Search

Background Various limitations have impacted research evaluating reader agreement for Liver Imaging Reporting and Data System (LI-RADS). Purpose To assess reader agreement of LI-RADS in an international multicenter multireader setting using scrollable images. Materials and Methods This retrospective study used deidentified clinical multiphase CT and MRI and reports with at least one untreated observation from six institutions and three countries; only qualifying examinations were submitted. Examination dates were October 2017 to August 2018 at the coordinating center. One untreated observation per examination was randomly selected using observation identifiers, and its clinically assigned features were extracted from the report. The corresponding LI-RADS version 2018 category was computed as a rescored clinical read. Each examination was randomly assigned to two of 43 research readers who independently scored the observation. Agreement for an ordinal modified four-category LI-RADS scale (LR-1, definitely benign; LR-2, probably benign; LR-3, intermediate probability of malignancy; LR-4, probably hepatocellular carcinoma [HCC]; LR-5, definitely HCC; LR-M, probably malignant but not HCC specific; and LR-TIV, tumor in vein) was computed using intraclass correlation coefficients (ICCs). Agreement was also computed for dichotomized malignancy (LR-4, LR-5, LR-M, and LR-TIV), LR-5, and LR-M. Agreement was compared between research-versus-research reads and research-versus-clinical reads. Results The study population consisted of 484 patients (mean age, 62 years ± 10 [SD]; 156 women; 93 CT examinations, 391 MRI examinations). ICCs for ordinal LI-RADS, dichotomized malignancy, LR-5, and LR-M were 0.68 (95% CI: 0.61, 0.73), 0.63 (95% CI: 0.55, 0.70), 0.58 (95% CI: 0.50, 0.66), and 0.46 (95% CI: 0.31, 0.61) respectively. Research-versus-research reader agreement was higher than research-versus-clinical agreement for modified four-category LI-RADS (ICC, 0.68 vs 0.62, respectively; P = .03) and for dichotomized malignancy (ICC, 0.63 vs 0.53, respectively; P = .005), but not for LR-5 (P = .14) or LR-M (P = .94). Conclusion There was moderate agreement for LI-RADS version 2018 overall. For some comparisons, research-versus-research reader agreement was higher than research-versus-clinical reader agreement, indicating differences between the clinical and research environments that warrant further study. © RSNA, 2023 Supplemental material is available for this article. See also the editorials by Johnson and Galgano and Smith in this issue.

Background & aimsNon-alcoholic steatohepatitis (NASH) is prevalent in adults with obesity and can progress to cirrhosis. In a secondary analysis of prospectively acquired data from the multicenter, randomized, placebo-controlled FLINT trial, we investigated the relationship between reduction in adipose tissue compartment volumes and hepatic histologic improvement.MethodsAdult participants in the FLINT trial with paired liver biopsies and abdominal MRI exams at baseline and end-of-treatment (72 weeks) were included (n = 76). Adipose tissue compartment volumes were obtained using MRI.ResultsTreatment and placebo groups did not differ in baseline adipose tissue volumes, or in change in adipose tissue volumes longitudinally (p = 0.107 to 0.745). Deep subcutaneous adipose tissue (dSAT) and visceral adipose tissue volume reductions were associated with histologic improvement in NASH (i.e., NAS [non-alcoholic fatty liver disease activity score] reductions of ≥2 points, at least 1 point from lobular inflammation and hepatocellular ballooning, and no worsening of fibrosis) (p = 0.031, and 0.030, respectively). In a stepwise logistic regression procedure, which included demographics, treatment group, baseline histology, baseline and changes in adipose tissue volumes, MRI hepatic proton density fat fraction (PDFF), and serum aminotransferases as potential predictors, reductions in dSAT and PDFF were associated with histologic improvement in NASH (regression coefficient = -2.001 and -0.083, p = 0.044 and 0.033, respectively).ConclusionsIn adults with NASH in the FLINT trial, those with greater longitudinal reductions in dSAT and potentially visceral adipose tissue volumes showed greater hepatic histologic improvements, independent of reductions in hepatic PDFF.Clinical trial numberNCT01265498.Impact and implicationsAlthough central obesity has been identified as a risk factor for obesity-related disorders including insulin resistance and cardiovascular disease, the role of central obesity in non-alcoholic steatohepatitis (NASH) warrants further clarification. Our results highlight that a reduction in central obesity, specifically deep subcutaneous adipose tissue and visceral adipose tissue, may be related to histologic improvement in NASH. The findings from this analysis should increase awareness of the importance of lifestyle intervention in NASH for clinical researchers and clinicians. Future studies and clinical practice may design interventions that assess the reduction of deep subcutaneous adipose tissue and visceral adipose tissue as outcome measures, rather than simply weight reduction.

ObjectivesTo assess reproducibility and fibrosis classification accuracy of magnetic resonance elastography (MRE)-determined liver stiffness measured manually at two different centers, and by automated analysis software in adults with nonalcoholic fatty liver disease (NAFLD), using histopathology as a reference standard.MethodsThis retrospective, cross-sectional study included 91 adults with NAFLD who underwent liver MRE and biopsy. MRE-determined liver stiffness was measured independently for this analysis by an image analyst at each of two centers using standardized manual analysis methodology, and separately by an automated analysis. Reproducibility was assessed pairwise by intraclass correlation coefficient (ICC) and Bland-Altman analysis. Diagnostic accuracy was assessed by receiver operating characteristic (ROC) analyses.ResultsICC of liver stiffness measurements was 0.95 (95% CI: 0.93, 0.97) between center 1 and center 2 analysts, 0.96 (95% CI: 0.94, 0.97) between the center 1 analyst and automated analysis, and 0.94 (95% CI: 0.91, 0.96) between the center 2 analyst and automated analysis. Mean bias and 95% limits of agreement were 0.06 ± 0.38 kPa between center 1 and center 2 analysts, 0.05 ± 0.32 kPa between the center 1 analyst and automated analysis, and 0.11 ± 0.41 kPa between the center 2 analyst and automated analysis. The area under the ROC curves for the center 1 analyst, center 2 analyst, and automated analysis were 0.834, 0.833, and 0.847 for distinguishing fibrosis stage 0 vs. ≥ 1, and 0.939, 0.947, and 0.940 for distinguishing fibrosis stage ≤ 2 vs. ≥ 3.ConclusionMRE-determined liver stiffness can be measured with high reproducibility and fibrosis classification accuracy at different centers and by an automated analysis.Key points• Reproducibility of MRE liver stiffness measurements in adults with nonalcoholic fatty liver disease is high between two experienced centers and between manual and automated analysis methods. • Analysts at two centers had similar high diagnostic accuracy for distinguishing dichotomized fibrosis stages. • Automated analysis provides similar diagnostic accuracy as manual analysis for advanced fibrosis.

ObjectivesTo investigate associations between histology and hepatic mechanical properties measured using multiparametric magnetic resonance elastography (MRE) in adults with known or suspected nonalcoholic fatty liver disease (NAFLD) without histologic fibrosis.MethodsThis was a retrospective analysis of 88 adults who underwent 3T MR exams including hepatic MRE and MR imaging to estimate proton density fat fraction (MRI-PDFF) within 180 days of liver biopsy. Associations between MRE mechanical properties (mean shear stiffness (|G*|) by 2D and 3D MRE, and storage modulus (G'), loss modulus (G″), wave attenuation (α), and damping ratio (ζ) by 3D MRE) and histologic, demographic and anthropometric data were assessed.ResultsIn univariate analyses, patients with lobular inflammation grade ≥ 2 had higher 2D |G*| and 3D G″ than those with grade ≤ 1 (p = 0.04). |G*| (both 2D and 3D), G', and G″ increased with age (rho = 0.25 to 0.31; p ≤ 0.03). In multivariable regression analyses, the association between inflammation grade ≥ 2 remained significant for 2D |G*| (p = 0.01) but not for 3D G″ (p = 0.06); age, sex, or BMI did not affect the MRE-inflammation relationship (p > 0.20).Conclusions2D |G*| and 3D G″ were weakly associated with moderate or severe lobular inflammation in patients with known or suspected NAFLD without fibrosis. With further validation and refinement, these properties might become useful biomarkers of inflammation. Age adjustment may help MRE interpretation, at least in patients with early-stage disease.Key points• Moderate to severe lobular inflammation was associated with hepatic elevated shear stiffness and elevated loss modulus (p =0.04) in patients with known or suspected NAFLD without liver fibrosis; this suggests that with further technical refinement these MRE-assessed mechanical properties may permit detection of inflammation before the onset of fibrosis in NAFLD. • Increasing age is associated with higher hepatic shear stiffness, and storage and loss moduli (rho = 0.25 to 0.31; p ≤ 0.03); this suggests that age adjustment may help interpret MRE results, at least in patients with early-stage NAFLD.

