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At least 523 records · Page 29Linked to original sources
PubMed1999

Fully automated microvessel counting and hot spot selection by image processing of whole tumour sections in invasive breast cancer.

BACKGROUND: Manual counting of microvessels is subjective and may lead to unacceptable interobserver variability, which may explain conflicting results. AIMS: To develop and test an automated method for microvessel counting and objective selection of the hot spot, based on image processing of whole sections, and to compare this with manual selection of a hot spot and counting of microvessels. METHODS: Microvessels were stained by CD31 immunohistochemistry in 10 cases of invasive breast cancer. The number of microvessels was counted manually in a subjectively selected hot spot, and also in the same complete tumour sections by interactive and automated image processing methods. An algorithm identified the hot spots from microvessel maps of the whole tumour section. RESULTS: No significant difference in manual microvessel counts was found between two observers within the same hot spot, and counts were significantly correlated. However, when the hot spot was reselected, significantly different results were found between repeated counts by the same observer. Counting all microvessels manually within the entire tumour section resulted in significantly different hot spots than manual counts in selected hot spots by the same observer. Within the entire tumour section no significant differences were found between the hot spots of the manual and automated methods using an automated microscope. The hot spot was found using an eight connective path search algorithm, was located at or near the border of the tumour, and (depending on the size of the hot spot) did not always contain the field with the largest number of microvessels. CONCLUSIONS: The automated counting of microvessels is preferable to the manual method because of the reduction in measurement time when the complete tumour is scanned, the greater accuracy and objectivity of hot spot selection, and the possibility of visual inspection and relocation of each measurement field afterwards.

Breast Neoplasms↗
PubMed2006

Automated microscopy of amniotic fluid cells: detection of FISH signals using the FastFISH imaging system.

OBJECTIVE: FISH (fluorescence in situ hybridization) analysis is a valuable adjunct to cytogenetics that provides a rapid screen for common abnormalities. However, FISH is expensive, labor-intensive, and requires a high skill level and subjective signal interpretation. A fully automated system for FISH analysis could improve laboratory efficiency and potentially reduce errors and costs. METHODS: In this study we blindly compared automated FISH signal acquisition and display against standard FISH analysis. A total of 62 amniocentesis samples were prepared using the AneuVysion multicolor DNA probe kit and probed for chromosomes 13, 18, 21, X, and Y. Two sets of slides were produced from each sample. Fifty cells were scored in each slide. One set was evaluated using standard manual microscopy and the other using the automated image acquisition and display capabilities of the Ikoniscope fastFISH amnio Test System. This system uses epifluorescence optics, along with optimized slide management to process slides automatically. RESULTS: A 100% concordance was observed between the results obtained using manual microscopy and the automated system. There was also 100% concordance between the FISH results and those obtained by conventional karyotyping. CONCLUSION: Our data suggest that the automated system is capable of providing accurate and rapid identification and display of cells and FISH signals.

Adolescent↗
PubMed1996

Significance of automated stenosis detection during quantitative angiography. Insights gained from intracoronary ultrasound imaging.

