Phase II clinical trial of combined natural interferon-beta plus recombinant interferon-gamma treatment of chronic hepatitis B

BACKGROUND/AIMS: Alpha-interferon (IFN-alpha) is an effective treatment for chronic hepatitis B but only 25-40% of patients will profit from a long-term beneficial response to the currently recommended schedule of 3-6 MU given 3 times a week for 6 months. Clinical trials are therefore needed to investigate alternative modifications of interferon therapy, including combinations of different antivirals or immune modulators in order to improve the therapeutic approach to chronic hepatitis B infection. In a phase II trial we evaluated whether a combination of natural interferon-beta (nIFN-beta) with strong antiviral activity plus recombinant interferon-gamma (rIFN-gamma) with a predominantly immunomodulatory activity is able to increase the response rate compared to historical controls treated with IFN-alpha in a conventional regimen. METHODOLOGY: Forty patients with chronic hepatitis B were included in this trial of combined interferon therapy at a dosage of 6 MU nIFN-beta during week 1 followed by 3 MU for weeks 2-4 plus rIFN-gamma at a daily subcutaneous (s.c.) injection of 150 microg during the entire 4 weeks of the treatment period. Patients entered the trial on the basis of the following criteria: hepatitis B surface antigen (HBsAG), HBeAG and HBV-DNA positive for at least 6 months, HDV, EBV, CMV, anti-HIV negative, and chronic hepatitis proven on biopsy taken within 4 weeks of entry as well as 6 and/or 12 months after interferon therapy. The final diagnosis and classification of chronic hepatitis has been based on guidelines according to a revised classification of chronic hepatitis (Desmet 1994). The post-treatment follow-up was 12 months. RESULTS: The combined interferon therapy achieved complete responses with seroconversion from HBeAG to anti-HBe and a negative HBV-DNA (dot blot) test, as well as normalization of ALT activity in 15 patients, and partial response with negativation of HBV-DNA concomitant to a decrease in aminotransferase activity to near normal levels in 6 patients. Nineteen patients showed no response to viral markers but showed relief of clinical symptoms as well as pronounced decrease of serumtransaminase activity. Grading of liver biopsies demonstrated an improvement of histologic parameters after the interferon regimen in half of the evaluable patients (n=22). Histological response has been quantified by a reduction in the score of histological activity (HAI-index) from 12.6 before to 7.6 after interferon therapy, and in the inflammation and cellular degeneration score (ICD) from 9.9 to 5.2. Histological response, however, failed to show a consistent correlation with serologic response. This medium-dose combination of interferon-beta and interferon-gamma was tolerated very well by the patients, this good tolerability being explained by tachyphylaxis in response to daily interferon doses. No serious side effects or decompensation of liver function were observed during the 4-week period of therapy or the follow-up, despite the special clinical situation where 60% of the patients included in the study presented with histologically proven cirrhosis (35% of them with clinical manifestation of mildly decompensated cirrhosis). CONCLUSIONS: This short-term regimen of combined nIFN-beta + rIFN-gamma therapy in patients with chronic hepatitis B proved to be equieffective to long-term treatment with interferon-alpha and combines high clinical tolerability with good practicability, as it can be administered on an in-patient basis, ensuring close patient monitoring.     

Investigating newcomer expectations and job-related outcomes.

The initial experiences of newcomers as they enter an organization can provide important information that substantially influences the subsequent relationship between the individual and the organization. For example, the application of realistic job previews (RJPs) often results in desirable organizational outcomes (e.g., increased satisfaction and reduced turnover). RJPs are typically job specific and job-content laden and serve to reduce the expectations of organizational newcomers. The present study indicates that an expectation lowering procedure (ELP), which is not job specific and is relatively content free, may yield similar benefits (i.e., reduce expectations). Both the organizational implications of this research and suggestions for using ELPs in conjunction with RJPs in the newcomer socialization process are offered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Scanning for mutations in the human prion protein open reading frame by temporal temperature gradient gel electrophoresis

Gerstmann-Str?ussler-Scheinker syndrome (GSS), fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (CJD) are caused by point mutations or octarepeat insertions in the prion protein (PrP) gene. In the present work a method was established that is appropriate for a thorough screening for mutations in the PrP gene and is generally applicable to screenings of any given gene. Temperature gradient gel electrophoresis (TGGE) was modified at two critical steps by UV cross-linking of the DNA strands and by replacing the spatial gradient with a temporal one. The shift of a DNA band in temporal temperature gradient gel electrophoresis (tTGGE) due to a mutation can be calculated as a function of the position of the mutation in the sequence. Appropriate DNA fragments were selected for polymerase chain reaction (PCR) amplification and analysis by tTGGE on the basis that the predicted band shifts amount to more than 10% of the migration distance for all possible mutations. The accuracy of the prediction was tested experimentally with ten known mutations in the human PrP gene, and quantitative agreement between theory and experiment was achieved. Thus, this screening method is also a suitable means to verify the absence of mutations in a given gene segment.     

