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Set-up of large laboratory-scale chromatographic separations of poly(ethylene glycol) derivatives of the growth hormone-releasing factor 1-29 analogue.

In this paper we report the scale-up of the purification of poly(ethylene glycol) (PEG) derivatives of the growth hormone-releasing factor 1-29, from laboratory scale (100 mg of bulk starting material) to larger scale (3 g of bulk), through the use of a cation-exchange TSK-SP-5PW chromatographic column. A one-step purification process capable of purifying large amounts of mono-PEGylated GRF species from the crude reaction mixture was developed. A simple, straightforward stepwise gradient elution separation was developed at laboratory scale and then scaled up with a larger column packed with a chromatographic resin with the same chemistry which maintained the laboratory-scale separation profile. Active material recovery and material purity remained constant through the scale-up from the 13-microm stationary phase to the 25-microm larger column. Overall, the gram GRF equivalent/batch process scale showed to be quite reproducible, and could be considered as a good platform for scale up to production scale.

Cation Exchange Resins↗

On the mechanism for scale invariance in orientation-defined textures.

Texture perception is generally found to be scale invariant, that is, the perceived properties of textures do not change with viewing distance. Previously, Kingdom, F. A. A., Keeble, D. R. T., & Moulden, B. (Vision Research, 1995, 35, 79-91) showed that the orientation modulation function (OMF), which describes sensitivity to sinusoidal modulations of micropattern orientation as a function of modulation spatial frequency, was scale invariant--peak sensitivity occurred at a modulation spatial frequency which was invariant with viewing distance when modulation frequency was plotted in object units, e.g. cycles cm-1. We have attempted to determine the mechanism underlying the scale invariant properties of the OMF. We first confirmed that the OMF was scale invariant using Gabor-micropattern textures. We then measured OMFs at a number of viewing distances, while holding constant various stimulus features in the retinal image. The question was which stimulus feature(s) disrupted scale invariance when manipulated in this way. We found that the scale (size) of the micropatterns was a critical factor and that the most important scale parameter was the micropatterns' carrier spatial frequency. Micropattern length and density were shown to have a small influence on scale invariance, while micropattern width had no influence at all. These results are consistent with the idea that scale invariance in orientation-defined textures is a consequence of 'second-stage' texture-sensitive mechanisms being tied in spatial scale selectivity to their 'first-stage' luminance-contrast-sensitive inputs.

Humans↗

Pain assessment in cognitively impaired and unimpaired older adults: a comparison of four scales.

The purpose of the study was to compare the psychometric properties of four established pain scales in a population of hospitalized older adults (mean age, 76 years) with varying levels of cognitive impairment. Patients made ratings of current pain three times/day for 7 days. They also made retrospective daily, weekly, and bi-weekly ratings of usual, worst, and least pain levels over a 14-day period. Ratings were made on four different scales, varying in numeric and verbal demands: a five-point verbal rating scale, a seven-point faces pain scale, a horizontal 21-point (0-100) box scale, and two vertical 21-point (0-20) box scales (measuring pain intensity and pain unpleasantness). The accuracy, reliability, construct validity, postdictive validity, and bias susceptibility of each scale were evaluated. The horizontal 21-point box scale emerged as the best scale with respect to both psychometrics and validity, regardless of mental status. Pain intensity did not vary as a function of mental status. Retrospective estimates of pain varied by mental status: a combination of usual/worst pain was best for cognitively impaired patients, while a combination of usual/least pain was best for unimpaired patients. These findings support the use of the 21-point box scale for pain assessment in older patients, including those with mild-to-moderate cognitive impairment. They also support the ability of older, cognitively impaired patients to rate pain reliably and validly.

Aged↗

The Faces Pain Scale-Revised: toward a common metric in pediatric pain measurement.

