The policy gradient approach is a flexible and powerful reinforcement learning method particularly for problems with continuous actions such as robot control. A common challenge is how to reduce the variance of policy gradient estimates for reliable policy updates. In this letter, we combine the following three ideas and give ...

There has been a growing awareness over the past decade that stiffening of the aorta, and its attendant effects on hemodynamics, is both an indicator and initiator of diverse cardiovascular, neurovascular, and renovascular diseases. Although different clinical metrics of arterial stiffness have been proposed and found useful in particular situations, ...

This work presents the modelling and simulation of the mechanical behaviour of the human aortic arch under in vivo conditions with pressure levels within the normal and hypertension physiological range. The cases studied correspond to young and aged arteries without cardiovascular pathologies. First, the tissue of these two groups is characterised ...

We propose a CFD-based approach for the non-invasive hemodynamic assessment of pre- and post-operative coarctation of aorta (CoA) patients. Under our approach, the pressure gradient across the coarctation is determined from computational modeling based on physiological principles, medical imaging data, and routine non-invasive clinical measurements. The main constituents of our ...

The objective of this study was to determine the orientation and magnitude of maximal displacement forces (DFs) in the thoracic aortic aneurysm endograft (TAA endograft) in three-dimensional (3D) space. Theoretical computer model representing the anatomically worst-case scenario with respect to DF magnitude was used to calculate the magnitude and orientation ...

The aim of this current opinion report is to discuss relevant issues of regulatory causality assessment methods related to initially suspected herb-induced liver injury (HILI). Herbal hepatotoxicity represents a major clinical, regulatory and public challenge since its diagnosis may be difficult to be established, requiring a sophisticated approach that includes ...

Mycophenolate Mofetil (MMF) is widely used in preventing acute rejection in liver transplantation. Only free MPA (fMPA) can exert the pharmacological effect. In this study, we aimed to develop the new model which could be best fit to predict the fMPA area under the plasma concentration-time curve (AUC) by limited ...

Drug-induced liver injury (DILI) is not only a major concern for all patients requiring drug therapy, but also for the pharmaceutical industry. Many new in vitro assays and pre-clinical animal models are being developed to help screen compounds for the potential to cause DILI. This study demonstrates that mechanistic, mathematical ...

Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the ...

A bicuspid aortic valve (BAV) is a congenital cardiac disorder where the valve consists of only two cusps instead of three in a normal tricuspid valve (TAV). Although 97% of BAVs include asymmetric cusps, little or no prior studies investigated the blood flow through physiological three-dimensional BAV and root. This ...

Purpose: Due to low frame rate of MRI and high radiation damage from fluoroscopy and CT, liver motion estimation using external respiratory surrogate signals seems to be a better approach to track liver motion in real-time for liver tumor treatments in radiotherapy and thermotherapy. This work proposes a liver motion ...

There is an increasing need for development of physiologically relevant in-vitro models for testing toxicity, however determining toxic effects of agents which undergo extensive hepatic metabolism can be particularly challenging. If a source of such metabolic enzymes is inadequate within a model system, toxicity from prodrugs may be grossly underestimated. ...

BACKGROUND: Experiments using animal models are the most common way to learn microsurgery. This expertise is necessary for liver research, microsurgical reconstruction of the esophagus by free jejunum or reconstruction of the hepatic artery during reimplantation from living donors. The goal of this prospective study is to assess the reliability ...

Acetaminophen (APAP) is the leading cause of acute liver injury in the developed world. Timely administration of N-acetylcysteine (N-Ac) prevents the progression of serious liver injury and disease, whereas failure to administer N-Ac within a critical time frame allows disease progression and in the most severe cases may result in ...

Objectives:  Up to now, vascular indicator dilution curves have been analyzed by numerical integration or by fitting empirical functions to the data. Here we apply a recently developed mechanistic model with the goal to quantitatively describe flow distribution in the sinusoidal network of normal rat livers and those with high-fat ...

Survival of patients with hepatocellular carcinoma (HCC) is determined by the extent of the tumor and the underlying liver function. We aimed to develop a survival model for HCC based on objective parameters including the Model for Endstage Liver Disease (MELD) as a gauge of liver dysfunction. This analysis is ...

This study aimed to assess which region of interest results in the best intraobserver reproducibility of mebrofenin clearance rate (MCR) processing. Mebrofenin clearance rate was calculated according to Ekman's formalism. Processing methods included smaller left ventricular (LV) versus larger regions, nearly the whole heart (WH), which were applied to either ...

A major objective of clinical research is to study outcome effects in subgroups. Such effects generally have stepping functions that are not strictly linear. Analyzing stepping functions in linear models thus raises the risk of underestimating the effects. In the past few years, recoding subgroup properties from continuous variables into ...

