GAMBLER’S FALLACY (Syn: Monte-Carlo fallacy) The notion that the probability of an event occurring increases with the length of time since the event previously occurred when no such relation exists (e.g., as with properly randomized games of chance).
GAME THEORY A branch of mathematical logic concerned with the range of possible reactions to a particular strategy; each reaction can be assigned a probability, and each reaction can lead to further action by the “adversary” in the game. Used in systems analysis. It has occasional applications in disease surveillance and control. It is one of the underlying theories used in clinical decision analysis and in determining utilities (e.g., in calculating QALYs).
GAMETE A mature sex cell: the ovum of the female or the spermatozoon of the male. Gametes are haploid, containing half the normal number of chromosomes of a somatic cell, and fusing with its counterpart at fertilization to produce a zygote, which has the normal number of diploid chromosomes and develops into an embryo.
GATEKEEPER A person or system that selectively regulates or controls access to a health care service.
GAUSSIAN DISTRIBUTION See normal distribution.
GCP (GOOD CLINICAL PRACTICE) An international set of ethical and scientific quality standards for designing, conducting, recording, and reporting trials that involve participation of human subjects. It originates from the International Conference for Harmo- nization (ICH) (www.ich.org) and derives from the Helsinki Declaration of the World Medical Association on Ethical Principles for Medical Research Involving Human Subjects (www.wma.net/e/policy/b3.htm). The GCP standards are implemented, among others, by the European Medicines Agency (www.emea.europa.eu/Inspections/GCP- general.html), and the U.S. Food and Drug Administration (FDA) (www.fda.gov/oc/ gcp/default.htm).
GDP Gross domestic product.
G-ESTIMATION A method to estimate the parameters of structural nested models (SNMs). The method requires the assumption of no unmeasured confounding, or the slightly weaker assumption of known magnitude of the unmeasured confounding. The general version of G-estimation was proposed by Robins.393, 394 The standard instrumental variable estimator is a particular case of g-estimator. A method for estimation of the causal effect of a time-varying treatment in the presence of time-varying confounders. Other methods for such estimation are the parametric G-computation algorithm formula estimator, the iterative conditional expectations (ICE) estimator, and inverse-probability-of-treatment weighted (IPTW) estimation of marginal structural models (MSMs). When MSMs cannot be used, G-estimation of structural nested models (SNMs) can be used instead (e.g., to estimate the effect of an exposure on mortality in occupational cohort studies). Logistic SNMs cannot be fit by G-estimation. An advantage of using MSMs over G-estimation to control for time-dependent confounding is their resemblance to standard modeling techniques. See also inverse probability weighting.
GENE A sequence of DNA that codes for a particular protein product or that regulates other genes. A DNA segment that is transcribed into messenger RNA and translated into a protein. Traditionally, genes have been deemed to comprise the exons that are actually translated plus the intervening introns.23 Today, the nature of genes is in the midst of a profound reanalysis by genetics and other branches of science. They are no longer what they used to be in number and in essence.43,134,207–209
GENE EXPRESSION The amount and timing of appearance of the functional product of a gene. The process by which the DNA sequence of a gene is converted into functional pro- teins. Non–proteincoding genes (e.g., rRNA genes, tRNA genes) are not translated into protein. Gene expression is a multistep process that begins with the transcription of DNA (of which genes are made) into messenger RNA. It is then followed by posttranscriptional modification and translation into a gene product, followed by folding, posttranslational modification, and targeting. The amount of protein that a cell expresses depends on the tissue, the developmental stage of the organism, and the physiologic state of the cell. The expression of many genes is known to be regulated after transcription; thus, an increase in the concentration of mRNA may not increase expression. See also epigenetics.
GENE POOL The total of all genes possessed by reproductive members of a population.
GENERAL FERTILITY RATE A more refined measure of fertility than the crude birthrate. The denominator is restricted to the number of women of childbearing age The upper age limit for this rate is 44—sometimes 49—years in most jurisdictions.
GENERALIZABILITY The degree to which results of a study may apply, be relevant, or be generalized to populations or groups that did not participate in the study. In etiological research, such inferences to an external population are not merely statistical in nature but must be based on theory, judgment, and evidence external to the study (e.g., on available knowledge on biological, clinical, or social mechanisms linking a given expo-sure to the risk of developing the disease). See validity, study.
GENERAL POPULATION All members of a human population, defined essentially on the basis of geographical location, as in a country, region, city, etc. All inhabitants of some given area. Everyone in the population being studied, irrespective of race, ethnic- ity, or professional status.188 Individuals admitted to hospitals, other health care facili- ties, and prisons are usually excluded from the concept (i.e., considered not to be part of the general population). The term is often used to underline the different results that studies tend to obtain in the general population and in specific populations, subgroups, or settings (e.g., in the professionally active or working population, the hospitalized population).
