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Concanavalin A-peroxidase labeling in cervical exfoliative cytopathology. I. Labeling of normal squamous cells and the detection of cancer.

The lectin binding capacity of the cell surface of normal flattened exfoliated epithelial cells of the uterine cervix was investigated looking for differences between specimens from normal and cancer patients. The method used was a modified concanavalin A-horseradish peroxidase (Con A-HRP) labeling procedure. Both normal and cancer specimens contain labeled as well as unlabeled usual flattened cells. There is a distinct difference between the labeling intensity of labeled and that of unlabeled cells. Quantification of the labeling results has been achieved using a light microscope equipped with a computerized video system. Apparently healthy persons, having a percentage of labeled flattened cells between 54 and 94% (mean = 73%, SD = 10%, N = 40), were totally discriminated by this method from the cancer patients. These patients with a histologically confirmed squamous cell carcinoma, showed a labeling percentage between 10 and 22% (mean = 15%, SD = 4%, N = 10). Hormonal factors, such as phase of cycle and pill use, appeared to have no significant influence. Statistical analysis revealed that at least 99% of all healthy persons will have a labeling percentage above 45%, while at most 1% of the cancer patients will show a labeling percentage above 30%. When choosing the labeling percentage of 45% as critical value, the Con A-HRP labeling might serve as an additional detection method for cancer of the uterine cervix. Moreover, as it is based on the abundantly present normal cells, and not on the often scarce abnormal cells, the method is not liable to sampling and screening errors.

Adult↗

Randomization tests: statistics for experimenters.

Randomization (permutation) tests free the experimenter from the constraints of random sampling, a known error distribution and equal variances, to give a direct answer to the question "how likely is such a large (or small) result if the applied treatments had no effect?" The "result" may be the difference in mean responses, a correlation coefficient or any other value of interest. A randomization test is not a different statistical test but a different, and always valid, method of determining statistical significance. The familiar t-test and F-test can be carried out by data permutation without any parametric assumptions being fulfilled. A particular advantage of this method is that unbalanced designs and missing values are easily accommodated. Even with only a small number of subjects the number of permutations will be large and a computer is necessary if the randomization test is to be of practical value. To make this method of determining statistical significance generally available an interactive microcomputer program, forming a comprehensive package for the design and analysis of experiments, has been prepared.

Mathematical Computing↗

Burns management and junior staff--what do they know?

This study examines the ability of junior doctors to initiate the management of burned patients. One hundred and twenty-four junior doctors were assessed using a questionnaire. Eighty per cent of the sample had had undergraduate lectures on the subject and 43 per cent had experience of managing patients with major burns. Despite this only 3 per cent could correctly carry out all the steps necessary to estimate the fluid requirements of a burned patient. Theoretical knowledge of the 'Rule of Nines' was adequate but 10 per cent of the sample made mathematical errors when supplied with a burns formula and the appropriate values. We suggest that postgraduate instruction be given to junior staff and that burns charts include details of a burns formula and an illustrative example of the calculation required.

Burns↗

The Biber Cognitive Estimation Test.

Normative data from 113 participants, and cross-validation data from 49 additional participants, are presented for the Biber Cognitive Estimation Test (BCET), a 20-item test with five estimation questions in each of four categories: time/duration, quantity, weight, and distance. In Study 1, the range of normal answers is provided for each item, and a cut-off for impaired performance is suggested. Although very low IQ or education levels would be expected to invalidate this test as a measure of estimation skills, participants in the current sample made few errors. In Study 2, a cross-validation suggested a slightly more conservative cut-off score for abnormality. Study 3 examined cognitive estimation in demented (dementia of the Alzheimer's type and dementia syndrome of Parkinson's disease) versus intact elderly participants. Results indicated that the BCET was able to distinguish between demented and intact elderly participants.

Adolescent↗

A method to determine 238U activity in environmental soil samples by using 63.3-keV-photopeak-gamma HPGe spectrometer.

