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Does pursuit abnormality in schizophrenia represent a deficit in the predictive mechanism?

Although an abnormality of smooth pursuit eye movement has been consistently noted in schizophrenia, the underlying ocular motor pathophysiology is unknown. It is unclear whether the abnormality represents deficits in processing of information provided by the moving target, generation of pursuit eye movements, or other ocular motor and related cognitive processes. To evaluate the ability to process information provided by a moving target, saccadic accuracies were studied in step-ramp and single step tasks. Schizophrenic (with and without tardive dyskinesia [TD]) and normal subjects made equally accurate initial corrective saccades to the moving target. Thus, when the target jumped and then smoothly moved (creating a position and a velocity error on the retina), the patients were able to process retinal motion information and generate a normally accurate saccadic response. After the initial corrective saccade, both groups followed the target with a combination of pursuit eye movements and occasional catch-up saccades. During this period, the retinal velocity error is minimal because the eye approximates the target motion, and the major source of target motion information both for the smooth pursuit and saccadic responses is extra-retinal (i.e., predictive mechanism). The accuracies of catch-up saccades were significantly lower in the schizophrenic patients than in the normal subjects. During this period, overall pursuit performance, measured by pursuit gain, was also significantly worse in the patients. Accuracies of subsequent catch-up saccades, but not initial corrective saccades, significantly predicted the pursuit gain. Low pursuit gain was associated with high numbers of saccades per time spent in pursuit, which were similar in both schizophrenic subgroups (i.e., with and without TD), but were only significantly higher in the patients with TD than in the normal subjects. These preliminary data suggest that schizophrenic patients are able to process retinal motion information but have difficulties in using extra-retinal motion information to generate an appropriate saccadic response.

Adult↗

Solution composition dependent variation in extinction coefficients for p-nitroaniline.

The dependence of the extinction coefficients for para-nitroaniline on solution composition has been investigated. The p-nitroaniline absorption spectrum is red-shifted with increasing ionic strength, with the consequence that the extinction coefficients at fixed wavelengths may vary significantly. The isosbestic wavelength for peptide p-nitroanilide/p-nitroaniline mixtures is similarly shifted. Poly(ethylene glycol) and bovine albumin, two additives frequently employed to eliminate enzyme loss from adsorption to cuvette and dilution vessel surfaces, also induce shifts in the p-nitroaniline spectrum. The use of a difference extinction coefficient at 381 nm, the p-nitroaniline maximum wavelength, is proposed to minimize the error resulting from solution composition dependent spectral shifts.

Aniline Compounds↗

Estrogen receptor analyses in breast cancer: comparison of monoclonal immunohistochemical and biochemical methods.

The estrogen receptor content in 100 female breast carcinomas was determined using the biochemical dextran-coated charcoal (DCC) method and the monoclonal estrogen receptor immunocytochemical assay (ER-ICA). Great care was taken to make procedures optimal in order to minimize preanalytical errors. A statistically highly significant correlation was found between the results of the two methods, which were qualitatively in accordance in 91 cases, while nine gave a negative ER-ICA but a weak positive DCC result. The quantitative correlations were also statistically significant but varied considerably in individual cases. Under optimal conditions, ER-ICA provides results similar to the DCC method, but it is still uncertain if it can stand alone in routine diagnosis.

Antibodies, Monoclonal↗

Polymerase chain reaction assay of mRNA using 28S rRNA as internal standard.

A method is developed for PCR assay of mRNA using 28S rRNA as internal standard and its applicability is reported for 4 types of mRNA. It consists of reverse transcription of total RNA using primers selective for 28S rRNA and the message of interest. Routinely the 28S reaction mix is diluted 20,000-fold and the dilution error is minimized by adding 10 microCi of 3H2O before the dilution and determining the level of 3H before and after the dilution. Aliquots from the diluted 28S mix and the undiluted reverse transcripts are co-amplified by PCR in the presence of 32P-dATP. The samples are analyzed by electrophoresis, bands detected by autoradiography and in each lane the ratio is determined between cpm in the band of interest and cpm in the 28S band. The ratio is a measure of the level of mRNA in the sample and can be used to monitor changes in mRNA during treatments, development and pathogenesis.

Animals↗

Pion treatment procedures and verification techniques.

