Human-factors aspects of designing computer voice output systems as communication aids for the disabled

Possible ways of meeting the user's needs when designing communication aids with synthetic voice output are discussed. The points raised evolved from a case study of the development of microcomputer based systems which the blind people can use to read page-oriented text. The ideas discussed in this paper may also enhance the performance of blind computer programmers. Essential facilities in communication aids for the non-vocal are also inferred.     

Regression of morphological alterations and oxidative stress-related parameters after acute lindane-induced hepatotoxicity in rats

Changes in rat liver oxidative stress-related parameters, morphological alterations, as well as circulating and tissue levels of lindane were studied 1-7 days after the administration of a single dose of 60 mg of lindane/kg. One day after lindane treatment, a significant enhancement in the oxidative stress status of the liver was observed, characterized by an increase in thiobarbituric acid reactants production and in the microsomal generation of superoxide radical (O.-2) coupled to cytochrome P450 induction, and a decrement in the activity of superoxide dismutase (SOD) and catalase. Consequently, the O.-2 production/SOD activity ratio was enhanced two-fold. In this condition, light microscopy studies revealed the incidence of liver lesions in periportal areas, together with significant changes at the mitochondrial level observed by electron microscopy, which coincide with the maximal levels of lindane in the liver, adipose tissue, plasma and whole blood. Changes in oxidative stress-related parameters observed after 1 day of lindane treatment regressed to normal from the third day and thereafter, together with the decrement in circulating and tissue levels of the insecticide. It is concluded that morphological and oxidative stress-related changes induced in the liver by acute lindane intoxication are readily reversible, depend on the hepatic content of the insecticide, and seem to be conditioned by the changes in O.-2 generation.     

Automatic timing of user-system interaction as an evaluation aid for microsystems

A technique is described for modifying a microcomputer-based system during the development stage to monitor its own performance. This evaluation aid reveals points of inefficiency within the system which are not easily identified by system users.     

Differential use of the betaL subunit of the type I interferon (IFN) receptor determines signaling specificity for IFNalpha2 and IFNbeta

The signaling specificity for cytokines that have common receptor subunits is achieved by the presence of additional cytokine-specific receptor components. In the type I interferon (IFN) family, all 14 subtypes of IFNalpha, IFNbeta, and IFNomega bind to the same alpha and betaL subunits of the type I IFN-R, yet differences in signaling and biological effects exist among them. Our data demonstrate that IFNalpha2 and IFNbeta utilize different regions of the betaL subunit for signaling. Thus, in contrast to other cytokine systems, signal diversity in the type I IFN system can be accomplished within the same receptor complex by utilizing different regions of the same receptor subunits.     

A successful system of scientific data audits for clinical trials. A report from the Cancer and Leukemia Group B

OBJECTIVE: To report on data collected during on-site audits of source documents in the Cancer and Leukemia Group B (CALGB). DESIGN: A retrospective review of audit reports in four audit cycles. SETTING: A cooperative group of institutions conducting clinical trials in cancer treatment. PARTICIPANTS: Patients taking part in clinical trials at collaborating CALGB institutions, members of the CALGB Data Audit Committee, and group chairmen of CALGB. MAIN OUTCOME MEASURE: The results of 691 institutional audits conducted by the CALGB in 1982 through 1992 with comparisons of main CALGB institutions vs affiliates. RESULTS: In four full reviews of all participating institutions in the CALGB, 3787 patients have had their on-site medical records compared with data submitted to the CALGB Data Management Center. Compliance with federal regulations for oversight by an institutional review board improved from a deficiency rate of 28.0% among the main institutions and 49.6% of the affiliate institutions in the first audit cycle to respective figures of 13.3% and 28.2% in the fourth cycle. Consent form deficiencies also dropped overall from 18.5% in the first cycle to 3.9% in the fourth. Patient eligibility was verified by auditors in 94.5%, and assessment of tumor changes in response to treatment was verified in 96.4% in the fourth cycle; both figures were only slightly lower in the first cycle. Two instances of scientific impropriety were discovered for a rate of only 0.28% of all audits. Both occurred prior to 1984, and none have occurred since. Major protocol deviations in drug dosing have held steady at about 11% over four audit cycles. Over the 11-year period of audits, three main institutions and 96 affiliate institutions have discontinued CALGB membership due solely, or at least partly, to unfavorable audit results. CONCLUSION: Scientific improprieties have occurred very rarely in clinical trials conducted by the CALGB. Protocol compliance in assessing patient eligibility and tumor responses has been high. Attention to administrative matters of consent forms, institutional review board approval, and ancillary data submission has measurably improved in the CALGB, which is at least partly due to the pressure from this on-site peer review of investigator performance.     

