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Variability and similarity of manual office and automated blood pressures.

The evaluation and management of hypertension is based on indirect blood pressures obtained in the office (COBPs) using the mercury sphygmomanometer. The usefulness of COBPs is limited by factors such as observer bias, which confound the ability to discern the true blood pressure value. Automated portable monitors have been marketed, which also measure blood pressure (ABP) indirectly throughout 24 hours, but without human intervention. Acceptance of a new device that indirectly records blood pressure depends largely on its the agreement with the established method of blood pressure measurement. This review compares the variability of blood pressures collected indirectly by standard mercury sphygmomanometer and by an auscultatory automated portable blood pressure monitor. The results indicate that blood pressure, when measured indirectly in a hypertensive patient, is quite variable. Automated blood pressures were lower and demonstrated less within-subject variability during repeated measures than COBPs. The agreement between ABPs and COBPs was better than the agreement between COBPs alone on successive visits. In addition, the mean hourly blood pressure profiles recorded throughout 24 hours by automated and manual methods from ten hypertensive patients were nearly identical. These data suggest that blood pressures measured by auscultatory automated methods are similar to and representative of those obtained manually.

Blood Pressure↗

CAFASP3: the third critical assessment of fully automated structure prediction methods.

We present the results of the fully automated CAFASP3 experiment, which was carried out in parallel with CASP5, using the same set of prediction targets. CAFASP participation is restricted to fully automatic structure prediction servers. The servers' performance is evaluated by using previously announced, objective, reproducible and fully automated evaluation methods. More than 60 servers participated in CAFASP3, covering all categories of structure prediction. As in the previous CAFASP2 experiment, it was possible to identify a group of 5-10 top performing independent servers. This group of top performing independent servers produced relatively accurate models for all the 32 "Homology Modeling" targets, and for up to 43% of the 30 "Fold Recognition" targets. One of the most important results of CAFASP3 was the realization of the value of all the independent servers as a group, as evidenced by the superior performance of "meta-predictors" (defined here as predictors that make use of the output of other CAFASP servers). The performance of the best automated meta-predictors was roughly 30% higher than that of the best independent server. More significantly, the performance of the best automated meta-predictors was comparable with that of the best 5-10 human CASP predictors. This result shows that significant progress has been achieved in automatic structure prediction and has important implications to the prospects of automated structure modeling in the context of structural genomics.

Computational Biology↗

A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco-2 samples.

Caco-2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time-consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS), is introduced. This novel approach requires an off-line ZipTip desalting step followed by automated nanoESI-MS/MS, using the NanoMate 100 and ESI Chip. In addition to reduced method development time, automated nanoESI-MS/MS also offers no carry-over between samples, low sample consumption, and ease-of-use as compared with conventional pulled-capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high-throughput. A comparison of Caco-2 samples analyzed both by LC/MS/MS and by automated nanoESI-MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI-MS/MS were in excellent agreement.

Algorithms↗

Automated data collection with a Tecnai 12 electron microscope: applications for molecular imaging by cryomicroscopy.

In high-resolution biological electron microscopy, the speed of collection of large numbers of high-quality micrographs is a rate-limiting step in the overall process of structure determination. Approaches to speed up data collection can be very useful, especially in "single-molecule" microscopy of large multiprotein and protein-nucleic acid complexes, where many thousands of individual molecular images need to be averaged to determine the three-dimensional structure. Toward this end, we report the development of automated low-dose image acquisition procedures on a Tecnai 12 electron microscope using the scripting functionality available on the microscope computer. At the lowest level of automation, the user is required to select regions of interest that are to be imaged. All subsequent steps of image acquisition are then carried out automatically to record high-resolution images on either film or CCD, at desired defocus values, under conditions that satisfy user-specified limits for drift rates of the specimen stage. At the highest level of automation, determination of the best grid squares and the best regions suitable for imaging are carried out automatically. A medium level of automation is also available in which the user can designate the most promising grid squares manually and leave the process of finding the best holes in those grid squares to the microscope computer. We also show that all steps subsequent to insertion of the specimen in the microscope can be carried out remotely by connecting to the microscope computer via the Internet. Both features are implemented using Windows NT and Web-based tools and provide tools for automated data collection on any Tecnai microscope from any location.

Cryoelectron Microscopy↗

Colorimetric in-situ hybridization in clinical virology: development of automated technology.