Procedures and techniques developed for the negative pi-meson (pion) radiotherapy program at the Los Alamos Meson Physics Facility, Los Alamos, NM, are reviewed and described. A particular pion patient is followed through the entire planning and treatment sequence to describe CT scanning procedures, bolus and collimator and treatment techniques developed to minimize positioning errors (less than 5 mm). Comparison of 2-D and 3-D isodose calculations developed at Los Alamos showed differences of less than 10% attributable to multiple scattering effects and the computational models used. Treatment verification methods using in vivo ion chamber dosimetry generally confirmed the prescribed dose delivery within 10% and using TLD within 18%.

Elementary Particles↗

Pediatric and adult emergency management assistance using computerized guidelines.

This study was performed to determine if computer assistance is able to improve the initial management of pediatric patients in critical emergencies. A computer program that provides an easily accessible, concise set of information to assist in the management of medical emergencies is described. It provides size- and age-specific endotracheal tube sizes, drug doses, continuous intravenous (IV) drug infusion preparation instructions, and emergency management guidelines for pediatric and adult patients with one of several acute emergencies. These emergencies include asystole, respiratory failure, anaphylaxis, shock, myocardial infarction, cardiac arrhythmias, seizures due to several common causes, and rapid sequence anesthesia induction. The use of this program was shown to reduce the time required for the preparation and administration of emergency therapy while minimizing management errors. A lap-top computer running this program may be a worthwhile addition to emergency departments and hospital resuscitation carts as a resource, especially for physicians less experienced in the care of children.

Adult↗

Does self-administration of a quality of life index for inflammatory bowel disease change the results?

We assessed the effect of self-administration of a disease-specific health-related quality of life instrument, the Inflammatory Bowel Disease Questionnaire (IBDQ), on score results. Patients were assessed at two visits in two tertiary centers. "Experienced" patients (N = 31) with Crohn's disease had previously completed the IBDQ several times while "novices" (N = 37) with Crohn's disease or ulcerative colitis had no prior exposure to the IBDQ. At each visit a self-administered IBDQ followed by a nurse-administered IBDQ (score range, 1-7; absolute score range, 32-224) and disease activity were assessed. At visit 1, the mean rates of discrepant responses between nurse and self-administered scores were 24 +/- 15% in experienced patients and 34 +/- 17% in novice patients (p = 0.018), which fell to 21 +/- 16 and 23 +/- 10%, respectively, by visit 2 (p = NS). However, discrepancy rates were not significantly different between novice and experienced patients when adjusted by center. Discrepancies occurred randomly in all 32 IBDQ items. Eighty percent of all discrepant responses differed by only one grade of a seven-point Likert scale. Baseline self-administered scores for all patients were 4.80 +/- 1.24 (absolute score, 153.0 +/- 39.9). Mean score differences at each visit (nurse minus self) were very small, ranging from 0.029 to 0.136, and would not be considered clinically important. Intraclass correlation coefficients between the nurse and self-administered IBDQ and the four dimensional scores were > or = 0.97 by visit 2, indicating excellent concordance and minimal observer error. Mean changes in score over time were of comparable magnitude for both self (0.320 +/- 0.819) and nurse (0.260 +/- 0.831) assessments. We conclude that the IBDQ may be reliably used as a self-administered instrument in clinical trials.

Adult↗

Should the Retention trial of the Test of Memory Malingering be optional?

The present study examined the false negative error rate associated with the optional use of the Retention trial the Test of Memory Malingering (TOMM). TOMM scores from 150 traumatic brain injury and 150 chronic pain patients were examined. Results indicated that early termination of the TOMM resulted in 3% of patients going undetected by the TOMM. The practical cost of this error was minimized by the inclusion of at least one other SVT. Clinical implications are discussed.

Brain Injuries↗

Cartilage volume quantification via Live Wire segmentation.

