Reference values: a review

Reference values are used to describe the dispersion of variables in healthy individuals. They are usually reported as population-based reference intervals (RIs) comprising 95% of the healthy population. International recommendations state the preferred method as a priori nonparametric determination from at least 120 reference individuals, but acceptable alternative methods include transference or validation from previously established RIs. The most critical steps in the determination of reference values are the selection of reference individuals based on extensively documented inclusion and exclusion criteria and the use of quality-controlled analytical procedures. When only small numbers of values are available, RIs can be estimated by new methods, but reference limits thus obtained may be highly imprecise. These recommendations are a challenge in veterinary clinical pathology, especially when only small numbers of reference individuals are available

Exercise capacity in Dutch children

The Bruce treadmill protocol is suitable for children 4 years of age and older. Dutch reference values were established in 1987. We considered that children's exercise capacity has deteriorated due to changes in physical activity patterns and eating habits. We determined new reference values and evaluated determinants of exercise capacity. Healthy Dutch children (n=267) aged 6-13 years participated in this cross-sectional observational study. The maximal endurance time on the treadmill was the criterion of exercise capacity. Furthermore, we obtained data on anthropometry, smoking habits, socioeconomic status, ethnicity, sports participation, and school transport habits. The maximal endurance time for children aged up till 10 was lower (up to 1.6 and 1.4 min in girls and boys, respectively) than previously published. Body mass index was negatively, and intense sports participation was positively associated with endurance time (β=-0.412 and 0.789, respectively; P<0.001). In conclusion, exercise capacity seems to have deteriorated in Dutch children aged up till 10 years whereas the values from the older children are remarkably similar to those from the previous study

Values for Human-to-Human Reference

published or submitted for publicatio

Income and Happiness across Europe: Do Reference Values Matter?

Using data from the European Social Survey (ESS), we examine the link between income and subjective well-being. We find that, for the whole sample of nineteen European countries, although income is positively correlated with both happiness and life satisfaction, reference income exerts a negative effect on individual well-being, a result consistent with the relative utility hypothesis. Performing separate analyses for some Eastern European countries, we also find some evidence of a ‘tunnel effect’, in that reference income has a positive impact on subjective well-being. Our findings support the view that in environments with stable income and employment, reference income serves as a basis for social comparisons, whereas in relatively volatile environments, it is used as a source of information for forming expectations about future status.comparison income, reference groups, happiness, life satisfaction

Estimation of reference intervals from small samples: an example using canine plasma creatinine

Background: According to international recommendations, reference intervals should be determined from at least 120 reference individuals, which often are impossible to achieve in veterinary clinical pathology, especially for wild animals. When only a small number of reference subjects is available, the possible bias cannot be known and the normality of the distribution cannot be evaluated. A comparison of reference intervals estimated by different methods could be helpful. Objective: The purpose of this study was to compare reference limits determined from a large set of canine plasma creatinine reference values, and large subsets of this data, with estimates obtained from small samples selected randomly. Methods: Twenty sets each of 120 and 27 samples were randomly selected from a set of 1439 plasma creatinine results obtained from healthy dogs in another study. Reference intervals for the whole sample and for the large samples were determined by a nonparametric method. The estimated reference limits for the small samples were minimum and maximum, mean +/-2 SD of native and Box–Cox-transformed values, 2.5th and 97.5th percentiles by a robust method on native and Box–Cox-transformed values, and estimates from diagrams of cumulative distribution functions. Results: The whole sample had a heavily skewed distribution, which approached Gaussian after Box–Cox transformation. The reference limits estimated from small samples were highly variable. The closest estimates to the 1439-result reference interval for 27-result subsamples were obtained by both parametric and robust methods after Box–Cox transformation but were grossly erroneous in some cases. Conclusion: For small samples, it is recommended that all values be reported graphically in a dot plot or histogram and that estimates of the reference limits be compared using different methods

