what is biological variance

Biological Variation

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What is a reference in biological variation measurement?

For the biological measurands, that reference is the relevant patient population, a clinical decision point based on … This Review will describe the increasing importance of the concepts of biological variation to clinical chemists. The idea of comparison to 'reference' is fundamental in measurement.

What are the two types of biological variation?

There are two types of biological variations: within-subject and between-subject. Within-subject variation is the random fluctuation around a homeostatic point. In individuals, the homeostatic points usually vary. The variation between individuals is called between-subject biological variation.

What is the importance of biological variation in chemistry?

Biological variation is an important concept for clinical chemists to understand, because it helps answer many questions that clinical chemists encounter on a daily basis. For example, it can be used to determine whether the changes that occur in an individual’s results are statistically significant or not.

Does biological variation follow a normal distribution?

Biological Variation. Biological variation follows a “normal” distribution sufficiently often for this to be the initial assumption when considering a parameter, and statistical tests like the t-test and analysis of variance are based on that assumption.

What is biological and analytical variation?

Biological variation calculations express the amount of variation in the data, expressed as coefficient of variation (CV), occurring within individuals (CVI; I for individual), between individuals (CVG; G for group), and caused by analyzer measurement performance (CVA; A for analytical).

Why is biological variation important?

Biological variation is essential to species survival because natural selection acts upon the phenotypic variation within a population: the more varied the population's genetic resources, the more likely that the population will persist into the future.

What is biological variation in nursing?

Biological Variation These factors include race, body structure, genetic variations, nutritional preferences and psychological characteristics (Davidhizar, & Giger, 2008). Nursing examples include diseases related to specific ethnic groups as well as rural versus urban health.

What is the source of biological variation?

The genetic diversity has three different sources: mutation, recombination and immigration of genes. Mutation is the driving force of genetic variation and evolution. There are three types of DNA mutations: base substitutions (also called point mutations), deletions and insertions (Figure 1) [4].

What is an example of biological variation?

Eye colour, body form, and disease resistance are genotypic variations. Individuals with multiple sets of chromosomes are called polyploid; many common plants have two or more times the normal number of chromosomes, and new species may arise by this type of variation.

What are the types of variation in biology?

More examplesContinuous variationDiscontinuous variationHeightBlood groupWeightHand used to write withArm spanEye colourHead circumference at birthAbility to roll tongue

What is within-subject biological variation?

Background: Within-subject biological variation data (CVI) are used to establish quality requirements for assays and allow calculation of the reference change value (RCV) for quantitative clinical laboratory tests.

What are biological variations of culture?

The biological variations between humans are summarized in the ideas of natural selection and evolution. Human variation is based on the principle that there is variation in traits that result for recombination of genes from sexual reproduction. These traits are variable and can be passed down generation to generation.

How do we account for biological variation in experiments?

Biological variation depends on the characteristic of the population being studied. For example, measuring the height of a random group of people will have a larger variability than a study limited to people of one age or sex.

What are the causes of variations?

The two main causes of variation are mutation and genetic recombination in sexual reproduction.

What are the four sources of genetic variation?

Genetic variation can be caused by mutation (which can create entirely new alleles in a population), random mating, random fertilization, and recombination between homologous chromosomes during meiosis (which reshuffles alleles within an organism's offspring).

What is the common meaning of variation?

1 : a change in form, position, or condition Our routine could use some variation. 2 : amount of change or difference Scientists record the variations in temperature.

Why is it important to study and understand variation in biological experiments?

Variation is an important concept that underlies experimental design and data analysis. Incomplete understanding of variation can preclude students from designing experiments that adequately manage organismal and experimental variation, and from accurately conducting and interpreting statistical analyses of data.

What are biological variations of culture?

The biological variations between humans are summarized in the ideas of natural selection and evolution. Human variation is based on the principle that there is variation in traits that result for recombination of genes from sexual reproduction. These traits are variable and can be passed down generation to generation.

How does genetic variation help a population adapt to changes in its environment?

Evolution and Adaptation to the Environment Variation allows some individuals within a population to adapt to the changing environment. Because natural selection acts directly only on phenotypes, more genetic variation within a population usually enables more phenotypic variation.

