Serum hyaluronate as a non-invasive marker of hepatic fibrosis and inflammation in HBeAg-negative chronic hepatitis B

Background: HBV infection is a serious global heath problem. It is crucial to monitor this disease more closely with a non-invasive marker in clinical trials. We aimed to evaluate the predictive value of serum hyaluronate for the presence of extensive liver fibrosis and inflammation. Methods: 28 healthy volunteers and 65 patients with HBeAg negative chronic hepatitis B were enrolled. Liver biopsies scored according to Ishak system. Association of serum hyaloronate with liver fibrosis and inflammation were assessed, and cut off points for serum hyaluronate levels were identified by receiver operating characteristics (ROC) curves and their values for prediction of fibrosis and inflammation were assessed. Results: In patients with CHB serum hyaluronate had the most significant correlation and predictive values for the liver fibrosis and inflammation comparing to the other variables. At the cut off point of 126.4 ngm/ml it could discriminate extensive fibrosis from milder ones with sensitivity of 90.9% and specificity of 98.1%. With the same value it could discriminate extensive inflammation from their milder counterparts with sensitivity of 63.6% and specificity of 92.6%. Conclusion: Serum hyaluronate was the best predictor of extensive liver fibrosis and inflammation and it could discriminate subgroups of patients with chronic hepatitis B. It could be used as a non-invasive test to monitor these patients more closely with developing anti viral agents in clinical trials

The effectiveness of moving masses in reducing the roll motion of floating vessels

Dynamic motions of Ships in severe conditions of sea may be undesired and should be controlled by some devices. The roll motion is much more significant than the other oscillations which can affect comfort, safety and efficiency of navigation at sea. This motion is controlled by some common stabilizers such as rudder, fins, etc. They may be divided into two categories of passive and active stabilizers or controllers. However controlling devices may be high in cost. Moving masses are employed to reduce the motions of floating vessels or offshore structures. This type of stabilizers consists of a mass with one or more springs and dampers. The movement of the mass produces an inertia force and moment to absorb wave excited motions. In this study the effectiveness of moving masses in vessels with large roll motion is investigated. A rolling vessel equipped with a moving mass can be modeled as a two-degree of freedom system. As in large amplitude roll motion the nonlinearities cannot be neglected, a mathematical model with second-order damping and fifth-order restoring moment is implemented as roll equation in beam waves. Applying to a trawler, this equation is solved simultaneously with the equation of movement of the mass in both frequency-domain and time-domain by analytical and numerical approaches. The computation shows that with an optimum passive control, a moving mass with 0.5% of the displacement of the ship is an effective device in roll minimization and enhance the vessel’s stability in high load conditions.</jats:p

Influence of B cells in liver fibrosis associated with hepatitis B virus harboring basal core promoter mutations

The development of the liver disease in chronic hepatitis B with common viral variants can be determined through the interaction between the virus and the host immune response. B cells constitute half of the intrahepatic lymphocyte population with an impact on fibrosis. A proliferation-inducing ligand (APRIL) has been shown to have a co-stimulatory activity on B cells. For this study HBV DNA was amplified and then sequenced to show the presence of the basal core promoter (BCP) mutations in the serum from 57 patients with chronic hepatitis B. The range of IgD-positive B cells was detected by immunohistochemistry in liver biopsies; and patients serum was assayed for APRIL levels by enzyme immunoassay. Twenty-seven patients (47.4) harbored the A1762T-G1764A BCP mutations. Coefficients of logistic regression showed that the effect of increasing IgD-positive B cells in rising odds of the liver disease is the same in the patients with BCP mutation A1762T-G1764A and in the patients without mutation, nevertheless the effect of APRIL is not similar in these two groups of patients. Logistic regression in patients with BCP A1762T-G1764A mutations demonstrated that increasing one score of APRIL decreased the odds of fibrosis stage about 8. These results suggest that in infection with viral variants of hepatitis B virus, the population of IgD-positive B cells may play a decisive role in later stages of the liver disease which is reduced by APRIL in chronic hepatitis patients with BCP mutations. J. Med. Virol. 84:18891896, 2012. (c) 2012 Wiley Periodicals, Inc

Drug-related mutational patterns in hepatitis B virus (HBV) reverse transcriptase proteins from Iranian treatment-Naïve chronic HBV patients

Background: Immunomodulators and Nucleotide analogues have been used globally for the dealing of chronic hepatitis B virus (HBV) infection. However, the development of drug resistance is a major limitation to their long-term effectiveness. Objectives: The aim of this study was to characterize the hepatitis B virus reverse transcriptase (RT) protein variations among Iranian chronic HBV carriers who did not receive any antiviral treatments. Materials and Methods: Hepatitis B virus partial RT genes from 325 chronic in active carrier patients were amplified and directly sequenced. Nucleotide/amino acid substitutions were identified compared to the sequences obtained from the database. Results: All strains belonging to genotype D.365 amino-acid substitutions were found. Mutations related to lamivudine, adefovir, telbivudine, and entecavir occurred in (YMDD) 4% (n = 13), (SVQ) 17.23% (n = 56), (M204I/V + L180M) 2.45% (n = 8) and (M204I) 2.76% (n = 9) of patients, respectively. Conclusions: RT mutants do occur naturally and could be found in HBV carriers who have never received antiviral therapy. However, mutations related to drug resistance in Iranian treatment-naïve chronic HBV patients were found to be higher than other studies published formerly. Chronic HBV patients should be monitored closely prior the commencement of therapy to achieve the best regimen option. © 2013, KOWSAR Corp

