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Impact of clinical environment on embolus detection: a comparison of automated and manual detection of Doppler embolic signals.

BACKGROUND: Transcranial Doppler ultrasound detection of weak embolic signals is inhibited by intrinsic limitations within the human auditory system. Psychoacoustics effects are likely to be exacerbated in a clinical environment, where automated embolus detection has potential to surpass manual detection. In this study we quantify the impact of clinical environment on manual detection of Doppler embolic signals following carotid surgery. We also discuss the implications of psychoacoustics considerations for the evaluation of automated detection systems. METHOD: Concurrent monitoring by vascular technologists and an automated embolus detection system were performed for 50 consecutive patients during postoperative recovery. Both detection methods were evaluated against a majority decision human expert panel analyzing under ideal conditions. RESULTS: Clinical environment reduced the overall sensitivity of manual monitoring by approximately 23%, mainly due to a approximately 2-dB increase in the lower threshold for detection. Clinical environment was also associated with a reduction in positive predictive value for manual detection of approximately 9% compared to ideal conditions. Automated monitoring, which is not affected by environment, was marginally more sensitive for detection of weaker embolic signals. CONCLUSIONS: One in 4 weak embolic signals was missed during routine clinical monitoring compared to ideal conditions. Automated detection (in this study) performed slightly better than human observers but did not approach the performance of the majority decision panel.

Aged↗

Modeling strategic behavior in human-automation interaction: why an "aid" can (and should) go unused.

Task-offload aids (e.g., an autopilot, an "intelligent" assistant) can be selectively engaged by the human operator to dynamically delegate tasks to automation. Introducing such aids eliminates some task demands but creates new ones associated with programming, engaging, and disengaging the aiding device via an interface. The burdens associated with managing automation can sometimes outweigh the potential benefits of automation to improved system performance. Aid design parameters and features of the overall multitask context combine to determine whether or not a task-offload aid will effectively support the operator. A modeling and sensitivity analysis approach is presented that identifies effective strategies for human-automation interaction as a function of three task-context parameters and three aid design parameters. The analysis and modeling approaches provide resources for predicting how a well-adapted operator will use a given task-offload aid, and for specifying aid design features that ensure that automation will provide effective operator support in a multitask environment.

Aerospace Medicine↗

Automated screening of neurite outgrowth.

Outgrowth of neurites in culture is used for assessing neurotrophic activity. Neurite measurements have been performed very slowly using manual methods or more efficiently with interactive image analysis systems. In contrast, medium-throughput and noninteractive image analysis of neurite screens has not been well described. The authors report the performance of an automated image acquisition and analysis system (IN Cell Analyzer 1000) in the neurite assay. Neuro-2a (N2a) cells were plated in 96-well plates and were exposed to 6 conditions of retinoic acid. Immunofluorescence labeling of the cytoskeleton was used to detect neurites and cell bodies. Acquisition of the images was automatic. The image set was then analyzed by both manual tracing and automated algorithms. On 5 relevant parameters (number of neurites, neurite length, total cell area, number of cells, neurite length per cell), the authors did not observe a difference between the automated analysis and the manual analysis done by tracing. These data suggest that the automated system addresses the same biology as human scorers and with the same measurement precision for treatment effects. However, throughput of the automated system is orders of magnitude higher than with manual methods.

Animals↗

Automated measurement of cell motility and proliferation.