Statistical evaluation of visual quality metrics for image denoising

This paper studies the problem of full reference visual quality assessment of denoised images with a special emphasis on images with low contrast and noise-like texture. Denoising of such images together with noise removal often results in image details loss or smoothing. A new test image database, FLT, containing 75 noise-free "reference" images and 300 filtered ("distorted") images is developed. Each reference image, corrupted by an additive white Gaussian noise, is denoised by the BM3D filter with four different values of threshold parameter (four levels of noise suppression). After carrying out a perceptual quality assessment of distorted images, the mean opinion scores (MOS) are obtained and compared with the values of known full reference quality metrics. As a result, the Spearman Rank Order Correlation Coefficient (SROCC) between PSNR values and MOS has a value close to zero, and SROCC between values of known full-reference image visual quality metrics and MOS does not exceed 0.82 (which is reached by a new visual quality metric proposed in this paper). The FLT dataset is more complex than earlier datasets used for assessment of visual quality for image denoising. Thus, it can be effectively used to design new image visual quality metrics for image denoising.Comment: Submitted to ICASSP 201

1000 Norms Project: Protocol of a cross-sectional study cataloging human variation

Background Clinical decision-making regarding diagnosis and management largely depends on comparison with healthy or ‘normal’ values. Physiotherapists and researchers therefore need access to robust patient-centred outcome measures and appropriate reference values. However there is a lack of high-quality reference data for many clinical measures. The aim of the 1000 Norms Project is to generate a freely accessible database of musculoskeletal and neurological reference values representative of the healthy population across the lifespan. Methods/design In 2012 the 1000 Norms Project Consortium defined the concept of ‘normal’, established a sampling strategy and selected measures based on clinical significance, psychometric properties and the need for reference data. Musculoskeletal and neurological items tapping the constructs of dexterity, balance, ambulation, joint range of motion, strength and power, endurance and motor planning will be collected in this cross-sectional study. Standardised questionnaires will evaluate quality of life, physical activity, and musculoskeletal health. Saliva DNA will be analysed for the ACTN3 genotype (‘gene for speed’). A volunteer cohort of 1000 participants aged 3 to 100 years will be recruited according to a set of self-reported health criteria. Descriptive statistics will be generated, creating tables of mean values and standard deviations stratified for age and gender. Quantile regression equations will be used to generate age charts and age-specific centile values. Discussion This project will be a powerful resource to assist physiotherapists and clinicians across all areas of healthcare to diagnose pathology, track disease progression and evaluate treatment response. This reference dataset will also contribute to the development of robust patient-centred clinical trial outcome measures

Randomized Predictive P-values: A Versatile Model Diagnostic Tool with Unified Reference Distribution

Examining residuals such as Pearson and deviance residuals, is a standard tool for assessing normal regression. However, for discrete response, these residuals cluster on lines corresponding to distinct response values. Their distributions are far from normality; graphical and quantitative inspection of these residuals provides little information for model diagnosis. Marshall and Spiegelhalter (2003) defined a cross-validatory predictive p-value for identifying outliers. Predictive p-values are uniformly distributed for continuous response but not for discrete response. We propose to use randomized predictive p-values (RPP) for diagnosing models with discrete responses. RPPs can be transformed to "residuals" with normal distribution, called NRPPs by us. NRPPs can be used to diagnose all regression models with scalar response using the same way for diagnosing normal regression. The NRPPs are nearly the same as the randomized quantile residuals (RQR), which are previously proposed by Dunn and Smyth (1996) but remain little known by statisticians. This paper provides an exposition of RQR using the RPP perspective. The contributions of this exposition include: (1) we give a rigorous proof of uniformity of RPP and illustrative examples to explain the uniformity under the true model; (2) we conduct extensive simulation studies to demonstrate the normality of NRPPs under the true model; (3) our simulation studies also show that the NRPP method is a versatile diagnostic tool for detecting many kinds of model inadequacies due to lack of complexity. The effectiveness of NRPP is further demonstrated with a health utilization dataset.Comment: 26 pages; we've updated some figures for better visualization, and fixed a few errors in text; R code for producing the results of this paper is available upon reques