Emergence and takeover of YMDD motif mutant hepatitis B virus during long-term lamivudine therapy and re-takeover by wild type after cessation of therapy

Treatment of hepatitis B virus (HBV) with lamivudine is effective in suppressing virus replication and results in reduced inflammatory activity. However, the emergence of lamivudine-resistant mutant virus, with amino acid substitution in the YMDD motif of DNA polymerase, has been reported. We report the emergence and takeover of YMDD mutant and re-takeover by wild type during and after long-term lamivudine therapy. YMDD mutants were detected in five patients who showed DNA breakthrough (HBV DNA becoming detectable after a period of DNA negativity), which occurred after 9 to 14 months of lamivudine therapy. Four of five mutants had amino acid sequence YIDD, and the remaining mutant had YVDD. Patients with high HBV-DNA titer and/or hepatitis B e antigen tended to develop breakthrough (P = .038). Using a sensitive and specific polymerase chain reaction (PCR)-based method developed in this study, the emergence of YMDD mutants was detected 1 to 4 months before DNA breakthrough, but not detected in any of the pretreatment sera. The mutants were predominant at breakthrough, but were replaced by wild-type virus 3 to 4 months after cessation of therapy in the two patients who discontinued therapy. One of these patients had a relapse of hepatitis. Mutant continued to replicate in the remaining three patients who continued to receive treatment, and relapse occurred in only one of these patients. Our results suggest that the replication of YMDD mutant viruses is less than wild type and is re-overtaken by wild type after cessation of therapy. Re-administration of lamivudine, possibly combined with other antiviral therapy, might be useful in some patients experiencing hepatitis with lamivudine-resistant variants.     

Facial identification system based on a high‐speed matching algorithm for isodensity lines

In this paper, a high‐speed personal identification system which is adaptable for slant faces is presented. In the proposed method, the 25 facial images which are taken with different angles are registered in the database as reference images. The similarity of an input image is first examined between all registered images and the three facial images, which are similar to the input image, are then extracted as the candidate facial images. The isodensity map, which is expected to have the maximum similarity to the input image, is created by the interpolation between two candidate images and the input facial image is judged identical or not with the interpolated images. A template matching is adopted to obtain a similarity between two isodensity lines. In general, template matching requires a lot of time to obtain maximum similarity, while on the other hand it is very simple to use. To reduce the processing time for the matching efficiently, the techniques which are suited for the line pictures and the Sequential Similarity Detection Algorithm (SSDA) are adopted. Computer simulation using 50 people shows an accuracy of 95.2% correct discrimination. In addition, processing time is reduced to approximately 1/12. From the experimental results, the prospects of using this method are very encouraging. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(4): 31–41, 2003; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.10147     

Stability of Large Space Structures Preserved Under Failures of Local Controllers

This note considers position and attitude control of large space structures composed of a number of subsystems (substructures) interconnected by flexible links. A decentralized control law of dynamic displacement feedback compatible with subsystems is applied under the assumption that sensors and actuators are collocated. It has been known that the overall closed-loop system is robustly stable against uncertainties in mass, damping, and stiffness, if rigid modes of each subsystem are controllable and observable. The objective of this note is to derive conditions for the overall system to be stable even when some local controllers fail. The conditions are expressed in terms of the stiffness (or damping) matrices and interconnection location matrices of the subsystems whose local controllers fail     

Polymer microstructure generated by laser stereo-lithography and its transfer to silicon substrate using reactive ion etching

Micro-fabrication combining stereo-lithography with reactive ion etching is proposed. Three-dimensional polymer structures smaller than 1 mm are fabricated on silicon wafer by He-Cd (325.0 nm) laser stereo-lithography. Using the polymer structure having a high-aspect ratio as resist for deep reactive ion etching, the microstructure is transferred to the silicon substrate with an etching ratio of 0.5. The proposed technique has been demonstrated by the fabrication of lens-like structures.     

Melt growth and characterization of Mg2Si bulk crystals

We have grown Mg₂Si bulk crystals by the vertical Bridgman method using a high-purity Mg (6N-up) source. The grown crystals were single-phase Mg₂Si and had well-developed grains (1-5 mm³). Laue observations and SEM-EDX observations confirmed that crystalline quality in the grains was single crystal with stoichiometric composition. Electron concentration of the single crystalline specimens grown from 6N-up-Mg was 4.0 × 10¹⁵ cm^− 3 at room temperature (RT). This value is more than one order of magnitude lower than that of specimens grown from 4N-Mg [(5-7) × 10¹⁶ cm^− 3]. The Hall mobility of 14,500 cm²/Vs was observed at 45 K in the crystals grown from 6N-up-Mg. We also found that Al impurity plays an important role in the crystals grown from a low-purity Mg source. From the optical absorption measurement, we estimated that the indirect energy gap was about 0.66 eV at 300 K and about 0.74 eV at 4 K.     

Design and modification of steam generator safety system of FBR MONJU

MONJU is a prototype fast breeder reactor (FBR) in Japan. The sodium–water reaction in the steam generator (SG) is one of the important safety assessment items for a sodium cooled reactor like MONJU. MONJU is equipped with hydrogen gas detectors for the small water leak detection, gas pressure gauges for the medium leak and sensors of rupture discs for the large leak. As a design basis accident, one tube failure then failure propagation of neighboring three tubes is assessed to verify the structural integrity of the secondary components. A latest evaluation method on the design margin against the overheating tube rupture showed that the present SG system had not an enough margin in the worst case. For improving the margin, it needs to shorten the time of the sodium–water reaction by earlier water leak detection in the SG and sooner water ejection from the SG tubes. Therefore, MONJU is now carrying out the following modification works: (1) addition of steam relief valves, (2) addition of a gas pressure gauge with changing the interlock logic and lowering the trigger level, (3) reducing the opening of the valves on the SG gas flow line to the dump tank because of earlier detection for the pressure rise. After this modification, the design margin of the SG system will be sufficiently improved.     