BACKGROUND: Time-lapse microscopic imaging provides a powerful approach for following changes in cell phenotype over time. Visible responses of whole cells can yield insight into functional changes that underlie physiological processes in health and disease. For example, features of cell motility accompany molecular changes that are central to the immune response, to carcinogenesis and metastasis, to wound healing and tissue regeneration, and to the myriad developmental processes that generate an organism. Previously reported image processing methods for motility analysis required custom viewing devices and manual interactions that may introduce bias, that slow throughput, and that constrain the scope of experiments in terms of the number of treatment variables, time period of observation, replication and statistical options. Here we describe a fully automated system in which images are acquired 24/7 from 384 well plates and are automatically processed to yield high-content motility and morphological data. RESULTS: We have applied this technology to study the effects of different extracellular matrix compounds on human osteoblast-like cell lines to explore functional changes that may underlie processes involved in bone formation and maintenance. We show dose-response and kinetic data for induction of increased motility by laminin and collagen type I without significant effects on growth rate. Differential motility response was evident within 4 hours of plating cells; long-term responses differed depending upon cell type and surface coating. Average velocities were increased approximately 0.1 microm/min by ten-fold increases in laminin coating concentration in some cases. Comparison with manual tracking demonstrated the accuracy of the automated method and highlighted the comparative imprecision of human tracking for analysis of cell motility data. Quality statistics are reported that associate with stage noise, interference by non-cell objects, and uncertainty in the outlining and positioning of cells by automated image analysis. Exponential growth, as monitored by total cell area, did not linearly correlate with absolute cell number, but proved valuable for selection of reliable tracking data and for disclosing between-experiment variations in cell growth. CONCLUSION: These results demonstrate the applicability of a system that uses fully automated image acquisition and analysis to study cell motility and growth. Cellular motility response is determined in an unbiased and comparatively high throughput manner. Abundant ancillary data provide opportunities for uniform filtering according to criteria that select for biological relevance and for providing insight into features of system performance. Data quality measures have been developed that can serve as a basis for the design and quality control of experiments that are facilitated by automation and the 384 well plate format. This system is applicable to large-scale studies such as drug screening and research into effects of complex combinations of factors and matrices on cell phenotype.

Automation↗

Toward automated nucleic acid enzyme selection.

Methods for automation of nucleic acid selections are being developed. The selection of aptamers has been successfully automated using a Biomek 2000 workstation. Several binding species with nanomolar affinities were isolated from diverse populations. Automation of a deoxyribozyme ligase selection is in progress. The process requires eleven times more robotic manipulations than an aptamer selection. The random sequence pool contained a 5' iodine residue and the ligation substrate contained a 3' phosphorothioate. Initially, a manual deoxyribozyme ligase selection was performed. Thirteen rounds of selection yielded ligators with a 400-fold increase in activity over the initial pool. Several difficulties were encountered during the automation of DNA catalyst selection, including effectively washing bead-bound DNA, pipetting 50% glycerol solutions, purifying single strand DNA, and monitoring the progress of the selection as it is performed. Nonetheless, automated selection experiments for deoxyribozyme ligases were carried out starting from either a naive pool or round eight of the manually selected pool. In both instances, the first round of selection revealed an increase in ligase activity. However, this activity was lost in subsequent rounds. A possible cause could be mispriming during the unmonitored PCR reactions. Potential solutions include pool redesign, fewer PCR cycles, and integration of a fluorescence microtiter plate reader to allow robotic 'observation' of the selections as they progress.

Automation↗

Validation of an automated enzyme immunoassay for Interleukin-6 for routine clinical use.

Serum levels of Interleukin-6 (IL-6), a proinflammatory cytokine, are increased in early stages of inflammatory diseases such as infection and sepsis. Assay systems which permit its measurement within a few hours and as a single measurement have not been reported so far. We therefore evaluated a now commercially available automated method for IL-6 measurement on the Cobas Core immunological analyzer (Roche Diagnostic Systems) which enables single IL-6 measurement within about 1 hour. The automated assay correlates well with an established, manual microtiter plate assay (Biosource GmbH) which uses the same antibodies and reagents (r=0.98). Accuracy of the automated method was established by adding known amounts of IL-6 international reference preparation. Recovery of the international standard was in the range of 92104%. The automated assay had a precision of singletons below 6% and was linear up to 2800 pg/ml. This automated assay provides a suitable, convenient and time saving method for measurement of IL-6 serum levels in the routine clinical laboratory.

Automation↗

Automated metabolic gas analysis systems: a review.