BACKGROUND: Automated stenosis analysis is a common feature of commercially available quantitative coronary angiography (QCA) systems, allowing automatic detection of the boundaries of the stenosis, interpolation of the expected dimensions of the coronary vessel at the point of obstruction, and angiographically derived estimation of atheromatous plaque size. However, the ultimate meaning of this type of analysis in terms of the degree of underlying atherosclerotic disease remains unclear. We investigated the relationship between stenosis analysis performed with QCA and the underlying degree of atherosclerotic disease judged by intracoronary ultrasound (ICUS) imaging. METHODS AND RESULTS: In 40 coronary stenoses, automated identification of the sites of maximal luminal obstruction and the start of the stenosis was performed with QCA by use of curvature analysis of the obtained diameter function. Plaque size at these locations also was estimated with ICUS, with an additional ICUS measurement immediately proximal to the start of the stenosis. Crescentlike distribution of plaque, indicating an atheroma-free arc of the arterial wall, was recorded. At the site of the obstruction, total vessel area measured with ICUS was 16.65 +/- 4.04 mm2, whereas an equivalent measurement obtained from QCA-interpolated reference dimensions was 7.48 +/- 3.30 mm2 (P = .0001). Plaque area derived from QCA data was significantly less than that calculated from ICUS (6.32 +/- 3.21 and 13.29 +/- 4.22 mm2, respectively; mean difference, 6.92 +/- 4.43 mm2; P = .0001). At the start of the stenosis identified by automated analysis, ICUS plaque area was 9.38 +/- 3.17 mm2, and total vessel area was 18.77 +/- 5.19 mm2 (50 +/- 11% total vessel area stenosis). The arterial wall presented a disease-free segment in 28 proximal locations (70%) but in only 5 sites (12%) corresponding to the start of the stenosis and none at the obstruction (P = .0001). At the site of obstruction, all vessels showed a complete absence of a disease-free segment, and the atheroma presented a cufflike or all-around distribution with a variable degree of eccentricity. CONCLUSIONS: At the site of maximal obstruction, QCA underestimated plaque size as measured with ICUS. Atherosclerotic disease was consistently present at the start of the stenosis and was used as a reference site by automated stenosis analysis. At the start of the stenosis, ICUS demonstrated a mean 50 +/- 11% total vessel area stenosis, with a characteristic loss of disease-free arcs of arterial wall present in proximal locations. Thus, the site identified by automated stenosis analysis as the start of the stenosis does not represent a disease-free site but rather the place where compensatory vessel enlargement fails to preserve luminal dimensions, a phenomenon that seems related to the observed loss of a remnant arc of normal arterial wall.

Aged↗
PubMed1997

ECG-gated three-dimensional intravascular ultrasound: feasibility and reproducibility of the automated analysis of coronary lumen and atherosclerotic plaque dimensions in humans.

BACKGROUND: Automated systems for the quantitative analysis of three-dimensional (3D) sets of intravascular ultrasound (IVUS) images have been developed to reduce the time required to perform volumetric analyses; however, 3D image reconstruction by these nongated systems is frequently hampered by cyclic artifacts. METHODS AND RESULTS: We used an ECG-gated 3D IVUS image acquisition workstation and a dedicated pullback device in atherosclerotic coronary segments of 30 patients to evaluate (1) the feasibility of this approach of image acquisition, (2) the reproducibility of an automated contour detection algorithm in measuring lumen, external elastic membrane, and plaque+media cross-sectional areas (CSAs) and volumes and the cross-sectional and volumetric plaque+media burden, and (3) the agreement between the automated area measurements and the results of manual tracing. The gated image acquisition took 3.9+/-1.5 minutes. The length of the segments analyzed was 9.6 to 40.0 mm, with 2.3+/-1.5 side branches per segment. The minimum lumen CSA measured 6.4+/-1.7 mm2, and the maximum and average CSA plaque+media burden measured 60.5+/-10.2% and 46.5+/-9.9%, respectively. The automated contour-detection required 34.3+/-7.3 minutes per segment. The differences between these measurements and manual tracing did not exceed 1.6% (SD<6.8%). Intraobserver and interobserver differences in area measurements (n=3421; r=.97 to.99) were <1.6% (SD<7.2%); intraobserver and interobserver differences in volumetric measurements (n=30; r=.99) were <0.4% (SD<3.2%). CONCLUSIONS: ECG-gated acquisition of 3D IVUS image sets is feasible and permits the application of automated contour detection to provide reproducible measurements of the lumen and atherosclerotic plaque CSA and volume in a relatively short analysis time.

Adult↗
PubMed1996

Automated measurement of infarct size with scanned images of triphenyltetrazolium chloride-stained rat brains.

BACKGROUND AND PURPOSE: The extent of brain infarction after local cerebral ischemia is frequently assessed with the mitochondrial activity indicator 2,3,5-triphenyltetrazolium chloride (TTC). We describe an automated procedure for analysis of infarct size in TTC-stained rat brains. METHODS: Rats were subjected to middle cerebral artery occlusion and killed after 24 to 36 hours, and their brains were processed for TTC staining. Digital images of coronal sections from these brains (n > 50) were acquired with a desktop color scanner. The resulting images were divided into red, blue, and green component images. Total brain and infarct areas were automatically determined on the basis of total pixel intensity and area after segmentation of the red and green images, respectively. Automated measurements were compared with those made with a video camera-based image acquisition system that required manual tracing of lesion boundaries. RESULTS: The spatial resolution of scanned brain images (approximately equal to 200 microns) was comparable to that of the camera-based system and provided sufficient detail to recognize infarct boundaries and neuroanatomical features. Scanner-based acquisition and analysis were faster than with the camera-based method. The green component image accurately distinguished infarcted from normal brain, and the red component image represented total brain dimensions. Infarct measurements obtained by the automated method correlated closely with those from conventional apparatus (R2 = .89, P < .001). Intraobserver reliability with the automated method (R2 = 1.00) was higher than with the conventional method (R2 = .77). CONCLUSIONS: Infarct size after middle cerebral artery occlusion in the rat can be rapidly and reproducibly assessed with inexpensive scanning equipment and automated image analysis of TTC-stained brains.