Automation of in situ hybridization is an important first step toward practical implementation of the widely recognized diagnostic potential of nucleic acid hybridization. Our laboratory has concentrated its efforts towards automating colorimetric in situ hybridization on formalin-fixed paraffin-embedded tissue sections. We have capitalized upon the technology developed for the automation of immunohistochemistry (Brigati et al. 1988) and are collaborating with Fisher Scientific in modifying the Fisher Code-On Stainer to achieve successful automated in situ hybridization. Preliminary results are encouraging. We feel that the capillary gap technology has the potential to be modified to automate other hybridization assay formats such as dot and sandwich blot hybridizations. While specifically developed for colorimetric hybridization, the instrumentation is self-contained and could be safely adapted to the use of radio-labeled probes if necessary.

Colorimetry↗

Automation: the competitive edge for HMOs and other alternative delivery systems.

Until recently, many, if not most, Health Maintenance Organizations (HMO) were not automated. Moreover, HMOs that were automated tended to be automated only on a limited basis. Recently, however, the highly competitive marketplace within which HMOs and other Alternative Delivery Systems (ADS) exist has required that they operate at a maximum effectiveness and efficiency. Given the complex nature of ADSs, the volume of transactions in ADSs, the large number of members served by ADSs, and the numerous providers who are paid at different rates and on different bases by ADSs, it is impossible for an ADS to operate effectively or efficiently, let alone show optimal performance, without a sophisticated, comprehensive automated system. Reliable automated systems designed specifically to address ADS functions such as enrollment and premium billing, finance and accounting, medical information and patient management, and marketing have recently become available at a reasonable cost.

Computer Systems↗

Automating the recording and improving the presentation of the anesthesia record.

Although anesthesia records have been kept for over a hundred years, there is still discussion of their value and content. Two uses of the record are widely accepted: (1) review after the anesthetic event (as in medicolegal disputes), and (2) support of patient care during the delivery of an anesthetic. Although the anesthetic record is mandatory in much of the world, there is not a single standard for its format. Automating the generation and presentation of the record will enhance its value and help develop a consensus as to content. Merely automating the steps used to produce the manually generated record does not realize the full benefit of automation. For maximum benefit, the primary goal of automation should be to support the uses of the record. Specific techniques that are discussed include increasing time resolution, optimizing the type and location of input and display equipment, and tailoring the human interface. Particular attention is paid to the issue of how much detail is acceptable in the record, how to use visual cues to present detail properly, how to exclude extraneous detail, and how to avoid misleading presentations (erroneous interpretation of the data). Specific elements discussed include line width, the use of color, presentation of gradients, statistical summaries, contexts for reporting data, graphical techniques for increasing data content, and pictorial presentations. Current records are more often confusing because presented information is inconsistently displayed or irrelevant than because too much information is offered, and automation can ameliorate this problem.

Anesthesiology↗

Medical Information Bus usage for automated IV pump data acquisition: evaluation of usage patterns.

OBJECTIVE: To identify factors which influence the choice of nurses to use automated collection of i.v. pump data from a prototype Medical Information Bus. DESIGN: Observational study for a duration of three and one-half months. SETTING: Four intensive care units, each with different missions, in an adult hospital. SUBJECTS: One hundred fifty-eight registered nurses including both full and part time. MEASUREMENTS AND MAIN RESULTS: Data were collected from the hospital information system about infusion orders including the type of medication, the number of rate changes, the method of documenting rate changes and the infusion methods. The method of documentation for infusion rate changes was defined as either automated, using a prototype Medical Information Bus (MIB), or manual, using the keyboard at a bedside computer terminal. The method of infusion was defined as either straight gravity feed without an i.v. pump ('no pump'), infusion using a pump but without connection to the hospital information system ('pump only') and infusion using a pump which was connected to the hospital information system using a prototype Medical Information Bus ('automated'). A total of 22,199 rate changes were documented during the study period and of those, 22,055 (99.35%) used the 'automated' method. Medications with the highest average rate change per single container were; Nitroprusside Sodium (9.50), Epinephrine (9.08) and Epoprostenol (7.50). CONCLUSIONS: The nurses used automated i.v. pump data acquisition with medications which required frequent rate changes.

Attitude of Health Personnel↗

Semi-automated digital image analysis of joint space width in knee radiographs.