PurposeTo evaluate repeatability of ROI-sampling strategies for quantifying hepatic proton density fat fraction (PDFF) and to assess error relative to the 9-ROI PDFF.MethodsThis was a secondary analysis in subjects with known or suspected nonalcoholic fatty liver disease who underwent MRI for magnitude-based hepatic PDFF quantification. Each subject underwent three exams, each including three acquisitions (nine acquisitions total). An ROI was placed in each hepatic segment on the first acquisition of the first exam and propagated to other acquisitions. PDFF was calculated for each of 511 sampling strategies using every combination of 1, 2, …, all 9 ROIs. Intra- and inter-exam intra-class correlation coefficients (ICCs) and repeatability coefficients (RCs) were estimated for each sampling strategy. Mean absolute error (MAE) was estimated relative to the 9-ROI PDFF. Strategies that sampled both lobes evenly ("balanced") were compared with those that did not ("unbalanced") using two-sample t tests.ResultsThe 29 enrolled subjects (23 male, mean age 24 years) had mean 9-ROI PDFF 11.8% (1.1-36.3%). With more ROIs, ICCs increased, RCs decreased, and MAE decreased. Of the 60 balanced strategies with 4 ROIs, all (100%) achieved inter- and intra-exam ICCs > 0.998, 55 (92%) achieved intra-exam RC

BACKGROUND Health authorities across nations differ markedly on their position regarding electronic cigarettes. For example, the Royal College of Physicians in the United Kingdom promoted e-cigarettes as a harm-reduction alternative to cigarettes, whereas the United States Centers for Disease Control and Prevention warned against the use of e-cigarettes. OBJECTIVE This study tests the effects of these different policy messages on the public’s perception of e-cigarettes. METHODS Participants (N=20,055) were sampled from an online panel with members from 19 major Chinese cities, and were randomized into three groups. Group 1 received brief messaging on e-cigarettes equivalent to the UK position, Group 2 received messaging equivalent to the US position, and Group 3 served as a control.Harm of cigarettes and e-cigarettes were rated on a 1–10 scale. Cigarettes smokers were asked if they intended to use e-cigarettes in a future quit attempt. RESULTS The group exposed to the US message rated e-cigarettes as significantly more risky than the control group, 5.87 (95%CI, 5.81-5.93) vs. 5.49 (5.43-5.55). The UK message group had a similar rating to the control, 5.42 (5.36-5.48). A lower percent of smokers in the US message group, 53.9% (51.8-56.0), intended to use e-cigarettes in future attempts to quit smoking than the control group, 60.1% (58.0-62.2), which was similar to that of the UK message group, 60.3% (58.3-62.4). CONCLUSIONS Messages from health authorities that cast e-cigarettes chiefly in a negative light could significantly increase the perceived risks of e-cigarettes and decrease smokers’ intentions to use e-cigarettes to quit smoking. In addressing the risk of e-cigarettes, policymakers should consider the net effect of a policy so as to maximize its potential to save lives.

PurposeTo compare longitudinal hepatic proton density fat fraction (PDFF) changes estimated by magnitude- vs. complex-based chemical-shift-encoded MRI during a weight loss surgery (WLS) program in severely obese adults with biopsy-proven nonalcoholic fatty liver disease (NAFLD).MethodsThis was a secondary analysis of a prospective dual-center longitudinal study of 54 adults (44 women; mean age 52 years; range 27-70 years) with obesity, biopsy-proven NAFLD, and baseline PDFF ≥ 5%, enrolled in a WLS program. PDFF was estimated by confounder-corrected chemical-shift-encoded MRI using magnitude (MRI-M)- and complex (MRI-C)-based techniques at baseline (visit 1), after a 2- to 4-week very low-calorie diet (visit 2), and at 1, 3, and 6 months (visits 3 to 5) after surgery. At each visit, PDFF values estimated by MRI-M and MRI-C were compared by a paired t test. Rates of PDFF change estimated by MRI-M and MRI-C for visits 1 to 3, and for visits 3 to 5 were assessed by Bland-Altman analysis and intraclass correlation coefficients (ICCs).ResultsMRI-M PDFF estimates were lower by 0.5-0.7% compared with those of MRI-C at all visits (p

PurposeMRI proton density fat fraction (PDFF) can be calculated using magnitude (MRI-M) or complex (MRI-C) MRI data. The purpose of this study was to identify, assess, and compare the accuracy of common PDFF thresholds for MRI-M and MRI-C for assessing hepatic steatosis in patients with obesity, using histology as reference.MethodsThis two-center prospective study included patients undergoing MRI-C- and MRI-M-PDFF estimations within 3 days before weight loss surgery. Liver biopsy was performed, and histology-determined steatosis grades were used as reference standard. Using receiver operating characteristics (ROC) analysis on data pooled from both methods, single common thresholds for diagnosing and differentiating none or mild (0-1) from moderate to severe steatosis (2-3) were selected as the ones achieving the highest sensitivity while providing at least 90% specificity. Selection methods were cross-validated. Performances were compared using McNemar's tests.ResultsOf 81 included patients, 54 (67%) had steatosis. The common PDFF threshold for diagnosing steatosis was 5.4%, which provided a cross-validated 0.88 (95% CI 0.77-0.95) sensitivity and 0.92 (0.75-0.99) specificity for MRI-M and 0.87 sensitivity (0.75-0.94) with 0.81 (0.61-0.93) specificity for MRI-C. The common PDFF threshold to differentiate steatosis grades 0-1 from 2 to 3 was 14.7%, which provided cross-validated 0.86 (95% CI 0.59-0.98) sensitivity and 0.95 (0.87-0.99) specificity for MRI-M and 0.93 sensitivity (0.68-0.99) with 0.97(0.89-0.99) specificity for MRI-C.ConclusionIf independently validated, diagnostic thresholds of 5.4% and 14.7% could be adopted for both techniques for detecting and differentiating none to mild from moderate to severe steatosis, respectively, with high diagnostic accuracy.