GENERATION EFFECT (Syn: cohort effect) Variation in health status that arises from the different causal factors to which each birth cohort in the population is exposed as the environment and society change. Each consecutive birth cohort is exposed to a unique environment that coincides with its life span.
GENERATION TIME The interval between receipt of infection by the host and the latter’s maximal infectivity. This applies to both clinical cases and inapparent infections. With person-to-person transmission of infection, the interval between cases is determined by the generation time. See serial interval. See also incubation period.
GENE SILENCING One of several epigenetic processes that regulate gene expression. A term commonly used to describe that instead of being expressed (“turned on”), a gene is “switched off” by an epigenetic mechanism. Transcriptional gene silencing is the result of histone modifications, creating an environment of heterochromatin around a gene that makes it inaccessible to transcriptional machinery (RNA polymerase, tran- scription factors). Posttranscriptional gene silencing results when the mRNA of a par- ticular gene has been destroyed, thus preventing its translation to form an active gene product (e.g., a protein). See also epigenetic inheritance.
GENETIC DIVERSITY The variety of different types of genes in a species or population. A form of biodiversity.
GENETIC DRIFT Random variation in gene frequency from generation to generation, most often observed in small populations. The process of evolution through random statistical fluctuation of genetic composition of populations.
GENETIC ENGINEERING Manipulation of the genome of a living organism.
GENETIC EPIDEMIOLOGY The specialty that deals with the etiology, distribution, and control of disease in groups of people (e.g., relatives), and with genetic and epigenetic inheritance of disease in populations. The study of the role of genetic factors and their interaction with environmental factors in the occurrence of disease in human popula- tions.23,134, 210–212 In recent years it has experienced a certain convergence with molecular epidemiology.
GENETIC LINKAGE The phenomenon whereby phenotypes and alleles at one or more marker alleles tend to be inherited together. Particular genes occupy specific sites in chromosomes, one member of each pair of chromosomes coming from each parent. When two genes are fairly close to each other in the same chromosome pair, they tend to be inherited together. Such genes are said to be linked, and the phenomenon is called genetic linkage. See also linkage disequilibrium.
GENETIC PENETRANCE The penetrance of a genetic variant is the frequency with which the characteristic that the variant controls (the phenotype) is seen in people who carry the variant. The extent to which a genetically determined condition is expressed in an individual. The proportion of individuals with a given genotype that show the phenotype under specific environmental conditions. When all individuals carrying a dominant mutation show the mutant phenotype, the gene is said to show complete penetrance. The relation between the frequency of a variant and its penetrance is often inverse: the more penetrant (e.g., deleterious) a variant, the less frequent it is in the population. Only highly penetrant mutations may act with no interaction with external factors. Gene-environment interactions are intrinsic to the mode of action of low-penetrant genes. Current knowledge suggests that low-penetrant genetic traits cause a smaller fraction of the burden of disease than certain environmental agents (e.g., smoking, air pollution, chemical carcinogens).213–215 See also epigenetics; monogenic diseases; polygenic diseases.
GENETIC POLYMORPHISM See polymorphism, genetic.
GENETICS The branch of biology dealing with genetic heredity and variation of individual members of a species. Its branches include population genetics, which partly overlaps with genetic and molecular epidemiology; therefore pertinent genetic terms are part of this dictionary.
GENETIC SCREENING The use of genetic, clinical and epidemiological knowledge, reasoning, and techniques to detect genetic variants that have been demonstrated to place an individual at increased risk of a given disease. Ethical problems may arise in genetic screening (e.g., regarding the provision of information to persons of their putative increased risk when there is no effective treatment, and potential loss of eligibility for employment and insurance benefits).134, 213 See also number needed to screen (NNS).
GENETIZATION The process by which issues traditionally considered to be medical but not necessarily genetic become defined as problems with a strong or a single genetic component or as having a genetic cause and, sometimes, also a genetic treatment. The expansion of genetics into the life and health sciences and professions (e.g., the genetization of prenatal medicine, oncology, primary care). More generally, the attribu- tion of physiological, pathological, behavioral, or social conditions and problems to genetic causes, often at the expense of clinical, environmental, cultural, economic, or social explanations. The expansion of genetics into the domains of everyday existence. In genetization processes genetic is often considered to be synonymous with inherited, and vice versa, thus neglecting somatic (acquired) genetic alterations and cultural inheritance.108, 142–144, 207, 216, 217 See also integration; medicalization; reductionism.
GENOME The array of genes carried by an individual. The total genetic material of an organism. The whole set of the DNA of a species. See also epigenome.
