Quantitative MRCP and metrics of bile duct disease over time in patients with primary sclerosing cholangitis:A prospective study

Background: Imaging markers of biliary disease in primary sclerosing cholangitis (PSC) have potential for use in clinical and trial disease monitoring. Herein, we evaluate how quantitative magnetic resonance cholangiopancreatography (MRCP) metrics change over time, as per the natural history of disease. Methods: Individuals with PSC were prospectively scanned using non‐contrast MRCP. Quantitative metrics were calculated using MRCP+ post‐processing software to assess duct diameters and dilated and strictured regions. Additionally, a hepatopancreatobiliary radiologist (blinded to clinical details, biochemistry and quantitative biliary metrics) reported each scan, including ductal disease assessment according to the modified Amsterdam Cholangiographic Score (MAS). Results: At baseline, 14 quantitative MRCP+ metrics were found to be significantly different in patients with PSC (N = 55) compared to those with primary biliary cholangitis (N = 55), autoimmune hepatitis (N = 57) and healthy controls (N = 18). In PSC specifically, baseline metrics quantifying the number of strictures and the number and length of bile ducts correlated with the MAS, transient elastography and serum ALP values (p < 0.01 for all correlations). Over a median 371‐day follow‐up (range: 364–462), 29 patients with PSC underwent repeat MRCP, of whom 15 exhibited quantitative changes in MRCP+ metrics. Compared to baseline, quantitative MRCP+ identified an increasing number of strictures over time (p < 0.05). Comparatively, no significant differences in biochemistry, elastography or the MAS were observed between timepoints. Quantitative MRCP+ metrics remained stable in non‐PSC liver disease. Conclusion: Quantitative MRCP+ identifies changes in ductal disease over time in PSC, despite stability in biochemistry, liver stiffness and radiologist‐derived cholangiographic assessment (trial registration: ISRCTN39463479)

Efeitos da densidade de população de plantas na cultura de couve-flor (Brassica oleracea L. var. botrytis)

An experiment was carried out to study the effects of the following population densities cauliflowers (plants per ha): 20,833 (0.60 m x 0.80 m), 25,641 (0.60 m x 0.65 m), ....37.037 (0.60 m x 0.45 m) , 55.555 (.0.60 m x 0.30 m), and 111,111 (0,60 m x 0,15 m) ; variety Snow ball. It was concluded that the effects of plant population density are greater on curd quality (weight and size) than on production per ha. The best plant population density to produce cauliflowers curd for Brazil market is from 20,000 to 25,000 plants/ha while for mini-curd is above 55,000 plants/ha.O experimento foi instalado na área experimental do Setor de Horticultura da ESALQ. (Piracicaba, SP), em um Latossol Roxo série "Luiz de Queiroz", em março de 1977, considerando as seguintes densidades de população: 20.833 plantas/ha (0,60 m x 0,80m), .. 25.641 plantas/ha (0,60 m x 0,65 m), 37.037 plantas/ha (..0.,60 m x 0,45 ml, 55.550 plantas/ha (,06Q m x 0,30 ,) e 111.111 plantas/ ha (0,60 m x 0,15 m). A partir dos resultados obtidos e para as condições do experimento concluiu-se que a densidade de população sobre a produção de couve-flor afeta mais a qualidade da cabeça (peso e tamanho), enquanto que o rendimento por área é pouco afetado. Para as condições do nosso mercado, a densidade ótima deve estar entre 20.000 a 25.000 plantas por ha e para a produção de mini-couve-flor mais de 55.000 plantas por ha, paraocultivar Bola de Neve

Plasmonically Enhanced Reflectance of Heat Radiation from Low-Bandgap Semiconductor Microinclusions

Increased reflectance from the inclusion of highly scattering particles at low volume fractions in an insulating dielectric offers a promising way to reduce radiative thermal losses at high temperatures. Here, we investigate plasmonic resonance driven enhanced scattering from microinclusions of low-bandgap semiconductors (InP, Si, Ge, PbS, InAs and Te) in an insulating composite to tailor its infrared reflectance for minimizing thermal losses from radiative transfer. To this end, we compute the spectral properties of the microcomposites using Monte Carlo modeling and compare them with results from Fresnel equations. The role of particle size-dependent Mie scattering and absorption efficiencies, and, scattering anisotropy are studied to identify the optimal microinclusion size and material parameters for maximizing the reflectance of the thermal radiation. For composites with Si and Ge microinclusions we obtain reflectance efficiencies of 57 - 65% for the incident blackbody radiation from sources at temperatures in the range 400 - 1600 {\deg}C. Furthermore, we observe a broadbanding of the reflectance spectra from the plasmonic resonances due to charge carriers generated from defect states within the semiconductor bandgap. Our results thus open up the possibility of developing efficient high-temperature thermal insulators through use of the low-bandgap semiconductor microinclusions in insulating dielectrics.Comment: Main article (8 Figures and 2 Tables) + Supporting Information (8 Figures

