Quantitative molecular monitoring of HIV-1 RNA during antiretroviral therapy

Plasma HIV-1 RNA testing was used to monitor 43 HIV-1 infected patients newly placed on antiretroviral therapy or whose therapy had been recently changed. A polymerase chain reaction kit was used to measure HIV-1 RNA in clinical samples or frozen plasma. The cutoff of this test was 200 RNA copies/ml. The first group (11 patients) was stable on long-term zidovudine monotherapy when switched to stavudine. The HIV-1 RNA of three patients who had a regular decline in CD4+ T cell count did not change despite this switch, with a mean follow-up of 630 days. The HIV-1 RNA copy numbers of eight patients whose CD4+ T cell counts were stable declined an average of 0.53 log10 between days 90 and 650. The second group (14 patients) was on long-term zidovudine monotherapy and had declining CD4+ T cell counts over the past 6 months. Lamivudine was added to this regimen on day 0. HIV-1 RNA copy number decreased rapidly within 30 d, reaching -0.86 log10 on day 90, and this effect was maintained thereafter, with a mean follow-up of 161 days. There was a concomitant mean gain of +33 CD4+ T cells on day 90. The third group (nine patients) had never received anti-retroviral therapy and was given zidovudine+didanosine. HIV-1 RNA copy number decreased in all cases but one, reaching -1.31 log10 on day 150. This decrease was transient in three cases. The last group (nine patients) had also not had previous anti-retroviral therapy and was given zidovudine + didanosine + lamivudine in combination. HIV-1 RNA copy numbers declined rapidly in all cases, to below the cutoff in eight cases within a mean period of 50.5 days. The CD4+ cell counts increased by 164 cells/microliter on day 14 and by 201 cells/microliter on day 180. The response to therapy of the total population of 43 patients varied according to cases. The relative changes in p24 antigen compared to HIV-1 RNA also differed between patients. Measurement of HIV-1 viremia appears to be a valuable tool in current practice for individualizing therapy.     

Identification of osteopontin in human dental calculus matrix

Osteopontin is a prominent non-collagenous component of bone matrix, although it is expressed in several other tissues. Recently, osteopontin was reported to be involved in urinary stone formation and atherosclerotic lesions of the aorta, suggesting that it may be a key protein associated with these types of pathological mineralization. In this study, whether or not human dental calculus contains osteopontin was investigated by immunoblotting and immunohistochemical analyses. After extraction of calculus proteins with EDTA and separation of the proteins by electrophoresis, immunoblotting analysis revealed the presence of osteopontin. Two forms of osteopontin appeared at 61 and 68 kDa on 10% polyacrylamide gel and the proteins were digested with thrombin, a highly specific protease. Moreover, immunohistochemical analysis revealed that osteopontin was localized in dental calculus adherent to tooth roots. These findings indicate that osteopontin is, in fact, present in human dental calculus and may be involved in calculus formation as the stone matrix.     

Issues affecting advanced passive light-water reactor safety analysis

Next generation commercial reactor designs emphasize enhanced safety by means of improved safety system reliability and performance. These objectives are achieved via safety system simplification and reliance on immutable natural forces for system operation. Simulating the performance of these safety systems will be central to analytical safety evaluation of advanced passive reactor designs. Yet, the characteristically small driving forces of these safety systems pose challenging computational problems to current thermal-hydraulic systems analysis codes. Additionally, the safety systems generally interact closely with one another, requiring accurate, integrated simulation of the nuclear steam supply system, engineered safeguards and containment. Furthermore, numerical safety analysis of these advanced passive reactor designs will necessitate simulation of long-duration, slowly-developing transients compared with current reactor designs. The composite effects of small computational inaccuracies on induced system interactions and perturbations over long periods may well lead to predicted results which are significantly different than would otherwise be expected or might actually occur. Comparisons between the engineered safety features of competing U.S. advanced light water reactor designs and analogous present day reactor designs are examined relative to the adequacy of existing thermal-hydraulic safety codes in predicting the mechanisms of passive safety. Areas where existing codes may require modification, extension or assessment relative to passive safety designs are identified. Conclusions concerning the applicability of these codes to advanced passive light water reactor safety analysis are presented.     

Using neural networks to select wavelet features for breast cancerdiagnosis

This study focuses on improving microcalcification classification by establishing an efficient computer-aided diagnosis system that extracts Daubechies-4 and biorthogonal wavelet features. These wavelets were chosen because they have been used in military target recognition and fingerprint recognition research with images characterized by low contrast, similar to mammography. Feature selection techniques are employed to further increase classification performance. The artificial neural network feature selection techniques are complemented by a conventional decision boundary-based feature selection method. The results using the wavelet features are compared to more conventional measures of image texture, angular second moment, and Karhunen Loeve coefficients. The use of alternative signal processing to compare wavelet and neural techniques allows for a measure of the problem difficulty. It is concluded that advances and contributions have been made with the introduction of two novel feature extraction methods for breast cancer diagnosis, wavelets and eigenmasses. Additionally, feature selection techniques are demonstrated, compared, and validated, transforming adequate discrimination power into promising classification results     

Caring for dying children: nurses' experiences

Interviews with 25 nurses in this grounded theory study show that when nurses recognized that a child's death was inevitable, they struggled with both grief distress and moral distress. Their distress occurred within the context of the nurse-patient relationship. Nurses employed a range of strategies to manage their distress. Several conditions facilitated or constrained nurses' strategies, and resulted in far-reaching implications both professionally and personally.