The paper presents a method of measuring 238U activity in environmental soil samples by a low background HPGe spectrometer at the 63.3 keV gamma photopeak. The low 238U activity requires a large size soil sample with a mass of about 100 g. The geometrical and self-absorption effects as well as the density dependence of soil samples were then investigated. A procedure of analyzing environmental soil samples was established with a relative error of about 10%. Two soil samples of known activity were tested and 106 surface soil samples collected from the Southern part of Vietnam were analyzed, and then these results were compared by instrumental neutron activation analytical method.

Algorithms↗

A biosensor based on co-immobilized L-glutamate oxidase and L-glutamate dehydrogenase for analysis of monosodium glutamate in food.

A monosodium glutamate (MSG) biosensor made by co-immobilized L-glutamate oxidase (L-GLOD) and L-glutamate dehydrogenase (L-GLDH) as the bio-component based on substrate recycling for highly sensitive MSG or L-glutamate determination, has been developed. Regeneration of MSG by substrate recycling provided an amplification of the sensor response. Higher signal amplification was found in the presence of ammonium ion. The sensor was standardized to determine MSG in the range of 0.02-3.0 mg/L. Linearity was obtained from 0.02 to 1.2 mg/L in presence of ammonium ion (10 mM) and NADPH (reduced nicotinamide adenine dinucleotide phosphate) (2 mM), but in absence of L-GLDH, the detection limit of MSG is confined to 0.1 mg/L. The apparent Km for MSG with L-GLOD-L-GLDH coupled reaction was 0.4451 mM but 1.9222 mM when only L-GLOD was immobilized. Cross linking with glutaraldehyde in the presence of bovine serum albumin (BSA) as a spacer molecule has been used for the method of immobilization. The response time of the sensor was 2 min. The optimum pH and temperature of the biosensor has been determined as 7+/-2 and 25+/-2 degrees C, respectively. The enzyme immobilized on the membrane was used for over 50 measurements. The standard error of the sample measurement was 4-5%. The activity of the enzyme-immobilized membrane was tested over a period of 60 days.

Amino Acid Oxidoreductases↗

The acquisition of allophonic rules: statistical learning with linguistic constraints.

Phonological rules relate surface phonetic word forms to abstract underlying forms that are stored in the lexicon. Infants must thus acquire these rules in order to infer the abstract representation of words. We implement a statistical learning algorithm for the acquisition of one type of rule, namely allophony, which introduces context-sensitive phonetic variants of phonemes. This algorithm is based on the observation that different realizations of a single phoneme typically do not appear in the same contexts (ideally, they have complementary distributions). In particular, it measures the discrepancies in context probabilities for each pair of phonetic segments. In Experiment 1, we test the algorithm's performances on a pseudo-language and show that it is robust to statistical noise due to sampling and coding errors, and to non-systematic rule application. In Experiment 2, we show that a natural corpus of semiphonetically transcribed child-directed speech in French presents a very large number of near-complementary distributions that do not correspond to existing allophonic rules. These spurious allophonic rules can be eliminated by a linguistically motivated filtering mechanism based on a phonetic representation of segments. We discuss the role of a priori linguistic knowledge in the statistical learning of phonology.

Humans↗

Quantitative analysis of brain NADH in the presence of hemoglobin using microfiber spectrofluorometry: a pre-calibration approach.

Dysfunction of mitochondria links a variety of central nervous system disorders and other neurodegenerative diseases. The primary respiratory chain substrate reduced-form nicotinamide adenine dinucleotide (NADH) is an important regulator of respiratory chain function in mitochondria and, because of its fluorescent properties, has been used to assess mitochondrial pathophysiology in cells and tissues. However, assessment of changes in tissue NADH has been limited to qualitative analysis primarily because hemoglobin (Hb) interferes with NADH fluorescence measurements by absorbing both excitation and emission light. This report presents a computer-assisted approach to estimate tissue NADH and Hb concentrations quantitatively at the same time. The method is based on a two-dimensionally interpolated database model that is calibrated by fluorescence emission spectra with known-value standard chemical solutions. Quantitative concentrations for NADH and Hb can be determined by the corresponding known-value spectral data that have the minimum error to the sample spectrum obtained from an experiment. Repeatability and reliability tests are also presented in this report. Results demonstrate that this method can feasibly quantify the NADH content regardless of the Hb background in living hippocampal cells during hypoxia, suggesting that it has the potential to be applied to in vivo experiments in the future.