FibroScan-AST (FAST) score for the non-invasive identification of patients with non-alcoholic steatohepatitis with significant activity and fibrosis: a prospective derivation and global validation study

BACKGROUND The burden of non-alcoholic fatty liver disease (NAFLD) is increasing globally, and a major priority is to identify patients with non-alcoholic steatohepatitis (NASH) who are at greater risk of progression to cirrhosis, and who will be candidates for clinical trials and emerging new pharmacotherapies. We aimed to develop a score to identify patients with NASH, elevated NAFLD activity score (NAS≥4), and advanced fibrosis (stage 2 or higher [F≥2]). METHODS This prospective study included a derivation cohort before validation in multiple international cohorts. The derivation cohort was a cross-sectional, multicentre study of patients aged 18 years or older, scheduled to have a liver biopsy for suspicion of NAFLD at seven tertiary care liver centres in England. This was a prespecified secondary outcome of a study for which the primary endpoints have already been reported. Liver stiffness measurement (LSM) by vibration-controlled transient elastography and controlled attenuation parameter (CAP) measured by FibroScan device were combined with aspartate aminotransferase (AST), alanine aminotransferase (ALT), or AST:ALT ratio. To identify those patients with NASH, an elevated NAS, and significant fibrosis, the best fitting multivariable logistic regression model was identified and internally validated using boot-strapping. Score calibration and discrimination performance were determined in both the derivation dataset in England, and seven independent international (France, USA, China, Malaysia, Turkey) histologically confirmed cohorts of patients with NAFLD (external validation cohorts). This study is registered with ClinicalTrials.gov, number NCT01985009. FINDINGS Between March 20, 2014, and Jan 17, 2017, 350 patients with suspected NAFLD attending liver clinics in England were prospectively enrolled in the derivation cohort. The most predictive model combined LSM, CAP, and AST, and was designated FAST (FibroScan-AST). Performance was satisfactory in the derivation dataset (C-statistic 0·80, 95% CI 0·76–0·85) and was well calibrated. In external validation cohorts, calibration of the score was satisfactory and discrimination was good across the full range of validation cohorts (C-statistic range 0·74–0·95, 0·85; 95% CI 0·83–0·87 in the pooled external validation patients' cohort; n=1026). Cutoff was 0·35 for sensitivity of 0·90 or greater and 0·67 for specificity of 0·90 or greater in the derivation cohort, leading to a positive predictive value (PPV) of 0·83 (84/101) and a negative predictive value (NPV) of 0·85 (93/110). In the external validation cohorts, PPV ranged from 0·33 to 0·81 and NPV from 0·73 to 1·0. INTERPRETATION The FAST score provides an efficient way to non-invasively identify patients at risk of progressive NASH for clinical trials or treatments when they become available, and thereby reduce unnecessary liver biopsy in patients unlikely to have significant disease

Practical diagnosis of cirrhosis in non-alcoholic fatty liver disease using currently available non-invasive fibrosis tests

Unlike for advanced liver fibrosis, the practical rules for the early non-invasive diagnosis of cirrhosis in NAFLD remain not well defined. Here, we report the derivation and validation of a stepwise diagnostic algorithm in 1568 patients with NAFLD and liver biopsy coming from four independent cohorts. The study algorithm, using first the elastography-based tests Agile3+ and Agile4 and then the specialized blood tests FibroMeterV3G and CirrhoMeterV3G, provides stratification in four groups, the last of which is enriched in cirrhosis (71% prevalence in the validation set). A risk prediction chart is also derived to allow estimation of the individual probability of cirrhosis. The predicted risk shows excellent calibration in the validation set, and mean difference with perfect prediction is only −2.9%. These tools improve the personalized non-invasive diagnosis of cirrhosis in NAFLD

Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Non-alcoholic Fatty Liver Disease.

