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Development of standards for laboratory automation.

In clinical laboratories, the installation of total laboratory automation systems and/or modular systems has grown dramatically in the 1990s, particularly in the US, Japan, and Europe. As the number of installations and level of interest grew, several individuals and corporations active in the automation field recognized that the development of prospective standards might enable customers of such systems or equipment to purchase analyzers, automation systems or devices, and software from different vendors and retain interconnectivity of such equipment. These individuals also believed that the total market for automation systems and equipment would be significantly greater with standards than without standards, especially if customers were not forced to purchase everything from one vendor, and that there might be competitive pricing and new technology fostered via the standards. This early interest in standards development led to the initiation of a program by NCCLS in 1996 to develop prospective standards for laboratory automation. Part of the NCCLS effort has involved interaction and cooperation with other standards organizations in the US and other countries. This report describes the current status of the development of prospective standards for laboratory automation by NCCLS and the relationship of those standards to those of other standards organizations.

Automation↗

Biological standards and pharmacopoeias.

The use of standards in the control of biological substances is of particular importance because the potency of such substances cannot be adequately determined by physical or chemical means. For these substances, therefore, it is necessary to compare the activity or potency of a given quantity with that of a similar quantity of a standard or reference preparation to which a unitage has been assigned. In order to eliminate as far as possible the inherent variables in biological tests, especially in tests involving animals, the comparison between the standard and the unknown must be made in a single test. Furthermore it is essential that the biological activity of the standard has the same properties as those products for which the standard is used as a control. The master standards are the International Standards held by the World Health Organization and it is necessary to establish European or National Standards calibrated in International Units in order to conserve the stocks of the master standards. Criteria for the quality of preparations suitable as standards will be considered and some examples of their use will be presented.

Biological Products↗

Demonstration results for the standard ENV 12924.

Within the working programme of CEN/TC251 (Health Informatics), a standard for Security Categorisation and Protection for Healthcare Information Systems has been developed. This document was formally adopted in 1997 by CEN as pre-standard CEN ENV 12924. A demonstration and implementation effort, which was to be effected in principle at one location, was planned and executed as part of the MEDSEC project. The standard CEN ENV 12924 contains a security categorisation model for information systems in Healthcare, distinguishing six categories, plus some refinements. For each category it specifies the required protection measures. The project task consisted of demonstrating and implementing the standard (as far as possible within a limited period) in a real life situation, and providing feedback on these results to the CEN organisation. To this end, the categorisation scheme, as specified in the standard, was applied to a large part of the information (sub)-systems in the Leiden University Medical Centre. A set of ten sub-systems was then selected for a more detailed investigation. The actual protection status for each sub-system was evaluated on the basis of the recommended protection profiles specified in the standard. For each of the relevant recommendations in the standard, its status was recorded, and remarks were added on its relevance, feasibility, etc. These detailed data have been gathered in separate reports for each sub-system. These reports evidently are confidential, in view of protection of the hospital's information security. A similar, though more limited exercise has been done at Magdeburg University Hospital (UHM), in order to be able to allow for possible differences in local situations. A thorough comparison of results for different hospitals was beyond the scope of the project, however. From the overall picture we have tried to draw conclusions on the quality, completeness and applicability of the standard, as well as on the actual level of protection of the systems. As a by-product of the investigation, for all systems out of the small group, implementation plans have been specified to bring the protection in the various (sub)-systems on a higher level, where necessary. Subsequently, these plans have been realised to a large extent. To facilitate the bookkeeping of the results, we have used the SIDERO model, resulting from the SEISMED project. This model has been enhanced, for this purpose, with the recommendations from this standard. A brief description of this database model has been included in Appendix B. As an overall conclusion, we may state that the standard has proven to be a very useful instrument, providing a good basis for a security review of the types of Healthcare information systems which are encountered in a hospital environment. Some suggestions have been presented, for amending recommendations that were found too unpractical or too heavy in the circumstances considered. Also, we suggest to add one category to the set of six which is being used now. Furthermore, the use of a 'bookkeeping tool' (like e.g. SIDERO) is strongly recommended.

Computer Security↗

[Standards in quality assurance in nursing].