OBJECTIVE: To design a semi-automated program to measure the minimum tibiofemoral joint space width (JSW) of knee radiographs. DESIGN: Bilateral knee radiographs were obtained twice within a 2 week period from 34 asymptomatic research participants. Radiographic images were analyzed to report both the variability of the image analysis program and the reproducibility of JSW measurements within a 2 week period. In addition, the results were compared with minimum JSW measurements read manually by an experienced musculoskeletal radiologist. RESULTS: The variability of the image analysis program was shown to be within one pixel. The results showed that reproducibility was better with the automated method. In addition, the manual method measured a greater minimum JSW than the automated method. There was no significant difference in between-day measurements. There was a significant difference reported between the automated and manual minimum JSW measurements. CONCLUSION: A novel semi-automated method for measurement of JSW has been developed.

Adult↗

Percutaneous CT-guided biopsy of the lung: comparison between aspiration and automated cutting needles using a coaxial technique.

PURPOSE: To compare the accuracy and complication rate of two different CT-guided transthoracic needle biopsy techniques: fine needle aspiration and an automated biopsy device. METHODS: Two consecutive series of respectively 125 (group A) and 98 (group B) biopsies performed using 20-22 gauge coaxial fine needle aspiration (group A) and an automated 19.5 gauge coaxial biopsy device (group B) were compared in terms of their accuracy and complication rate. RESULTS: Groups A and B included respectively 100 (80%) and 77 (79%) malignant lesions and 25 (20%) and 18 (21%) benign lesions. No significant difference was found between the two series concerning patients, lesions, and procedural variables. For a diagnosis of malignancy, a statistically significant difference in sensitivity was found (82.7% vs 97.4%) between results obtained with the automated biopsy device and fine needle aspiration respectively. For a diagnosis of malignancy, the false negative rate of the biopsy result was significantly higher (p <0.005) in group A (17%) than in group B (2.6%). For a specific diagnosis of benignity, no statistically significant difference was found between the two groups (44% vs 26%) but the automated biopsy device provided fewer indeterminate cases. There was no difference between the two groups concerning the pneumothorax rate, which was 20% in group A and 15% in group B, or the hemoptysis rate, which was 2.4% in group A and 4% in group B. CONCLUSION: For a diagnosis of malignancy when a cytopathologist is not available on-site, automated biopsy devices provide a lower rate of false negative results and a similar complication rate to fine needle aspiration.

Adult↗

Carotid artery stenosis: reproducibility of automated 3D CT angiography analysis method.

The aim of this study was to assess the reproducibility and anatomical accuracy of automated 3D CT angiography analysis software in the evaluation of carotid artery stenosis with reference to rotational DSA (rDSA). Seventy-two vessels in 36 patients with symptomatic carotid stenosis were evaluated by 3D CT angiography and conventional DSA (cDSA). Thirty-one patients also underwent rotational 3D DSA (rDSA). Multislice CT was performed with bolus tracking and slice thickness of 1.5 mm (1-mm collimation, table feed 5 mm/s) and reconstruction interval of 1.0 mm. Two observers independently performed the stenosis measurements on 3D CTA and on MPR rDSA according to the NASCET criteria. The first measurements on CTA utilized an analysis program with automatic stenosis recognition and quantitation. In the subsequent measurements, manual corrections were applied when necessary. Interfering factors for stenosis quantitation, such as calcifications, ulcerations, and adjacent vessels, were registered. Intraobserver and interobserver correlation for CTA were 0.89 and 0.90, respectively (p<0.001). The interobserver correlation between two observers for MPR rDSA was 0.90 (p<0.001). The intertechnique correlation between CTA and rDSA was 0.69 (p<0.001) using automated measurements but increased to 0.81 (p<0.001) with the manually corrected measurements. Automated stenosis recognition achieved a markedly poorer correlation with MPR rDSA in carotids with interfering factors than those in cases where there were no such factors. Automated 3D CT angiography analysis methods are highly reproducible. Manually corrected measurements facilitated avoidance of the interfering factors, such as ulcerations, calcifications, and adjacent vessels, and thus increased anatomical accuracy of arterial delineation by automated CT angiography with reference to MPR rDSA.

Aged↗

Automated protein NMR structure determination using wavelet de-noised NOESY spectra.

A major time-consuming step of protein NMR structure determination is the generation of reliable NOESY cross peak lists which usually requires a significant amount of manual interaction. Here we present a new algorithm for automated peak picking involving wavelet de-noised NOESY spectra in a process where the identification of peaks is coupled to automated structure determination. The core of this method is the generation of incremental peak lists by applying different wavelet de-noising procedures which yield peak lists of a different noise content. In combination with additional filters which probe the consistency of the peak lists, good convergence of the NOESY-based automated structure determination could be achieved. These algorithms were implemented in the context of the ARIA software for automated NOE assignment and structure determination and were validated for a polysulfide-sulfur transferase protein of known structure. The procedures presented here should be commonly applicable for efficient protein NMR structure determination and automated NMR peak picking.

