss of tertiary interactions remains unclear. Furthermore, in human mt-tRNA(Ser), lengthening the variable loop by the 7472insC mutation reduces mt-tRNA(Ser) concentration in vivo through poorly understood mechanisms and is strongly associated with diseases such as deafness and epilepsy. Using simulations of the TOPRNA coarse-grained model, we show that increased topological constraints encoded by the unique secondary structure of wild-type mt-tRNA(Ser) decrease the entropic cost of folding by ∼2.5 kcal/mol compared to canonical tRNA, offsetting its loss of tertiary interactions. Further simulations show that the pathogenic 7472insC mutation disrupts topological constraints and hence destabilizes the mutant mt-tRNA(Ser) by ∼0.6 kcal/mol relative to wild-type. UV melting experiments confirm that insertion mutations lower mt-tRNA(Ser) melting temperature by 6-9 °C and increase the folding free energy by 0.8-1.7 kcal/mol in a largely sequence- and salt-independent manner, in quantitative agreement with our simulation predictions. Our results show that topological constraints provide a quantitative framework for describing key aspects of RNA folding behavior and also provide the first evidence of a pathogenic mutation that is due to disruption of topological constraints.