The purpose of this article is to describe what kind of nursing standards have been written in Finland. The quality assurance process of nursing includes setting of nursing standards. They express the desired quality level of nursing. They would also guide the practice of nursing. The analysed nursing standards were collected from five university hospitals, 15 central hospitals and nine health centers. The standards were collected with the questionnaire studying the present situation of quality assurance of nursing in Finland. The total number of analysed nursing standards was 190. According to the results the standards were mostly set to evaluate and characterize the quality of nursing of the certain patient group (e.g. new born child, dying patient, cancer patient in chemotherapy) and to evaluate the realization of nursing principles. Safety and individuality of nursing and independence and autonomy of patient were the most often appeared nursing principles in the analysed standards. The standards were written in passive and the level of quality was the ideal optimum. The nursing standards were expressed often abstractively and in such a form that the measurement and evaluation of reached level of the standard is a very difficult task.

Finland↗

Importance and applicability of approved clinical instructor standards and criteria to certified athletic trainers in different clinical education settings.

CONTEXT: For optimal clinical education of athletic training students, Clinical Instructor Educators and program directors need to proactively select, train, and evaluate their Approved Clinical Instructors (ACIs). OBJECTIVE: To assess the relative importance and applicability of ACI standards to certified athletic trainers employed in different athletic training clinical education settings. DESIGN: Respondents rated and ranked the importance and applicability of the 7 standards presented by Weidner and Henning. Crucial standards to warrant dropping an ACI from the clinical education program were also listed. SETTING: Mailed questionnaire. PATIENTS OR OTHER PARTICIPANTS: A total of 55 program directors invited their ACIs, representing different types of clinical settings, to complete the questionnaire. Of the 399 ACIs who responded, 30 (8%) worked in clinics, 50 (13%) in high schools, and 319 (79%) in colleges or universities. MAIN OUTCOME MEASURE(S): We compared the mean scores of the importance and applicability ratings and rankings by employment setting. Chi-square analyses were calculated to measure associations between employment settings and whether a standard was crucial. Respondents' comments were also assessed. RESULTS: No significant differences were noted among employment settings for overall importance and applicability ratings. A difference was seen for only interpersonal relationships, with clinic and high school respondents giving this standard higher importance and applicability ratings than college/university respondents. No associations were shown between the settings and whether a standard was marked as crucial. The importance of a standard and barriers to implementing a standard (particularly ACI role strain) were the most common themes. CONCLUSIONS: The Weidner and Henning standards are considered to be important and applicable across a variety of athletic training clinical education settings. Legal and ethical behavior was considered the most crucial standard. The ACIs seemed to be encountering role strain in their dual roles as clinicians and clinical instructors, a problem warranting further investigation.

Journal Article↗

Lyophilized standards for the calibration of real time PCR assay for hepatitis C virus RNA.

BACKGROUND: Since October 1997, an international standard for hepatitis C virus (HCV) nucleic acid amplification technology assay, 96/790, has been available. We compared a series of lyophilized standards with known HCV RNA concentrations against the international standard in fluorescence quantitative PCR detection. METHODS: A series of lyophilized sera were calibrated by ROCHE COBAS AMPLICOR HCV Monitor test against the international standard and sent to various manufacturers to analyse the samples using their own kits. Then calibration curves from the series were compared with that obtained from the external standard calibration curve with the manufacture's series. RESULTS: The standard calibration curve with the series of lyophilized serum showed an excellent correlation (R(2) > 0.98), slope and intercept that were similar to those from the manufacture's series. When the standard calibration curve from the series of lyophilized standards were used to define the values of the given sample, lower coefficients of variation between kits from different manufactures were obtained. CONCLUSION: The results showed that the lyophilized standards could be used to setup the standard calibration curve for clinical HCV RNA quantitative PCR detection.

Calibration↗

[Current state of national or international standards of interferons and cytokines].