GENOTOXIC A substance, setting or process that is toxic or harmful to the genetic material. An agent or process that interacts with cellular DNA, either directly or after metabolic biotransformation, resulting in alteration of DNA structure. DNA-adduct formation is one type of genotoxicity.218 See also carcinogen.
GENOTOXIC CARCINOGENS Chemical carcinogens capable of causing damage to DNA. They can be mutagenic, clastogenic, or aneugenic. Inside the cell, carcino- gens or their metabolic products can either directly or indirectly affect the regulation and expression of genes involved in cell-cycle control, DNA repair, cell differentia- tion, or apoptosis. Some carcinogens act by genotoxic mechanisms, such as forming DNA adducts or inducing chromosome breakage, fusion, deletion, missegregation and nondisjunction; for example, carcinogenic ions or compounds of nickel, arsenic, and cadmium can induce structural and numerical chromosomal aberrations. DNA binding and induction of mutations in cancer-related genes, such as TP53 and K-ras, are impor- tant genotoxic mechanisms of tumor initiation. Also important in causing diseases of complex etiology, such as cancer, is the accompanying ability of many compounds to promote the outgrowth of transformed cell clones through nongenotoxic mechanisms.219
GENOTYPE The genetic constitution inherited by an organism or a person, as distinct from the physical characteristics and appearance that emerge with development (i.e., the phenotype). The genetic constitution of an organism; modulated by the envi- ronment, it is then expressed as a phenotype.
GEOGRAPHICAL INFORMATION SYSTEM (GIS) An information system that incorpo- rates digitally constructed maps and uses sophisticated modeling techniques to analyze and display information patterns. Satellite imaging and remote sensing have greatly expanded the scope of GISs (e.g., trends in specific diseases are suggested after analyz- ing the composition of vegetation and the amounts of precipitation in tropical regions, which relate to changes in the distribution and abundance of predators and insect vectors). Another application is digitally prepared spot maps of disease clusters using postal codes and notified cases.220 An important application is in geomatics.
GEOGRAPHICAL PATHOLOGY (Syn: medical geography) The comparative study of countries or of regions within them with regard to variations in morbidity/mortality. The (implied) aim of such study is usually to demonstrate that the variations are caused by or related to differences in the geographical environment.
GEOMATICS The collection, processing, storage, and analysis of geographical infor- mation. An important application is sequentially generated computer maps to show regional and temporal trends and variations in various sectors of society, including the health sector. Its uses include the assessment of time trends in the geographical distri- bution of diseases such as malaria.
GEOMETRIC MEAN See mean, geometric.
GESTATIONAL AGE Strictly speaking, the gestational age of a fetus is the elapsed time since conception. However, as the moment when conception occurred is rarely known precisely, the duration of gestation is measured from the first day of the last normal menstrual period. Gestational age is expressed in completed days or completed weeks (e.g., events occurring 280–286 days after the onset of the last normal menstrual period are considered to have occurred at 40 weeks of gestation).
Measurements of fetal growth, as they represent continuous variables, are expressed in relation to a specific week of gestational age (e.g., the mean birth weight for 40 weeks is that obtained at 280–286 days of gestation on a weight-for-gestational-age curve). Some specified variations of gestational age are preterm, less than 37 completed weeks (less than 259 days); term, from 37 to less than 42 completed weeks (259–293 days); postterm, 42 completed weeks or more (294 days or more).
GESTATION LENGTH An ambiguous term for the duration of pregnancy because it can be calculated in different ways:
GINI COEFFICIENT A measure of dispersion in a set of values. Devised by Corrado Gini (1884–1965), Italian demographer and economist. A common measure of income inequality derived from the Lorenz curve; the curve shows the percentage of total income earned by the cumulative percentage of the population. In a “perfectly equal society,” the poorest 15% of the population would earn 15% of the total income, the poorest 65% of the population would earn 65% of the total income, and the Lorenz curve would equal the 45-degree “theoretical line of perfect equality.” As inequality increases in a community, the Lorenz curve deviates from the line of equality. The Gini coefficient is the size of the area between the line of equality and the Lorenz curve (area A in the figure) divided by the total area under the line of equality (A+B). Thus, the more the Lorenz curve departs from the theoretical line, the higher the Gini coefficient is. The coefficient can take a value between 0 and 1: a 0 would be obtained in a society where all income was equally shared, and a 1 (or 100%) in a totally unequal society. Assumptions and properties of the Lorenz curve and the Gini coefficient must be assessed before comparing values across different groups.221
GLOBAL BURDEN OF DISEASE See burden of disease.
GLOVER PHENOMENON An old term referring to the wide variation in rates at which many common medical procedures are conducted in seemingly comparable communities with similar morbidity rates—a phenomenon analyzed by J.A. Glover221 and many others.