RATIONALE AND OBJECTIVES: A reduction in cartilage volume is characteristic of osteoarthritis and hence there exists a need for an accurate and reproducible method to measure in vivo cartilage volume. Quantification of cartilage volume from magnetic resonance (MR) images requires a segmentation technique such as the user-driven "Live Wire" strategy that can reliably delineate object volumes in a time-efficient manner. In the present work, the accuracy and reproducibility of the Live Wire method for the quantification of cartilage volume in MR images is evaluated. MATERIALS AND METHODS: The accuracy of the Live Wire method was assessed by comparing the MR-based volume measurement of a patellar cartilage-shaped phantom versus data calculated via water displacement. The inter- and intra-operator reproducibility of the technique was evaluated from Live Wire segmentation of the patellar cartilage volume from fat-suppressed 3-dimensional spoiled-gradient-echo images of five healthy human volunteers performed by three operators. To provide data for analysis of inter-scan reproducibility, the human scans were repeated five times with the aid of a leg-restraining jig to minimize repositioning error. RESULTS: The volume of the patellar cartilage-shaped phantom measured via Live Wire segmentation of MR images was within 97.8% of its true volume. The average inter- and intra-operator coefficients of variation of three operators were 3.0% and 0.4%, respectively. The average inter-scan coefficient of variation of five repeated scans of each volunteer was 2.7%. CONCLUSION: The data suggest that the Live Wire strategy is an accurate, reproducible, and efficient technique to measure cartilage volume in vivo in a feasible amount of operator time.

Adult↗

Meta-analysis of ischemia-modified albumin to rule out acute coronary syndromes in the emergency department.

BACKGROUND: Because of possible adverse outcomes, many of the >6 million annual emergency department (ED) patients with suspected acute coronary syndromes (ACS) undergo extensive evaluations. To minimize medical errors, chest pain evaluations are structured to identify accurately nearly 100% of patients with ACS. This is at a cost of negative evaluation rates that can exceed 90%. Ischemia-modified albumin (IMA), a serum biomarker with a high negative predictive value (NPV) at ED presentation, may exclude ACS. Our objective was to perform a meta-analysis of IMA use for ACS risk stratification. METHODS: By computer literature search and communication with authors of unpublished information, all IMA data were considered. This analysis included studies if they reported IMA results from an ED presentation for suspected ACS. We defined a negative triple prediction test (TPT) as a nondiagnostic electrocardiogram, negative troponin, and negative IMA. RESULTS: Eight studies of >1800 patients met the entry criteria. The TPT sensitivity and NPV for acute ACS were 94.4% and 97.1% and, for longer-term outcomes, were 89.2% and 94.5%, respectively. CONCLUSIONS: A negative TPT of a nondiagnostic electrocardiogram, negative troponin, and negative IMA has a high NPV for excluding ACS in the ED.

Angina, Unstable↗

Evaluation of vardenafil and sildenafil on cardiac repolarization.

This novel study evaluated the effects of vardenafil and sildenafil on QT and corrected QT (QTc) duration using a model that minimizes experimental error to obtain the most accurate assessment of observed QTc effects. A placebo-controlled and positive-controlled, period-balanced, double-blinded, 6-way crossover study evaluated therapeutic and supratherapeutic oral doses of vardenafil (10 and 80 mg, respectively) and sildenafil (50 and 400 mg, respectively), therapeutic doses of moxifloxacin (400 mg), and a placebo in 58 healthy men (mean age 53 years), with dosing every 3 days. Six replicate, 12-lead, digital electrocardiograms (ECGs) were recorded at 3 time points before and 5 time points after dosing to cover the time course of maximum exposure to study drugs and their metabolites. An independent laboratory blindly analyzed approximately 17,000 ECGs. For the placebo, mean change in QTcF (Fridericia) duration 1 hour after dose (approximate Tmax of vardenafil and sildenafil) was 0 ms (+/-0.7 SD). QT/QTc variability was small across regimens, indicating statistically powerful results. Moxifloxacin demonstrated an expected 8-ms mean change and was the only drug to prolong absolute QT. Placebo-corrected mean changes in QTcF duration (90% confidence interval) at 1 hour after dose were 8 ms (range 6 to 9) for vardenafil 10 mg and 6 ms (range 5 to 8) for sildenafil 50 mg. QTci (linear and nonlinear per patient) yielded similar trends: 4 ms (range 3 to 6) for vardenafil 10 mg and 4 ms (range 2 to 5) for sildenafil 50 mg. Dose response demonstrated very shallow QTc relations for study drugs. Therapeutic and supratherapeutic doses produced only small increases in the QTcF interval, which were considered to be clinically irrelevant. This well-controlled, statistically powerful study in middle-aged men demonstrated that vardenafil and sildenafil produced no increase of absolute QT and only similar, small increases of the QTc interval, with a shallow dose-response curve. The study design and conduct may serve as a guide for future QT assessment of new drugs.

