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Principles of morphometric grading.

Grading of the severity of lesions has increased in importance in histopathology. The simplest grading system has 2 grades. If there is variation in the measuring system, the grading will not be perfect, and there are also misgraded samples. We estimated the fraction of falsely graded cases by applying th NAG (Numerical Algorithm Group) Fortran Library. If all possible measurement values are equally probable the grades based on measurements within +/- 1 SD around the division line are false in 31.6% of cases. The corresponding figures for regions +/- 2 SD, +/- 3 SD, 1 to 2 SD, 1 to 3 SD, and 2 to 3 SD are 19.6, 13.3, 7.5, 4.2, and 0.8%, respectively. Detailed calculations were made which allowed accurate determination of the probability of a grade being false in different positions of the measurement scale. The results suggest that for diagnostic grading a borderline region should be defined (e.g. +/- 2 SD or +/- 3 SD around the division line).

Diagnostic Errors

Verification of the heart rate threshold.

Among the methods for determining anaerobic threshold (AT), the heart rate (HR) method seems to be the simplest. On the other hand, many conflicting results from comparing this method with others have been presented over the last 10 years. Therefore, the aim of this study was to compare the heart rate threshold (HRT) with the lactate turn point (LTP)-"second" break point of dependence of lactate (LA) to power output, ventilatory threshold (VT) and threshold determined by electromyography (EMGAT), all determined by the same exercise test and evaluated by the same computer algorithm. A group of 24 female students [mean age 20.5 (SD 1.6) years, maximal oxygen consumption 48.8 (SD 4.7) ml.kg-1.min-1] performed an incremental exercise test on a cycle ergometer (modified Conconi test) starting with an initial power output (PO) of 40 W with intensity increments of 10 W.min-1 until the subjects were exhausted. The HRT, LTP and EMGAT determination was done by computer-aided break-point regression analysis from dependence of functional measures on PO. The same computer algorithm was used for VT determination from the relationship between ventilation (V) and oxygen uptake (VO2) or carbon dioxide output (VCO2).(ABSTRACT TRUNCATED AT 250 WORDS)

Anaerobic Threshold

An inverse approach to determining myocardial material properties.

Passive myocardial material properties have been measured previously by subjecting test samples of myocardium to in vitro load-deformation analysis or, in the intact heart, by pressure-volume relationships. A new method for determining passive material properties, described in this paper, couples a p-version finite element model of the heart, a nonlinear optimization algorithm and a dense set of transmural measured strains that could be obtained in the intact heart by magnetic resonance imaging (MRI) radiofrequency tissue tagging. Unknown material parameters for a nonlinear, nonhomogeneous material law are determined by solving an inverse boundary value problem. An objective function relating the least-squares difference of model-predicted and measured strains is minimized with respect to the unknown material parameters using a novel optimization algorithm that utilizes forward finite element solutions to calculate derivatives of model-predicted strains with respect to the material parameters. Test cases incorporating several salient features of the inverse material identification problem for the heart are formulated to test the performance of the inverse algorithm in typical experimental conditions. Known true material parameters can be determined to within a small tolerance and random noise is shown not to affect the stability of the inverse solution appreciably. On the basis of these validation experiments, we conclude that the inverse material identification problem for the heart can be extended to solve for unknown material parameters that describe in vivo myocardial material behavior.

Algorithms

Performance evaluation of implantable artificial organs by sound spectrum analysis.

In this paper, a sound spectrum analyzing method was proposed to pre detect malfunctions of implantable artificial organs, such as an electromechanical total artificial heart (TAH) or prosthetic valves, without any percutaneous invasion. For this purpose, a sound detecting device was developed using a high sensitivity condenser microphone with a frequency range of more than 13 kHz. Output signals of this device are sampled at 100 kHz maximally, and sampled data are stored in an IBM PC (SamBo, Korea). To remove environmental noises in the measured sound, an adaptive least-mean square algorithm was employed. Using the squared value of the sound signal, the best position where only sounds from mechanical components can be measured was found. The sound spectrum was obtained by the periodogram spectral estimating method. Experiments were performed with this system, and the results indicated that: 1) by using an adaptive noise cancelling algorithm, a more noise-free signal can be obtained; 2) the harmonics from the mechanical components of a pendulum type electromechanical TAH were approximately 1.3 KHz; 3) a spectral change was observed when we compared the power spectral densities of a normal and failed TAH; 4) the spectral shift to higher harmonics occurred with an increase in heart rate; and 5) the sound propagation properties of tissue were investigated with animal experiments. The method proposed was found to be applicable in the detection of implantable artificial organ mechanical failure by sound spectrum analysis without the need for percutaneous invasion.