Why is variation beneficial to the species but not necessarily for the individual?

Solution : Variations are beneficial to the species than individual because sometime for a species, the environmental conditions change so drastically that their survival becomes difficult. During that period, only few variants that are resistant would be able to survive. Thus, variants help in survival of the species.

What is normal biological variation?

The normal variability in the test species is called normal biological variation. The distribution of measurements typically follows a normal or Gaussian distribution. This distribution is described as a “bell-shaped” curve (as shown in Fig. 1 ), an essential underpinning of many statistical analyses. In essence, this is the background of “noise” against which backdrop observations are made. Mathematics can help clarify whether the results seen in an experiment are a result of biological “noise” or a treatment-related “signal.” Just as the experimenter cannot be sure that the treatment did have an effect, statistical analyses do not give a definite yes or no answer, rather a probability statement.

Why is biological variation important?

Biological variation is important for survival of individuals and species, and is the underpinning force behind evolution. The intricacies of human biology with its many layers of interconnecting networks and inbuilt redundancy evolved over many millions of years to maximize an individual's chance of survival.

What is the probability of rejecting a null hypothesis?

The experimenter can then review the probability of the treatment groups being the same and then decide whether to reject that they are or not. This decision point is referred to as rejecting the null hypothesis; the null hypothesis being that the variability of effects is due to normal biological variation, and hence groups are the same. By convention, we reject this hypothesis when the probability of making a false rejection is 5% or less. Hypothesis testing is discussed in more detail later.

How does biological variation affect our lives?

Biological variation is central to all our lives. Diversity in our own species is recognized in a number of visible characteristics, such as height, and functional characteristics, such as biotransformation abilities. The latter source of variability has led to the developing field of pharmacogenomics. Unfortunately, biological diversity interferes with efforts to test treatment effects, even when the experiment is designed and controlled a priori. No matter how inbred study animals are, and consequently how alike their physiological responses are likely to be, there is always a range of response displayed in measurements made on these animals. This fact has been confirmed many times in monozygotic human twins, and more recently in cloned animals.

What is the goal set up of analytical variation?

The goal set-up is that variance due to analytical error should not exceed 20% of the variation ( Fraser, 1983 ). It can be shown that this is acceptable when CV analytical ≤1/2CV intra-individual or ≤1/2CV biological ( Fraser and Harris, 1989 ).

Why is diversity important in biology?

Within each species, diversity is essential for survival and finding a niche in which to develop. Without exploring the theory of evolution, diversity in our own species is recognized in a number of visible characteristics, such as height, and functional characteristics, such as biotransforming abilities. The latter source of variability has led to the developing field of pharmacogenomics. Unfortunately, biological diversity interferes with efforts to test treatment effects, even when the experiment is designed and controlled a priori. No matter how inbred study animals are, there is always a range of response displayed in measurements made on these animals.

Why is bioavailability subject to biological variation?

No two individuals will handle the same substance in the same way, and even the same individual will handle the same substance in different ways at different times, because of factors such as health status, nutritional status, age, integrity of skin, and metabolism (see Pharmacogenetics below). For example, in atopic dermatitis, the skin is likely to be broken so its function as a barrier to exogenous substances is compromised (see Percutaneous absorption below). This has obvious implications not only for the choice and dose of an oil for its therapeutic effects, but also for minimizing its toxicity.

How to find total variation?

The total variation is the square root of the sum of the squares of the component variations, CVt = (CVa 2 + CVb 2) 1/2. To calculate the RCV, CVt is multiplied by 2 1/2 because there are two samples, and then by a factor, conventionally called Z, which is equal to the number of standard deviations appropriate for the probability selected.

Why are preanalytical variations called preanalytical variations?

These sources of variation, both in sample collection and in handling, are termed “preanalytical variation” by laboratory professionals because they occur before the analysis is performed.

Why do numerical test results vary?

Test results vary in individuals over time due to preanalytical variation, analytical imprecision and biological variation. The important question is whether changes seen in patients do infer clinical improvement or deterioration. To interpret serial results in an individual objectively, ...