PurposeTo describe a single-center preliminary experience with gadoxetate disodium-enhanced abbreviated MRI for hepatocellular carcinoma (HCC) screening and surveillance in patients with cirrhosis or chronic hepatitis B virus (cHBV).Materials and methodsThis was a retrospective study of consecutive patients aged 18 years and older with cirrhosis or cHBV who underwent at least one gadoxetate-enhanced abbreviated MRI examination for HCC surveillance from 2014 through 2016. Examinations were interpreted prospectively by one of six abdominal radiologists for clinical care. Clinical, imaging, and other data were extracted from electronic medical records. Diagnostic adequacy was assessed in all patients. Diagnostic accuracy was assessed in the subset of patients who could be classified as having HCC or not having HCC on the basis of a composite reference standard.ResultsIn this study, 330 patients (93% with cirrhosis; 45% women; mean age, 59 years) underwent gadoxetate-enhanced abbreviated MRI. In the 330 patients, 311 (94.2%) baseline gadoxetate-enhanced abbreviated MRI examinations were diagnostically adequate. Of 141 (43%) of the 330 patients, 91.4% (129 of 141) could be classified as not having HCC and 8.6% (12 of 141) could be classified as having HCC. Baseline gadoxetate-enhanced abbreviated MRI had 0.92 sensitivity (95% confidence interval [CI]: 0.62, 1.00) and 0.91 specificity (95% CI: 0.84, 0.95) for detection of HCC. Of the 330 patients who underwent baseline gadoxetate-enhanced abbreviated MRI, 187 (57%) were lost to follow-up.ConclusionGadoxetate-enhanced abbreviated MRI is feasible clinically, has a high diagnostic adequacy rate, and, on the basis of our preliminary experience, accurately depicts HCC in high-risk patients. Strategies to enhance follow-up compliance are needed.© RSNA, 2019Keywords: Abdomen/GI, Cirrhosis, Liver, MR-Imaging, Oncology, ScreeningSupplemental material is available for this article.

ObjectivesThis study assesses the risk of progression of Liver Imaging Reporting and Data System (LI-RADS) categories, and the effects of inter-exam changes in modality or radiologist on LI-RADS categorization.MethodsClinical LI-RADS v2014 CT and MRI exams at our institution between January 2014 and September 2017 were retrospectively identified. Untreated LR-1, LR-2, LR-3, and LR-4 observations with at least one follow-up exam were included. Three hundred and seventy-two observations in 214 patients (149 male, 65 female, mean age 61 ± 10 years) were included during the study period (715 exams total). Cumulative incidence curves for progression to malignant LI-RADS categories (LR-5 or LR-M) and to LR-4 or higher were generated for each index category and compared using log-rank tests with a resampling extension. Relationships between inter-exam changes in LI-RADS category and modality or radiologist, adjusted for inter-exam time intervals, were modeled using mixed effect logistic regressions.ResultsMedian inter-exam follow-up interval and total follow-up duration were 123 and 227 days, respectively. Index LR-1, LR-2, LR-3, and LR-4 differed significantly in their cumulative incidences of progression to malignant categories (p

ObjectivesThe purpose of this study was to (1) evaluate proton density fat fraction (PDFF) distribution across liver segments at baseline and (2) compare longitudinal segmental PDFF changes across time points in adult patients undergoing a very low-calorie diet (VLCD) and subsequent bariatric weight loss surgery (WLS).MethodsWe performed a secondary analysis of data from 118 morbidly obese adult patients enrolled in a VLCD-WLS program. PDFF was estimated using magnitude-based confounder-corrected chemical-shift-encoded (CSE) MRI in each hepatic segment and lobe at baseline (visit 1), after completion of VLCD (visit 2), and at 1, 3, and 6 months (visits 3-5) following WLS. Linear regressions were used to estimate the rate of PDFF change across visits. Lobar and segmental rates of change were compared pairwise.ResultsBaseline PDFF was significantly higher in the right lobe compared to the left lobe (p

BackgroundThe liver R2* value is widely used as a measure of liver iron but may be confounded by the presence of hepatic steatosis and other covariates.PurposeTo identify the most influential covariates for liver R2* values in patients with nonalcoholic fatty liver disease (NAFLD).Study typeRetrospective analysis of prospectively acquired data.PopulationBaseline data from 204 subjects enrolled in NAFLD/NASH (nonalcoholic steatohepatitis) treatment trials.Field strength1.5T and 3T; chemical-shift encoded multiecho gradient echo.AssessmentCorrelation between liver proton density fat fraction and R2*; assessment for demographic, metabolic, laboratory, MRI-derived, and histological covariates of liver R2*.Statistical testsPearson's and Spearman's correlations; univariate analysis; gradient boosting machines (GBM) multivariable machine-learning method.ResultsHepatic proton density fat fraction (PDFF) was the most strongly correlated covariate for R2* at both 1.5T (r = 0.652, P

Purpose To longitudinally monitor liver fat before and after bariatric surgery by using quantitative chemical shift-encoded (CSE) MRI and to compare with changes in body mass index (BMI), weight, and waist circumference (WC). Materials and Methods For this prospective study, which was approved by the internal review board, a total of 126 participants with obesity who were undergoing evaluation for bariatric surgery with preoperative very low calorie diet (VLCD) were recruited from June 27, 2010, through May 5, 2015. Written informed consent was obtained from all participants. Participants underwent CSE MRI measuring liver proton density fat fraction (PDFF) before VLCD (2-3 weeks before surgery), after VLCD (1-3 days before surgery), and 1, 3, and 6-10 months following surgery. Linear regression was used to estimate rates of change of PDFF (ΔPDFF) and body anthropometrics. Initial PDFF (PDFF0), initial anthropometrics, and anthropometric rates of change were evaluated as predictors of ΔPDFF. Mixed-effects regression was used to estimate time to normalization of PDFF. Results Fifty participants (mean age, 51.0 years; age range, 27-70 years), including 43 women (mean age, 50.8 years; age range, 27-70 years) and seven men (mean age, 51.7 years; age range, 36-62 years), with mean PDFF0 ± standard deviation of 18.1% ± 8.6 and mean BMI0 of 44.9 kg/m2 ± 6.5 completed the study. By 6-10 months following surgery, mean PDFF decreased to 4.9% ± 3.4 and mean BMI decreased to 34.5 kg/m2 ± 5.4. Mean estimated time to PDFF normalization was 22.5 weeks ± 11.5. PDFF0 was the only strong predictor for both ΔPDFF and time to PDFF normalization. No body anthropometric correlated with either outcome. Conclusion Average liver proton density fat fraction (PDFF) decreased to normal (< 5%) by 6-10 months following surgery, with mean time to normalization of approximately 5 months. Initial PDFF was a strong predictor of both rate of change of PDFF and time to normalization. Body anthropometrics did not predict either outcome. Online supplemental material is available for this article. © RSNA, 2018.

BackgroundE-cigarettes are purchased through multiple channels, including general retail, online, and specialty smoke and vape shops. We examine how e-cigarette users' primary purchase place relates to e-cigarette use and smoking cessation behaviors.MethodsProbability-based samples of the U.S. population who were current e-cigarette users were surveyed in 2014 (N = 879) and 2016 (N = 743), with responses combined for most analyses. E-cigarette use and smoking cessation behaviors were compared across users' primary purchase place.ResultsHigher percentages of vape shop (59.1%) and internet (42.9%) customers were current daily users of e-cigarettes compared to retail (19.7%) and smoke shop (23.2%) customers (p-values < 0.001). Higher percentages of vape shop (40.2%) and internet (35.1%) customers were also former smokers, compared to 17.7% of retail and 19.3% of smoke shop customers (p's < 0.001). Among those smoking 12 months prior to survey, smoking cessation rates were higher for vape shop (22.2%) and internet customers (22.5%) than for retail customers (10.7%, p = 0.010 and p = 0.022, respectively), even though retail customers were more likely to use FDA-approved smoking cessation aids. The percentage of customers purchasing from vape shops increased from 20.4% in 2014 to 37.6% in 2016, surpassing general retail (27.7%) as the most likely channel in 2016.ConclusionsE-cigarette customers differed in significant ways by channels of purchase, most notably in their smoking cessation behaviors. Previous population studies have relied mostly on retail channel data, which accounted for less than 30% of all products sold by 2016. Future studies of e-cigarette use should consider a broader set of channels.