Expert committee on Biological standardization (ECBS) of WHO had asked for an advisory committee for preparation of WHO international cytokine standards because of complexities by the rapid increase of number of cytokine molecules some of which are entered into clinical trials. The new meeting of the WHO informal Consultation on Cytokine standards was started from last spring and going to be held annually. The main mission of the committee was considered to be promoting the use of WHO international cytokine standards and reference materials etc., which must be available world wide. Various standard preparations of cytokines and growth factors are available at the National Institute of Biological Standards and Control (NIBSC) in the United Kingdom, some of which have been accepted by WHO as international standards (Table 1). Japanese national standards which had been prepared before establishment of WHO standards, and being labeled as Japanese reference Units (JRU) have to be calibrated with WHO standards to know International Units (IU). Japanese national references of IL-2 and TNF alpha were calibrated by collaboration with related companies and NIH Japan and the concluded results are obtained as follows. IL-2 (rec. DNA):1JRU = 1 IU TNF alpha (rec. DNA):1JRU = 35 IU

Cytokines↗

Compliance and acceptance problems with standardized extracts.

In summary, there are a number of segments of the allergy community that are affected by compliance and acceptance of allergen standardization: regulators, allergen products manufacturers, allergists and allergy patients. To maximize compliance and acceptance of new products, these different groups must be considered when making decisions that impact on standardization and utilization of allergens. In closing it is essential that the following issues are addressed: Units--The number of different units currently used in the same extracts during the transition and the different units used throughout the world are particularly troublesome, both for physicians and patients that they treat. Uniform units or at least a formula to calibrate different units to an international system will go a long way in enhancing the compliance and acceptance of standardized products among those who produce them, use them and are treated by them. Cost--Cost of standardization continues to be a concern. The good news is that the new standardized extracts probably will not cost that much more than the old unstandardized extracts. However, implementation of new extracts can be expensive and we need to find ways in which we can minimize such costs to the allergy patients. Support is needed to continue allergen characterization. We need to encourage traditional sources of funds such as the NIH and manufacturers to continue to provide support for the allergen characterization and the standardization process. Commitment--Is the allergy community really committed to allergen standardization? Are regulators committed to provide the resources to develop standardized extracts? Does the allergist want to use standardized extracts? Do allergy sufferers really want standardized extracts in their treatment?(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗

Metastasis suppression by the standard CD44 isoform does not require the binding of prostate cancer cells to hyaluronate.

Previous studies from this laboratory have demonstrated that down-regulation of the standard CD44 isoform at the mRNA and protein level is associated with the acquisition of high metastatic ability within the Dunning R-3327 system of rat prostate cancers. Additional studies demonstrated that transfection-induced enhanced expression of the standard CD44 isoform suppresses the metastatic ability of the AT3.1 Dunning subline without suppressing tumorigenicity. The standard CD44 isoform is a major cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronate. In this study, an investigation was made to resolve whether the ability of the standard CD44 isoform to suppress metastasis of the AT3.1 prostate cancer cells critically requires enhanced hyaluronate binding. Highly metastatic Dunning AT3.1 rat prostate cancer cells were transfected with expression plasmids encoding either the wild-type or mutant standard CD44 isoform. The mutant standard CD44 isoform construct encoded a protein unable to bind to hyaluronate. Transfectants were isolated and characterized with regard to their level of standard CD44 isoform expression, hyaluronate binding, tumorigenicity, and metastatic ability. Expression of the wild-type standard CD44 isoform increased the hyaluronate binding of prostate cancer cells and suppressed their metastatic ability without suppressing their tumorigenicity. Expression of the mutant CD44 standard isoform did not increase hyaluronate binding; however, it equally suppressed the metastatic ability of the AT3.1 prostate cancer cells. These results demonstrate that the metastasis suppression by the standard CD44 isoform is independent of its ability to bind to hyaluronate.

Animals↗

[Evaluation of the Humphrey perimetry programs SITA Standard and SITA Fast in normal probands and patients with glaucoma].