Algorithms↗

Involvement of the transmitter systems of the neostriatum in automation of motor skills in dogs.

Chronic experiments were performed on six dogs to address the influence of automation of a motor skill on the components of an operant defensive reflex, rearrangement of posture, and the characteristics of the projection of the center of mass on a tensometric platform by the forepaws; the effects of activation and blockade of muscarinic and dopamine receptors on the process of automation of the motor skill were also studied. Despite high criteria for execution of the operant reflex, the reproducibility of reflex performance, increases in the tonic component of the response, and the clear diagonal pattern of the postural rearrangement, a local (as opposed to diffuse) projection of the position of the center of mass on the tensometric platform by the forepaws was seen only after prolonged training leading to automation of the skill. The effect of automation of the operant response could be obtained immediately following bilateral microinjection of the muscarinic receptor agonist carbachol into the neostriatum. The same effect, but weaker, was obtained using bilateral microinjections of the dopamine D2 receptor blocker raclopride into the neostriatum. Conversely, bilateral microinjections of the selective muscarinic M1 receptor blocker pirenzepine into the neostriatum gave the opposite result, with increases in the phasic component of the response, impairment of the diagonal pattern of the postural rearrangement, and diffuseness of the projection of the center of mass on the tensometric platform by the forelimbs. It is concluded that the indirect efferent output of the neostriatum has an important role in the process of learning the motor operant reflex involving maintenance of a defined degree of flexion (where the main role is played by the tonic component of the movement) and during the process of automation of the motor skill.

Animals↗

Comparison of left ventricular function by echocardiographic automated border detection and by radionuclide ejection fraction.

Echocardiographic automated border detection can provide on-line estimates of left ventricular cavity area by differentiating blood from tissue backscatter characteristics. The objective of this study was to assess the ability of short-axis measurements of left ventricular cavity area by automated border detection to determine left ventricular function by comparing these measurements to radionuclide measures of ejection fraction in the same patients. Eighty-eight consecutive patients, aged 53 +/- 14 years, underwent automated border detection studies within 2 hours of radionuclide ventriculography. Short-axis imaging with automated border detection was attempted at basal, midpapillary muscle, and apical levels. Maximal left ventricular length was also measured from apical 4- and 2-chamber views by standard imaging. Fractional area change--(end-diastolic area-end-systolic area)/end-diastolic area--was determined at each short-axis level. Volumes and ejection fractions were calculated using: volume = 5/6 (midventricular area).length. Simpson's rule for 3 short-axis measurements was calculated using: volume = (length/12) (5.basal area + 2.mid-area + 4.apical area). Technically adequate automated border detection data could be obtained on 69 patients (78%) at basal and mid-levels, and at all 3 short-axis levels in 66 patients (75%). Correlations with radionuclide ejection fraction were as follows: midventricular fractional area change--R = 0.84, SEE = 12%, y = 0.86 x - 7; area-length ejection fraction--R = 0.89, SEE = 9%, y = 0.96 x - 4; and Simpson's rule--R = 0.91, SEE = 8%, y = 0.89 x + 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pilot performance and preference for short cycles of automation in adaptive function allocation.

The present experiment examined pilot response to the rapid cycling of automation. The experiment was conducted using a multi-task simulation environment consisting of tracking, fuel management, and system monitoring sub-tasks. Monitoring and fuel management sub-tasks were performed manually in all conditions. The tracking sub-task cycled between manual and automated control at fixed intervals of either 15, 30 or 60 sec. These cycle times were completely crossed with three levels of tracking difficulty giving nine within-subject conditions which lasted 5 min each. Performance was measured on each of the sub-tasks, as was pilot fatigue level and subjective workload for the respective conditions. Results indicated that both difficulty and cycle duration significantly affected tracking performance which was degraded with task difficulty and longer cycle times. Fuel management and system monitoring performance were unaffected by tracking difficulty and automation duration. However, a subsequent analysis was conducted using the 15 sec period immediately following each automation episode as a 'window' of performance. A different pattern of results was observed. Tracking performance was similarly affected by difficulty, but was no longer affected by cycle duration. Furthermore, fuel management error indicated a trend toward better performance in low difficulty conditions. Results illustrate micro trade-offs within sub-tasks and macro trade-offs between sub-tasks. Overall, the results support the contention that excessively short cycles of automation prove disruptive to performance in multi-task conditions.

