Prediction of response during interferon alfa 2b therapy in chronic hepatitis C patients using viral and biochemical characteristics: a comparison

Patients with chronic hepatitis C (n = 103) were treated for 24 weeks with interferon alfa 2b and followed up for 24 weeks after cessation of therapy (week 48). When hepatitis C virus (HCV) RNA at week 48 was used to assess interferon response, 15 (14.6%) were virological complete responders, and all have remained HCV RNA negative for a mean of 3 years. At week 48, 3 of 15 virological complete responders had elevated alanine transaminase (ALT) values. When serum ALT level was used at week 48 to determine response to interferon, 20 (19.4%) were biochemical complete responders. However, 8 of the 20 patients with normal ALT levels were HCV RNA positive at week 48, and 7 of these individuals have had a recurrence of elevated ALT levels within 3 years after cessation of treatment. These findings indicate that measurement of HCV RNA was more accurate than ALT in determining true responses to interferon therapy. Identification of nonresponders early during the course of interferon treatment showed that an elevated ALT level at week 12 was 92% predictive (odds ratio 3.7) but misidentified 33% (5 of 15) of the patients who were virological complete responders at week 48. In contrast, a positive HCV RNA at week 12 of treatment was 98% predictive (odds ratio 35.5) and misidentified only 6.7% (1 of 15) of the virological complete responders. Thus, positive HCV RNA at week 12 of therapy was more accurate in identifying eventual virological nonresponders than measurement of ALT at this time. Termination of interferon therapy in patients who were HCV RNA positive at week 12 would result in a 27% reduction in the direct medical costs and keep patients from undergoing unnecessary treatment. Therefore, testing for HCV RNA at week 12 to identify nonresponders and then discontinuing their treatment is practical, cost-efficient and beneficial both to patients and to third-party payers.     

Captopril modifies gene expression in hypertrophied and failing hearts of aged spontaneously hypertensive rats

The spontaneously hypertensive rat (SHR) exhibits a transition from stable compensated left ventricular (LV) hypertrophy to heart failure (HF) at a mean age of 21 months that is characterized by a decrease in alpha-myosin heavy chain (alpha-MHC) gene expression and increases in the expression of the atrial natriuretic factor (ANF), pro-alpha1(III) collagen, and transforming growth factor beta1 (TGF-beta1) genes. We tested the hypotheses that angiotensin-converting enzyme inhibition (ACEI) in SHR would prevent and reverse HF-associated changes in gene expression when administered prior to and after the onset of HF, respectively. We also investigated the effect of ACEI on circulating and cardiac components of the renin-angiotensin system. ACEI (captopril 2 g/L in the drinking water) was initiated at 12, 18, and 21 months of age in SHR without HF and in SHR with HF. Results were compared with those of age-matched normotensive Wistar-Kyoto (WKY) rats, and to untreated SHR with and without evidence of HF. ACEI initiated prior to failure prevented the changes in alpha-MHC, ANF, pro-alpha1(III) collagen, and TGF-beta1 gene expression that are associated with the transition to HF. ACEI initiated after the onset of HF lowered levels of TGF-beta1 mRNA by 50% (P<.05) and elevated levels of alpha-MHC mRNA two- to threefold (P<.05). Circulating levels of renin and angiotensin I were elevated four- to sixfold by ACEI, but surprisingly, plasma levels of angiotensin II were not reduced. ACEI increased LV renin mRNA levels in WKY and SHR by two- to threefold but did not influence LV levels of angiotensinogen mRNA. The results suggest that the anti-HF benefits of ACEI in SHR may be mediated, at least in part, by effects on the expression of specific genes, including those encoding alpha-MHC, ANF, TGF-beta1, pro-alpha1(III) collagen, and renin-angiotensin system components.     

On the stabilization of a cable with a tip mass

In this note, we consider a vertical cable which is pinched at the upper end. A mass is attached at the lower end where a control force is also applied. We show that this hybrid system is uniformly stabilized by choosing a suitable control law for the control force depending on the velocity and angular velocity at the free end. Moreover for specific values of the feedback coefficients, we obtain the rate of decay of the energy of the system     

Adapting selected nucleic acid ligands (aptamers) to biosensors

A flexible biosensor has been developed that utilizes immobilized nucleic acid aptamers to specifically detect free nonlabeled non-nucleic acid targets such as proteins. In a model system, an anti-thrombin DNA aptamer was fluorescently labeled and covalently attached to a glass support. Thrombin in solution was selectively detected by following changes in the evanescent-wave-induced fluorescence anisotropy of the immobilized aptamer. The new biosensor can detect as little as 0.7 amol of thrombin in a 140-pL interrogated volume, has a dynamic range of 3 orders of magnitude, has an inter-sensing-element measurement precision of better than 4% RSD over the range 0-200 nM, and requires less than 10 min for sample analysis. The aptamer-sensor format is generalizable and should allow sensitive, selective, and fast determination of a wide range of analytes.     