How can preanalytical variation be minimized?

As already agreed, preanalytical variation can be minimized by adherence to SOP for sample collection and handling and with good and ongoing training. Thus, changes in serial results are significant only if they exceed the inherent analytical imprecision plus biological variation.

How does bias affect test results?

Analytical bias also affects test result interpretation when population-based reference values are used. Bias should be less than one-quarter of the group biological variation to allow the same reference values to be used in alternate sites.

Is within or between subject variation less?

For most analytes, the within-subject variation is much less than the between-subject variation [2]. This has very interesting consequences for clinical investigation that are detailed elsewhere [1].

What is normal biological variation?

The normal variability in the test species is called normal biological variation. The distribution of measurements typically follows a normal or Gaussian distribution. This distribution is described as a “bell-shaped” curve (as shown in Fig. 1 ), an essential underpinning of many statistical analyses. In essence, this is the background of “noise” against which backdrop observations are made. Mathematics can help clarify whether the results seen in an experiment are a result of biological “noise” or a treatment-related “signal.” Just as the experimenter cannot be sure that the treatment did have an effect, statistical analyses do not give a definite yes or no answer, rather a probability statement.

Why is biological variation important?

Biological variation is important for survival of individuals and species, and is the underpinning force behind evolution. The intricacies of human biology with its many layers of interconnecting networks and inbuilt redundancy evolved over many millions of years to maximize an individual's chance of survival.

What is the goal set up of analytical variation?

The goal set-up is that variance due to analytical error should not exceed 20% of the variation ( Fraser, 1983 ). It can be shown that this is acceptable when CV analytical ≤1/2CV intra-individual or ≤1/2CV biological ( Fraser and Harris, 1989 ).

What is normal variability in the test species?

The normal variability in the test species (normal biological variation) provides a distribution of measurements that typically follow a normal or Gaussian distribution. This distribution is described as a bell-shaped curve (as shown in Figure 30.1 ), and is an essential underpinning of many statistical analyses. In essence, this distribution is the background of “noise” against which backdrop observations are made. Mathematics can help clarify whether the results seen in an experiment are a result of biological noise or a treatment-related signal. Just as the experimenter cannot be sure that the treatment did have an effect, statistical analyses does not give a definite yes or no answer, but rather renders a probability statement regarding the likelihood that the treatment is responsible for inducing the effect.

What is the x axis of a normal biological variability curve?

FIGURE 30.1. Normal biological variability – bell shaped curve. The x-axis reports the frequency of the observation; the y -axis reports the measurement. SD, standard deviation.

How does biological variation affect our lives?

Biological variation is central to all our lives. Diversity in our own species is recognized in a number of visible characteristics, such as height, and functional characteristics, such as biotransformation abilities. The latter source of variability has led to the developing field of pharmacogenomics. Unfortunately, biological diversity interferes with efforts to test treatment effects, even when the experiment is designed and controlled a priori. No matter how inbred study animals are, and consequently how alike their physiological responses are likely to be, there is always a range of response displayed in measurements made on these animals. This fact has been confirmed many times in monozygotic human twins, and more recently in cloned animals.

Why is diversity important in biology?

Within each species, diversity is essential for survival and finding a niche in which to develop. Without exploring the theory of evolution, diversity in our own species is recognized in a number of visible characteristics, such as height, and functional characteristics, such as biotransforming abilities. The latter source of variability has led to the developing field of pharmacogenomics. Unfortunately, biological diversity interferes with efforts to test treatment effects, even when the experiment is designed and controlled a priori. No matter how inbred study animals are, there is always a range of response displayed in measurements made on these animals.

What is biological variation?

Biological variation is a significant factor in interpretation of clinical and diagnostic data used in toxicology. A single toxicity figure will not define the range of toxicity and effects in a given population. Because LD50 or other values are usually defined in very similar animals (e.g., laboratory rats and laboratory beagles), the laboratory toxicity figure does not reflect the biological variation and differences in toxicity that may occur in a diverse group of breeds within the canine or any other species. For animals of veterinary importance there is usually insufficient information on the variability of effects from low or moderate exposures. Furthermore, individual environmental and husbandry conditions vary widely and can affect the severity of response in any particular group of animals for a specific toxicant and dosage. Therefore, thorough clinical and environmental investigation and good laboratory diagnostic procedures are essential to toxicological evaluation in a suspected exposure.