PURPOSE:To determine the inter-reader agreement of magnetic resonance imaging proton density fat fraction (PDFF) and its longitudinal change in a clinical trial of adults with nonalcoholic steatohepatitis (NASH). STUDY TYPE:We performed a secondary analysis of a placebo-controlled randomized clinical trial of a bile acid sequestrant in 45 adults with NASH. A six-echo spoiled gradient-recalled-echo magnitude-based fat quantification technique was performed at 3 T. Three independent readers measured MRI-PDFF by placing one primary and two additional regions of interest (ROIs) in each segment at both time points. Cross-sectional agreement between the three readers was evaluated using intra-class correlation coefficients (ICCs) and coefficients of variation (CV). Additionally, we used Bland-Altman analyses to examine pairwise agreement between the three readers at baseline, end of treatment (EOT), and for longitudinal change. RESULTS:Using all ROIs by all readers, mean PDFF at baseline, at EOT, and mean change in PDFF was 16.1%, 16.0%, and 0.07%, respectively. The 27-ROI PDFF measurements had 0.998 ICC and 1.8% CV at baseline, 0.998 ICC and 1.8% CV at EOT, and 0.997 ICC for longitudinal change. The 9-ROI PDFF measurements had corresponding values of 0.997 and 2.6%, 0.996 and 2.4%, and 0.994. Using 27 ROIs, the magnitude of the bias between readers for whole-liver PDFF measurement ranged from 0.03% to 0.06% points at baseline, 0.01% to 0.07% points at EOT, and 0.01% to 0.02% points for longitudinal change. CONCLUSION:Inter-reader agreement for measuring whole-liver PDFF and its longitudinal change is high. 9-ROI measurements have only slightly lower agreement than 27-ROI measurements.

BackgroundImproving the signal-to-noise ratio (SNR) of chemical-shift-encoded MRI acquisition with complex reconstruction (MRI-C) may improve the accuracy and precision of noninvasive proton density fat fraction (PDFF) quantification in patients with hepatic steatosis.PurposeTo assess the accuracy of high SNR (Hi-SNR) MRI-C versus standard MRI-C acquisition to estimate hepatic PDFF in adult and pediatric nonalcoholic fatty liver disease (NAFLD) using an MR spectroscopy (MRS) sequence as the reference standard.Study typeProspective.Population/subjectsIn all, 231 adult and pediatric patients with known or suspected NAFLD.Field strength/sequencePDFF estimated at 3T by three MR techniques: standard MRI-C; a Hi-SNR MRI-C variant with increased slice thickness, decreased matrix size, and no parallel imaging; and MRS (reference standard).AssessmentMRI-PDFF was measured by image analysts using a region of interest coregistered with the MRS-PDFF voxel.Statistical testsLinear regression analyses were used to assess accuracy and precision of MRI-estimated PDFF for MRS-PDFF as a function of MRI-PDFF using the standard and Hi-SNR MRI-C for all patients and for patients with MRS-PDFF

IntroductionMost successful trials of financial incentives for smoking cessation have offered large rewards contingent on outcomes. This study examines whether more modest incentives to encourage engagement, non-contingent on outcomes, also increase cessation; whether sending medications directly to participants boosts quitting; and whether these strategies are effective in Medicaid.Study designThree-group RCT of usual care (UC); nicotine patch (NP); and NP and financial incentive (NP+FI).Setting/participantsMedicaid beneficiaries calling the California Smokers' Helpline, 2012-2013 (N=3,816). Data were analyzed in 2017.InterventionAll participants enrolled in evidence-based, multisession telephone counseling. All received proof of enrollment with which they could obtain free quitting aids at their pharmacy. NP and NP+FI also received nicotine patches sent to their homes. NP+FI received up to $60 for completing counseling calls.Main outcome measuresQuit attempt rate, 7-day and 30-day abstinence at 2 and 7 months, and 6-month prolonged abstinence (primary outcome).ResultsIn both complete-case and intention-to-treat analyses, outcomes trended upward from UC to NP to NP+FI. Differences between NP and UC were generally nonsignificant. By contrast, the NP+FI group significantly outperformed the other groups on all measures. In intention-to-treat analysis, compared with UC, NP+FI was more likely to make a quit attempt (68.4% vs 54.3%, p

Residual pulmonary vascular obstruction (RPVO) and chronic thromboembolic pulmonary hypertension (CTEPH) are both long-term complications of acute pulmonary embolism, but it is unknown whether RPVO can be predicted by variants of fibrinogen associated with CTEPH.We used the Akaike information criterion to select the best predictive models for RPVO in two prospectively followed cohorts of acute pulmonary embolism patients, using as candidate variables the extent of the initial obstruction, clinical characteristics and fibrinogen-related data. We measured the selected models' goodness of fit by analysis of deviance and compared models using the Chi-squared test.RPVO occurred in 29 (28.4%) out of 102 subjects in the first cohort and 46 (25.3%) out of 182 subjects in the second. The best-fit predictive model derived in the first cohort (p=0.0002) and validated in the second cohort (p=0.0005) implicated fibrinogen Bβ-chain monosialylation in the development of RPVO. When the derivation procedure excluded clinical characteristics, fibrinogen Bβ-chain monosialylation remained a predictor of RPVO in the best-fit predictive model (p=0.00003). Excluding fibrinogen characteristics worsened the predictive model (p=0.03).Fibrinogen Bβ-chain monosialylation, a common structural attribute of fibrin, helped predict RPVO after acute pulmonary embolism. Fibrin structure may contribute to the risk of developing RPVO.

PURPOSE:Gadoxetate-disodium (Gd-EOB-DTPA)-enhanced 3D T1- weighted (T1w) MR cholangiography (MRC) is an efficient method to evaluate biliary anatomy due to T1 shortening of excreted contrast in the bile. A method that exploits both T1 shortening and T2* effects may produce even greater bile duct conspicuity. The aim of our study is to determine feasibility and compare the diagnostic performance of two-dimensional (2D) T1w multi-echo (ME) spoiled gradient-recalled-echo (SPGR) derived R2* maps against T1w MRC for bile duct visualization in living liver donor candidates. MATERIALS AND METHODS:Ten potential living liver donor candidates underwent pretransplant 3T MRI and were included in our study. Following injection of Gd-EOBDTPA and a 20-min delay, 3D T1w MRC and 2D T1w ME SPGR images were acquired. 2D R2* maps were generated inline by the scanner assuming exponential decay. The 3D T1w MRC and 2D R2* maps were retrospectively and independently reviewed in two separate sessions by three radiologists. Visualization of eight bile duct segments was scored using a 4-point ordinal scale. The scores were compared using mixed effects regression model. RESULTS:Imaging was tolerated by all donors and R2* maps were successfully generated in all cases. Visualization scores of 2D R2* maps were significantly higher than 3D T1w MRC for right anterior (p = 0.003) and posterior (p = 0.0001), segment 2 (p

PURPOSE:To determine the relationship between hepatic proton density fat fraction (PDFF) and R2* in vivo. MATERIALS AND METHODS:In this Health Insurance Portability and Accountability Act (HIPAA)-compliant, Institutional Review Board (IRB)-approved, cross-sectional study, we conducted a secondary analysis of 3T magnetic resonance imaging (MRI) exams performed as part of prospective research studies in children in whom conditions associated with iron overload were excluded clinically. Each exam included low-flip-angle, multiecho magnitude (-M) and complex (-C) based chemical-shift-encoded MRI techniques with spectral modeling of fat to generate hepatic PDFF and R2* parametric maps. For each technique and each patient, regions of interest were placed on the maps in each of the nine Couinaud segments, and composite whole-liver PDFF and R2* values were calculated. Pearson's correlation coefficients between PDFF and R2* were computed for each MRI technique. Correlations were compared using Steiger's test. RESULTS:In all, 184 children (123 boys, 61 girls) were included in this analysis. PDFF estimated by MRI-M and MRI-C ranged from 1.1-35.4% (9.44 ± 8.76) and 2.1-38.1% (10.1 ± 8.7), respectively. R2* estimated by MRI-M and MRI-C ranged from 32.6-78.7 s-1 (48.4 ± 9.8) and 27.2-71.5 s-1 (42.2 ± 8.6), respectively. There were strong and significant correlations between hepatic PDFF and R2* values estimated by MRI-M (r = 0.874; P