The use of automated metabolic gas analysis systems or metabolic measurement carts (MMC) in exercise studies is common throughout the industrialised world. They have become essential tools for diagnosing many hospital patients, especially those with cardiorespiratory disease. Moreover, the measurement of maximal oxygen uptake (VO2max) is routine for many athletes in fitness laboratories and has become a defacto standard in spite of its limitations. The development of metabolic carts has also facilitated the noninvasive determination of the lactate threshold and cardiac output, respiratory gas exchange kinetics, as well as studies of outdoor activities via small portable systems that often use telemetry. Although the fundamental principles behind the measurement of oxygen uptake (VO2) and carbon dioxide production (VCO2) have not changed, the techniques used have, and indeed, some have almost turned through a full circle. Early scientists often employed a manual Douglas bag method together with separate chemical analyses, but the need for faster and more efficient techniques fuelled the development of semi- and full-automated systems by private and commercial institutions. Yet, recently some scientists are returning back to the traditional Douglas bag or Tissot-spirometer methods, or are using less complex automated systems to not only save capital costs, but also to have greater control over the measurement process. Over the last 40 years, a considerable number of automated systems have been developed, with over a dozen commercial manufacturers producing in excess of 20 different automated systems. The validity and reliability of all these different systems is not well known, with relatively few independent studies having been published in this area. For comparative studies to be possible and to facilitate greater consistency of measurements in test-retest or longitudinal studies of individuals, further knowledge about the performance characteristics of these systems is needed. Such information, along with the costs and the common features associated with these systems, may aid physicians and scientists to select a system that is best suited to their requirements and may also improve the quality of these frequently-reported physiological measures.

Automation↗

Clinical or industrial pharmacy? Case studies of hospital pharmacy automation in Canada and France.

Automated medication dispensing systems for hospital pharmacies, heralded as an important means of reducing drug errors and improving labor productivity, have also been seen as a means of furthering the transformation of the pharmacy profession from its role in dispensing prescriptions to a clinical profession concerned with treatments and patient outcomes. Automation aids this transformation by transferring the responsibility for routine dispensing to technicians performing rationalized and computer-mediated tasks. Not all pharmacists agree with these trends. Some fear a loss of professional status and employment as their knowledge is expropriated and incorporated into machinery operated by those with lesser qualifications. They fear an industrial rather than a clinical future. Their concerns are compounded by health care cutbacks. These issues were studied at two hospitals in Canada and one in France, all mid-sized public hospitals with automated unit dose drug delivery systems installed in the late 1980s and early 1990s. Preliminary results indicated national differences in approaches to hospital pharmacy automation. In Canada, pharmacists have resisted major changes in their control of the dispensing process and in their traditional roles vis à vis doctors and pharmacy technicians. In France, where hospital pharmacy as a profession is less developed than in North America, automation has brought about a far more radical substitution for pharmacists' labor.

Automation↗

Automated assessment of the quality of depression websites.

BACKGROUND: Since health information on the World Wide Web is of variable quality, methods are needed to assist consumers to identify health websites containing evidence-based information. Manual assessment tools may assist consumers to evaluate the quality of sites. However, these tools are poorly validated and often impractical. There is a need to develop better consumer tools, and in particular to explore the potential of automated procedures for evaluating the quality of health information on the web. OBJECTIVE: This study (1) describes the development of an automated quality assessment procedure (AQA) designed to automatically rank depression websites according to their evidence-based quality; (2) evaluates the validity of the AQA relative to human rated evidence-based quality scores; and (3) compares the validity of Google PageRank and the AQA as indicators of evidence-based quality. METHOD: The AQA was developed using a quality feedback technique and a set of training websites previously rated manually according to their concordance with statements in the Oxford University Centre for Evidence-Based Mental Health's guidelines for treating depression. The validation phase involved 30 websites compiled from the DMOZ, Yahoo! and LookSmart Depression Directories by randomly selecting six sites from each of the Google PageRank bands of 0, 1-2, 3-4, 5-6 and 7-8. Evidence-based ratings from two independent raters (based on concordance with the Oxford guidelines) were then compared with scores derived from the automated AQA and Google algorithms. There was no overlap in the websites used in the training and validation phases of the study. RESULTS: The correlation between the AQA score and the evidence-based ratings was high and significant (r=0.85, P<.001). Addition of a quadratic component improved the fit, the combined linear and quadratic model explaining 82 percent of the variance. The correlation between Google PageRank and the evidence-based score was lower than that for the AQA. When sites with zero PageRanks were included the association was weak and non-significant (r=0.23, P=.22). When sites with zero PageRanks were excluded, the correlation was moderate (r=.61, P=.002). CONCLUSIONS: Depression websites of different evidence-based quality can be differentiated using an automated system. If replicable, generalizable to other health conditions and deployed in a consumer-friendly form, the automated procedure described here could represent an important advance for consumers of Internet medical information.

