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Threshold Dose
Threshold dose is the minimum dose of drug that triggers minimal detectable biological effect in an animal. At extremely low doses, biological responses are absent for some of the drugs. The increase in dose above threshold dose induces an increase in the percentage of biological responses. Several benchmarks have been established to describe the effects of a particular dose of drug in a particular species, such as NOEL(no-observed-effect-level), NOAEL(no-observed-adverse-effect-level) and LOAEL(lowest-observed-adverse-effect-level). They are established by reviewing the available studies and animal studies. The application of threshold dose in risk assessment safeguards the participants in human clinical trials and evaluates the risks of chronic exposure to certain substances. However, the nature of animal studies also limits the applicability of experimental results in the human population and its significance in evaluating potential risk of certain substances. In toxicology, there ...
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NOAEL
The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an organism, found by experiment or observation, at which there is no biologically or statistically significant increase in the frequency or severity of any adverse effects of the tested protocol. In drug development, the NOAEL of a new drug is assessed in laboratory animals, such as mice, prior to initiation of human trials in order to establish a safe clinical starting dose in humans. The OECD publishes guidelines for Preclinical Safety Assessments, in order to help scientists discover the NOAEL. Synopsis Some adverse effects in the exposed population when compared to its appropriate control might include alteration of morphology, functional capacity, growth, development or life span. The NOAEL is determined or proposed by qualified personnel, often a pharmacologist or a toxicologist. The NOAEL could be defined as "the highest experimental point that is without adverse effect," meaning that under labo ...
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Radiation
In physics, radiation is the emission or transmission of energy in the form of waves or particles through space or through a material medium. This includes: * ''electromagnetic radiation'', such as radio waves, microwaves, infrared, visible light, ultraviolet, x-rays, and gamma radiation (γ) * '' particle radiation'', such as alpha radiation (α), beta radiation (β), proton radiation and neutron radiation (particles of non-zero rest energy) * '' acoustic radiation'', such as ultrasound, sound, and seismic waves (dependent on a physical transmission medium) * '' gravitational radiation'', that takes the form of gravitational waves, or ripples in the curvature of spacetime Radiation is often categorized as either '' ionizing'' or '' non-ionizing'' depending on the energy of the radiated particles. Ionizing radiation carries more than 10 eV, which is enough to ionize atoms and molecules and break chemical bonds. This is an important distinction due to the large ...
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Cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss, and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans. Tobacco use is the cause of about 22% of cancer deaths. Another 10% are due to obesity, poor diet, lack of physical activity or excessive drinking of alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world, 15% of cancers are due to infections such as '' Helicobacter pylori'', hepatitis B, hepatitis C, human papillomavirus infection, Epstein–Barr virus and human immunodeficiency virus (HIV). These factors act, at least partly, by changing the genes o ...
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Linear No-threshold Model
The linear no-threshold model (LNT) is a dose-response model used in radiation protection to estimate stochastic health effects such as radiation-induced cancer, genetic mutations and teratogenic effects on the human body due to exposure to ionizing radiation. The model statistically extrapolates effects of radiation from very high doses (where they are observable) into very low doses, where no biological effects may be observed. The LNT model lies at a foundation of a postulate that all exposure to ionizing radiation is harmful, regardless of how low the dose is, and that the effect is cumulative over lifetime. The LNT model is commonly used by regulatory bodies as a basis for formulating public health policies that set regulatory dose limits to protect against the effects of radiation. The model has also been used in the assessment of cancer risks of mutagenic chemicals. The validity of the LNT model, however, is disputed, and other significant models exist: the threshold mo ...
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Carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substances are considered carcinogens, but their carcinogenic activity is attributed to the radiation, for example gamma rays and alpha particles, which they emit. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise from both natural and synthetic substances. Carcinogens are not necessarily immediately toxic; thus, their effect can be insidious. Carcinogens, as mentioned, are agents in the environment capable of contributing to cancer growth. Carcinogens can be categorized into two different types: activation-dependent and activation-independent, and each nature impacts their ...