The Faces Pain Scale (FPS; Bieri et al., Pain 41 (1990) 139) is a self-report measure used to assess the intensity of children's pain. Three studies were carried out to revise the original scale and validate the adapted version. In the first phase, the FPS was revised from its original seven faces to six, while maintaining its desirable psychometric properties, in order to make it compatible in scoring with other self-rating and observational scales which use a common metric (0-5 or 0-10). Using a computer-animated version of the FPS developed by Champion and colleagues (Sydney Animated Facial Expressions Scale), psychophysical methods were applied to identify four faces representing equal intervals between the scale values representing least pain and most pain. In the second phase, children used the new six-face Faces Pain Scale-Revised (FPS-R) to rate the intensity of pain from ear piercing. Its validity is supported by a strong positive correlation (r=0.93, N=76) with a visual analogue scale (VAS) measure in children aged 5-12 years. In the third phase, a clinical sample of pediatric inpatients aged 4-12 years used the FPS-R and a VAS or the colored analogue scale (CAS) to rate pain during hospitalization for surgical and non-surgical painful conditions. The validity of the FPS-R was further supported by strong positive correlations with the VAS (r=0.92, N=45) and the CAS (r=0.84, N=45) in this clinical sample. Most children in all age groups including the youngest were able to use the FPS-R in a manner that was consistent with the other measures. There were no significant differences between the means on the FPS-R and either of the analogue scales. The FPS-R is shown to be appropriate for use in assessment of the intensity of children's acute pain from age 4 or 5 onward. It has the advantage of being suitable for use with the most widely used metric for scoring (0-10), and conforms closely to a linear interval scale.

Adult↗

Master scaling of perceived intensity of touch, cold and warmth.

A new approach is presented for scaling perceived intensity of touch, cold and warmth based on magnitude estimation. In this method named master scaling thenar is utilized as common reference area for scaling and calibrating perceived intensity. The master scaling is particularly well suited for clinical applications in which the stimulation in pain-affected body areas creates a complex perception (e.g., paradoxical heat for cold stimulation) and/or aberrant psychophysical functions for perceived intensity. The results from three different experiments showed that: (a) All patients and healthy subjects were able to scale adequately the perceived intensity of touch, cold, and warmth at unaffected body areas. (b) Thenar stimulations were shown to be adequate common references in the joint scaling of perceived intensity of other body areas in pain patients as well as healthy persons. (c) Individual thenar psychophysical functions can be used for screening patients and healthy persons with regard to their ability to scale perceived intensity of touch, cold and warmth. (d) Master scaled perceived intensity scales can be used for determining if various pain-unaffected body areas are normal or abnormal in patients and in healthy persons. (e) The interindividual variation in perceived intensity is considerably reduced after master scaling and approaches that of intraindividual variation as found in olfaction and hearing. Finally, empirically based thenar Master Functions of perceived intensity for touch, cold and warmth are proposed to be used in future sensory testing of patients, as well as of healthy persons.

Adult↗

[Comparative analysis of rate scales of urinary incontinence in women].

OBJECTIVE: Rate scales are used to analyse urinary incontinence. There are many scales making it difficult to compare the different studies of urinary incontinence. The purpose of this study was to evaluate and compare the rate scales pertaining specifically to urinary incontinence. PATIENTS AND METHOD: A review of the literature was performed for publications specifically addressing rate scales of urinary incontinence. Each scale was evaluated using the following four criteria: principal characteristics (reference source, number of items addressed, scoring method, language), objectives (type of incontinence, severity and quality of life measures), psychometric properties (scientific validity, reliability and responsiveness) and linguistic validation. RESULTS: Thirteen scales were identified. These were divided into two groups: (1) those based on "classifications" and (2) those based on specific questionnaires. Scales based on classifications were not precise and are never scientifically validated. Scales based on questionnaires were more elaborate and more detailed; nevertheless, the study of their psychometric properties was often incomplete. DISCUSSION AND CONCLUSION: Classification-based rate scales are inadequate to analyse urinary incontinence. Questionnaire-based rate scales are superior, but at minimum, they should address the previously stated objective and psychometric criteria. The choice of questionnaire should depend on whether it is to be used in clinical practice or for research protocol.

Female↗

Beyond the '3/4-power law': variation in the intra- and interspecific scaling of metabolic rate in animals.

