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Background Crohn’s disease (CD) patients have more than double the risk of nonalcoholic fatty liver disease (NAFLD) compared with the general population after considering traditional risk factors. NAFLD remains underappreciated because routine imaging and liver biochemistries are neither sensitive nor specific for the diagnosis. Here we developed a Clinical Prediction Tool for NAFLD in CD (CPN-CD) using readily accessible parameters to diagnose NAFLD, as determined by magnetic resonance proton density fat fraction (PDFF). Methods A total of 311 consecutive CD patients who underwent magnetic resonance enterography from June 1, 2017, to May 31, 2018, were screened for NAFLD, defined as a PDFF >5.5% after excluding other liver diagnoses. CPN-CD was derived using binary multivariate logistic regression and internally validated with a 10-fold cross-validation. CPN-CD was compared with the Hepatic Steatosis Index (HSI) by the C-statistic and categorical Net Reclassification Improvement (NRI). Results CPN-CD included age, sex, ethnicity/race, serum alanine aminotransferase, body mass index, known cardiometabolic diagnoses, CD duration, and current use of azathioprine/6-mercaptopurine. At <20% risk, NAFLD could be excluded with a sensitivity of 86% (negative predictive value, 86%). At ≥50% risk, NAFLD was diagnosed with a specificity of 87% (positive predictive value, 75%). CPN-CD exhibited good discrimination (C-statistic 0.85) compared with fair discrimination of the HSI (C-statistic, 0.76). CPN-CD was superior to the HSI by net reclassification improvement (+0.20; P < 0.001) and decision curve analysis. Conclusions CPN-CD outperforms HSI in detecting NAFLD in patients with CD. Future directions include external validation, outcome validation, and testing generalizability to patients with ulcerative colitis.

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INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease affecting one-quarter of the world population. NAFLD is also an extra-intestinal manifestation of Crohn's Disease (CD), where it is associated with higher morbidity and mortality. We aimed to (1) characterize risk factors for NAFLD in South Asian CD pts, and (2) externally validate a clinical prediction score for NAFLD in CD, the St. Louis Steatosis Index (SLSI). METHODS: We prospectively enrolled CD pts from 2/1/2019-5/31/2019 at the Asian Institute of Gastroenterology, a tertiary referral center for Inflammatory Bowel Disease (IBD) in India. Exclusion criteria included an alternative etiology of liver disease (e.g., chronic viral hepatitis). Controlled attenuation parameter (CAP) with transient elastography was measured using FibroScan® (Echosens, Waltham, MA) to quantitate hepatic steatosis and fibrosis. The outcome of NAFLD was defined as CAP ≥ 240 dB/m with the secondary outcome of hepatic fibrosis defined as ≥7 kPa. The SLSI operating characteristics were compared at re-calibrated low risk (<10%) and high risk (>40%) thresholds. The discrimination was compared to the Hepatic Steatosis Index (HSI) by both the C-statistic and net reclassification improvement (NRI) for the primary outcome and to both the HSI and the NAFLD fibrosis score (NFS) for the secondary outcome. RESULTS: 100 pts (63% male, median age 35 years) were enrolled with 42 (42%) demonstrating NAFLD and 6 (6%) demonstrating hepatic fibrosis. Univariate risk factors for NAFLD are shown (Table 1). Older age, male gender, elevated BMI, and presence of hypertension were significantly associated with a diagnosis of NAFLD. A low-risk SLSI was 71% sensitive and a high-risk SLSI was 93% specific for a diagnosis of NAFLD. SLSI showed fair discrimination for NAFLD but this was not different from the HSI (C statistic 0.747 vs 0.722; NRI +0.02). For the diagnosis of hepatic fibrosis, a low-risk SLSI was 83% sensitive and a high-risk score was 90% specific. The SLSI showed fair discrimination (0.767) that was superior to both the HSI (C statistic 0.587, NRI +0.47) and the NFS (C statistic 0.688, NR +0.23). CONCLUSION: NAFLD was common among this South Asian cohort with CD despite few traditional risk factors. The SLSI has fair discrimination for both NAFLD and the more clinically relevant subgroup with hepatic fibrosis. Further steps include exploring alternate mechanisms for this finding and devising more sensitive CD-specific screening tools for NAFLD.

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Reliability of solid rocket motors has steadily increased since the beginning of solid propulsion systems. Increased reliability of solid rocket motors has produced a 100 percent success rate in orbital space launched rocket systems in the United States over the past 20 years. Historical failures have been attributed to different components of these systems including nozzles, propellant, cases, joints, propellant/liner/insulation bonds, and insulation. Attribution to improvements in testing, nondestructive evaluation (NDE), materials, manufacturing, processes, technology, and analytical tools is indicated for the increased reliability of these systems. This paper includes the following: 1) reviews of trends in historical reliability of solid rocket motors, 2) identification of historical failures modes and their implications to modern systems, and 3) a brief summary review of approaches that have been developed to improve reliability. Nomenclature