Animals↗

Ankle orthoses effect on single-limb standing balance in athletes with functional ankle instability.

OBJECTIVE: To test whether a rigid or a flexible ankle orthosis affects postural sway in single-limb stance as quantified by stabilometry. DESIGN: Crossover trial. SETTING: University laboratory. PARTICIPANTS: Twenty-two athletes with functional ankle instability (consecutive sample of patients with recurrent ankle sprains but without mechanical instability) and 22 healthy athletes (control group of volunteers matched to age, height, weight, physical activity). INTERVENTIONS: Stabilometry in single-limb stance on a force platform. Participants were tested on each leg with and without a rigid or a flexible ankle orthosis. The order of test conditions was randomized. MAIN OUTCOME MEASURES: Sway velocities, sway pattern, and sway area as calculated from center of pressure movements. The two groups were compared by Mann-Whitney test, and the different orthoses within each group were compared by Wilcoxon test, paired samples (type I error 5%, Bonferroni adjustment). RESULTS: In athletes with functional ankle instability, both a rigid and a flexible ankle orthosis significantly reduced mediolateral sway velocity. A flexible ankle orthosis also changed sway pattern significantly, by reducing the percentage of linear movements of less than 5 degrees per .01 sec. CONCLUSIONS: In athletes with functional ankle instability, ankle orthoses reduce mediolateral sway velocity, possibly because of improved mediolateral proprioception.

Adult↗

ABO, phosphoglucomutase and erythrocyte acid phosphatase typing of blood samples containing added fluoride.

Blood samples containing approximately 2% and 4% sodium fluoride have been stored at 4 degrees C for up to 5 months and 4 weeks respectively. ABO typing by absorption-elution was successful on stains made from almost all of the samples. PGM subtyping by isoelectric focusing was successful on most samples, with clearer results from whole blood than from stains. Failure to type appears to be slightly more common at the higher preservative level and yields no result rather than an erroneous one. Apparent phenotypic changes in the 1+ and 1- bands have been seen after 5 months storage. EAP typing by isoelectric focusing was successful on most samples, again with clearer results from whole bloods than from stains. Possible errors can occur in samples containing C bands, but it is not clear whether they are caused by the presence of preservative. The results obtained are illustrated by two casework examples.

ABO Blood-Group System↗

Saralasin test as a diagnostic and prognostic aid in renovascular hypertensive patients subjected to renal operation.

A positive saralasin test in patients with angiographic evidence of renovascular disease and other positive functional tests gives further assurance that these patients will achieve normal or substantially reduced blood pressure postoperatively. In our experience with proved renovascular hypertension there was a 19 per cent incidence of falsely negative saralasin tests. Therefore, saralasin should not be used as the sole screening test in hypertensive patients suspected of having surgically correctable lesions. There is a direct correlation between elevated renin activity and a positive saralasin test. In some patients saralasin may be more sensitive than any other currently used test to detect overactivity of the renin-angiotensin system. This would determine those patients with technical errors in renin sampling and assays. Of the 16 patients (all normotensive) who had 6-month followup tests 5 had elevated peripheral renin activity, probably owing to furosemide stimulation. Of these 5 patients 2 had a positive postoperative saralasin test, raising the question of potential falsely positive responses in cases of essential hypertension and coincidental non-functional renal artery stenosis. Patients with high renin essential hypertension may respond to saralasin, even in the absence of renal artery lesions. A saralasin test should be done in a hospital where all specific conditions can be met and potential complications handled promptly.

Adolescent↗

New technologies in cervical cytology screening: a word of caution.