Fatal hyperthrombotic condition complicating nephrotic syndrome

A twenty-year old woman was admitted to hospital with impaired consciousness and a left hemiparesis. A cerebral CAT-scanning was reported normal. Convulsions and respiratory insufficiency made intubation and mechanical ventilation necessary. Laboratory examination showed an extremely low concentration of albumin in plasma (109 microM) and gross albuminuria was present. No other signs of renal failure occurred. The patient deteriorated during three days and died with signs of cerebral incarceration, despite efforts to reduce intracranial pressure. Autopsy showed a large thrombus of the sagittal sinus as the presumed cause of death. No thrombus was found in the renal vein. The association between nephrotic syndrome and thrombosis is discussed.     

The release and absorption of small ribonucleoprotein complexes (alpha RNPs) in cultures of transformed rat fibroblasts and human epidermoid carcinoma

The release of alpha RNPs and their absorbtion by the cells from culture medium were studied. The rat fibroblasts of parental serum-dependent cell line LRec-1, and of selected serum-free cell line LRec-1sf rapidly released and absorbed alpha RNPs. In the latter case, both auto- and heterologous alpha RNPs were seen to penetrate, whereas only autologous alpha RNPs entered LRec-1 cells. Besides, the ability to rapid export and absorbtion of autocrine alpha RNPs was demonstrated for human epidermoid carcinoma cell line A431. Both LRec-1 and LRec-1sf cells expressed mRNAs with homology to ID-like nucleotide sequences, the level of mRNA expression decreasing markedly when serum-dependent LRec-1 cells were grown in serum-free medium.     

Discriminative power of visual evoked potential characteristics in multiple sclerosis

To investigate the discriminative power of pattern-reversal visual evoked potential characteristics (peak latencies and amplitude) and to test whether the addition of visual evoked potential amplitude can increase the power of the visual evoked potential in the diagnosis of multiple sclerosis, we retrospectively studied visual evoked potentials in 59 patients with definite multiple sclerosis and 126 control subjects. Two check sizes (17' and 10') were used. Females had significantly higher amplitudes and shorter latencies than males. N80 latency showed a gradual increase and P100 amplitude a decrease with age. P100 latency was stable between the ages of 20 and 55 years but was increased in childhood and the elderly. The significance of visual evoked potential peak latencies and amplitude in separating the two groups was investigated by means of a (multivariate) discriminant analysis. The visual evoked potential with a pattern of 10' could be measured in 58% of patients with multiple sclerosis. The exclusive use of the P100 amplitude in the discriminant analysis resulted in a percentage of correctly classified cases of 84%, whereas for P100 and N80 latency it was 85% and 90%, respectively. With the 17' pattern, the N80 latency yielded also a higher correct percentage than did the P100 latency. Although N80 latency is, to a greater extent than P100 latency, influenced by age, sex and size of stimulus pattern, when these influences are accounted for, the N80 latency is a more sensitive measure than P100 latency in the classification of multiple sclerosis. Combined use of latency and amplitude for discriminant analysis yielded no significant improvement of the percentage of correctly classified cases.     

Electrical impedance spectroscopy and electrical response in metal/non-metal systems

A new analysis of the electrical response of a macroscopic solid state system to an arbitrary electrical voltage input is presented. The results indicate that with a small, sinusoidal voltage input within the classical frequency range (ω < 10¹⁰Hz), the electrical response in spatially homogeneous systems mirrors first of all the static, spatial distribution of the mobile charge carrier density through the local electrical conductivity relaxation time. This enables any system, inclusive interface and electrical contact regions to be modelled by a simple, passive R, C electrical network, where each of the network elements has a very direct physical meaning. Ultra pure, single crystal silicon, pure polycrystalline silicon and Al-Al₂O₃-Au metal-insulator-metal (MIM) structure are used as illustrative examples.     

HPLC analysis of quinolinic acid, a NAD biosynthesis intermediate, after fluorescence derivatization in an aqueous matrix

Quinolinic acid (2,3-pyridine dicarboxylic acid), a biological intermediate in nicotinamide adenine dinucleotide (NAD) biosynthesis in microbes and mammals and a brain excitotoxin, is not fluorescent nor electrochemically active and its detection sensitivity by UV absorption is comparatively low. Quinolinic acid was successfully derivatized in water-based samples by monodansylcadaverine, a fluorescence tag, and analysed by high-performance liquid chromatography (HPLC). No extraction procedure was needed and quinolinic acid was activated by water-soluble carbodiimide and derivatized under mild conditions. As little as 3 pmol (500 pg) of quinolinic acid in 5 microliter of artificial cerebrospinal fluid sample volume could be derivatized and detected at a signal to noise ratio of 3:1. Thus, detection on a mass basis by HPLC after fluorescence derivatization is about 300 times as sensitive as direct determination of quinolinic acid by UV absorbance (500 pg vs 150 ng). A variety of activators, fluorescent tags and reaction solvents and conditions were tested but found to be less effective.