Acoustics

Jitter correction: a computer algorithm for reduction of the velocity recovery function artifact.

The measurement of neuromuscular jitter in single fiber electromyography may be artifactually raised by a component of interdischarge interval (IDI)-dependent jitter caused by the velocity recovery function (VRF) in muscle fibers. We have developed a computer algorithm for on-line mathematical correction for this artifact, thus improving the reliability of neuromuscular jitter estimates. The method, based on a modeling technique, was validated using intramuscular stimulation in order to either exclude an IDI-dependent component (using regular stimulation) or to include an IDI-dependent component (using pseudorandom stimulation). In 10 normal subjects the distribution of 106 corrected jitter values obtained using voluntary activity showed no difference from the measured values. This finding implies that previously published values for normal jitter are not likely to have been influenced by the VRF effect.

Action Potentials

A new algorithm for the identification of multiple input Wiener systems.

Multiple-input Wiener systems consist of two or more linear dynamic elements, whose outputs are transformed by a multiple-input static non-linearity. Korenberg (1985) demonstrated that the linear elements of these systems can be estimated using either a first order input-output cross-covariance or a slice of the second, or higher, order input-output cross-covariance function. Korenberg's work used a multiple input LNL structure, in which the output of the static nonlinearity was then filtered by a linear dynamic system. In this paper we show that by restricting our study to the slightly simpler Wiener structure, it is possible to improve the linear subsystem estimates obtained from the measured cross-covariance functions. Three algorithms, which taken together can identify any multiple-input Wiener system, have been developed. We present the theory underlying these algorithms and detail their implementation. Simulation results are then presented which demonstrate that the algorithms are robust in the presence of output noise, and provide good estimates of the system dynamics under a wide set of conditions.

Algorithms

EIT image reconstruction using sensitivity weighted filtered backprojection.

A set of specifications thought useful to advance the utility of electrical impedance tomography as a clinical imaging modality is proposed, together with an approach to image reconstruction designed to fulfil these specifications. Computer simulations are used to investigate the performance of this reconstruction approach on simple, known, impedance distributions and to develop the method to the stage of a complete reconstruction algorithm. The algorithm is then tested on data sets produced by measurements on a physical phantom, and on a set of measurements made on a volunteer human subject.

Algorithms

Real-time tracking of parameters of lung mechanics: emphasis on algorithm tuning.

We consider the problem of tracking rapid changes in the viscous and elastic properties of the respiratory system by using mouth flow and transpulmonary pressure data measured during mechanical ventilation. A recursive least-squares algorithm with adjustable compensator is used for online estimation of an R-C model of the breathing mechanics. Specific simulation experiments are presented to provide guidelines to select suitable values for the key variable, which controls the compromise between tracking ability and noise sensitivity. The results obtained confirm the critical role of the optimum tuning in relation to the noise level. Experimental results obtained from data measured on mechanically-ventilated dogs, in which respiratory distress syndrome was intravenously induced by oleic acid, demonstrate that the tuned algorithm is able to track appropriately both the viscous and elastic properties of lung mechanics. Parameter estimates are consistent with those obtained by standard and robust offline algorithms and their time course is in qualitative agreement with known physiopathological behaviour.

Airway Resistance

A fast spot segmentation algorithm for two-dimensional gel electrophoresis analysis.

An important issue in the automation of two-dimensional gel electrophoresis image analysis is the detection and quantification of protein spots. A spot segmentation algorithm must detect, define the extent of, and measure the integrated density of spots under a wide variety of actual gel image conditions. Besides these functions, the algorithm must be memory efficient to be able to process very large gel images and do this in a reasonable amount of computation time on low-cost computers, such as workstations and personal computers. We have developed a fast spot segmentation algorithm, extending the GELLAB-II segmenter, which extracts spots in a single raster scanning pass through the gel image. The performance analysis of the algorithm will be given in the paper as well as a discussion of the algorithm.