PURPOSE: To evaluate the new threshold strategies of the Humphrey Field Analyser, SITA Standard and SITA Fast, in normals and glaucoma patients. METHODS: Fifty healthy volunteers and 50 glaucoma patients were tested twice with three algorithms: Full Threshold, SITA Standard and SITA Fast in two sessions. The second test was taken into account to eliminate learning effect. Glaucoma patients were chosen to cover a large range of deficits. Quantitative analysis of global indexes was performed as well as qualitative comparison of visual fields by a trained optometrist. RESULTS: Compared to Full Threshold, testing time was reduced by 51% in normals and 49% in glaucoma with SITA Standard and by 72% and 69% with SITA Fast, respectively. In glaucoma, mean testing time dropped from 16'01" with Full Threshold to 8'05" with SITA Standard and to 4'55" with SITA Fast. Quantitative comparison showed a high correlation between indexes (MD Full Threshold vs MD SITA Standard: r = 0.98, p < 0.01; PSD Full Threshold vs PSD SITA Standard: r = 0.94, p < 0.01). However SITA Standard and SITA Fast had a tendency to underestimate visual field defects. In glaucomatous subjects, mean MD ameliorated by 1.01 dB with SITA Standard and by 1.71 dB with SITA Fast. Mean PSD ameliorated by 0.04 dB and 0.43 dB, respectively. Qualitative analysis confirmed these last results showing artificial slight or important improvement of visual fields in 21% of the cases with SITA Standard and 30% with SITA Fast, compared to Full Threshold. CONCLUSION: SITA Standard and SITA Fast strategies improve dramatically visual field testing time, by 51% and 72% respectively. However, one should be cautious in comparing results obtained with different algorithms, as these new strategies improve the mean defect and, to a lesser extent, the localized defect.

Adult↗

Quantification of EGFP expression on Molt-4 T cells using calibration standards.

BACKGROUND: Enhanced green fluorescent protein (EGFP) is used extensively to assess gene expression on cells; however, quantification of this expression by flow cytometry has been limited by the unavailability of calibration standards. Thus, we characterized the response of an experimental set of EGFP calibration standards to environmental changes and then quantitate the expression of EGFP, in molecules of equivalent soluble fluorochrome (MESF) units, of a transfected Molt-4 T cell line by flow cytometry. METHODS: Characterization of the EGFP standards: EGFP standards were equilibrated in suspension solutions having a pH range of 5.0-9.0, temperatures of 37-80 degrees C, and osmolalities of 100-600 mOsm/kg. Quantification of EGFP on cells: For transfections, Molt-4 T cells were incubated with two different concentrations (0.2 microg and 0.4 microg) of pEGFP-N2 vector and the EGFP expression was quantified after 48 h by flow cytometry using the EGFP standards and by the cytofluor technique using a standard curve of known EGFP solutions. RESULTS: The fluorescence intensity of the EGFP standards increased from pH 5.0 to 9.0 and remained relatively constant from 37 degrees C to 65 degrees C, and from 100 to 600 mOsm/kg. After transfection, the expression of the populations with high and low EGFP expression averaged 8,098 +/- 584 MESF and 3,808 +/- 375 MESF respectively. No significant differences were observed after comparing the MESF values obtained by flow cytometry and the values obtained by Cytofluor technique (high: 8,791 +/- 492 MESF; low: 4,082 +/- 398 MESF). CONCLUSIONS: Our data demonstrate the feasibility of using calibration standards to quantify EGFP expression on cells. Our results emphasize the importance of monitoring the effects of environmental changes in the fluorescence intensity of both standards and samples when quantifying the expression of EGFP on living cells.

Calibration↗

NIST physical standards for DNA-based medical testing.

As DNA and RNA become major targets for clinical laboratory analysis, benchmark reagents will play an increasingly important role in standardization. Reliable national and international nucleic acid standards promote automation and third-party reimbursement for clinical testing. Furthermore, nucleic acid standards provide materials for quality assurance and quality control (QA/QC), and proficiency testing. Standard methods and training initially evolved from consensus guidelines endorsed by professional societies and governmental agencies. The National Institute of Standards and Technology (NIST), a nonregulatory agency of the U.S. Department of Commerce, develops and certifies physical and chemical standards in support of national commerce, manufacturing, and science. In its role supporting U.S. science and industry, the NIST responds to specific standards needs, most recently for medically and biologically important analytes. Broad-based consensus developed through interdisciplinary NIST workshops initiated development of NIST-certified DNA standards. Such materials serve the diagnostic community and help manufacturers benchmark a variety of DNA diagnostic testing platforms. Here we summarize the NIST experience and programs for development of national standards for DNA-based medical diagnostic testing.

Clinical Laboratory Techniques↗

Standardized versus open-ended assessment of psychosocial and medical concerns among African American breast cancer patients.