How to ensure reliability of BV estimates?

To assure the reliability of BV estimates, several preanalytical factors should be controlled. Subject s should maintain their normal lifestyle and protected, as much as possible, from emotional and environmental changes during the time of sample collections. If samples are collected over multiple days, collection times should be within a narrow time range of the day. Sample collection should be performed by the same phlebotomist with the same tourniquet application time. Subjects should be allowed to rest for few minutes, and samples should be collected while subjects are in the same posture, for example, sitting or lying down.

How many subjects are used in BV assay?

More samples and subjects, if feasible, can be better but 4 samples from 10 subjects were used and seemed enough [8]. Typically, BV studies are conducted on healthy individuals who are not suffering from any disease or trivial conditions, for example, allergy or flu. Some [26–28] reported intrasubject BV in diseased subjects but, in such cases, disease should not be expected to change over the sampling time window.

What is clinical biochemist?

The Clinical Biochemist referred to a previous ward round at which the concepts of within-subject and between-subject biological variation had been discussed [2]. As briefly mentioned then, knowledge of these was very relevant to population-based reference intervals.

What is a reference interval?

Reference intervals are generally of low utility in monitoring individuals over time and reference change values (RCV) are preferred. Individuals can have results that vary over time within and outside reference intervals, often causing clinical confusion. The utility of reference intervals is much improved through stratification according ...

Is the within subject variation smaller than the between subject variation?

It was clear that the within-subject variation (the ranges – the length of the bars) was smaller than the between-subject variation (the difference between the means – the central dots).

Abstract

Based on theoretical considerations, a new approach to deal with the variation in properties and quality attributes inherently occurring in all products and batches is presented. It leads to a better understanding of the processes involved and enables the mathematical description and modelling of the observed phenomena.

1. Introduction

The strategies followed in developing human skills are simple. Humans like to have a simple life, with simple rules and simple applications. Nature however, is very simple in structure, but tremendously complex in interactions. When a behaviour is encountered in nature that is not understood, its effects are avoided as much as possible.

2. Biological variance, the burden

In every conceivable batch of agricultural produce, some variation in properties is present. When this variation occurs in properties or attributes, directly or indirectly important for the acceptance or behaviour of the product, problems may arise in handling and storing the batches.

3. Avoiding and decreasing biological variance

The examples in the previous section make absolutely clear why people have tried to decrease biological variance and its effects for such a long time. The seemingly incomprehensible behaviour of product properties and quality attributes in batches of produce prevented a logical approach to the problem.

4. Biological variance, the benefit

That biological variance is a major issue for the improvement of sensory and production quality of our food has long been recognised. A vast effort has been devoted in the areas of growing and sorting.

5. Consequences for storage conditions

Optimisation can be achieved without explicit knowledge of processes, mechanisms and rules involved in the storage of agricultural produce (see for example Section 4.5 ).

Acknowledgements

The many discussions on biological variance in all his aspects with colleagues M. Hertog, E. Biekman, R. Schouten, C. van Dijk and G. Jongbloed are gratefully acknowledged. The authors thank the editors in chief of Postharvest Biology and Technology for the kind invitation for this paper.

What is intra-individual biochemical variation?

Further, he postulated the ‘principle of genetic gradients,’ which stated that, ‘Whenever an extreme genetic character appears in an individual organism, it should be taken as an indication (unless there is proof to the contrary) that less extreme and graduated genetic characters of the same sort exist in other individual organisms.’ Williams termed this ‘biochemical individuality.’ Some analytes are tightly controlled within an individual around a setpoint, but the setpoint may vary between individuals; the classic example is creatinine. The significance of this to diagnosis is that an individual may be within a reference interval for the population but have significant renal function loss. With these analytes, there is a need to have more granularity in the reference interval by partitioning by age, sex, and body mass; however, this may still not be sufficient. A comparison with previous results may be necessary. However, there have not been many databases containing histories of patient results that could be used for this purpose in practice until recently.