BACKGROUND & AIMS: We estimated the accuracy of FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP) and liver stiffness measurements (LSMs) in assessing steatosis and fibrosis in patients with suspected NAFLD. METHODS: We collected data from 450 consecutive adults who underwent liver biopsy analysis for suspected NAFLD at 7 centers in the United Kingdom from March 2014 through January 2017. FibroScan examinations with M or XL probe were completed within the 2 weeks of the biopsy analysis (404 had a valid examination). The biopsies were scored by 2 blinded expert pathologists according to non-alcoholic steatohepatitis clinical research network criteria. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROC) for the categories of steatosis and fibrosis. We assessed effects of disease prevalence on positive and negative predictive values. For LSMs, the effects of histological parameters and probe type were appraised using multivariable analysis. RESULTS: Using biopsy analysis as the reference standard, we found that CAP identified patients with steatosis with an AUROCs of 0.87 (95% CI, 0.82-0.92) for S≥S1, 0.77 (95% CI, 0.71-0.82) for S≥S2, and 0.70 (95% CI, 0.64-0.75) for S=S3. Youden cut-off values for S≥S1, S≥S2 and S≥S3 were 302 dB/m, 331 dB/m, and 337 dB/m respectively. LSM identified patients with fibrosis with AUROCs of 0.77 (95% CI, 0.72-0.82) for F≥F2, 0.80 (95% CI, 0.75-0.84) for F≥F3, and 0.89 (95% CI, 0.84-0.93) for F=F4. Youden cut-off values for F≥F2, F≥F3 and F=F4 were 8.2 kPa, 9.7 kPa, and 13.6 kPa respectively. Applying the optimal cut-off values, determined from this cohort, to populations of lower fibrosis prevalence increased negative predictive values and reduced positive predictive values. Multivariable analysis found that the only parameter that significantly affect LSMs was fibrosis stage (P<10-16); we found no association with steatosis or probe type. CONCLUSIONS: In a prospective analysis of patients with NAFLD, we found CAP and LSMs by FibroScan to assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.7 to 0.89. Probe type and steatosis did not affect LSMs

Accuracy of FibroScan Controlled Attenuation Parameter and Liver Stiffness Measurement in Assessing Steatosis and Fibrosis in Patients With Non-alcoholic Fatty Liver Disease.

BACKGROUND & AIMS: We estimated the accuracy of FibroScan vibration-controlled transient elastography controlled attenuation parameter (CAP) and liver stiffness measurements (LSMs) in assessing steatosis and fibrosis in patients with suspected NAFLD. METHODS: We collected data from 450 consecutive adults who underwent liver biopsy analysis for suspected NAFLD at 7 centers in the United Kingdom from March 2014 through January 2017. FibroScan examinations with M or XL probe were completed within the 2 weeks of the biopsy analysis (404 had a valid examination). The biopsies were scored by 2 blinded expert pathologists according to non-alcoholic steatohepatitis clinical research network criteria. Diagnostic accuracy was estimated using the area under the receiver operating characteristic curves (AUROC) for the categories of steatosis and fibrosis. We assessed effects of disease prevalence on positive and negative predictive values. For LSMs, the effects of histological parameters and probe type were appraised using multivariable analysis. RESULTS: Using biopsy analysis as the reference standard, we found that CAP identified patients with steatosis with an AUROCs of 0.87 (95% CI, 0.82-0.92) for S≥S1, 0.77 (95% CI, 0.71-0.82) for S≥S2, and 0.70 (95% CI, 0.64-0.75) for S=S3. Youden cut-off values for S≥S1, S≥S2 and S≥S3 were 302 dB/m, 331 dB/m, and 337 dB/m respectively. LSM identified patients with fibrosis with AUROCs of 0.77 (95% CI, 0.72-0.82) for F≥F2, 0.80 (95% CI, 0.75-0.84) for F≥F3, and 0.89 (95% CI, 0.84-0.93) for F=F4. Youden cut-off values for F≥F2, F≥F3 and F=F4 were 8.2 kPa, 9.7 kPa, and 13.6 kPa respectively. Applying the optimal cut-off values, determined from this cohort, to populations of lower fibrosis prevalence increased negative predictive values and reduced positive predictive values. Multivariable analysis found that the only parameter that significantly affect LSMs was fibrosis stage (P\u3c10-16); we found no association with steatosis or probe type. CONCLUSIONS: In a prospective analysis of patients with NAFLD, we found CAP and LSMs by FibroScan to assess liver steatosis and fibrosis, respectively, with AUROC values ranging from 0.7 to 0.89. Probe type and steatosis did not affect LSMs