Estimating the dynamics and dependencies of accumulating mutations with applications to HIV drug resistance

We introduce a new model called the observed time conjunctive Bayesian network (OT-CBN) that describes the accumulation of genetic events (mutations) under partial temporal ordering constraints. Unlike other CBN models, the OT-CBN model uses sampling time points of genotypes in addition to genotypes themselves to estimate model parameters. We developed an expectation-maximization algorithm to obtain approximate maximum likelihood estimates by accounting for this additional information. In a simulation study, we show that the OT-CBN model outperforms the continuous time CBN (CT-CBN) (Beerenwinkel and Sullivant, 2009. Markov models for accumulating mutations. Biometrika 96(3), 645-661), which does not take into account individual sampling times for parameter estimation. We also show superiority of the OT-CBN model on several datasets of HIV drug resistance mutations extracted from the Swiss HIV Cohort Study databas

Fluctuations, dissipation and the dynamical Casimir effect

Vacuum fluctuations provide a fundamental source of dissipation for systems coupled to quantum fields by radiation pressure. In the dynamical Casimir effect, accelerating neutral bodies in free space give rise to the emission of real photons while experiencing a damping force which plays the role of a radiation reaction force. Analog models where non-stationary conditions for the electromagnetic field simulate the presence of moving plates are currently under experimental investigation. A dissipative force might also appear in the case of uniform relative motion between two bodies, thus leading to a new kind of friction mechanism without mechanical contact. In this paper, we review recent advances on the dynamical Casimir and non-contact friction effects, highlighting their common physical origin.Comment: 39 pages, 4 figures. Review paper to appear in Lecture Notes in Physics, Volume on Casimir Physics, edited by Diego Dalvit, Peter Milonni, David Roberts, and Felipe da Rosa. Minor changes, a reference adde

Assessing breast cancer risk among Iranian women using the gail model

Background: Breast cancer risk assessment is a helpful method for estimating development of breast cancer at the population level. Materials and Methods: In this cross-sectional study, participants consisted of a group of 3,847 volunteers (mean ± SD age: 463 ± 7.59 years) in a convenience sample of women referred to health centers affiliated to Tehran University of Medical Sciences in Tehran, Iran. The risk of breast cancer was estimated by applying the National Cancer Institute's online version of the Gail Risk Assessment Tool. Results: Some 24.9 of women reported having one first-degree female relative with breast cancer, with 8.05 of them having two or more first-degree relatives with breast cancer. The mean five-year risk of breast cancer for all participants was 1.61±0.73, and 9.36 of them had a five-year risk of breast cancer > 1.66. The mean lifetime risk of breast cancer was 11.7±3.91. Conclusions: The Gail model is useful for assessing probability of breast cancer in Iranian women. Based on the their breast cancer risk, women may decide to accept further screening services

Patient-reported utilities in advanced or metastatic melanoma, including analysis of utilities by time to death

Background: Health-related quality of life is often collected in clinical studies, and forms a cornerstone of economic evaluation. This study had two objectives, firstly to report and compare pre- and post-progression health state utilities in advanced melanoma when valued by different methods and secondly to explore the validity of progression-based health state utility modelling compared to modelling based upon time to death. Methods: Utilities were generated from the ipilimumab MDX010-20 trial (Clinicaltrials.gov Identifier: NCT00094653) using the condition-specific EORTC QLQ-C30 (via the EORTC-8D) and generic SF-36v2 (via the SF-6D) preference-based measures. Analyses by progression status and time to death were conducted on the patient-level data from the MDX010-20 trial using generalised estimating equations fitted in Stata®, and the predictive abilities of the two approaches compared. Results: Mean utility showed a decrease on disease progression in both the EORTC-8D (0.813 to 0.776) and the SF-6D (0.648 to 0.626). Whilst higher utilities were obtained using the EORTC-8D, the relative decrease in utility on progression was similar between measures. When analysed by time to death, both EORTC-8D and SF-6D showed a large decrease in utility in the 180 days prior to death (from 0.831 to 0.653 and from 0.667 to 0.544, respectively). Compared to progression status alone, the use of time to death gave similar or better estimates of the original data when used to predict patient utility in the MDX010-20 study. Including both progression status and time to death further improved model fit. Utilities seen in MDX010-20 were also broadly comparable with those seen in the literature. Conclusions: Patient-level utility data should be analysed prior to constructing economic models, as analysis solely by progression status may not capture all predictive factors of patient utility and time to death may, as death approaches, be as or more important. Additionally this study adds to the body of evidence showing that different scales lead to different health state values. Further research is needed on how different utility instruments (the SF-6D, EORTC-8D and EQ-5D) relate to each other in different disease areas