Purpose To determine in a large multicenter multireader setting the interreader reliability of Liver Imaging Reporting and Data System (LI-RADS) version 2014 categories, the major imaging features seen with computed tomography (CT) and magnetic resonance (MR) imaging, and the potential effect of reader demographics on agreement with a preselected nonconsecutive image set. Materials and Methods Institutional review board approval was obtained, and patient consent was waived for this retrospective study. Ten image sets, comprising 38-40 unique studies (equal number of CT and MR imaging studies, uniformly distributed LI-RADS categories), were randomly allocated to readers. Images were acquired in unenhanced and standard contrast material-enhanced phases, with observation diameter and growth data provided. Readers completed a demographic survey, assigned LI-RADS version 2014 categories, and assessed major features. Intraclass correlation coefficient (ICC) assessed with mixed-model regression analyses was the metric for interreader reliability of assigning categories and major features. Results A total of 113 readers evaluated 380 image sets. ICC of final LI-RADS category assignment was 0.67 (95% confidence interval [CI]: 0.61, 0.71) for CT and 0.73 (95% CI: 0.68, 0.77) for MR imaging. ICC was 0.87 (95% CI: 0.84, 0.90) for arterial phase hyperenhancement, 0.85 (95% CI: 0.81, 0.88) for washout appearance, and 0.84 (95% CI: 0.80, 0.87) for capsule appearance. ICC was not significantly affected by liver expertise, LI-RADS familiarity, or years of postresidency practice (ICC range, 0.69-0.70; ICC difference, 0.003-0.01 [95% CI: -0.003 to -0.01, 0.004-0.02]. ICC was borderline higher for private practice readers than for academic readers (ICC difference, 0.009; 95% CI: 0.000, 0.021). Conclusion ICC is good for final LI-RADS categorization and high for major feature characterization, with minimal reader demographic effect. Of note, our results using selected image sets from nonconsecutive examinations are not necessarily comparable with those of prior studies that used consecutive examination series. © RSNA, 2017.

To assess and compare the diagnostic performance of magnitude-reconstruction chemical-shift-encoded magnetic resonance imaging (MRI-M) and complex-reconstruction chemical-shift-encoded magnetic resonance imaging (MRI-C) for diagnosis of hepatic steatosis in subjects with severe obesity without known non-alcoholic fatty liver disease (NAFLD), using contemporaneous histology as reference. This is an IRB-approved, HIPAA-compliant, two-center, cross-sectional study of a larger prospective trail that recruited patients without known NAFLD consecutively between October 2010 and March 2015 to undergo research MRI exams 1-2 days prior to clinical-care weight-loss surgery. Proton denisty fat fraction (PDFF) was estimated using MRI-M and MRI-C. Liver biopsies were obtained intraoperatively. Using histologically-determined presence of steatosis as the reference standard, receiver operating characteristics (ROC) analyses were used to identify MRI-M- and MRI-C-derived PDFF thresholds for diagnosing steatosis. Bootstrapped-based tests were used to compare their diagnostic performace. A total of 81 patients (67 female, 14 maile, average age 48.2) were recruited for this study. MRI-M and MRI-C had areas under the ROC curve of 0.951 and 0.947, respectively, for diagnosing hepatic steatosis. for MRI-M, the Youden-index-based PDFF threshold of 6.5% provided 0.87 sensitivity (95% confidence internal: 0/75, 0.95), 0.96 specificity (0.81, 0.99), and 0.90 total accuracy (0.82, 0.96). For MRI-C, a PDFF threshold of 6.8%, provided a 0.90 sensitivity (0.77, 0.96), 0.96 specificity (0.81, 0.99), and 0.91 total accuracy (0.83, 0.97). Differences in performance parameters between MRI-M and MRI-C were not statistically significant. Conclusion: MRI-M- and MRI-C-derived PDFF is accurate for non-invasive diagnosis of hepatic steatosis in subjects with severe obesity.

Background and aimsThe California Tobacco-Use Prevention Education (TUPE) program promotes the use of evidence-based tobacco-specific prevention and cessation programs for adolescents within the school setting. Through a competitive grant process, schools are funded to provide programs for grades 6-12. This research evaluates the association between TUPE funding and tobacco prevention activities and tobacco use prevalence.MethodsThis study utilized two data sources: (1) 2016 California Educator Tobacco Survey (CETS), and (2) 2015-2016 California Student Tobacco Survey (CSTS). The CETS collected data from educators about school prevention efforts, priority of tobacco prevention, and confidence in addressing tobacco issues with students. A total of 3,564 educators from 590 schools participated in CETS. The CSTS collected data from 8th, 10th, and 12th graders in California on their exposure to, attitudes about, and utilization of tobacco products. A total of 47,981 students from 117 schools participated in CSTS.ResultsThis study found that TUPE-funded schools were more likely to provide tobacco-specific health education programs, to place a priority on tobacco-prevention efforts, and to prepare educators to address tobacco use than non-TUPE schools. Educators at both types of schools felt better prepared to talk with students about traditional tobacco products than about emerging products such as e-cigarettes. Overall, students at TUPE-funded schools were more likely to report receiving anti-tobacco messages from school-based programs than those at non-TUPE schools. The former were also less likely to use tobacco products, even when the analysis controlled for demographics and school-level characteristics (OR = 0.82 [95% CI = 0.70-0.96]).ConclusionsTUPE funding was associated with an increase in schools' tobacco-specific prevention activities and these enhanced activities were associated with lower tobacco use among students. This study also found that education and prevention efforts regarding emerging tobacco products need to be strengthened across all schools.

Magnetic resonance elastography (MRE) is a promising technique for noninvasive assessment of fibrosis, a major determinant of outcome in nonalcoholic fatty liver disease (NAFLD). However, data in children are limited. The purpose of this study was to determine the accuracy of MRE for the detection of fibrosis and advanced fibrosis in children with NAFLD and to assess agreement between manual and novel automated reading methods. We performed a prospective, multicenter study of two-dimensional (2D) MRE in children with NAFLD. MR elastograms were analyzed manually at two reading centers, and using a new automated technique. Analysis using each approach was done independently. Correlations were determined between MRE analysis methods and fibrosis stage. Thresholds for classifying the presence of fibrosis and of advanced fibrosis were computed and cross-validated. In 90 children with a mean age of 13.1 ± 2.4 years, median hepatic stiffness was 2.35 kPa. Stiffness values derived by each reading center were strongly correlated with each other (r = 0.83). All three analyses were significantly correlated with fibrosis stage (center 1, ρ = 0.53; center 2, ρ = 0.55; and automated analysis, ρ = 0.52; P

ObjectiveIndividuals with anorexia nervosa (AN) have anxious and inhibited temperaments with high concern for consequences. Studies using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI) suggest involvement of the middle and dorsal caudate (DC) in individuals recovered (REC) from AN. For example, dopamine (DA) D2/D3 receptor binding in the middle caudate and DC was associated with anxiety and harm avoidance, and blood-oxygen-level-dependent (BOLD) response in the DC was positively related to trait anxiety. It has not been shown yet whether BOLD response in individuals REC from AN was related to DA function.MethodsPost-hoc correlation analyses between the PET and fMRI studies by correlating D2/D3 binding in striatal regions and BOLD signal in the anteroventral striatum (AVS) and DC for wins and losses respectively in 12 individuals REC from AN.ResultsIndividuals REC from AN with the greatest BOLD response in the DC in a monetary choice task had higher middle caudate D2/D3 binding, and greater anxiety and/or harm avoidance.DiscussionThough preliminary, these findings suggest that increased dorsal striatal D2/D3 binding is associated with enhanced cognitive response to feedback, potentially related to anxious anticipation of consequences. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:593-596).