Neurotoxicity of CI-980, a novel mitotic inhibitor

PURPOSE: To compare the simulated keratometric results of the PAR CTS and the EyeSys corneal imaging systems with Javal keratometer readings in keratoconus eyes, in eyes after corneal grafting, and in healthy eyes. SETTING: Cornea Service, Wills Eye Hospital, Philadelphia, Pennsylvania, USA. METHODS: This prospective study evaluated 69 patients divided into three groups (keratoconus; 6 to 12 months postkeratoplasty; normal corneas) treated at the cornea service. The eyes were measured with each of the three instruments. Keratometry results and number of attempts needed to obtain the results were collected. RESULTS: Thirty keratoconus, 18 transplanted, and 21 normal corneas were examined. The PAR CTS Imaged all corneas and the EyeSys, 86% (P = .000627). The PAR CTS and Javal flat and steep K-readings in all three groups were the same. The EyeSys simulated keratometry results were lower than those of Javal keratometer in the flat K (P < .00001) and steep K (P < .00001) in the normal group and in the steep K in the transplanted cornea group (P = .00823). The EyeSys also measured less astigmatism than the Javal in the normal (P = .00124) and transplanted cornea groups (P = .00376). CONCLUSION: The PAR CTS was better able than the EyeSys to provide keratometric values that agreed with those obtained with the Javal keratometer.     

Effect of extraction methods and UHT treatment conditions on the level of isoflavones during soymilk manufacture

The objective of this study was to compare the effect of hot and cold grinding as well as the effect of direct and indirect ultra high temperature (UHT) treatment conditions on the level of isoflavones during the manufacture of soymilk. Soymilks were manufactured from dehulled soybeans by hot grinding or cold grinding processes. After inactivation of lipoxygenase at 85 °C, the resulting slurries were decanted and supernatants were held at 120 °C for 80 s to inactivate the trypsin inhibitor. The decanted soya bases were cooled and subjected to different temperature/time regimes by direct and indirect UHT treatments. Samples were drawn at different points in the processing operation and a reversed phase high performance liquid chromatography method was used to determine the concentration of isoflavones. Results showed that hot grinding caused a higher extraction of isoflavones into the soymilk than the cold-grinding process. However, direct or indirect heating in the UHT process did not significantly influence the concentration of isoflavones.     

Piecewise empirical model (PEM) of resistive memory for pulsed analog and neuromorphic applications

With the end of Dennard scaling and the ever-increasing need for more efficient, faster computation, resistive switching devices (ReRAM), often referred to as memristors, are a promising candidate for next generation computer hardware. These devices show particular promise for use in an analog neuromorphic computing accelerator as they can be tuned to multiple states and be updated like the weights in neuromorphic algorithms. Modeling a ReRAM-based neuromorphic computing accelerator requires a compact model capable of correctly simulating the small weight update behavior associated with neuromorphic training. These small updates have a nonlinear dependence on the initial state, which has a significant impact on neural network training. Consequently, we propose the piecewise empirical model (PEM), an empirically derived general purpose compact model that can accurately capture the nonlinearity of an arbitrary two-terminal device to match pulse measurements important for neuromorphic computing applications. By defining the state of the device to be proportional to its current, the model parameters can be extracted from a series of voltages pulses that mimic the behavior of a device in an analog neuromorphic computing accelerator. This allows for a general, accurate, and intuitive compact circuit model that is applicable to different resistance-switching device technologies. In this work, we explain the details of the model, implement the model in the circuit simulator Xyce, and give an example of its usage to model a specific \(\hbox {Ta}/\hbox {TaO}_{\mathrm{x}}\) device.     

Contribution of the space charge to the grain boundary energy in yttria-stabilized zirconia

A model based on the effect of a modest applied dc electric field on grain growth is proposed for the contribution of the space charge to the grain boundary (GB) energy in 3 mol % yttria-stabilized zirconia (3 YSZ). The model considers that the total GB energy \( \gamma_{\text{b}}^0 \) (the capillary driving force for grain growth) consists of three major components: (a) \( \gamma_{\text{b}}^\varSigma \) due to the misorientation between neighboring grains, (b) \( \gamma_{\text{b}}^{\text{s}} \) due to the size misfit between the segregated solute and the solvent cations, and (c) \( \gamma_{\text{b}}^{\text{e}} \) the electrostatic (space charge) component, which results from the segregation of the aliovalent yttrium ions to the grain boundaries. The former two components combined comprise 40 % of the total GB energy in 3 YSZ and the electrostatic component 60 %. Based on the model, the calculated magnitudes of the three components were in qualitative accord with theoretical considerations and with values reported in the literature. A reduction in \( \gamma_{\text{b}}^{\text{e}} , \) and in turn in \( \gamma_{\text{b}}^0 , \) results from the bias exerted by the applied field on the space charge potential that occurs with the segregation of the yttrium ions to the grain boundaries. The observed reduction of grain growth in 3 YSZ by an applied electric field is attributed mainly to the reduction in \( \gamma_{\text{b}}^{\text{e}} \) by the field.     

A situated approach to the acquisition of shared SA in team contexts

Theories of team situation awareness (SA) differ in the information they require operators to have for effective coordination. Endsley stresses shared SA, whereas distributed SA argues that coordination involves transactive and compatible SA. We distinguish between weak and strong shared SA, and argue the latter enhances communication and increases team cohesion. Although we agree with Endsley on the importance of shared SA, we argue her account of how it is acquired exceeds the working memory capacity of individual team members. We offer an account consistent with our situated SA perspective that claims individuals off-load information to their environment whenever possible to minimise effortful internal processing. We argue that our approach, in conjunction with Pickering and Garrod's (2004, Towards a mechanistic psychology of dialogue. Behavioral and Brain Sciences, 27, pp. 169–226) interactive-alignment model, can explain how shared SA is acquired, relying on automatic processes enacted when individuals interact in conversations. This approach can be used to study team SA in many complex and distributed systems.