Animals↗
PubMed1999

Improved automated detection of embolic signals using a novel frequency filtering approach.

BACKGROUND AND PURPOSE: Asymptomatic embolic signal detection with the use of Doppler ultrasound has a number of potential clinical applications. However, its more widespread clinical use is severely limited by the lack of a reliable automated detection system. Design of such a system depends on accurate characterization of the unique features of embolic signals, which allow their differentiation from artifact and background Doppler speckle. We used a processing system with high temporal resolution to describe these features. We then used this information to design a new automated detection system. METHODS: We used a signal processing approach based on multiple overlapping band-pass filters to characterize 100 consecutive embolic signals from patients with carotid artery disease as well as both episodes of artifact resulting from probe tapping and facial movement and episodes of Doppler speckle. We then designed an automated detection system based both on these embolic signal characteristics and on the fact that embolic signals have maximum intensity over a narrow frequency range. This system was tested in real time on stored 5-second segments of data. RESULTS: The value of peak velocity at maximal intensity discriminated best between embolic signals and artifact and allowed differentiation with 100% sensitivity and specificity. Relative intensity increase, intensity volume, area under volume, average rise rate, and average fall rate appeared to discriminate best between embolic signals and Doppler speckle. For the majority of embolic signals, the intensity increase was spread over a narrow frequency or velocity range. The automated system we developed detected 296 of 325 carotid stenosis embolic signals from a new data set (sensitivity, 91.1%). All 200 episodes of artifact from a new data set were differentiated from embolic signals. Only 2 of 100 episodes of speckle were misidentified as embolic signals. CONCLUSIONS: Using a novel system for automated detection, which utilizes the fact that embolic signals have maximum intensity over a narrow frequency range, we have achieved detection with a high sensitivity and high specificity. These results are considerably better than those previously reported. We tested this initial system on short 5-second segments of data played in real time. This approach now needs to be developed for use in a true online system to determine whether it has sufficient sensitivity and specificity for clinical use.

Artifacts↗
PubMed2006

Automated assessment of diabetic retinal image quality based on clarity and field definition.

PURPOSE: To evaluate the performance of an automated retinal image quality assessment system for use in automated diabetic retinopathy grading. METHODS: Algorithmic methods have been developed for assessing the quality of 45 degrees single field retinal images for use in diabetic retinopathy screening. For this purpose, image quality was defined by two aspects: image clarity and field definition. An image with adequate clarity was defined as one that shows sufficient detail for automated retinopathy grading. The visibility of the macular vessels was used as an indicator of image clarity, since these vessels are known to be narrow and become less visible with any image degradation. An image with adequate field definition was defined as one that shows the desired field of view for retinopathy grading, including the full 45 degrees field of view, the optic disc, and at least two optic disc diameters of visible retina around the fovea. From 489 patients attending a diabetic retinopathy screening program, 1039 retinal images were obtained. The images were graded by a clinician for image clarity and field definition, with a comprehensive image-quality grading scheme. RESULTS: The sensitivity and specificity were, respectively, 100% and 90.9% for inadequate clarity detection, 95.3% and 96.4% for inadequate field definition detection, and 99.1% and 89.4% for inadequate overall quality detection. CONCLUSIONS: The automated system performs with sufficient accuracy to form part of an automated diabetic retinopathy grading system.

Adolescent↗
PubMed2005

Reliability of automated blood pressure devices used by hypertensive patients.