ObjectiveThe purpose of this study is to explore the diagnostic performance of two investigational quantitative ultrasound (QUS) parameters, attenuation coefficient and backscatter coefficient, in comparison with conventional ultrasound (CUS) and MRI-estimated proton density fat fraction (PDFF) for predicting histology-confirmed steatosis grade in adults with nonalcoholic fatty liver disease (NAFLD).Subjects and methodsIn this prospectively designed pilot study, 61 adults with histology-confirmed NAFLD were enrolled from September 2012 to February 2014. Subjects underwent QUS, CUS, and MRI examinations within 100 days of clinical-care liver biopsy. QUS parameters (attenuation coefficient and backscatter coefficient) were estimated using a reference phantom technique by two analysts independently. Three-point ordinal CUS scores intended to predict steatosis grade (1, 2, or 3) were generated independently by two radiologists on the basis of QUS features. PDFF was estimated using an advanced chemical shift-based MRI technique. Using histologic examination as the reference standard, ROC analysis was performed. Optimal attenuation coefficient, backscatter coefficient, and PDFF cutoff thresholds were identified, and the accuracy of attenuation coefficient, backscatter coefficient, PDFF, and CUS to predict steatosis grade was determined. Interobserver agreement for attenuation coefficient, backscatter coefficient, and CUS was analyzed.ResultsCUS had 51.7% grading accuracy. The raw and cross-validated steatosis grading accuracies were 61.7% and 55.0%, respectively, for attenuation coefficient, 68.3% and 68.3% for backscatter coefficient, and 76.7% and 71.3% for MRI-estimated PDFF. Interobserver agreements were 53.3% for CUS (κ = 0.61), 90.0% for attenuation coefficient (κ = 0.87), and 71.7% for backscatter coefficient (κ = 0.82) (p < 0.0001 for all).ConclusionPreliminary observations suggest that QUS parameters may be more accurate and provide higher interobserver agreement than CUS for predicting hepatic steatosis grade in patients with NAFLD.

Purpose To determine the repeatability and accuracy of a commercially available magnetic resonance (MR) imaging-based, semiautomated method to quantify abdominal adipose tissue and thigh muscle volume and hepatic proton density fat fraction (PDFF). Materials and Methods This prospective study was institutional review board- approved and HIPAA compliant. All subjects provided written informed consent. Inclusion criteria were age of 18 years or older and willingness to participate. The exclusion criterion was contraindication to MR imaging. Three-dimensional T1-weighted dual-echo body-coil images were acquired three times. Source images were reconstructed to generate water and calibrated fat images. Abdominal adipose tissue and thigh muscle were segmented, and their volumes were estimated by using a semiautomated method and, as a reference standard, a manual method. Hepatic PDFF was estimated by using a confounder-corrected chemical shift-encoded MR imaging method with hybrid complex-magnitude reconstruction and, as a reference standard, MR spectroscopy. Tissue volume and hepatic PDFF intra- and interexamination repeatability were assessed by using intraclass correlation and coefficient of variation analysis. Tissue volume and hepatic PDFF accuracy were assessed by means of linear regression with the respective reference standards. Results Adipose and thigh muscle tissue volumes of 20 subjects (18 women; age range, 25-76 years; body mass index range, 19.3-43.9 kg/m2) were estimated by using the semiautomated method. Intra- and interexamination intraclass correlation coefficients were 0.996-0.998 and coefficients of variation were 1.5%-3.6%. For hepatic MR imaging PDFF, intra- and interexamination intraclass correlation coefficients were greater than or equal to 0.994 and coefficients of variation were less than or equal to 7.3%. In the regression analyses of manual versus semiautomated volume and spectroscopy versus MR imaging, PDFF slopes and intercepts were close to the identity line, and correlations of determination at multivariate analysis (R2) ranged from 0.744 to 0.994. Conclusion This MR imaging-based, semiautomated method provides high repeatability and accuracy for estimating abdominal adipose tissue and thigh muscle volumes and hepatic PDFF. © RSNA, 2017.

PurposeTo investigate the regional variability of adipose tissue triglyceride composition in vivo using 1 H MRS, examining potential confounders and corrections for artifacts, to allow for adipose tissue spectrum estimation.Materials and methods1 H magnetic resonance (MR) stimulated echo acquisition mode (STEAM) spectra were acquired in vivo at 3T from 340 adult patients (mean age 48.9 years, range 21-79 years; 172 males, 168 females; mean body mass index [BMI] 34.0, range 22-49 kg/m2 ) with known or suspected nonalcoholic fatty liver disease (NAFLD) in deep (dSCAT), surface (sSCAT) subcutaneous adipose tissue, and visceral adipose tissue (VAT). Triglyceride composition was characterized by the number of double bonds (ndb) and number of methylene-interrupted double bonds (nmidb). A subset of patients (dSCAT n = 80, sSCAT n = 55, VAT n = 194) had the acquisition repeated three times to examine the repeatability of ndb and nmidb estimation.ResultsMean ndb and nmidb showed significant (P < 0.0001) differences between depots except for dSCAT and sSCAT nmidb (dSCAT ndb 2.797, nmidb 0.745; sSCAT ndb 2.826, nmidb 0.737; VAT ndb 2.723, nmidb 0.687). All ndb and nmidb estimates were highly repeatable (VAT ndb ICC = 0.888, nmidb ICC = 0.853; sSCAT: ndb ICC = 0.974, nmidb ICC = 0.964; dSCAT: ndb ICC = 0.959, nmidb ICC = 0.948).ConclusionAdipose tissue composition can be estimated repeatably using 1 H MRS and different fat depots have different triglyceride compositions.Level of evidence2 J. MAGN. RESON. IMAGING 2017;45:1455-1463.

PurposeTo investigate the regional variability of adipose tissue triglyceride composition in vivo using 1 H MRS, examining potential confounders and corrections for artifacts, to allow for adipose tissue spectrum estimation.Materials and methods1 H magnetic resonance (MR) stimulated echo acquisition mode (STEAM) spectra were acquired in vivo at 3T from 340 adult patients (mean age 48.9 years, range 21-79 years; 172 males, 168 females; mean body mass index [BMI] 34.0, range 22-49 kg/m2 ) with known or suspected nonalcoholic fatty liver disease (NAFLD) in deep (dSCAT), surface (sSCAT) subcutaneous adipose tissue, and visceral adipose tissue (VAT). Triglyceride composition was characterized by the number of double bonds (ndb) and number of methylene-interrupted double bonds (nmidb). A subset of patients (dSCAT n = 80, sSCAT n = 55, VAT n = 194) had the acquisition repeated three times to examine the repeatability of ndb and nmidb estimation.ResultsMean ndb and nmidb showed significant (P < 0.0001) differences between depots except for dSCAT and sSCAT nmidb (dSCAT ndb 2.797, nmidb 0.745; sSCAT ndb 2.826, nmidb 0.737; VAT ndb 2.723, nmidb 0.687). All ndb and nmidb estimates were highly repeatable (VAT ndb ICC = 0.888, nmidb ICC = 0.853; sSCAT: ndb ICC = 0.974, nmidb ICC = 0.964; dSCAT: ndb ICC = 0.959, nmidb ICC = 0.948).ConclusionAdipose tissue composition can be estimated repeatably using 1 H MRS and different fat depots have different triglyceride compositions.Level of evidence2 J. MAGN. RESON. IMAGING 2017;45:1455-1463.