Friedreich's ataxia (FRDA) is the most common hereditary ataxia in the caucasian population and is characterized by a mixed spinocerebellar and sensory ataxia, hypertrophic cardiomyopathy and increased incidence of diabetes. FRDA is caused by impaired expression of the FXN gene coding for the mitochondrial protein frataxin. During the past ten ...

The European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) introduced the first guidelines on the use of contrast-enhanced ultrasound (CEUS) in 2004. This EFSUMB document focused mainly on liver applications. However, new applications extending beyond the liver were subsequently developed. Therefore, in the update of the clinical ...

ABSTRACT: BACKGROUND: Artificial neural networks (ANNs) are widely studied for evaluating diseases. This paper discusses the intelligence mode of an ANN in grading the diagnosis of liver fibrosis by duplex ultrasonogaphy. METHODS: 239 patients who were confirmed as having liver fibrosis or cirrhosis by ultrasound guided liver biopsy were investigated ...

Wu, H., Baynes, R. E., Leavens, T., Tell, L. A., Riviere, J. E. Use of population pharmacokinetic modeling and Monte Carlo simulation to capture individual animal variability in the prediction of flunixin withdrawal times in cattle. J. vet. Pharmacol. Therap. doi: 10.1111/j.1365-2885.2012.01420.x. The objective of this study was to develop ...

Various models are employed for investigating human liver diseases and for testing new drugs. However, data generated in such models have only limited relevance for the respective in-vivo conditions in humans. We here present an ex-vivo perfusion system utilizing human liver samples that enables to characterize parameters in a functionally ...

Purpose: The recently published TG 204 report established conversion factors based on measurements and Monte Carlo simulations, which adjust scanner-reported CTDIvol for patient size, called size specific dose estimates (SSDE). However, those estimates were based on fixed tube current scans, while most performed clinical protocols make use of Tube Current ...

The alkenylbenzene estragole is a constituent of several herbs and spices. It induces hepatomas in rodents at high doses following bioactivation by cytochromes P450 and sulfotransferases (SULTs) giving rise to the ultimate carcinogenic metabolite 1'-sulfooxyestragole which forms DNA adducts. Methanolic extracts from different alkenylbenzene-containing herbs and spices were able to ...

Filtering the discriminative metabolites from high dimension metabolome data is very important in metabolomics study. Support vector machine-recursive feature elimination (SVM-RFE) is an efficient feature selection technique and has shown promising applications in the analysis of the metabolome data. SVM-RFE measures the weights of the features according to the support ...

Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic ...

N-acetylcysteine (NAC) is the treatment of choice for acetaminophen poisoning; standard 72-hour oral or 21-hour intravenous protocols are most frequently employed. There is controversy regarding which protocol is optimal and whether the full treatment course is always necessary. It would be challenging to address these questions in a clinical trial. ...

The ability to accurately predict the toxicity of drug candidates from their chemical structure is critical for guiding experimental drug discovery towards safer medicines. Under the guidance of the MetaTox consortium (Thomson Reuters, CA, USA), which comprised toxicologists from the pharmaceutical industry and government agencies, we created a comprehensive ontology ...

The fatty liver of mule ducks, i.e. French 'foie gras', is the most valuable product in duck production systems. Its quality is measured by the technological yield, which is the opposite of the fat loss during cooking. The purpose of this study was to determine whether biochemical measures of fatty ...

Abstract Objective. A model for living donor liver transplantation (LDLT) outcomes, in concert with pretransplant disease severity assessment, would facilitate informed decision-making on both sides considering donation and transplantation. So far, however, few of studies have focused on models specifically for adult-to-adult right-lobe LDLT recipients with benign end-stage liver diseases. ...

The purpose of this study was to compare a dual-freeze protocol with a triple-freeze protocol for hepatic cryoablation in a porcine model. Eighteen cryoablations were performed over an exposed operation field in nine normal porcine livers, using dual- (10-5-10-5) and triple-freeze (5-5-5-5-10-5) protocols. Changes in the temperature of the cryoprobes ...

Estimation of standard liver volume (SLV) is an important component in the evaluation of potential live liver donors or for surgical planning for resection of tumor. At least 16 different formulae have been published in the world-wide literature to estimate SLV. More recently, several proprietary Software-Assisted Image Post-processing (SAIP) programs ...

PURPOSE OF REVIEW: The model for end-stage liver disease (MELD) driven liver allocation system has been in place for 10 years now. Understanding what the driving forces were, what principles were developed and employed, and assessing how these have stood the test of time will help future policy makers further ...