Automated blood pressure (BP) devices are used by many hypertensive patients in Hong Kong, with or without medical advice. At two community clinics, we invited hypertensive patients aged between 40 and 70 years who used such a device to fill in a questionnaire and to have four sets of BP measurements, automated and mercury, at two visits. Of 290 hypertensive patients 120 fulfilled the criteria, and 73 of these agreed to participate. 53 devices measured arm BP, 21 measured forearm BP. The agreement between the mercury sphygmomanometer and the automated devices was poor, with average differences of 9.5 mmHg for systolic and 9.4 mmHg for diastolic and no clear advantage for either site of measurement. As a means of screening for BP >140/90 mmHg the sensitivity of the automated devices was 81% and the specificity was 80%. There were large variations in how often and under what circumstances the devices had been used. One-fifth of the devices had been acquired on medical advice but only 11% of the participants were aware of the three important conditions for operating such devices. Discussion of automated devices, their role and proper use, should now be part of routine hypertensive care.

Adult↗
PubMed2001

A simple automated solution for removing and applying sealing microplate lids.

With the improved reliability and efficiency of automation, there has been an increased desire to integrate automated sample management with automated screening systems. In order to store samples "on line" for an extended period of time, an automation-compatible means for sealing and unsealing microplates is necessary. Numerous commercial solutions are available for removing loose-fitting microplate lids; however, the task of removing a tight-fitting matted lid such as the RoboLid is more challenging. This paper discusses the design of an automated workstation for the application and removal of such tight-fitting microplate lids.

Equipment Design↗
PubMed2003

Simultaneous identification of various antinuclear antibodies using an automated multiparameter line immunoassay system.

The objective was to determine the sensitivity and specificity of an automated multiparameter line immunoassay system compared with other techniques for the identification of autoantibodies in rheumatic diseases. We studied sera from 90 patients. Anti-U1RNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Jo 1 and anti-Scl 70 antibodies were identified by counterimmunoelectrophoresis (CIE) techniques, enzyme-linked immunosorbent assay (ELISA), immunoblotting (IB) using extracts of rabbit thymus and human placenta, and an automated multiparameter line immunoassay system (INNO-LIA ANA UPDATE K-1090) that detects nine different antibodies simultaneously (anti-U1RNP, anti-Sm, anti-Ro/SS-A, anti-La/SS-B, anti-Scl 70, anti-Jo 1, anticentromere, antihistone, and antiribosomal P protein). The line immunoassay system equaled or surpassed the other techniques in the identification of anti-Sm, anti-La/SS-B, anti-Jo 1 and anti-Scl 70 antibodies (sensitivity 100%, specificity 94-100%) and was similarly effective in the case of anti-U1RNP (sensitivity 87.5%, specificity 93.9%) and anti-Ro/SS-A (sensitivity 91.4%, specificity 87.2%) antibodies. In addition, this technique detected more 52 and 60 kD anti-Ro/SS-A sera than IB. Nine antibodies can be detected with this method at a cost of 25.38 Euros per serum sample. In five hours, 19 sera can be studied. The approximate cost of detecting these nine antibodies with an automated ELISA system would be 28.93 Euros, which allows 10 sera to be studied in four hours. In conclusion, the automated multiparameter line immunoassay system is a valid method for the detection of autoantibodies in rheumatic diseases. Its most notable advantages are automated simultaneous detection of several autoantibodies in the same serum and its lower cost compared with ELISA techniques.

Antibodies, Antinuclear↗
PubMed2006

Detection of a paternally inherited fetal mutation in maternal plasma by the use of automated sequencing.

The discovery of circulating fetal DNA in maternal blood has been an encouraging step forward in the prenatal diagnostic field. It has opened up the possibility of development of a noninvasive method for the genetic analysis of the fetus. Many techniques have been applied to the study of this fetal DNA, but automated sequencing has been seldom used. The intention of this study was to use the automated sequencing technique for the detection of a paternally inherited fetal mutation in maternal plasma. Maternal plasma samples from a pregnant woman, whose husband had a mutation (Q134X) in the RP2 gene, which is located in the X-chromosome, were collected at two different gestational ages (10th and 19th week of gestation) in order to determine whether the paternally inherited fetal mutation could be detected by automated sequencing. Restriction analysis was also performed to confirm the results. The fetal mutation was clearly detected in the maternal plasma by the use of automated sequencing. The automated sequencing enables the possibility of analyzing fetal sequences, at a nucleotide level, in order to detect mutations or polymorphisms which are distinguishable from maternal sequences.