Why do we use squared components in variance?

The variance model uses squared components because this weighs outliers more heavily than data closer to the mean, and it prevents differences above the mean from canceling out those below.

How to deal with bias in clinical practice?

The approach to dealing with bias involves quantifying patients’ misclassification caused by the shift in patient results relative to the reference limits . This may be an unrecognised problem. When a clinical decision point is used, the laboratory must be using a method/calibration which is traceable to the laboratory where the decision point was determined, which is not often the case [ 100 ].

What is the reference interval?

They suggested a new name, the ‘Reference Interval,’ which would describe fluctuations of analyte concentrations in well-characterised groups of individuals. The fundamental idea was to have a point of reference against which to interpret an individual’s results, rather than defining normality [ 28 ]. The population reference interval may not account for factors such as age, ethnicity, or gender unless they have a significant impact. Therefore, the reference interval approximates what can be expected in the population from which the patient belongs.

What is the difference between a reference interval and a clinical laboratory test?

A reference interval is derived from a reference population , whereas detecting a significant change in consecutive results requires an understanding of analytical and biological variation (BV).

What is BV in biomarkers?

BV for a biomarker entails in each individual a “subject mean” or central tendency, control level, or “setpoint” concentration of homeostatic regulation arising from such factors as genetic characteristics, diet, physical activity, and age [ 18, 19 ].

What is measurement in medicine?

Measurement is defined by the International Bureau of Weights and Measures [ 1] to be the process of experimentally obtaining one or more quantity values that can reasonably be attributed to a quantity. The measurement process commonly used in laboratory medicine uses a ratio scale, where proportions are constant, and there are no zero points [ 2 ]. Other ratios, particularly the ‘signal to noise,’ will play a part in the discussion.

What is biological variation?

As the name suggests, biological variation is a source of variance in laboratory test results. These data are commonly expressed as percent coefficient of variation (CV) or relative standard deviation (RSD). Both terms are equivalent and are calculated by first converting variance to SD, dividing SD by the Mean value of the data set, and then multiplying by 100% to express as percentage value. BV data presented in this Pearl are expressed in % CV terms.#N#There are two components of importance: First, the between-subject component: CV-G, which can be viewed as “group” variation. Second, the within-subject component: CV-I, which can be viewed as “individual” variation. These terms and subscripts can vary across publications, although today the generally agreed-upon nomenclature is CV-G and CV-I.

Who provides the most recent biological variation estimates?

The most recent biological variation estimates and database are provided online by the European Federation of Clinical Chemistry and Laboratory Medicine, or EFLM.

How to find mean bias of instrument B?

Mean bias of Instrument B is determined by comparing it to an established ALT method, “Instrument A”. In this example, bias equals 2.3 U/L, or 8.0% relative to the mean value of the two instruments (29 U/L).

How much bias should be in a method?

It has been recommended that any method bias should be less than one-fourth, or 0.25, of total BV. We can think of “bias” as a difference between people which is why both CV-I and CV-G values are included in the calculation.

What happens when CV-A approaches 0%?

For example, when CV-A approaches 0% (ideal), the person’s true test result from a single measurement has uncertainty due only to within-subject BV. By contrast, what happens when CV-A is exactly equal to one-half (50%) of CV-I at the desirable goal?

Why is it helpful to express BV data in percent CV terms?

Expressing these limits and BV data in percent CV terms is helpful because they apply equally to any unit of measure, whether conventional U.S. units or international units.

Is a reference interval based on biological grouping?

Since reference intervals for a clinical test are determined based on biological grouping of individuals, it is reasonable to expect that any method bias could shift the proportion of individuals correctly classified as true positive and true negatives.

Table I.

Table II.

How Is It Used in Everyday Practice?

• The medical, nursing and other professional staff on the ward round all understood the concept that variation in test results in individuals was due, not only to improvement or deterioration, but also to preanalytical variation, analytical imprecision and within-subject biological variation. However, they wondered why clinical biochemists had spent...

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