3',5'-Cyclic-GMP Phosphodiesterases↗

A new method for adjusting neural response jitter in the STRF obtained by spike-trigger averaging.

Sensitivity of central auditory neurons to frequency modulated (FM) sound is often characterized based on spectro-temporal receptive field (STRF), which is generated by spike-trigger averaging a random stimulus. Due to the inherent property of time variability in neural response, this method erroneously represents the response jitter as stimulus jitter in the STRF. To reveal the trigger features more clearly, we have implemented a method that minimizes this error. Neural spikes from the brainstem of urethane-anesthetized rats were first recorded in response to two sets of FM stimuli: (a) a random FM tone for the generation of STRF and (b) a family of linear FM ramps for the determination of FM 'trigger point'. Based on the first dataset, STRFs were generated using spike-trigger averaging. Individual modulating waveforms were then matched with respect to their mean waveform at time-windows of a systematically varied length. A stable or optimal variance time profile was found at a particular window length. At this optimal window length, we performed delay adjustments. A marked sharpening in the FM bands in the STRF was found. Results were consistent with the FM 'trigger point' as estimated by the linear FM ramps. We concluded that the present approach of adjusting response jitter was effective in delineating FM trigger features in the STRF.

Action Potentials↗

Improving systems of care in primary angioplasty.

AMI is a life-threatening condition. Poor performance on the part of caregivers can result in the death of a patient. It is critical that a PPCI capability be developed in such a way that error is minimized. It is not enough that the system works well or very well. Aviation is often used as the example that medical systems should emulate. In developing the many interrelated systems required to function properly to ensure safe, effective,prompt, and appropriate application of PPCI,an aviation parallel should be kept in mind. If you were walking on the jetway toward a plane and were greeted by the pilot who said to you, "You know, I can land this thing 99% of the time," you would never get on that plane. It is important to develop a PPCI system that is absolutely never the cause of harm to any patient. Doing so requires exquisite attention to detail, algorithms of care when possible, redundancy, and clear orders for all drugs and procedures.

Angioplasty, Balloon, Coronary↗

High-performance liquid chromatography-diode array detection assay for the detection and quantification of the Beauveria metabolite oosporein from potato tubers.

A high-performance liquid chromatography-diode array detection (HPLC-DAD) assay is described for the detection and quantification of the secreted Beauveria brongniartii metabolite oosporein from potato tubers. Analyte recovery was achieved with a Britton-Robinson buffer system at pH 5.5 diluted with methanol 3:7 (v/v) (BR5.5-MeOH). An internal standard protocol using 2-iodobenzoic acid was established to minimize analytical error. The resulting assay, using a binary solvent gradient with acidic modifiers and detecting the metabolite at 287 nm, showed a limit of detection (LOD) of 2.4 mg oosporein/kg potato tubers. The oosporein content of potato tuber samples obtained from a field trial using the biological pest control B. brongniartii formulation Melocont-Pilzgerste in up to five-fold higher doses (250 kg Melocont-Pilzgerste/ha) as recommended per year was found to be below the established LOD.

Ascomycota↗

Physiochemical properties of various polymer substrates and their effects on microchip electrophoresis performance.

