Clinical and histological outcome after hepatitis B e antigen to antibody seroconversion in children with chronic hepatitis B

Data regarding the outcome of children with chronic hepatitis B after seroconversion are scarce. We describe the long-term evolution of these patients. One hundred and three children with antibody against hepatitis B e antigen and normal alanine aminotransferase (ALT) levels were followed for 0.6 to 12.5 years (mean, 6.3 years). Paired liver biopsies (before and after seroconversion) were available in 83 cases. Final biopsies were obtained 0.5 to 12.5 years (mean, 4.5 years) after seroconversion. ALT levels remained normal in most of the children (79%) throughout the follow-up. All children, except five who lost hepatitis B surface antigen, had serum viral DNA detected by polymerase chain reaction. When comparing baseline and final liver biopsies, a significant improvement (P <.001) was found in the histological activity index and in the necrosis, cytolysis, inflammation, and fibrosis scores. The histological diagnosis improvement in the final biopsy was significantly related (P <.001) to the time from seroconversion to the biopsy performance. All children had viral DNA on their final liver biopsy. In summary, seroconversion and ALT normalization are quite stable findings in children, and no differences in the long-term outcome between treated and untreated children were found. In light of the histological outcome, it seems unnecessary to perform a follow-up liver biopsy in these cases.     

Comparison of shelf-life estimates for a human insulin pharmaceutical preparation using the matrix and full-testing approaches

The design of a stability study is intended to establish a shelf-life based on testing a limited number of batches of a drug product, which is applicable to all future batches of the drug product manufactured under similar circumstances. In the FDA guidelines for stability testing of new drug products, the matrix design is suggested as the alternative statistical design to the full testing approach. In the last few years, the matrix design has received increasing attention from pharmaceutical companies in order to reduce the cost of stability studies. For this, the full and matrix stability test plans were used on three batches of human insulin pharmaceutical preparation stored under a kinetic mean temperature of 22.7 degrees C for 3 years. The statistical method was suggested by Ruberg and Stegeman (Biometrics, 1991, 47, 1059-1069) and Llabrés et al. (Int. J. Pharm. 2000, 204, 61-68), and was used for comparing batches, and the maximum allowable difference in slopes between batches was used as criteria for estimating a common shelf-life. The results obtained show the conservative nature of the matrix approach, although the difference between the matrix and full shelf-life was less than 1 month. The effect of the matrix method on shelf-life was also studied. The results showed that the model for estimating the shelf-life varied as a function of the permutation used, after testing for both slope and intercept poolability at alpha = 0.25. The batches should be pooled for both full testing and matrix design since the critical significance level required to obtain a power of 0.80 was achieved when the maximum allowable difference in slopes between batches was 1%/month, according to Ruberg and Stegeman. In contrast, when the proposed method by Llabrés et al. was used, the results varied in function of the maximum allowable difference in slopes.     

On relational possibilistic clustering

This paper initially describes the relational counterpart of possibilistic c-means (PCM) algorithm, called relational PCM (or RPCM). RPCM is then improved to better handle arbitrary dissimilarity data. First, a re-scaling of the PCM membership function is proposed in order to obtain zero membership values when the distance to prototype equals the maximum value allowed in bounded dissimilarity measures. Second, a heuristic method of reference distance initialisation is provided which diminishes the known PCM tendency of producing coincident clusters. Finally, RPCM improved with our initialisation strategy is tested on both synthetic and real data sets with satisfactory results.     

Classification of scene photographs from local orientations features

Natural image understanding is a very active and promising research domain both in psychology for visual perception modelling and in computer science for image retrieval. In this study, we investigate the efficiency of orientation distributions over the whole image in the scale space. The global distribution of the local dominant orientations (LDO) appears to be a powerful feature for discriminating between four semantic categories of real world scenes (indoor scenes, urban scenes, open landscapes, closed landscapes). The selected optimal scale is compatible with psychological experiments and classification performances show that a global representation of dominant orientations is a simple, efficient and compact method for scene recognition.     

Models and methods for frequency assignment with cumulative interference constraints

In this paper, a realistic modeling of interferences for frequency assignment in hertzian telecommunication networks is presented. In contrast with traditional interference models based only on binary interference constraints involving two frequencies, this new approach considers the case of cumulative disruptions that are modeled through a unique non‐binary constraint. To deal with these complex constraints, we propose extensions of classical integer linear programming formulations. On a set of realistic instances, we propose hybrid constraint programming and large neighborhood search solution methods to solve minimum interference and minimum span frequency assignment problems. We compare their performances with those of existing heuristics. Finally, we show how the end‐user benefits from using the cumulative model instead of the traditional one.     

Plasmon excitation and electron promotion in the interaction of slow Na ions with Al surfaces

We studied the energy distributions of electrons emitted in the interaction of slow Na⁺ ions with polycrystalline Al surfaces. To study sub-threshold plasmon excitation we performed measurements as a function of emission angle which showed the excitation of bulk plasmons, confirming the kinetic nature of the excitation process.