Australia↗

Automated insufflation of carbon dioxide for MDCT colonography: distension and patient experience compared with manual insufflation.

OBJECTIVE: The purpose of our study was to compare the effects of automated and manual carbon dioxide insufflation before CT colonography on distention and patient acceptance. SUBJECTS AND METHODS: One hundred forty-one symptomatic subjects underwent CT colonography using either an automated device (n = 47) or a manual method (n = 94) for carbon dioxide insufflation. CT data sets were assessed retrospectively in consensus by two blinded observers who graded distention for six colonic segments using a 4-point scale. An additional assessment of the overall clinical adequacy of distention (yes/no) was also made, and any learning curve was sought. Each patient completed a validated 24-point patient questionnaire reflecting patient satisfaction and discomfort. Distention scores, clinical adequacy, and questionnaire responses were analyzed using ordered logistic regression, Fisher's exact test, and the Mann-Whitney test statistic, respectively. RESULTS: Automated insufflation significantly improved distention overall (p = 0.001). For individual segments, distention was significantly improved in the sigmoid (p = 0.007) and descending (p < 0.001) colons when the patient was supine; and in the sigmoid (p = 0.02), descending (p = 0.001), and transverse (p = 0.02) colons when supine and prone positions were combined. No significant difference was seen in the clinical adequacy of distention, nor was there evidence of any learning curve for either insufflation method. Subjects were more weary after automated insufflation (p = 0.03), but no significant difference was seen for the remaining 23 questionnaire items or for feelings of bloating or discomfort. CONCLUSION: Automated carbon dioxide insufflation significantly improves colonic distention compared with manual insufflation. Benefit is greatest in the left colon, particularly when the patient is supine. Patient acceptance is similar to that for manual insufflation.

Aged↗

Use of an automated device for alternative site blood glucose monitoring.

OBJECTIVE: To evaluate the accuracy, comfort, and ease of use of a new automated device for blood glucose monitoring using the arm as an alternative sampling site. RESEARCH DESIGN AND METHODS: These studies use an automated hand-held device that applies a small vacuum, lances the skin, transfers blood onto an electrochemical test strip, and measures glucose. Patients who had type 1 or type 2 diabetes and had received no prior training using this device were recruited from five diabetes clinics. Testing was performed by the patients using this device and by trained healthcare professionals. Blood glucose was measured by 354 patients: from the arm using the device, from the finger using a laboratory reference instrument, and from the finger using the device via the secondary test port. Each patient completed a questionnaire rating the level of pain and ease of use of the device. RESULTS: Blood glucose results in samples obtained from the arm with the automated device agreed well with finger-stick plasma glucose results using a reference instrument (regression slope 0.98, intercept 0.01 mmol/l [0.1 mg/dl], r = 0.96). Error grid analysis showed that 100% of the measurements fell within zones A and B. In the survey, 60% of the patients reported that arm testing with the automated device was "painless;" another 31% of the patients stated that it was "much less painful," and 6% of patients considered using the device "less painful" than finger-stick testing. In a survey containing 15 questions for rating the ease of use with a scale of 1 to 6, the overall mean rating was 5.5. CONCLUSIONS: The automated device is easy to use and provides accurate glucose results; 97% of the patients found it less painful than finger-stick testing.

Adolescent↗

[Advances in the clinical laboratory automation system of Akita University Hospital].

Abstract Clinical laboratory automation, which was widely discussed in the 1960's, was developed in late he 1970's. The computerized automatic analyzing system for clinical laboratories spread nationwide in the 1980's. Akita University Hospital was established in 1971. We have been making efforts to establish the automated clinical laboratory system. The hematological and clinical chemistry divisions were automated in 1981. In 1988, in order to establish a fully automated clinical laboratory, we introduced sample-conveying systems in each division including hematological, clinical chemistry, urinalysis, serological and immunological divisions. In 1998, we connected the sample-conveying systems which had been separately established in each division to create a fully automated clinical laboratory with an integrated sample-conveying system.

Automation↗

[Standardization of operation monitoring and control of the clinical laboratory automation system].