A suite of polymers were evaluated for their suitability as viable substrate materials for microchip electrophoresis applications, which were fabricated via replication technology. The relevant physiochemical properties investigated included the glass transition temperature (T(g)), UV-vis absorption properties, autofluorescence levels, electroosmotic flow (EOF) and hydrophobicity/hydrophilicity as determined by sessile water contact angle measurements. These physiochemical properties were used as a guide to select the proper substrate material for the intended microchip electrophoretic application. The T(g) of these polymers provided a guide for optimizing embossing parameters to minimize replication errors (REs), which were evaluated from surface profilometer traces. RE values ranged from 0.4 to 13.6% for the polymers polycarbonate (PC) and low-density polyethylene (LDPE), respectively. The absorption spectra and autofluorescence levels of the polymers were also measured at several different wavelengths. In terms of optical clarity (low absorption losses and small autofluorescence levels), poly(methyl methacrylate), PMMA (clear acrylic), provided ideal characteristics with autofluorescence levels comparable to glass at excitation wavelengths that ranged from 488-780 nm. Contact angle measurements showed a maximum (i.e., high degree of hydrophobicity) for polypropylene (PP), with an average contact angle of 104 degrees +/-3 degrees and a minimum exhibited by gray acrylic, G-PMMA, with an average contact angle of 27 degrees +/-2 degrees. The EOF was also measured for thermally assembled chips both before and after treatment with bovine serum albumin (BSA). The electrophoretic separation of a mixture of dye-labeled proteins including; carbonic anhydrase, phosphorylase B, beta-galactosidase, and myosin, was performed on four different polymer microchips using laser-induced fluorescence (LIF) excitation at 632.8 nm. A maximum average resolution of 5.04 for several peak pairs was found with an efficiency of 6.68 x 10(4) plates for myosin obtained using a BSA-treated PETG microchip.

Electrophoresis, Microchip↗

Analysis of EEG tracings in frequency and time domain in hepatic encephalopathy.

Spectral EEG analysis in hepatic encephalopathy (HE) is usually performed disregarding the effect of epoch length, statistical errors and equipment noise. A study on these items was carried out. In addition, spectral analysis and a new analysis, performed in time domain, were compared in the assessment of HE. The EEG tracings of 73 cirrhotic patients with HE were analyzed. Artifact-free periods of about 1 min were selected. Equipment noise was measured by short-circuiting all the electrodes. The equipment noise was notable below 1.5 Hz; the best epoch length was 4s and the statistical errors were minimal for the band with the highest relative power. Nineteen per cent of the tracings were unstable. The spectral values were found to be related to liver function and to the degree of HE, whereas the relationship with psychometric variables was poor. The indexes computed by time-domain analysis were found to be better related to psychometric findings. We have provided information on the optimisation of spectral EEG analysis and presented a time-domain analysis giving results related to psychometric tests and liver function.

Aged↗

The corner of the coloproctologist: what to ask to radiologist.

Defecation disorders, fecal incontinence, often associated to urinary and genital dysfunction, represent symptoms of a large number of functional and structural alterations of pelvic floor. They can be evaluated by functional and morphologic tests. A perfect anatomic and functional knowledge of the anorectum and pelvic floor is indispensable for a correct diagnostic and therapeutic path. Incontinence due to sphincter lesions can be diagnosed only by imaging techniques. In defecation disorders the issue is complex because functional and anatomic alterations can coexist. The radiological diagnosis of dyssynergic defecation is a diagnosis of confidence that enhances its value when manometric and electromyographic evidence of pelvic dyssynergia are detected. When anatomical alterations are detected the aim is to understand their physiopathology, to make a more precise diagnosis and treatment, and to minimize the errors of an inappropriate therapy. Our attention is focused on the information provided by imaging techniques about anorectum and pelvic floor abnormalities for optimal therapeutic planning.

Anal Canal↗

Modeling data from titration, amide H/D exchange, and mass spectrometry to obtain protein-ligand binding constants.

We recently reported a new method for quantification of protein-ligand interaction by mass spectrometry, titration and H/D exchange (PLIMSTEX) for determining the binding stoichiometry and affinity of a wide range of protein-ligand interactions. Here we describe the method for analyzing the PLIMSTEX titration curves and evaluate the effect of various models on the precision and accuracy for determining binding constants using H/D exchange and a titration. The titration data were fitted using a 1:n protein:ligand sequential binding model, where n is the number of binding sites for the same ligand. An ordinary differential equation was used for the first time in calculating the free ligand concentration from the total ligand concentration. A nonlinear least squares regression method was applied to minimize the error between the calculated and the experimentally measured deuterium shift by varying the unknown parameters. A resampling method and second-order statistics were used to evaluate the uncertainties of the fitting parameters. The interaction of intestinal fatty-acid-binding protein (IFABP) with a fatty-acid carboxylate and that of calmodulin with Ca(2+) are used as two tests. The modeling process described here not only is a new tool for analyzing H/D exchange data acquired by ESI-MS, but also possesses novel aspects in modeling experimental titration data to determine the affinity of ligand binding.

Amides↗