Electron spectra show narrow transition lines due to Auger decay in vacuum of sodium projectiles excited in the 2p-shell by electron promotion in collisions with Al target atoms. Several previously unidentified transition lines could be attributed to the autoionization of doubly excited projectiles.     

Apoptosis Pathways Triggered by a Potent Antiproliferative Hybrid Chalcone on Human Melanoma Cells

The World Health Organization reported that approximately 324,000 new cases of melanoma skin cancer were diagnosed worldwide in 2020. The incidence of melanoma has been increasing over the past decades. Targeting apoptotic pathways is a potential therapeutic strategy in the transition to preclinical models and clinical trials. Some naturally occurring products and synthetic derivatives are apoptosis inducers and may represent a realistic option in the fight against the disease. Thus, chalcones have received considerable attention due to their potential cytotoxicity against cancer cells. We have previously reported a chalcone containing an indole and a pyridine heterocyclic rings and an α-bromoacryloylamido radical which displays potent antiproliferative activity against several tumor cell lines. In this study, we report that this chalcone is a potent apoptotic inducer for human melanoma cell lines SK-MEL-1 and MEL-HO. Cell death was associated with mitochondrial cytochrome c release and poly(ADP-ribose) polymerase cleavage and was prevented by a non-specific caspase inhibitor. Using SK-MEL-1 as a model, we found that the mechanism of cell death involves (i) the generation of reactive oxygen species, (ii) activation of the extrinsic and intrinsic apoptotic and mitogen-activated protein kinase pathways, (iii) upregulation of TRAIL, DR4 and DR5, (iv) downregulation of p21^Cip1/WAF1 and, inhibition of the NF-κB pathway.     

An Approach to the Analysis of Mixing in Reactive Systems

A simple mixing approach for use in reactive systems is considered. This mixing approach has so far been applied to reburning and selective non‐catalytic reduction (SNCR) processes, two well‐known techniques to reduce NO_x emissions. Detailed kinetic models together with the mixing approaches, based on the work of Zwietering, are used to simulate both the chemistry and mixing of the reactants. Two different configurations for the mixing approach have been considered: the so‐called direct and reverse approach. The study includes a comparison between different experimental results obtained in pilot installations and theoretical results calculated with the present approach.     

Multiwalled carbon nanotubes functionalized with maleated poly(propylene) by a dry mechano-chemical process

Ball milling was used to graft maleated polypropylene (MAPP) on the surface of multiwalled carbon nanotubes (MWCNTs), with a view to preparing MWCNT/polypropylene composites with improved matrix/nanotube compatibility. The occurrence of the grafting reaction was evaluated by FTIR spectroscopy and the yield was quantified by thermogravimetric analysis, as a function of the milling time. Dispersion experiments confirmed the nanotube surface modification of the nanotubes since functionalized MWCNTs remained stably dispersed in an ethanol/xylene solution for more than 48 h after sonication. No evidences of significant structural damage after the mechano-chemical treatment were shown by Raman spectroscopy. Moreover, a layer attributable to the presence of grafted MAPP chains on MWCNT walls was clearly detected by transmission electron microscopy. The average thickness of this amorphous layer was evaluated and compared with quantitative TGA data.     

Bulk polymerization of styrene in presence of polybutadiene: Calculation of molecular macrostructure

In our previous publication the detailed molecular macrostructure generated in a solution polymerization of styrene (St) in the presence of polybutadiene (PB) at 60°C, was theoretically calculated. In this work, an extended kinetic mechanism that incorporates monomer thermal initiation, chain transfer to the rubber, chain transfer to the monomer, and the gel effect is proposed, with the aim of simulating a bulk high-impact polystyrene (HIPS) process. The mathematical model enables the calculation of the bivariate weight chainlength distributions (WCLDs) for the total copolymer and for each of the generated copolymer topologies and the univariate WCLDs for the free polystyrene (PS), the residual PB, and the crosslinked PB topologies. These last topologies are characterized by the number of initial PB chains per molecule; copolymer topologies are characterized by the number of PS and PB chains per molecule. The model was validated with published literature data and with new pilot plant experiments that emulate an industrial HIPS process. The literature data correspond to a dilute solution polymerization at a constant low temperature with chemical initiation and a bulk polymerization at a constant high temperature with thermal initiation. The new experiments consider different combinations of prepolymerization temperature, initiator concentration, and solvent concentration. One of the main conclusions is that most of the initial PB is transformed into copolymer. For example, for a prepolymerization temperature of 120°C with addition of initiator, the experimental measurements indicate that the final total rubber mass is approximately three times higher than the initial PB. Also, according to the model predictions, the final weight fractions are: free PS, 0.778; graft copolymer, 0.220; initial PB, 0.0015; and purely crosslinked PB, 0.0005. The final graft copolymer exhibits the following characteristics: average molecular weights, M _n,C = 492,000 and M _w,C = 976,000; average weight fraction of St, 0.722; and average number of PS and PB branches per molecule, 5.19 and 1.13, respectively. © 1996 John Wiley & Sons, Inc.