Algorithms

Closed-loop control of airway occlusion pressure at 0.1 second (P0.1) applied to pressure-support ventilation: algorithm and application in intubated patients.

OBJECTIVE: Airway occlusion pressure at 0.1 sec (P0.1) is an index of respiratory center output. During pressure-support ventilation, P0.1 correlates with the mechanical output of the inspiratory muscles and has an inverse relationship with the amount of pressure-support ventilation. Based on these observations, we designed a closed-loop control which, by automatically adjusting pressure-support ventilation, stabilizes P0.1, and hence patient inspiratory activity, at a desired target. The purpose of the study was to demonstrate the feasibility of the method, rather than its efficacy or even its influence on patient outcome. DESIGN: Prospective, randomized trial. SETTING: A general intensive care unit of a university hospital in Italy. PATIENTS: Eight stable patients intubated and ventilated with pressure-support ventilation for acute respiratory failure. INTERVENTIONS: Patients were transiently connected to a computer-controlled ventilator on which the algorithm for closed-loop control was implemented. The closed-loop control was based on breath by breath measurement of P0.1, and on comparison with a target set by the user. When actual P0.1 proved to be higher than the target value, the P0.1 controller automatically increased pressure-support ventilation, and decreased it when P0.1 proved to be lower than the target value. For safety, a volume controller was also implemented. Four P0.1 targets (1.5, 2.5, 3.5, and 4.5 cm H2O) were applied at random for 15 mins each. MEASUREMENTS AND MAIN RESULTS: The closed-loop algorithm was able to control P0.1, with a difference from the set targets of 0.59 +/- 0.27 (SD) cm H2O. CONCLUSIONS: The study shows that P0.1 can be automatically controlled by pressure-support ventilation adjustments with a computer. Inspiratory activity can thus be stabilized at a level prescribed by the physician.

Acute Disease

Variceal hemorrhage.

Figure 2 is the algorithm followed in our institution for management of acute variceal hemorrhage. A small percentage of patients who present with active variceal hemorrhage will stop bleeding after gastric lavage alone. However, most patients require an intravenous vasopressin infusion at a dose of 0.4 units per minute, preferably combined with intravenous administration of nitroglycerin. Although glypressin and somatostatin may be associated with fewer side effects than vasopressin, the superiority of these drugs remains to be determined. Whether pharmacologic therapy succeeds or fails, most patients then proceed to endoscopic sclerotherapy. Sclerotherapy may be used as a temporizing measure in preparation for elective surgery or as a long-term, definitive treatment for prevention of recurrent hemorrhage. Balloon tamponade is reserved for patients who are bleeding too rapidly for effective sclerotherapy and for sclerotherapy failures in preparation for emergency surgery. Because recurrent hemorrhage frequently occurs after balloon deflation, a more definitive treatment (surgery or endoscopic sclerotherapy) should be planned for all patients who undergo balloon tamponade. Because operative risk is unacceptably high for patients with hepatic functional decompensation secondary to variceal hemorrhage, we believe that a policy of routine emergency surgery is unwise. Rather, emergency surgical intervention is reserved for the relatively small number of patients (15 to 25 per cent) who continue to bleed after nonoperative options have failed. Shunt surgery should be considered early in the course of patients with bleeding secondary to gastric varices and portal hypertensive gastropathy, both of which respond poorly to nonoperative measures.

Algorithms

In vivo dosimetry during pelvic treatment.

High precision in vivo entrance and exit dose measurements have been performed with p-type diodes on patients during 8 MV X-ray irradiation of the pelvis, to investigate the accuracy of dose calculations in this region. Based on phantom measurements the accuracy of the p-type diode measuring system itself, i.e. the agreement with ionisation chamber dose measurements, was shown to be better than 0.7% while the reproducibility in the dose determination was 1.1%, 1.5% and 1.6% (1 S.D.) at the entrance point, isocentre and exit point, respectively, for the wedged lateral fields. Patient movement and the uncertainty in the diode position increased these values to 1.7%, 1.5% and 3.1% (1 S.D.) for dose determinations on patients. From the entrance and exit in vivo dose values the dose actually delivered to the isocentre was determined. For the anterior-posterior beams a good correspondence for most patients was observed at the entrance and exit point and at the isocentre between the in vivo and calculated dose values. For the wedged lateral beams a systematic deviation of about 3% was observed. In addition to the in vivo dose measurements phantom dose measurements have been performed to quantify the accuracy of the dose calculation algorithms including the computation of the number of monitor units. These measurements also served to quantify the effects of the actual patient on the dose delivery. The measurements showed that accurate calculation of the dose requires a separation of the head and phantom scatter contribution of the output of the treatment machine. The dependence of the wedge factor on field size, depth and source-skin-distance has also to be considered for accurate dose calculations. The effect of the patient on the dose calculation is mainly related to the actual electron densities of fat and bone structures compared to water: neglecting these densities in the dose computation could yield deviations up to 8.5% for the exit point in wedged beams. Based on these results, improvements in the dose calculation algorithms and monitor unit calculation including the use of the actual electron densities will be implemented in the treatment planning procedure.