In this review I show that the '3/4-power scaling law' of metabolic rate is not universal, either within or among animal species. Significant variation in the scaling of metabolic rate with body mass is described mainly for animals, but also for unicells and plants. Much of this variation, which can be related to taxonomic, physiological, and/or environmental differences, is not adequately explained by existing theoretical models, which are also reviewed. As a result, synthetic explanatory schemes based on multiple boundary constraints and on the scaling of multiple energy-using processes are advocated. It is also stressed that a complete understanding of metabolic scaling will require the identification of both proximate (functional) and ultimate (evolutionary) causes. Four major types of intraspecific metabolic scaling with body mass are recognized [based on the power function R=aMb, where R is respiration (metabolic) rate, a is a constant, M is body mass, and b is the scaling exponent]: Type I: linear, negatively allometric (b<1); Type II: linear, isometric (b=1); Type III: nonlinear, ontogenetic shift from isometric (b=1), or nearly isometric, to negatively allometric (b<1); and Type IV: nonlinear, ontogenetic shift from positively allometric (b>1) to one or two later phases of negative allometry (b<1). Ontogenetic changes in the metabolic intensity of four component processes (i.e. growth, reproduction, locomotion, and heat production) appear to be important in these different patterns of metabolic scaling. These changes may, in turn, be shaped by age (size)-specific patterns of mortality. In addition, major differences in interspecific metabolic scaling are described, especially with respect to mode of temperature regulation, body-size range, and activity level. A 'metabolic-level boundaries hypothesis' focusing on two major constraints (surface-area limits on resource/waste exchange processes and mass/volume limits on power production) can explain much, but not all of this variation. My analysis indicates that further empirical and theoretical work is needed to understand fully the physiological and ecological bases for the considerable variation in metabolic scaling that is observed both within and among species. Recommended approaches for doing this are discussed. I conclude that the scaling of metabolism is not the simple result of a physical law, but rather appears to be the more complex result of diverse adaptations evolved in the context of both physico-chemical and ecological constraints.

Adaptation, Physiological↗

Universal scaling of respiratory metabolism, size and nitrogen in plants.

The scaling of respiratory metabolism to body size in animals is considered to be a fundamental law of nature, and there is substantial evidence for an approximate (3/4)-power relation. Studies suggest that plant respiratory metabolism also scales as the (3/4)-power of mass, and that higher plant and animal scaling follow similar rules owing to the predominance of fractal-like transport networks and associated allometric scaling. Here, however, using data obtained from about 500 laboratory and field-grown plants from 43 species and four experiments, we show that whole-plant respiration rate scales approximately isometrically (scaling exponent approximately 1) with total plant mass in individual experiments and has no common relation across all data. Moreover, consistent with theories about biochemically based physiological scaling, isometric scaling of whole-plant respiration rate to total nitrogen content is observed within and across all data sets, with a single relation common to all data. This isometric scaling is unaffected by growth conditions including variation in light, nitrogen availability, temperature and atmospheric CO2 concentration, and is similar within or among species or functional groups. These findings suggest that plants and animals follow different metabolic scaling relations, driven by distinct mechanisms.

Body Size↗

A risk assessment scale for the prediction of pressure sore development: reliability and validity.

BACKGROUND: The ability to assess the risk of a patient developing pressure sores is a major issue in pressure sore prevention. Risk assessment scales should be valid, reliable and easy to use in clinical practice. AIM: To develop further a risk assessment scale, for predicting pressure sore development and, in addition, to present the validity and reliability of this scale. METHODS: The risk assessment pressure sore (RAPS) scale, includes 12 variables, five from the re-modified Norton scale, three from the Braden scale and three from other research results. Five hundred and thirty patients without pressure sores on admission were included in the study and assessed over a maximum period of 12 weeks. Internal consistency was examined by item analysis and equivalence by interrater reliability. To estimate equivalence, 10 pairs of nurses assessed a total of 116 patients. The underlying dimensions of the scale were examined by factor analysis. The predictive validity was examined by determination of sensitivity, specificity and predictive value. RESULTS: Two variables were excluded as a result of low item-item and item-total correlations. The average percentage of agreement and the intraclass correlation between raters were 70% and 0.83, respectively. The factor analysis gave three factors, with a total variance explained of 65.1%. Sensitivity, specificity and predictive value were high among patients at medical and infection wards. CONCLUSION: The RAPS scale is a reliable scale for predicting pressure sore development. The validity is especially good for patients undergoing treatment in medical wards and wards for infectious diseases. This indicates that the RAPS scale may be useful in clinical practice for these groups of patients. For patients undergoing surgical treatment, further analysis will be performed.