Laboratory automation systems showed up in the 1980s and have been introduced to many clinical laboratories since early 1990s. Meanwhile, it was found that the difference in the specimen tube dimensions, specimen identification formats, specimen carrier transportation equipment architecture, electromechanical interfaces between the analyzers and the automation systems was preventing the systems from being introduced to a wider extent. To standardize the different interfaces and reduce the cost of laboratory automation, NCCLS and JCCLS started establishing standards for laboratory automation in 1996 and 1997 respectively. Operation monitoring and control of the laboratory automation system have been included in their activities, resulting in the publication of an NCCLS proposed standard in 1999.

Automation↗

Automation in clinical microbiology.

Automation was introduced into the clinical microbiology laboratory in the 1960s but initially met with limited success. Today, instruments are an integral part of many clinical laboratories and are used for microbial detection, identification, and susceptibility testing; detection of positive blood cultures; screening urine samples for potential pathogens; and assaying levels of antimicrobial agents in body fluids. Automation has allowed more rapid diagnosis and elimination of the subjective interpretation of many manual tests. In addition, in some cases, automated tests are more sensitive and specific than manual techniques. However, automated testing often is more expensive than manual testing and is associated with the possibility of mechanical failure. Automation will continue to be an important part of the clinical microbiology laboratory and in the future will include more molecular biology technologies, such as the polymerase chain reaction. Perhaps practical applications of flow cytometry will be identified.

Automation↗

Manual and automated AgNOR count in differentiating reactive mesothelial from metastatic malignant cells in serous effusions.

OBJECTIVE: To distinguish reactive mesothelial cells from malignant cells in serous effusions using manual and automated methods of enumeration of argyrophilic nucleolar organizer regions (AgNORs). STUDY DESIGN: In this prospective study, 38 samples of benign (19 cases) and malignant (19 cases) serous effusions were included. AgNOR stain was used in each case along with routine Papanicolaou stain. The smears were examined under an oil immersion objective, and AgNOR dots were counted by direct observation independently by 2 observers. Automated AgNOR counting and morphometry were performed with a Quantimet 600 image cytometer (Leica, Cambridge, England). At least 100 cells were counted in each case. The number of AgNOR dots in individual cells, AgNOR area, nuclear area, AgNOR vs. nuclear area and nuclear perimeter were measured. Data on benign and malignant cells were compared. RESULTS: The AgNOR dots were discrete and smaller in benign effusion cases as compared to coarse and aggregated in malignant effusion cases. In benign reactive effusion cases the mean number of AgNOR dots per nucleus was 2.33 +/- 0.71 and 2.83 +/- 1.15 by the manual and automated method, respectively, whereas that for malignant effusion cases was 7.48 +/- 2.51 and 8.09 +/- 1.69 by the manual and automated method, respectively. Mean total AgNOR areas in benign and malignant groups were 4.77 +/- 2.66 microns 2 and 38.22 +/- 13.71 microns 2, respectively. Mean nuclear area, nuclear perimeter and ratio of AgNORs vs. nuclear area were 48.72 +/- 19.30 microns 2, 24.68 +/- 10.25 microns and .098 in benign effusion cases as compared to 174.25 +/- 82.36 microns 2, 69.03 +/- 27.23 microns and 0.22 in malignant effusion samples. All these values were significantly higher (P < .001, Student's t test) in malignant cells as compared to benign reactive cells. CONCLUSION: AgNOR dot enumeration, AgNOR area and ratio of AgNORs to nuclear area are valuable adjuncts to cytomorphology in differentiating reactive mesothelial cells from malignant cells in serous effusions. Automated AgNOR counting is rapid and less cumbersome.

Adenocarcinoma↗

The application of an automated allele concordance analysis system (CompareCalls) to ensure the accuracy of single-source STR DNA profiles.