Standardized quality of life measures have been developed and used primarily with Caucasian and middle-class cancer patients. This study assessed the ability of several widely used standardized measures to capture the concerns and problems of 89 African American breast cancer patients. Concerns and problems were assessed using both an open-ended format and standardized measures. The degree of overlap in responses from these two formats was examined. The most frequently reported problems in the open-ended format included physical (43%), financial (40%), and worry about others (30%). Overall, standardized measures had significant overlap with open-ended concerns and problems. The Cancer Rehabilitation Evaluation System-Short Form subscales/items were associated with corresponding open-ended physical, financial, and social problems (R2 change = 0.07-0.16, p's < or = 0.02), the Interpersonal Support Evaluation List-Short Form was associated with open-ended social problems (R2 change = 0.11, p = 0.004), and the Mental Health Inventory was associated with open-ended psychological distress problems (R2 change = 0.08, p = 0.01). One category of open-ended problems, worry about others, was not captured by standardized measures. With the exception of associations between open-ended physical problems and psychological distress measures, there were few significant correlations between standardized measures and dissimilar problem categories. These findings suggest that the standardized measures in this study reflected the concerns and problems of African American breast cancer patients. Additional studies are needed to evaluate the utility of other widely used standardized measures that have not been developed or standardized among non-white samples.

Adaptation, Psychological↗

The First International Standard for Antitetanus Immunoglobulin, Human; pharmaceutical evaluation and international collaborative study.

The First International Standard (IS) for Antitetanus Immunoglobulin, Human (coded 26/488) was established by the WHO Expert Committee on Biological Standardization in October 1992 on the basis of an extensive pharmaceutical evaluation and an international collaborative study. Fifteen laboratories from 15 countries performed the toxin neutralization assay in vivo in the study. Twelve laboratories also performed an alternative in vitro assay. The new International Standard is a purified human immunoglobulin containing antibodies which are able to neutralize tetanus toxin. This new standard replaces the Second International Standard for Tetanus antitoxin, Equine, for testing of human antitetanus immunoglobulin preparations used clinically as well as for titration of human serum samples for tetanus antitoxin. The new International Standard was assigned a potency of 120 International Units (IU) of Tetanus Antitoxin per ampoule on the basis of its calibration in terms of the International Unit defined by the Second International Standard for Tetanus Antitoxin, Equine by toxin neutralization assay in vivo. The same preparation was also established as the first European Pharmacopoeia Standard for Antitetanus Immunoglobulin, Human by the European Pharmacopoeia Commission, Biological Standardization Programme in March 1993.

Animals↗

Validation of anatomical standardization of FDG PET images of normal brain: comparison of SPM and NEUROSTAT.

PURPOSE: Statistical parametric mapping (SPM) and NEUROSTAT (NS) are widely used for intersubject statistical analysis of brain images. We investigated individual anatomical variations after standardization of 18F-fluorodeoxyglucose positron emission tomography (FDG PET) images of normal brain and compared the differences in the standardized images obtained from SPM and NS. METHODS: Twenty healthy normal subjects were recruited for FDG PET and magnetic resonance imaging (MRI) studies. Sylvian fissures (SF), cingulate sulci (CingS) and central sulci (CtlS) were marked on the brain surface of each individual's co-registered MR images. Then spatial standardization was performed on each subject's PET images using SPM99 and NS with NS's FDG template image, and each subject's MR images (with the SF, CingS, and CtlS marked in advance) were standardized using the sets of parameters obtained from PET standardization by SPM and NS, respectively. The coordinates of each subject's SF, CingS, and CtlS detected on the MR images standardized by the two methods were measured and compared with those on the template images. RESULTS: The mean individual deviations from the averaged coordinates for the markers on the SF, CingS and CtlS standardized by SPM and by NS were no more than 0.21-1.15 mm. The number of voxels within the brain volume on standardized MR images of all 20 subjects was 88.0% of the total number of brain volume voxels for SPM and 85.3% for NS. CONCLUSION: This study demonstrates that SPM and NS yield relatively small differences in standardization and that both methods are effective and valid for PET studies in normal subjects.

Adolescent↗

Choice of standard plasma for diagnosis and quantitation of lupus anticoagulants.

