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Fed-batch cultures of Chinese Hamster Ovary cells have been used to produce high quantities of biotherapeutics, particularly monoclonal antibodies. However, a growing number of next-generation biotherapeutics, such as bi-specific antibodies and fusion proteins, are difficult to express using standard fed-batch processes. Decoupling cell growth and biotherapeutic production is becoming an increasingly desired strategy for the biomanufacturing industry, especially for difficult-to-express products. Cells are grown to a high cell density in the absence of recombinant protein production (the growth phase), then expression of the recombinant protein is induced and cell proliferation halted (the production phase), usually by combining an inducible gene expression system with a proliferation control strategy. Separating the growth and production phases allows cell resources to be more efficiently directed toward either growth or production, improving growth characteristics and enhancing the production of difficult to express proteins. However, current mammalian cell proliferation control methods rely on temperature shifts and chemical agents, which interact with many non-proliferation pathways, leading to variable impacts on product quality and culture viability. Synthetic biology offers an alternative approach by strategically targeting proliferation pathways to arrest cell growth but have largely remained unused in industrial bioproduction. Due to recent developments in microbial decoupling systems and advances in available mammalian cell engineering tools, we propose that the synthetic biology approach to decoupling growth and production needs revisiting.

Background Hypertension is diagnosed in 1–5% of children, and 5–10% of those hypertensive children have renovascular disease. The gold standard for a diagnosis of renal artery stenosis is arteriography, and Doppler ultrasound (Doppler US) continues to be advocated as a useful screening test. Objective The purpose of this study was to determine the utility of Doppler US in children as a screening tool and to better define clinical features of children in whom arteriography should be performed. Materials and methods This retrospective study evaluated the imaging and clinical parameters for all children who had a renal US with Doppler followed by a diagnostic arteriogram for the evaluation of hypertension during a 12-year period at a tertiary children’s hospital. Sixty-two children were included. We evaluated each child’s clinical parameters and placed each child into one of three categories of hypertension: mild, moderate or severe. Results Eleven of 17 kidneys with proven renal artery stenosis were detected with Doppler US (sensitivity 64%). Six children with renal artery stenosis were missed by Doppler US, four of whom had segmental artery lesions. Of the children with positive renal artery stenosis on arteriography, all but three (79%) were classified as having moderate to severe hypertension. Conclusion Doppler US is a useful screening examination when evaluating children with hypertension, detecting renal artery stenosis in most affected children. The clinical risk classifications are helpful in guiding which children should proceed with arteriography regardless of the Doppler US results.

The job of the pediatric radiologist long ago ceased to be an 8-to-5 role. Many practices have adopted evening shifts of in-house attending radiologists to cover the busy evening activity. With the ever-increasing role of imaging in clinical decisions and patient management, there is a need — if not a demand — to further extend attending pediatric radiology coverage. In this article, we discuss the needs and justification for extending pediatric radiology coverage at a tertiary-care children’s hospital. We also describe the approach we took toward implementing 24/7 attending in-house coverage of pediatric radiology.

Background Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The gold standard for diagnosis is liver biopsy. MRI is a non-invasive imaging method to provide quantitative measurement of hepatic fat content. The methodology is particularly appealing for the pediatric population because of its rapidity and radiation-free imaging techniques. Objective To develop a multi-point Dixon MRI method with multi-interference models (multi-fat-peak modeling and bi-exponential T2* correction) for accurate hepatic fat fraction (FF) and T2* measurements in pediatric patients with NAFLD. Materials and methods A phantom study was first performed to validate the accuracy of the MRI fat fraction measurement by comparing it with the chemical fat composition of the ex-vivo pork liver-fat homogenate. The most accurate model determined from the phantom study was used for fat fraction and T2* measurements in 52 children and young adults referred from the pediatric hepatology clinic with suspected or identified NAFLD. Separate T2* values of water (T2* W ) and fat (T2* F ) components derived from the bi-exponential fitting were evaluated and plotted as a function of fat fraction. In ten patients undergoing liver biopsy, we compared histological analysis of liver fat fraction with MRI fat fraction. Results In the phantom study the 6-point Dixon with 5-fat-peak, bi-exponential T2* modeling demonstrated the best precision and accuracy in fat fraction measurements compared with other methods. This model was further calibrated with chemical fat fraction and applied in patients, where similar patterns were observed as in the phantom study that conventional 2-point and 3-point Dixon methods underestimated fat fraction compared to the calibrated 6-point 5-fat-peak bi-exponential model ( P  < 0.0001). With increasing fat fraction, T2* W (27.9 ± 3.5 ms) decreased, whereas T2* F (20.3 ± 5.5 ms) increased; and T2* W and T2* F became increasingly more similar when fat fraction was higher than 15–20%. Histological fat fraction measurements in ten patients were highly correlated with calibrated MRI fat fraction measurements (Pearson correlation coefficient r  = 0.90 with P  = 0.0004). Conclusion Liver MRI using multi-point Dixon with multi-fat-peak and bi-exponential T2* modeling provided accurate fat quantification in children and young adults with non-alcoholic fatty liver disease and may be used to screen at-risk or affected individuals and to monitor disease progress noninvasively.