Modeling of heat flow in sand castings: Part II. Applications of the boundary curvature method

In Part I of this paper, a new method was presented for modeling heat flow in sand castings. In this paper, the method is used to simulate the solidification of parts of varying complexities. Comparisons are made between conventional calculations (with the mold enmeshed), calculations using the boundary curvature method, and experimental results. The results are shown to agree well with each other. Reductions in cpu time up to 96 pct are found by adopting the new method.     

Fatigue analysis of miniaturized lead-free solder contacts based on a novel test concept

The paper presents the method of generating lifetime-prediction-laws on special prepared very stiff specimen. The combination of thin- and thick-film technology allows building up test samples on ceramic very similar to electronic packages including the measurement issues. Influences of pad surface metallurgy, microstructure of solder, ineutectic solder alloys and assembly process parameter are regarded now. The investigation objects provide monitoring of electrical and mechanical damage process of SnAgCu solder bump. Different thermo-mechanical loads will be applied in temperature ranges of 0 to +80 °C, −40 to +125 °C and −50 to +150 °C, where the temperature gradient and cycle frequency also vary. A Variation of four different chip sizes allows the determination of fatigue laws for each temperature profile, to be able to compare in between them. The results of these tests will give universal lifetime-prediction laws for SnAgCu base solder joints. Main goals are to find coefficients for lifetime prediction models such as Coffin–Manson- or Norris–Landzberg-relation, which are transferable in between different electronic packages.     

General strategy for performing temperature programming in high performance liquid chromatography: prediction of linear temperature gradients

This paper describes how an empirical retention model is transferred from temperature-programmed gas chromatography (GC) to high temperature liquid chromatography (HT-HPLC). In order to evaluate the retention prediction, a temperature range from 50 to 180 °C was investigated using two test mixtures consisting of steroids and polycyclic aromatic hydrocarbons. In this temperature range, heating rates from 1.5 °C min(-1) up to 30 °C min(-1) were applied using four different high temperature stable HPLC columns with inner diameters of 1.0, 2.1, 3.0, and 4.6 mm. Temperature lag phenomena in the HPLC column as well as in the column oven are discussed, and it is shown that the linear elution strength (LES) model can be applied without any mathematical extension in order to take a temperature-dependent delay time into account. On the basis of this approximation, it is possible to perform a systematic method development using linear temperature gradients in liquid chromatography. Furthermore, it is shown that only two initial temperature gradient runs are necessary to predict the retention times of the analytes with a maximal relative error of less than 2%.     

Electricity generation from renewable energy sources in Germany — Potentials, costs and implementation strategies

The objective of this paper is to analyse the technical potentials and the costs of renewable energy sources for electricity generation in Germany and to define and discuss possible strategies for a largescale implementation of such renewable sources into the German power generation system. Four renewable options are discussed: hydropower, windtechnical and photovoltaic electricity generation and the possible electricity production of biomass. First the technical potentials are identified for the present and future reference years. Then the specific costs are analysed, as well for the present and the future. Finally an exemplary implementation strategy is defined and discussed leading to a total renewable electricity generation in the year 2020 of about 86 TWh/a which would be a share of about 19 % of the total present electrical energy demand.     

Effects of multiple carbon fillers on the rheology of polycarbonate‐based composites

Adding conductive carbon fillers to insulating thermoplastic polymers increases the electrical conductivity of the resulting composite, which could allow them to be used in electrostatic dissipative and semiconductive applications. Adding fillers often increases viscosity, which can make the material more difficult to process. In this study, three different carbon fillers [carbon black (CB), carbon nanotubes (CNT), and exfoliated graphite nanoplatelets (GNP)] were studied via three different combinations of two different fillers (CB/CNT, CB/GNP, and CNT/GNP). These filler combinations were studied via three 3² factorial designs, which considered the following loading levels: CB: 0, 2, and 5 wt%; CNT: 0, 1, and 5 wt%; and GNP: 0, 2, and 5 wt%. These composites were compounded, injection molded, and tested for electrical conductivity and steady shear viscosity. CB and GNP exhibited classic filler behavior, increasing the composite viscosity with increased filler loading. CNT acted differently, lowering the composite viscosity with increased filler loading. When CB and GNP were combined, the viscosity increase was additive. When CNT was combined with either CB or GNP, the resultant composite had a lower viscosity than the corresponding single filler composite with equivalent loadings of CB or GNP. This viscosity lowering effect of CNT, even at loadings as low as 1 wt%, allows for increased filler loadings of CB or GNP with little impact on processability. Five different formulations (four containing two filler combinations) could be used for electrostatic dissipative applications and seven different formulations (six containing two filler combinations) may be used for semiconductive applications. POLYM. COMPOS., 2012. © 2011 Society of Plastics Engineers     

Miniplants — Ein Beitrag zur inhärenten Sicherheit?

The scale minimisation of a chemical plant can increase its safety almost to the inherent safety level because the amounts of hazardous substances are greatly reduced. Because of the small amounts of hazardous substances usually present, miniplants, which have proved themselves in research and development, do not pose a serious danger to the environment. With regard to inherent safety, two concepts are presented which could help to avoid problems encountered in storage and transportation of hazardous substances and to lessen the hazardous potential of a chemical plant.