GOAL A desired state to be achieved within a specified time. See also target.
“GOLD STANDARD” A method, procedure, or measurement that is widely accepted as being the best available. Often used to compare with new methods of unknown effectiveness (e.g., a potential new diagnostic test is assessed against the best available diag-
GOMPERTZ-MAKEHAM FORMULA A formula describing the relationship of mortality rate to age. There is an age-independent component and a component that increases exponentially with age. Benjamin Gompertz, a nineteenth-century demographer, first identified the proportionate relationship of mortality to age. This was refined by W. M. Makeham in 1867 to provide a better model of the age-specific pattern of the instantaneous death rate. If qx is the probability of dying at age x and A, B, and C are constants, qx = A + BCx. For ages beyond childhood, the Gompertz-Makeham formula closely fits observed patterns.
GONADOTROPHIC CYCLE One complete round of ovarian development in the mos- quito (or other insect vector) from the time when the blood meal is taken to the time when the fully developed eggs are laid.
GOBI/FFF Growth monitoring, oral rehydration, breast-feeding, immunization/family planning, food production, female education (WHO/UNICEF/World Bank).
GOODNESS OF FIT Degree of agreement between an empirically observed distribution and a mathematical or theoretical distribution.
GOODNESS-OF-FIT TEST A statistical test of the hypothesis that data have been randomly sampled or generated from a population that follows a particular theoretical distribution or model. Perhaps the most common such tests are chi-square tests.
GPA Global Programme on AIDS (WHO); superseded by UNAIDS.
GPHIN Global Public Health Intelligence Network of the World Health Organization. See also epidemiological intelligence.
GRAB SAMPLE See sample.
GRADIENT OF INFECTION The variety of host responses to infection ranging from inapparent infection to fatal illness.
GRAPH A general term for visual display of the relationship between variables; for example, the values of one set of variables are plotted along the horizontal, or x, axis, of a second variable, along the vertical, or y, axis. Three-dimensional graphs of relationships between three variables can be represented and comprehended visually in two dimensions. The relationship between x and y may be linear, exponential, logarithmic, etc. See also axis; abscissa, ordinate. “Graph” is also a descriptive term for histograms, bar charts, etc.
GRAVIDITY The number of pregnancies (completed or incomplete) experienced by a woman. See also parity.
“GRAY LITERATURE” (Syn: fugitive literature) Technical reports, studies, and essays that are not specifically aimed for conventional publication, have restricted distribu- tion, and are hence seldom included in the bibliographic retrieval systems commonly available to scholars, officers, and the public. They may be commissioned, sponsored, or owned by companies, academic units, financial institutions, or government agencies, including local or regional health departments. This literature used to include many unpublished masters’ or doctoral dissertations, but these and many other papers are nowadays enjoying wider access in digital formats. Scientific articles published in jour- nals using languages other than English do not per se have the features mentioned above (e.g., they have wide circulations among scholars and health professionals).
Gray literature, including epidemiological studies, may not be peer reviewed. Nonetheless, such literature may contain highly valid and relevant scientific findings, including information useful in meta-analysis and in public health impact assessment.
GROSS REPRODUCTION RATE (Syn: raw coefficient of reproduction) The aver- age number of female children a woman would have if she survived to the end of her childbearing years and if, throughout that period, she were subject to a given set of age-specific fertility rates and a given sex ratio at birth. It provides a measure of replacement-level fertility (or of the replacement of the generations) in the absence of mortality. In a hypothetical generation, it is equal to the number of girls born to a woman until the end of the reproduction period at a given (current year) age-specific fertility. See also net reproduction rate.
GROUP COMPARISONS Comparisons that consist in contrasting what is observed in a group of people in the presence of exposure to what would have occurred had the group of interest not been exposed to the postulated cause. Differences in frequency of disease occurrence between groups can logically be interpreted as being caused by the exposure. This is the main mode of knowledge acquisition in epidemiology.10 See also population thinking.
GROWTH RATE OF POPULATION A measure of population growth (in the absence of migration) comprising addition of newborns to the population and subtraction of deaths. The result, known as natural rate of increase, is calculated as
GUIDELINES A formal statement about a defined task or function. Examples include clinical practice guidelines, guidelines for application of preventive screening procedures, and guidelines for ethical conduct of epidemiological practice and research.184–187,222 Contrast code of conduct, in which the rules are intended to be strictly adhered to and may include penalties for violation. In the terminology developed by the European Community, directives are stronger than recommendations, which are stronger than guidelines. In North America, guidelines is normal usage also for recommendations.
GUTTMAN SCALE A measurement scale that ranks response categories to a question, with each unit representing an increasingly strong expression of an attribute, such as pain or disability, or an attitude.