A powerful method for validating a scientific result is to confirm specific results utilizing independent methodologies and processing pathways. Thus, we have designed, developed and validated an automated allele concordance analysis system (CompareCalls, patent pending) that performs comparisons between two independent DNA analysis platforms to ensure the highest accuracy for allele calls. Application of this system in a quality assurance role has shown the potential to eliminate greater than 90% of the STR analysis required of a DNA data analyst. While this system is broadly applicable for use with any two independent STR analysis programs, either prior to or following human data review, we are presenting its application to data generated with the ABI Prism Genotyper software system versus data generated with the SurelockID system. With the automated allele concordance analysis system, the GeneScan DNA fragment data generated from an ABI 377 gel image are analyzed in two independent pathways. In one analysis pathway, the GeneScan data are imported into Genotyper software where STR labels are assigned to the fragment data based upon the criteria of the Kazam 20% macro. The "Kazam" macro provided with the Genotyper program works by labeling all peaks in a category (or locus) and then filtering (or removing) the labels from peaks, such as those in stutter positions, that meet predefined criteria. In the second pathway, the GeneScan data are imported into the SurelockID analysis platform where STR labels and error messages are assigned to the fragment data based upon hard-coded allele calling criteria and quality parameters. The resulting STR allele calls for each analysis platform are then compared, utilizing the automated allele concordance analysis system. Any differences in the STR allele calls between the two systems are flagged in a discordance report for further review by a qualified DNA data analyst. The automated allele concordance analysis system guides the DNA data analyst to the discordant data generated by either analysis platform. Additionally, the analyst is also directed to data that are of less than pristine quality which may have an increased potential for errors in interpretation by either analysis platform or by a human DNA data analyst. Implementation of an automated allele concordance analysis system will yield high-quality data for CODIS and free the human DNA data analyst to perform other critical duties within the laboratory.

Alleles↗

Detecting human CD34+ and CD34- hematopoietic stem and progenitor cells using a Sysmex automated hematology analyzer.

In clinical medicine, particularly in the newly developing stem cell therapies required to support the practice of regenerative medicine, the measurement of both CD34+ and CD34- hematopoietic stem cells (HSC)/hematopoietic progenitor cells (HPC) is important in obtaining more accurate information about the total HSC/HPC content in various stem/progenitor cell sources. We report the results of an investigation into methods of detecting CD34+ and CD34- HSC/HPC using the immature information (IMI) channel incorporated into the Sysmex XE-2100 and SE-9000 automated hematology analyzers. In this study, CD34+ and CD34- HSC/HPC were separated by immunologic methods and quantified by flow cytometry (FACScan) and IMI channel analysis. In addition, CD34-/CD133+ HSC were prepared by a sequential antibody-based positive selection strategy. These cells appeared in the same area as CD34+ cells in the IMI channel of the automated hematology analyzer. These findings confirmed that an automated hematology analyzer can be used to measure both CD34+ and CD34- HSC. These results may explain the difference in HSC/HPC counts sometimes observed between the automated hematology analyzer and flow cytometric methods for CD34+ measurement. The results of this study demonstrated the potential of automated cell counting methods for measuring HSC content in cellular products for both research and clinical applications.

AC133 Antigen↗

The international consensus group for hematology review: suggested criteria for action following automated CBC and WBC differential analysis.

In the half century since the first use of automated analyzers, manual techniques, especially microscopic examination of a stained blood film, have complemented analyzer results to provide a comprehensive hematology report on a patient's blood sample. Over the years, as the capabilities and performance of automated analyzers have improved, the respective roles of the automated analyzer and the complementary procedures have changed. Manual action (most commonly smear review) following automated analyzer results is usually triggered by determining whether the results trigger one of a series of criteria for review of results. There is little uniformity among different laboratories on criteria for action. Recognizing the long-standing need for generally accepted guidelines ("rules") which could be applied to criteria for review of CBC and differential results from automated hematology analyzers, Dr. Berend Houwen invited 20 experts to a meeting in the Spring of 2002 to discuss the issues and determine the most appropriate criteria. At this meeting, 83 rules were developed by consensus agreement. These rules were then tested in 15 laboratories on a total of 13,298 blood samples. After a detailed analysis of the data, the rules were refined and consolidated to produce 41 rules that are presented here. They include rules for first-time samples as well as delta rules for repeat samples within 72 hours from a patient. It is hoped that these rules will be useful to a large number of hematology laboratories worldwide. To facilitate validating these rules in individual laboratories before implementation in routine operation for patient samples, a suggested protocol is attached to this paper.

Automation↗