Algorithms

Effects of solutes on optical properties of biological materials: models, cells, and tissues.

Perturbations of scattering background for absorbance measurements by photon diffusion techniques complicate algorithms used for determining the concentration of blood and the saturation of hemoglobin in tissues. In order to better define these perturbations, we have undertaken a study of the effect of solutes, some of physiological importance, upon the scattering of three types of model systems: a lipid vessel suspension (Intralipid), a cell suspension (Baker's yeast), and a tissue (perfused liver). A simple formula relates absorbancy change to proportional changes of the input/output separation rho and the square root of mu a and mu's in relation to a relevant model system. Thus, absorbance changes at 850 nm slopes and intercepts are measured as a function of rho; the absorption and reduced scattering coefficient, mu a and mu's, are calculated. We studied each of these cases as a function of the perturbation induced by low-molecular-weight polyhydroxy solutes, generally sugars (mannitol, fructose, sucrose, and glucose), alcohols (propanediol and methanol), and electrolytes (sodium and potassium chloride). Dilatometric studies indicate volume changes of the solvent system and afford correction factors. The slopes are approximately +/- 0.5 x 10(-4) OD/mM solute per centimeter separation of input/output per percent scatter (yeast or Intralipid) and indicate possible physiological detection of solutes in tissues in the millimolar range. The large optical effects of temperature upon the solute effect on model systems and of osmotic and perfusion pressures on the perfused liver further complicate the possibility of quantitative in vivo studies of these solutes.

Animals

Thyroid function testing based on assay of thyroid-stimulating hormone: assessing an algorithm's reliability.

OBJECTIVE: To assess the ability of an algorithm for thyroid-function testing (based on assay of thyroid-stimulating hormone [TSH]) to discern euthyroidism in patients with and without conditions affecting thyroid function. DESIGN: The Australian Health Insurance Commission (HIC) specifies clinical categories for which Medicare rebate is given for assay of both TSH and free thyroxine (FT4), but otherwise rebates for thyroid function testing are given for TSH assay only. A prospective study was made of paired TSH and FT4 results of 1000 consecutive assays categorised by indication for testing. An FT4 value within the reference range was accepted as indicating euthyroidism; the reliability of an initial TSH measurement as the sole indicator of thyroid disease was assessed against this criterion standard. SETTING: A large suburban teaching hospital. OUTCOME MEASURE: Success or failure of the algorithm, with failure defined as an abnormal FT4 level missed because the TSH level was normal. RESULTS: The algorithm failure rate both overall and in the patients not in the HIC clinical categories was 2.7%, and there was no significant difference in algorithm failure rate in the patients in the various HIC clinical categories. The categories and failure rates were: patients being monitored for thyroid disease, 3.4%; patients with the "sick euthyroid" syndrome, nil; patients with psychosis or dementia, 1.1%; patients taking drugs affecting thyroid function, 2.1%; and patients with pituitary dysfunction, one of six cases. The range of FT4 values in patients in whom the algorithm failed was 6.4-29.5 pmol/L in those without thyroid disease and 3.4-27.4 pmol/L in those with thyroid disease. In patients being monitored for thyroid disease, the proportion of abnormal values of TSH alone was significant (P<0.001). CONCLUSION: We have shown that the HIC's imposition of a TSH-based algorithm by financial fiat is also scientifically acceptable. Use of this algorithm in hospitals (including psychiatric hospitals) will result in substantial savings.