Dissolution properties of some fly ash fillers applying to geopolymeric materials in alkali solution

Dissolution properties of three kinds of fly ash including a Pressurized Fluidized Bed Combustion (PFBC) ash from a novel type of fluidized bed combustion boiler have been studied by leaching in different concentrations of caustic soda solution up to 15 N at 25 °C and 80 °C, stirring for 1 h with liquor/solid ratio = 10. Liquors sampled by a centrifugal separator were chemically analyzed by ICP technique. A blast furnace slag was also studied for reference. Results showed that Ca²⁺ dissolved relatively large amount in genuine water, but no marked dissolution was detected with increasing NaOH concentrations of the leaching solution. No enhanced dissolution of Al³⁺ was detected for ordinary fly ashes collected from pulverized coal combustion boilers even with increasing concentrations of solution at 25 °C, whereas enhanced dissolution of Al³⁺ was observed at 80 °C, when 5 N was reached and more. On the contrary, appreciable increasing was noted on the dissolution of Si⁴⁺ with increasing NaOH concentrations even at 25 °C for the ordinary fly ashes and the Si⁴⁺ dissolution became enhanced at 80 °C, specifically in 5 N and more.     

Stress intensity factor analysis of an interface crack between dissimilar anisotropic materials under thermal stress using the finite element analysis

New numerical methods were presented for stress intensity factor analyses of two-dimensional interfacial crack between dissimilar anisotropic materials subjected to thermal stress. The virtual crack extension method and the thermal M-integral method for a crack along the interface between two different materials were applied to the thermoelastic interfacial crack in anisotropic bimaterials. The moving least-squares approximation was used to calculate the value of the thermal M-integral. The thermal M-integral in conjunction with the moving least-squares approximation can calculate the stress intensity factors from only nodal displacements obtained by the finite element analysis. The stress intensity factors analyses of double edge cracks in jointed dissimilar isotropic semi-infinite plates subjected to thermal load were demonstrated. Excellent agreement was achieved between the numerical results obtained by the present methods and the exact solution. In addition, the stress intensity factors of double edge cracks in jointed dissimilar anisotropic semi-infinite plates subjected to thermal loads were analyzed. Their results appear reasonable.     

Evolution of the nutritional support pattern in pediatric intensive care

OBJECTIVES: To evaluate patterns of usage and monitoring of nutritional support in a Pediatric ICU of a teaching hospital and the role of an education program in nutritional support given throughout the resident physician training. DESIGN: In a historical cohort study, records from children who received nutritional support during the year 1992 were analyzed. Thereafter a continuing education program in Nutritional Support was conveyed to the residents. In a second phase of the study, the same parameters were reevaluated in children who received nutritional support throughout the year 1995. SETTING: Pediatric Intensive Care Unit of Department of Pediatrics, Escola Paulista de Medicina. PATIENTS: All the children who were given nutritional support during a period of five days or more. Based on this criteria 37 children were selected for the first phase of this study, and 35 for the second one. INTERVENTION: The education program included theoretical lectures about basic themes of nutritional support and journal article reading sessions. It was given to successive groups of residents on a weekly schedule. MEASUREMENTS: Daily records of fluid, protein, caloric and micronutrient supply, nutritional assessment and metabolic monitoring. RESULTS: In the first phase of the study, an exclusively parenteral route was utilized for 80.5%, and a digestive route 19.5% of the time period. Nutritional assessment was performed on 3 children; no patient had the nutritional goals set. The nitrogen to nonprotein calories ratio and the vitamin supply were inadequate, whilst the supply of trace elements was adequate except for zinc. Nutritional monitoring was performed on almost all patients but without uniformity. In the second phase, the exclusive parenteral route was used for 69.7% and the digestive route for 30.3% of the time period; no significant increase in the use of the digestive route was detected. The nonprotein calories to nitrogen ratio and micronutrient supply were adequate. The frequency of nutritional assessment increased, but deficiency in nutritional monitoring and infrequent enteral feeding were still detected. CONCLUSION: There were deficiencies in the implementation of nutritional support, which were partially corrected in the second phase of the study by the training of the residents. Reinforcement of the education program, which should be applied to the whole medical staff, and the organization of a multidisciplinary team in charge of coordinating the provision of nutritional support are suggested.     

Severe antecollis during antipsychotics treatment: a report of three cases

1. The authors report on three patients with severe antecollis that developed after chronic treatment with antipsychotics. These patients had been treated with neuroleptics for their delusions and hallucinations. Antecollis is a rare form of tardive dystonia that has drawn little attention. To our knowledge, there have been no reports on this disorder. 2. The patients developed the symptom after receiving a number of antipsychotics for 4 months to 14 years. Neither discontinuation of antipsychotics nor administration of anticholinergic agents affected the symptom. 3. Although spontaneous improvement of dystonia was obtained after several months without any specific treatment in one patient, the symptom persisted for several years in another. The last patient could not be followed after discharge from our hospital since she and her family did not come to the hospital. 4. Severe antecollis may cause disturbances in various functions, such as vision, speaking and swallowing. Forward bending of the neck may cause inspiratory obstruction. Severe antecollis may not be unusual and psychiatrists should be aware of this symptom in routine clinical practice.