New mathematical models from physiologically interpreted parameters capable of evaluating glucose metabolism within the liver and/or the whole body were developed. The group of pigs in a fasting state and the group of pigs with euglycemic supraphysiological hyperinsulinemia were scanned by positron emission tomography after a single dose of [(18)F]FDG ...

In this study, six biomechanical models for simulating lamb liver behaviour are presented. They are validated using similarity coefficients from Medical Image on reconstructed volumes from computerised tomography images. In particular, the Jaccard and Hausdorff coefficients are used. Loads of 20 and 40 g are applied to the livers and their ...

PURPOSE: The purpose was to propose and evaluate a semiautomatic postprocessing method to measure liver R2(⁎) values in patients with a broad range of liver iron content. MATERIALS AND METHODS: Multiecho gradient echo magnetic resonance images were acquired in patients diagnosed with thalassemia or other types of congenital anemias. Liver ...

PURPOSE: Surgeons frequently describe the shape of intraoperative findings using visual judgement and their own sense of proportion or describing these findings in comparison to commonly used or metaphoric subjects. The aim of the study was to analyse the reliability of surgeon's estimations of dimensions. METHODS: The study was performed ...

In positron emission tomography (PET) studies involving organs different from the brain, ignoring the metabolite contribution to the tissue time-activity curves (TAC), as in the standard single-input (SI) models, may compromise the accuracy of the estimated parameters. We employed here double-input (DI) compartmental modeling (CM), previously used for [(11)C]thymidine, and ...

A biocatalytic cascade for the analysis of the simultaneous increase in the concentration of two biomarkers characteristic of liver injury (alanine transaminase, ALT, and lactate dehydrogenase, LDH) was tested on real samples acquired from an animal model (domestic pigs, Sus scrofa domesticus) suffering from traumatic liver injury. A two-step reaction ...

Phospholipid accumulation manifests as an adverse effect of cationic amphiphilic drugs in particular. Detection, however, by histopathology examination is time-consuming and may require repeated administration of compounds for several weeks. To eliminate compounds with potential for inducing phospholipidosis from the discovery pipeline, we have identified and validated a set of ...

This paper describes a paper-based microfluidic device that measures two enzymatic markers of liver function (alkaline phosphatase, ALP, and aspartate aminotransferase, AST) and total serum protein. A device consists of four components: (i) a top plastic sheet, (ii) a filter membrane, (iii) a patterned paper chip containing the reagents necessary ...

: To prevent abdominal organs' traumas in crash situations, the definition of efficient safety devices should be based on a detailed knowledge of human tolerance, i.e., injury mechanisms and related injury criteria. This knowledge should be based on experimental observation of these mechanisms through damage and failure analysis. : In ...

Background/Aims: To establish an objective and precise vascular naming method to explore the segmental anatomy of the liver with major anomalies using threedimensional (3D) simulations. Methodology: Two algorithms, "Alternative vascular visualization method" (Algorithm A) and "Cholecystic axis based definition" (Algorithm B), were devised. Twenty livers with typical anatomy and four ...

The mixture-of-experts (ME) network uses a modular type of neural network architecture optimized for supervised learning. This model has been applied to a variety of areas related to pattern classification and regression. In this research, we applied a ME model to classify hidden subgroups and test its significance by measuring ...

BACKGROUND: Children have lower resting energy expenditure (REE) but higher ratio of resting energy expenditure to body mass (REE/BM) than do adults. This well-known observation has never been quantitatively explained. OBJECTIVES: The aim of the present study is to understand the high REE/BM in childhood and adolescence. DESIGN: A mechanistic ...

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of abnormal liver function and correlates with central adiposity, obesity, insulin resistance, the metabolic syndrome and type 2 diabetes mellitus. The pathological spectrum of NAFLD ranges from fatty liver to non-alcoholic steatohepatitis (NASH), advanced fibrosis, cirrhosis, and even ...

AIM: To assess the validity of standard liver volume (SLV) calculated using various formulae in the Indian population. METHODS: Data on liver weights of 366 cadavers with no intrinsic liver disease were obtained retrospectively from autopsy records. From these, liver volume (LV) was calculated using the density of formalin-preserved livers, ...

The patients with end-stage liver disease (ESLD) on the liver transplant waiting list are prioritized for transplant based on the model for end-stage liver disease (MELD) score. We developed and used an innovative approach to compare MELD to six proposed alternatives with respect to waiting list mortality. Our analysis was ...

Stereology offers a number of tools for the analysis of sections in microscopy (which usually provide only two-dimensional information) for the purpose of estimating geometric quantities, such as volume, surface area, length or number of particles (cells or other structures). The use of these tools enables recovery of the three-dimensional ...