We have recently developed a computer-assisted, semi-automated test for lupus anticoagulants (LA), based on the Activated Partial Thromboplastin Time (APTT) and the Russell's Viper Venom Time (RVVT). In this test, plasma samples mixed 1:1 with pooled normal plasma are tested at one low (screening procedure) and one high (confirming procedure) cephalin concentration, using an automated clot timer. The ratio of these two clotting times, divided by the corresponding ratio for normal plasma, was defined as the Lupus Ratio (LR). Based on the LR of several dilutions of a strong LA positive plasma, a standard curve was constructed for LA quantitation in both the APTT and the RVVT system. In the present article, we discuss the use of different LA positive plasma as standards for the identification as well as quantitation of LA. Due to the heterogeneity of LA, the shape and slope of the standard curves as well as the cut-off points between "normal" and "pathological" values varied from one plasma to another. Thus, the result of LA quantitation of a given plasma varied considerably, according to the choice of standard plasma. A strong LA plasma should be chosen as a standard, since any standard plasma only allows the quantitation of plasmas with a lower LR than its own. A pool of several plasmas is also suitable as a standard. In addition to LA quantitation, such a standard could be used to define the cut-off between "normal" and "abnormal" results in each assay, as a certain dilution of the standard plasma. The present study also confirms the greater sensitivity of the APTT as compared to the RVVT for LA detection.

Adolescent↗

Report of a collaborative study to calibrate the Second International Standard for parvovirus B19 antibody.

A collaborative study was undertaken to assess the suitability of a replacement for the First International Standard for parvovirus B19 IgG, human serum and to calibrate it in IU. The proposed standard, which is a pool of sera from 16 US blood donors, was assayed along with the First International Standard, a coded duplicate of the proposed standard and a plasma sample from a single blood donor. Nine laboratories from eight countries participated in the studies and five different assay kits were used. Two kits contained VP1+VP2, one kit contained VP1 only and two kits, one of which was used by five participants contained VP2 only. Differences in detection of the proposed standard and the individual plasma were observed with assay kits containing different antigens, VP1, VP2 or VP1+VP2. However, since VP1 is a minor capsid protein and on its own does not assemble into virus like particles and the dominant response in individuals appears to be against VP2, it was considered reasonable to utilize only the data from kits containing VP2 antigen for the calibration of the proposed standard. The results of this study demonstrated that the proposed standard coded 01/602 was suitable to serve as the replacement International Standard for parvovirus B19, serum IgG, and this preparation was established as the Second International Standard for parvovirus B19 antibody, plasma human, with an assigned unitage of 77 IU per ampoule by the Expert Committee on Biological Standardisation of the World Health Organisation in February 2003.

Calibration↗

Prevalence and correlates of adequate performance on a measure of abilities related to decisional capacity: differences among three standards for the MacCAT-CR in patients with schizophrenia.

Despite the availability of structured decision-making capacity assessment tools, insufficient guidance exists for applying their results. Investigators often use cutpoints on these instruments to identify potential subjects in need of further assessment or education. Yet, information is lacking regarding the effects of different cutpoints on the proportion and characteristics of individuals categorized as possessing adequate or impaired decisional abilities for consent to research. To demonstrate the potential impact of different standards, we informed 91 individuals, aged 50 or older with a diagnosis of schizophrenia or schizoaffective disorder, about a hypothetical clinical trial, and assessed their decisional abilities with the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR). Three published MacCAT-CR-based standards were applied to participants' scores to examine the rates and correlates of categorical determinations of adequate performance. The three standards ranged in stringency: the most stringent incorporated cutpoints on all three of the major MacCAT-CR subscales (Understanding, Appreciation, and Reasoning); the other two standards required threshold performance only on the Understanding subscale. The most stringent standard resulted in a 57% rate of impaired performance; the intermediate standard, 19%; and the least stringent standard, 8%. Nearly half of the participants (n=45) were classified as having performed adequately by the least stringent standard yet inadequately by the most stringent. The majority of these 45 were impaired on the Appreciation subscale (n=9), Reasoning (n=15), or both (n=18). Cognitive functioning was correlated with performance status for the more stringent standards. These findings underscore the need for refinement of capacity assessment procedures and for improvements in the use of capacity assessment tools for screening purposes and to assist in categorical capacity determinations.

Aged↗