PurposeThe aim of the study was to determine in patients undergoing gadoxetate disodium (Gx)-enhanced MR exams whether proton density fat fraction (PDFF) estimation accuracy of magnitude-based multi-gradient-echo MRI (MRI-M) could be improved by using high flip angle (FA) on post-contrast images.Materials and methodsThirty-one adults with known or suspected hepatic steatosis undergoing 3T clinical Gx-enhanced liver MRI were enrolled prospectively. MR spectroscopy (MRS), the reference standard, was performed before Gx to measure MRS-PDFF. Low (10°)- and high (50°)-flip angle (FA) MRI-M sequences were acquired before and during the hepatobiliary phase after Gx administration; MRI-PDFF was estimated in the MRS-PDFF voxel location. Linear regression parameters (slope, intercept, average bias, R 2) were calculated for MRS-PDFF as a function of MRI-PDFF for each MRI-M sequence (pre-Gx low-FA, pre-Gx high-FA, post-Gx low-FA, post-Gx high-FA) for all patients and for patients with MRS-PDFF

PurposeTo compare agreement between region-of-interest (ROI)- and parametric map-based methods of hepatic proton density fat fraction (PDFF) estimation in adults with known or suspected hepatic steatosis secondary to chronic liver disease over a range of imaging and analysis conditions.Materials and methodsIn this IRB approved HIPAA compliant prospective single-site study, 31 adults with chronic liver disease undergoing clinical gadoxetic acid-enhanced liver magnetic resonance imaging at 3 T were recruited. Multi-echo gradient-echo imaging at flip angles of 10° and 50° was performed before and after administration of gadoxetic acid. Six echoes were acquired at successive nominally out-of-phase and in-phase echo times. PDFF was estimated with a nonlinear fitting algorithm using the first two, three, four, five, and (all) six echoes. Hence, 20 different imaging and analysis conditions were used (pre/post contrast x low/high flip angle x 2/3/4/5/6 echoes). For each condition, PDFF estimation was done in corresponding liver locations using two methods: a region-of-interest (ROI)-based method in which mean signal intensity values within ROIs were run through the fitting algorithm, and a parametric map-based method in which individual signal intensities were run through the fitting algorithm pixel by pixel. Agreement between ROI- and map-based PDFF estimation was assessed by Bland-Altman and intraclass correlation (ICC) analysis.ResultsDepending on the condition and method, PDFF ranged from -2.52% to 45.57%. Over all conditions, mean differences between ROI- and map-based PDFF estimates ranged from 0.04% to 0.24%, with all ICCs ≥0.999.ConclusionAgreement between ROI- and parametric map-based PDFF estimation is excellent over a wide range of imaging and analysis conditions.

BackgroundIn recent decades the overall smoking prevalence in the US has fallen steadily. This study examines whether the same trend is seen in the Medicaid population.Methods and findingsNational Health Interview Survey (NHIS) data from 17 consecutive annual surveys from 1997 to 2013 (combined N = 514,043) were used to compare smoking trends for 4 insurance groups: Medicaid, the Uninsured, Private Insurance, and Other Coverage. Rates of chronic disease and psychological distress were also compared.ResultsAdjusted smoking prevalence showed no detectable decline in the Medicaid population (from 33.8% in 1997 to 31.8% in 2013, trend test P = 0.13), while prevalence in the other insurance groups showed significant declines (38.6%-34.7% for the Uninsured, 21.3%-15.8% for Private Insurance, and 22.6%-16.8% for Other Coverage; all P's

The space of metastable materials offers promising new design opportunities for next-generation technological materials, such as complex oxides, semiconductors, pharmaceuticals, steels, and beyond. Although metastable phases are ubiquitous in both nature and technology, only a heuristic understanding of their underlying thermodynamics exists. We report a large-scale data-mining study of the Materials Project, a high-throughput database of density functional theory-calculated energetics of Inorganic Crystal Structure Database structures, to explicitly quantify the thermodynamic scale of metastability for 29,902 observed inorganic crystalline phases. We reveal the influence of chemistry and composition on the accessible thermodynamic range of crystalline metastability for polymorphic and phase-separating compounds, yielding new physical insights that can guide the design of novel metastable materials. We further assert that not all low-energy metastable compounds can necessarily be synthesized, and propose a principle of 'remnant metastability'-that observable metastable crystalline phases are generally remnants of thermodynamic conditions where they were once the lowest free-energy phase.

Materials scientists increasingly employ machine or statistical learning (SL) techniques to accelerate materials discovery and design. Such pursuits benefit from pooling training data across, and thus being able to generalize predictions over, k-nary compounds of diverse chemistries and structures. This work presents a SL framework that addresses challenges in materials science applications, where datasets are diverse but of modest size, and extreme values are often of interest. Our advances include the application of power or Hölder means to construct descriptors that generalize over chemistry and crystal structure, and the incorporation of multivariate local regression within a gradient boosting framework. The approach is demonstrated by developing SL models to predict bulk and shear moduli (K and G, respectively) for polycrystalline inorganic compounds, using 1,940 compounds from a growing database of calculated elastic moduli for metals, semiconductors and insulators. The usefulness of the models is illustrated by screening for superhard materials.

Purpose To determine the proportion of untreated Liver Imaging Reporting and Data System (LI-RADS) version 2014 category 2, 3, and 4 observations that progress, remain stable, or decrease in category and to compare the cumulative incidence of progression in category. Materials and Methods In this retrospective, longitudinal, single-center, HIPAA-compliant, institutional review board-approved study, 157 patients (86 men and 71 women; mean age ± standard deviation, 59.0 years ± 9.7) underwent two or more multiphasic computed tomographic (CT) or magnetic resonance (MR) imaging examinations for hepatocellular carcinoma surveillance, with the first examination in 2011 or 2012. One radiologist reviewed baseline and follow-up CT and MR images (mean follow-up, 614 days). LI-RADS categories issued in the clinical reports by using version 1.0 or version 2013 were converted to version 2014 retrospectively; category modifications were verified with another radiologist. For index category LR-2, LR-3, and LR-4 observations, the proportions that progressed, remained stable, or decreased in category were calculated. Cumulative incidence curves for progression were compared according to baseline LI-RADS category (by using log-rank tests). Results All 63 index LR-2 observations remained stable or decreased in category. Among 166 index LR-3 observations, seven (4%) progressed to LR-5, and eight (5%) progressed to LR-4. Among 52 index LR-4 observations, 20 (38%) progressed to a malignant category. The cumulative incidence of progression to a malignant category was higher for index LR-4 observations than for index LR-3 or LR-2 observations (each P < .001) but was not different between LR-3 and LR-2 observations (P = .155). The cumulative incidence of progression to at least category LR-4 was trend-level higher for index LR-3 observations than for LR-2 observations (P = .0502). Conclusion Observations classified according to LI-RADS version 2014 categories are associated with different imaging outcomes. (©) RSNA, 2016 Online supplemental material is available for this article.

IntroductionMost smokers abstain from smoking during hospitalization but relapse upon discharge. This study tests the effectiveness of two proven treatments (i.e., nicotine patches and telephone counseling) in helping these patients stay quit after discharge from the hospital, and assesses a model of hospital-quitline partnership.Study designThis study had a 2×2 factorial design in which participants were stratified by recruitment site and smoking rate and randomly assigned to usual care, nicotine patches only, counseling only, or patches plus counseling. They were evaluated at 2 and 6 months post-randomization.Setting/participantsA total of 1,270 hospitalized adult smokers were recruited from August 2011 to November 2013 from five hospitals within three healthcare systems.InterventionParticipants in the patch condition were provided 8 weeks of nicotine patches at discharge (or were mailed them post-discharge). Quitline staff started proactively calling participants in the counseling condition 3 days post-discharge to provide standard quitline counseling.Main outcome measuresThe primary outcome measure was self-reported 30-day abstinence at 6 months using an intention-to-treat analysis. Data were analyzed from September 2015 to May 2016.ResultsThe 30-day abstinence rate at 6 months was 22.8% for the nicotine patch condition and 18.3% for the no-patch condition (p=0.051). Nearly all participants (99%) in the patch condition were provided nicotine patches, although 36% were sent post-discharge. The abstinence rates were 20.0% and 21.1% for counseling and no counseling conditions, respectively (p=0.651). Fewer than half of the participants in the counseling condition (47%) received counseling (mean follow-up sessions, 3.6).ConclusionsProvision of nicotine patches proved feasible, although their effectiveness in helping discharged patients stay quit was not significant. Telephone counseling was not effective, in large part because of low rates of engagement. Future interventions will need to be more immediate to be effective.Trial registrationThis study is registered at www.clinicaltrials.gov NCT01289275.