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Reference Dose
A reference dose is the United States Environmental Protection Agency's maximum acceptable oral dose of a toxic substance.Reference doses are most commonly determined for pesticides. The EPA defines an oral reference dose (abbreviated RfD) as: estimate, with uncertainty spanning perhaps an order of magnitude, of a daily oral exposure to the human population (including sensitive subgroups) that is likely to be without an appreciable risk of deleterious effects during a lifetime. Regulatory status Unlike National Ambient Air Quality Standards, RfDs are not enforceable standards. Instead, the EPA uses RfDs as risk assessment benchmarks and tries to set other regulations so that people are not exposed to chemicals in amounts that exceed RfDs. According to the EPA, " aggregate daily exposure to a hemicalat or below the RfD (expressed as 100 percent or less of the RfD) is generally considered acceptable by EPA." For example, the EPA set an acute RfD for children of 0.0015 mg/kg/d ...
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Necropsy
An autopsy (post-mortem examination, obduction, necropsy, or autopsia cadaverum) is a surgical procedure that consists of a thorough Physical examination, examination of a Cadaver, corpse by dissection to determine the cause, mode, and manner of death or to evaluate any disease or injury that may be present for research or educational purposes. (The term "necropsy" is generally reserved for non-human animals). Autopsies are usually performed by a specialized medical doctor called a pathology, pathologist. In most cases, a medical examiner or coroner can determine the cause of death. However, only a small portion of deaths require an autopsy to be performed, under certain circumstances. Purposes of performance Autopsies are performed for either legal or medical purposes. Autopsies can be performed when any of the following information is desired: * Determine if death was natural or unnatural * Injury source and extent on the corpse * Manner of death must be determined * Post-mor ...
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Placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general, placebos can affect how patients perceive their condition and encourage the body's chemical processes for relieving pain and a few other symptoms, but have no impact on the disease itself. Improvements that patients experience after being treated with a placebo can also be due to unrelated factors, such as regression to the mean (a statistical effect where an unusually high or low measurement is likely to be followed by a less extreme one). The use of placebos in clinical medicine raises ethical concerns, especially if they are disguised as an active treatment, as this introduces dishonesty into the doctor–patient relationship and bypasses informed consent. While it was once assumed that this deception was necessary for placebos to have ...
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Extrapolation
In mathematics, extrapolation is a type of estimation, beyond the original observation range, of the value of a variable on the basis of its relationship with another variable. It is similar to interpolation, which produces estimates between known observations, but extrapolation is subject to greater uncertainty and a higher risk of producing meaningless results. Extrapolation may also mean extension of a method, assuming similar methods will be applicable. Extrapolation may also apply to human experience to project, extend, or expand known experience into an area not known or previously experienced so as to arrive at a (usually conjectural) knowledge of the unknownExtrapolation
entry at Merriam–Webster
(e.g ...
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Observational Studies
In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample to a population where the independent variable is not under the control of the researcher because of ethical concerns or logistical constraints. One common observational study is about the possible effect of a treatment on subjects, where the assignment of subjects into a treated group versus a control group is outside the control of the investigator. This is in contrast with experiments, such as randomized controlled trials, where each subject is randomly assigned to a treated group or a control group. Observational studies, for lacking an assignment mechanism, naturally present difficulties for inferential analysis. Motivation The independent variable may be beyond the control of the investigator for a variety of reasons: * A randomized experiment would violate ethical standards. Suppose one wanted to investigate the abortion – breast cancer ...
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Confounders
In statistics, a confounder (also confounding variable, confounding factor, extraneous determinant or lurking variable) is a variable that influences both the dependent variable and independent variable, causing a spurious association. Confounding is a causal concept, and as such, cannot be described in terms of correlations or associations.Pearl, J., (2009). Simpson's Paradox, Confounding, and Collapsibility In ''Causality: Models, Reasoning and Inference'' (2nd ed.). New York : Cambridge University Press. The existence of confounders is an important quantitative explanation why correlation does not imply causation. Confounds are threats to internal validity. Definition Confounding is defined in terms of the data generating model. Let ''X'' be some independent variable, and ''Y'' some dependent variable. To estimate the effect of ''X'' on ''Y'', the statistician must suppress the effects of extraneous variables that influence both ''X'' and ''Y''. We say that ''X'' and ...
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