Activities of Daily Living↗

Impact of quality scales on levels of evidence inferred from a systematic review of exercise therapy and low back pain.

OBJECTIVE: To assess whether the scale used affects levels of evidence inferred from a systematic review of studies on exercise therapy and chronic low back pain (LBP). DESIGN: Twenty trials previously analyzed in a systematic review were assessed by 2 readers using 16 different scales. SETTING: Tertiary care teaching hospital in France. PARTICIPANTS: Chronic LBP patients. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: For the scales allowing classification into high- and low-quality trials, a rating system with 4 levels of evidence was used to summarize conclusions drawn. The Spearman rank correlation coefficient was used to assess correlations between the scores obtained with the different scales. Interrater reliability of the scales was assessed with the intraclass correlation coefficient and the Bland and Altman method, and the degree of agreement between the readers was calculated using the kappa coefficient. RESULTS: Two of the 3 main results of the systematic review (conflicting evidence on the effectiveness of exercise therapy compared with inactive treatments; strong evidence that exercise therapy is more effective than usual care by a general practitioner) were influenced by the scale used. The range of the Spearman rank correlation coefficients between the different scales was wide (range,.49-.94), the interreader reliability of the scales was heterogeneous, and the interreader agreement was often low (kappa<or=.60 for 7/10 tests). CONCLUSIONS: The use of summary scores to identify physical therapy trials of high quality is questionable. Different quality assessment scales should probably be used to assess pharmacologic interventions and physical therapies. Development and validation of quality scales specific to physical treatments are needed.

Chronic Disease↗

Validity and reliability study of three tinnitus self-assessment scales: loudness, annoyance and change.

CONCLUSIONS: The three tinnitus self-rating scales described herein can be employed as part of "minimal datasets" to reflect the patient's current tinnitus status. These tests are simple and easy to use and can be completed by the patient alone. The results are easy to interpret and provide a good foundation for an effective doctor-patient dialogue. OBJECTIVE: To investigate the reliability and validity of three tinnitus self-rating scales: a six-point response scale for tinnitus loudness; an eight-point response scale for tinnitus annoyance; and a six-point response scale for tinnitus change. MATERIAL AND METHODS: The data for 273 patients participating in 2 separate studies were assessed in terms of their validity and reliability. We used criterion validity to determine whether the scales had empirical associations with external criteria, in this case an already firmly established tinnitus questionnaire. In addition we examined construct validity, i.e. its subcategories convergent and discriminant validity, in order to find out how related or unrelated items or scales were. We tested the reliability and repeatability of the scales using patients on our waiting list for tinnitus desensitization. RESULTS: The test-retest reliability was 0.72 for tinnitus loudness and 0.62 for tinnitus annoyance. Calculations showed that all three scales correlated positively with validated complex scales and thus we considered convergent validity to be adequate.

Adolescent↗

Clinical scales for the assessment of spasticity, associated phenomena, and function: a systematic review of the literature.

PURPOSE: To characterise clinical assessment methods for spasticity and/or its functional consequences in clinical patient populations at risk to suffer from spasticity. METHOD: Systematic literature search and manual-based two-step review process of psychometric properties of clinical assessment scales for spasticity and associated phenomena, as well as of functional scales with an association with spasticity. Reviewed psychometric properties included internal consistency, interrater, intrarater as well as retest reliability, construct validity, ecological validity, and responsiveness. RESULTS: Until May 2003 electronic database searches established a reference pool of 4151 references of which 90 references contributed to the review objectives. An additional 20 references were identified by an informal reference search. Twenty-four clinical scales that assess spasticity and/or related phenomena as well as 10 scales for 'active function' and three scales for 'passive function' with an association with spasticity could be identified. Some evidence signals that a high interrater reliability of the Ashworth and modified Ashworth scales can be achieved, however not in all circumstances. For many scales, reliability data is, however, missing. This is especially true for test retest reliability. Information about construct validity can promote our understanding of what individual scales are likely to assess. Many scales have been able to document changes after therapeutic intervention. CONCLUSIONS: The collated evidence can guide our clinical decision about when to use which scale and can promote evidence-based assessment of spasticity and related clinical phenomena.

Adult↗

Validation of the NHANES ADL scale in a sample of patients with report of cervical pain: factor analysis, item response theory analysis, and line item validity.