Prospective memory (PM) is associated with antiretroviral (ARV) adherence in HIV, but little is known about how pill burden and age might affect this association. One hundred seventeen older (≥50 years) and 82 younger (

BackgroundThe Veterans Aging Cohort Study (VACS) Index, a composite marker of disease severity among human immunodeficiency virus (HIV)-infected persons, has been associated with concurrent risk for neurocognitive impairment (NCI). The present study examined whether the VACS Index predicts longitudinal neurocognitive change.MethodsParticipants included 655 HIV-infected persons followed for up to 6 years in cohort studies at the University of California, San Diego, HIV Neurobehavioral Research Program (mean age at baseline, 42.5 years; 83% male; 60% white; AIDS in 67%; median current CD4(+) T-cell count, 346/μL; 61% receiving antiretroviral therapy). The VACS Index was calculated through standard methods. Participants completed a comprehensive neurocognitive battery. Neurocognitive status was plotted over time using demographically and practice-adjusted global and domain T scores. NCI was defined by global deficit scores derived from T scores.ResultsBaseline VACS Index scores were not predictive of changes in global T scores during the follow-up period (P = .14). However, in time-dependent analyses adjusting for covariates, higher VACS Index scores were significantly associated with worse global and domain neurocognitive performance (Ps < .01), as well as increased risk for developing NCI in a subgroup of persons who were neurocognitively normal at baseline (hazard ratio [HR], 1.17; P < .001). We categorized VACS Index scores by quartiles and found that the upper-quartile group was significantly more likely to develop NCI than the lower quartile (HR, 2.16; P < .01) and middle groups (HR, 1.76; P < .01).ConclusionsChanges in VACS Index scores correspond to changes in neurocognitive function. HIV-infected persons with high VACS Index scores are at increased risk for decline and incident NCI. The VACS Index shows promise as a tool for identifying HIV-infected persons at risk for NCI.

BACKGROUND: Varenicline is known to have greater efficacy than other pharmacotherapy for treating nicotine dependence and has gained popularity since its introduction in 2006. This study examines if adding varenicline to existing pharmacotherapies increased the population cessation rate. METHODS: Data are from two cross-sectional US Current Population Surveys-Tobacco Use Supplements (2003 and 2010-2011). Smokers and recent quitters 18 or older (N=34 869 in 2003, N=27 751 in 2010-2011) were asked if they had used varenicline, bupropion or nicotine replacement therapies (NRT) in their most recent quit attempt. The annual cessation rate, as well as the per cent of smokers who had quit for ≥3 months, was compared between surveys. RESULTS: Varenicline use increased from 0% in 2003 to 10.9% in 2010-2011, while use of bupropion decreased from 9.1% to 3.5%, and NRT from 24.5% to 22.4%. Use of any pharmacotherapy increased by 2.4 percentage points. Varenicline users stayed on cessation aids longer and were less likely to relapse than users of other pharmacotherapies in the first 3 months of a quit attempt, after which the difference was no longer significant. The change in annual cessation rate was negligible, from 4.5% in 2003 to 4.7% in 2010-2011 (p=0.36). CONCLUSIONS: Addition of varenicline to the list of approved cessation aids has mainly led to displacement of other therapies. As a result, there was no meaningful change in population cessation rate despite a remarkable increase in varenicline use. The population impact of a new therapy is a function of more than efficacy or reach of the therapy.

Gabapentin is prescribed for analgesia in chronic low back pain, yet there are no controlled trials supporting this practice. This randomized, 2-arm, 12-week, parallel group study compared gabapentin (forced titration up to 3600 mg daily) with inert placebo. The primary efficacy measure was change in pain intensity from baseline to the last week on treatment measured by the Descriptor Differential Scale; the secondary outcome was disability (Oswestry Disability Index). The intention-to-treat analysis comprised 108 randomized patients with chronic back pain (daily pain for ≥6 months) whose pain did (43%) or did not radiate into the lower extremity. Random effects regression models which did not impute missing scores were used to analyze outcome data. Pain intensity decreased significantly over time (P < 0.0001) with subjects on gabapentin or placebo, reporting reductions of about 30% from baseline, but did not differ significantly between groups (P = 0.423). The same results pertained for disability scores. In responder analyses of those who completed 12 weeks (N = 72), the proportion reporting at least 30% or 50% reduction in pain intensity, or at least "Minimal Improvement" on the Physician Clinical Global Impression of Change did not differ significantly between groups. There were no significant differences in analgesia between participants with radiating (n = 46) and nonradiating (n = 62) pain either within or between treatment arms. There was no significant correlation between gabapentin plasma concentration and pain intensity. Gabapentin appears to be ineffective for analgesia in chronic low back pain with or without a radiating component.

ObjectivesRecent studies show two-dimensional (2D)-magnetic resonance elastography (MRE) is accurate in diagnosing advanced fibrosis (stages 3 and 4) in nonalcoholic fatty liver disease (NAFLD) patients. Three-dimensional (3D)-MRE is a more advanced version of the technology that can image shear-wave fields in 3D of the entire liver. The aim of this study was to prospectively compare the diagnostic accuracy of 3D-MRE and 2D-MRE for diagnosing advanced fibrosis in patients with biopsy-proven NAFLD.MethodsThis cross-sectional analysis of a prospective study included 100 consecutive patients (56% women) with biopsy-proven NAFLD who also underwent MRE. Area under the receiver operating characteristic (AUROC) analysis was performed to assess the accuracy of 2D- and 3D-MRE in diagnosing advanced fibrosis.ResultsThe mean (±s.d.) of age and body mass index were 50.2 (±13.6) years and 32.1 (±5.0) kg/m(2), respectively. The AUROC for diagnosing advanced fibrosis was 0.981 for 3D-MRE at 40 Hz, 0.927 for 3D-MRE at 60 Hz (standard shear-wave frequency), and 0.921 for 2D-MRE at 60 Hz (standard shear-wave frequency). At a threshold of 2.43 kPa, 3D-MRE at 40 Hz had sensitivity 1.0, specificity 0.94, positive predictive value 0.72, and negative predictive value 1.0 for diagnosing advanced fibrosis. 3D-MRE at 40 Hz had significantly higher AUROC (P

ObjectiveTo estimate points along the spectrum of β-amyloid pathology at which rates of change of several measures of neuronal injury and cognitive decline begin to accelerate.MethodsIn 460 patients with mild cognitive impairment (MCI), we estimated the points at which rates of florbetapir PET, fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to baseline CSF Aβ42. Points of initial acceleration in rates of decline were estimated using mixed-effects regression.ResultsRates of neuronal injury and cognitive and even functional decline accelerate substantially before the conventional threshold for amyloid positivity, with rates of florbetapir PET and FDG PET accelerating early. Temporal lobe atrophy rates also accelerate prior to the threshold, but not before the acceleration of cognitive and functional decline.ConclusionsA considerable proportion of patients with MCI would not meet inclusion criteria for a trial using the current threshold for amyloid positivity, even though on average, they are experiencing cognitive/functional decline associated with prethreshold levels of CSF Aβ42. Future trials in early Alzheimer disease might consider revising the criteria regarding β-amyloid thresholds to include the range of amyloid associated with the first signs of accelerating rates of decline.