Journal Article↗

Development of an automated closed system for generation of human lymphokine-activated killer (LAK) cells for use in adoptive immunotherapy.

Immunotherapy utilizing the adoptive transfer of lymphokine-activated killer (LAK) cells in conjunction with recombinant interleukin-2 (IL-2) can mediate tumor regression in some patients with advanced cancer. The activation of large numbers of LAK cells was performed in roller bottles in a research laboratory setting and required meticulous aseptic technique, at least one skilled technician per patient and one laminar flow hood per patient. To reduce the complexity and expense of LAK cell generation for human immunotherapy trials we have developed a closed-system automated procedure using a continuous flow blood cell separator. PBL were obtained by standard apheresis techniques. Platelets and plasma were elutriated using countercentrifugal flow of saline in the cell separator machine. The washed PBL were underlaid with Ficoll-Hypaque (FH) in the original separation bag. Lymphocytes were then flushed into a collection bag where they were concentrated and washed with 2 liters of saline. Mean recovery from the automated FH technique was 54.6 +/- 4.3% compared to 62.3 +/- 4.0% using manual methods in 50 ml tubes (P greater than 0.05). Cells were diluted in the collection bag with RPMI 1640 +/- 2% human AB serum and could be dispensed in an automated fashion to polyolefin bags via a sample port with 1000-1500 U/ml IL-2. After 3-4 days of culture in 5% CO2 at 37 degrees C, activated cells from the bags were harvested and washed in a closed system using the continuous flow cell separator. Cell yield from the harvest was 79.2 +/- 5.4% in the automated system compared to 64.9 +/- 5.0% in the standard procedure using manual harvest of roller bottles (P less than 0.01). Lytic capacity of the cells against fresh human tumor in a 4 h 51Cr release assay was equivalent in cells processed either by the automated or the conventional manual method. The advantages of a closed system include decreased potential for microbial contamination and reduced labor and capital equipment costs. This technique may be easily adapted for use with other cell collection and culture systems.

Cell Separation↗

An automated high capacity data capture and analysis system for the in vitro assessment of leukocyte adhesion under shear-stress conditions.

Parallel-plate flow chambers have been used to model the vascular microcirculation and study the in vitro dynamic adhesive interactions of leukocytes and human umbilical vein endothelial cells (HUVECs). We describe here a high capacity system which can simultaneously monitor the adhesive interaction of neutrophils and HUVECs in ten flow chambers. Automated data collection was achieved with an image analyzer controlling the autostage and autofocus attachments of an inverted microscope. Images from the flow chambers were captured via phase-contrast microscopy using a video camera and laser videodisk recorder. The images were downloaded off-line into an image analyzer for automated counting of rolling and adherent cells. Neutrophils were detected by their "phase bright' characteristics. An automated optimization procedure allowed the computer to choose the best setting for the selective detection of neutrophils. In addition, a method which utilized image averaging was used to distinguish between rolling and adherent cells. A comparison of the results obtained from the manual and automated counting methods revealed linear relationships for the counting of both adherent (r = 0.98) and rolling cells (r = 0.96) with counting efficiencies of 59% and 46%, respectively. The utility of the system was demonstrated by its ability to measure the adhesive interaction between neutrophils and HUVEC in response to stimulus such as interleukin-1 alpha (IL-1 alpha), histamine, or formyl-1-methionyl-1-leucyl-1-phenylalanine (fMLP). In conclusion, we have developed an automated assay which combines the capacity of ten flow chambers with a computerized data analysis system; the result is an efficient and reproducible assay which minimizes operator associated errors and biological variability.

Cell Adhesion↗

Managing data quality through automation.

Traditional definitions of data quality deal primarily with individual data sets and the data collection process. Today's standards for ensuring data quality have not changed with respect to the desired results, but have simply been expanded to take advantage of modern technology. Computers are used to acquire, review, store, analyze, and report data. Because each of these steps can be automated, the need for human intervention and manual review is minimized. As a result, the potential for invalid data to reach the data analysis stage has increased significantly. To reduce this potential, efforts must be devoted to developing automated procedures that cover every conceivable validation possibility. Relationships between data and data sets must be well defined [1], and data base support that facilitates ready access to the data for the purpose of analysis must be provided. For small data sets, automation may therefore be impractical; but for large, interrelated data sets, automation is highly desirable. Computer automation has therefore expanded the traditional concept of ensuring data quality to include a complex array of interrelated tasks that must be properly managed to achieve the desired results.

Animals↗