BACKGROUND: Few functional outcomes scales have used Item Response Theory (IRT) for validation. IRT allows individual line item validations and offers substantial advantages over classic methods of scale validation or the simplest from of IRT known as Rasch. Rasch analysis reduces data to dichotomous variables thus decreasing the sensitivity of Likert-type data responses. PURPOSE: The purpose of this study was to create an outcome scale associated with the latent trait of functioning and disability, validated using IRT, in a population with report of cervical pain. METHODS: Using the NHANES database, a recently created scale (NHANES ADL scale) was analysed using factor analysis, internal analyses of consistency, IRT, and comparison with internal measures of functioning and disability. RESULTS: The newly created NHANES ADL scale demonstrated uni-dimensionality, was internally reliable, and was correlated to internal measures of functioning and disability. Additionally, the majority of the scale items demonstrate strong discrimination and suitable thresholds. DISCUSSION: The NHANES ADL scale effectively measures physical, social, and emotional disability in patients with a cervical impairment, and may be an efficient measure of perceived limitations from working and generalized daily physical activity. CONCLUSION: The newly created NHANES ADL scale demonstrates internal consistency, unidimensionality, and line item validity. The NHANES ADL scale appears to be a useful instrument in measurement of functioning and disability in patients with report of cervical pain.

Activities of Daily Living↗

Complications inherent in scaling the basal rate of metabolism in mammals.

The scaling of the basal rate of metabolism in mammals is reexamined. Both the power and level of the scaling function are sensitive to various factors that interact with body mass and rate of metabolism, including the precision of temperature regulation, food habits, and activity level. This sensitivity implies that the rate of metabolism is a highly plastic character in the course of evolution. Consequently, the singular effect of mass on the rate of metabolism is most effectively analyzed in ecologically and physiologically uniform sets of species, rather than in taxonomically defined groups, which often are ecologically and physiologically diverse. Otherwise, all fitted curves for mammals integrate a variety of competing factors, thereby reflecting the species used and denying unique analytic significance to the power in scaling relations. Kleiber's eutherian curve may represent a relatively uniform set of data because all the species included were domesticated and because selection for high rates of production (and high rates of metabolism) occurred in the process of domestication. In the analysis of scaling relationships, the standard error of estimate (Sy.x) is a more valuable measure of the residual variation than is (1.0-r2) because r2 is a non-linear measure of the conformation of data to the relation and because Sy.x, unlike r2, is independent of the units used in the scaling relationship. At present the best estimate indicates that total rate of metabolism scales proportionally to approximately m0.60 at small masses (less than 300 g), as long as small species do not enter torpor, and scales proportionally to approximately m0.75 at large masses (greater than or equal to 300 g). Physiological properties other than metabolism are potentially sensitive to secondary factors, so their scaling functions also would be most clearly defined for physiologically uniform groups of species. This view suggests that insight into the significance of scaling relations can be obtained by examining the residual variation around a scaling function as well as by examining conformation to the function.

Animals↗

A comparison of postoperative pain scales in neonates.

BACKGROUND: Practical, valid and reliable pain measuring tools in neonates are required in clinical practice for effective pain management and prevention of the evaluator bias. METHODS: This prospective study was designed to cross-validate three pain scales: CRIES (cry, requires O(2), increased vital signs, expression, sleeplessness), CHIPPS (children's and infants' postoperative pain scale) and NIPS (neonatal infant pain scale) in terms of validity, reliability and practicality. The pain scales were translated. Concurrent validity, predictive validity and interrater reliability in postoperative pain were studied in 22 neonates after major surgery. Construct validity and concurrent validity in procedural pain were determined in 24 neonates before and during frenulectomy under topical anaesthesia. RESULTS: All scales had excellent interrater reliability (intraclass correlation >0.9). Construct validity was determined for all pain scales by the ability to differentiate the group with low pain scores before surgery and high scores during surgery (P<0.001). The positive correlations among all scales, ranging between r=0.30 and r=0.91, supported concurrent validity. CRIES showed the lowest correlation with other scales with correlation coefficients of r=0.30 and r=0.35. All scales yielded very good agreement (K>0.9) with routine decisions to treat postoperative pain. High sensitivity and specificity (>90%) for postoperative pain from all scales were achieved with the same cut-off point of 4. In terms of practicality, NIPS was the most acceptable (65%). CONCLUSIONS: Based on our findings, we recommended NIPS as a valid, reliable and practical tool.