Algorithms

Prevalence and identification of abnormal lipoprotein levels in a biracial population aged 23 to 35 years (the CARDIA Study). The Coronary Artery Risk Development in Young Adults Study.

This study examines the prevalence of abnormal low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels in young adults to determine the ability of National Cholesterol Education Program Adult Treatment Panel (ATP) guidelines to identify persons with elevated LDL cholesterol, to compare other algorithms with those of the ATP, and to determine the contributions of race, gender, and other coronary artery disease risk factors to identifying patients with elevated LDL and low HDL cholesterol. The cohort was population-based, aged 23 to 35 years, and included relatively equal numbers of blacks and whites, and men and women. The prevalence of LDL cholesterol > or = 160 mg/dl (> 4.1 mmol/L) was 5% in black women, 4% in white women, 10% in black men, and 9% in white men. ATP identified most participants with elevated LDL cholesterol (range: 58.8% of white men to 70.7% of black women). Lipoprotein panels would have been required in 6% to 7% of women and to 15% to 18% of men. Algorithms that used nonlipid risk factors required more lipoprotein panels and identified fewer additional participants at risk. The prevalence of HDL cholesterol < 35 mg/dl (0.9 mmol/L) was 3% in women, 7% in black men, and 13% in white men. Algorithms that used nonlipid risk factors before measuring HDL cholesterol would require HDL cholesterol measurements in 35% of whites and 56% of blacks, but reduced sensitivity for identifying low HDL cholesterol (range: 58% in white men to 93% in black women). In young adults, algorithms based on nonlipid risk factors and family history have lower sensitivity, and increase rather than decrease the number of fasting lipoprotein panels required when compared with ATP levels.

Adult

A reliable potentiometric measurement of ionized calcium and pH on the ICA2 Radiometer in clinical practice.

A second generation analyser for potentiometric measurement of ionized calcium and pH (ICA2 Radiometer, Copenhagen) was tested with respect to analytical performance in two different laboratories. Newly-developed aqueous buffered solutions were used at different Ca2+ concentrations as well as biological specimens prepared from human subjects. The overall precision of ICA2 was very good: CV = 0.0-0.4% for within-run and 0.4-1.7% for day-to-day precision with protein-free solutions and CV = 0.3-0.9% for within-run precision on biological specimens. The adjusted value of Ca2+ to pH 7.40 is an analytical advantage for which the calculation is correct but the assumption made for this algorithm may limit its clinical relevance. Measurements were comparable on ICA2 when performed on either whole blood, serum or plasma. Pre-analytical conditions should be observed such as the choice of anticoagulant and anaerobic conditions. Such a reliable and accurate instrument may promote the use of ionized calcium measurement in daily clinical practice.

Calcium

Diffraction tomography using arbitrary transmitter and receiver surfaces.

The theory of diffraction tomography for two-dimensional objects within the Born approximation is presented for cases where the scattered field is measured over arbitrarily shaped boundaries surrounding the object. Reconstruction algorithms are presented for both plane wave (parallel beam) and cylindrical wave (fan beam) insonification. Special attention is devoted to cases where the measurement and source boundaries are either lines or circles. The theory and algorithms presented are shown to be readily extended to the case of three-dimensional objects.

Filtration

The choice of approach in surgery for acoustic neuromas (vestibular schwannomas).

The advantages and disadvantages of the different surgical approaches for surgery of vestibular schwannomas are described, as well as the problems in evaluating the outcome of the treatment, regarding especially the evaluation of facial nerve function and hearing capacity. The eclectic Copenhagen treatment algorithm is outlined: 1) All tumors measuring 25 mm or more on MRI are operated via the translabyrinthine approach. 2) All patients with PTA poorer than 30 dB, and SDS poorer than 70% are operated via the translabyrinthine approach. 3) Tumors less than 10mm extrameatally, and PTA better than 30 dB and SDS better than 70% are removed via the middle fossa route. 4) Tumors measuring 10-25 mm and PTA better than 30 dB and SDS better than 70% are operated via the suboccipital route. Finally some consequences of postponing surgical treatment is described, demonstrating that 74% of 127 tumors continued to grow with a mean of 3.4 mm increased tumor diameter per year, and that 75% of patients, who were candidates for hearing preservation surgery lost the candidature in the observation period.

Algorithms