Nearly 5000 women in the United States will die of cervical cancer this year and many of those deaths could be prevented. Most incident cases (60%) are associated with absent or deficient screening. Approximately 25% of screening failures are due to errors in cervical sampling or smear interpretation. New techniques for cytology screening such as liquid-based smears and computerized rescreening of slides are being promoted to physicians and the lay public despite limited scientific evaluation. Improving the validity of screening tests is important, but shifting resources for this purpose might cause net harm if the result is fewer screening opportunities for high-risk women. New screening technologies do not address this utilization gap and might widen it by driving the cost of screening out of the reach of high-risk women. Greater decreases in cervical cancer morbidity and mortality would likely result if the same resources were invested in a comprehensive national screening program that targeted women at highest risk.

Female↗

Hydrodynamic drag on non-spherical floc and free-settling test.

This work numerically investigates the hydrodynamic drag force exerted on a porous spheroid floc moving steadily through a quiescent Newtonian fluid over a wide range of the Reynolds number. The flow patterns for a highly porous spheroid moving at an elevated Reynolds number are basically the same as those at a low Reynolds number, which extends the applicable range of a creeping-flow based correlation to the higher Reynolds number regime. The shape effect becomes more prominent as the spheroid becomes more porous. Using the equivalent diameter, defined as the geometric mean diameter of the principal axes, leads to a universal correlation relating to the drag force, aspect ratio, and interior permeability. In addition, free-settling experiments are performed to estimate how the non-spherical shape affects the three sludge samples. The possible errors in data reduction for the free-settling test are attributed to the a/b ratio and the internal permeability. The errors range from 16-34% for a/b = 0.6-2.0.

Flocculation↗

Measurements of mercury in the near-surface layer of the atmosphere of the Russian Arctic.

A series of measurements of gaseous elemental mercury concentrations in near-surface air of the Russian Arctic Region were carried out from 1994 to 1997. The measurements were conducted in Murmansk at a stationary site in April-May 1994, on a cruise in Motovsky Bay and Kola Bay during May-June 1996, and along the Russian Northern Sea Route in April-May 1997 on board the nuclear icebreaker 'Soviet Union'. Silver absorption was used for trapping of mercury and the mass of mercury was determined by cold vapour atomic absorption spectrophotometery. Detection limits were approximately 0.3 ng/m(3) (+/- error 46%). Sixty samples were selected and analysed. Sample volumes were 2.2 m(3) ashore, and up to 6.6 m(3) over water. The meteorological conditions, including a wind speed and direction, during the sampling period were typical of the spring-summer period of year, and therefore the concentrations of atmospheric mercury are regarded as representative for this season. The mean concentrations of mercury ranged from 2.2 ng/m(3) for Murmansk city, 1.7 ng/m(3) for Kola Bay, 1.6 ng/m(3) for Motovsky Bay, 1.1 ng/m(3) for the eastern part of the Barents Sea and 0.7 ng/m(3) for the western part of the Kara Sea. The levels of mercury in Murmansk, and over Kola and Motovsky Bays were associated with a primary direction of a near-surface wind from the nearest sources of mercury emission located in the Russian North region. These are the non-ferrous metallurgical plants in Nickel in the case of Motovsky Bay and Murmansk garbage-disposal plant, for sampling points in Murmansk and over Kola Bay. These concentrations of mercury, measured in the spring-summer season, in near-surface air of the Russian North, are more than two-fold lower than the concentrations that are typical of continental background regions in western Russia, and are comparable to the concentrations measured in the Arctic regions of other countries.

Air Pollutants↗

Optimal design of regularization term and regularization parameter by subspace information criterion.

The problem of designing the regularization term and regularization parameter for linear regression models is discussed. Previously, we derived an approximation to the generalization error called the subspace information criterion (SIC), which is an unbiased estimator of the generalization error with finite samples under certain conditions. In this paper, we apply SIC to regularization learning and use it for: (a) choosing the optimal regularization term and regularization parameter from the given candidates; (b) obtaining the closed form of the optimal regularization parameter for a fixed regularization term. The effectiveness of SIC is demonstrated through computer simulations with artificial and real data.

Linear Models↗

Freehand three-dimensional echocardiography for determination of left ventricular volume and mass in patients with abnormal ventricles: comparison with magnetic resonance imaging.