Critical Care↗

The psychometric properties of clinical rating scales used in multiple sclerosis.

OullII;l y Many clinical rating scales have been proposed to assess the impact of multiple sclerosis on patients, but only few have been evaluated formally for reliability, validity and responsiveness. We assessed the psychometric properties of five commonly used scales in multiple sclerosis, the Expanded Disability Status Scale (EDSS), the Scripps Neurological Rating Scale (SNRS), the Functional Independence Measure (FIM), the Ambulation Index (AI) and the Cambridge Multiple Sclerosis Basic Score (CAMBS). The score frequency distributions of all five scales were either bimodal (EDSS and AI) or severely skewed (SNRS, FIM and CAMBS). The reliability of each scale depended on the definition of 'agreement'. Inter-and intra-rater reliabilities were high when 'agreement' was considered to exist despite a difference of up to 1.0 EDSS point (two 0.5 steps), 13 SNRS points, 9 FIM points, 1 AI point and 1 point on the various CAMBS domains. The FIM, AI, and the relapse and progression domains of the CAMBS were sensitive to clinical change, but the EDSS and the SNRS were unresponsive. The validity of these scales as impairment (SNRS and EDSS) and disability (EDSS, FIM, AI and the disability domain of the CAMBS) measures was established. All scales correlated closely with other measures of handicap and quality of life. None of these scales satisfied the psychometric requirements of outcome measures completely, but each had some desirable properties. The SNRS and the EDSS were reliable and valid measures of impairment and disability, but they were unresponsive. The FIM was a reliable, valid and responsive measure of disability, but it is cumbersome to administer and has a limited content validity. The AI was a reliable and valid ambulation-related disability scale, but it was weakly responsive. The CAMBS was a reliable (all four domains) and responsive (relapse and progression domains) outcome measure, but had a limited validity (handicap domain). These psychometric properties should be considered when designing further clinical trials in multiple sclerosis.

Activities of Daily Living↗

Reliability and validity of five mental health scales in older persons.

Five scales were assessed as mental health measures for older persons: Affect Balance, The Center for Epidemiological Studies Depression Scale, General Well-Being, LSI-Z Life Satisfaction, and Trait-Anxiety Inventory. These scales were administered to a community sample of 279 older persons and a clinical sample of 109 older persons who were in psychiatric inpatient units. In both samples, the internal consistency reliabilities for the anxiety, depression, and well-being scales were moderately high to high, for the life satisfaction scale they were acceptable, but the reliabilities for the affect balance scale suggest some caution in its use. For validity, multivariate analyses of variance found that all scales significantly discriminated between the two samples. The well-being and then depression scales were the strongest discriminators while the life satisfaction scale had the weakest validity. Cutting points for the well-being and depression scales are suggested for estimating the proportions of older persons who would be probable at-risk for disorder that requires intervention.

Aged↗

The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups.

The widespread use of standardized health surveys is predicated on the largely untested assumption that scales constructed from those surveys will satisfy minimum psychometric requirements across diverse population groups. Data from the Medical Outcomes Study (MOS) were used to evaluate data completeness and quality, test scaling assumptions, and estimate internal-consistency reliability for the eight scales constructed from the MOS SF-36 Health Survey. Analyses were conducted among 3,445 patients and were replicated across 24 subgroups differing in sociodemographic characteristics, diagnosis, and disease severity. For each scale, item-completion rates were high across all groups (88% to 95%), but tended to be somewhat lower among the elderly, those with less than a high school education, and those in poverty. On average, surveys were complete enough to compute scales scores for more than 96% of the sample. Across patient groups, all scales passed tests for item-internal consistency (97% passed) and item-discriminant validity (92% passed). Reliability coefficients ranged from a low of 0.65 to a high of 0.94 across scales (median = 0.85) and varied somewhat across patient subgroups. Floor effects were negligible except for the two role disability scales. Noteworthy ceiling effects were observed for both role disability scales and the social functioning scale. These findings support the use of the SF-36 survey across the diverse populations studied and identify population groups in which use of standardized health status measures may or may not be problematic.

Aged↗