Base Sequence↗
PubMed2005

Performance of an automated immature granulocyte count as a predictor of neonatal sepsis.

Neonatologists use immature granulocytes (IG) in manual differential counts as an indicator of sepsis. This study was designed to compare the predictive ability of automated vs manual IG counts for neonatal sepsis. Infants undergoing sepsis evaluation were identified prospectively for study if a CBC count was obtained in temporal proximity to the blood culture. Automated IG counts were obtained from the research software of the Sysmex XE-2100 (Sysmex, Kobe, Japan). Manual average IG counts were obtained from two 100-cell manual differential counts independently performed by a technologist and a hematopathology resident. A comparative analysis of manual and automated IG counts showed considerable overlap of ranges. The highest positive blood culture rate occurred in the nonneutropenic preterm subset of infant older than 7 days (21/55 [38%]). For these infants, elevated IG counts by manual and automated methods were associated significantly with positive blood culture results (odds ratio, manual, 3.74; odds ratio, automated, 3.63), albeit with low sensitivity.

Autoanalysis↗
PubMed1995

Automated 24-hour ambulatory blood pressure monitoring in preeclampsia.

A prospective controlled study was designed to compare automated 24-hour ambulatory blood pressure monitoring with intermittent blood pressure recordings obtained using a sphymomanometer. Blood pressure was measured in 20 hospitalized preeclamptic women in the third trimester. Data obtained using the Spacelabs automated blood pressure monitor was recorded over a period of 24 hours, and thereafter stored and processed in a computer. During the same 24 hour period, blood pressure and heart rate were measured by experienced staff at 07.00, 10.00, 13.00, 15.00, 18.00 and 21.00 hours, with the patient in a semi-recumbent position using a conventional mercury sphygmomanometer with a cuff of appropriate size. Korotkoff phase 5 was used as the indicator of diastolic blood pressure in all recordings by the staff. The main outcome measures were systolic and diastolic blood pressure, mean arterial blood pressure and maternal heart rate. Automated ambulatory monitoring was well tolerated and gave 91.6% successful readings. The mean differences between the blood pressure readings recorded by the monitor and of intermittent mercury sphygmomanometry during daytime were 0.7 (95% confidence interval -2.6 to 4.0) mmHg for the mean arterial blood pressure, -1.7 (95% confidence interval -6.8 to 3.5) mmHg for the systolic blood pressure, and 1.9 (95% confidence interval -2.2 to 6.0) mmHg for the diastolic blood pressure. The mean differences between day-time and night-time monitored blood pressures were 4.3 (95% confidence interval 0.8 to 7.8) mmHg, 4.6 (95% confidence interval 2.0 to 7.2) mmHg, and 4.4 (95% confidence interval 1.5 to 7.2) mmHg, respectively. The number of patients diagnosed as being hypertensive was similar whether automated blood pressure monitor or mercury sphymomanometry was used. Mean maternal heart rate recorded by the monitor or by the staff did not differ. Automated ambulatory blood pressure monitoring is reliable and might improve our understanding of the dynamic changes in blood pressure in pre-eclamptic women and may be a more suitable method to assess the blood pressure control achieved by different drugs.

Autoanalysis↗
PubMed1994

Automated and manual serum free thyroxine assays evaluated with equilibrium dialysis.

Two fully automated serum FT4 assays (Ciba Corning: ACS-180; Abbott Diagnostics: IMx) and two manual/semiautomated assays (Wallac: Delfia; Diagnostic Products Corp.: Coat-A-Count) were compared with a FT4 reference method based on equilibrium dialysis (ED) using routine clinical samples (n = 105-150). For the full range of FT4 concentrations the correlation with ED was good (r = 0.932-0.959), except for Coat-A-Count (r = 0.852), a single-step analogue-type method. Analytical inaccuracy of the automated methods at low FT4 concentrations was revealed by the differential plot: the IMx assay overestimated concentrations < 10 pmol l-1 and the ACS-180 assay concentrations < 6 pmol l-1. The between-assay CVs for the automated methods were not better than for the non-automated assays indicating problems of calibration curve stability for the automated assays.

Autoanalysis↗
PubMed1994

Pharmacy-based automated medication records: methods, application, and a survey of use.