OBJECTIVE: The objective of this study was to validate the freehand three-dimensional echocardiographic method in patients with abnormal ventricular geometry compared with two-dimensional echocardiography using magnetic resonance imaging as a standard. BACKGROUND: Two-dimensional echocardiographic methods for estimating left ventricular volume and mass in clinical use today are limited by inaccuracies and variations caused by use of geometric assumptions and errors in image plane positioning. Freehand three-dimensional echocardiography with operator guidance by a "line of intersection" display eliminates these assumptions and errors. This method of volume and mass computation has been validated as highly accurate and reproducible in healthy subjects. METHODS: Left ventricular end-systolic and end-diastolic volumes and myocardial mass were determined by freehand three-dimensional echocardiography, by conventional two-dimensional echocardiography using the apical biplane summation of discs method (volume) and the truncated ellipsoid method (mass), by M-mode echocardiography using the Penn method (mass), and by magnetic resonance imaging in 30 patients selected only for the presence of an abnormal ventricle. Results were compared by means of linear regression and the Bland-Altman method of analysis. RESULTS: There was excellent correlation, low bias, and low variability between three-dimensional echocardiography and magnetic resonance imaging for end-diastolic volume (r = 0.90, standard error of the estimate = 31.8 ml, bias = -28.4 ml), end-systolic volume (r = 0.93, standard error of the estimate = 24.1 ml, bias = -13.1 ml), and mass (r = 0.90, standard error of the estimate = 27.3 gm, bias = -22.6 ml). Two-dimensional echocardiography was less accurate and more variable as follows: end-diastolic volume (r = 0.70, standard error of the estimate = 39.8 ml, bias = -33.5 ml), end-systolic volume (r = 0.78, standard error of the estimate = 31.2 ml, bias = -26.7 ml), and mass (r = 0.80, standard error of the estimate = 37.3 gm, bias = 28.9 ml). M-mode echocardiography mass determination (Penn method) was least accurate and most variable (r = 0.075, standard error of the estimate = 78.3 gm, bias = 78.3 gm). CONCLUSIONS: Freehand three-dimensional echocardiography is a method of high accuracy and low variability for computing left ventricular volume and mass in clinical patients with abnormal ventricles. It is superior to conventional one- and two-dimensional echocardiography. The improvement achieved is attributed to elimination of geometric assumptions and image plane positioning errors and additional sampling of the ventricle.

Adolescent↗

The development and implementation of an expert system for the analysis of umbilical cord blood.

An assessment of neonatal outcome may be obtained from analysis of blood in the umbilical cord of the infant immediately after delivery. This can provide information on the health of the newborn infant, guide requirements for neonatal care, and is recommended practice of the Royal College of Obstetricians and Gynaecologists. However, there are problems with the technique. Samples frequently contain errors in one or more of the important parameters, preventing accurate interpretation and many clinical staff lack the expert knowledge required to interpret error-free results. In this paper the development and implementation of an expert system to overcome these difficulties is described. The expert system validates results, provides a textual interpretation and archives all results to database for audit, research and medico-legal purposes. The system has now been in routine clinical use for over 3 years in Plymouth, and has also been installed in several other hospitals in the UK. Results are presented in which the types and frequency of errors are established and the user acceptance of the system is determined.

Expert Systems↗

The evaluation of an expert system for the analysis of umbilical cord blood.

An assessment of neonatal outcome may be obtained from analysis of blood in the umbilical cord of an infant immediately after delivery. This can provide information on the health of the new-born infant, guide requirements for neonatal care, but there are problems with the technique. Samples frequently contain errors in one or more of the important parameters, preventing accurate interpretation and many clinical staff lack the expert knowledge required to interpret error-free results. The development and implementation of an expert system to overcome these difficulties has previously been described. This expert system validates the raw data, provides an interpretation of the results for clinicians and archives all the results, including the quality control and calibration data, for permanent storage. Issues regarding the clinical evaluation of this system are now detailed further, along with some clinical results illustrating the potential of such a system.

Acid-Base Equilibrium↗