A literature review of articles describing the development and implementation of automated medication administration records is summarized, and the results of a survey undertaken of all hospitals in Missouri to determine the extent of an automated medication administration record (MAR) are reported. For hospitals with an automated MAR, the survey compiled information about the demographics of responding facilities and production and distribution, design, implementation, and procedures for use of automated MARs. The most frequently reported advantages of an automated MAR were a more legible document, increased accuracy, savings in nursing personnel time, and fewer medication errors. The most frequently reported disadvantages were increases in pharmacy personnel time, different interpretation of orders by pharmacy and nursing, and multiple entries required for a medication order to appear correctly on the MAR.

Clinical Pharmacy Information Systems↗
PubMedDate not supplied

Automation of steroid radioimmunoassays using a robotics workstation.

OBJECTIVE: To automate the radioimmunoassay (RIA) of steroids in a diagnostic clinical laboratory. SETTING: The Laboratory of Pediatric Endocrinology, Cornell Medical Center-New York Hospital. PRACTICE DESCRIPTION: A tertiary-care center supporting the diagnosis and treatment of pediatric patients with endocrine disorders. PRODUCT COMPARISON: The Packard MultiPROBE Model 100 Automated Liquid Handling System (Packard Instrument Company, Meriden, CT 06450) was compared with the assays typically used to assist in the diagnosis of steroidogenic disorders in children: extraction of biologic fluids, celite partition chromatography, and RIA. MAIN OUTCOME MEASUREMENT: The comparative efficiency, cost-effectiveness, specificity, and sensitivity of the two methods. RESULT: The automated RIAs correlated (r = 0.963) with the established manual assays for steroids. The specificity and sensitivity of the assays were uniformly maintained after automation. CONCLUSION: The automation of steroid RIAs has made the method a highly efficient and cost-effective one for diagnostic clinical laboratories.

Diagnosis, Computer-Assisted↗
PubMed1999

Automated filtration-based high-throughput plasmid preparation system.

Current methods of plasmid preparation do not allow for large capacity automated processing. We have developed an automated high-throughput system that prepares plasmid DNA for large-scale sequencing. This system is based on our previously reported filtration method. In this method, cell harvesting, alkaline lysis, and plasmid purification occur in a single 96-well microtiter plate from which sequence-ready DNA samples are collected. The plates are designed to allow all reagents to be injected from above the wells and the spent reagents to be aspirated from below. This design has enabled us to build a linear process plasmid preparation system consisting of an automated filter plate stacker and a 21-stage automated plasmid preparator. The 96-well plates used are outfitted with glass-filters that trap Escherichia coli before the plates are stacked in the automated stacker. The plates move from the stacker to each of the 21 stages of the preparator. At specific stages, various reagents or chemicals are injected into the wells from above. Finally, the plates are collected in the second stacker. The optimal throughput of the preparator is 40,000 samples in 17.5 hr. Here, we describe a pilot experiment preparing 15,360 templates in 160 specially designed 96-well glass-filter plates. The prepared plasmids were subjected to restriction digestion, DNA sequencing, and transcriptional sequencing.

Base Sequence↗
PubMedDate not supplied

The challenges of automating a real-time clinical practice guideline.

OBJECTIVE: To elucidate the types of problems encountered during implementation of a World Wide Web-based clinical practice guideline to manage hyperbilirubinemia in newborn infants. DESIGN: Formative assessment of an automated clinical-practice guideline in a large-scale implementation. SETTING: Primary-care clinics and offices, inpatient clinics, and emergency department affiliated with an academic children's hospital. PARTICIPANTS: General pediatricians, neonatologists, pediatric nurses, and computer scientists. RESULTS: Existing guidelines for hyperbilirubinemia management could not be translated directly into web pages. Modifications of the original guidelines were required to represent the clinical intent of the guidelines accurately. In addition, the automated guideline was augmented to incorporate a mechanism for generating clinical encounter forms in order for the system to be accepted into the clinical work flow. Other clinical considerations that influenced the final form of the automated guideline included limitations of computer resources and time constraints during patient encounters. CONCLUSIONS: Many existing guidelines are not amenable to straightforward implementation in automated systems. Strategies to increase the efficacy of the automated guidelines included guideline modifications, as well as careful consideration of the flow of clinical work. Repeated cycles of development and pilot testing are needed to design methods to accommodate the constraints imposed by clinical use.

Boston↗